Annals of Human GeneticsThis is an RSS file. You can use it to subscribe to this data in your favourite RSS reader, such as GoogleReader, or to display this data on your own website or blog. Subscribe to this data using MyMedWorm.Subscribe to this data using GoogleReader.Subscribe to this data using Bloglines.Subscribe to this data using MyYahoo.

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HMGA2 Is Confirmed To Be Associated with Human Adult HeightEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Recent genome-wide association studies have identified a novel polymorphism, rs1042725, in the HMGA2 gene for human adult height, a highly heritable complex trait. Replications in independent populations are needed to evaluate a positive finding and determine its generality. Thus, we performed a replication study to examine the associations between polymorphisms in HMGA2 and adult height in two US Caucasian populations (an unrelated sample of 998 subjects and a family-based sample of 8385 subjects) and a Chinese population (1638 unrelated Han subjects). We confirmed the association between rs1042725 in HMGA2 and adult heig...
Source: Annals of Human Genetics - November 21, 2009 Category: Genetics & Stem Cells Authors: Tie-Lin Yang, Yan Guo, Li-Shu Zhang, Qing Tian, Han Yan, Yan-Fang Guo, Hong-Wen Deng Source Type: journals

Attributing Hardy-Weinberg Disequilibrium to Population Stratification and Genetic Association in Case-Control StudiesEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Loci exhibiting Hardy-Weinberg disequilibrium (HWD) are often excluded from association studies, because HWD may indicate genotyping error, population stratification or selection bias. For case-control studies, HWD can result from a genetic effect at the locus. We extend the modelling to accommodate both stratification and genetic effects. Theoretical genotype frequencies and HWD coefficients are derived under a general genetic model for a population with two strata. Maximum likelihood is used to estimate model parameters and a test for lack of fit identifies the models most consistent with the data. Simulations were used ...
Source: Annals of Human Genetics - November 20, 2009 Category: Genetics & Stem Cells Authors: Vaneeta K. Grover, David E. C. Cole, David C. Hamilton Source Type: journals

Fitness Among Individuals with Early Childhood Deafness: Studies in Alumni Families from Gallaudet UniversityEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The genetic fitness of an individual is influenced by their phenotype, genotype and family and social structure of the population in which they live. It is likely that the fitness of deaf individuals was quite low in the Western European population during the Middle Ages. The establishment of residential schools for deaf individuals nearly 400 years ago resulted in relaxed genetic selection against deaf individuals which contributed to the improved fitness of deaf individuals in recent times. As part of a study of deaf probands from Gallaudet University, we collected pedigree data, including the mating type and the number ...
Source: Annals of Human Genetics - November 20, 2009 Category: Genetics & Stem Cells Authors: Susan H. Blanton, Walter E. Nance, Virginia W. Norris, Katherine O. Welch, Amber Burt, Arti Pandya, Kathleen S. Arnos Source Type: journals

Effect of Gene-environment Interactions on Mental Development in African American, Dominican, and Caucasian Mothers and NewbornsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The health impact of environmental toxins has gained increasing recognition over the years. Polycyclic aromatic hydrocarbons (PAHs) and environmental tobacco smoke (ETS) are known to affect nervous system development in children, but no studies have investigated how polymorphisms in PAH metabolic genes affect child cognitive development following PAH exposure during pregnancy. In two parallel prospective cohort studies of non-smoking African American and Dominican mothers and children in New York City and of Caucasian mothers and children in Krakow, Poland, we explored the effect of gene-PAH interaction on child mental dev...
Source: Annals of Human Genetics - October 27, 2009 Category: Genetics & Stem Cells Authors: Shuang Wang, Stephen Chanock, Deliang Tang, Zhigang Li, Susan Edwards, Wieslaw Jedrychowski, Frederica P. Perera Source Type: journals

Variable selection method for quantitative trait analysis based on parallel genetic algorithmEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In this study, we use parallel genetic algorithm (PGA) to identify genetic and environmental factors in genetic association studies of complex human diseases. Our method can take account of both multiple markers across the genome and environmental factors, and also can be used to do fine mapping based on the results of haplotype analysis to select the markers that are associated with the quantitative traits. Using both simulated and real examples, we show that PGA is able to choose the variables correctly and is also an easy-to-use variable selection tool. (Source: Annals of Human Genetics)
Source: Annals of Human Genetics - October 1, 2009 Category: Genetics & Stem Cells Authors: Siuli Mukhopadhyay, Varghese George, Hongyan Xu Source Type: journals

A Variable-Sized Sliding-Window Approach for Genetic Association Studies via Principal Component AnalysisEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In this study, we propose a new approach for genetic association analysis that is based on a variable-sized sliding-window framework and employs principal component analysis to find the optimum window size. With the help of the bisection algorithm in window-size searching, our method is more computationally efficient than available approaches. We evaluate the performance of the proposed method by comparing it with two other methods[mdash]a single-marker method and a variable-length Markov chain method. We demonstrate that, in most cases, the proposed method out-performs the other two methods. Furthermore, since the propose...
Source: Annals of Human Genetics - September 6, 2009 Category: Genetics & Stem Cells Authors: Rui Tang, Tao Feng, Qiuying Sha, Shuanglin Zhang Source Type: journals

