MedWorm.com provides a medical RSS filtering service. Over 6000 RSS medical sources are combined and output via different filters. This feed contains the latest items from the 'Human Genetics' source. Thu, 09 Feb 2012 09:43:39 +0100 http://www.medworm.com/index.php?rid=5654693&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F60t5u407878g7067%2F Abstract  Many smokers attempt to quit smoking but few are successful in the long term. The heritability of nicotine addiction and smoking relapse have been documented, and research is focused on identifying specific genetic influences on the ability to quit smoking and response to specific medications. Research in genetically modified cell lines and mice has identified nicotine acetylcholine receptor subtypes that mediate the pharmacological and behavioral effects of nicotine sensitivity and withdrawal. Human genetic association studies have identified single nucleotide polymorphisms (SNPs) in genes encoding nicotine acetylcholine receptor subunits and nicotine metabolizing enzymes that influence smoking cessation phenotypes. There is initial promising evidence for a role ... Human Genetics journals http://www.medworm.com/rss/comments.php?id=5654693 Mon, 30 Jan 2012 16:06:58 +0100 5654693 http://www.medworm.com/index.php?rid=5642411&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fx2321t31883gm625%2F Abstract  Phenotypic variation results from variation in gene expression, which is modulated by genetic and/or epigenetic factors. To understand the molecular basis of human disease, interaction between genetic and epigenetic factors needs to be taken into account. The asthma-associated region 17q12-q21 harbors three genes, the zona pellucida binding protein 2 (ZPBP2), gasdermin B (GSDMB) and ORM1-like 3 (ORMDL3), that show allele-specific differences in expression levels in lymphoblastoid cell lines (LCLs) and CD4+ T cells. Here, we report a molecular dissection of allele-specific transcriptional regulation of the genes within the chromosomal region 17q12-q21 combining in vitro transfection, formaldehyde-assisted isolation of regulatory elements, chromatin immunoprecipitatio... Human Genetics journals http://www.medworm.com/rss/comments.php?id=5642411 Tue, 24 Jan 2012 07:34:56 +0100 5642411 http://www.medworm.com/index.php?rid=5642412&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F68k0r564077nt733%2F Abstract  Genetic variation on the Y chromosome has not been convincingly implicated in prostate cancer risk. To comprehensively analyze the role of inherited Y chromosome variation in prostate cancer risk in individuals of European ancestry, we genotyped 34 binary Y chromosome markers in 3,995 prostate cancer cases and 3,815 control subjects drawn from four studies. In this set, we identified nominally significant association between a rare haplogroup, E1b1b1c, and prostate cancer in stage I (P = 0.012, OR = 0.51; 95% confidence interval 0.30–0.87). Population substructure of E1b1b1c carriers suggested Ashkenazi Jewish ancestry, prompting a replication phase in individuals of both European and Ashkenazi Jewish ancestry. The association was not signific... Human Genetics journals http://www.medworm.com/rss/comments.php?id=5642412 Tue, 24 Jan 2012 07:34:54 +0100 5642412 http://www.medworm.com/index.php?rid=5623726&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F528x526r43684450%2F Abstract  The adiponutrin (PNPLA3) rs738409 polymorphism has been found to be associated with susceptibility to non-alcoholic fatty liver disease (NAFLD) in various cohorts. We further investigated the association of this polymorphism with non-alcoholic steatohepatitis (NASH) severity and with histological features of NAFLD. A total of 144 biopsy-proven NAFLD patients and 198 controls were genotyped for PNPLA3 gene polymorphism (rs738409 C>G). The biopsy specimens were histologically graded by a qualified pathologist. We observed an association of G allele with susceptibility to NAFLD in the pooled subjects (OR 2.34, 95% CI 1.69–3.24, p < 0.0001), and following stratification, in each of the three ethnic subgroups, namely Chinese, Indian and Malay (OR 1.94, ... Human Genetics journals http://www.medworm.com/rss/comments.php?id=5623726 Thu, 19 Jan 2012 06:56:47 +0100 5623726 http://www.medworm.com/index.php?rid=5623727&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fcv421u7824j36620%2F Abstract  Lactase is the intestinal enzyme responsible for digestion of the milk sugar lactose. Lactase gene expression declines dramatically upon weaning in mammals and during early childhood in humans (lactase nonpersistence). In various ethnic groups, however, lactase persists in high levels throughout adulthood (lactase persistence). Genetic association studies have identified that lactase persistence in northern Europeans is strongly associated with a single nucleotide polymorphism (SNP) located 14 kb upstream of the lactase gene: −13910*C/T. To determine whether the −13910*T SNP can function in vivo to mediate lactase persistence, we generated transgenic mice harboring human DNA fragments with the −13910*T SNP or the ancestral −13910*C SNP cloned upstream ... Human Genetics journals http://www.medworm.com/rss/comments.php?id=5623727 Thu, 19 Jan 2012 06:56:46 +0100 5623727 http://www.medworm.com/index.php?rid=5602622&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fg4836v5634013472%2F Abstract  Abnormalities in type III collagen in the arterial walls cause certain familial intracranial aneurysms (IAs); however, it remains unknown whether COL3A1 variants contribute to the risk of sporadic IAs. To study whether COL3A1 variants are associated with sporadic IAs, the association of COL3A1 variants with sporadic IAs was tested in 298 cases and 488 controls, replicated in an independent population of 192 cases and 1,690 controls, and further verified in 633 patients with intra-cerebral hemorrhage, 1,074 hypertensives, and 1,883 controls. We found that allele A of SNP rs1800255 conferred a 1.71-fold increased risk for IAs (adjusted odds ratio: OR = 1.71, 95% confidence interval: CI 1.19–2.45, P = 0.004) and results in an amino acid change of ... Human Genetics journals http://www.medworm.com/rss/comments.php?id=5602622 Thu, 12 Jan 2012 16:48:50 +0100 5602622 http://www.medworm.com/index.php?rid=5567094&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F62k7235k00p252g7%2F In this report, we aim to offer an updated review of the classical and novel genetic associations with SSc, analyzing the firmest and replicated signals within HLA and non-HLA genes, identified by both candidate gene and genome-wide association (GWA) studies. We will also provide an insight into the future perspectives and approaches that might shed more light into the complex genetic background underlying SSc. In spite of the remarkable advance in the field of SSc genetics during the last decade, the use of the new genetic technologies such as next generation sequencing (NGS), as well as the deep phenotyping of the study cohorts, to fully characterize the genetic component of this disease is imperative. Content Type Journal ArticleCategory Review PaperPages 1-15DOI 10.1007/s0043... Human Genetics journals http://www.medworm.com/rss/comments.php?id=5567094 Wed, 04 Jan 2012 16:51:11 +0100 5567094 http://www.medworm.com/index.php?rid=5567095&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fb575w56848837188%2F Abstract  Clopidogrel has been used to prevent recurrent ischemic events after acute coronary syndrome and/or coronary stent implantation. An impaired platelet response to this drug (residual high platelet reactivity) has been identified as a risk factor for recurrent ischemic events. The platelet response to clopidogrel is highly heritable (73%) suggesting a substantial genetic component. Two sequential cytochrome P450-dependent oxidative steps are required to convert clopidogrel to its active metabolite. The first step leads to the formation of 2-oxo-clopidogrel, which is then metabolized to the active metabolite. Cytochrome P450s are large highly polymorphic family of mono-oxygenases. Many alleles have been reported, and some of these are able to modify the activity of p... Human Genetics journals http://www.medworm.com/rss/comments.php?id=5567095 Fri, 30 Dec 2011 07:07:59 +0100 5567095 http://www.medworm.com/index.php?rid=5567096&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fj4h7k1u40j524647%2F We present a review of major genes involved in serotonergic, dopaminergic, GABAergic, and adrenoreceptor signaling that are considered to be directly involved in nicotine, opioid, cannabinoid, and ethanol use and dependence. The zebrafish genome encodes likely homologs of the vast majority of these loci. We also review the known expression patterns of these genes in zebrafish. The information presented in this review provides support for the use of zebrafish as a viable model for studying genetic factors related to drug addiction. Expansion of investigations into drug response using model organisms holds the potential to advance our understanding of drug response and addiction in humans. Content Type Journal ArticleCategory Review PaperPages 1-32DOI 10.1007/s00439-011-1128-0Autho... Human Genetics journals http://www.medworm.com/rss/comments.php?id=5567096 Fri, 30 Dec 2011 07:07:58 +0100 5567096 http://www.medworm.com/index.php?rid=5556117&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fr8w3130740117571%2F We describe a severe form of congenital myasthenic syndrome (CMS) caused by two heteroallelic mutations: a nonsense and a missense mutation in the gene encoding agrin (AGRN). The identified mutations, Q353X and V1727F, are located at the N-terminal and at the second laminin G-like (LG2) domain of agrin, respectively. A motor-point muscle biopsy demonstrated severe disruption of the architecture of the neuromuscular junction (NMJ), including: dispersion and fragmentation of endplate areas with normal expression of acetylcholinesterase; simplification of postsynaptic membranes; pronounced reduction of the axon terminal size; widening of the primary synaptic cleft; and, collection of membranous debris material in the primary synaptic cleft and in the subsynaptic cytoplasm. Expression stu... Human Genetics journals http://www.medworm.com/rss/comments.php?id=5556117 Wed, 28 Dec 2011 16:48:32 +0100 5556117 http://www.medworm.com/index.php?rid=5556116&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fj810k17508x9tk83%2F Content Type Journal ArticleCategory Short ReportPages 1-3DOI 10.1007/s00439-011-1134-2Authors Muhammad Hashim Raza, National Institute on Deafness and Other Communication Disorders (NIDCD), National Institutes of Health, Bethesda, USARana Amjad, Allama Iqbal Medical Research Centre, University of Punjab, Lahore, PakistanSheikh Riazuddin, Allama Iqbal Medical Research Centre, University of Punjab, Lahore, PakistanDennis Drayna, National Institute on Deafness and Other Communication Disorders (NIDCD), National Institutes of Health, Bethesda, USA Journal Human GeneticsOnline ISSN 1432-1203Print ISSN 0340-6717 (Source: Human Genetics) Human Genetics journals http://www.medworm.com/rss/comments.php?id=5556116 Wed, 28 Dec 2011 16:48:32 +0100 5556116 http://www.medworm.com/index.php?rid=5556118&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fb311g5n3mg8767g7%2F Abstract  Autosomal dominant conditions are known to be associated with advanced paternal age, and it has been suggested that retinoblastoma (Rb) also exhibits a paternal age effect due to the paternal origin of most new germline RB1 mutations. To further our understanding of the association of parental age and risk of de novo germline RB1 mutations, we evaluated the effect of parental age in a cohort of Rb survivors in the United States. A cohort of 262 Rb patients was retrospectively identified at one institution, and telephone interviews were conducted with parents of 160 survivors (65.3%). We classified Rb survivors into three groups: those with unilateral Rb were classified as sporadic if they had no or unknown family history of Rb, those with bilateral Rb were classifie... Human Genetics journals http://www.medworm.com/rss/comments.php?id=5556118 Tue, 27 Dec 2011 17:04:34 +0100 5556118 http://www.medworm.com/index.php?rid=5556119&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F863873716t422182%2F Abstract  Two primary chitinases have been identified in humans—acid mammalian chitinase (AMCase) and chitotriosidase (CHIT1). Mammalian chitinases have been observed to affect the host’s immune response. The aim of this study was to test for association between genetic variation in the chitinases and phenotypes related to chronic obstructive pulmonary disease (COPD). Polymorphisms in the chitinase genes were selected based on previous associations with respiratory diseases. Polymorphisms that were associated with lung function level or rate of decline in the Lung Health Study (LHS) cohort were analyzed for association with COPD affection status in four other COPD case–control populations. Chitinase activity and protein levels were also related to genotypes. In the ca... Human Genetics journals http://www.medworm.com/rss/comments.php?id=5556119 Tue, 27 Dec 2011 06:34:36 +0100 5556119 http://www.medworm.com/index.php?rid=5548744&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fe3w64t23888h2l01%2F Abstract  Multiple prostate cancer (PCa) risk-related loci have been discovered by genome-wide association studies (GWAS) based on case–control designs. However, GWAS findings may be confounded by population stratification if cases and controls are inadvertently drawn from different genetic backgrounds. In addition, since these loci were identified in cases with predominantly sporadic disease, little is known about their relationships with hereditary prostate cancer (HPC). The association between seventeen reported PCa susceptibility loci was evaluated with a family-based association test using 1,979 hereditary PCa families of European descent collected by members of the International Consortium for Prostate Cancer Genetics, with a total of 5,730 affected men. The risk al... Human Genetics journals http://www.medworm.com/rss/comments.php?id=5548744 Sat, 24 Dec 2011 16:45:05 +0100 5548744 http://www.medworm.com/index.php?rid=5541601&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fc0r2587qw66p1713%2F In conclusion, we demonstrated that the rs1564282 variant in GAK (PARK17) increases the risk of PD in Han Chinese patients from mainland China and the meta-analysis with European populations revealed a similar finding. However, carriers cannot be distinguished from non-carriers based on their clinical features or motor severity. Functional studies of GAK to unravel its role in the pathophysiologic pathway of PD will be useful. Content Type Journal ArticleCategory Original InvestigationPages 1-5DOI 10.1007/s00439-011-1133-3Authors Nan-Nan Li, Department of Neurology, West China Hospital, Sichuan University, Chengdu, 610041 Sichuan, ChinaXue-Li Chang, Department of Neurology, West China Hospital, Sichuan University, Chengdu, 610041 Sichuan, ChinaXue-Ye Mao, Department of Neurology,... Human Genetics journals http://www.medworm.com/rss/comments.php?id=5541601 Fri, 23 Dec 2011 16:53:40 +0100 5541601 http://www.medworm.com/index.php?rid=5541602&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F4511q6n115071151%2F In conclusion, abnormalities of DNA methylation at the MAOA promoter may be associated with schizophrenia in males. Content Type Journal ArticleCategory Original InvestigationPages 1-7DOI 10.1007/s00439-011-1131-5Authors Yanbo Chen, National Lab of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, No.5 Dong Dan San Tiao, Beijing, 100005 P. R. ChinaJiexu Zhang, National Lab of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, No.5 Dong Dan San Tiao, Beijing, 100005 P. R. ChinaLi Zhang, Health Human Resources Development Center, MOH, Beijing, ChinaYan Shen, National Lab of Medical Molecular Biology, Institute of Basic M... Human Genetics journals http://www.medworm.com/rss/comments.php?id=5541602 Fri, 23 Dec 2011 16:53:39 +0100 5541602 http://www.medworm.com/index.php?rid=5541603&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fbq4mn02526q64640%2F This study investigates signatures of selection at 76 pigmentation candidate genes that may contribute to skin pigmentation differences between Indigenous Americans and Europeans. Analysis was performed on two samples of Indigenous Americans genotyped on genome-wide SNP arrays. Using four tests for natural selection—locus-specific branch length (LSBL), ratio of heterozygosities (lnRH), Tajima’s D difference, and extended haplotype homozygosity (EHH)—we identified 14 selection-nominated candidate genes (SNCGs). SNPs in each of the SNCGs were tested for association with skin pigmentation in 515 admixed Indigenous American and European individuals from regions of the Americas with high ground-level ultraviolet radiation. In addition to SLC24A5 and SLC45A2, genes previously associat... Human Genetics journals http://www.medworm.com/rss/comments.php?id=5541603 Fri, 23 Dec 2011 16:53:38 +0100 5541603 http://www.medworm.com/index.php?rid=5541604&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F1388803j723714n2%2F Abstract  Advances in our ability to modify the mouse genome have enhanced our understanding of the genetic and neurobiological mechanisms contributing to addiction-related behaviors underlying substance use and abuse. These experimentally induced manipulations permit greater spatial and temporal specificity for modification of gene expression within specific cellular populations and during select developmental time periods. In this review, we consider the current mouse genetic model systems that have been employed to understand aspects of addiction and highlight significant conceptual advances achieved related to substance use and abuse. The mouse models reviewed herein include conventional knockout and knockin, conditional knockout, transgenic, inducible transgenic, mice ... Human Genetics journals http://www.medworm.com/rss/comments.php?id=5541604 Wed, 21 Dec 2011 20:08:01 +0100 5541604 http://www.medworm.com/index.php?rid=5541605&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F0817t5880rpp76tv%2F Abstract  The association between schizophrenia and