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. Sat, 20 Mar 2010 15:47:19 +0100 http://www.medworm.com/index.php?rid=3357681&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fy573h06627624207%2F Content Type Journal ArticleCategory Book ReviewDOI 10.1007/s00439-010-0809-4Authors Ray Waters, Cardiff University Pathology Department Tenovus Building, Heath Park Cardiff UK Journal Human GeneticsOnline ISSN 1432-1203Print ISSN 0340-6717 (Source: Human Genetics) Human Genetics journals http://www.medworm.com/rss/comments.php?id=3357681 Wed, 10 Mar 2010 15:24:44 +0100 3357681 http://www.medworm.com/index.php?rid=3357683&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fx003186l132g97l1%2F Abstract  Genetic ancestry and environmental factors may contribute to the ethnic differences in risk of coronary heart disease (CHD), metabolic syndrome (MS) or its individual components. The population of the Central Valley of Costa Rica offers a unique opportunity to assess the role of genetic ancestry in these chronic diseases because it derived from the admixture of a relatively small number of founders of Southern European, Amerindian, and West African origin. We aimed to determine whether genetic ancestry is associated with risk of myocardial infarction (MI), MS and its individual components in the Central Valley of Costa Rica. We genotyped 39 ancestral informative markers in cases (n = 1,998) with a first non-fatal acute MI and population-based controls (n&... Human Genetics journals http://www.medworm.com/rss/comments.php?id=3357683 Wed, 10 Mar 2010 15:24:42 +0100 3357683 http://www.medworm.com/index.php?rid=3357682&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F770n356536711330%2F Abstract  The most significant and widely studied remodeling of the African genetic landscape is the Bantu expansion, which led to an almost total replacement of the previous populations from the sub-Saharan region. However, a poor knowledge exists about other population movements, namely, the Nilotic migration, which is a pastoralist dispersal that, contrary to the Bantu expansion, impacted only East African populations. Here, samples from a Ugandan Nilotic-speaking population were studied for 37 Y chromosome-specific SNPs, and the obtained data were compared with those already available for other sub-Saharan population groups. Although Uganda lies on the fringe of both Bantu and Nilotic expansions, a low admixture with Bantu populations was detected, with haplogroups carr... Human Genetics journals http://www.medworm.com/rss/comments.php?id=3357682 Wed, 10 Mar 2010 15:24:42 +0100 3357682 http://www.medworm.com/index.php?rid=3337531&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fk71643300785h20t%2F Content Type Journal ArticleCategory Book ReviewDOI 10.1007/s00439-010-0806-7Authors Dhavendra Kumar, University Hospital of Wales, Cardiff University Institute of Medical Genetics Cardiff Wales UK Journal Human GeneticsOnline ISSN 1432-1203Print ISSN 0340-6717 (Source: Human Genetics) Human Genetics journals http://www.medworm.com/rss/comments.php?id=3337531 Wed, 03 Mar 2010 08:50:45 +0100 3337531 http://www.medworm.com/index.php?rid=3313918&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fm5116v3074k67231%2F Abstract  Controversy remains as to which gene at the chromosome 10q26 locus confers risk for age-related macular degeneration (AMD) and statistical genetic analysis is confounded by the strong linkage disequilibrium (LD) across the region. Functional analysis of related genetic variations could solve this puzzle. Recently, Fritsche et al. reported that AMD is associated with unstable ARMS2 transcripts possibly caused by a complex insertion/deletion (indel; consisting of a 443 bp deletion and an adjacent 54 bp insertion) in its 3′UTR (untranslated region). To validate this indel, we sequenced our samples. We found that this indel is even more complex and is composed of two side-by-side indels separated by 17 bp: (1) 9 bp deletion with 10 bp inserti... Human Genetics journals http://www.medworm.com/rss/comments.php?id=3313918 Thu, 25 Feb 2010 06:53:02 +0100 3313918 http://www.medworm.com/index.php?rid=3305538&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fd4j5364712553488%2F Abstract  Bardet–Biedl syndrome (BBS), an emblematic disease in the rapidly evolving field of ciliopathies, is characterized by pleiotropic clinical features and extensive genetic heterogeneity. To date, 14 BBS genes have been identified, 3 of which have been found mutated only in a single BBS family each (BBS11/TRIM32, BBS13/MKS1 and BBS14/MKS4/NPHP6). Previous reports of systematic mutation detection in large cohorts of BBS families (n > 90) have dealt only with a single gene, or at most small subsets of the known BBS genes. Here we report extensive analysis of a cohort of 174 BBS families for 12/14 genes, leading to the identification of 28 novel mutations. Two pathogenic mutations in a single gene have been found in 117 families, and a single heterozygous ... Human Genetics journals http://www.medworm.com/rss/comments.php?id=3305538 Tue, 23 Feb 2010 07:20:39 +0100 3305538 http://www.medworm.com/index.php?rid=3297493&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fv8277708u26798u1%2F Content Type Journal ArticleCategory ErratumDOI 10.1007/s00439-010-0802-yAuthors Hui-Mei Hong, Chung Shan Medical University Department of BioMedical Sciences Taichung Taiwan, ROCJiann-Jou Yang, Chung Shan Medical University Department of BioMedical Sciences Taichung Taiwan, ROCJia-Ching Shieh, Chung Shan Medical University Department of BioMedical Sciences Taichung Taiwan, ROCMei-Ling Lin, Chung Shan Medical University Department of BioMedical Sciences Taichung Taiwan, ROCShuan-Yow Li, Chung Shan Medical University Department of BioMedical Sciences Taichung Taiwan, ROC Journal Human GeneticsOnline ISSN 1432-1203Print ISSN 0340-6717 (Source: Human Genetics) Human Genetics journals http://www.medworm.com/rss/comments.php?id=3297493 Sun, 21 Feb 2010 06:54:36 +0100 3297493 http://www.medworm.com/index.php?rid=3286642&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fv5k14333332l9181%2F Abstract  Tuberous sclerosis complex (TSC) is an autosomal dominant neurocutaneous syndrome caused by mutations in TSC1 and TSC2. However, 10–15% TSC patients have no mutation identified with conventional molecular diagnostic studies. We used the ultra-deep pyrosequencing technique of 454 Sequencing to search for mosaicism in 38 TSC patients who had no TSC1 or TSC2 mutation identified by conventional methods. Two TSC2 mutations were identified, each at 5.3% read frequency in different patients, consistent with mosaicism. Both mosaic mutations were confirmed by several methods. Five of 38 samples were found to have heterozygous non-mosaic mutations, which had been missed in earlier analyses. Several other possible low-frequency mosaic mutations were identified by deep sequenc... Human Genetics journals http://www.medworm.com/rss/comments.php?id=3286642 Wed, 17 Feb 2010 18:28:10 +0100 3286642 http://www.medworm.com/index.php?rid=3278906&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fk24743n504551128%2F Abstract  Basques are a cultural isolate, and, according to mainly allele frequencies of classical polymorphisms, also a genetic isolate. We investigated the differentiation of Spanish Basques from the rest of Iberian populations by means of a dense, genome-wide SNP array. We found that F ST distances between Spanish Basques and other populations were similar to those between pairs of non-Basque populations. The same result is found in a PCA of individuals, showing a general distinction between Iberians and other South Europeans independently of being Basques. Pathogen-mediated natural selection may be responsible for the high differentiation previously reported for Basques at very specific genes such as ABO, RH, and HLA. Thus, Basques cannot be considered a genetic outlier... Human Genetics journals http://www.medworm.com/rss/comments.php?id=3278906 Mon, 15 Feb 2010 17:59:52 +0100 3278906 http://www.medworm.com/index.php?rid=3278911&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fj7339u12355q3533%2F Abstract  Schizencephaly (SCH) is a clinically and etiologically heterogeneous cerebral malformation presenting as unilateral or bilateral hemispheric cleft with direct connection between the inner and outer liquor spaces. The SCH cleft is usually lined by gray matter, which appears polymicrogyric implying an associated impairment of neuronal migration. The majority of SCH patients are sporadic, but familial SCH has been described. An initial report of heterozygous mutations in the homeobox gene EMX2 could not be confirmed in 52 patients investigated in this study in agreement with two independent SCH patient cohorts published previously. SCH frequently occurs with additional cerebral malformations like hypoplasia or aplasia of the septum pellucidum or optic nerve, suggestin... Human Genetics journals http://www.medworm.com/rss/comments.php?id=3278911 Mon, 15 Feb 2010 17:59:51 +0100 3278911 http://www.medworm.com/index.php?rid=3278908&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Ft47127623k934556%2F Content Type Journal ArticleCategory Book ReviewDOI 10.1007/s00439-010-0799-2Authors Sandeep Jayawant, University of Oxford Paediatric Neurology, Oxford Childrens Hospital Headley Way, Headington Oxford OX3 9DU UK Journal Human GeneticsOnline ISSN 1432-1203Print ISSN 0340-6717 (Source: Human Genetics) Human Genetics journals http://www.medworm.com/rss/comments.php?id=3278908 Mon, 15 Feb 2010 17:59:51 +0100 3278908 http://www.medworm.com/index.php?rid=3278914&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fh9341t7832673732%2F Abstract  Despite calls for greater clarity and precision of population description, studies have documented persistent ambiguity in the use of race/ethnicity terms in genetic research. It is unclear why investigators tolerate such ambiguity, or what effect these practices have on the evaluation of reported associations. To explore the way that population description is used to replicate and/or extend previously reported genetic observations, we examined articles describing the association of the peroxisome proliferator-activated receptor-gamma-γ Pro12Ala polymorphism with type 2 diabetes mellitus and related phenotypes, published between 1997 and 2005. The 80 articles identified were subjected to a detailed content analysis to determine (1) how sampled populations were des... Human Genetics journals http://www.medworm.com/rss/comments.php?id=3278914 Mon, 15 Feb 2010 17:59:48 +0100 3278914 http://www.medworm.com/index.php?rid=3248402&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F783216158627p107%2F Content Type Journal ArticleCategory Book ReviewDOI 10.1007/s00439-010-0796-5Authors Peter S. Harper, Cardiff University Institute of Medical Genetics, School of Medicine 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=3248402 Fri, 05 Feb 2010 17:53:43 +0100 3248402 http://www.medworm.com/index.php?rid=3248403&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F21n8l62061366255%2F Content Type Journal ArticleCategory Human Gene MutationsDOI 10.1007/s00439-010-0788-5 Journal Human GeneticsOnline ISSN 1432-1203Print ISSN 0340-6717 (Source: Human Genetics) Human Genetics journals http://www.medworm.com/rss/comments.php?id=3248403 Thu, 04 Feb 2010 18:10:27 +0100 3248403 http://www.medworm.com/index.php?rid=3248404&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fh7536x2147v6p03n%2F Content Type Journal ArticleCategory Book ReviewDOI 10.1007/s00439-010-0795-6Authors James Colley, Cardiff University Wales Gene Park Cardiff UK Journal Human GeneticsOnline ISSN 1432-1203Print ISSN 0340-6717 (Source: Human Genetics) Human Genetics journals http://www.medworm.com/rss/comments.php?id=3248404 Thu, 04 Feb 2010 18:10:26 +0100 3248404 http://www.medworm.com/index.php?rid=3242719&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F57tk20478g415441%2F This study compares the intracellular distribution and assembly of three CX43 mutants expressed in HeLa cells with their wild-type (WT) counterparts and the effects of the mutant proteins on those cells. Localization assay of WT CX43 reveals a typical punctuate fluorescence pattern of a gap junction channel between neighboring expression cells. Additionally, immunoblotting analysis of the transfectants confirms the production of mutant proteins, in which their distributions along appositional membranes are determined using immunofluorescent staining procedures. Furthermore, dye transfer assay results demonstrate that gap junctional intercellular communication is less in HeLa cells carrying mutant GJA1 or ρGJA1 gene than in WT-expressing cells. The results of this study suggest that t... Human Genetics journals http://www.medworm.com/rss/comments.php?id=3242719 Wed, 03 Feb 2010 17:56:02 +0100 3242719 http://www.medworm.com/index.php?rid=3242720&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Ff81k84l565164401%2F Abstract  The amelogenin gene on the Y chromosome (AMELY) is a homolog of the X chromosome amelogenin gene (AMELX), and the marker is employed for sexing in forensic casework. Deletion of the sequences in the Yp11.2 region containing the AMELY locus has been found in males from various ethnic populations. Two cases of AMELY null males found in the Japanese population had different Y haplogroups and deletion mapping. Proximal and distal breakpoints of a sample of haplogroup D2* were located in TSPYA and TSPYB arrays, respectively, suggesting that the deletion mechanism was non-allelic homologous recombination (NAHR). On the other hand, a sample of haplogroup O3a3c* had the distal breakpoint in the TSPYB array and the proximal breakpoint at position 7.94 Mb, not in the TSPYA ar... Human Genetics journals http://www.medworm.com/rss/comments.php?id=3242720 Tue, 02 Feb 2010 17:48:55 +0100 3242720 http://www.medworm.com/index.php?rid=3234638&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fw13w852r6n16052p%2F Content Type Journal ArticleCategory ErratumDOI 10.1007/s00439-010-0793-8Authors Kristin K. Nicodemus, Intramural Research Program, National Institute of Mental Health, National Institutes of Health Genes, Cognition and Psychosis Program Room 4S-235, 10 Center Drive Bethesda MD 20892 USAJoseph H. Callicott, Intramural Research Program, National Institute of Mental Health, National Institutes of Health Genes, Cognition and Psychosis Program Room 4S-235, 10 Center Drive Bethesda MD 20892 USARachel G. Higier, Intramural Research Program, National Institute of Mental Health, National Institutes of Health Genes, Cognition and Psychosis Program Room 4S-235, 10 Center Drive Bethesda MD 20892 USAAugustin Luna, Intramural Research Program, National Institute of Mental Health, National Institute... Human Genetics journals http://www.medworm.com/rss/comments.php?id=3234638 Mon, 01 Feb 2010 18:03:05 +0100 3234638 http://www.medworm.com/index.php?rid=3230450&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fu321l8475282612r%2F Abstract  Multiple sclerosis (MS) is characterized as an autoimmune demyelinating disease. Numerous family studies have confirmed a strong genetic component underlying its etiology. After several decades of frustrating research, the advent and application of affordable genotyping of dense SNP maps in large data sets has ushered in a new era in which rapid progress is being made in our understanding of the genetics underlying many complex traits. For MS, one of the first discoveries to emerge in this new era was the association with rs6897932[T244I] in the interleukin-7 receptor alpha chain (IL7RA) gene (Gregory et al. in Nat Genet 39(9):1083–1091, 2007; International Multiple Sclerosis Genetics Consortium in N Engl J Med 357(9):851–862, 2007; Lundmark in Nat Genet 39(9):1... Human Genetics journals http://www.medworm.com/rss/comments.php?id=3230450 Fri, 29 Jan 2010 12:15:38 +0100 3230450 http://www.medworm.com/index.php?rid=3224650&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fm17j377p505871q0%2F Abstract  Cerebrovascular and cardiovascular diseases are the leading causes of death and disability worldwide. They are complex disorders resulting from the interplay of genetic and environmental factors, and may share several susceptibility genes. Several recent studies have implicated variants of the Kalirin (KALRN) gene with susceptibility to cardiovascular and metabolic phenotypes, but no studies have yet been performed in stroke patients. KALRN is involved, among others, in the inhibition of inducible nitric oxide synthase, in the regulation of ischemic signal transduction, and in neuronal morphogenesis, plasticity, and stability. The goal of the present study was to determine whether SNPs in the KALRN region on 3q13, which includes the Ropporin gene (ROPN1), predispos... Human Genetics journals http://www.medworm.com/rss/comments.php?id=3224650 Wed, 27 Jan 2010 20:27:11 +0100 3224650 http://www.medworm.com/index.php?rid=3215414&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F10x760hl88h1j256%2F Abstract  Osteoporosis is characterized by low bone mineral density and structural deterioration of bone tissue, leading to an increased risk of fractures. It is the most common metabolic bone disorder worldwide, affecting one in three women and one in eight men over the age of 50. In the past 15 years, a