Binomial Mixture Model-based Association Tests under Genetic HeterogeneityEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Most of the existing association tests for population-based case-control studies are based on comparing the mean genotype scores between the case and control groups, which may not be efficient under genetic heterogeneity. Given that most common diseases are genetically heterogeneous, caused by mutations in multiple loci, it may be beneficial to fully account for genetic heterogeneity in an association test. Here we first propose a binomial mixture model for such a purpose and develop a corresponding mixture likelihood ratio test (MLRT) for a single locus. We also consider two methods to combine single-locus-based MLRTs acr...
Source: Annals of Human Genetics - September 1, 2009 Category: Genetics & Stem Cells Authors: Hui Zhou, Wei Pan Source Type: journals

Validation Study of Genetic Associations with Coronary Artery Disease on Chromosome 3q13-21 and Potential Effect Modification by SmokingEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
This study attempted to independently validate those associations. Eleven single nucleotide polymorphisms (SNPs) were examined (rs10934490, rs16834817, rs6810298, rs9289231, rs12637456, rs1444768, rs1444754, rs4234218, rs2335052, rs3803, rs2713604) in patients (N = 1618) from the Intermountain Heart Collaborative Study (IHCS). Given the higher smoking prevalence in CATHGEN than IHCS (41% vs. 11% in controls, 74% vs. 29% in cases), smoking stratification and genotype-smoking interactions were evaluated. Suggestive association was found for GATA2 (rs2713604, p = 0.057, OR = 1.2). Among smokers, associations were found in CDG...
Source: Annals of Human Genetics - August 24, 2009 Category: Genetics & Stem Cells Authors: Benjamin D. Horne, Elizabeth R. Hauser, Liyong Wang, Joseph B. Muhlestein, Jeffrey L. Anderson, John F. Carlquist, Svati H. Shah, William E. Kraus Source Type: journals

Genetic Evidence for Complexity in Ethnic Differentiation and History in East AfricaEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The Afro-Asiatic and Nilo-Saharan language families come into contact in Western Ethiopia. Ethnic diversity is particularly high in the South, where the Nilo-Saharan Nyangatom and the Afro-Asiatic Daasanach dwell. Despite their linguistic differentiation, both populations rely on a similar agripastoralist mode of subsistence. Analysis of mitochondrial DNA extracted from Nyangatom and Daasanach archival sera revealed high levels of diversity, with most sequences belonging to the L haplogroups, the basal branches of the mitochondrial phylogeny. However, in sharp contrast with other Ethiopian populations, only 5% of the Nyang...
Source: Annals of Human Genetics - August 24, 2009 Category: Genetics & Stem Cells Authors: Estella S. Poloni, Yamama Naciri, Rute Bucho, Régine Niba, Barbara Kervaire, Laurent Excoffier, André Langaney, Alicia Sanchez-Mazas Source Type: journals

Tests of Association for Quantitative Traits in Nuclear Families Using Principal Components to Correct for Population StratificationEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Traditional transmission disequilibrium test (TDT) based methods for genetic association analyses are robust to population stratification at the cost of a substantial loss of power. We here describe a novel method for family-based association studies that corrects for population stratification with the use of an extension of principal component analysis (PCA). Specifically, we adopt PCA on unrelated parents in each family. We then infer principal components for children from those for their parents through a TDT-like strategy. Two test statistics within the variance-components model are proposed for association tests. Simu...
Source: Annals of Human Genetics - August 20, 2009 Category: Genetics & Stem Cells Authors: Lei Zhang, Jian Li, Yu-Fang Pei, Yongjun Liu, Hong-Wen Deng Source Type: journals

Geographical Structure of the Y-chromosomal Genetic Landscape of the Levant: A coastal-inland contrastEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
We have examined the male-specific phylogeography of the Levant and its surroundings by analyzing Y-chromosomal haplogroup distributions using 5874 samples (885 new) from 23 countries. The diversity within some of these haplogroups was also examined. The Levantine populations showed clustering in SNP and STR analyses when considered against a broad Middle-East and North African background. However, we also found a coastal-inland, east-west pattern of diversity and frequency distribution in several haplogroups within the small region of the Levant. Since estimates of effective population size are similar in the two regions,...
Source: Annals of Human Genetics - August 16, 2009 Category: Genetics & Stem Cells Authors: Mirvat El-Sibai, Daniel E. Platt, Marc Haber, Yali Xue, Sonia C. Youhanna, R. Spencer Wells, Hassan Izaabel, May F. Sanyoura, Haidar Harmanani, Maziar Ashrafian Bonab, Jaafar Behbehani, Fuad Hashwa, Chris Tyler-Smith, Pierre A. Zalloua Source Type: journals

The Reduced Folate Carrier (SLC19A1) c.80G>A Polymorphism is Associated with Red Cell Folate Concentrations Among WomenEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Low folate status may be a consequence of suboptimal intake, transport or cellular utilization of folate and, together with elevated homocysteine, is a recognized risk factor or marker for several human pathologies. As folate transport across cell membranes is mediated in part by the reduced folate carrier (RFC1), variants within SLC19A1, the gene that encodes RFC1, may influence disease risk via an effect on folate and/or homocysteine levels. The present study was undertaken to assess the association between the SLC19A1 c.80G>A polymorphism and folate/homocysteine concentrations in healthy young adults from Northern Irela...
Source: Annals of Human Genetics - July 29, 2009 Category: Genetics & Stem Cells Authors: Anna Stanisławska-Sachadyn, Laura E. Mitchell, Jayne V. Woodside, Peter T. Buckley, Carmel Kealey, Ian S. Young, John M. Scott, Liam Murray, Colin A. Boreham, Helene McNulty, J. J. Strain, Alexander S. Whitehead Source Type: journals