tobacco smoking has been described in more than 1,000 articles, many with inadequate methodology. The studies on this association can focus on: (1) current smoking, ever smoking or smoking cessation; (2) non-psychiatric controls or controls with severe mental illness (e.g., bipolar disorder); and (3) higher smoking frequency or greater usage in smokers. The association with the most potential for genetic studies is that between ever daily smoking and schizophrenia; it may reflect a shared genetic vulnerability. To reduce the number of false-positive genes, we propose a three-stage approach derived from epidemiological knowledge. In the first stage, only genetic variations associated with ever daily smoking that are simulta... Human Genetics journals http://www.medworm.com/rss/comments.php?id=5541605 Wed, 21 Dec 2011 20:07:59 +0100 5541605 http://www.medworm.com/index.php?rid=5531275&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fe2441j0tg4411780%2F Abstract  It is not well known whether genetic markers identified through genome-wide association studies (GWAS) confer similar or different risks across people of different ancestry. We screened a regularly updated catalog of all published GWAS curated at the NHGRI website for GWAS-identified associations that had reached genome-wide significance (p ≤ 5 × 10−8) in at least one major ancestry group (European, Asian, African) and for which replication data were available for comparison in at least two different major ancestry groups. These groups were compared for the correlation between and differences in risk allele frequencies and genetic effects’ estimates. Data on 108 eligible GWAS-identified associations with a total of 900 datasets (European,... Human Genetics journals http://www.medworm.com/rss/comments.php?id=5531275 Mon, 19 Dec 2011 16:52:09 +0100 5531275 http://www.medworm.com/index.php?rid=5510700&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fw041w43148871h56%2F Abstract  While substance abuse disorders only occur in humans, mice and other model organisms can make valuable contributions to genetic studies of these disorders. In this review, we consider a few specific examples of how model organisms have been used in conjunction with studies in humans to study the role of genetic factors in substance use disorders. In some examples genes that were first discovered in mice were subsequently studied in humans. In other examples genes or specific polymorphisms in genes were first studied in humans and then modeled in mice. Using anatomically and temporally specific genetic, pharmacological and other environmental manipulations in conjunction with histological analyses, mechanistic insights that would be difficult to obtain in humans ha... Human Genetics journals http://www.medworm.com/rss/comments.php?id=5510700 Wed, 14 Dec 2011 16:41:19 +0100 5510700 http://www.medworm.com/index.php?rid=5510701&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F7k7m72810t2174m0%2F Abstract  Transgenic systems are widely used to study the cellular and molecular basis of human neurodegenerative diseases. A wide variety of model organisms have been utilized, including bacteria (Escherichia coli), plants (Arabidopsis thaliana), nematodes (Caenorhabditis elegans), arthropods (Drosophila melanogaster), fish (zebrafish, Danio rerio), rodents (mouse, Mus musculus and rat, Rattus norvegicus) as well as non-human primates (rhesus monkey, Macaca mulatta). These transgenic systems have enormous value for understanding the pathophysiological basis of these disorders and have, in some cases, been instrumental in the development of therapeutic approaches to treat these conditions. In this review, we discuss the most commonly used model organisms and the methodologies ... Human Genetics journals http://www.medworm.com/rss/comments.php?id=5510701 Tue, 13 Dec 2011 17:05:00 +0100 5510701 http://www.medworm.com/index.php?rid=5499891&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F7260129x58193w60%2F Abstract  The phosphodiesterase 4B (PDE4B) is a candidate susceptibility gene for schizophrenia (SCZ), interacting with DISC1, a known genetic risk factor for SCZ. To examine if variants within PDE4B gene are associated with SCZ in Northwestern Han Chinese, and if these effects vary in gender-specific subgroup, we analyzed 20 SNPs, selected from previous studies and preliminary HapMap data analyses with minor allele frequency (MAF) ≥20%, in a cohort of 428 cases and 572 controls from genetically independent Northwestern Han Chinese. Single SNP association, haplotype association and sex-specific association analysis were performed. We found that rs472952 is significantly associated with SCZ and rs7537440 is associated with SCZ in females. Further analysis indicated that a ha... Human Genetics journals http://www.medworm.com/rss/comments.php?id=5499891 Sat, 10 Dec 2011 16:55:49 +0100 5499891 http://www.medworm.com/index.php?rid=5499892&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fvq2759t088750215%2F Abstract  We have previously examined characteristics of maternal chromosomes 21 that exhibited a single recombination on 21q and proposed that certain recombination configurations are risk factors for either meiosis I (MI) or meiosis II (MII) nondisjunction. The primary goal of this analysis was to examine characteristics of maternal chromosomes 21 that exhibited multiple recombinant events on 21q to determine whether additional risk factors or mechanisms are suggested. In order to identify the origin (maternal or paternal) and stage (MI or MII) of the meiotic errors, as well as placement of recombination, we genotyped over 1,500 SNPs on 21q. Our analyses included 785 maternal MI errors, 87 of which exhibited two recombinations on 21q, and 283 maternal MII errors, 81 of wh... Human Genetics journals http://www.medworm.com/rss/comments.php?id=5499892 Thu, 08 Dec 2011 18:10:57 +0100 5499892 http://www.medworm.com/index.php?rid=5491460&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fx8v15815r7nm7v38%2F Abstract  The human genome is constantly subjected to evolutionary forces which shape its architecture. Insertions of mitochondrial DNA sequences into nuclear genome (NumtS) have been described in several eukaryotic species, including Homo sapiens and other primates. The ongoing process of the generation of NumtS has made them valuable markers in primate phylogenetic studies, as well as potentially informative loci for reconstructing the genetic history of modern humans. Here, we report the identification of 53 human-specific NumtS by inspection of the UCSC genome browser, showing that they may be direct insertions of mitochondrial DNA into the human nuclear DNA after the human-chimpanzee split. In silico analyses allowed us to identify 14 NumtS which are polymorphic in term... Human Genetics journals http://www.medworm.com/rss/comments.php?id=5491460 Wed, 07 Dec 2011 16:43:51 +0100 5491460 http://www.medworm.com/index.php?rid=5481658&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fxu848j7775r2r755%2F Abstract  Current genome-wide association studies (GWAS) use commercial genotyping microarrays that can assay over a million single nucleotide polymorphisms (SNPs). The number of SNPs is further boosted by advanced statistical genotype-imputation algorithms and large SNP databases for reference human populations. The testing of a huge number of SNPs needs to be taken into account in the interpretation of statistical significance in such genome-wide studies, but this is complicated by the non-independence of SNPs because of linkage disequilibrium (LD). Several previous groups have proposed the use of the effective number of independent markers (M e) for the adjustment of multiple testing, but current methods of calculation for M e are limited in accuracy or computational sp... Human Genetics journals http://www.medworm.com/rss/comments.php?id=5481658 Mon, 05 Dec 2011 17:42:22 +0100 5481658 http://www.medworm.com/index.php?rid=5453119&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F35626g7421206363%2F Abstract  Both taking folic acid-containing vitamins around conception and consuming food fortified with folic acid have been reported to reduce omphalocele rates. Genetic factors are etiologically important in omphalocele as well; our pilot study showed a relationship with the folate metabolic enzyme gene methylenetetrahydrofolate reductase (MTHFR). We studied 169 non-aneuploid omphalocele cases and 761 unaffected, matched controls from all New York State births occurring between 1998 and 2005 to look for associations with single nucleotide polymorphisms (SNPs) known to be important in folate, vitamin B12, or choline metabolism. In the total study population, variants in the transcobalamin receptor gene (TCblR), rs2232775 (p.Q8R), and the MTHFR gene, rs1801131 (c.1298A>C)... Human Genetics journals http://www.medworm.com/rss/comments.php?id=5453119 Thu, 24 Nov 2011 17:44:18 +0100 5453119 http://www.medworm.com/index.php?rid=5446413&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Ffj47hx85068g0128%2F Abstract  Alcohol is oxidized to acetaldehyde, which in turn is oxidized to acetate. The aldehyde dehydrogenase 2 gene (ALDH2) is the most important gene responsible for acetaldehyde metabolism. Individuals heterozygous or homozygous for the lys (A or *2) allele at the single nucleotide polymorphism (SNP) glu504lys (rs671) of ALDH2 have greatly reduced ability to metabolize acetaldehyde, which greatly decreases their risk for alcohol dependence (AD). Case–control studies have shown association between this SNP and alcohol dependence as well as alcohol-induced liver disease. However, some studies have produced insignificant results. Using cumulative data from the past 20 years predominately from Asian populations (from both English and Chinese publications), this meta-a... Human Genetics journals http://www.medworm.com/rss/comments.php?id=5446413 Sat, 19 Nov 2011 16:53:46 +0100 5446413 http://www.medworm.com/index.php?rid=5415593&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F914h186804560731%2F This study provides evidence for a novel ADRP locus on chromosome 6q23. Content Type Journal ArticleCategory Original InvestigationPages 1-7DOI 10.1007/s00439-011-1115-5Authors Chitra Kannabiran, Kallam Anji Reddy Molecular Genetics Laboratory, Hyderabad Eye Research Foundation, L.V. Prasad Eye Institute, L.V. Prasad Marg, Banjara Hills, Hyderabad, 500034 Andhra Pradesh, IndiaHardeep Pal Singh, Kallam Anji Reddy Molecular Genetics Laboratory, Hyderabad Eye Research Foundation, L.V. Prasad Eye Institute, L.V. Prasad Marg, Banjara Hills, Hyderabad, 500034 Andhra Pradesh, IndiaSubhadra Jalali, Smt Kannuri Santhamma Retina-Vitreous Centre, L.V. Prasad Eye Institute, L.V. Prasad Marg, Banjara Hills, Hyderabad, 500034 Andhra Pradesh, India Journal Human GeneticsOnline ISSN 1432-12... Human Genetics journals http://www.medworm.com/rss/comments.php?id=5415593 Mon, 14 Nov 2011 16:53:32 +0100 5415593 http://www.medworm.com/index.php?rid=5415594&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F72561n6l42731616%2F Abstract  Host immune response against Mycobacterium leprae plays an important role in providing resistance to infection and disease progression. Genome-wide linkage and association studies suggest the possibility of multiple risk loci within HLA (6p21.3) region. Any systematic study of relevance within the histocompatibility complex of importance in host immune response would be pertinent because of non-replication of the known loci and unavailable information on some of the unexplored genes and regions. A systematic scan was performed of the selected region involving LTA-TNF-LTB genes within 6p21.3 with a resolution of 1SNP/127 bp; and the SNPs in flanking BAT1, NFKBIL and BTNL2-DRA genes on the basis of their tag status or their presence in promoter/exonic regions wi... Human Genetics journals http://www.medworm.com/rss/comments.php?id=5415594 Wed, 09 Nov 2011 17:56:29 +0100 5415594 http://www.medworm.com/index.php?rid=5415595&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fc12747726271n740%2F Abstract  Some highland populations have genetic adaptations that enable their successful existence in a hypoxic environment. Tibetans are protected against many of the harmful responses exhibited by non-adapted populations upon exposure to severe hypoxia, including elevated hemoglobin concentration (i.e., polycythemia). Recent studies have highlighted several genes subject to natural selection in native high-altitude Tibetans. Three of these genes, EPAS1, EGLN1 and PPARA, regulate or are regulated by hypoxia inducible factor, a principal controller of erythropoiesis and other organismal functions. Uncovering the molecular basis of hypoxic adaptation should have implications for understanding hematological and other adaptations involved in hypoxia tolerance. Because the hypo... Human Genetics journals http://www.medworm.com/rss/comments.php?id=5415595 Wed, 09 Nov 2011 07:00:30 +0100 5415595 http://www.medworm.com/index.php?rid=5415596&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fd850440102g14773%2F Abstract  White blood cell count (WBC) is unique among identified inflammatory predictors of chronic disease in that it is routinely measured in asymptomatic patients in the course of routine patient care. We led a genome-wide association analysis to identify variants associated with WBC levels in 13,923 subjects in the electronic Medical Records and Genomics (eMERGE) Network. We identified two regions of interest that were each unique to subjects of genetically determined ancestry to the African continent (AA) or to the European continent (EA). WBC varies among different ancestry groups. Despite being ancestry specific, these regions were identifiable in the combined analysis. In AA subjects, the region surrounding the Duffy antigen/chemokine receptor gene (DARC) on 1q21 e... Human Genetics journals http://www.medworm.com/rss/comments.php?id=5415596 Tue, 08 Nov 2011 19:15:31 +0100 5415596 http://www.medworm.com/index.php?rid=5415597&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F5t778214365687m7%2F In conclusion, our study points to a novel regulatory mechanism of ATXN2 expression involving an epigenetic event resulting in differential disease course in SCA2 patients. Content Type Journal ArticleCategory Original InvestigationPages 1-14DOI 10.1007/s00439-011-1101-yAuthors José Miguel Laffita-Mesa, Center for Research and Rehabilitation of Hereditary Ataxia, CIRAH, Carlos Juan Finlay, Carretera Central Vía Habana km 51/2, Reparto Edecio Pérez, CP 80100 Holguín, CubaPeter O. Bauer, Laboratory for Structural Neuropathology, RIKEN Brain Science Institute, 2-1 Hirosawa, Wako, Saitama 351-0198, JapanVivian Kourí, Virology Department, Institute of Tropical Medicine “Pedro Kourí”, Autopista Novia del Mediodía, km 6½, La Lisa, PO Box 601, Marianao, Havana, 13, CubaLeodani ... Human Genetics journals http://www.medworm.com/rss/comments.php?id=5415597 Tue, 08 Nov 2011 19:15:30 +0100 5415597 http://www.medworm.com/index.php?rid=5404023&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F01571g578913354v%2F Abstract  Congenital motor nystagmus (CMN) is characterized by bilateral involuntary ocular oscillation without any other underlying ocular or systemic diseases. An autosomal dominant CMN was identified in a large Chinese family where all patients had nystagmus since infancy. The nystagmus in the family is independent of any known ocular or systemic diseases. After exclusion of known CMN loci, a genome-wide scan was performed by genotyping microsatellite markers at about 10 cM intervals, together with two-point linkage analysis. Exome sequencing was used to screen coding exons of well-annotated genes. Sanger-dideoxy sequencing was used to verify candidate variations inside the linkage interval. Congenital motor nystagmus in this family shows linkage to markers in a 11.... Human Genetics journals http://www.medworm.com/rss/comments.php?id=5404023 Mon, 07 Nov 2011 17:11:30 +0100 5404023 http://www.medworm.com/index.php?rid=5404024&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F7564702v82936v46%2F We report that the blue-eye associated alleles at all three haplotypes were found at high frequencies in Europe; however, one is restricted to Europe and surrounding regions, while the other two are found at moderate to high frequencies throughout the world. We also observed that the derived allele of rs1800414 is essentially limited to East Asia where it is found at high frequencies. Long-range haplotype tests provide evidence of selection for the blue-eye allele at the three haplotyped systems but not for the green/hazel eye SNP allele. We also saw evidence of selection at the derived allele of rs1800414 in East Asia. Our data suggest that the haplotype restricted to Europe is the strongest marker for blue eyes globally and add further inferential evidence that the derived allele o... Human Genetics journals http://www.medworm.com/rss/comments.php?id=5404024 Mon, 07 Nov 2011 17:11:29 +0100 5404024 http://www.medworm.com/index.php?rid=5394478&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Ff5785061521l056l%2F Abstract  Interferon-γ (IFN-γ) is a key molecule of T helper 1 (Th1)-immune response against tuberculosis (TB), and rare genetic defects of IFN-γ receptors cause disseminated mycobacterial infection. The aim of the present study was to investigate whether genetic polymorphisms found in the Th1-immune response genes play a role in TB. In our study, DNA samples were collected from two series of cases including 832 patients with new smear-positive TB and 506 unrelated individuals with no history of TB in the general population of Hanoi, Vietnam. Alleles of eight microsatellite markers located around Th1-immune response-related genes and single nucleotide polymorphisms near the promising microsatellites were genotyped. A set of polymorphisms within the interferon gamma recep... Human Genetics journals http://www.medworm.com/rss/comments.php?id=5394478 Sat, 05 Nov 2011 17:10:06 +0100 5394478 http://www.medworm.com/index.php?rid=5394479&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fbn142u9660847085%2F Abstract  We have investigated whether regions of the genome showing signs of positive selection in scans based on haplotype structure also show evidence of