large number of genes have been reported as being associated with osteoporosis. However, only in the past 4 years we have witnessed an accelerated pace in identifying and validating osteoporosis susceptibility loci. This increase in pace is mostly due to large-scale association studies, meta-analyses, and genome-wide association studies of both single nucleotide polymorphisms and copy number variations. A comprehensive review of these developments revealed that, ... Human Genetics journals http://www.medworm.com/rss/comments.php?id=3215414 Tue, 26 Jan 2010 07:03:02 +0100 3215414 http://www.medworm.com/index.php?rid=3207488&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fu01268205004j832%2F Abstract  It has been anticipated that new, much more sensitive, next generation sequencing (NGS) techniques, using massively parallel sequencing, will likely provide radical insights into the genetics of multifactorial diseases. While NGS has been used initially to analyze individual human genomes, and has revealed considerable differences between healthy individuals, we have used NGS to examine genetic variation within individuals, by sequencing tissues “in depth”, i.e., oversequencing many thousands of times. Initial studies have revealed intra-tissue genetic heterogeneity, in the form of multiple variants of a single gene that exist as distinct “majority and “minority” variants. This highly specialized form of somatic mosaicism has been found within both cance... Human Genetics journals http://www.medworm.com/rss/comments.php?id=3207488 Sat, 23 Jan 2010 07:41:26 +0100 3207488 http://www.medworm.com/index.php?rid=3192548&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fl7168jwn0052g763%2F Abstract  The etiology of schizophrenia likely involves genetic interactions. DISC1, a promising candidate susceptibility gene, encodes a protein which interacts with many other proteins, including CIT, NDEL1, NDE1, FEZ1 and PAFAH1B1, some of which also have been associated with psychosis. We tested for epistasis between these genes in a schizophrenia case–control study using machine learning algorithms (MLAs: random forest, generalized boosted regression and Monte Carlo logic regression). Convergence of MLAs revealed a subset of seven SNPs that were subjected to 2-SNP interaction modeling using likelihood ratio tests for nested unconditional logistic regression models. Of the 7C2 = 21 interactions, four were significant at the α = 0.05 level: DISC1 rs... Human Genetics journals http://www.medworm.com/rss/comments.php?id=3192548 Mon, 18 Jan 2010 18:45:52 +0100 3192548 http://www.medworm.com/index.php?rid=3192549&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F440t044236v86g37%2F In this study, we analyzed 25 single nucleotide polymorphisms (SNPs) within GRIN3A for association with nicotine dependence (ND), which was assessed by smoking quantity, heaviness of smoking index, and the Fagerström test for ND. Both individual SNP and haplotype association tests were performed in African-American (AA) and European-American (EA) samples as well as in the pooled sample consisting of 2,037 individuals from 602 nuclear families. Individual SNP analysis revealed significant associations of 5, 5, and 4 SNPs with at least one ND measure in the pooled, EA, and AA samples, respectively. Of them, SNPs rs17189632 and rs10121600 in the pooled sample and rs11788456 in the EA sample remained significant after correction for multiple testing. On the basis of the blocks determined... Human Genetics journals http://www.medworm.com/rss/comments.php?id=3192549 Mon, 18 Jan 2010 18:45:51 +0100 3192549 http://www.medworm.com/index.php?rid=3170415&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fxk135263583j7k12%2F Abstract  Although the exact pathogenesis of subacute sclerosing panencephalitis (SSPE) remains to be determined, our previous data suggested a genetic contribution to the host susceptibility to SSPE. During chronic viral infection, virus-specific cytotoxic T lymphocytes display poor effector functions. Since co-inhibitory molecules are involved in the suppression of T lymphocytes, we investigated whether single nucleotide polymorphisms (SNPs) of genes encoding co-inhibitory molecules contributed to a susceptibility to SSPE. Association studies on a total of 20 SNPs in 8 genes (CTLA4, CD80, CD86, PD1, PDL1, PDL2, BTLA and HVEM) and subsequent haplotype analysis of 4 SNPs in the PD1 genes were performed in Japanese and Filipino SSPE patients and controls. Then, we investigated... Human Genetics journals http://www.medworm.com/rss/comments.php?id=3170415 Mon, 11 Jan 2010 18:20:36 +0100 3170415 http://www.medworm.com/index.php?rid=3170416&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fe64226732m5m855m%2F Abstract  Holoprosencephaly (HPE) is the most common developmental forebrain anomaly in humans. Both environmental and genetic factors have been identified to play a role in the HPE phenotype. Previous studies of the genetic bases of HPE have taken a phenotype-first approach by examining groups of patients with HPE for specific mutations or deletions in known or candidate HPE genes. In this study, we characterized the presence or absence of HPE or a microform in 136 individuals in which microarray-based comparative genomic hybridization (aCGH) identified a deletion of one of 35 HPE loci. Frank holoprosencephaly was present in 11 individuals with deletions of one of the common HPE genes SHH, ZIC2, SIX3, and TGIF1, in one individual with a deletion of the HPE8 locus at 14q13, ... Human Genetics journals http://www.medworm.com/rss/comments.php?id=3170416 Mon, 11 Jan 2010 18:20:35 +0100 3170416 http://www.medworm.com/index.php?rid=3170417&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fjg003q370l358655%2F Abstract  Advanced maternal age is a well-documented risk factor of chromosome 21 nondisjunction in humans, but understanding of this association at the genetic level is still limited. In particular, the state of maternal genetic age is unclear. In the present study, we estimated maternal genetic age by measuring telomere length of peripheral blood lymphocytes among age-matched mothers of children with Down syndrome (cases: N = 75) and mothers of euploid children (controls: N = 75) in an age range of 18–42 years. All blood samples were taken within 1 week of the birth of the child in both cases and controls. The telomere length estimation was performed by restriction digestion—Southern blot hybridization method. We stratified the cases on th... Human Genetics journals http://www.medworm.com/rss/comments.php?id=3170417 Sun, 10 Jan 2010 06:44:06 +0100 3170417 http://www.medworm.com/index.php?rid=3162825&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fe63472517109q654%2F Content Type Journal ArticleCategory Book ReviewDOI 10.1007/s00439-009-0780-0Authors Peter S. Harper, Cardiff University Institute of Medical Genetics, School of Medicine 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=3162825 Fri, 08 Jan 2010 21:37:36 +0100 3162825 http://www.medworm.com/index.php?rid=3155482&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F21073u6493070711%2F Abstract  Autosomal recessive hypotrichosis is a rare form of human genetic disorder characterized by sparse to absent hair on scalp and rest of the body of affected individuals. Over the past few years at least five autosomal recessive forms of hypotrichosis loci have been mapped on different human chromosomes. In the present study, we report localization of another novel autosomal recessive hypotrichosis locus on human chromosome 10q11.23–22.3 in a four generation consanguineous Pakistani family. All the four patients in the family showed typical features of hereditary hypotrichosis including sparse hair on the scalp and rest of the body. Human genome scan using highly polymorphic microsatellite markers mapped the disease locus to a large region on chromosome 10. This n... Human Genetics journals http://www.medworm.com/rss/comments.php?id=3155482 Wed, 06 Jan 2010 18:04:56 +0100 3155482 http://www.medworm.com/index.php?rid=3155483&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fh8441p4257063361%2F Abstract  A number of association studies have investigated the role of the nitric oxide synthase 3 (NOS3) gene in the development of diabetic nephropathy (DN). However, results have been inconclusive, largely because the studies have focused on a variety of different polymorphisms and generate inconsistent results. We performed a meta-analysis of 28 association studies focusing on three polymorphisms in the NOS3 gene (G894T (Glu289Asp), 4b/a, and T-786C) and the risk of DN published before July 2009, covering a total of 10,364 subjects. Although significant heterogeneity was initially found in the analysis of G894T, it did not remain when analysis was done by ethnic subgroups. 894T was negatively associated with DN in Caucasian populations of European origin (OR =&nbs... Human Genetics journals http://www.medworm.com/rss/comments.php?id=3155483 Mon, 04 Jan 2010 18:18:36 +0100 3155483 http://www.medworm.com/index.php?rid=3141505&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F917x2116g6128477%2F Abstract  On 19q13, TGFB1 and the cystic fibrosis modifier 1 locus (CFM1) have been identified as modifiers of the course of the monogenic disease cystic fibrosis (CF). Recently, we have described a transmission disequilibrium at the microsatellite D19S197, localized between TGFB1 and CFM1. To map the corresponding molecular variants, we have selected informative SNP markers within a 600-kb area and compared two-marker-haplotype-distributions between phenotypically contrasting sib pair groups, intending to type only phylogenetically old markers by aiming for close-to-maximal polymorphism information content of the SNPs. Starting with a seed set of five SNPs that cover intermarker distances of up to 50 kb, we have iteratively added more SNPs to the map, until we could ide... Human Genetics journals http://www.medworm.com/rss/comments.php?id=3141505 Sat, 02 Jan 2010 16:53:55 +0100 3141505 http://www.medworm.com/index.php?rid=3128359&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fpq20x25543u81531%2F In this report, we proposed statistical approaches to precisely model a measured susceptibility gene fitted to family data and simultaneously determine the combined effects of individual risk factors and their interactions. Our approaches are structured for age-specific risk models based on Cox proportional hazards regression methods. They are useful for analyses of families and extended pedigrees in which measured risk genotypes are segregated within the family and are robust even when the genotypes are available only in some members of a family. We exemplified these methods by analyzing six extended pedigrees ascertained through soft-tissue sarcoma patients with p53 germ-line mutations. Our analyses showed that germ-line p53 mutations and sex had significant interaction effects on... Human Genetics journals http://www.medworm.com/rss/comments.php?id=3128359 Mon, 28 Dec 2009 19:17:44 +0100 3128359 http://www.medworm.com/index.php?rid=3123235&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fm73vq5275q68kh63%2F Abstract  The chromosomal region 10p13 has been linked to paucibacillary leprosy in two independent studies. The MRC1 gene, encoding the human mannose receptor (MR), is located in the 10p13 region and non-synonymous SNPs in exon 7 of the gene have been suggested as leprosy susceptibility factors. We determined that G396S is the only non-synonymous exon 7-encoded polymorphism in 396 unrelated Vietnamese subjects. This SNP was genotyped in 490 simplex and 90 multiplex leprosy families comprising 704 patients (47% paucibacillary; 53% multibacillary). We observed significant under-transmission of the serine allele of the G396S polymorphism with leprosy per se (P = 0.036) and multibacillary leprosy (P = 0.034). In a sample of 384 Brazilian leprosy cases (51% pa... Human Genetics journals http://www.medworm.com/rss/comments.php?id=3123235 Fri, 25 Dec 2009 00:18:48 +0100 3123235 http://www.medworm.com/index.php?rid=3117998&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fp2842745877m6644%2F We report the diagnosis of three attenuated FAP families due to a 1.4-kb deletion within intron 14 of APC, originally reported clinically as a variant of unknown significance (VUS). Sequence analysis suggests that this arose through an Alu-mediated recombination event with a locus on chromosome 6q22.1. This mutation is inherited by family members who presented with an attenuated FAP phenotype, with variable age of onset and severity. Sequence analysis of mRNA revealed an increase in the level of aberrant splicing of exon 14, resulting in the generation of an exon 13–exon 15 splice-form that is predicted to lead to a frameshift and protein truncation at codon 673. The relatively mild phenotypic presentation and the intra-familial variation are consistent with the leaky nature of exo... Human Genetics journals http://www.medworm.com/rss/comments.php?id=3117998 Mon, 21 Dec 2009 23:00:07 +0100 3117998 http://www.medworm.com/index.php?rid=3106550&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fl652r86k542u4445%2F Abstract   Fgfrl1 (also known as Fgfr5; OMIM 605830) homozygous null mice have thin, amuscular diaphragms and die at birth because of diaphragm hypoplasia. FGFRL1 is located at 4p16.3, and this chromosome region can be deleted in patients with congenital diaphragmatic hernia (CDH). We examined FGFRL1 as a candidate gene for the diaphragmatic defects associated with 4p16.3 deletions and re-sequenced this gene in 54 patients with CDH. We confirmed six known coding single nucleotide polymorphisms (SNPs): c.209G > A (p.Pro20Pro), c.977G > A (p.Pro276Pro), c.1040T > C (p.Asp297Asp), c.1234C > A (p.Pro362Gln), c.1420G > T (p.Arg424Leu), and c.1540C > T (p.Pro464Leu), but we did not identify any gene muta... Human Genetics journals http://www.medworm.com/rss/comments.php?id=3106550 Fri, 18 Dec 2009 16:38:42 +0100 3106550 http://www.medworm.com/index.php?rid=3066031&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fjk243282gj251j24%2F Content Type Journal ArticleCategory ErratumDOI 10.1007/s00439-009-0772-0Authors Fiona Connell, St George’s University of London Medical Genetics Unit, Clinical Developmental Sciences Cranmer Terrace London SW17 0RE UKKamini Kalidas, St George’s University of London Medical Genetics Unit, Clinical Developmental Sciences Cranmer Terrace London SW17 0RE UKPia Ostergaard, St George’s University of London Medical Genetics Unit, Clinical Developmental Sciences Cranmer Terrace London SW17 0RE UKGlen Brice, St George’s University of London South West Thames Regional Genetics Unit Cranmer Terrace London SW17 0RE UKTessa Homfray, St George’s University of London South West Thames Regional Genetics Unit Cranmer Terrace London SW17 0RE UKLesley Roberts, King’s College Hospital Harris ... Human Genetics journals http://www.medworm.com/rss/comments.php?id=3066031 Fri, 04 Dec 2009 21:15:03 +0100 3066031 http://www.medworm.com/index.php?rid=3043430&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F172705764063h408%2F Content Type Journal ArticleCategory Book ReviewDOI 10.1007/s00439-009-0764-0Authors Peter Holmans, Cardiff University Department of Psychological Medicine Cardiff UKLesley Jones, Cardiff University Department of Psychological Medicine Cardiff UK Journal Human GeneticsOnline ISSN 1432-1203Print ISSN 0340-6717 (Source: Human Genetics) Human Genetics journals http://www.medworm.com/rss/comments.php?id=3043430 Thu, 26 Nov 2009 07:59:20 +0100 3043430 http://www.medworm.com/index.php?rid=3032935&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fx16hr76kh7558318%2F Abstract  An efficient method to uniquely identify every individual would have value in quality control and sample tracking of large collections of cell lines or DNA as is now often the case with whole genome association studies. Such a method would also be useful in forensics. SNPs represent the best markers for such purposes. We have developed a globally applicable resource of 92 SNPs for individual identification (IISNPs) with extremely low probabilities of any two unrelated individuals from anywhere in the world having identical genotypes. The SNPs were identified by screening over 500 likely/candidate SNPs on samples of 44 populations representing the major regions of the world. All 92 IISNPs have an average heterozygosity >0.4 and the F st values are all <0.06 o... Human Genetics journals http://www.medworm.com/rss/comments.php?id=3032935 Mon, 23 Nov 2009 16:51:39 +0100 3032935 http://www.medworm.com/index.php?rid=3016825&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fp713p21x71468030%2F Abstract  Recent research into the human genome has generated a wealth of scientific knowledge and increased both public and professional interest in the concept of personalised medicine. Somewhat unexpectedly, in addition to increasing our understanding about the genetic basis for numerous diseases, these new discoveries have also spawned a burgeoning new industry of ‘consumer genetic testing’. In this paper, we present the principles learnt though the evaluation of tests for single gene disorders and suggest a comparable framework for the evaluation of genetic tests for susceptibility to common complex diseases. Both physicians and