The Late Pleistocene Colonization of South America: An Interdisciplinary PerspectiveEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In this article, we briefly review scenarios for the first peopling of the New World, including the Clovis First/Single Origin, Tripartite, and Dual Migration models. We then discuss bioanthropological, molecular genetic, archaeological and biogeographic evidence for the peopling of the continent. To conclude, we draw on different lines of evidence to make inferences concerning the timing, direction, and type of early human dispersion in South America. (Source: Annals of Human Genetics)
Source: Annals of Human Genetics - July 21, 2009 Category: Genetics & Stem Cells Authors: Francisco Rothhammer, Tom D. Dillehay Source Type: journals

Founder Effects for ATM Gene Mutations in Italian Ataxia Telangiectasia FamiliesEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
We screened ATM gene mutations in 104 Italian Ataxia-Telangiectasia patients from 91 unrelated families (detection rate 90%) and found 21 recurrent mutations in 63 families. The majority (67%) of patients were compound heterozygotes, while 33% were homozygotes. To determine the existence of common haplotypes and potential founder effects, we analyzed five microsatellite markers within and flanking the ATM gene. Haplotype analysis was carried out in 48/63 families harbouring 16 of the 21 recurrent mutations. Forty different haplotypes were detected in the 48 A-T families studied. We found that the majority of patients with ...
Source: Annals of Human Genetics - July 20, 2009 Category: Genetics & Stem Cells Authors: Luciana Chessa, Maria Piane, Monia Magliozzi, Isabella Torrente, Camilla Savio, Patrizia Lulli, Alessandro De Luca, Bruno Dallapiccola Source Type: journals

A Regression-based Association Test for Case-control Studies that Uses Inferred Ancestral Haplotype SimilarityEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Association methods based on haplotype similarity (HS) can overcome power and stability issues encountered in standard haplotype analyses. Current HS methods can be generally classified into evolutionary and two-sample approaches. We propose a new regression-based HS association method for case-control studies that incorporates covariate information and combines the advantages of the two classes of approaches by using inferred ancestral haplotypes. We first estimate the ancestral haplotypes of case individuals and then, for each individual, an ancestral-haplotype-based similarity score is computed by comparing that individ...
Source: Annals of Human Genetics - July 19, 2009 Category: Genetics & Stem Cells Authors: Youfang Liu, Yi-Ju Li, Glen A. Satten, Andrew S. Allen, Jung-Ying Tzeng Source Type: journals

Haplotypes Encompassing the KIAA0391 and PSMA6 Gene Cluster Confer a Genetic Link for Myocardial Infarction and Coronary Artery DiseaseEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The role of the KIAA0391 and PSMA6 genes in predisposing individuals to disease is still not fully understood. We evaluated by molecular beacon-based genotyping assays the roles of five single nucleotide polymorphisms (SNPs) in the chromosomal region 14q13.2 harbouring the KIAA0391 and PSMA6 gene cluster in coronary artery disease (CAD) in the Saudi population. Two of the studied SNPs rs8008319 (denoted as 1) and rs7157492 (2), reside in the KIAA0391 locus, two others rs1048990 (3) and rs12878391 (4) are components of the PSMA6, while rs4981283 (5) resides downstream of both genes. In a study involving 1071 patients and 92...
Source: Annals of Human Genetics - July 15, 2009 Category: Genetics & Stem Cells Authors: Osama Alsmadi, Paul Muiya, Hanif Khalak, Haya Al-Saud, Brian F. Meyer, Futwan Al-Mohanna, Maie Alshahid, Nduna Dzimiri Source Type: journals

PedStr Software for Cutting Large Pedigrees for Haplotyping, IBD Computation and Multipoint Linkage AnalysisEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
We propose an automatic heuristic algorithm for splitting large pedigrees into fragments of no more than a user-specified bit size. The algorithm specifically aims to split large pedigrees where many close relatives are genotyped and to produce a set of sub-pedigrees for haplotype reconstruction, IBD computation or multipoint linkage analysis with the help of the Lander-Green-Kruglyak algorithm. We demonstrate that a set of overlapping pedigree fragments constructed with the help of our algorithm allows fast and effective haplotype reconstruction and detection of an allele's parental origin. Moreover, we compared pedigree ...
Source: Annals of Human Genetics - July 9, 2009 Category: Genetics & Stem Cells Authors: Anatoly V. Kirichenko, Nadezhda M. Belonogova, Yurii S. Aulchenko, Tatiana I. Axenovich Source Type: journals

Genomic Convergence of Genome-wide Investigations for Complex TraitsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In this study, a genomic convergence approach of GWAS and GWLS was implemented for the first time in order to identify genomic loci supported by both methods. A database with 376 GWLS and 102 GWAS for 19 complex traits was created. Data regarding the location and statistical significance for each genetic marker were extracted from articles or web-based databases. Convergence was quantified as the proportion of significant GWAS markers located within linked regions. Convergence was variable (0[ndash]73.3%) and was found to be significantly higher than expected by chance only for two of the 19 phenotypes. Seventy five loci o...
Source: Annals of Human Genetics - July 8, 2009 Category: Genetics & Stem Cells Authors: Georgios D. Kitsios, Elias Zintzaras Source Type: journals