positive selection when sequence-based tests are applied, whether the target of selection can be localized more precisely, and whether such extra evidence can lead to increased biological insights. We used two tools: simulations under neutrality or selection, and experimental investigation of two regions identified by the HapMap2 project as putatively selected in human populations. Simulations suggested that neutral and selected regions should be readily distinguished and that it should be possible to localize the selected variant to within 40 kb at least half of the time. Re-sequencing of two ~300 kb regions ... Human Genetics journals http://www.medworm.com/rss/comments.php?id=5394479 Fri, 04 Nov 2011 16:50:03 +0100 5394479 http://www.medworm.com/index.php?rid=5394480&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fx2624107302w03w3%2F Abstract  Both nicotine and alcohol addictions are common chronic brain disorders that are of great concern to individuals and society. Although genetics contributes significantly to these disorders, the susceptibility genes and variants underlying them remain largely unknown. Many years of genome-wide linkage and association studies have implicated a number of genes and pathways in the etiology of nicotine and alcohol addictions. In this communication, we focus on current evidence, primarily from human genetic studies, supporting the involvement of genes and variants in the GABAergic signaling system in the etiology of nicotine dependence and alcoholism based on linkage, association, and gene-by-gene interaction studies. Current efforts aim not only to replicate these find... Human Genetics journals http://www.medworm.com/rss/comments.php?id=5394480 Wed, 02 Nov 2011 16:55:54 +0100 5394480 http://www.medworm.com/index.php?rid=5342114&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F13671741555m6x8q%2F Abstract  Genome-wide association studies (GWASs) have primarily focused on marginal effects for individual markers and have incorporated external functional information only after identifying robust statistical associations. We applied a new approach combining the genetics of gene expression and functional classification of genes to the GWAS of basal cell carcinoma (BCC) to identify potential biological pathways associated with BCC. We first identified 322,324 expression-associated single-nucleotide polymorphisms (eSNPs) from two existing GWASs of global gene expression in lymphoblastoid cell lines (n = 955), and evaluated the association of these functionally annotated SNPs with BCC among 2,045 BCC cases and 6,013 controls in Caucasians. We then grouped them into... Human Genetics journals http://www.medworm.com/rss/comments.php?id=5342114 Mon, 17 Oct 2011 16:04:10 +0100 5342114 http://www.medworm.com/index.php?rid=5342113&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F98317x1150071645%2F Abstract  We have analyzed human genetic diversity in 33 Old World populations including 23 populations obtained through Genographic Project studies. A set of 1,536 SNPs in five X chromosome regions were genotyped in 1,288 individuals (mostly males). We use a novel analysis employing subARG network construction with recombining chromosomal segments. Here, a subARG is constructed independently for each of five gene-free regions across the X chromosome, and the results are aggregated across them. For PCA, MDS and ancestry inference with STRUCTURE, the subARG is processed to obtain feature vectors of samples and pairwise distances between samples. The observed population structure, estimated from the five short X chromosomal segments, supports genome-wide frequency-based analy... Human Genetics journals http://www.medworm.com/rss/comments.php?id=5342113 Mon, 17 Oct 2011 16:04:10 +0100 5342113 http://www.medworm.com/index.php?rid=5342115&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fgr33583764758j3k%2F Abstract  Diseases related to smoking are the second leading cause of death in the world. Cigarette smoking is a risk factor for several diseases such as cancer and cardiovascular and respiratory disorders. Despite increasing evidence of genetic determination, the susceptibility genes and loci underlying various aspects of smoking behavior are largely unknown. Moreover, almost all reported genome-wide association studies (GWASs) have been performed on samples of European origin, limiting the applicability of the results to other ethnic populations. In this first GWAS on smoking behavior in an Asian population, after analyzing 8,842 DNA samples from the Korea Association Resource project with 352,228 single nucleotide polymorphisms (SNPs) genotyped for each sample, we identi... Human Genetics journals http://www.medworm.com/rss/comments.php?id=5342115 Mon, 17 Oct 2011 16:04:08 +0100 5342115 http://www.medworm.com/index.php?rid=5329096&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fp69674455478q073%2F In this study, two new technologies, resequencing array technology (ResAT) and next-generation sequencing (NGS), were used to analyze eight genes associated with syndromic AAD in 70 patients with non-syndromic AAD. Eighteen sequence variants were detected using both ResAT and NGS. In addition one of these sequence variants was detected by ResAT only and two additional variants by NGS only. Three of the 18 variants are likely to be pathogenic (in 4.3% of AAD patients and in 8.6% of a subset of patients with thoracic AAD), highlighting the importance of genetic analysis in non-syndromic AAD. ResAT and NGS similarly detected most, but not all, of the variants. Resequencing array technology was a rapid and efficient method for detecting most nucleotide substitutions, but was unable to de... Human Genetics journals http://www.medworm.com/rss/comments.php?id=5329096 Fri, 14 Oct 2011 15:44:52 +0100 5329096 http://www.medworm.com/index.php?rid=5329095&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fy163433xvp0v13q2%2F In conclusion, seizures were relatively more common in premutation carriers who presented clinically as probands of the family and seizures were commonly associated with ASD in these boys. Therefore, boys with the premutation, particularly if they are probands should be assessed carefully for both ASD and seizures. Content Type Journal ArticleCategory Original InvestigationPages 1-9DOI 10.1007/s00439-011-1106-6Authors Weerasak Chonchaiya, Medical Investigation of Neurodevelopmental Disorders (M.I.N.D.) Institute, University of California Davis Health System, 2825 50th Street, Sacramento, CA 95817, USAJacky Au, Medical Investigation of Neurodevelopmental Disorders (M.I.N.D.) Institute, University of California Davis Health System, 2825 50th Street, Sacramento, CA 95817, USAAndrea S... Human Genetics journals http://www.medworm.com/rss/comments.php?id=5329095 Fri, 14 Oct 2011 15:44:52 +0100 5329095 http://www.medworm.com/index.php?rid=5329097&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fu48w844341025540%2F We present a large scale analysis to identify candidate genes which may contain low-frequency recessive variation contributing to ASD while taking into account the potential contribution of population differences to the genetic heterogeneity of ASD. Our strategy, homozygous haplotype (HH) mapping, aims to detect homozygous segments of identical haplotype structure that are shared at a higher frequency amongst ASD patients compared to parental controls. The analysis was performed on 1,402 Autism Genome Project trios genotyped for 1 million single nucleotide polymorphisms (SNPs). We identified 25 known and 1,218 novel ASD candidate genes in the discovery analysis including CADM2, ABHD14A, CHRFAM7A, GRIK2, GRM3, EPHA3, FGF10, KCND2, PDZK1, IMMP2L and FOXP2. Furthermore, 10 of the previou... Human Genetics journals http://www.medworm.com/rss/comments.php?id=5329097 Thu, 13 Oct 2011 15:49:52 +0100 5329097 http://www.medworm.com/index.php?rid=5309492&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fv60335863667376p%2F Abstract  Facioscapulohumeral muscular dystrophy (FSHD) is the third most common muscular dystrophy after the dystrophinopathies and myotonic dystrophy and is associated with a typical pattern of muscle weakness. Most patients with FSHD carry a large deletion in the polymorphic D4Z4 macrosatellite repeat array at 4q35 and present with 1–10 repeats whereas non-affected individuals possess 11–150 repeats. An almost identical repeat array is present at 10q26 and the high sequence identity between these two arrays can cause difficulties in molecular diagnosis. Each 3.3-kb D4Z4 unit contains a DUX4 (double homeobox 4) gene that, among others, is activated upon contraction of the 4q35 repeat array due to the induction of chromatin remodelling of the 4qter region. A number of 4... Human Genetics journals http://www.medworm.com/rss/comments.php?id=5309492 Sat, 08 Oct 2011 15:43:34 +0100 5309492 http://www.medworm.com/index.php?rid=5300907&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fn45061m764088453%2F Abstract  Novel methodologies for detection of chromosomal abnormalities have been made available in the recent years but their clinical utility in prenatal settings is still unknown. We have conducted a comparative study of currently available methodologies for detection of chromosomal abnormalities after invasive prenatal sampling. A multicentric collection of a 1-year series of fetal samples with indication for prenatal invasive sampling was simultaneously evaluated using three screening methodologies: (1) karyotype and quantitative fluorescent polymerase chain reaction (QF-PCR), (2) two panels of multiplex ligation-dependent probe amplification (MLPA), and (3) chromosomal microarray-based analysis (CMA) with a targeted BAC microarray. A total of 900 pregnant women provi... Human Genetics journals http://www.medworm.com/rss/comments.php?id=5300907 Thu, 06 Oct 2011 06:29:24 +0100 5300907 http://www.medworm.com/index.php?rid=5300908&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Ft65lj8x383186557%2F In conclusion, GC and NADSYN1/DHCR7 loci individually and collectively contribute to variation in plasma vitamin D levels in Chinese Hans. Content Type Journal ArticleCategory Original InvestigationPages 1-8DOI 10.1007/s00439-011-1099-1Authors Ling Lu, Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 294 Tai-Yuan Rd., Shanghai, 200031 People’s Republic of ChinaHongguang Sheng, Endocrine Branch, The Central Hospital of Xuhui District, Shanghai, 200031 People’s Republic of ChinaHuaixing Li, Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 294 Tai-Yuan Rd., Shanghai, 200031 P... Human Genetics journals http://www.medworm.com/rss/comments.php?id=5300908 Wed, 05 Oct 2011 05:49:51 +0100 5300908 http://www.medworm.com/index.php?rid=5280061&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fg31m3k2785l21740%2F Abstract  Waardenburg syndrome (WS) is an auditory–pigmentary disorder resulting from melanocyte defects, with varying combinations of sensorineural hearing loss and abnormal pigmentation of the hair, skin, and inner ear. WS is classified into four subtypes (WS1–WS4) based on additional symptoms. PAX3 and SOX10 are two transcription factors that can activate the expression of microphthalmia-associated transcription factor (MITF), a critical transcription factor for melanocyte development. Mutations of PAX3 are associated with WS1 and WS3, while mutations of SOX10 cause WS2 and WS4. Recently, we identified some novel WS-associated mutations in PAX3 and SOX10 in a cohort of Chinese WS patients. Here, we further identified an E248fsX30 SOX10 mutation in a family of WS2. We an... Human Genetics journals http://www.medworm.com/rss/comments.php?id=5280061 Sat, 01 Oct 2011 06:45:55 +0100 5280061 http://www.medworm.com/index.php?rid=5280063&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F4213015303u58143%2F This study demonstrated the utility of next-generation sequencing in identifying genetic variants and loci associated with complex traits. Content Type Journal ArticleCategory Original InvestigationPages 1-8DOI 10.1007/s00439-011-1096-4Authors Jae-Jung Kim, Asan Institute for Life Sciences, University of Ulsan College of Medicine, 388-1 Pungnap-2-Dong, Songpa-Gu, Seoul, 138-736 KoreaYoung-Mi Park, Asan Institute for Life Sciences, University of Ulsan College of Medicine, 388-1 Pungnap-2-Dong, Songpa-Gu, Seoul, 138-736 KoreaKyu-Heum Baik, Macrogen Inc, Seoul, KoreaHye-Yeon Choi, Macrogen Inc, Seoul, KoreaGap-Seok Yang, Macrogen Inc, Seoul, KoreaInSong Koh, Department of Physiology, College of Medicine, Hanyang University, Seoul, KoreaJung-Ah Hwang, National Cancer Center, Goyang, Ko... Human Genetics journals http://www.medworm.com/rss/comments.php?id=5280063 Fri, 30 Sep 2011 05:50:14 +0100 5280063 http://www.medworm.com/index.php?rid=5280062&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fc627j28w3372221k%2F Abstract  In the National Cancer Institute Cancer Genetic Markers of Susceptibility (CGEMS) genome-wide association study of breast cancer, a single nucleotide polymorphism (SNP) marker, rs999737, in the 14q24.1 interval, was associated with breast cancer risk. In order to fine map this region, we imputed a 3.93 MB region flanking rs999737 for Stages 1 and 2 of the CGEMS study (5,692 cases, 5,576 controls) using the combined reference panels of the HapMap 3 and the 1000 Genomes Project. Single-marker association testing and variable-sized sliding-window haplotype analysis were performed, and for both analyses the initial tagging SNP rs999737 retained the strongest association with breast cancer risk. Investigation of contiguous regions did not reveal evidence for an ad... Human Genetics journals http://www.medworm.com/rss/comments.php?id=5280062 Fri, 30 Sep 2011 05:50:14 +0100 5280062 http://www.medworm.com/index.php?rid=5280064&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fb1436l32423w21q4%2F Content Type Journal ArticleCategory Book ReviewPages 1-2DOI 10.1007/s00439-011-1097-3Authors John Dupré, ESRC Centre for Genomics in Society (Egenis), University of Exeter, Byrne House, St. German’s Road, Exeter, EX4 4PJ, UK Journal Human GeneticsOnline ISSN 1432-1203Print ISSN 0340-6717 (Source: Human Genetics) Human Genetics journals http://www.medworm.com/rss/comments.php?id=5280064 Fri, 30 Sep 2011 05:50:12 +0100 5280064 http://www.medworm.com/index.php?rid=5256152&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fp5mp66816506grr8%2F Abstract  Arsenic is a carcinogen that contaminates drinking water worldwide. Accumulating evidence suggests that both exposure and genetic factors may influence susceptibility to arsenic-induced malignancies. We sought to identify novel susceptibility loci for arsenic-related bladder cancer in a US population with low to moderate drinking water levels of arsenic. We first screened a subset of bladder cancer cases using a panel of approximately 10,000 non-synonymous single nucleotide polymorphisms (SNPs). Top ranking hits on the SNP array then were considered for further analysis in our population-based case–control study (n = 832 cases and 1,191 controls). SNPs in the fibrous sheath interacting protein 1 (FSIP1) gene (rs10152640) and the solute carrier family 39,... Human Genetics journals http://www.medworm.com/rss/comments.php?id=5256152 Sat, 24 Sep 2011 15:46:55 +0100 5256152 http://www.medworm.com/index.php?rid=5256153&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fx6083731222391g6%2F Abstract  Bone size (BS) is one of the major risk factors for osteoporotic fractures. BS variation is genetically determined to a substantial degree with heritability over 50%, but specific genes underlying variation of BS are still largely unknown. To identify specific genes for BS in Chinese, initial genome-wide association scan (GWAS) study and follow-up replication study were performed. In initial GWAS study, a group of 12 contiguous single-nucleotide polymorphism (SNP)s, which span a region of ~25 kb and locate at the upstream of HMGN3 gene (high-mobility group nucleosomal binding domain 3), achieved moderate association signals for spine BS, with P values ranging from 6.2E−05 to 1.8E−06. In the follow-up replication study, eight of the 12 SNPs were detected su... Human Genetics journals http://www.medworm.com/rss/comments.php?id=5256153 Sat, 24 Sep 2011 15:46:54 +0100 5256153 http://www.medworm.com/index.php?rid=5244738&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fk227x16w77240kj2%2F In this study, we set out to examine this association using a different population. We first performed a gene-centric association study of the KCNJ3 gene, by genotyping 38 tagSNPs in the Chinese population. We detected nine SNPs that displayed significant association with schizophrenia (lowest P = 0.0016 for rs3106658, Global significance = 0.036). The initial marker SNP (rs3106653) examined in our prior GWAS in the Japanese population also showed nominally significant association in the Chinese population (P = 0.028). Next, we analyzed transcript levels in the dorsolateral prefrontal cortex of postmortem brains from patients with schizophrenia and bipolar disorder and from healthy controls, using real-time quantitative RT-PCR. We found significantly lowe... Human Genetics journals http://www.medworm.com/rss/comments.php?id=5244738 Sat, 17 Sep 2011 05:52:37 +0100 5244738 http://www.medworm.com/index.php?rid=5231302&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F2hqj1l5175666552%2F Abstract  Over the last decade, the search for gene variants with the potential to influence transplant outcomes or predispose individuals to host–recipient-related phenotypes has generated a considerable number of studies with conflicting results. Thousands of genotypes have been associated with complex traits related to transplant medicine, including acute rejection, immunosuppressive drug metabolism and side effects, infections, long-term outcomes, and cardiovascular complications. However, these efforts have given disappointing results, both in terms of gaining understanding of the biological basis of disease and in patient management. The methodological weaknesses that constitute the major limitations of most of these studies have been discussed widely. A new generat... Human Genetics journals http://www.medworm.com/rss/comments.php?id=5231302 Fri, 16 Sep 2011 05:48:14 +0100 5231302 