the general public will need to be able to assess the claims made by providers of genetic testing services, and ultimately policy-makers w... Human Genetics journals http://www.medworm.com/rss/comments.php?id=3016825 Thu, 19 Nov 2009 20:00:56 +0100 3016825 http://www.medworm.com/index.php?rid=3016826&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fv67h614x58p15373%2F This study revealed that all the three reported loci and the α-globin gene locus are the best and common predictors of the disease severity in β-thalassemia. Content Type Journal ArticleCategory Original InvestigationDOI 10.1007/s00439-009-0770-2Authors Manit Nuinoon, Mahidol University Thalassemia Research Center, Institute of Molecular Biosciences Phutthamonthon Nakhonpathom 73170 ThailandWattanan Makarasara, Mahidol University Thalassemia Research Center, Institute of Molecular Biosciences Phutthamonthon Nakhonpathom 73170 ThailandTaisei Mushiroda, RIKEN Center for Genomic Medicine Laboratory for Pharmacogenetics Yokohama 230-0045 JapanIswari Setianingsih, The Eijkman Institute for Molecular Biology Jalan Diponegoro 69 Jakarta 10430 IndonesiaPustika Amalia Wahidiyat, University ... Human Genetics journals http://www.medworm.com/rss/comments.php?id=3016826 Wed, 18 Nov 2009 19:15:27 +0100 3016826 http://www.medworm.com/index.php?rid=3011268&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fe537uv4u87425741%2F Content Type Journal ArticleCategory Short ReportDOI 10.1007/s00439-009-0760-4Authors Binbin Wang, Peking Union Medical College Graduate School Beijing ChinaZhimin Miao, Gout laboratory, Medical School Hospital of Qingdao University 16 Jiangsu Road Qingdao 266003 ChinaShiguo Liu, Gout laboratory, Medical School Hospital of Qingdao University 16 Jiangsu Road Qingdao 266003 ChinaJing Wang, Peking Union Medical College Graduate School Beijing ChinaShiyi Zhou, Peking Union Medical College Graduate School Beijing ChinaLin Han, Gout laboratory, Medical School Hospital of Qingdao University 16 Jiangsu Road Qingdao 266003 ChinaDongmei Meng, Gout laboratory, Medical School Hospital of Qingdao University 16 Jiangsu Road Qingdao 266003 ChinaYunlong Wang, Gout laboratory, Medical School Hospital o... Human Genetics journals http://www.medworm.com/rss/comments.php?id=3011268 Tue, 17 Nov 2009 23:47:37 +0100 3011268 http://www.medworm.com/index.php?rid=3011267&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fn6250522805x6817%2F In conclusion, common variants in MYH9 polymorphisms may not confer an increased risk of CKD in American Indian populations. Identification of the actual functional genetic variation responsible for the associations seen in African-Americans will likely help to clarify the lack of replication of this gene in our population of American Indians. Content Type Journal ArticleCategory Original InvestigationDOI 10.1007/s00439-009-0769-8Authors Nora Franceschini, University of North Carolina Department of Epidemiology 137 E. Franklin St., Suite 306 CB#8050 Chapel Hill NC 27514 USAV. Saroja Voruganti, Southwest Foundation for Biomedical Research Department of Genetics San Antonio TX USAKarin Haack, Southwest Foundation for Biomedical Research Department of Genetics San Antonio TX USALaura A... Human Genetics journals http://www.medworm.com/rss/comments.php?id=3011267 Tue, 17 Nov 2009 23:47:37 +0100 3011267 http://www.medworm.com/index.php?rid=3011266&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fx71657350505578m%2F This study examined the association of a promoter polymorphism of the leptin gene (LEP), G-2548A (rs7799039), and two non-synonymous single nucleotide polymorphisms of the leptin receptor gene (LEPR), K109R (rs1137100) and Q223R (rs1137101), with body weight, body mass index (BMI) and obesity (BMI ≥ 30) in Pacific Islanders. A total of 745 Austronesian (AN)-speaking participants were analyzed after adjusting for age, gender, and population differences. The results revealed that carriers of the 223Q alleles of LEPR had significantly higher body weight (P = 0.0009) and BMI (P = 0.0022) than non-carriers (i.e., 223R homozygotes); furthermore, the 223Q carriers also had a significantly higher risk of obesity in comparison to non-carriers (P = 0.022... Human Genetics journals http://www.medworm.com/rss/comments.php?id=3011266 Tue, 17 Nov 2009 23:47:37 +0100 3011266 http://www.medworm.com/index.php?rid=2998533&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fh6457q8856881nn7%2F This study was to investigate the association between gout and the MAOA single-nucleotide polymorphisms (SNPs) rs5953210, rs2283725, and rs1137070 as well as between gout and the COMT SNPs rs4680 Val158Met for 374 gout cases and 604 controls. MAO-A activity was also measured. All three MAOA SNPs were significantly associated with gout. A synonymous MAOA SNP, rs1137070 Asp470Asp, located in exon 14, was associated with the risk of having gout (P = 4.0 × 10−5, adjusted odds ratio 1.46, 95% confidence intervals [CI]: 1.11–1.91). We also showed that, when compared to individuals with the MAOA GAT haplotype, carriers of the AGC haplotype had a 1.67-fold (95% CI: 1.28–2.17) higher risk of gout. Moreover, we found that MAOA enzyme activity correlated positively with ... Human Genetics journals http://www.medworm.com/rss/comments.php?id=2998533 Fri, 13 Nov 2009 18:22:33 +0100 2998533 http://www.medworm.com/index.php?rid=2991941&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fy727j6220hu04101%2F Abstract  Generalised lymphatic dysplasia (GLD) is characterised by extensive peripheral lymphoedema with visceral involvement. In some cases, it presents in utero with hydrops fetalis. Autosomal dominant and recessive inheritance has been reported. A large, non-consanguineous family with three affected siblings with generalised lymphatic dysplasia is presented. One child died aged 5 months, one spontaneously miscarried at 17 weeks gestation, and the third has survived with extensive lymphoedema. All three presented with hydrops fetalis. There are seven other siblings who are clinically unaffected. Linkage analysis produced two loci on chromosome 18, covering 22 Mb and containing 150 genes, one of which is CCBE1. A homozygous cysteine to serine change in CCBE1... Human Genetics journals http://www.medworm.com/rss/comments.php?id=2991941 Thu, 12 Nov 2009 18:39:20 +0100 2991941 http://www.medworm.com/index.php?rid=2983980&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Ft06540u7060558g5%2F Abstract  Toll-like, vitamin A and D receptors and other innate proteins participate in various immune functions. We determined whether innate gene-sequence variations are associated with rubella vaccine-induced cytokine immune responses. We genotyped 714 healthy children (11–19 years of age) after two doses of rubella-containing vaccine for 148 candidate SNP markers. Rubella virus-induced cytokines were measured by ELISA. Twenty-two significant associations (range of P values 0.002–0.048) were found between SNPs in the vitamin A receptor family (RARA, RARB, TOP2B and RARG), vitamin D receptor and downstream mediator of vitamin D signaling (RXRA) genes and rubella virus-specific (IFN-γ, IL-2, IL-10, TNF-α, and GM-CSF) cytokine immune responses. A TLR3 gene promote... Human Genetics journals http://www.medworm.com/rss/comments.php?id=2983980 Mon, 09 Nov 2009 19:14:44 +0100 2983980 http://www.medworm.com/index.php?rid=2971750&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fh0747n0722482061%2F Content Type Journal ArticleCategory Human Gene MutationsDOI 10.1007/s00439-009-0757-z Journal Human GeneticsOnline ISSN 1432-1203Print ISSN 0340-6717 (Source: Human Genetics) Human Genetics journals http://www.medworm.com/rss/comments.php?id=2971750 Fri, 06 Nov 2009 18:58:01 +0100 2971750 http://www.medworm.com/index.php?rid=2969536&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Ft346521j61nh3562%2F In conclusion, we identified common haplotypes in the CFTR gene that influence survival and body composition in the population at large with no evidence for heterozygote advantage. Content Type Journal ArticleCategory Original InvestigationDOI 10.1007/s00439-009-0762-2Authors Maris Kuningas, Leiden University Medical Center (LUMC) Department of Gerontology and Geriatrics C2-R PO Box 9600 2300 RC Leiden The NetherlandsDavid van Bodegom, Leiden University Medical Center (LUMC) Department of Gerontology and Geriatrics C2-R PO Box 9600 2300 RC Leiden The NetherlandsLinda May, Leiden University Medical Center (LUMC) Department of Gerontology and Geriatrics C2-R PO Box 9600 2300 RC Leiden The NetherlandsJohannes J. Meij, Leyden Academy on Vitality and Ageing Leiden The NetherlandsP. Eline ... Human Genetics journals http://www.medworm.com/rss/comments.php?id=2969536 Wed, 04 Nov 2009 19:55:19 +0100 2969536 http://www.medworm.com/index.php?rid=2962233&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fl07757084x225808%2F Content Type Journal ArticleCategory Book ReviewDOI 10.1007/s00439-009-0759-xAuthors F. Lucy Raymond, Addenbrooke’s Hospital Cambridge Institute for Medical Research, Wellcome Trust/MRC Building Hills Road Cambridge CB2 0XY UK Journal Human GeneticsOnline ISSN 1432-1203Print ISSN 0340-6717 (Source: Human Genetics) Human Genetics journals http://www.medworm.com/rss/comments.php?id=2962233 Tue, 03 Nov 2009 11:09:19 +0100 2962233 http://www.medworm.com/index.php?rid=2962234&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fc55354232680453m%2F Abstract  The transcription factor GATA2 was reported to associate with coronary artery disease (CAD) in the family-based Genecard sample (Connelly et al. in PLoS Genet 2:e139, 2006). We asked whether GATA2 associates with sporadic cases of CAD in the Ottawa Heart Genomics Study (OHGS) and Cleveland Clinic (CC) populations. We genotyped the lead single nucleotide polymorphism (SNP) from Genecard, rs2713604 which is located in intron 5–6 of GATA2 in 600 CAD cases and 625 controls, as well as a tag SNP rs1573949 (r 2 = 0.87 in Caucasians of European ancestry in Utah from HapMap) in 1,136 cases and 1,162 controls in the OHGS1 population. A further 1,838 CAD cases and 913 controls derived from an independent sample combining genotypes from CC and OHGS2 populati... Human Genetics journals http://www.medworm.com/rss/comments.php?id=2962234 Tue, 03 Nov 2009 11:09:18 +0100 2962234 http://www.medworm.com/index.php?rid=2948160&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F18q0571598723218%2F This study compared the intracellular distribution and assembly of mutant Cx29 (Cx29E269D) with that of the wild-type Cx29 (Cx29WT) in HeLa cells and the effect the mutant protein had on those cells. Cx29TW showed continuous staining along apposed cell membranes in the fluorescent localization assay. In contrast, the p.E269D missense mutation resulted in accumulation of the Cx29 mutant protein in the endoplasmic reticulum (ER) rather than in the cytoplasmic membrane. Co-expression of Cx29WT and Cx29E269D proteins by a bi-directional tet-on expression system demonstrated that the heteromeric connexon accumulated in the cytoplasm, thereby impairing the formation of the gap junction. Based on these findings, we suggest that Cx29E269D has a dominant negative effect on the formation and f... Human Genetics journals http://www.medworm.com/rss/comments.php?id=2948160 Thu, 29 Oct 2009 19:39:10 +0100 2948160 http://www.medworm.com/index.php?rid=2937816&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fj6462013nw144785%2F Abstract  Given their involvement in processes necessary for life, mitochondrial damage and subsequent dysfunction can lead to a wide range of human diseases. Previous studies of both animal models and humans have suggested that presenilins-associated rhomboid-like protein (PARL) is a key regulator of mitochondrial integrity and function, and plays a role in cellular apoptosis. As a surrogate measure of mitochondrial integrity, we previously measured mitochondrial content in a Caucasian population consisting of large extended pedigrees, with results highlighting a substantial genetic component to this trait. To assess the influence of variation in the PARL gene on mitochondrial content, we re-sequenced 6.5 kb of the gene, identifying 16 SNPs and genotyped these in 1,086... Human Genetics journals http://www.medworm.com/rss/comments.php?id=2937816 Tue, 27 Oct 2009 17:59:55 +0100 2937816 http://www.medworm.com/index.php?rid=2937815&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Ft3n2k612525r802n%2F Content Type Journal ArticleCategory Book ReviewDOI 10.1007/s00439-009-0755-1Authors Michael Krawczak, Christian Albrechts University of Kiel Institute of Medical Informatics and Statistics Brunswiker Straße 10 24105 Kiel Germany Journal Human GeneticsOnline ISSN 1432-1203Print ISSN 0340-6717 (Source: Human Genetics) Human Genetics journals http://www.medworm.com/rss/comments.php?id=2937815 Tue, 27 Oct 2009 17:59:55 +0100 2937815 http://www.medworm.com/index.php?rid=2937817&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fl2g9574352711rpq%2F Abstract  Nitric oxide (NO) mediates host resistance to severe malaria and other infectious diseases. NO production and mononuclear cell expression of the NO producing enzyme-inducible nitric oxide synthase (NOS2) have been associated with protection from severe falciparum malaria. The purpose of this study was to identify single nucleotide polymorphisms (SNPs) and haplotypes in the NOS2 promoter, to identify associations of these haplotypes with malaria severity and to test the effects of these polymorphisms on promoter activity. We identified 34 SNPs in the proximal 7.3 kb region of the NOS2 promoter and inferred NOS2 promoter haplotypes based on genotyping 24 of these SNPs in a population of Tanzanian children with and without cerebral malaria. We identified 71 hapl... Human Genetics journals http://www.medworm.com/rss/comments.php?id=2937817 Mon, 26 Oct 2009 17:59:56 +0100 2937817 http://www.medworm.com/index.php?rid=2922633&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fw7260787k770132h%2F Abstract  Otosclerosis is a common form of hearing loss characterized by abnormal bone remodeling in the otic capsule. It is considered a complex disease caused by both genetic and environmental factors. In a previous study, we identified a region on chr7q22.1 located in the RELN gene that is associated with otosclerosis in Belgian–Dutch and French populations. Evidence for allelic heterogeneity was found in this chromosomal region in the form of two independent signals. To confirm this finding, we have completed a replication study that includes four additional populations from Europe (1,141 total samples). Several SNPs in this region replicated in these populations separately. While the power to detect significant association in each population is small, when all four p... Human Genetics journals http://www.medworm.com/rss/comments.php?id=2922633 Wed, 21 Oct 2009 19:29:23 +0100 2922633 http://www.medworm.com/index.php?rid=2897731&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fr241n5v030721703%2F Abstract  The cytochromes P450 (CYPs) are very efficient catalysts of foreign compound metabolism and are responsible for the major part of metabolism of clinically important drugs. The enzymes are important in cancer since they (a) activate dietary and environmental components to ultimate carcinogens, (b) activate or inactivate drugs used for cancer treatment, and (c) are potential targets for anticancer therapy. The genes encoding the CYP enzymes active in drug metabolism are highly polymorphic, whereas those encoding metabolism of precarcinogens are relatively conserved. A vast amount of literature is present where investigators have tried to link genetic polymorphism in CYPs to cancer susceptibility, although not much conclusive data have hitherto been obtained, with ex... Human Genetics journals http://www.medworm.com/rss/comments.php?id=2897731 Tue, 13 Oct 2009 08:17:25 +0100 2897731 http://www.medworm.com/index.php?rid=2897730&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F2708514264265235%2F Abstract  Transposable elements (TEs) make up a half of the human genome, but the extent of their contribution to cryptic exon activation that results in genetic disease is unknown. Here, a comprehensive survey of 78 mutation-induced cryptic exons previously identified in 51 disease genes revealed the presence of TEs in 40 cases (51%). Most TE-containing exons were derived from short interspersed nuclear elements (SINEs), with Alus and mammalian interspersed repeats (MIRs) covering >18 and >16% of the exonized sequences, respectively. The majority of SINE-derived cryptic exons had splice sites at the same positions of the Alu/MIR consensus as existing SINE exons and their inclusion in the mRNA was facilitated by phylogenetically conserved changes that improved both tra... Human Genetics journals http://www.medworm.com/rss/comments.php?id=2897730 Tue, 13 Oct 2009 08:17:25 +0100 2897730 http://www.medworm.com/index.php?rid=2897729&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fa7j684055m17g041%2F Abstract  Single nucleotide polymorphisms (SNPs) in the KLK3 gene on chromosome 19q13.33 are associated with serum prostate-specific antigen (PSA) levels. Recent genome wide association studies of prostate cancer have yielded conflicting results for association of the same SNPs with prostate cancer risk. Since the KLK3 gene encodes