Association Study and Mutation Analysis of Adiponectin Shows Association of Variants in APM1 with Complex Obesity in WomenEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In conclusion, we found an association of an APM1 haplotype with obesity and found that APM1 mutations are not a common cause of monogenic obesity in our cohort. (Source: Annals of Human Genetics)
Source: Annals of Human Genetics - July 4, 2009 Category: Genetics & Stem Cells Authors: Sigri Beckers, Armand V. Peeters, Fenna de Freitas, Ilse L. Mertens, Stijn L. Verhulst, Dominique Haentjens, Kristine N. Desager, Luc F. Van Gaal, Wim Van Hul Source Type: journals

Combining Microarray-based Genomic Selection (MGS) with the Illumina Genome Analyzer Platform to Sequence Diploid Target RegionsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Novel methods of targeted sequencing of unique regions from complex eukaryotic genomes have generated a great deal of excitement, but critical demonstrations of these methods efficacy with respect to diploid genotype calling and experimental variation are lacking. To address this issue, we optimized microarray-based genomic selection (MGS) for use with the Illumina Genome Analyzer (IGA). A set of 202 fragments (304 kb total) contained within a 1.7 Mb genomic region on human chromosome X were MGS/IGA sequenced in ten female HapMap samples generating a total of 2.4 GB of DNA sequence. At a minimum coverage threshold of 5X, 9...
Source: Annals of Human Genetics - June 30, 2009 Category: Genetics & Stem Cells Authors: David T. Okou, Adam E. Locke, Karyn M. Steinberg, Katie Hagen, Prashanth Athri, Amol C. Shetty, Viren Patel, Michael E. Zwick Source Type: journals

Testing Hardy-Weinberg Equilibrium using Family Data from Complex SurveysEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Genetic data collected during the second phase of the Third National Health and Nutrition Examination Survey (NHANES III) enable us to investigate the association of a wide variety of health factors with regard to genetic variation. The classic question when looking into the genetic variations in a population is whether the population is in the state of Hardy-Weinberg Equilibrium (HWE). Our objective was to develop test procedures using family data from complex surveys such as NHANES III. We developed six Pearson [chi]2 based tests for a diallelic locus of autosomal genes. The finite sample properties of the proposed test ...
Source: Annals of Human Genetics - June 5, 2009 Category: Genetics & Stem Cells Authors: Dewei She, Hong Zhang, Zhaohai Li Source Type: journals

Multivariate Association Test Using Haplotype Trend RegressionEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In this study, we propose a haplotype based test of association for multivariate quantitative traits in unrelated samples. Specifically, we extend a population based haplotype trend regression (HTR) approach to multivariate scenarios. We mainly focused on bivariate HTR, and the simulation results showed that the proposed method had correct pre-specified type-I error rates. The power of the proposed method was largely influenced by the size and source of correlation between variables, being greatest when correlation of a specific gene was opposite in sign to the residual correlation. (Source: Annals of Human Genetics)
Source: Annals of Human Genetics - June 1, 2009 Category: Genetics & Stem Cells Authors: Yu-Fang Pei, Lei Zhang, Jianfeng Liu, Hong-Wen Deng Source Type: journals

Analysis of Gene Polymorphisms Associated with K+ Ion Circulation in the Inner Ear of Patients Susceptible and Resistant to Noise-induced Hearing LossEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Noise-induced hearing loss (NIHL) is one of the leading occupational health risks in industrialized countries. It results from an interaction between environmental and genetic factors, however the nature of the genetic factors contributing to NIHL has not yet been clarified. Here, we investigated whether genetic variations in 10 genes putatively involved in the potassium recycling pathway in the inner ear may influence susceptibility to noise. 99 SNPs were genotyped in Polish noise-exposed workers, categorized into susceptible and resistant subjects. The most interesting results were obtained for KCNE1 and KCNQ4 as we repl...
Source: Annals of Human Genetics - May 28, 2009 Category: Genetics & Stem Cells Authors: Malgorzata Pawelczyk, Lut Van Laer, Erik Fransen, Elzbieta Rajkowska, Annelies Konings, Per-Inge Carlsson, Erik Borg, Guy Van Camp, Mariola Sliwinska-Kowalska Source Type: journals

Ancient DNA and Family Relationships in a Pompeian HouseEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
This study revealed that six of the thirteen individuals are indeed closely related. (Source: Annals of Human Genetics)
Source: Annals of Human Genetics - May 28, 2009 Category: Genetics & Stem Cells Authors: Giovanni Di Bernardo, Stefania Del Gaudio, Umberto Galderisi, Antonino Cascino, Marilena Cipollaro Source Type: journals

Association between SNP Heterozygosity and Quantitative Traits in the Framingham Heart StudyEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Associations between multilocus heterozygosity and fitness traits, also termed heterozygosity and fitness correlations (HFCs), have been reported in numerous organisms. These studies, in general, indicate a positive relationship between heterozygosity and fitness traits. We studied the association between genome-wide heterozygosity at 706 non-synonymous and synonymous SNPs and 19 quantitative traits, including morphological, biochemical and fitness traits in the Framingham Heart Study. Statistically significant association was found between heterozygosity and systolic and diastolic blood pressures as well as left ventricul...
Source: Annals of Human Genetics - May 28, 2009 Category: Genetics & Stem Cells Authors: Didahally R. Govindaraju, Martin G. Larson, Xiaoyan Yin, Emelia J. Benjamin, Marepalli B. Rao, Ramachandran S. Vasan Source Type: journals