http://www.medworm.com/index.php?rid=5231303&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F2231236823214m87%2F Content Type Journal ArticleCategory Book ReviewPages 1-2DOI 10.1007/s00439-011-1091-9Authors Reinhardt Rüdel, Division of Neurophysiology, Ulm University, Ulm, Germany Journal Human GeneticsOnline ISSN 1432-1203Print ISSN 0340-6717 (Source: Human Genetics) Human Genetics journals http://www.medworm.com/rss/comments.php?id=5231303 Thu, 15 Sep 2011 05:47:59 +0100 5231303 http://www.medworm.com/index.php?rid=5231304&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fc5766516510t1349%2F In this study, we describe an autosomal recessive family that presents with a progressive and early-onset form of generalized dystonia. The nuclear family consists of two healthy parents and two affected daughters. To elucidate the genetic causes underlying disease, whole-exome sequencing analysis was performed in one affected sibling, followed by validation, biochemical analyses and MRI brain imaging. A homozygous, disease-segregating mutation (p.Val400Met) was identified in the glutaryl-CoA dehydrogenase (GCDH) gene at chromosome 19p13. The mutation, in an amino acid that is highly conserved among species, was absent in large number of neurologically normal individuals. Biochemical analyses demonstrated increased 3-hydroxy glutaric acid present in urine samples from both patients. ... Human Genetics journals http://www.medworm.com/rss/comments.php?id=5231304 Mon, 12 Sep 2011 15:52:00 +0100 5231304 http://www.medworm.com/index.php?rid=5216622&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Ft42u35072ux32313%2F Content Type Journal ArticleCategory Book ReviewPages 1-2DOI 10.1007/s00439-011-1087-5Authors Abeer Alsaegh, Princess Anne Hospital, Level G, Mailpoint 105, Coxford Road, Southampton, SO16 5YA UKDiana M. Eccles, Faculty of Medicine, University of Southampton, Southampton University Hospitals, NHS Trust MP824, Southampton, SO16 6YD UK Journal Human GeneticsOnline ISSN 1432-1203Print ISSN 0340-6717 (Source: Human Genetics) Human Genetics journals http://www.medworm.com/rss/comments.php?id=5216622 Sat, 10 Sep 2011 06:03:30 +0100 5216622 http://www.medworm.com/index.php?rid=5216623&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fa67u0564v55j5g81%2F Abstract  We have surveyed 15 high-altitude adaptation candidate genes for signals of positive selection in North Caucasian highlanders using targeted re-sequencing. A total of 49 unrelated Daghestani from three ethnic groups (Avars, Kubachians, and Laks) living in ancient villages located at around 2,000 m above sea level were chosen as the study population. Caucasian (Adygei living at sea level, N = 20) and CEU (CEPH Utah residents with ancestry from northern and western Europe; N = 20) were used as controls. Candidate genes were compared with 20 putatively neutral control regions resequenced in the same individuals. The regions of interest were amplified by long-PCR, pooled according to individual, indexed by adding an eight-nucleotide tag, and se... Human Genetics journals http://www.medworm.com/rss/comments.php?id=5216623 Fri, 09 Sep 2011 05:59:03 +0100 5216623 http://www.medworm.com/index.php?rid=5189773&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fr29633574748j103%2F Abstract  Postaxial Polydactyly (PAP) is characterized by fifth digit duplication in hands and/or feet. Two types of PAP including PAP-A, representing the development of well-formed extra digit, and PAP-B, representing the presence of rudimentary fifth digit, have been described. Both isolated and syndromic forms of PAP have been reported. Isolated forms of PAP usually segregate as an autosomal dominant trait and to date four loci have been identified. In the present study, we have described mapping of the first locus of autosomal recessive PAP type A on chromosome 13q13.3–13q21.2 in a consanguineous Pakistani family. Using polymorphic microsatellite markers, the disease locus was mapped to a 17.87-cM (21.13 Mb) region flanked by markers D13S1288 and D13S632, on chro... Human Genetics journals http://www.medworm.com/rss/comments.php?id=5189773 Mon, 29 Aug 2011 15:58:01 +0100 5189773 http://www.medworm.com/index.php?rid=5189774&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fqmp76p4t46958352%2F Abstract  Alström syndrome is a clinically complex disorder characterized by childhood retinal degeneration leading to blindness, sensorineural hearing loss, obesity, type 2 diabetes mellitus, cardiomyopathy, systemic fibrosis, and pulmonary, hepatic, and renal failure. Alström syndrome is caused by recessively inherited mutations in the ALMS1 gene, which codes for a putative ciliary protein. Alström syndrome is characterized by extensive allelic heterogeneity, however, founder effects have been observed in some populations. To date, more than 100 causative ALMS1 mutations have been identified, mostly frameshift and non-sense alterations resulting in termination signals in ALMS1. Here, we report a complex Turkish kindred in which sequence analysis uncovered an insertion of ... Human Genetics journals http://www.medworm.com/rss/comments.php?id=5189774 Mon, 29 Aug 2011 15:57:59 +0100 5189774 http://www.medworm.com/index.php?rid=5189775&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fq5v2q88817wu671x%2F This study identifies, for the first time, the fatty acid metabolism disruption in EBS. Content Type Journal ArticleCategory Original InvestigationPages 1-14DOI 10.1007/s00439-011-1077-7Authors Mbarka Bchetnia, Département des sciences fondamentales, Université du Québec à Chicoutimi, Saguenay, CanadaMarie-Lou Tremblay, Département des sciences fondamentales, Université du Québec à Chicoutimi, Saguenay, CanadaGeorgette Leclerc, Centre de santé et de services sociaux de Chicoutimi, Saguenay, CanadaAudrey Dupérée, Centre de santé et de services sociaux de Chicoutimi, Saguenay, CanadaJulie Powell, Hôpital Sainte-Justine, Montréal, CanadaCatherine McCuaig, Hôpital Sainte-Justine, Montréal, CanadaCharles Morin, Centre de santé et de services sociaux de Chicoutimi, Saguen... Human Genetics journals http://www.medworm.com/rss/comments.php?id=5189775 Mon, 29 Aug 2011 15:57:58 +0100 5189775 http://www.medworm.com/index.php?rid=5167582&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F15875853j80l3807%2F Abstract  The proportion of never smoker non-small cell lung cancer (NSCLC) in Asia is about 30–40%. Despite the striking demographics and high prevalence of never smoker NSCLC, the exact causes still remain undetermined. Although several genome wide association (GWA) studies were conducted to find susceptibility loci for lung cancer in never smokers, no regions were replicated except for 5p15.33, suggesting locus heterogeneity and different environmental toxic effects. To identify genetic loci associated with susceptibility of lung cancer in never smokers, we performed a GWA analysis using the Affymetrix 6.0 SNP array. For discovery GWA set, we recruited 446 never smoking Korean patients with NSCLC and 497 normal subjects. We tested association of SNPs with lung cancer s... Human Genetics journals http://www.medworm.com/rss/comments.php?id=5167582 Wed, 24 Aug 2011 16:03:54 +0100 5167582 http://www.medworm.com/index.php?rid=5167581&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F9462566m25725728%2F Abstract  Schizophrenia is a complex genetic disorder. Gene set-based analytic (GSA) methods have been widely applied for exploratory analyses of large, high-throughput datasets, but less commonly employed for biological hypothesis testing. Our primary hypothesis is that variation in ion channel genes contribute to the genetic susceptibility to schizophrenia. We applied Exploratory Visual Analysis (EVA), one GSA application, to analyze European-American (EA) and African-American (AA) schizophrenia genome-wide association study datasets for statistical enrichment of ion channel gene sets, comparing GSA results derived under three SNP-to-gene mapping strategies: (1) GENIC; (2) 500-Kb; (3) 2.5-Mb and three complimentary SNP-to-gene statistical reduction methods: (1) minimum p ... Human Genetics journals http://www.medworm.com/rss/comments.php?id=5167581 Wed, 24 Aug 2011 16:03:54 +0100 5167581 http://www.medworm.com/index.php?rid=5153415&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fa8m4l35368124785%2F Abstract  Men and women differ in susceptibility to many diseases and in responses to treatment. Recent advances in genome-wide association studies (GWAS) provide a wealth of data for associating genetic profiles with disease risk; however, in general, these data have not been systematically probed for sex differences in gene-disease associations. Incorporating sex into the analysis of GWAS results can elucidate new relationships between single nucleotide polymorphisms (SNPs) and human disease. In this study, we performed a sex-differentiated analysis on significant SNPs from GWAS data of the seven common diseases studied by the Wellcome Trust Case Control Consortium. We employed and compared three methods: logistic regression, Woolf’s test of heterogeneity, and a novel s... Human Genetics journals http://www.medworm.com/rss/comments.php?id=5153415 Fri, 19 Aug 2011 15:53:18 +0100 5153415 http://www.medworm.com/index.php?rid=5153416&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fhjw78n63j854h215%2F Abstract  There is increasing evidence suggesting that higher intakes of fish or n-3 polyunsaturated fatty acids supplements may decrease the risk of preterm delivery (PTD). We hypothesized that genetic variants of the enzymes critical to fatty acids biosynthesis and metabolism may be associated with PTD. We genotyped 231 potentially functional single nucleotide polymorphisms (SNPs) and tagSNPs in 9 genes (FADS1, FADS2, PTGS1, PTGS2, ALOX5, ALOX5AP, PTGES, PTGES2, and PTGES3) among 1,110 black mothers, including 542 mothers who delivered preterm (<37 weeks gestation) and 568 mothers who delivered full-term babies (≥37 weeks gestation) at Boston Medical Center. After excluding SNPs that are in complete linkage disequilibrium or have lower minor allele frequency... Human Genetics journals http://www.medworm.com/rss/comments.php?id=5153416 Wed, 17 Aug 2011 06:05:46 +0100 5153416 http://www.medworm.com/index.php?rid=5136754&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fp60701368058778m%2F Abstract  Holprosencephaly (HPE) is the most common disorder of the developing forebrain in humans, and is characterized by varying degrees of abnormal union of the cerebral hemispheres. These defects are typically co-associated with midline craniofacial anomalies. The combination of forebrain and craniofacial defects that comprise HPE can present along a broad and variable phenotypic spectrum. Both the SHH and NODAL signaling pathways play important roles in the pathogenesis of this disorder. Disruption of these pathways by chromosomal rearrangements, mutations in pathway-related genes and/or biochemical alterations are proposed to contribute to HPE in a large number of patients. Additional factors that are not yet fully delineated are also very likely to be involved in th... Human Genetics journals http://www.medworm.com/rss/comments.php?id=5136754 Sat, 13 Aug 2011 06:15:03 +0100 5136754 http://www.medworm.com/index.php?rid=5105664&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Frx9753g3767w71h4%2F Abstract  Development of protective immunity against Plasmodium falciparum is partially mediated through binding of malaria-specific IgG to Fc gamma (γ) receptors. Variations in human FcγRIIA-H/R-131 and FcγRIIIB-NA1/NA2 affect differential binding of IgG sub-classes. Since variability in FcγR may play an important role in severe malarial anemia (SMA) pathogenesis by mediating phagocytosis of red blood cells and triggering cytokine production, the relationship between FcγRIIA-H/R131 and FcγRIIIB-NA1/NA2 haplotypes and susceptibility to SMA (Hb < 6.0 g/dL) was investigated in Kenyan children (n = 528) with acute malaria residing in a holoendemic P. falciparum transmission region. In addition, the association between carriage of the haplotypes ... Human Genetics journals http://www.medworm.com/rss/comments.php?id=5105664 Fri, 05 Aug 2011 05:58:10 +0100 5105664 http://www.medworm.com/index.php?rid=5105665&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fu1u0g1u14k7h7650%2F This article describes the consequences of using residual human material from different sources in distinct situations and why signed informed consent is not always the preferred choice of individual countries regarding the use of residual material. In addition, signed informed consent is overdone when using residual tissues in medical research. We maintain that the opt-out system is a balanced choice if certain requirements are met, relating to sufficient transparency about using residual tissue for research, the purpose of such research and to the confidentiality of the data used in that research. Finally, the international exchange of samples can be based on the laws and regulations of the countries of origin. Respecting these form the basis of what can and cannot be done in the c... Human Genetics journals http://www.medworm.com/rss/comments.php?id=5105665 Thu, 04 Aug 2011 15:31:52 +0100 5105665 http://www.medworm.com/index.php?rid=5084507&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fn2355n06l2665811%2F Abstract  Although gene-free areas compose the great majority of eukaryotic genomes, a significant fraction of genes overlaps, i.e., unique nucleotide sequences are part of more than one transcription unit. In this work, the evolutionary history and origin of a same-strand gene overlap is dissected through the analysis of COG8 (component of oligomeric Golgi complex 8) and PDF (peptide deformylase). Comparative genomic surveys reveal that the relative locations of these two genes have been changing over the last 445 million years from distinct chromosomal locations in fish to overlapping in rodents and primates, indicating that the overlap between these genes precedes their divergence. The overlap between the two genes was initiated by the gain of a novel splice donor site be... Human Genetics journals http://www.medworm.com/rss/comments.php?id=5084507 Fri, 29 Jul 2011 16:02:58 +0100 5084507 http://www.medworm.com/index.php?rid=5084506&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fx324l0017rp35378%2F We present simulation studies based on Multi-Ethnic Study of Atherosclerosis (MESA) pedigree structures to compare the performance of several popular methods of GWA analysis for both quantitative and dichotomous traits in cohort studies. We evaluate approaches suitable for analysis of families, and combined the best performing methods with population-based samples either by meta-analysis, or by pooled analysis of family- and population-based samples (mega-analysis), comparing type 1 error and power. We further assess practical considerations, such as availability of software and ability to incorporate covariates in statistical modeling, and demonstrate our recommended approaches through quantitative and binary trait analysis of HDL cholesterol (HDL-C) in 2,553 MESA family- and popula... Human Genetics journals http://www.medworm.com/rss/comments.php?id=5084506 Fri, 29 Jul 2011 16:02:58 +0100 5084506 http://www.medworm.com/index.php?rid=5084508&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fk858w417w160475q%2F In this study, the largest of pure interstitial and terminal deletions of 1q43q44 to date, we characterized 22 individuals by high-resolution oligonucleotide microarray-based comparative genomic hybridization. We propose critical regions and candidate genes for the MIC, ACC, and SZR phenotypes associated with this microdeletion syndrome. Three cases with MIC had small overlapping or intragenic deletions of AKT3, an isoform of the protein kinase B family. The deletion of only AKT3 in two cases implicates haploinsufficiency of this gene in the MIC phenotype. Likewise, based on the smallest region of overlap among the affected individuals, we suggest a critical region for ACC that contains ZNF238, a transcriptional and chromatin regulator highly expressed in the developing and adult brain... Human Genetics journals http://www.medworm.com/rss/comments.php?id=5084508 Thu, 28 Jul 2011 15:54:41 +0100 5084508 http://www.medworm.com/index.php?rid=5075060&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fx38jq152p9105431%2F Abstract  Modern day Latin America resulted from the encounter of Europeans with the indigenous peoples of the Americas in 1492, followed by waves of migration from Europe and Africa. As a result, the genomic structure of present day Latin Americans was determined both by the genetic structure of the founding populations and the numbers of migrants from these different populations. Here, we analyzed DNA collected from two well-established communities in Colorado (33 unrelated individuals) and Ecuador (20 unrelated individuals) with a measurable prevalence of the BRCA1 c.185delAG and the GHR c.E180 mutations, respectively, using Affymetrix Genome-wide Human SNP 6.0 arrays to identify their ancestry. These mutations are thought to have been brought to these communities by Seph... Human Genetics journals http://www.medworm.com/rss/comments.php?id=5075060 Mon, 25 Jul 2011 15:45:24 +0100 5075060 http://www.medworm.com/index.php?rid=5060897&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Ff7g832q61833l244%2F Abstract  The future holds the possibility to link and network biobanks, existing biorepositories and reference databases for research purposes in ways that have not been possible before. There is the potential to develop 'research portals' that will enable researchers to access these research resources that are located around the globe with the click of a mouse. In this paper, I will argue that our current governance system for research is unable to provide all of the oversight and accountability mechanisms that are required for this new way of doing research that is based upon flows of data across international borders. For example, our current governance framework for research is nationally based, with a complex system of laws, policies and practice that can be unique to... Human Genetics journals http://www.medworm.com/rss/comments.php?id=5060897 Fri, 22 Jul 2011 17:06:26 +0100 5060897 