the PSA protein that forms the basis for a widely used screening test for prostate cancer, it is critical to fully characterize genetic variation in this region and assess its relationship with the risk of prostate cancer. We have conducted a next-generation sequence analysis in 78 individuals of European ancestry to characterize common (minor allele frequency, MAF >1%) genetic variation in a 56 kb region on chromosome 19q13.33 center... Human Genetics journals http://www.medworm.com/rss/comments.php?id=2897729 Tue, 13 Oct 2009 08:17:25 +0100 2897729 http://www.medworm.com/index.php?rid=2881041&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fg4h6l2777k40021u%2F In this study we analyzed all four known nonsynonymous SNPs within PCDH15 in 1,268 individuals from Finnish and Dutch multigenerational families with FCHL. Association analyses of quantitative traits for SNPs were performed using the QTDT test. The nonsynonymous SNP rs10825269 resulted in a P = 0.0006 for the quantitative TG trait. Additional evidence for association was observed with the same SNP for apolipoprotein B levels (apo-B) (P = 0.0001) and total cholesterol (TC) levels (P = 0.001). None of the other three SNPs tested showed a significant association with any lipid-related trait. We investigated the expression of PCDH15 in different human tissues and observed that PCDH15 is expressed in several tissues including liver and pancreas. In addition, we... Human Genetics journals http://www.medworm.com/rss/comments.php?id=2881041 Fri, 09 Oct 2009 06:07:02 +0100 2881041 http://www.medworm.com/index.php?rid=2878568&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F7vp6810373074738%2F Content Type Journal ArticleCategory ResponseDOI 10.1007/s00439-009-0747-1Authors Michael F. Hammer, University of Arizona ARL Division of Biotechnology Tucson AZ 85721 USADoron M. Behar, Rambam Health Care Campus Molecular Medicine Laboratory 31096 Haifa IsraelTatiana M. Karafet, University of Arizona ARL Division of Biotechnology Tucson AZ 85721 USAFernando L. Mendez, University of Arizona Department of EEB Tucson AZ 85721 USABrian Hallmark, University of Arizona ARL Division of Biotechnology Tucson AZ 85721 USATamar Erez, University of Arizona ARL Division of Biotechnology Tucson AZ 85721 USALev A. Zhivotovsky, Russian Academy of Sciences Institute of General Genetics 119991 Moscow RussiaSaharon Rosset, Tel Aviv University Department of Statistics and Operations Research, School of ... Human Genetics journals http://www.medworm.com/rss/comments.php?id=2878568 Thu, 08 Oct 2009 07:16:48 +0100 2878568 http://www.medworm.com/index.php?rid=2878569&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fe7701424635633p7%2F Content Type Journal ArticleCategory Letter to the EditorDOI 10.1007/s00439-009-0739-1Authors Anatole Alex Klyosov, Newton MA USA Journal Human GeneticsOnline ISSN 1432-1203Print ISSN 0340-6717 (Source: Human Genetics) Human Genetics journals http://www.medworm.com/rss/comments.php?id=2878569 Thu, 08 Oct 2009 07:16:47 +0100 2878569 http://www.medworm.com/index.php?rid=2878570&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F67412k40t870l152%2F Abstract  Corticotropin-releasing hormone receptor 2 (CRHR2) plays a role in both the central nervous system (CNS) and the peripheral nervous system. CRHR2 together with its ligands, urocortins (Ucns) and corticotropin-releasing hormone (CRH), functions as a mediator of inflammatory response and inhibitor of angiogenesis. Recently, it has been reported to be expressed in many human cancers. An association between rs2267716 polymorphism in the CRHR2 gene and susceptibility to hepatocellular carcinoma (HCC) was found in patients with chronic hepatitis C virus (HCV) infection. In the present study we analyzed, using a polymerase chain reaction–ligation detection reaction (PCR–LDR), the rs2267716 polymorphism in 364 hepatitis B virus (HBV)-related HCC patients, 196 non-HCC p... Human Genetics journals http://www.medworm.com/rss/comments.php?id=2878570 Thu, 08 Oct 2009 07:16:46 +0100 2878570 http://www.medworm.com/index.php?rid=2827184&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F4347533117458q31%2F Abstract  Tuberculosis (TB) is a global public health problem and a source of preventable deaths each year, with 8.8 million new cases of TB and 1.6 million deaths worldwide in 2005. Approximately, 10% of infected individuals develop pulmonary or extrapulmonary TB, suggesting that host defense factors influence development of active disease. Toll-like receptor’ (TLR) polymorphisms have been associated with regulation of TLR expression and development of active TB. In the present study, 71 polymorphisms in TLR1, TLR2, TLR4, TLR6, and TLR9 were examined from 474 (295 cases and 179 controls) African-Americans, 381 (237 cases and 144 controls) Caucasians, and from 667 (321 cases and 346 controls) Africans from Guinea-Bissau for association with pulmonary TB using generalized est... Human Genetics journals http://www.medworm.com/rss/comments.php?id=2827184 Mon, 21 Sep 2009 16:05:05 +0100 2827184 http://www.medworm.com/index.php?rid=2812006&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fb403m45216545628%2F In conclusion, the CEL gene is highly polymorphic, but mutations in CEL are likely to be a rare cause of monogenic diabetes. Content Type Journal ArticleCategory Original InvestigationDOI 10.1007/s00439-009-0740-8Authors Janniche Torsvik, University of Bergen Department of Clinical Medicine Bergen NorwayStefan Johansson, University of Bergen Department of Clinical Medicine Bergen NorwayAnders Johansen, Hagedorn Research Institute Gentofte DenmarkJakob Ek, Hagedorn Research Institute Gentofte DenmarkJayne Minton, Peninsula Medical School Institute of Biomedical and Clinical Science Exeter UKHelge Ræder, University of Bergen Department of Clinical Medicine Bergen NorwaySian Ellard, Peninsula Medical School Institute of Biomedical and Clinical Science Exeter UKAndrew Hattersley, Peninsu... Human Genetics journals http://www.medworm.com/rss/comments.php?id=2812006 Thu, 17 Sep 2009 12:09:40 +0100 2812006 http://www.medworm.com/index.php?rid=2812007&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F3318j26778784w12%2F We present here results of multiplex ligation-dependent probe amplification (MLPA) analysis performed in 22 of the 23 remaining probands, in whom sequencing had revealed no mutation. Large deletions, present at the heterozygous state, were detected in 10 patients: whole gene deletions in 5 and partial deletions removing either exon 6 (n = 2), exons 1–2 (n = 1) or exons 5–7 (n = 2) in 5 others. Exon 6 partial deletions are a 2,769-bp deletion and a 1,892-bp deletion associated with a 10-bp insertion, both having 5′ and/or 3′ breakpoints located within Alu repeat elements. In addition, we identified the 5′ breakpoint of a previously reported deletion of exons 1–2 within an extragenic Alu repeat. Distinct mutational mechanisms explaining these Alu... Human Genetics journals http://www.medworm.com/rss/comments.php?id=2812007 Thu, 17 Sep 2009 12:09:39 +0100 2812007 http://www.medworm.com/index.php?rid=2768094&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fl089w80136g2mwp6%2F Abstract  Over 300 blood group specificities on red cells have been identified, many of which are polymorphic. The molecular mechanisms responsible for these polymorphisms are diverse, though many simply represent single nucleotide polymorphisms (SNPs). Other mechanisms include the following: gene deletion; single nucleotide deletion and sequence duplication, which introduce reading-frame shifts; nonsense mutation; intergenic recombination between closely linked genes, giving rise to hybrid genes and hybrid proteins; and a SNP in the promoter region of a blood group gene. Examples of these various genetic mechanisms are taken from the ABO, Rh, Kell, and Duffy blood group systems. Null phenotypes, in which no antigens of a blood group system are expressed, are not generally ... Human Genetics journals http://www.medworm.com/rss/comments.php?id=2768094 Thu, 03 Sep 2009 06:26:40 +0100 2768094 http://www.medworm.com/index.php?rid=2745360&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fy6156x4113404v2j%2F In this study, we explored the relationship between type 1 collagen genes and the quantitative trait central corneal thickness (CCT). CCT was measured in a cohort of 28 Australian type I OI patients and mean CCT was found to be significantly lower compared to a normal population (P < 0.001). We then investigated CCT and corneal collagen fibril diameter and density in a mouse model of OI with a col1a2 mutation. Mean CCT was significantly lower in mutant mice (P = 0.002), as was corneal collagen fibril diameter (P = 0.034), whilst collagen fibril density was significantly greater in mutants (P = 0.034). Finally, we conducted a genetic study to determine whether common single nucleotide polymorphisms (SNPs) in COL1A1 and COL1A2 are associated with ... Human Genetics journals http://www.medworm.com/rss/comments.php?id=2745360 Fri, 28 Aug 2009 16:58:52 +0100 2745360 http://www.medworm.com/index.php?rid=2736855&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F8l628qv12t3p3783%2F Abstract  Atrial fibrillation (AF) is the most common arrhythmia in the clinical setting and an independent risk factor for stroke. Approximately 10 million Chinese people are affected by AF, but the genetic basis is largely unknown. A recent genome-wide association study in Iceland identified association between SNP rs2200733 on 4q25 and AF; however, many independent replication studies are essential to unequivocally validate this association. To assess the association between rs2200733 and AF as well as that between rs2200733 and ischemic stroke in a mainland Chinese Han population, we carried out case–control association studies with 383 AF patients versus 851 non-AF controls and 811 ischemic stroke patients versus 688 non-stroke controls. Highly significant associatio... Human Genetics journals http://www.medworm.com/rss/comments.php?id=2736855 Tue, 25 Aug 2009 16:46:13 +0100 2736855 http://www.medworm.com/index.php?rid=2736856&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F03732j256g7342p7%2F We report a three generation family with five affected members, all of whom have hearing loss, craniofacial defects, and a paracentric inversion of the long arm of chromosome 7, inv(7)(q21.3q35). High resolution mapping of the inversion showed that the 7q21.3 breakpoint is located 65 and 80 kb centromeric of DLX6 and DLX5, respectively. Further analysis revealed a 5,115 bp deletion at the 7q21.3 breakpoint. While the breakpoint does not disrupt either DLX5 or DLX6, the syndrome present in the family is similar to that observed in Dlx5 knockout mice and includes a subset of the features observed in individuals with DLX5 and DLX6 deletions, implicating dysregulation of DLX5 and DLX6 in the family’s phenotype. Bioinformatic analysis indicates that the 5,115 bp deletion at... Human Genetics journals http://www.medworm.com/rss/comments.php?id=2736856 Tue, 25 Aug 2009 16:46:12 +0100 2736856 http://www.medworm.com/index.php?rid=2729139&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fk3h41v38w300v014%2F Abstract  Infantile hypertrophic pyloric stenosis (IHPS) is the most common inherited form of gastrointestinal obstruction in infancy with a striking male preponderance. Infants present with vomiting due to gastric outlet obstruction caused by hypertrophy of the smooth muscle of the pylorus. Two loci specific to extended pedigrees displaying autosomal dominant inheritance have been identified. A genome scan identified loci on chromosomes 11q14–q22 and Xq23–q24 which are predicted to be responsible for a subset of smaller families with IHPS demonstrating non-Mendelian inheritance. The two linked chromosomal regions both harbour functional candidate genes which are members of the canonical transient receptor potential (TRPC) family of ion channels. Both TRPC5 (Xq23–q24)... Human Genetics journals http://www.medworm.com/rss/comments.php?id=2729139 Sat, 22 Aug 2009 18:53:20 +0100 2729139 http://www.medworm.com/index.php?rid=2729140&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fj0051212mlt50l22%2F Abstract  Proximal spinal muscular atrophy (SMA) is a neuromuscular disease caused by low levels of the survival motor neuron (SMN) protein. In humans there are two nearly identical SMN genes, SMN1 and SMN2. The SMN2 gene generates a truncated protein, due to a C to T nucleotide alteration in exon 7, which leads to inefficient RNA splicing of exon 7. This exclusion of SMN exon 7 is central to the onset of the SMA disease. Exon 7 splicing is regulated by a number of exonic and intronic splicing regulatory sequences and the trans-factors that bind them. Here, we identify conserved intronic sequences in the SMN genes. Five regions were examined due to conservation and their proximity to exons 6 through 8. Using mutagenesis two conserved elements located in intron 7 of the SMN ge... Human Genetics journals http://www.medworm.com/rss/comments.php?id=2729140 Sat, 22 Aug 2009 18:53:19 +0100 2729140 http://www.medworm.com/index.php?rid=2724090&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Few6146081171863m%2F Content Type Journal ArticleCategory Book ReviewDOI 10.1007/s00439-009-0734-6Authors Ray Waters, Cardiff University Department of Pathology Tenovus Building, Heath Park Cardiff UK Journal Human GeneticsOnline ISSN 1432-1203Print ISSN 0340-6717 (Source: Human Genetics) Human Genetics journals http://www.medworm.com/rss/comments.php?id=2724090 Fri, 21 Aug 2009 15:28:43 +0100 2724090 http://www.medworm.com/index.php?rid=2718757&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F5526818475586708%2F In this study, we have carried out fine linkage mapping in the 18q region previously linked to diabetic nephropathy in AAs by genotyping both microsatellite and single nucleotide polymorphisms (SNPs) for linkage analysis in an expanded set of 223 AA families multiplexed for type 2 diabetes associated ESRD (T2DM-ESRD). Several approaches were used to evaluate evidence of linkage with the strongest evidence for linkage in ordered subset analysis with an earlier age of T2DM diagnosis compared to the remaining pedigrees (LOD 3.9 at 90.1 cM, ∆P = 0.0161, NPL P value = 0.00002). Overall, the maximum LODs and LOD-1 intervals vary in magnitude and location depending upon analysis. The linkage mapping was followed up by performing a dense SNP map, genotyping 2,81... Human Genetics journals http://www.medworm.com/rss/comments.php?id=2718757 Wed, 19 Aug 2009 08:31:19 +0100 2718757 http://www.medworm.com/index.php?rid=2707990&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F59601r6k12vvg61p%2F Abstract  Mutations in the transcription factor encoding TFAP2A gene underlie branchio-oculo-facial syndrome (BOFS), a rare dominant disorder characterized by distinctive craniofacial, ocular, ectodermal and renal anomalies. To elucidate the range of ocular phenotypes caused by mutations in TFAP2A, we took three approaches. First, we screened a cohort of 37 highly selected individuals with severe ocular anomalies plus variable defects associated with BOFS for mutations or deletions in TFAP2A. We identified one individual with a de novo TFAP2A four amino acid deletion, a second individual with two non-synonymous variations in an alternative splice isoform TFAP2A2, and a sibling-pair with a paternally inherited whole gene deletion with variable phenotypic expression. Second, we d... Human Genetics journals http://www.medworm.com/rss/comments.php?id=2707990 Sat, 15 Aug 2009 11:03:39 +0100 2707990 http://www.medworm.com/index.php?rid=2707991&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fpl63350084870354%2F Abstract  ATP-sensitive K+ (KATP) channels maintain cardiac homeostasis under stress, as revealed by murine gene knockout models of the KCNJ11-encoded Kir6.2 pore. However, the translational significance of KATP channels in human cardiac physiology remains largely unknown. Here, the frequency of the minor K23 allele of the common functional Kir6.2 E23K polymorphism was found overrepresented in 115 subjects with congestive heart failure compared to 2,031 community-based controls (69 vs. 56%, P < 0.001). Moreover, the KK genotype, present in 18% of heart failure patients, was associated with abnormal cardiopulmonary exercise stress testing. In spite of similar baseline heart rates at rest among genotypic subgroups (EE: 72.2 ± 2.3, EK: 75.0 ± 1.... Human Genetics journals http://www.medworm.com/rss/comments.php?id=2707991 Fri, 14 Aug 2009 17:47:51 +0100 2707991 http://www.medworm.com/index.php?rid=2687450&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F357176p177623m41%2F Abstract  It has been known for over a decade that a majority of men who self report as members of the Jewish priesthood (Cohanim) carry a characteristic Y chromosome haplotype termed the Cohen Modal Haplotype (CMH). The CMH has since been used to trace putative Jewish ancestral origins of various populations. However, the limited number of binary and STR Y chromosome markers used previously did not provide the phylogenetic resolution needed to infer the number of independent paternal lineages that are encompassed within the Cohanim or their coalescence times. Accordingly, we have genotyped 75 binary markers and 12 Y-STRs in a sample of 215 