Parkinson's Disease and Low Frequency Alleles Found Together Throughout LRRK2Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Mutations within LRRK2, most notably p.G2019S, cause Parkinson's disease (PD) in rare monogenic families, and sporadic occurrences in diverse populations. We investigated variation throughout LRRK2 (84 SNPs; genotype or diplotype found for 49 LD blocks) for 275 cases (European ancestry, onset at age 60 or older) and 275 neurologically healthy control subjects (NINDS Neurogenetics Repository). Three grade-of-membership groups, i.e. genetic risk sets, were identified that exactly matched many subjects (cases: 46, 4, 137; controls: 0, 178, 0), and distinguished 94% of the subjects (i.e. >50% likeness to one set). Set I, affec...
Source: Annals of Human Genetics - May 21, 2009 Category: Genetics & Stem Cells Authors: Coro Paisán-Ruiz, Nicole Washecka, Priti Nath, Andrew B. Singleton, Elizabeth H. Corder Source Type: journals

First Genetic Insight into Libyan Tuaregs: A Maternal PerspectiveEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The Tuaregs are a semi-nomadic pastoralist people of northwest Africa. Their origins are still a matter of debate due to the scarcity of genetic and historical data. Here we report the first data on the mitochondrial DNA (mtDNA) genetic characterization of a Tuareg sample from Fezzan (Libyan Sahara). A total of 129 individuals from two villages in the Acacus region were genetically analysed. Both the hypervariable regions and the coding region of mtDNA were investigated. Phylogeographic investigation was carried out in order to reconstruct human migratory shifts in central Sahara, and to shed light on the origin of the Lib...
Source: Annals of Human Genetics - May 20, 2009 Category: Genetics & Stem Cells Authors: Claudio Ottoni, Cristina Martínez-Labarga, Eva-Liis Loogväli, Erwan Pennarun, Alessandro Achilli, Flavio De Angelis, Emiliano Trucchi, Irene Contini, Gianfranco Biondi, Olga Rickards Source Type: journals

Haplotype Analysis of the Stromelysin-1 (MMP3) and Gelatinase B (MMP9) Genes in Relation to Coronary Heart DiseaseEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The functional genetic polymorphisms present in the promoters of stromelysin-1 (MMP3) and gelatinase B (MMP9) have been shown to be associated with angiographically measured atherosclerosis; however, haplotype analysis of the genetic polymorphisms occurring in the promoters and coding regions of MMP3 and MMP9 has been infrequently performed in the past. The aim of this study was to analyze the occurrence of the -1612 5A/6A, -376C/G, and Glu45Lys polymorphisms of MMP3 and the -1562C/T and R279Q polymorphisms of MMP9 and their relation to the risk of coronary heart disease (CHD; stenosis [ge]50% of the diameter in at least o...
Source: Annals of Human Genetics - May 15, 2009 Category: Genetics & Stem Cells Authors: Naqiong Wu, Xiangfeng Lu, Yihong Hua, Li Song, Jue Ye, Jianxin Li, Xianmin Meng, Dongfeng Gu, Yuejin Yang Source Type: journals

Inter- and Extra-Indian Admixture and Genetic Diversity in Reunion Island Revealed by Analysis of Mitochondrial DNAEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Reunion Island is a French territory located in the western Indian Ocean. The genetic pattern of the Reunionese population has been shaped by contributions from highly contrasting regions of the world. Over the last 350 years, several migration waves and cultural and socio-economic factors have led to the emergence of six main ethnic groups in Reunion. India is one of the principal regions that contributed to the setting up of the Reunionese population. Diversity, demographic and admixture analyses were performed on mtDNA variation of the Reunionese of Indian ancestry, including the Malbar and Zarab ethnic groups, in order...
Source: Annals of Human Genetics - April 21, 2009 Category: Genetics & Stem Cells Authors: Vincent Dubut, Pascal Murail, Nicolas Pech, Marie-Dominique Thionville, François Cartault Source Type: journals

Genetic Admixture in Brazilians Exposed to Infection with Leishmania chagasiEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Visceral leishmaniasis (VL) in northeast Brazil is a disease caused by infection with the protozoan Leishmania chagasi. Infection leads to variable clinical outcomes ranging from asymptomatic infection to potentially fatal disease. Prior studies suggest the genetic background of the host contributes to the development of different outcomes after infection, although it is not known if ancestral background itself influences outcomes. VL is endemic in peri-urban areas around the city of Natal in northeast Brazil. The population of northeast Brazil is a mixture of distinct racial and ethnic groups. We hypothesized that some su...
Source: Annals of Human Genetics - April 20, 2009 Category: Genetics & Stem Cells Authors: Nicholas A. Ettinger, Priya Duggal, Regina F. S. Braz, Eliana T. Nascimento, Terri H. Beaty, Selma M. B. Jeronimo, Richard D. Pearson, Jenefer M. Blackwell, Lina Moreno, Mary E. Wilson Source Type: journals

SNP Discovery and Haplotype Analysis in the Segmentally Duplicated DRD5 Coding RegionEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The dopamine receptor 5 gene (DRD5) holds much promise as a candidate locus for contributing to neuropsychiatric disorders and other diseases influenced by the dopaminergic system, as well as having potential to affect normal behavioral variation. However, detailed analyses of this gene have been complicated by its location within a segmentally duplicated chromosomal region. Microsatellites and SNPs upstream from the coding region have been used for association studies, but we find, using bioinformatics resources, that these markers all lie within a previously unrecognized second segmental duplication (SD). In order to acc...
Source: Annals of Human Genetics - April 20, 2009 Category: Genetics & Stem Cells Authors: Donna J. E. Housley, Molly Nikolas, Patrick J. Venta, Kathrine A. Jernigan, Irwin D. Waldman, Joel T. Nigg, Karen H. Friderici Source Type: journals