http://www.medworm.com/index.php?rid=5060898&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F2794630041647364%2F Content Type Journal ArticlePages 1-4DOI 10.1007/s00439-011-1067-9Authors Bartha Maria Knoppers, Centre of Genomics and Policy, McGill University and Genome Quebec Innovation Centre, Montreal, QC, CanadaThomas J. Hudson, Ontario Institute for Cancer Research, 101 College Street, Toronto, ON, Canada Journal Human GeneticsOnline ISSN 1432-1203Print ISSN 0340-6717 (Source: Human Genetics) Human Genetics journals http://www.medworm.com/rss/comments.php?id=5060898 Thu, 21 Jul 2011 18:03:16 +0100 5060898 http://www.medworm.com/index.php?rid=5060899&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fn037t827n2634040%2F Abstract  This paper surveys the current state of knowledge about the relationship between different national publics and biobanks, how different publics perceive biobanks, and which issues are identified as important by various stakeholders. We discuss existing studies and emerging governance strategies dealing with the biobank–publics interface and argue that the search for phantom (biobank) public(s) is on, but still much needs to be done. We argue that the existing data originate in a relatively few regions, among them Northern Europe, the United Kingdom, and in certain U.S. states and are often based on survey research with small samples and short questionnaires. Combined usage of qualitative and quantitative methodology in studies is still rare though of great impor... Human Genetics journals http://www.medworm.com/rss/comments.php?id=5060899 Tue, 19 Jul 2011 23:22:51 +0100 5060899 http://www.medworm.com/index.php?rid=5060900&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F64g8n580p6557752%2F Content Type Journal ArticlePages 1-2DOI 10.1007/s00439-011-1070-1Authors Peter S. Harper, Institute of Medical Genetics, School of Medicine, Cardiff University, Heath Park, Cardiff, CF14 4XN UK Journal Human GeneticsOnline ISSN 1432-1203Print ISSN 0340-6717 (Source: Human Genetics) Human Genetics journals http://www.medworm.com/rss/comments.php?id=5060900 Tue, 19 Jul 2011 23:22:50 +0100 5060900 http://www.medworm.com/index.php?rid=5060901&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fy152k71u25x12483%2F We describe a male patient (patient DGAP113) with a balanced translocation, 46,XY,t(1;3)(q31.3;q13.13), severe bilateral congenital cataracts, CNS abnormalities and mild developmental delay. Fluorescence in situ hybridization (FISH) and suppression PCR demonstrated that the chromosome 3 breakpoint lies ~515 kb upstream of the PVRL3 gene, while the chromosome 1 breakpoint lies ~50 kb upstream of the NEK7 gene. Despite the fact that NEK7 is closer to a translocation breakpoint than PVRL3, NEK7 transcript levels are unaltered in patient DGAP113 lymphoblastoid cells and Nek7-deficient mice exhibit no detectable ocular phenotype. In contrast, the expression of PVRL3, which encodes the cell adhesion protein Nectin 3, is significantly reduced in patient DGAP113 lymphoblastoid cells, l... Human Genetics journals http://www.medworm.com/rss/comments.php?id=5060901 Tue, 19 Jul 2011 06:40:24 +0100 5060901 http://www.medworm.com/index.php?rid=5056604&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fg90l038u61111818%2F Content Type Journal ArticlePages 1-1DOI 10.1007/s00439-011-1069-7Authors Michael A. Quail, The Wellcome Trust Sanger Institute, Room H134, Wellcome Trust Genome Campus, Hinxton, Cambs, CB10 1SA UK Journal Human GeneticsOnline ISSN 1432-1203Print ISSN 0340-6717 (Source: Human Genetics) Human Genetics journals http://www.medworm.com/rss/comments.php?id=5056604 Mon, 18 Jul 2011 15:53:26 +0100 5056604 http://www.medworm.com/index.php?rid=5046565&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fy8741t3236345pt7%2F This article critically analyses this policy-driven phenomenon asking how effectively policy—often as an alternative to law—serves to police and to promote biobanking. It argues that a policy of reflexive governance—defined and developed herein—can best meet the challenges faced by many biobanks and without the need for recourse to law. Content Type Journal ArticlePages 1-10DOI 10.1007/s00439-011-1066-xAuthors Graeme Laurie, The Arts and Humanities Research Council (AHRC) Research Centre for Studies in Intellectual Property and Technology Law, School of Law, University of Edinburgh, Old College, South Bridge, Edinburgh, EH8-9YL Scotland, UK Journal Human GeneticsOnline ISSN 1432-1203Print ISSN 0340-6717 (Source: Human Genetics) Human Genetics journals http://www.medworm.com/rss/comments.php?id=5046565 Fri, 15 Jul 2011 15:58:15 +0100 5046565 http://www.medworm.com/index.php?rid=5046566&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F326305628433368v%2F Abstract  We performed homozygosity mapping in a consanguineous Pakistani family segregating autosomal-recessive congenital cataracts and identified linkage to a 3.03 Mb locus on chromosome 6p24 containing the GCNT2 gene. GCNT2 encodes glucosaminyl (N-acetyl) transferase 2, an enzyme responsible for the formation of the blood group I antigen. Rare biallelic GCNT2 mutations have been shown to cause the association of congenital cataracts and the adult i blood group, making GCNT2 the prime candidate gene for the observed phenotype. Indeed, we identified a homozygous deletion segregating with cataracts that encompasses exons 1B, 1C, 2 and 3 of GCNT2. Long-range polymerase chain reaction and breakpoint sequencing revealed that affected individuals in this and in a second, app... Human Genetics journals http://www.medworm.com/rss/comments.php?id=5046566 Thu, 14 Jul 2011 16:48:46 +0100 5046566 http://www.medworm.com/index.php?rid=5046567&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fj04750333v88h415%2F Abstract  Colorectal cancer is the second leading cause of cancer death in developed countries. Genome-wide association studies (GWAS) have successfully identified novel susceptibility loci for colorectal cancer. To follow up on these findings, and try to identify novel colorectal cancer susceptibility loci, we present results for GWAS of colorectal cancer (2,906 cases, 3,416 controls) that have not previously published main associations. Specifically, we calculated odds ratios and 95% confidence intervals using log-additive models for each study. In order to improve our power to detect novel colorectal cancer susceptibility loci, we performed a meta-analysis combining the results across studies. We selected the most statistically significant single nucleotide polymorphisms... Human Genetics journals http://www.medworm.com/rss/comments.php?id=5046567 Thu, 14 Jul 2011 16:48:45 +0100 5046567 http://www.medworm.com/index.php?rid=5046568&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F22074330860u3010%2F Abstract  Ethical principles guiding public health and genomic medicine are often at odds: whereas public health practice adopts collectivist principles that emphasize population-based benefits, recent advances in genomic and personalized medicine are grounded in an individualist ethic that privileges informed consent, and the balancing of individual risk and benefit. Indeed, the attraction of personalized medicine is the promise it holds out to help individuals get the “right medicine for the right problem at the right time.” Research biobanks are an effective tool in the genomic medicine toolbox. Biobanking in public health presents a unique case study to unpack some of these issues in more detail. For example, there is a long history of using banked tissue obtained u... Human Genetics journals http://www.medworm.com/rss/comments.php?id=5046568 Thu, 14 Jul 2011 16:48:44 +0100 5046568 http://www.medworm.com/index.php?rid=5046569&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F153456713mj09864%2F Abstract  In terms of sample exchange, international collaborations between biobanks, or between biobanks and their research partners, have two important aspects. First, the donors’ consent usually implies that the scope and purpose of any sample transfer to third parties is subject to major constraints. Since the legal, ethical and political framework of biobanking may differ substantially, even between countries of comparable jurisdictional systems, general rules for the international sharing of biomaterial are difficult, if not impossible, to define. Issues of uncertainty include the right to transfer the material, the scope of research allowed, and intellectual property rights. Since suitable means of international law enforcement may not be available in the context o... Human Genetics journals http://www.medworm.com/rss/comments.php?id=5046569 Thu, 14 Jul 2011 16:48:43 +0100 5046569 http://www.medworm.com/index.php?rid=5034564&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F468j16252lj6k32t%2F Abstract  Avoiding disease, maintaining physical and cognitive function, and continued social engagement in long-lived individuals describe successful aging (SA). Mitochondrial lineages described by patterns of common genetic variants (“haplogroups”) have been associated with increased longevity in different populations. We investigated the influence of mitochondrial haplogroups on SA in an Amish community sample. Cognitively intact volunteers aged ≥80 years (n = 261) were enrolled in a door-to-door survey of Amish communities in Indiana and Ohio. Individuals scoring in the top third for lower extremity function, needing little assistance with self-care tasks, having no depression symptoms, and expressing high life satisfaction were considered SA (n&nbsp... Human Genetics journals http://www.medworm.com/rss/comments.php?id=5034564 Wed, 13 Jul 2011 06:17:33 +0100 5034564 http://www.medworm.com/index.php?rid=5034565&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fx3805u2012277411%2F Abstract  For the last 20 years, preimplantation genetic diagnosis (PGD) has been mostly performed on cleavage stage embryos after the biopsy of 1–2 cells and PCR and FISH have been used for the diagnosis. The main indications have been single gene disorders and inherited chromosome abnormalities. Preimplantation genetic screening (PGS) for aneuploidy is a technique that has used PGD technology to examine chromosomes in embryos from couples undergoing IVF with the aim of helping select the chromosomally ‘best’ embryo for transfer. It has been applied to patients of advanced maternal age, repeated implantation failure, repeated miscarriages and severe male factor infertility. Recent randomised controlled trials (RCTs) have shown that PGS performed on cleavage stag... Human Genetics journals http://www.medworm.com/rss/comments.php?id=5034565 Tue, 12 Jul 2011 06:07:46 +0100 5034565 http://www.medworm.com/index.php?rid=5034566&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fn31x063816t63685%2F Abstract  The X-linked cyclin-dependent kinase-like 5 (CDKL5) gene is an important molecular determinant of early-onset intractable seizures with infantile spasms and Rett syndrome-like phenotype. The gene encodes a kinase that may influence components of molecular pathways associated with MeCP2. In humans there are two previously reported splice variants that differ in the 5′ untranslated exons and produce the same 115 kDa protein. Furthermore, very recently, a novel transcript including a novel exon (16b) has been described. By aligning both the human and mouse CDKL5 proteins to the orthologs of other species, we identified a theoretical 107 kDa isoform with an alternative C-terminus that terminates in intron 18. In human brain and all other tissues investigate... Human Genetics journals http://www.medworm.com/rss/comments.php?id=5034566 Tue, 12 Jul 2011 06:07:44 +0100 5034566 http://www.medworm.com/index.php?rid=5015980&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fa470784073666533%2F Abstract  Copy number variations (CNVs) have provided a dynamic aspect to the apparently static human genome. We have analyzed CNVs larger than 100 kb in 477 healthy individuals from 26 diverse Indian populations of different linguistic, ethnic and geographic backgrounds. These CNVRs were identified using the Affymetrix 50K Xba 240 Array. We observed 1,425 and 1,337 CNVRs in the deletion and amplification sets, respectively, after pooling data from all the populations. More than 50% of the genes encompassed entirely in CNVs had both deletions and amplifications. There was wide variability across populations not only with respect to CNV extent (ranging from 0.04–1.14% of genome under deletion and 0.11–0.86% under amplification) but also in terms of functional enrich... Human Genetics journals http://www.medworm.com/rss/comments.php?id=5015980 Sat, 09 Jul 2011 06:21:12 +0100 5015980 http://www.medworm.com/index.php?rid=5015981&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F15x1353n3r324x5n%2F Content Type Journal ArticlePages 1-2DOI 10.1007/s00439-011-1059-9Authors Peter S. Harper, Institute of Medical Genetics, School of Medicine, Cardiff University, Heath Park, Cardiff, CF14 4XN UK Journal Human GeneticsOnline ISSN 1432-1203Print ISSN 0340-6717 (Source: Human Genetics) Human Genetics journals http://www.medworm.com/rss/comments.php?id=5015981 Fri, 08 Jul 2011 06:30:13 +0100 5015981 http://www.medworm.com/index.php?rid=5015982&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fg842q5587v250k55%2F Abstract  The collection and sharing of person-specific biospecimens has raised significant questions regarding privacy. In particular, the question of identifiability, or the degree to which materials stored in biobanks can be linked to the name of the individuals from which they were derived, is under scrutiny. The goal of this paper is to review the extent to which biospecimens and affiliated data can be designated as identifiable. To achieve this goal, we summarize recent research in identifiability assessment for DNA sequence data, as well as associated demographic and clinical data, shared via biobanks. We demonstrate the variability of the degree of risk, the factors that contribute to this variation, and potential ways to mitigate and manage such risk. Finally, we di... Human Genetics journals http://www.medworm.com/rss/comments.php?id=5015982 Fri, 08 Jul 2011 06:30:12 +0100 5015982 http://www.medworm.com/index.php?rid=5015983&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fw838p2316n12h536%2F Abstract  X-chromosome inactivation (XCI) is an essential mechanism in females that compensates for the genome imbalance between females and males. It is known that XCI can spread into an autosome of patients with X;autosome translocations. The subject was a 5-year-old boy with Prader–Willi syndrome (PWS)-like features including hypotonia, hypo-genitalism, hypo-pigmentation, and developmental delay. G-banding, fluorescent in situ hybridization, BrdU-incorporated replication, human androgen receptor gene locus assay, SNP microarrays, ChIP-on-chip assay, bisulfite sequencing, and real-time RT-PCR were performed. Cytogenetic analyses revealed that the karyotype was 46,XY,der(X)t(X;15)(p21.1;q11.2),−15. In the derivative chromosome, the X and half of the chromosome 15 segme... Human Genetics journals http://www.medworm.com/rss/comments.php?id=5015983 Thu, 07 Jul 2011 05:43:48 +0100 5015983 http://www.medworm.com/index.php?rid=5015984&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F5523352q80273u76%2F Abstract  Atrial fibrillation (AF) affects more than 5 million people worldwide; however, none of the anti-arrhythmic drugs available now are entirely optimal in terms of efficacy and safety. A better understanding of the molecular mechanism of AF will facilitate the process of finding new strategies to prevent AF. As the non-familial AF is the major form of AF, identifying common variants for AF in these populations by genome-wide association studies will definitely accelerate this process. This review summarizes the recently identified common AF variants on 4q25, 16q22, and 1q21 and discusses their implications for the clinic. Content Type Journal ArticlePages 1-7DOI 10.1007/s00439-011-1052-3Authors Xinyuan Liu, Department of Pediatrics, Tongji Hospital, Tongji ... Human Genetics journals http://www.medworm.com/rss/comments.php?id=5015984 Thu, 07 Jul 2011 05:43:47 +0100 5015984 http://www.medworm.com/index.php?rid=5015985&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fl3649h70407l0123%2F Abstract  Increasing experimental evidence supports a connection between inflammation and mitochondrial dysfunction. Both acute and chronic inflammatory diseases course with elevated free radicals production that may affect mitochondrial proteins, lipids, and mtDNA. The subsequent mitochondrial impairment produces more reactive oxygen species that further reduce the ATP generation, increasing the probability of cell death. Mitochondrial impairment in now considered a key factor in inflammation because (1) there are specific pathologies directly derived from mtDNA mutations, causing chronic inflammatory diseases such as neuromuscular and neurodegenerative disorders, (2) there are neurodegenerative, metabolic, and other inflammatory diseases in which their progression is acco... Human Genetics journals http://www.medworm.com/rss/comments.php?id=5015985 Thu, 07 Jul 2011 05:43:46 +0100 5015985 http://www.medworm.com/index.php?rid=5015986&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fu33575676x31lqh8%2F Abstract  Including previously genotyped controls in a genome-wide association study can provide cost-savings, but can also create design biases. When cases and controls are genotyped on different platforms, the imputation needed to provide genome-wide coverage will introduce differential measurement error and may lead to false positives. We compared genotype frequencies of two healthy control groups from the Nurses’ Health Study genotyped on different platforms [Affymetrix 6.0 (n = 1,672) and Illumina HumanHap550 (n = 1,038)]. Using standard imputation quality filters, we observed 9,841 single-nucleotide polymorphisms (SNPs) out of 2,347,809 (0.4%) significant at the 5 × 10−8 level. We explored three methods for controlling for this Type I ... Human Genetics journals http://www.medworm.com/rss/comments.php?id=5015986 Thu, 07 Jul 2011 05:43:45 +0100 5015986 http://www.medworm.com/index.php?rid=5015987&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fkl567r0r223066x2%2F