Cohanim from diverse Jewish communities, 1,575 Jewish men from across the range of the Jewish Diaspora, and 2,099 non-Jewish men from t... Human Genetics journals http://www.medworm.com/rss/comments.php?id=2687450 Sun, 09 Aug 2009 07:10:46 +0100 2687450 http://www.medworm.com/index.php?rid=2683613&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F380122nh077u0m53%2F Abstract  Cystic fibrosis (CF) is a monogenic disease due to mutations in the CFTR gene. Yet, variability in CF disease presentation is presumed to be affected by modifier genes, such as those recently demonstrated for the pulmonary aspect. Here, we conduct a modifier gene study for meconium ileus (MI), an intestinal obstruction that occurs in 16–20% of CF newborns, providing linkage and association results from large family and case–control samples. Linkage analysis of modifier traits is different than linkage analysis of primary traits on which a sample was ascertained. Here, we articulate a source of confounding unique to modifier gene studies and provide an example of how one might overcome the confounding in the context of linkage studies. Our linkage analysis provi... Human Genetics journals http://www.medworm.com/rss/comments.php?id=2683613 Fri, 07 Aug 2009 11:16:44 +0100 2683613 http://www.medworm.com/index.php?rid=2680997&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fwt24314k75120p70%2F Abstract  The immensity of genes and molecules implicated in gastric carcinogenesis is overwhelming and the relevant importance of some of these molecules is too often unclear. This review serves to bring us up-to-date with the latest findings as well as to look at the larger picture in terms of how to tackle the problem of solving this multi-piece puzzle. In this review, the environmental nurturing of intestinal cancer is discussed, beginning with epidemiology (known causative factors for inducing molecular change), an update of H. pylori research, including the role of inflammation and stem cells in premalignant lesions. The role of E-cadherin in the nature (genotype) of diffuse gastric cancer is highlighted, and finally the ever growing discipline of SNP analysis (includi... Human Genetics journals http://www.medworm.com/rss/comments.php?id=2680997 Wed, 05 Aug 2009 18:31:15 +0100 2680997 http://www.medworm.com/index.php?rid=2681000&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fy0503p6747715906%2F Abstract  Endurance performance is a complex phenotype subject to the influence of both environmental and genetic factors. Although the last decade has seen a variety of specific genetic factors proposed, many in metabolic pathways, each is likely to make a limited contribution to an ‘elite’ phenotype: it seems more likely that such status depends on the simultaneous presence of multiple such variants. The aim of the study was to investigate individually and in combination the association of common metabolic gene polymorphisms with endurance athlete status, the proportion of slow-twitch muscle fibers and maximal oxygen consumption. A total of 1,423 Russian athletes and 1,132 controls were genotyped for 15 gene polymorphisms, of which most were previously reported to be ... Human Genetics journals http://www.medworm.com/rss/comments.php?id=2681000 Mon, 03 Aug 2009 20:45:23 +0100 2681000 http://www.medworm.com/index.php?rid=2680999&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fy801077h4373g730%2F Content Type Journal ArticleCategory ErratumDOI 10.1007/s00439-009-0725-7Authors Maj Hultén, University of Warwick Department of Biological Sciences, Warwick Medical School Coventry CV4 7AL UK Journal Human GeneticsOnline ISSN 1432-1203Print ISSN 0340-6717 (Source: Human Genetics) Human Genetics journals http://www.medworm.com/rss/comments.php?id=2680999 Mon, 03 Aug 2009 20:45:23 +0100 2680999 http://www.medworm.com/index.php?rid=2680998&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F81262q507005306r%2F Content Type Journal ArticleCategory Book ReviewDOI 10.1007/s00439-009-0726-6Authors Willatt Lionel, Addenbrooke’s Hospital East Anglian Medical Genetics Service, Molecular Genetics Cambridge UKSian M. Morgan, University Hospital of Wales Cytogenetics Laboratory, Medical Genetics Service for Wales Heath Park Cardiff UK Journal Human GeneticsOnline ISSN 1432-1203Print ISSN 0340-6717 (Source: Human Genetics) Human Genetics journals http://www.medworm.com/rss/comments.php?id=2680998 Mon, 03 Aug 2009 20:45:23 +0100 2680998 http://www.medworm.com/index.php?rid=3099439&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fpv372ru817082661%2F Abstract  Genome-wide association studies of prostate cancer have identified single nucleotide polymorphism (SNP) markers in a region of chromosome 10q11.2, harboring the microseminoprotein-β (MSMB) gene. Both the gene product of MSMB, the prostate secretory protein 94 (PSP94) and its binding protein (PSPBP), have been previously investigated as serum biomarkers for prostate cancer progression. Recent functional work has shown that different alleles of the significantly associated SNP in the promoter of MSMB found to be associated with prostate cancer risk, rs10993994, can influence its expression in tumors and in vitro studies. Since it is plausible that additional variants in this region contribute to the risk of prostate cancer, we have used next-generation sequencing te... Human Genetics journals http://www.medworm.com/rss/comments.php?id=3099439 Thu, 30 Jul 2009 19:54:42 +0100 3099439 http://www.medworm.com/index.php?rid=2662230&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fpv372ru817082661%2F Abstract  Genome-wide association studies of prostate cancer have identified single nucleotide polymorphism (SNP) markers in a region of chromosome 10q11.2, harboring the microseminoprotein-β (MSMB) gene. Both the gene product of MSMB, the prostate secretory protein 94 (PSP94) and its binding protein (PSPBP), have been previously investigated as serum biomarkers for prostate cancer progression. Recent functional work has shown that different alleles of the significantly associated SNP in the promoter of MSMB found to be associated with prostate cancer risk, rs10993994, can influence its expression in tumors and in vitro studies. Since it is plausible that additional variants in this region contribute to the risk of prostate cancer, we have used next-generation sequencing te... Human Genetics journals http://www.medworm.com/rss/comments.php?id=2662230 Thu, 30 Jul 2009 19:54:42 +0100 2662230 http://www.medworm.com/index.php?rid=2662231&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F7353784j86644158%2F Content Type Journal ArticleCategory Human Gene MutationsDOI 10.1007/s00439-009-0717-7 Journal Human GeneticsOnline ISSN 1432-1203Print ISSN 0340-6717 (Source: Human Genetics) Human Genetics journals http://www.medworm.com/rss/comments.php?id=2662231 Thu, 30 Jul 2009 19:54:41 +0100 2662231 http://www.medworm.com/index.php?rid=2644237&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fy2101158w30h5336%2F This study provides evidence for the involvement of host genetic factors in susceptibility/resistance to HCV infection in endemic conditions. Content Type Journal ArticleCategory Original InvestigationDOI 10.1007/s00439-009-0721-yAuthors Cédric Laouénan, Institut National de la Santé et de la Recherche Médicale (INSERM), U550 Laboratoire de Génétique Humaine des Maladies Infectieuses, Faculté de Médecine Necker 156 rue de Vaugirard 75015 Paris FranceSabine Plancoulaine, Institut National de la Santé et de la Recherche Médicale (INSERM), U550 Laboratoire de Génétique Humaine des Maladies Infectieuses, Faculté de Médecine Necker 156 rue de Vaugirard 75015 Paris FranceMostafa Kamal Mohamed, Ain Shams University Department of Community, Environmental and Occupational Medici... Human Genetics journals http://www.medworm.com/rss/comments.php?id=2644237 Sat, 25 Jul 2009 04:21:25 +0100 2644237 http://www.medworm.com/index.php?rid=2605073&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fe348278wt501p1j8%2F Abstract  Hot water epilepsy is a reflex or sensory epilepsy in which seizures are triggered by the stimulus of bathing in hot water. Although there is evidence of a genetic basis to its etiology, no gene associated with this disorder has so far been found. In order to identify the genetic locus involved in the pathophysiology of hot water epilepsy, we performed a genome-wide linkage analysis in a four-generation family manifesting the disorder in an autosomal dominant manner. Significant linkage was detected on chromosome 4q24-q28, with the highest two-point LOD score of 3.50 at recombination value (θ) of 0 for the marker D4S402. Centromere-proximal and centromere-distal boundaries of this locus were defined by the markers D4S1572 and D4S2277, respectively. The critical ge... Human Genetics journals http://www.medworm.com/rss/comments.php?id=2605073 Tue, 14 Jul 2009 09:57:25 +0100 2605073 http://www.medworm.com/index.php?rid=2605074&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fm0nmg8w270325655%2F Abstract  To confirm and refine associations of human leukocyte antigen (HLA) genotypes with variable antibody (Ab) responses to hepatitis B vaccination, we have analyzed 255 HIV-1 seropositive (HIV+) youth and 80 HIV-1 seronegatives (HIV−) enrolled into prospective studies. In univariate analyses that focused on HLA-DRB1, -DQA1, and -DQB1 alleles and haplotypes, the DRB1*03 allele group and DRB1*0701 were negatively associated with the responder phenotype (serum Ab concentration ≥ 10 mIU/mL) (P = 0.026 and 0.043, respectively). Collectively, DRB1*03 and DRB1*0701 were found in 42 (53.8%) out of 78 non-responders (serum Ab <10 mIU/mL), 65 (40.6%) out of 160 medium responders (serum Ab 10–1,000 mIU/mL), and 27 (27.8%) out of 97 high r... Human Genetics journals http://www.medworm.com/rss/comments.php?id=2605074 Tue, 14 Jul 2009 09:57:24 +0100 2605074 http://www.medworm.com/index.php?rid=2592849&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fw34m021640662l63%2F Abstract  Hyperuricemia is associated with the metabolic syndrome, gout, renal and cardiovascular disease (CVD). American Indians have high rates of CVD and 25% of individuals in the strong heart family study (SHFS) have high serum uric acid levels. The aim of this study was to investigate the genetic determinants of serum uric acid variation in American Indian participants of the SHFS. A variance component decomposition approach (implemented in SOLAR) was used to conduct univariate genetic analyses in each of three study centers and the combined sample. Serum uric acid was adjusted for age, sex, age × sex, BMI, estimated glomerular filtration rate, alcohol intake, diabetic status and medications. Overall mean ± SD serum uric acid for all individuals w... Human Genetics journals http://www.medworm.com/rss/comments.php?id=2592849 Fri, 10 Jul 2009 08:10:31 +0100 2592849 http://www.medworm.com/index.php?rid=2592850&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fd44l76l745705442%2F Abstract  Sequence tag analysis using serial analysis of gene expression (SAGE) is a powerful strategy for the quantitative analysis of gene expression in human genetic disorders. SAGE facilitates the measurement of mRNA transcripts and generates a non-biased gene expression profile of normal and pathological disease tissue. In addition, the SAGE technique has the capacity of detecting the expression of novel transcripts allowing for the identification of previously uncharacterised genes, thus providing a unique advantage over the traditional microarray-based approach for expression profiling. The technique has been successful in providing pathological gene expression profiles in a number of common genetic disorders including diabetes, cardiovascular disease, Parkinson dise... Human Genetics journals http://www.medworm.com/rss/comments.php?id=2592850 Fri, 10 Jul 2009 08:10:30 +0100 2592850 http://www.medworm.com/index.php?rid=2592852&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F7w478l41r7mvg68k%2F Abstract  The genetic basis of melanoma is complex and has both inherited and acquired components. Different genomic approaches have been used to identify a number of inherited risk factors, which can be stratified by penetrance and prevalence. Rare high-penetrance factors are expressed in familial clustering of melanoma and include mutations in CDKN2A (encoding p16INK4a and p14ARF) and CDK4. These genes are involved in cell-cycle arrest and melanocyte senescence and are nearly invariably targeted by somatic mutations during melanoma progression. Low-penetrance factors are common in the general population and include single-nucleotide polymorphisms in or near MC1R, ASIP, TYR and TYRP1. These genes are major determinants of hair and skin pigmentation, but their role in melanom... Human Genetics journals http://www.medworm.com/rss/comments.php?id=2592852 Thu, 09 Jul 2009 12:14:00 +0100 2592852 http://www.medworm.com/index.php?rid=2592851&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Ff25442465371627u%2F Content Type Journal ArticleCategory Book ReviewDOI 10.1007/s00439-009-0709-7Authors Maj Hulten, University of Warwick Department of Biological Sciences, Warwick Medical School Coventry CV4 7AL UK Journal Human GeneticsOnline ISSN 1432-1203Print ISSN 0340-6717 (Source: Human Genetics) Human Genetics journals http://www.medworm.com/rss/comments.php?id=2592851 Thu, 09 Jul 2009 12:14:00 +0100 2592851 http://www.medworm.com/index.php?rid=2590479&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fj6r0478776413t6j%2F Abstract  Preeclampsia is a heritable pregnancy disorder that presents new onset hypertension and proteinuria. We have previously reported genetic linkage to preeclampsia on chromosomes 2q, 5q and 13q in an Australian/New Zealand (Aust/NZ) familial cohort. This current study centered on identifying the susceptibility gene(s) at the 5q locus. We first prioritized candidate genes using a bioinformatic tool designed for this purpose. We then selected a panel of known SNPs within ten prioritized genes and genotyped them in an extended set of the Aust/NZ families and in a very large, independent Norwegian case/control cohort (1,139 cases, 2,269 controls). In the Aust/NZ cohort we identified evidence of a genetic association for the endoplasmic reticulum aminopeptidase 1 (ERAP1) ... Human Genetics journals http://www.medworm.com/rss/comments.php?id=2590479 Mon, 06 Jul 2009 20:15:19 +0100 2590479 http://www.medworm.com/index.php?rid=2579225&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fwk832573j444j415%2F Abstract  Tuberculosis (TB) has substantial mortality worldwide with 5–10% of those exposed progressing to active TB disease. Studies in mice and humans indicate that the inducible nitric oxide synthase (iNOS) molecule plays an important role in immune response to TB. A mixed case–control association study of individuals with TB, relatives, or close contact controls was performed in 726 individuals (279 case and 166 control African-Americans; 198 case and 123 control Caucasians). Thirty-nine single nucleotide polymorphisms (SNPs) were selected from the NOS2A gene for single SNP, haplotype, and multilocus interaction analyses with other typed candidate genes using generalized estimating equations. In African-Americans, ten NOS2A SNPs were associated with TB. The strongest... Human Genetics journals http://www.medworm.com/rss/comments.php?id=2579225 Mon, 06 Jul 2009 16:51:23 +0100 2579225 http://www.medworm.com/index.php?rid=2568191&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fq36q678240137887%2F In conclusion, we confirmed ancestry associations on 8q24, and identified additional ancestry-associated regions potentially harboring prostate cancer susceptibility loci. Content Type Journal ArticleCategory Original InvestigationDOI 10.1007/s00439-009-0712-zAuthors Cathryn Hufford Bock, Wayne State University School of Medicine 110 E. Warren Ave Detroit MI 48201 USAAnn G. Schwartz, Wayne State University School of Medicine 110 E. Warren Ave Detroit MI 48201 USAJulie J. Ruterbusch, Karmanos Cancer Institute 4100 John R Detroit MI 48201 USAAlbert M. Levin, Henry Ford Health System One Ford Place Detroit MI 48202 USAChristine Neslund-Dudas, Henry Ford Health System One Ford Place Detroit MI 48202 USASusan J. Land, Wayne State University School of Medicine 110 E. Warren Ave Detroit MI... Human Genetics journals http://www.medworm.com/rss/comments.php?id=2568191 Wed, 01 Jul 2009 06:14:51 +0100 2568191 http://www.medworm.com/index.php?rid=2568193&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fx44j652054l67t05%2F In conclusion, in addition to the association of CNR2 polymorphisms with low BMD at selected clinically relevant skeletal sites, we now report their significant association with hand bone strength phenotypes using a family-based study design implying an even broader impact of genetic variation at the CNR2 locus on bone structure and function. Content Type Journal ArticleCategory Original InvestigationDOI 10.1007/s00439-009-0708-8Authors Meliha Karsak, University of Bonn Department of Molecular Psychiatry, Life and Brain Center Sigmund-Freud-Strasse 25 53127 Bonn GermanyIda Malkin, Tel Aviv University Human Population Biology Research Unit, Department of Anatomy and Anthropology, Sackler Faculty of Medicine 69978 Tel Aviv IsraelMohammad R. Toliat, University of Cologne Institute for... Human