The Cost Effectiveness of Duplicate Genotyping for Testing Genetic AssociationEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
We consider a modification to the traditional genome wide association (GWA) study design: duplicate genotyping. Duplicate genotyping (re-genotyping some of the samples) has long been suggested for quality control reasons; however, it has not been evaluated for its statistical cost-effectiveness. We demonstrate that when genotyping error rates are at least m%, duplicate genotyping provides a cost-effective (more statistical power for the same price) design alternative when relative genotype to phenotype/sample acquisition costs are no more than m%. In addition to cost and error rate, duplicate genotyping is most cost-effect...
Source: Annals of Human Genetics - April 10, 2009 Category: Genetics & Stem Cells Authors: Nathan Tintle, Derek Gordon, Dirk Van Bruggen, Stephen Finch Source Type: journals

Spastic Paraplegia, Optic Atrophy, and Neuropathy: New Observations, Locus Refinement, and Exclusion of Candidate GenesEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
SPOAN is an autosomal recessive neurodegenerative disorder which was recently characterized by our group in a large inbred Brazilian family with 25 affected individuals. This condition is clinically defined by: 1. congenital optic atrophy; 2. progressive spastic paraplegia with onset in infancy; and 3. progressive motor and sensory axonal neuropathy. Overall, we are now aware of 68 SPOAN patients (45 females and 23 males, with age ranging from 5 to 72 years), 44 of which are presented here for the first time. They were all born in the same geographic micro region. Those 68 patients belong to 43 sibships, 40 of which exhibi...
Source: Annals of Human Genetics - March 29, 2009 Category: Genetics & Stem Cells Authors: Lúcia Inês Macedo-Souza, Fernando Kok, Silvana Santos, Luciana Licinio, Karina Lezirovitz, Natale Cavaçana, Clarissa Bueno, Simone Amorim, André Pessoa, Zodja Graciani, Áurea Ferreira, Abdísio Prazeres, Áurea Nogueira de Melo, Paulo Alberto Otto, M Source Type: journals

New Mutations of EXT1 and EXT2 Genes in German Patients with Multiple OsteochondromasEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Mutations in either the EXT1 or EXT2 genes lead to Multiple Osteochondromas (MO), an autosomal dominantly inherited disorder. This is a report on clinical findings and results of molecular analyses of both genes in 23 German patients affected by MO. Mutation screening was performed by using denaturing high performance liquid chromatography (dHPLC) and automated sequencing. In 17 of 23 patients novel pathogenic mutations have been identified; eleven in the EXT1 and six in the EXT2 gene. Five patients were carriers of recurrent mutations in the EXT2 gene (p.Asp227Asn, p.Gln172X, p.Gln258X) and one patient had no detectable m...
Source: Annals of Human Genetics - March 29, 2009 Category: Genetics & Stem Cells Authors: Wolfram Heinritz, Ulrike Hüffmeier, Sibylle Strenge, Bianca Miterski, Christiane Zweier, Steffen Leinung, Axel Bohring, Beate Mitulla, Usha Peters, Ursula G. Froster Source Type: journals

Using Case-parent Triads to Estimate Relative Risks Associated with a Candidate HaplotypeEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Estimating haplotype relative risks in a family-based study is complicated by phase ambiguity and the many parameters needed to quantify relative risks for all possible diplotypes. This problem becomes manageable if a particular haplotype has been implicated previously as relevant to risk. We fit log-linear models to estimate the risks associated with a candidate haplotype relative to the aggregate of other haplotypes. Our approach uses existing haplotype-reconstruction algorithms but requires assumptions about the distribution of haplotypes among triads in the source population. We consider three levels of stringency for ...
Source: Annals of Human Genetics - March 29, 2009 Category: Genetics & Stem Cells Authors: Min Shi, David M. Umbach, Clarice R. Weinberg Source Type: journals

Evaluating the Ability of Tree-Based Methods and Logistic Regression for the Detection of SNP-SNP InteractionEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In conclusion, tree-based methods and LR are important statistical tools for the detection of unknown interactions among true risk-associated SNPs with marginal effects and in the presence of a significant number of noise SNPs. In pure interaction models, RF performs reasonably well in the presence of large sample sizes and low percentages of missing data. However, when the study design is suboptimal (unfavourable to detect interaction in terms of e.g. sample size and MAF) there is a high chance of detecting false, spurious associations. (Source: Annals of Human Genetics)
Source: Annals of Human Genetics - March 12, 2009 Category: Genetics & Stem Cells Authors: Manuel García-Magariños, Iñaki López-de-Ullibarri, Ricardo Cao, Antonio Salas Source Type: journals

CALHM1 Polymorphism is not Associated with Late-onset Alzheimer DiseaseEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Data suggests that the P86L polymorphism (rs2986017) in the calcium homeostasis modulator 1 (CALHM1) gene interferes with CALHM1 functionality, increases A[beta] levels, and is associated with late-onset Alzheimer's disease (LOAD). Previous studies have demonstrated association with P86L and LOAD in three of five case-control cohorts, and a joint analysis of all datasets showed association with a p-value of 2 × 10[minus]10 and an allele-specific odds ratio of 1.44 (2,043 cases, 1,361 controls total). In this short communication we attempt to replicate these results in our case-control cohort (510 cases, 524 controls). We ...
Source: Annals of Human Genetics - March 8, 2009 Category: Genetics & Stem Cells Authors: Gary W. Beecham, Nathalie Schnetz-Boutaud, Jonathan L. Haines, Margaret A. Pericak-Vance Source Type: journals