Abstract  Contrasting results have been reported concerning the association of a splice-site polymorphism (rs10774671) in OAS1 with multiple sclerosis (MS). We analysed two OAS1 regions encompassing alternatively spliced exons. While the region carrying the splice-site variant is neutrally evolving, a signature of long-standing balancing selection was observed across an alternative exon 7. Analysis of variants in this exon identified an insertion/deletion polymorphism (rs11352835, A/−) that originates predicted products with distinct C termini. This variant is located along the major branch of the haplotype genealogy, suggesting that it may represent the selection target. A case/control study for MS indicated that rs11352835 is associated with disease susceptibility (for an... Human Genetics journals http://www.medworm.com/rss/comments.php?id=5015987 Thu, 07 Jul 2011 05:43:44 +0100 5015987 http://www.medworm.com/index.php?rid=5015988&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Ft41q770m17509j15%2F Abstract  The CASK gene encoding a member of the membrane-associated guanylate kinase protein family is highly expressed in the mammalian nervous system of both adults and fetuses, playing several roles in neural development and synaptic function. Recently, CASK aberrations caused by both mutations and deletions have been reported to cause severe mental retardation (MR), microcephaly and disproportionate pontine and cerebellar hypoplasia (MICPCH) in females. Here, mutations and copy numbers of CASK were examined in ten females with MR and MICPCH, and the following changes were detected: nonsense mutations in three cases, a 2-bp deletion in one case, mutations at exon–intron junctions in two cases, heterozygous deletions encompassing CASK in two cases and interstitial duplica... Human Genetics journals http://www.medworm.com/rss/comments.php?id=5015988 Thu, 07 Jul 2011 05:43:43 +0100 5015988 http://www.medworm.com/index.php?rid=4990375&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fh117455020115t32%2F Content Type Journal ArticlePages 1-2DOI 10.1007/s00439-011-1046-1Authors Andrew V. Biankin, Cancer Research Program, Garvan Institute of Medical Research, Darlinghurst, Sydney, NSW 2010, AustraliaStephen J. Chanock, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-4605, USA Journal Human GeneticsOnline ISSN 1432-1203Print ISSN 0340-6717 Journal Volume Volume 130 Journal Issue Volume 130, Number 1 (Source: Human Genetics) Human Genetics journals http://www.medworm.com/rss/comments.php?id=4990375 Tue, 28 Jun 2011 15:49:22 +0100 4990375 http://www.medworm.com/index.php?rid=4973896&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F47h7k51844361j12%2F This study represents a new and unique approach to predisposition gene identification; and it is the first genome-wide association study performed in related cases in high-risk pedigrees. Our approach illustrates an example of using high-risk pedigrees for the identification of new melanoma predisposition variants. Content Type Journal ArticlePages 1-9DOI 10.1007/s00439-011-1048-zAuthors Craig Teerlink, Division of Genetic Epidemiology, Department of Internal Medicine, University of Utah School of Medicine, 4C104, 30 N 1900 E, Salt Lake City, UT 84132, USAJames Farnham, Division of Genetic Epidemiology, Department of Internal Medicine, University of Utah School of Medicine, 4C104, 30 N 1900 E, Salt Lake City, UT 84132, USAKristina Allen-Brady, Division of Genetic Epidemiology, Dep... Human Genetics journals http://www.medworm.com/rss/comments.php?id=4973896 Sat, 25 Jun 2011 15:53:18 +0100 4973896 http://www.medworm.com/index.php?rid=4973895&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fl17lgjt4654k5373%2F Abstract  Genetic research gained new momentum with the completion of the Human Genome Project in 2003. Formerly centered on the investigation of single-gene disorders, genetic research is increasingly targeting common complex diseases and in doing so is studying the whole genome, the environment and its impact on genomic variation. Consequently, biobanking initiatives have emerged around the world as a tool to sustain such progress. Whether they are small scale or longitudinal, public or private, commercial or non-commercial, biobanks should consider the possibility of closure. Interestingly, while raising important ethical issues, this topic has hardly been explored in the literature. Indeed, ethical issues associated with sale, insolvency, end of funding, or transfer of ... Human Genetics journals http://www.medworm.com/rss/comments.php?id=4973895 Sat, 25 Jun 2011 15:53:18 +0100 4973895 http://www.medworm.com/index.php?rid=4973894&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fv160118455264rr6%2F Abstract  Sarcopenia, which is characterized by a progressive decrease of skeletal muscle mass and function with aging, is closely related to several common diseases (such as cardiovascular and airway diseases) and functional impairment/disability. Strong genetic determination has been reported for muscle mass and muscle strength, two most commonly recognized and studied risk phenotypes for sarcopenia, with heritability ranging from 30 to 85% for muscle strength and 45–90% for muscle mass. Sarcopenia has been the subject of increasing genetic research over the past decade. This review is designed to comprehensively summarize the most important and representative molecular genetic studies designed to identify genetic factors associated with sarcopenia. We have methodically... Human Genetics journals http://www.medworm.com/rss/comments.php?id=4973894 Sat, 25 Jun 2011 15:53:18 +0100 4973894 http://www.medworm.com/index.php?rid=4973897&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fu93733220724011r%2F Abstract  Personalized medicine uses traditional, as well as emerging concepts of the genetic and environmental basis of disease to individualize prevention, diagnosis and treatment. Personalized genomics plays a vital, but not exclusive role in this evolving model of personalized medicine. The distinctions between genetic and genomic medicine are more quantitative than qualitative. Personalized genomics builds on principles established by the integration of genetics into medical practice. Principles shared by genetic and genomic aspects of medicine, include the use of variants as markers for diagnosis, prognosis, prevention, as well as targets for treatment, the use of clinically validated variants that may not be functionally characterized, the segregation of these varian... Human Genetics journals http://www.medworm.com/rss/comments.php?id=4973897 Sat, 25 Jun 2011 15:53:17 +0100 4973897 http://www.medworm.com/index.php?rid=4973899&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fu003325xw332621l%2F Abstract  Hirschsprung disease (HSCR, congenital colon aganglionosis) is a relatively common complex genetic condition caused by abnormal development of the enteric nervous system (ENS). Through a recent genome-wide association study conducted on Chinese HSCR patients, we identified a new HSCR contributing locus, neuregulin 1 (NRG1; 8p12), a gene known to be involved in the development of the ENS. As genes in which disease-associated common variants are found are to be considered as candidates for the search of deleterious rare variants (RVs) in the coding sequences, we sequenced the NRG1 exons of 358 sporadic HSCR patients and 333 controls. We identified a total of 13 different heterozygous RVs including 8 non-synonymous (A28G, E134K, V266L, H347Y, P356L, V486M, A511T, P608... Human Genetics journals http://www.medworm.com/rss/comments.php?id=4973899 Fri, 24 Jun 2011 16:03:25 +0100 4973899 http://www.medworm.com/index.php?rid=4973898&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F46301717l566j45v%2F Abstract  Large-scale, public genomic databases have greatly improved the capacity of researchers to do genomic research. In order to ensure that the scientific community uses data from these public resources properly, data access agreements have been developed to complement already existing legal and ethical norms. Sanctions to address cases of data misuse constitute an essential part of this compliance framework meant to protect stakeholders in genomic research. Yet very little research and community debate has been done on this most important topic. This paper presents a review of different sanctions that could be invoked in cases of non-compliance from data users. They have been identified through comprehensive research and analysis of over 450 documents (journal articl... Human Genetics journals http://www.medworm.com/rss/comments.php?id=4973898 Fri, 24 Jun 2011 16:03:25 +0100 4973898 http://www.medworm.com/index.php?rid=4973900&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fk516h7l375u642u4%2F Abstract  Early biomedical research focused primarily on the study of specific diseases or sets of diseases within small groups of living research participants. Accordingly, the first ethical frameworks governing biomedical research addressed short-term, limited-scope research involving living research participants. Due to recent interest in longitudinal population studies and biobanking, research is increasingly long term. This shift raises several ethical and legal issues concerning the impact of a participant’s death on research. This paper offers an overview of these issues in the context of longitudinal biobanking genetic research. Our first part outlines the legal and ethical frameworks that govern the effect of the participants’ death on consent. This will be fol... Human Genetics journals http://www.medworm.com/rss/comments.php?id=4973900 Fri, 24 Jun 2011 16:03:24 +0100 4973900 http://www.medworm.com/index.php?rid=4973901&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fj5722u1r534373r4%2F Abstract  The promise of science lies in expectations of its benefits to societies and is matched by expectations of the realisation of the significant public investment in that science. In this paper, we undertake a methodological analysis of the science of biobanking and a sociological analysis of translational research in relation to biobanking. Part of global and local endeavours to translate raw biomedical evidence into practice, biobanks aim to provide a platform for generating new scientific knowledge to inform development of new policies, systems and interventions to enhance the public’s health. Effectively translating scientific knowledge into routine practice, however, involves more than good science. Although biobanks undoubtedly provide a fundamental resource ... Human Genetics journals http://www.medworm.com/rss/comments.php?id=4973901 Fri, 24 Jun 2011 16:03:23 +0100 4973901 http://www.medworm.com/index.php?rid=4973902&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fb286184612181424%2F Abstract  Autism spectrum disorders (ASDs) are a group of conditions characterized by impairments in communication and reciprocal social interaction, and the presence of restricted and repetitive behaviors. The spectrum of autistic features is variable, with severity of symptoms ranging from mild to severe, sometimes with poor clinical outcomes. Twin and family studies indicate a strong genetic basis for ASD susceptibility. Recent progress in defining rare highly penetrant mutations and copy number variations as ASD risk factors has prompted early uptake of these research findings into clinical diagnostics, with microarrays becoming a ‘standard of care’ test for any ASD diagnostic work-up. The ever-changing landscape of the generation of genomic data coupled with the va... Human Genetics journals http://www.medworm.com/rss/comments.php?id=4973902 Thu, 23 Jun 2011 16:07:45 +0100 4973902 http://www.medworm.com/index.php?rid=4973903&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F938253870106425r%2F Abstract  Mutations in the gene encoding the mitochondrial protein high temperature requirement A2 (HTRA2) are inconsistently associated with a risk of Parkinson’s disease (PD). We assessed the presence of HTRA2 mutations among patients with PD and performed functional assay of identified mutations or variants. Among the total 1,373 subjects, the entire HTRA2 coding region was sequenced in 113 early-onset PD (EOPD), 20 familial PD patients and 150 control subjects. An additional 390 sporadic late-onset PD patients and 700 controls were subsequently screened to validate possible mutations found in the first set. We identified two novel heterozygous variants, c.427C > G (Pro143Ala) and c.906 +3 G > A, in 2 (1.5%) EOPD patients. The missense variant,... Human Genetics journals http://www.medworm.com/rss/comments.php?id=4973903 Thu, 23 Jun 2011 16:07:34 +0100 4973903 http://www.medworm.com/index.php?rid=4973904&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fqr84213431r40706%2F This study showed a novel association between rs11554159 (p.R76Q) polymorphism at the IFI30 locus and the risk of hyperglycemia/diabetes in severely obese individuals. Content Type Journal ArticlePages 1-10DOI 10.1007/s00439-011-1043-4Authors V. Turcot, Institute of Nutraceuticals and Functional Foods (INAF), Pavillon des Services, Laval University, local 2729K, Quebec, G1V 0A6 CanadaL. Bouchard, Department of Biochemistry, Faculty of Medicine and Health Sciences, University of Sherbrooke, and ECOGENE-21 Research Center, Chicoutimi Hospital, Quebec, CanadaG. Faucher, Institute of Nutraceuticals and Functional Foods (INAF), Pavillon des Services, Laval University, local 2729K, Quebec, G1V 0A6 CanadaA. Tchernof, Molecular Endocrinology and Genomics, CHUQ, Laval University, Quebec, Can... Human Genetics journals http://www.medworm.com/rss/comments.php?id=4973904 Thu, 23 Jun 2011 16:07:24 +0100 4973904 http://www.medworm.com/index.php?rid=4966373&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fu13v454847120454%2F Abstract  The DNA ancestry testing industry is more than a decade old, yet details about it remain a mystery: there remain no reliable, empirical data on the number, motivations, and attitudes of customers to date, the number of products available and their characteristics, or the industry customs and standard practices that have emerged in the absence of specific governmental regulations. Here, we provide preliminary data collected in 2009 through indirect and direct participant observation, namely blog post analysis, generalized survey analysis, and targeted survey analysis. The attitudes include the first available data on attitudes of those of individuals who have and have not had their own DNA ancestry tested as well as individuals who are members of DNA ancestry-relat... Human Genetics journals http://www.medworm.com/rss/comments.php?id=4966373 Wed, 22 Jun 2011 15:59:25 +0100 4966373 http://www.medworm.com/index.php?rid=4966374&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fj374m9q602210347%2F Abstract  The major histocompatibility complex (MHC) on chromosome 6p21 is a key contributor to the genetic basis of systemic lupus erythematosus (SLE). Although SLE affects African Americans disproportionately compared to European Americans, there has been no comprehensive analysis of the MHC region in relationship to SLE in African Americans. We conducted a screening of the MHC region for 1,536 single nucleotide polymorphisms (SNPs) and the deletion of the C4A gene in a SLE case–control study (380 cases, 765 age-matched controls) nested within the prospective Black Women’s Health Study. We also genotyped 1,509 ancestral informative markers throughout the genome to estimate European ancestry to control for population stratification due to population admixture. The most ... Human Genetics journals http://www.medworm.com/rss/comments.php?id=4966374 Wed, 22 Jun 2011 06:09:29 +0100 4966374 http://www.medworm.com/index.php?rid=4966375&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fp521045130041206%2F Abstract  Over the past two decades, high-throughput (HTP) technologies such as microarrays and mass spectrometry have fundamentally changed clinical cancer research. They have revealed novel molecular markers of cancer subtypes, metastasis, and drug sensitivity and resistance. Some have been translated into the clinic as tools for early disease diagnosis, prognosis, and individualized treatment and response monitoring. Despite these successes, many challenges remain: HTP platforms are often noisy and suffer from false positives and false negatives; optimal analysis and successful validation require complex workflows; and great volumes of data are accumulating at a rapid pace. Here we discuss these challenges, and show how integrative computational biology can help diminish... Human Genetics journals http://www.medworm.com/rss/comments.php?id=4966375 Tue, 21 Jun 2011 20:38:15 +0100 4966375 http://www.medworm.com/index.php?rid=4966376&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F987912147x31h427%2F Abstract  Germline mutations in the tumor suppressor gene TP53 occur in the majority of families with Li-Fraumeni syndrome, who are at an increased risk for a wide spectrum of early onset cancers. Several genetic polymorphisms in TP53 modify its effect on cancer risk. While some studies indicate that the TP53 PIN3 deletion allele (D) accelerate tumor onset in carriers with TP53 germline mutations, other studies have shown that the TP53 PIN3 insertion allele (I) confers a significantly higher risk of developing cancer than D allele. To further determine the effects of the TP53 PIN3 polymorphism on cancer development among TP53 germline mutations and to evaluate if those are differenence between male and female carriers, we studied a total of 152 germline mutation carriers with ... Human Genetics journals http://www.medworm.com/rss/comments.php?id=4966376 Tue, 21 Jun 2011 17:58:51 +0100 4966376 http://www.medworm.com/index.php?rid=4966377&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F3q3418r8263713wr%2F The objective of this study was to conduct linkage studies of childhood-onset OCD, which is thought to have the strongest genetic etiology, in several OCD-affected families from the genetically isolated population of the Central Valley of Costa Rica (CVCR). The authors used parametric and non-parametric approaches to conduct genome-wide linkage analyses using 5,786 single nucleotide repeat polymorphisms (SNPs) in three