Genetics journals http://www.medworm.com/rss/comments.php?id=2568193 Tue, 30 Jun 2009 15:40:55 +0100 2568193 http://www.medworm.com/index.php?rid=2568192&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F78565x20m608147q%2F Content Type Journal ArticleCategory Historical and Personal PerspectivesDOI 10.1007/s00439-009-0690-1Authors Marthe Gautier, 6 Rue de Douai 75009 Paris FrancePeter S. Harper, Cardiff University Institute of Medical Genetics, School of Medicine 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=2568192 Tue, 30 Jun 2009 15:40:55 +0100 2568192 http://www.medworm.com/index.php?rid=2550005&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Ft03847r0311472r6%2F We report four new patients with a submicroscopic deletion in 15q24 manifesting developmental delay, short stature, hypotonia, digital abnormalities, joint laxity, genital abnormalities, and characteristic facial features. These clinical features are shared with six recently reported patients with a 15q24 microdeletion, supporting the notion that this is a recognizable syndrome. We describe a case of an ~2.6 Mb microduplication involving a portion of the minimal deletion critical region in a 15-year-old male with short stature, mild mental retardation, attention deficit hyperactivity disorder, Asperger syndrome, decreased joint mobility, digital abnormalities, and characteristic facial features. Some of these features are shared with a recently reported case with a 15q24 microdu... Human Genetics journals http://www.medworm.com/rss/comments.php?id=2550005 Fri, 26 Jun 2009 07:14:10 +0100 2550005 http://www.medworm.com/index.php?rid=2550006&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fg1070h252t881164%2F Content Type Journal ArticleCategory EditorialDOI 10.1007/s00439-009-0705-yAuthors Michael C. O’Donovan, MRC Centre for Neuropsychiatric Genetics and Genomics Department of Psychological Medicine and Neurology, School of Medicine Heath Park Cardiff CF23 6BQ UKMichael J. Owen, MRC Centre for Neuropsychiatric Genetics and Genomics Department of Psychological Medicine and Neurology, School of Medicine Heath Park Cardiff CF23 6BQ UK Journal Human GeneticsOnline ISSN 1432-1203Print ISSN 0340-6717 (Source: Human Genetics) Human Genetics journals http://www.medworm.com/rss/comments.php?id=2550006 Thu, 25 Jun 2009 06:53:12 +0100 2550006 http://www.medworm.com/index.php?rid=2500645&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F59145157631m1866%2F Content Type Journal ArticleCategory Book ReviewDOI 10.1007/s00439-009-0710-1Authors Angus J. Clarke, Cardiff University Institute of Medical Genetics, School of Medicine Heath Park Cardiff UK Journal Human GeneticsOnline ISSN 1432-1203Print ISSN 0340-6717 (Source: Human Genetics) Human Genetics journals http://www.medworm.com/rss/comments.php?id=2500645 Tue, 23 Jun 2009 06:03:40 +0100 2500645 http://www.medworm.com/index.php?rid=2500646&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fl16048m2647631x7%2F Content Type Journal ArticleCategory Book ReviewDOI 10.1007/s00439-009-0711-0Authors Arianna Di Florio, Cardiff University Department of Psychological Medicine and Neurology, School of Medicine Cardiff CF14 4XN UKNick Craddock, Cardiff University Department of Psychological Medicine and Neurology, School of Medicine 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=2500646 Mon, 22 Jun 2009 06:34:00 +0100 2500646 http://www.medworm.com/index.php?rid=2500647&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fcj2767812p2t1421%2F Abstract  Epilepsy is the most common neurological disorder affecting young people. The etiologies are multiple and most cases are sporadic. However, some rare families with Mendelian inheritance have provided evidence of genes’ important role in epilepsy. Two important but apparently different groups of disorders have been extensively studied: epilepsies associated with malformations of cortical development (MCDs) and epilepsies associated with a structurally normal brain (or with minimal abnormalities only). This review is focused on clinical and molecular aspects of focal cortical dysplasia, polymicrogyria, periventricular nodular heterotopia, subcortical band heterotopia, lissencephaly and schizencephaly as examples of MCDs. Juvenile myoclonic epilepsy, childhood abse... Human Genetics journals http://www.medworm.com/rss/comments.php?id=2500647 Thu, 18 Jun 2009 15:45:56 +0100 2500647 http://www.medworm.com/index.php?rid=2500648&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fq7t73736hg8p5124%2F Abstract  Alcohol dependence (AD), a genetically influenced phenotype, is extremely costly to individuals and to society in the United States and throughout the world, contributing to morbidity and mortality and a host of economic, interpersonal, and societal problems. Although until recently the only genes established to affect risk for AD were those encoding several alcohol metabolizing enzymes, there are now several other genes that can be regarded as confirmed risk loci, discovered through linkage and candidate gene association studies. While the mechanism of action of the effects of alcohol-metabolizing enzymes on AD risk is thought to be well understood, we are still in the early stages of understanding the physiology of other risk loci. Further, it is clear that only... Human Genetics journals http://www.medworm.com/rss/comments.php?id=2500648 Wed, 17 Jun 2009 07:06:03 +0100 2500648 http://www.medworm.com/index.php?rid=2500649&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fjv7558659u562518%2F Abstract  Posterior microphthalmia (PM) is a relatively rare autosomal recessive condition with normal anterior segment and small posterior segment resulting in high hyperopia and retinal folding. It is an uncommon subtype of microphthalmia that has been mostly reported to coexist with several other ophthalmic conditions and to occur in sporadic cases. The membrane-type frizzled-related protein (MFRP) is the only gene so far reported implicated in autosomal recessive, non-syndromic and syndromic forms of PM. Here, we performed a clinical and genetic analysis using six consanguineous families ascertained from different regions of Tunisia and affected with non-syndromic PM that segregates as an autosomal recessive trait. To identify the disease-causing defect in these families... Human Genetics journals http://www.medworm.com/rss/comments.php?id=2500649 Mon, 15 Jun 2009 07:22:49 +0100 2500649 http://www.medworm.com/index.php?rid=2500650&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F0202764204r62604%2F Abstract  Postprandial triglyceridemia is an emerging risk factor for cardiovascular disease. However, most of the genes that influence postprandial triglyceridemia are not known. We evaluated whether a common nonsynonymous SNP rs1260326/P446L in the glucokinase regulatory protein (GCKR) gene influenced variation in the postprandial lipid response after a high-fat challenge in seven hundred and seventy participants in the Amish HAPI Heart Study who underwent an oral high-fat challenge and had blood samples taken in the fasting state and during the postprandial phase at 1, 2, 3, 4, and 6 h. We found that the minor T allele at rs1260326 was associated with significantly higher fasting TG levels after adjusting for age, sex, and family structure (P a = 0.06 for ... Human Genetics journals http://www.medworm.com/rss/comments.php?id=2500650 Sat, 13 Jun 2009 08:38:37 +0100 2500650 http://www.medworm.com/index.php?rid=2500651&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fp775078136347645%2F Abstract  Down syndrome (DS) is caused by trisomy of all or part of human chromosome 21 (HSA21) and is the most common genetic cause of significant intellectual disability. In addition to intellectual disability, many other health problems, such as congenital heart disease, Alzheimer’s disease, leukemia, hypotonia, motor disorders, and various physical anomalies occur at an elevated frequency in people with DS. On the other hand, people with DS seem to be at a decreased risk of certain cancers and perhaps of atherosclerosis. There is wide variability in the phenotypes associated with DS. Although ultimately the phenotypes of DS must be due to trisomy of HSA21, the genetic mechanisms by which the phenotypes arise are not understood. The recent recognition that there are ma... Human Genetics journals http://www.medworm.com/rss/comments.php?id=2500651 Sat, 13 Jun 2009 08:38:34 +0100 2500651 http://www.medworm.com/index.php?rid=2500652&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fa54808054h587k82%2F Abstract  The major psychotic illnesses, schizophrenia and bipolar disorder (BD), are among the most heritable common disorders, but finding specific susceptibility genes for them has not been straightforward. The reasons are widely assumed to include lack of valid phenotypic definition, absence of good theories of pathophysiology for candidate gene studies, and the involvement of many genes, each making small contributions to population risk. Within the last year or so, a number of genome wide association (GWAS) of schizophrenia and BD have been published. These have produced stronger evidence for association to specific risk loci than have earlier studies, specifically for the zinc finger binding protein 804A (ZNF804A) locus in schizophrenia and for the calcium channel, vo... Human Genetics journals http://www.medworm.com/rss/comments.php?id=2500652 Fri, 12 Jun 2009 10:44:20 +0100 2500652 http://www.medworm.com/index.php?rid=2500653&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F222r50876101086l%2F Abstract  In vitro studies have shown that p53 mediates a protective response against DNA damage by causing either cell-cycle arrest and DNA repair, or apoptosis. These responses have not yet been demonstrated in humans. A common source of DNA damage in humans is cigarette smoke, which should activate p53 repair mechanisms. As the level of p53 is regulated by MDM2, which targets p53 for degradation, the G-allele of a polymorphism in intron 1 of MDM2 (rs2279744:G/T), that results in higher MDM2 levels, should be associated with a reduced p53 response and hence more DNA damage and corresponding tissue destruction. Similarly, the alleles of rs1042522 in TP53 that encode arginine (G-allele) or proline (C-allele) at codon 72, which cause increased pro-apoptotic (G-allele) or cell-... Human Genetics journals http://www.medworm.com/rss/comments.php?id=2500653 Fri, 12 Jun 2009 10:44:19 +0100 2500653 http://www.medworm.com/index.php?rid=2500654&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F64851423n05v7104%2F Abstract  Atopic dermatitis (AD) is a common, itchy skin disease of complex inheritance characterized by dermal and epidermal inflammation. The heritability is considerable and well documented. To date, four genome scans have examined the AD phenotype, showing replicated linkage at 3p26-22, 3q13-21 and 18q11-21. Our previous AD scan showed evidence of linkage to loci at 3p and 18q, and furthermore at 4p15-14. In order to further investigate the genetic basis of AD, we collected and analysed a new Danish family sample consisting of 130 AD sib pair families (555 individuals including 295 children with AD). AD was diagnosed after clinical examination, AD severity was scored and specific IgE was determined. A linkage scan of chromosome 3, 4 and 18 was performed using 91 microsat... Human Genetics journals http://www.medworm.com/rss/comments.php?id=2500654 Thu, 11 Jun 2009 14:04:44 +0100 2500654 http://www.medworm.com/index.php?rid=2500656&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fg45vt512l1276078%2F This report concerns a type I BS patient due to compound heterozygosity for the SLC12A1 gene. Genomic DNA sequencing disclosed the presence of two novel heterozygous mutations of c.724 + 4A > G in intron 5 and c.2095delG in intron 16, but it remains to be determined whether the former would be likely to influence the transcription. In this report, we conducted both in vivo assay of RT-PCR analysis using RNA extracted from the proband’s urinary sediments and in vitro functional splicing study by minigene construction, and obtained evidence that this intronic mutation leads to complete exon 5 skipping. To the best of our knowledge, this is the first study to use non-invasive methods for both an in vivo assay and an in vitro functional splicing assay of inherited... Human Genetics journals http://www.medworm.com/rss/comments.php?id=2500656 Wed, 10 Jun 2009 10:03:23 +0100 2500656 http://www.medworm.com/index.php?rid=2500655&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fq66x25lr38517m6w%2F Abstract  Coronary artery disease (CAD) is based on the atherosclerosis of coronary artery and may manifest with myocardial infarction or angina pectoris. Although it is widely accepted that genetic factors are linked to CAD and several disease-related genes have been reported, only a few could be replicated suggesting that there might be some other CAD-related genes. To identify novel susceptibility loci for CAD, we used microsatellite markers in the screening and found six different candidate CAD loci. Subsequent single nucleotide polymorphism (SNP) association studies revealed an association between CAD and megakaryoblastic leukemia factor-1 gene (MKL1). The association with a promoter SNP of MKL1, −184C > T, was found in a Japanese population and the assoc... Human Genetics journals http://www.medworm.com/rss/comments.php?id=2500655 Wed, 10 Jun 2009 10:03:23 +0100 2500655 http://www.medworm.com/index.php?rid=2500658&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F9618392j74274231%2F Abstract  Quantitative genetic studies (i.e., twin and adoption studies) suggest that genetic influences contribute substantially to the development of attention deficit hyperactivity disorder (ADHD). Over the past 15 years, considerable efforts have been made to identify genes involved in the etiology of this disorder resulting in a large and often conflicting literature of candidate gene associations for ADHD. The first aim of the present study was to conduct a comprehensive meta-analytic review of this literature to determine which candidate genes show consistent evidence of association with childhood ADHD across studies. The second aim was to test for heterogeneity across studies in the effect sizes for each candidate gene as its presence might suggest moderating v... Human Genetics journals http://www.medworm.com/rss/comments.php?id=2500658 Tue, 09 Jun 2009 12:48:47 +0100 2500658 http://www.medworm.com/index.php?rid=2500657&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fh580428n60667643%2F Abstract  A consideration of the evolutionary, physiological and anthropological aspects of aggression suggests that individual differences in such behaviour will have important genetic as well as environmental underpinning. Surveys of the likely pathways controlling the physiological and neuronal processes involved highlight, as obvious targets to investigate, genes implicated in sexual differentiation, anxiety, stress response and the serotonin neurotransmitter pathway. To date, however, association studies on single candidates have provided little evidence for any such loci with a major effect size. This may be because genes do not operate independently, but function against a background in which other genetic and environmental factors are crucial. Indeed, a series of re... Human Genetics journals http://www.medworm.com/rss/comments.php?id=2500657 Tue, 09 Jun 2009 12:48:47 +0100 2500657 http://www.medworm.com/index.php?rid=2500659&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fq27704282u154324%2F Content Type Journal ArticleCategory Book ReviewDOI 10.1007/s00439-009-0682-1Authors Mark Davies, University Hospital of Wales Institute of Medical Genetics 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=2500659 Tue, 09 Jun 2009 12:48:41 +0100 2500659 http://www.medworm.com/index.php?rid=2462382&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F75551rr2521m2668%2F In this study, we present mitochondrial DNA (mtDNA) sequence data for the first hypervariable region (HVR-I) in 477 unrelated individuals belonging to 11 different native populations from Mexico. Almost all of the Native Mexican mtDNAs could be classified into the four pan-Amerindian haplogroups (A2, B2, C1, and D1); only two of them could be allocated to the rare Native American lineage D4h3. Their haplogroup phylogenies are clearly star-like, as expected from relatively young populations that have experienced diverse episodes of genetic drift (e.g., extensive isolation, genetic drift, and founder effects) and posterior population expansions. In agreement with this observation, Native Mexican populations show a high degree of heterogeneity in their patterns of haplogroup frequencies... Human Genetics journals http://www.medworm.com/rss/comments.php?id=2462382 Thu, 04 Jun 2009 10:06:01 +0100 2462382 http://www.medworm.com/index.php?rid=2462383&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fn17683u151763102%2F Content Type Journal ArticleCategory ErratumDOI 10.1007/s00439-009-0685-yAuthors Al Balwi Mohammed, King Abdulaziz Medical City Division of Molecular Patholody and Genetics P.O. Box 22490 MC1122 Riyadh 11426 Saudi ArabiaEyaid Wafaa, King Abdulaziz Medical City Division of Molecular Patholody and Genetics P.O. Box 22490 MC1122 Riyadh 