High-resolution Melting Facilitates Mutation Screening of PYGM in Patients with McArdle DiseaseEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Mutations in PYGM, encoding the muscle-specific glycogen phosphorylase (myophosphorylase), are responsible for McArdle disease. Among Caucasians, a large proportion of patients are homozygous for the R50X mutation, but other mutations can affect all the 20 exons of PYGM, making mutation detection laborious. We have developed a high-resolution melting (HRM) assay for mutation detection in PYGM. Twelve McArdle patients were investigated, in whom pre-screening had ruled out homozygosity or compound heterozygosity for the two common G205S and R50X mutations. In total, we identified 16 different variations. Thirteen of these ar...
Source: Annals of Human Genetics - March 8, 2009 Category: Genetics & Stem Cells Authors: Morten Duno, Ros Quinlivan, John Vissing, Marianne Schwartz Source Type: journals

Reply to ParsonEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
(Source: Annals of Human Genetics)
Source: Annals of Human Genetics - February 17, 2009 Category: Genetics & Stem Cells Authors: M. Stoneking, I. Nasidze Source Type: journals

Robust Tests for Single-marker Analysis in Case-Control Genetic Association StudiesEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Choosing an appropriate single-marker association test is critical to the success of case-control genetic association studies. An ideal single-marker analysis should have robust performance across a wide range of potential disease risk models. MAX was designed specifically to achieve such robustness. In this work, we derived the power calculation formula for MAX and conducted a comprehensive power comparison between MAX and two other commonly used single-marker tests, the one-degree-of-freedom (1-df) Cochran-Armitage trend test and the 2-df Pearson [chi]2 test. We used a single-marker disease risk model and a two-marker ha...
Source: Annals of Human Genetics - February 5, 2009 Category: Genetics & Stem Cells Authors: Qizhai Li, Gang Zheng, Xueying Liang, Kai Yu Source Type: journals

Detection of Rare Nonsynonymous Variants in TGFB1 in Otosclerosis PatientsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Otosclerosis is one of the most common forms of hearing loss in the European population. We have identified a SNP in the TGFB1 (transforming growth factor beta 1) gene that is associated with susceptibility to otosclerosis. The protective allele of this variant, with isoleucine at position 263 of the protein, is more biologically active than the risk allele, which has a threonine in this position. Because recent studies have shown that not only common, but also rare variants can be involved in complex diseases, we performed DNA sequence analysis of the exons and intron-exon boundaries of TGFB1 in 755 otosclerosis patients ...
Source: Annals of Human Genetics - February 4, 2009 Category: Genetics & Stem Cells Authors: M. Thys, I. Schrauwen, K. Vanderstraeten, N. Dieltjens, E. Fransen, M. Ealy, C. W. R. J. Cremers, P. van de Heyning, R. Vincent, E. Offeciers, R. H. Smith, G. van Camp Source Type: journals

Interactions Between HERC2, OCA2 and MC1R May Influence Human Pigmentation PhenotypeEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Human pigmentation is a polygenic trait which may be shaped by different kinds of gene[ndash]gene interactions. Recent studies have revealed that interactive effects between HERC2 and OCA2 may be responsible for blue eye colour determination in humans. Here we performed a population association study, examining important polymorphisms within the HERC2 and OCA2 genes. Furthermore, pooling these results with genotyping data for MC1R, ASIP and SLC45A2 obtained for the same population sample we also analysed potential genetic interactions affecting variation in eye, hair and skin colour. Our results confirmed the association o...
Source: Annals of Human Genetics - February 4, 2009 Category: Genetics & Stem Cells Authors: Wojciech Branicki, Urszula Brudnik, Anna Wojas-Pelc Source Type: journals

Robust Quantitative Trait Association Tests in the Parent-Offspring Triad Design: Conditional Likelihood-Based ApproachesEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Association studies, based on either population data or familial data, have been widely applied to mapping of genes underlying complex diseases. In family-based association studies, using case-parent triad families, the popularly used transmission/disequilibrium test (TDT) was proposed for avoidance of spurious association results caused by other confounders such as population stratification. Originally, the TDT was developed for analysis of binary disease data. Extending it to allow for quantitative trait analysis of complex diseases and for robust analysis of binary diseases against the uncertainty of mode of inheritance...
Source: Annals of Human Genetics - February 1, 2009 Category: Genetics & Stem Cells Authors: J.-Y. Wang, J. J. Tai Source Type: journals

Candidate Gene Association Study for Noise-induced Hearing Loss in Two Independent Noise-exposed PopulationsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In this study, we performed an association study for NIHL based on a candidate gene approach. 644 Single Nucleotide Polymorphisms (SNPs) in 53 candidate genes were analyzed in two independent NIHL sample sets, a Swedish set and part of a Polish set. Eight SNPs with promising results were selected and analysed in the remaining part of the Polish samples. One SNP in PCDH15 (rs7095441), resulted in significant associations in both sample sets while two SNPs in MYH14 (rs667907 and rs588035), resulted in significant associations in the Polish sample set and significant interactions with noise exposure level in the Swedish sampl...
Source: Annals of Human Genetics - January 31, 2009 Category: Genetics & Stem Cells Authors: A. Konings, L. Van Laer, A. Wiktorek-Smagur, E. Rajkowska, M. Pawelczyk, P. I. Carlsson, M. L. Bondeson, A. Dudarewicz, A. Vandevelde, E. Fransen, J. Huyghe, E. Borg, M. Sliwinska-Kowalska, G. Van Camp Source Type: journals