CVCR families with multiple childhood-onset OCD-affected individuals. We identified areas of suggestive linkage (LOD score ≥2) on chromosomes 1p21, 15q14, 16q24, and 17p12. The strongest evidence for linkage was on chromosome 15q14 (LOD = 3.13), identified using parametric linkage analysis with a recessive model, and overlapping a region identified in a pri... Human Genetics journals http://www.medworm.com/rss/comments.php?id=4966377 Tue, 21 Jun 2011 16:43:29 +0100 4966377 http://www.medworm.com/index.php?rid=4958466&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fb642134054271220%2F Abstract  X-chromosome inactivation (XCI) results in the transcriptional silencing of one X-chromosome in females to attain gene dosage parity between XX female and XY male mammals. Mammals appear to have developed rather diverse strategies to initiate XCI in early development. In placental mammals XCI depends on the regulatory noncoding RNA X-inactive specific transcript (Xist), which is absent in marsupials and monotremes. Surprisingly, even placental mammals show differences in the initiation of XCI in terms of Xist regulation and the timing to acquire dosage compensation. Despite this, all placental mammals achieve chromosome-wide gene silencing at some point in development, and this is maintained by epigenetic marks such as chromatin modifications and DNA methylation. I... Human Genetics journals http://www.medworm.com/rss/comments.php?id=4958466 Mon, 20 Jun 2011 14:18:55 +0100 4958466 http://www.medworm.com/index.php?rid=4950547&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F261w11q434400582%2F Abstract  Genome-wide association studies in cancer have already identified over 150 regions associated with two dozen specific cancers. Already, a handful of multi-cancer susceptibility regions have been uncovered, providing new insights into perhaps common mechanisms of carcinogenesis. For each new susceptibility allele, investigators now face the arduous task of interrogating each region beginning with fine mapping prior to pursuing the biological basis for the direct association of one or more variants. It appears that there may be a significant number of common alleles that contribute to the heritability of a specific cancer. Since each region confers a small contribution to the risk for cancer, it is daunting to consider any single nucleotide polymorphism (SNP) as a c... Human Genetics journals http://www.medworm.com/rss/comments.php?id=4950547 Thu, 16 Jun 2011 05:53:10 +0100 4950547 http://www.medworm.com/index.php?rid=4950548&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F9557lj222h4l1016%2F Abstract  Since the groundbreaking hypothesis of X chromosome inactivation (XCI) proposed by Mary Lyon over 50 years ago, a great amount of knowledge has been gained regarding this essential dosage compensation mechanism in female cells. For the mammalian system, most of the mechanistic studies of XCI have so far been investigated in the mouse model system, but recently, a number of interesting XCI studies have been extended to human pluripotent stem cells, including both embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs). Emerging data indicate that XCI in hESCs and hiPSCs is much more complicated than that of their mouse counterparts. XCI in human pluripotent stem cells is not as stable and is subject to environmental influences and epigenetic reg... Human Genetics journals http://www.medworm.com/rss/comments.php?id=4950548 Thu, 16 Jun 2011 05:53:08 +0100 4950548 http://www.medworm.com/index.php?rid=4950549&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F419l484437524u51%2F Abstract  The goal of this study is to define the effects of TCF4 hemizygosity in the context of a larger segmental deletion of chromosome 18q. Our cohort included 37 individuals with deletions of 18q. Twenty-seven had deletions including TCF4 (TCF4 +/−); nine had deletions that did not include TCF4 (TCF4 +/+); and one individual had a microdeletion that included only the TCF4 gene. We compared phenotypic data from the participants’ medical records, survey responses, and in-person evaluations. Features unique to the TCF4 +/− individuals included abnormal corpus callosum, short neck, small penis, accessory and wide-spaced nipples, broad or clubbed fingers, and sacral dimple. The developmental data revealed that TCF4 +/+ individuals were only moderately developmentally... Human Genetics journals http://www.medworm.com/rss/comments.php?id=4950549 Tue, 14 Jun 2011 05:59:29 +0100 4950549 http://www.medworm.com/index.php?rid=4930484&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Frq3k78w836wp0v74%2F Abstract  X-chromosome inactivation is an epigenetic hallmark of mammalian development. Chromosome-wide regulation of the X-chromosome is essential in embryonic and germ cell development. In the male germline, the X-chromosome goes through meiotic sex chromosome inactivation, and the chromosome-wide silencing is maintained from meiosis into spermatids before the transmission to female embryos. In early female mouse embryos, X-inactivation is imprinted to occur on the paternal X-chromosome, representing the epigenetic programs acquired in both parental germlines. Recent advances revealed that the inactive X-chromosome in both females and males can be dissected into two elements: repeat elements versus unique coding genes. The inactive paternal X in female preimplantation emb... Human Genetics journals http://www.medworm.com/rss/comments.php?id=4930484 Sun, 12 Jun 2011 06:03:22 +0100 4930484 http://www.medworm.com/index.php?rid=4930483&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fr4ku4w55863n276l%2F Abstract  In the mid-nineteenth century, it was commonly believed that hereditary disease struck at the same time in succeeding generations, except for those cases in which it appeared at an earlier age. This exception to the rule was the precursor for the concept of anticipation in hereditary disease, a pattern of inheritance where a hereditary illness strikes earlier and often more severely in succeeding generations. Anticipation underwent cycles of acceptance and rejection over the course of the twentieth century and the ways in which this concept was received reveal complex interactions between science, medicine, and society. Content Type Journal ArticlePages 1-10DOI 10.1007/s00439-011-1022-9Authors Judith E. Friedman, Office of History, National Institutes of Heal... Human Genetics journals http://www.medworm.com/rss/comments.php?id=4930483 Sun, 12 Jun 2011 06:03:22 +0100 4930483 http://www.medworm.com/index.php?rid=4930485&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fc66j343k550340x4%2F Abstract  A missense mutation of Gipc3 was previously reported to cause age-related hearing loss in mice. Point mutations of human GIPC3 were found in two small families, but association with hearing loss was not statistically significant. Here, we describe one frameshift and six missense mutations in GIPC3 cosegregating with DFNB72 hearing loss in six large families that support statistically significant evidence for genetic linkage. However, GIPC3 is not the only nonsyndromic hearing impairment gene in this region; no GIPC3 mutations were found in a family cosegregating hearing loss with markers of chromosome 19p. Haplotype analysis excluded GIPC3 from the obligate linkage interval in this family and defined a novel locus spanning 4.08 Mb and 104 genes. This closely lin... Human Genetics journals http://www.medworm.com/rss/comments.php?id=4930485 Fri, 10 Jun 2011 06:28:49 +0100 4930485 http://www.medworm.com/index.php?rid=4930487&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F37m67n528658x033%2F Abstract  The use of tissue samples from children is vital to genetic research. Collections of such tissue, in so-called biobanks, can take the form of large-scale prospective cohort studies or disease-specific studies using tissue of children with that specific disease. Collections of samples gathered in a diagnostics context, such as blood spot cards, can also be used for genetic research. Research on stored tissue samples from children poses ethical questions that are different from those posed by the use of samples from adults. Also, the ethical questions raised by the participation of children in biobanks are not analogous to those raised by the participation of children in clinical trials. In this review we first give an overview of the international ethical guideline... Human Genetics journals http://www.medworm.com/rss/comments.php?id=4930487 Fri, 10 Jun 2011 06:28:47 +0100 4930487 http://www.medworm.com/index.php?rid=4930486&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fkh465151310215qh%2F Abstract  X chromosome inactivation (XCI), the silencing of one of the two X chromosomes in XX female cells, equalises the dosage of X-linked genes relative to XY males. The process is mediated by the non-coding RNA X inactive specific transcript (Xist) that binds in cis and propagates along the inactive X chromosome elect, triggering chromosome-wide silencing. The mechanisms by which Xist RNA binds and spreads along the chromosome, and initiates Xist-mediated chromosome silencing remain poorly understood. Accumulating evidence suggests that chromosome and nuclear organisation are important in both processes. Notably, recent studies have identified specific factors, previously shown to be components of the nuclear matrix or scaffold, to play a role both in Xist RNA-binding ... Human Genetics journals http://www.medworm.com/rss/comments.php?id=4930486 Fri, 10 Jun 2011 06:28:47 +0100 4930486 http://www.medworm.com/index.php?rid=4930488&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fj2666207k1824608%2F Abstract  UDP-glucuronosyltransferase 2 family, polypeptide B4 (UGT2B4) is an important metabolizing enzyme involved in the clearance of many xenobiotics and endogenous substrates, especially steroid hormones and bile acids. The HapMap data show that numerous SNPs upstream of UGT2B4 are in near-perfect linkage disequilibrium with each other and occur at intermediate frequency, indicating that this region might contain a target of natural selection. To investigate this possibility, we chose three regions (4.8 kb in total) for resequencing and observed a striking excess of intermediate-frequency alleles that define two major haplotypes separated by many mutation events and with little differentiation across populations, thus suggesting that the variation pattern upstream ... Human Genetics journals http://www.medworm.com/rss/comments.php?id=4930488 Fri, 10 Jun 2011 06:28:46 +0100 4930488 http://www.medworm.com/index.php?rid=4918931&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fk11502rjnwu71279%2F Abstract  Psoriasis (PS; MIM#177900) is a chronic inflammatory immune-mediated skin disorder. Although the disease is believed to be caused by a combination of genetic, immunologic and environmental factors, its complete etiology has not been fully understood. Here, we focused on the BSG (MIM#109480), a member of the immunoglobulin superfamily expressed ubiquitously in circulating immune cell populations. We observed that the expression level of BSG in PBMCs was elevated in psoriasis patients. To understand the underlying mechanism for this change, we genotyped the rs8259 T>A SNP located in the 3′UTR of the BSG gene from 668 psoriasis patients and 1,143 healthy controls. The rs8259 T allele was associated with significantly decreased psoriasis susceptibility (OR =&n... Human Genetics journals http://www.medworm.com/rss/comments.php?id=4918931 Tue, 07 Jun 2011 09:40:00 +0100 4918931 http://www.medworm.com/index.php?rid=4918932&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fj4274588h1224j31%2F Abstract  All mammals compensate for sex differences in numbers of X chromosomes by transcribing only a single X chromosome in cells of both sexes; however, they differ from one another in the details of the compensatory mechanisms. These species variations result from chance mutations, species differences in the staging of developmental events, and interactions between events that occur concurrently. Such variations, which have only recently been appreciated, do not interfere with the strategy of establishing a single active X, but they influence how it is carried out. In an overview of X dosage compensation in human cells, I point out the evolutionary variations. I also argue that it is the single active X that is chosen, rather than inactive ones. Further, I suggest that... Human Genetics journals http://www.medworm.com/rss/comments.php?id=4918932 Tue, 07 Jun 2011 09:39:58 +0100 4918932 http://www.medworm.com/index.php?rid=4918934&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fqx2376776v222285%2F Abstract  Female eutherians silence one of their X chromosomes to accomplish an equal dose of X-linked gene expression compared with males. The mouse is the most widely used animal model in XCI research and has proven to be of great significance for understanding the complex mechanism of X-linked dosage compensation. Although the basic principles of XCI are similar in mouse and humans, differences exist in the timing of XCI initiation, the genetic elements involved in XCI regulation and the form of XCI in specific tissues. Therefore, the mouse has its limitations as a model to understand early human XCI and analysis of human tissues is required. In this review, we describe these differences with respect to initiation of XCI in human and mouse preimplantation embryos, the ex... Human Genetics journals http://www.medworm.com/rss/comments.php?id=4918934 Mon, 06 Jun 2011 14:55:22 +0100 4918934 http://www.medworm.com/index.php?rid=4918933&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F13511m7kv4337625%2F Abstract  Type 2 diabetes (T2D) and obesity represent major challenges for global public health. They are at the forefront of international efforts to identify the genetic variation contributing to complex disease susceptibility, and recent years have seen considerable success in identifying common risk-variants. Given the clinical impact of molecular diagnostics in rarer monogenic forms of these diseases, expectations have been high that genetic discoveries will transform the prospects for risk stratification, development of novel therapeutics and personalised medicine. However, so far, clinical translation has been limited. Difficulties in defining the alleles and transcripts mediating association effects have frustrated efforts to gain early biological insights, whilst t... Human Genetics journals http://www.medworm.com/rss/comments.php?id=4918933 Mon, 06 Jun 2011 14:55:22 +0100 4918933 http://www.medworm.com/index.php?rid=4918935&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fhg13342268651472%2F Abstract  Historically, large-scale longitudinal genomic research studies have not returned individual research results to their participants, as these studies are not intended to find clinically significant information for individuals, but to produce ‘generalisable’ knowledge for future research. However, this stance is now changing. Commentators now argue that there is an ethical imperative to return clinically significant results and individuals are now expressing a desire to have them. This shift reflects societal changes, such as the rise of social networking and an increased desire to participate in medical decision-making, as well as a greater awareness of genetic information and the increasing ability of clinicians to use this information in health care treatmen... Human Genetics journals http://www.medworm.com/rss/comments.php?id=4918935 Sun, 05 Jun 2011 05:45:30 +0100 4918935 http://www.medworm.com/index.php?rid=4918936&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F943r4951426k3t12%2F This article explores issues relevant to the clinical translation of sequence-based mutation profiles in the clinical development of targeted therapies and in the future management of cancer patients. Content Type Journal ArticlePages 1-13DOI 10.1007/s00439-011-1010-0Authors Andrew V. Biankin, Cancer Research Program, Garvan Institute of Medical Research, 384 Victoria St, Darlinghurst, Sydney, NSW 2010, AustraliaThomas J. Hudson, Ontario Institute for Cancer Research, 101 College Street, Toronto, ON M5G 0A3, Canada Journal Human GeneticsOnline ISSN 1432-1203Print ISSN 0340-6717 (Source: Human Genetics) Human Genetics journals http://www.medworm.com/rss/comments.php?id=4918936 Sun, 05 Jun 2011 05:45:29 +0100 4918936 http://www.medworm.com/index.php?rid=4918938&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F0l122203392qg64q%2F Abstract  To understand the importance of chr11q22.3–23.2 region in the development of cervical cancer, we have studied the genetic and epigenetic alterations of the candidate genes ATM, PPP2R1B, SDHD and CADM1 in cervical intraepithelial neoplasia (CIN) and cervical carcinoma (CACX) samples. Our study revealed low expression and high alterations (methylation/deletion) (55–59%) of ATM and CADM1 genes along with poor patient outcome. The alterations of ATM and CADM1 are associated with the progression of tumor from CIN to Stage I/II, thus implying their role in early invasiveness. The two genes, PPP2R1B and SDHD, lying in between ATM and CADM1, have low frequency of alterations, and majority of the alterations are in CACX samples, indicating that their alterations might be... Human Genetics journals http://www.medworm.com/rss/comments.php?id=4918938 Sun, 05 Jun 2011 05:45:28 +0100 4918938 http://www.medworm.com/index.php?rid=4918937&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F87470mv787nqm302%2F Abstract  The 50th anniversary of Mary Lyon’s 1961 Nature paper, proposing random inactivation in early embryonic life of one of the two X chromosomes in the cells of mammalian females, provides an opportunity to remember and celebrate the work of those involved. While the hypothesis was initially put forward by Lyon based on findings in the mouse, it was founded on earlier studies, notably the work of Susumu Ohno; it was also suggested independently by Beutler and colleagues using experimental evidence from a human X-linked disorder, glucose-6-phosphate dehydrogenase deficiency, and has proved to be of as great importance for human and medical genetics as it has for general mammalian genetics. Alongside the