11426 Saudi ArabiaAl Abdulkareem Ibrahim, King Abdulaziz Medical City Division of Molecular Patholody and Genetics P.O. Box 22490 MC1122 Riyadh 11426 Saudi Arabia Journal Human GeneticsOnline ISSN 1432-1203Print ISSN 0340-6717 (Source: Human Genetics) Human Genetics journals http://www.medworm.com/rss/comments.php?id=2462383 Thu, 04 Jun 2009 10:06:00 +0100 2462383 http://www.medworm.com/index.php?rid=2454490&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fb5wp813n1r33271l%2F Abstract  Deletion of chromosome 9p21 is a crucial event for the development of several cancers including acute lymphoblastic leukemia (ALL). Double strand breaks (DSBs) triggering 9p21 deletions in ALL have been reported to occur at a few defined sites by illegitimate action of the V(D)J recombination activating protein complex. We have cloned 23 breakpoint junctions for a total of 46 breakpoints in 17 childhood ALL (9 B- and 8 T-lineages) showing different size deletions at one or both homologous chromosomes 9 to investigate which particular sequences make the region susceptible to interstitial deletion. We found that half of 9p21 deletion breakpoints were mediated by ectopic V(D)J recombination mechanisms whereas the remaining half were associated to repeated sequences, ... Human Genetics journals http://www.medworm.com/rss/comments.php?id=2454490 Sat, 30 May 2009 08:20:50 +0100 2454490 http://www.medworm.com/index.php?rid=2435777&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F14085mjx30g46201%2F Abstract  Despite extensive research of genetic determinants of human adult height, the genes identified up until now allow to predict only a small proportion of the trait’s variance. To identify new genes we analyzed 2,486 genotyped and phenotyped individuals in a large pedigree including 23,612 members in 18 generations. The pedigree was derived from a young genetically isolated Dutch population, where genetic heterogeneity is expected to be low and linkage disequilibrium has been shown to be increased. Complex segregation analysis confirmed high heritability of adult height, and suggested mixed model of height inheritance in this population. The estimates of the model parameters obtained from complex segregation analysis were used in parametric linkage analysis, which ... Human Genetics journals http://www.medworm.com/rss/comments.php?id=2435777 Sun, 24 May 2009 06:09:29 +0100 2435777 http://www.medworm.com/index.php?rid=2435776&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F9145227000162426%2F In conclusion, this study substantiates that gross gene abnormalities in PROS1 are relatively common in hereditary PS deficient patients and that MLPA is a useful tool for direct screening of CNVs in PROS1 point mutation-negative individuals. Content Type Journal ArticleCategory Original InvestigationDOI 10.1007/s00439-009-0687-9Authors Maria C. Pintao, Leiden University Medical Center Einthoven Laboratory for Experimental Vascular Medicine, C2-143, Department of Thrombosis and Haemostasis P.O. Box 9600 2300 RC Leiden The NetherlandsA. A. Garcia, Leiden University Medical Center Einthoven Laboratory for Experimental Vascular Medicine, C2-143, Department of Thrombosis and Haemostasis P.O. Box 9600 2300 RC Leiden The NetherlandsD. Borgel, University Paris Sud IFR 141, Faculty of Pharm... Human Genetics journals http://www.medworm.com/rss/comments.php?id=2435776 Sun, 24 May 2009 06:09:29 +0100 2435776 http://www.medworm.com/index.php?rid=2431436&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fr8j4165j3g9t3742%2F Abstract  Mutations affecting the Na+, K+ ATPase alpha subunit have been implicated in at least two distinct human diseases, rapid-onset dystonia Parkinsonism (RDP), and familial hemiplegic migraine (FHM). Over 40 mutations have been mapped to the human ATP1A2 and ATP1A3 genes and are known to result in RDP, FHM or a variant of FHM with neurological complications. To develop a genetically tractable model system for investigating the role of the Na+, K+ ATPase in neural pathologies we performed genetic screens in Drosophila melanogaster to isolate loss-of-function alleles affecting the Na+, K+ ATPase alpha subunit. Flies heterozygous for these mutations all exhibit reduced respiration, consistent with a loss-of-function in the major ATPase. However, these mutations do not affec... Human Genetics journals http://www.medworm.com/rss/comments.php?id=2431436 Wed, 20 May 2009 06:21:02 +0100 2431436 http://www.medworm.com/index.php?rid=2431437&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F1nm7n34825225551%2F Abstract  Migraine is an episodic neurovascular disorder that is clinically divided into two main subtypes that are based on the absence or presence of an aura: migraine without aura (MO) and migraine with aura (MA). Current molecular genetic insight into the pathophysiology of migraine predominantly comes from studies of a rare monogenic subtype of migraine with aura called familial hemiplegic migraine (FHM). Three FHM genes have been identified, which all encode ion transporters, suggesting that disturbances in ion and neurotransmitter balances in the brain are responsible for this migraine type, and possibly the common forms of migraine. Cellular and animal models expressing FHM mutations hint toward neuronal hyperexcitability as the likely underlying disease mechanism. ... Human Genetics journals http://www.medworm.com/rss/comments.php?id=2431437 Wed, 20 May 2009 06:21:01 +0100 2431437 http://www.medworm.com/index.php?rid=2421800&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F4462755368m322k8%2F Abstract  To help unravel some of the early Eurasian steppe migration movements, we determined the Y-chromosomal and mitochondrial haplotypes and haplogroups of 26 ancient human specimens from the Krasnoyarsk area dated from between the middle of the second millennium BC. to the fourth century AD. In order to go further in the search of the geographic origin and physical traits of these south Siberian specimens, we also typed phenotype-informative single nucleotide polymorphisms. Our autosomal, Y-chromosomal and mitochondrial DNA analyses reveal that whereas few specimens seem to be related matrilineally or patrilineally, nearly all subjects belong to haplogroup R1a1-M17 which is thought to mark the eastward migration of the early Indo-Europeans. Our results also confirm th... Human Genetics journals http://www.medworm.com/rss/comments.php?id=2421800 Sat, 16 May 2009 05:52:56 +0100 2421800 http://www.medworm.com/index.php?rid=2421802&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fak41741v553q3102%2F Abstract  Mutations in the GIGYF2 gene at the PARK11 locus have recently been reported in Parkinson’s disease (PD). However, the pathogenicity of some of these mutations has been debated. We conducted a comprehensive genetic analysis of the entire GIGYF2 gene in a cohort of young onset and familial PD patients, followed up with screening of specific variants in a separate group of PD and healthy controls. A total of 850 study subjects [450 Parkinson’s disease (PD) patients and 400 controls] from two Asian countries were included. Our analysis revealed 17 variants distributed across the entire GIGYF2 gene. Ten of these were novel variants out of which eight were non-synonymous (all heterozygous). Out of these eight, half were novel polymorphic variants (0.2–2%) whereas f... Human Genetics journals http://www.medworm.com/rss/comments.php?id=2421802 Sat, 16 May 2009 05:52:55 +0100 2421802 http://www.medworm.com/index.php?rid=2421801&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Ft601th0vl2n3148t%2F We examined 792 DMD/BMD clinical samples by oligonucleotide array-CGH and report on the junction sequence analysis of 15 unique deletion cases and three complex intragenic rearrangements to elucidate potential underlying mechanism(s). Furthermore, we present three cases with intergenic rearrangements involving DMD and neighboring loci. The cases with intragenic rearrangements include an inversion with flanking deleted sequences; a duplicated segment inserted in direct orientation into a deleted region; and a splicing mutation adjacent to a deletion. Bioinformatic analysis demonstrated that 7 of 12 breakpoints combined among 3 complex cases aligned with repetitive sequences, as compared to 4 of 30 breakpoints for the 15 deletion cases. Moreover, the inversion/deletion case may involve ... Human Genetics journals http://www.medworm.com/rss/comments.php?id=2421801 Sat, 16 May 2009 05:52:55 +0100 2421801 http://www.medworm.com/index.php?rid=2421803&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F4h542108884xg631%2F This study examined the association between markers in transforming growth factor alpha (TGFA) and isolated, non-syndromic cleft lip with/without palate (CL/P) using a case–parent trio design, considering parent-of-origin effects. We also tested for gene–environmental interaction with common maternal exposures, and for gene–gene interaction using markers in TGFA and another recognized causal gene, IRF6. CL/P case–parent trios from four populations (76 from Maryland, 146 from Taiwan, 35 from Singapore, and 40 from Korea) were genotyped for 17 single nucleotide polymorphisms (SNPs) in TGFA. The transmission disequilibrium test was used to test individual SNPs, and the parent-of-origin likelihood ratio test (PO-LRT) was used to assess parent-of-origin effects. We also screened for... Human Genetics journals http://www.medworm.com/rss/comments.php?id=2421803 Fri, 15 May 2009 05:54:06 +0100 2421803 http://www.medworm.com/index.php?rid=2421804&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fv77317726l612510%2F Abstract  The insulin variable number of tandem repeats (INS VNTR) has been variably associated with size at birth in non-African populations. Small size at birth is a major determinant of neonatal mortality, so the INS VNTR may influence survival. We tested the hypothesis, therefore, that genetic variation around the INS VNTR in a rural Gambian population, who experience seasonal variation in nutrition and subsequently birth weight, may be associated with foetal and early growth. Six polymorphisms flanking the INS VNTR were genotyped in over 2,500 people. Significant associations were detected between the maternally inherited SNP 27 (rs689) allele and birth length [effect size 17.5 (5.2–29.8) mm; P = 0.004; n = 361]. Significant associations were al... Human Genetics journals http://www.medworm.com/rss/comments.php?id=2421804 Tue, 12 May 2009 05:56:19 +0100 2421804 http://www.medworm.com/index.php?rid=2421805&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fc86418m69u475231%2F Abstract  Cancer is a genetic disease that results from a variety of genomic alterations. Identification of some of these causal genetic events has enabled the development of targeted therapeutics and spurred efforts to discover the key genes that drive cancer formation. Rapidly improving sequencing and genotyping technology continues to generate increasingly large datasets that require analytical methods to identify functional alterations that deserve additional investigation. This review examines statistical and computational approaches for the identification of functional changes among sets of single-nucleotide substitutions. Frequency-based methods identify the most highly mutated genes in large-scale cancer sequencing efforts while bioinformatics approaches are effecti... Human Genetics journals http://www.medworm.com/rss/comments.php?id=2421805 Tue, 12 May 2009 05:56:18 +0100 2421805 http://www.medworm.com/index.php?rid=2395715&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fy1k34743063134hw%2F Abstract  Genomic deletions have long been known to play a causative role in microdeletion syndromes. Recent whole-genome genetic studies have shown that deletions can increase the risk for several psychiatric disorders, suggesting that genomic deletions play an important role in the genetic basis of complex traits. However, the association between genomic deletions and common, complex diseases has not yet been systematically investigated in gene mapping studies. Likelihood-based statistical methods for identifying disease-associated deletions have recently been developed for familial studies of parent-offspring trios. The purpose of this study is to develop statistical approaches for detecting genomic deletions associated with complex disease in case–control studies. Our... Human Genetics journals http://www.medworm.com/rss/comments.php?id=2395715 Tue, 05 May 2009 06:08:07 +0100 2395715 http://www.medworm.com/index.php?rid=2395714&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fg72257235631j7u2%2F Content Type Journal ArticleCategory Book ReviewDOI 10.1007/s00439-009-0675-0Authors Laura E. Machuca-Tzili, Queen’s Medical Centre Department of Genetics Derby Road Nottingham NG7 2UH UK Journal Human GeneticsOnline ISSN 1432-1203Print ISSN 0340-6717 (Source: Human Genetics) Human Genetics journals http://www.medworm.com/rss/comments.php?id=2395714 Tue, 05 May 2009 06:08:07 +0100 2395714 http://www.medworm.com/index.php?rid=2385776&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fw71637562825v0v3%2F Abstract  A fundamental question in human genetics is the degree to which the polygenic character of complex traits derives from polymorphism in genes with similar or with dissimilar functions. The many genome-wide association studies now being performed offer an opportunity to investigate this, and although early attempts are emerging, new tools and modeling strategies still need to be developed and deployed. Towards this goal, we implemented a new algorithm to facilitate the transition from genetic marker lists (principally those generated by PLINK) to pathway analyses of representational gene sets in either threshold or threshold-free downstream applications (e.g. DAVID, GSEA-P, and Ingenuity Pathway Analysis). This was applied to several large genome-wide association st... Human Genetics journals http://www.medworm.com/rss/comments.php?id=2385776 Fri, 01 May 2009 06:42:52 +0100 2385776 http://www.medworm.com/index.php?rid=2373488&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fl47t3knt7w3u1617%2F Abstract  The ongoing debate about the relationship between race and genetics is more than a century old and has yet to be resolved. Recent emphasis on population-based patterns in human genetic variation and the implications of those for disease susceptibility and drug response have revitalized that long-standing debate. Both sides in the debate use the same rhetorical device of treating geographic, ancestral, population-specific, and other categories as surrogates for race, but otherwise share no evidentiary standards, analytic frameworks, or scientific goals that might resolve the debate and result in some productive outcome. Setting a common goal of weighing the scientific benefits of using racial and other social heuristics with testable estimates of the potential soci... Human Genetics journals http://www.medworm.com/rss/comments.php?id=2373488 Sat, 25 Apr 2009 07:28:25 +0100 2373488 http://www.medworm.com/index.php?rid=2373489&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fu422132811052440%2F Abstract  X chromosome inactivation (XCI) is the transcriptional silencing of the majority of genes on one of the two X chromosomes in mammalian females. Females are, therefore, mosaics for two cell lines, one with the maternal X and one with the paternal X as the active chromosome. The relative proportion of the two cell lines, the X inactivation pattern, may be analyzed by simple assays in DNA from available tissues. This review focuses on medical issues related to XCI in X-linked disorders, and on the value of X inactivation analysis in clinical practice. Content Type Journal ArticleCategory Review ArticleDOI 10.1007/s00439-009-0670-5Authors Karen Helene Ørstavik, University of Oslo Department of Medical Genetics, Oslo University Hospital, Rikshospitalet and Faculty ... Human Genetics journals http://www.medworm.com/rss/comments.php?id=2373489 Sat, 25 Apr 2009 07:28:23 +0100 2373489 http://www.medworm.com/index.php?rid=2367598&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F9128849762548322%2F Abstract  Definition of disease phenotype is a necessary preliminary to research into genetic causes of a complex disease. Clinical diagnosis of migraine is currently based on diagnostic criteria developed by the International Headache Society. Previously, we examined the natural clustering of these diagnostic symptoms using latent class analysis (LCA) and found that a four-class model was preferred. However, the classes can be ordered such that all symptoms progressively intensify, suggesting that a single continuous variable representing disease severity may provide a better model. Here, we compare two models: item response theory and LCA, each constructed within a Bayesian context. A deviance information criterion is used to assess model fit. We phenotyped our population... Human Genetics journals http://www.medworm.com/rss/comments.php?id=2367598 Fri, 24 Apr 2009 06:55:09 +0100 2367598 http://www.medworm.com/index.php?rid=2367592&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fh7v3t500860l8179%2F Abstract  Population genetic screening programs for carrier detection of severe genetic disorders exist worldwide, mainly for beta-thalassemia. These screening