Variants in Intron 13 of the ELMO1 Gene are Associated with Diabetic Nephropathy in African AmericansEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Variants in the engulfment and cell motility 1 (ELMO1) gene are associated with nephropathy due to type 2 diabetes mellitus (T2DM) in a Japanese cohort. We comprehensively evaluated this gene in African American (AA) T2DM patients with end-stage renal disease (ESRD). Three hundred and nine HapMap tagging SNPs and 9 reportedly associated SNPs were genotyped in 577 AA T2DM-ESRD patients and 596 AA non-diabetic controls, plus 43 non-diabetic European American controls and 45 Yoruba Nigerian samples for admixture adjustment. Replication analyses were conducted in 558 AA with T2DM-ESRD and 564 controls without diabetes. Extensi...
Source: Annals of Human Genetics - January 31, 2009 Category: Genetics & Stem Cells Authors: T. S. Leak, P. S. Perlegas, S. G. Smith, K. L. Keene, P. J. Hicks, C. D. Langefeld, J. C. Mychaleckyj, S. S. Rich, J. K. Kirk, B. I. Freedman, D. W. Bowden, M. M. Sale Source Type: journals

Pearson's Test, Trend Test, and MAX Are All Trend Tests with Different Types of ScoresEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Pearson's test is one of the most commonly used statistics for testing genetic association of case-control data. The trend test is another one which assumes a dose-response model between the risk of the disease and genotypes. To apply the trend test, a set of ordered scores is assigned a priori based on the underlying genetic model. Pearson's test is model-free and robust, but is less powerful for common genetic models. MAX is another robust test statistic, which takes the maximum of the trend tests over a family of scientifically plausible genetic models. We show that the three test statistics are all trend tests but with...
Source: Annals of Human Genetics - January 31, 2009 Category: Genetics & Stem Cells Authors: Gang Zheng, Jungnam Joo, Yaning Yang Source Type: journals

Testing for linkage and Hardy-Weinberg disequilibriumEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
This paper concerns several important points when testing for Hardy-Weinberg equilibrium (HWE) and linkage disequilibrium (LD) in genetics. First, we challenge the necessity of using exclusively two-sided tests for LD. Next, we show that the exact 2-sided tests based on the most popular measures of LD are not equivalent, and neither are the standard statistical tests even though the 1-sided tests are equivalent. We show how this results in different inference about LD for two data sets consisting of small groups of markers. Finally, we advocate the use of the conditional p-value for both LD and HWE testing. An important ad...
Source: Annals of Human Genetics - January 31, 2009 Category: Genetics & Stem Cells Authors: E. Kulinskaya, A. Lewin Source Type: journals

Analysis of RET, ZEB2, EDN3 and GDNF Genomic Rearrangements in 80 Patients with Hirschsprung Disease (Using multiplex ligation-dependent probe amplification)Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Hirschsprung disease (HSCR) is transmitted in a complex pattern of inheritance and is mostly associated with variants in the RET proto-oncogene. However, RET mutations are only identified in 15[ndash]20% of sporadic HSCR cases and solely in 50% of the familial cases. Since genomic rearrangements in particularly sensitive areas of the RET proto-oncogene and/or associated genes may account for the HSCR phenotype in patients without other detectable RET variants, the aim of the present study was to identify rearrangements in the coding sequence of RET as well as in three HSCR-associated genes (ZEB2, EDN3 and GDNF) in HSCR pat...
Source: Annals of Human Genetics - January 29, 2009 Category: Genetics & Stem Cells Authors: A. Serra, H. Görgens, K. Alhadad, A. Ziegler, G. Fitze, H. K. Schackert Source Type: journals

Testing for Genetic Association With Constrained Models Using TriadsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
It has been shown that it is preferable to use a robust model that incorporated constraints on the genotype relative risk rather than rely on a model that assumes the disease operates in a recessive or dominant fashion. Previous methods are applicable to case-control studies, but not to family based studies of case children along with their parents (triads). We show here how to implement analogous constraints while analyzing triad data. The likelihood, conditional on the parents genotype, is maximized over the appropriately constrained parameter space. The asymptotic distribution for the maximized likelihood ratio statisti...
Source: Annals of Human Genetics - January 28, 2009 Category: Genetics & Stem Cells Authors: J. F. Troendle, K. F. Yu, J. L. Mills Source Type: journals

Distinct clinical characteristics of Tuberous Sclerosis Complex patients with no mutation identifiedEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Tuberous Sclerosis Complex (TSC) is a multi-system disorder that is highly variable in its clinical presentation. Current molecular diagnostic methods permit identification of mutations in either TSC1 or TSC2 in 75[ndash]85% of TSC patients. Here we examine the clinical characteristics of those TSC patients who have no mutation identified (NMI). A retrospective review of our patient population that had comprehensive testing for mutations in TSC1/TSC2 identified 23/157 (15%) that were NMI. NMI patients had a lower incidence of brain findings on imaging studies, neurological features, and renal findings than those with TSC2 ...
Source: Annals of Human Genetics - December 29, 2008 Category: Genetics & Stem Cells Authors: S. E. Camposano, E. Greenberg, D. J. Kwiatkowski, E. A. Thiele Source Type: journals