hypothesis itself, previous cytological studies of mouse and huma... Human Genetics journals http://www.medworm.com/rss/comments.php?id=4918937 Sun, 05 Jun 2011 05:45:28 +0100 4918937 http://www.medworm.com/index.php?rid=4900165&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F92827q5k232x4184%2F Abstract  X chromosome inactivation (XCI) is a process in mammals that ensures equal transcript levels between males and females by genetic inactivation of one of the two X chromosomes in females. Central to XCI is the long non-coding RNA Xist, which is highly and specifically expressed from the inactive X chromosome. Xist covers the X chromosome in cis and triggers genetic silencing, but its working mechanism remains elusive. Here, we review current knowledge about Xist regulation, structure, function and conservation and speculate on possible mechanisms by which its action is restricted in cis. We also discuss dosage compensation mechanisms other than XCI and how knowledge from invertebrate species may help to provide a better understanding of the mechanisms of mammalian XC... Human Genetics journals http://www.medworm.com/rss/comments.php?id=4900165 Fri, 27 May 2011 18:14:24 +0100 4900165 http://www.medworm.com/index.php?rid=4900166&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fql0216h83k2421gp%2F Content Type Journal ArticlePages 1-2DOI 10.1007/s00439-011-1017-6Authors Peter S. Harper, Institute of Medical Genetics, Cardiff University, Heath Park, Cardiff, CF14 4XN UK Journal Human GeneticsOnline ISSN 1432-1203Print ISSN 0340-6717 (Source: Human Genetics) Human Genetics journals http://www.medworm.com/rss/comments.php?id=4900166 Fri, 27 May 2011 18:14:23 +0100 4900166 http://www.medworm.com/index.php?rid=4900167&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F874463177359k571%2F We describe many new, associated variants for both CAD and HTN and describe their known genetic mechanisms. Content Type Journal ArticlePages 1-9DOI 10.1007/s00439-011-1009-6Authors Thomas P. Slavin, Department of Genetics, Center for Human Genetics, University Hospitals of Cleveland and Case Western Reserve University, 10524 Euclid Avenue, Cleveland, OH, USATao Feng, Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, OH 44106, USAAudrey Schnell, Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, OH 44106, USAXiaofeng Zhu, Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, OH 44106, USARobert C. Elston, Department of Epidemiology and Biostatistics, Case Western Reser... Human Genetics journals http://www.medworm.com/rss/comments.php?id=4900167 Fri, 27 May 2011 18:14:22 +0100 4900167 http://www.medworm.com/index.php?rid=4900169&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fl40271075w372267%2F Abstract  To achieve a balanced gene expression dosage between males (XY) and females (XX), mammals have evolved a compensatory mechanism to randomly inactivate one of the female X chromosomes. Despite this chromosome-wide silencing, a number of genes escape X inactivation: in women about 15% of X-linked genes are bi-allelically expressed and in mice, about 3%. Expression from the inactive X allele varies from a few percent of that from the active allele to near equal expression. While most genes have a stable inactivation pattern, a subset of genes exhibit tissue-specific differences in escape from X inactivation. Escape genes appear to be protected from the repressive chromatin modifications associated with X inactivation. Differences in the identity and distribution of e... Human Genetics journals http://www.medworm.com/rss/comments.php?id=4900169 Wed, 25 May 2011 16:04:30 +0100 4900169 http://www.medworm.com/index.php?rid=4900168&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fv72x714k67164534%2F Lionizing lyonization 50 years on Content Type Journal ArticlePages 1-2DOI 10.1007/s00439-011-1012-yAuthors David N. Cooper, Institute of Medical Genetics, Cardiff University, Heath Park, Cardiff, CF14 4XN UK Journal Human GeneticsOnline ISSN 1432-1203Print ISSN 0340-6717 (Source: Human Genetics) Human Genetics journals http://www.medworm.com/rss/comments.php?id=4900168 Wed, 25 May 2011 16:04:30 +0100 4900168 http://www.medworm.com/index.php?rid=4900170&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fv27jgw5q1107w3l9%2F Abstract  Kabuki syndrome (KS) is one of the classical, clinically well-known multiple anomalies/mental retardation syndromes, mainly characterized by a very distinctive facial appearance in combination with additional clinical signs such as developmental delay, short stature, persistent fingerpads, and urogenital tract anomalies. In our study, we sequenced all 54 coding exons of the recently identified MLL2 gene in 34 patients with Kabuki syndrome. We identified 18 distinct mutations in 19 patients, 11 of 12 tested de novo. Mutations were located all over the gene and included three nonsense mutations, two splice-site mutations, six small deletions or insertions, and seven missense mutations. We compared frequencies of clinical symptoms in MLL2 mutation carriers versus non-... Human Genetics journals http://www.medworm.com/rss/comments.php?id=4900170 Mon, 23 May 2011 16:50:47 +0100 4900170 http://www.medworm.com/index.php?rid=4851675&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fk07u821557t4613h%2F Abstract  X-chromosome inactivation (XCI) results in the differential marking of the active and inactive X with epigenetic modifications including DNA methylation. Consistent with the previous studies showing that CpG island-containing promoters of genes subject to XCI are approximately 50% methylated in females and unmethylated in males while genes which escape XCI are unmethylated in both sexes; our chromosome-wide (Methylated DNA ImmunoPrecipitation) and promoter-targeted methylation analyses (Illumina Infinium HumanMethylation27 array) showed the largest methylation difference (D = 0.12, p < 2.2 E−16) between male and female blood at X-linked CpG islands promoters. We used the methylation differences between males and females to predict XCI statu... Human Genetics journals http://www.medworm.com/rss/comments.php?id=4851675 Thu, 19 May 2011 16:34:46 +0100 4851675 http://www.medworm.com/index.php?rid=4851676&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fjv003p3t81844155%2F Abstract  Three founder mutations in BRCA1 and BRCA2 contribute to the risk of hereditary breast and ovarian cancer in Ashkenazi Jews (AJ). They are observed at increased frequency in the AJ compared to other BRCA mutations in Caucasian non-Jews (CNJ). Several authors have proposed that elevated allele frequencies in the surrounding genomic regions reflect adaptive or balancing selection. Such proposals predict long-range linkage disequilibrium (LD) resulting from a selective sweep, although genetic drift in a founder population may also act to create long-distance LD. To date, few studies have used the tools of statistical genomics to examine the likelihood of long-range LD at a deleterious locus in a population that faced a genetic bottleneck. We studied the genotypes of h... Human Genetics journals http://www.medworm.com/rss/comments.php?id=4851676 Thu, 19 May 2011 16:34:45 +0100 4851676 http://www.medworm.com/index.php?rid=4851678&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fb866261746227188%2F Abstract  Autosomal dominant osteogenesis imperfecta (OI) is caused by mutations in COL1A1 or COL1A2. We identified a dominant missense mutation, c.3235G>A in COL1A1 exon 45 predicting p.G1079S, in a Japanese family with mild OI. As mutations in exon 45 exhibit mild to lethal phenotypes, we tested if disruption of an exonic splicing cis-element determines the clinical phenotype, but detected no such mutations. In the Japanese family, juvenile-onset hyperuricemia cosegregated with OI, but not in the previously reported Italian and Canadian families with c.3235G>A. After confirming lack of a founder haplotype in three families, we analyzed PRPSAP1 and PRPSAP2 as candidate genes for hyperuricemia on chr 17 where COL1A1 is located, but found no mutation. We next resequenced ... Human Genetics journals http://www.medworm.com/rss/comments.php?id=4851678 Wed, 18 May 2011 18:19:15 +0100 4851678 http://www.medworm.com/index.php?rid=4851677&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fb2770v5673v24268%2F Abstract  “Genomic medicine” refers to the diagnosis, optimized management, and treatment of disease—as well as screening, counseling, and disease gene identification—in the context of information provided by an individual patient’s personal genome. Genomic medicine, to some extent synonymous with “personalized medicine,” has been made possible by recent advances in genome technologies. Genomic medicine represents a new approach to health care and disease management that attempts to optimize the care of a patient based upon information gleaned from his or her personal genome sequence. In this review, we describe recent progress in genomic medicine as it relates to neurological disease. Many neurological disorders either segregate as Mendelian phenotypes or occu... Human Genetics journals http://www.medworm.com/rss/comments.php?id=4851677 Wed, 18 May 2011 18:19:15 +0100 4851677 http://www.medworm.com/index.php?rid=4838141&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F1845w4j371v27215%2F In conclusion, consistent with imprinting, common polymorphic variation in foetal H19 alleles transmitted only from the mother are associated with birth weight and other markers of size at birth. Polymorphic variation in H19 is not associated with significant changes in maternal glucose tolerance in the third trimester of pregnancy. Content Type Journal ArticlePages 1-8DOI 10.1007/s00439-011-1005-xAuthors Clive J. Petry, Department of Paediatrics, University of Cambridge, Box 116, Addenbrooke’s Hospital, Hills Road, Cambridge, CB2 0QQ UKRachel V. Seear, Department of Paediatrics, University of Cambridge, Box 116, Addenbrooke’s Hospital, Hills Road, Cambridge, CB2 0QQ UKDianne L. Wingate, Department of Paediatrics, University of Cambridge, Box 116, Addenbrooke’s Hospital, Hil... Human Genetics journals http://www.medworm.com/rss/comments.php?id=4838141 Sat, 14 May 2011 16:02:26 +0100 4838141 http://www.medworm.com/index.php?rid=4838142&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F31463r31165t8705%2F Abstract  In mammals, one of the two X chromosomes in female cells is transcriptionally silenced for dosage compensation between the sexes. Chromosome-wide silencing is initiated by the non-coding Xist RNA that accumulates within the inactive X chromosome territory and triggers gene repression and chromatin modifications. Epigenetic changes of the inactive X chromosome in a developmentally regulated manner result in stable gene repression in female somatic cells. X inactivation is a model for understanding the formation of facultative heterochromatin in mammalian development and represents a paradigm for RNA mediated regulation of gene expression. In this review, we summarize the present knowledge of the mechanism of chromosome-wide silencing and give an outlook on future di... Human Genetics journals http://www.medworm.com/rss/comments.php?id=4838142 Thu, 12 May 2011 16:44:57 +0100 4838142 http://www.medworm.com/index.php?rid=4810921&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F655l24623337263h%2F Abstract  X-chromosome inactivation is an epigenetic process whereby one X chromosome is silenced in mammalian female cells. Since it was first proposed by Lyon in 1961, mouse models have been valuable tools to uncover the molecular mechanisms underlying X inactivation. However, there are also inherent differences between mouse and human X inactivation, ranging from sequence content of the X inactivation center to the phenotypic outcomes of X-chromosome abnormalities. X-linked gene dosage in males, females, and individuals with X aneuploidies and X/autosome translocations has demonstrated that many human genes escape X inactivation, implicating cis-regulatory elements in the spread of silencing. We discuss the potential nature of these elements and also review the elements ... Human Genetics journals http://www.medworm.com/rss/comments.php?id=4810921 Fri, 06 May 2011 16:24:35 +0100 4810921 http://www.medworm.com/index.php?rid=4810922&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fp4520844447u6127%2F In this study, we performed an in-depth analysis of the neurologic and ophthalmologic phenotype in a patient with Pitt–Hopkins syndrome (PTHS), a disorder characterized by severe mental and motor retardation, carrying a uniallelic TCF4 deletion, and studied a zebrafish model. The PTHS-patient was characterized by high-resolution magnetic resonance imaging (MRI) with diffusion tensor imaging to analyze the brain structurally, spectral-domain optical coherence tomography to visualize the retinal layers, and electroretinography to evaluate retinal function. A zebrafish model was generated by knockdown of tcf4-function by injection of morpholino antisense oligos into zebrafish embryos and the morphant phenotype was characterized for expression of neural differentiation genes neurog1, as... Human Genetics journals http://www.medworm.com/rss/comments.php?id=4810922 Wed, 04 May 2011 14:54:41 +0100 4810922 http://www.medworm.com/index.php?rid=4810924&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fx5399528x5567751%2F Abstract  X-inactivation, the molecular mechanism enabling dosage compensation in mammals, is tightly controlled during mouse early embryogenesis. In the morula, X-inactivation is imprinted with exclusive silencing of the paternally inherited X-chromosome. In contrast, in the post-implantation epiblast, X-inactivation affects randomly either the paternal or the maternal X-chromosome. The transition from imprinted to random X-inactivation takes place in the inner cell mass (ICM) of the blastocyst from which embryonic stem (ES) cells are derived. The trigger of X-inactivation, Xist, is specifically downregulated in the pluripotent cells of the ICM, thereby ensuring the reactivation of the inactive paternal X-chromosome and the transient presence of two active X-chromosomes. Mo... Human Genetics journals http://www.medworm.com/rss/comments.php?id=4810924 Wed, 04 May 2011 14:54:40 +0100 4810924 http://www.medworm.com/index.php?rid=4810923&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fn924p172676465l7%2F Abstract   IRX4 was the first identified cardiac transcription factor that is restricted to the ventricles at all stages of heart development. Irx4-deficient mice show ventricular dysfunction and develop cardiomyopathy. To study the potential impact of sequence variations in IRX4 on congenital heart disease (CHD) in humans, we examined the coding region of IRX4 in a cohort of 698 Chinese people with congenital heart disease and 250 healthy individuals as the controls. We found two potential disease-causing mutations, p. Asn85Tyr and p. Glu92Gly. A mammalian two-hybrid assay showed that both of the mutations significantly affected the interaction between IRX4 and RXRA. It demonstrated that IRX4 had a potential causative impact on the development of congenital heart disease, p... Human Genetics journals http://www.medworm.com/rss/comments.php?id=4810923 Wed, 04 May 2011 14:54:40 +0100 4810923 http://www.medworm.com/index.php?rid=4793484&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fe81875j573770w05%2F Abstract  Next-generation sequencing and genome-wide association studies represent powerful tools to identify genetic variants that confer disease risk within populations. On their own, however, they cannot provide insight into how these variants contribute to individual risk for diseases that exhibit complex inheritance, or alternatively confer health in a given individual. Even in the case of well-characterized variants that confer a significant disease risk, more healthy individuals carry the variant, with no apparent ill effect, than those who manifest disease. Access to low-cost genome sequence data promises to provide an unprecedentedly detailed view of the nature of the hereditary component of complex diseases, but requires the large-scale comparison of sequence data... Human Genetics journals http://www.medworm.com/rss/comments.php?id=4793484 Tue, 03 May 2011 05:56:16 +0100 4793484 http://www.medworm.com/index.php?rid=4787141&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fm6525448380x2387%2F In conclusion, the findings of ATXN-2 expansions in pure ALS cases suggest that ALS may be a third phenotype (alongside ataxia/parkinsonism and pure Parkinson) associated with ATXN-2 interrupted alleles. Content Type Journal ArticlePages 1-6DOI 10.1007/s00439-011-1000-2Authors Lucia Corrado, Department of Medical Sciences, Interdisciplinary Research Center of Autoimmune Diseases (IRCAD), University of Eastern Piedmont, Via Solaroli, 17, 28100 Novara, ItalyLetizia Mazzini, Department of Neurology, A. Avogadro University and Maggiore della Carità Hospital, Novara, ItalyGaia Donata Oggioni, Department of Neurology, A. Avogadro University and Maggiore della Carità Hospital, Novara, ItalyBernadetta Luciano, Department of Medical Sciences, Interdisciplinary Research Center of Autoimmun... Human Genetics journals http://www.medworm.com/rss/comments.php?id=4787141 Mon, 02 May 2011 15:56:49 +0100 4787141 http://www.medworm.com/index.php?rid=4787142&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Flu64v3u522074002%2F Abstract  Dominant negative genetic disorders, in which a mutant allele of a gene causes disease in the presence of a second, normal copy, have been challenging since there is no cure and treatments are only to alleviate the symptoms. Current therapies involving pharmacological and biological drugs are not suitable to target mutant genes selectively due to structural indifference of the normal variant of their targets from the disease-causing mutant ones. In instances when the target contains single nucleotide polymorphism (SNP), whether it is an enzyme or structural or receptor protein are not ideal for treatment using conventional drugs due to their lack of selectivity. Therefore, there is a need to develop new approaches to accelerate targeting these previously inaccessi... Human Genetics journals http://www.medworm.com/rss/comments.php?id=4787142 Mon, 02 May 2011 14:57:29 +0100 4787142