programs are either mandatory or voluntary. In several Arab countries and Iran, the state has made thalassemia carrier detection mandatory, while tests for detecting carriers are required by the religious authorities in Cyprus. In all the existing mandatory genetic screening programs, the couples have to get the information about the tests before marriage, but the decision whether or not to marry is left to them. Voluntary programs exist for instance in several Mediterranean countries for the prevention of thalassemia and for several genetic diseases among Jews. While voluntary programs leave the decision to be scree... Human Genetics journals http://www.medworm.com/rss/comments.php?id=2367592 Fri, 24 Apr 2009 06:55:09 +0100 2367592 http://www.medworm.com/index.php?rid=2363017&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F3365284h57083610%2F In conclusion, the GWAS performed so far in ADHD, though far from conclusive, provide a first glimpse at genes for the disorder. Many more (much larger studies) will be needed. For this, collaboration between researchers as well as standardized protocols for phenotyping and DNA-collection will become increasingly important. Content Type Journal ArticleCategory Review ArticleDOI 10.1007/s00439-009-0663-4Authors Barbara Franke, Radboud University Nijmegen Medical Centre Department of Psychiatry, Donders Institute for Brain, Cognition and Behavior Nijmegen The NetherlandsBenjamin M. Neale, King’s College London Social, Genetic, and Developmental Psychiatry Centre, Institute of Psychiatry London SE5 8AF UKStephen V. Faraone, SUNY Upstate Medical University Department of Psychiatry Syr... Human Genetics journals http://www.medworm.com/rss/comments.php?id=2363017 Wed, 22 Apr 2009 08:12:58 +0100 2363017 http://www.medworm.com/index.php?rid=2355893&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fe7r8547719j242m6%2F Abstract  Genetic variants in the human androgen receptor gene (AR) are associated with male pattern baldness (androgenetic alopecia, AGA) in Europeans. Previous observations of long-range linkage disequilibrium at the AR locus are consistent with the hypothesis of recent positive selection. Here, we further investigate this signature and its relationship to the AGA risk haplotype. The haplotype homozygosity suggests that the AGA risk haplotype was driven to high frequency by positive selection in Europeans although a low meiotic recombination rate contributed to the high haplotype homozygosity. Further, we find high levels of population differentiation as measured by F ST and a series of fixed derived alleles along an extended region centromeric to AR in the Asian HapMap sa... Human Genetics journals http://www.medworm.com/rss/comments.php?id=2355893 Fri, 17 Apr 2009 07:29:01 +0100 2355893 http://www.medworm.com/index.php?rid=2355891&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fn3647717lw22w621%2F This study aimed to explore the association between gene–gene interactions and stroke in Chinese in a large case–control study. Nearly 4,000 participants were recruited from seven clinical centers. Eight variants in five candidate genes were examined for stroke risk. Gene–gene interactions were explored by using Generalized Multifactor Dimensionality Reduction (GMDR). A significant gene–gene interaction was found by GMDR. The best model including MTHFR C677T, ALOX5AP T2354A and NOTCH3 C381T scored 10 for Cross-Validation Consistency and 9 for Sign Test (P = 0.0107). The individuals with combination of MTHFR 677TT, ALOX5AP 2354AA and NOTCH3 381TT/TC had a significantly higher risk of thrombotic stroke (OR 3.165, 95% CI 1.461–6.858, P = 0.003). Our results s... Human Genetics journals http://www.medworm.com/rss/comments.php?id=2355891 Fri, 17 Apr 2009 07:29:01 +0100 2355891 http://www.medworm.com/index.php?rid=2355889&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fx0lg76508n335416%2F Abstract  Four genome wide linkage scans for diabetic nephropathy have mapped susceptibility loci to chromosome 18q22.3-23 in the region of the carnosinase genes, CNDP1 and CNDP2. CNDP1 has been associated with diabetic nephropathy in Europeans and European Americans, but not African-Americans. Individuals homozygous for a five tri-nucleotide repeat allele (5L; D18S880) are protected from diabetic nephropathy. We identified 64 variants after sequencing the exons, promoter, and 3′ UTR of CNDP1 and CNDP2 in African-American and European American DNA samples. After scanning 44 of these variants, extensive genotyping of 12 SNPs and D18S880 was performed in 1,025 African-American cases with type 2 diabetes (DM)-associated end-stage renal disease (ESRD) and 1,064 African-America... Human Genetics journals http://www.medworm.com/rss/comments.php?id=2355889 Fri, 17 Apr 2009 07:29:01 +0100 2355889 http://www.medworm.com/index.php?rid=2338401&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Feku15v3305644732%2F Abstract  Chronic gastro-oesophageal reflux disease can induce a metaplastic change of the distal oesophagus called Barrett’s oesophagus whereby the normal squamous epithelium is substituted by a columnar epithelium. Patients with Barrett’s oesophagus are at increased risk of oesophageal adenocarcinoma which occurs through dysplastic stages with increasing degree of cellular and architectural disorganization. Barrett’s oesophagus represents an ideal model to study the genetic events supporting the onset of an invasive tumour since patients with this condition are surveilled with endoscopic tissue sampling until high grade dysplasia or intramucosal carcinoma develop. However, due to the relatively low incidence of this disease compared to other cancers, i.e. colon and ... Human Genetics journals http://www.medworm.com/rss/comments.php?id=2338401 Tue, 14 Apr 2009 06:01:54 +0100 2338401 http://www.medworm.com/index.php?rid=2338402&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F562p1h4138163841%2F Abstract  Idiopathic pulmonary fibrosis (IPF) is a progressive and lethal lung disorder of unknown etiology. IPF is likely the result of complex interrelationships between environmental and host factors, although the genetic risk factors are presently uncertain. Because we have found that some MHC polymorphisms confer susceptibility to IPF, in the present study we aimed to evaluate the role of the MHC class I chain-related gene A (MICA) in the risk of developing the disease. MICA molecular typing was done by reference strand mediated conformation analysis in a cohort of 80 IPF patients and 201 controls. In addition, the lung cellular source of the protein was examined by immunohistochemistry, the expression of the MICA receptor NKG2D in lung cells by flow cytometry and solu... Human Genetics journals http://www.medworm.com/rss/comments.php?id=2338402 Sun, 12 Apr 2009 05:48:57 +0100 2338402 http://www.medworm.com/index.php?rid=2338403&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fhh00r02971u22122%2F Abstract  Modern epidemiology suggests a potential interactive association between diet, lifestyle, genetics and the risk of many chronic diseases. As such, many epidemiologic studies attempt to consider assessment of dietary intake alongside genetic measures and other variables of interest. However, given the multi-factorial complexities of dietary exposures, all dietary intake assessment methods are associated with measurement errors which affect dietary estimates and may obscure disease risk associations. For this reason, dietary biomarkers measured in biological specimens are being increasingly used as additional or substitute estimates of dietary intake and nutrient status. Genetic variation may influence dietary intake and nutrient metabolism and may affect the utilit... Human Genetics journals http://www.medworm.com/rss/comments.php?id=2338403 Thu, 09 Apr 2009 09:36:21 +0100 2338403 http://www.medworm.com/index.php?rid=2338404&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fy475074n56315731%2F In conclusion, our results suggest that the Pro allele at p53 codon 72 is emerging as a low-penetrance susceptibility allele for lung cancer development. Content Type Journal ArticleCategory Original InvestigationDOI 10.1007/s00439-009-0664-3Authors Shengming Dai, The Fourth Hospital Affiliated to Guangxi Medical University Department of Lab Liuzhou ChinaChen Mao, Southern Medical University Department of Epidemiology, School of Public Health and Tropical Medicine Guangzhou ChinaLijun Jiang, The Fourth Hospital Affiliated to Guangxi Medical University Department of Lab Liuzhou ChinaGuisheng Wang, The Fourth Hospital Affiliated to Guangxi Medical University Department of Lab Liuzhou ChinaHongge Cheng, The Fourth Hospital Affiliated to Guangxi Medical University Department of Lab Liuzh... Human Genetics journals http://www.medworm.com/rss/comments.php?id=2338404 Thu, 09 Apr 2009 09:36:17 +0100 2338404 http://www.medworm.com/index.php?rid=2321230&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fm3106u0g62721772%2F We present a database-search guided overview of balanced translocations identified in patients with mental retardation. We divide those in four categories: (1) balanced translocations that helped to identify a causative gene within a contiguous gene syndrome, (2) balanced translocations that led to the identification of a mental retardation gene confirmed by independent methods, (3) balanced translocations disrupting candidate genes that have not been confirmed by independent methods and (4) balanced translocations not reported to disrupt protein coding sequences. It can safely be concluded that balanced translocations have been instrumental in the identification of multiple genes that are involved in mental retardation. In addition, many more candidate genes were identified with a s... Human Genetics journals http://www.medworm.com/rss/comments.php?id=2321230 Sun, 05 Apr 2009 12:55:11 +0100 2321230 http://www.medworm.com/index.php?rid=2321231&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fw0267w2n46043j79%2F Content Type Journal ArticleCategory Book ReviewDOI 10.1007/s00439-009-0658-1Authors Sally J. Davies, University Hospital of Wales Institute of Medical Genetics Cardiff CF 14 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=2321231 Fri, 03 Apr 2009 07:02:26 +0100 2321231 http://www.medworm.com/index.php?rid=2321232&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fmr14811276121877%2F Abstract  Many studies have reported the association between the autophagy-related 16-like 1 gene (ATG16L1) T300A polymorphism (rs2241880) and Crohn’s disease (CD) susceptibility, but the results were inconclusive. To derive a more precise estimation of the relationship, a meta-analysis was performed. A total of 24 studies including 13,022 cases and 17,532 controls were included in this meta-analysis. Logistic regression analysis indicated that the ATG16L1 T300A polymorphism was associated with CD risk in Caucasians (P < 0.01). The pooled estimations of OR1 (GG vs. AA) and OR2 (GA vs. AA) in Caucasian studies by Bayesian meta-analysis method was [1.87, 95% confidence interval (CI) 1.69–2.05] and (1.39, 95% CI 1.27–1.51), respectively. The mode of heritance o... Human Genetics journals http://www.medworm.com/rss/comments.php?id=2321232 Wed, 01 Apr 2009 05:52:17 +0100 2321232 http://www.medworm.com/index.php?rid=2321233&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fr56vj3t877h15143%2F The objective of the study was to determine whether FTO variants were associated with adiposity, including visceral and subcutaneous adipose tissue (VAT, SAT), and glucose homeostasis measures in the Insulin Resistance Atherosclerosis Family Study (IRASFS). A total of 27 SNPs in FTO intron 1, including SNPs prominent in the literature (rs9939609, rs8050136, rs1121980, rs17817449, rs1421085, and rs3751812), were genotyped in 1,424 Hispanic Americans and 604 African Americans. Multiple SNPs were associated with BMI and SAT (P values ranging from 0.001 to 0.033), and trending or associated with waist circumference (P values ranging from 0.008 to 0.099) in the Hispanic Americans. No association was observed with VAT, illustrating that FTO variants are associated with overall fat mass instea... Human Genetics journals http://www.medworm.com/rss/comments.php?id=2321233 Thu, 26 Mar 2009 08:05:12 +0100 2321233 http://www.medworm.com/index.php?rid=2294203&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fe4tw3234095917n2%2F Abstract  The purpose of this review is to summarize the evidence that can be used to reconstruct the etiology of human cancers from mutations found in tumors. Mutational spectra of the tumor suppressor gene p53 (TP53) are tumor specific. In several cases, these mutational spectra can be linked to exogenous carcinogens, most notably for sunlight-associated skin cancers, tobacco-associated lung cancers, and aristolochic acid-related urothelial tumors. In the TP53 gene, methylated CpG dinucleotides are sequences selectively targeted by endogenous and exogenous mutagenic processes. Recent high-throughput sequencing efforts analyzing a large number of genes in cancer genomes have so far, for the most part, produced mutational spectra similar to those in TP53 but have unveiled a ... Human Genetics journals http://www.medworm.com/rss/comments.php?id=2294203 Tue, 24 Mar 2009 07:08:45 +0100 2294203 http://www.medworm.com/index.php?rid=2294204&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F5g5410u443nm2155%2F Abstract  The admixture of different ancestral populations in America may have important implications for the risk for psychiatric disorders, as it appears to have for other medical disorders. The present study investigated the role of population admixture in risk for several psychiatric disorders in European-Americans (EAs) and African-Americans (AAs). This is a multisite study with 3,792 subjects recruited from across the United States, including 3,119 EAs and 673 AAs. These subjects included healthy controls and those with substance dependence (SD) [including alcohol dependence (AD), cocaine dependence, and opioid dependence], social phobia, affective disorders, and schizophrenia. In addition, DNA was included from 78 West Africans. The degree of admixture for each subje... Human Genetics journals http://www.medworm.com/rss/comments.php?id=2294204 Sun, 22 Mar 2009 06:11:40 +0100 2294204 http://www.medworm.com/index.php?rid=2281688&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F359603829640n188%2F Abstract  Atherosclerosis is a complex multifocal arterial disease involving interactions of multiple genetic and environmental factors. Advances in techniques of molecular genetics have revealed that genetic polymorphisms significantly influence susceptibility to atherosclerotic vascular diseases. A large number of candidate genes, genetic polymorphisms and susceptibility loci associated with atherosclerotic diseases have been identified in recent years and their number is rapidly increasing. In this review we focus on some of the major candidate genes and genetic polymorphisms associated with human atherosclerotic vascular diseases. Content Type Journal ArticleCategory Review ArticleDOI 10.1007/s00439-009-0654-5Authors Himadri Roy, University of Kuopio Department of Mo... Human Genetics journals http://www.medworm.com/rss/comments.php?id=2281688 Fri, 20 Mar 2009 10:41:33 +0100 2281688 http://www.medworm.com/index.php?rid=2281690&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fb6p0720111nv741r%2F Abstract  Dihydropyrimidine dehydrogenase (DPD) deficiency is an infrequently described autosomal recessive disorder of the pyrimidine degradation pathway and can lead to mental and motor retardation and convulsions. DPD deficiency is also known to cause a potentially lethal toxicity following administration of the antineoplastic agent 5-fluorouracil. In an ongoing study of 72 DPD deficient patients, we analysed the molecular background of 5 patients in more detail in whom initial sequence analysis did not reveal pathogenic mutations. In three patients, a 13.8 kb deletion of exon 12 was found and in one patient a 122 kb deletion of exon 14–16 of DPYD. In the fifth patient, a c.299_302delTCAT mutation in exon 4 was found and also loss of heterozygosity of the enti... Human Genetics journals http://www.medworm.com/rss/comments.php?id=2281690 Fri, 20 Mar 2009 09:53:17 +0100 2281690 http://www.medworm.com/index.php?rid=2281689&cid=s_33401_50_f&fid=33401&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fkx04u55n279112t6%2F Abstract  Migraine is a painful disorder for which the etiology remains obscure. Diagnosis is largely based on International Headache Society criteria. However, no feature occurs in all patients who meet these criteria, and no single symptom is required for diagnosis. Consequently, this definition may not accurately reflect the phenotypic heterogeneity or genetic basis of the disorder. Such phenotypic uncertainty is typical for complex genetic disorders and has encouraged interest in multivariate statistical methods for classifying disease phenotypes. We applied three popular statistical phenotyping methods—latent class analysis, grade of membership and grade of membership “fuzzy” clustering (Fanny)—to migraine symptom data, and compared heritability and genome-wide... Human Genetics journals http://www.medworm.com/rss/comments.php?id=2281689 Fri, 20 Mar 2009 09:53:17 +0100 2281689