The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform
Huw Dorkins - One of the best experts on this subject based on the ideXlab platform.
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verifying nomenclature of dna variants in submitted manuscripts guidance for journals
Human Mutation, 2020Co-Authors: Jan Higgins, Johan Den T Dunnen, Raymond Dalgleish, Greg Barsh, Peter J Freeman, David Neil Cooper, Sara Cullinan, Kay E Davies, Huw DorkinsAbstract:Documenting Variation in our genomes is important for research and clinical care. Accuracy in the description of DNA variants is therefore essential. To address this issue, the Human Variome Project convened a committee to evaluate the feasibility of requiring authors to verify that all variants submitted for publication complied with a widely accepted standard for description. After a pilot study at two journals, the committee agreed that requiring authors to verify that variants complied with Human Genome Variation Society nomenclature is a reasonable step toward standardizing the worldwide inventory of Human Variation. This article is protected by copyright. All rights reserved.
Stephen W Scherer - One of the best experts on this subject based on the ideXlab platform.
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genomic Variation in a global village report of the 10th annual Human genome Variation meeting 2008
Human Mutation, 2009Co-Authors: Anthony J Brookes, Stephen J Chanock, Thomas J Hudson, Leena Peltonen, Goncalo R Abecasis, Puiyan Kwok, Stephen W SchererAbstract:The Centre for Applied Genomics of the Hospital for Sick Children and the University of Toronto hosted the 10th Human Genome Variation (HGV) Meeting in Toronto, Canada, in October 2008, welcoming about 240 registrants from 34 countries. During the 3 days of plenary workshops, keynote address, and poster sessions, a strong cross-disciplinary trend was evident, integrating expertise from technology and computation, through biology and medicine, to ethics and law. Single nucleotide polymorphisms (SNPs) as well as the larger copy number variants (CNVs) are recognized by ever-improving array and next-generation sequencing technologies, and the data are being incorporated into studies that are increasingly genome-wide as well as global in scope. A greater challenge is to convert data to information, through databases, and to use the information for greater understanding of Human Variation. In the wake of publications of the first individual genome sequences, an inaugural public forum provided the opportunity to debate whether we are ready for personalized medicine through direct-to-consumer testing. The HGV meetings foster collaboration, and fruits of the interactions from 2008 are anticipated for the 11th annual meeting in September 2009.
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copy number Variation in control population cohorts
Human Molecular Genetics, 2007Co-Authors: Dalila Pinto, Lars Feuk, Stephen W Scherer, Christian R MarshallAbstract:Copy-number Variation (CNV) is the most prevalent type of structural Variation in the Human genome, and contributes significantly to genetic heterogeneity. It has already been recognized that some CNVs can contribute to Human phenotype, including rare genomic disorders and Mendelian diseases. Other CNVs are now amenable to genome-wide association studies so that their influence on Human phenotypic diversity and disease susceptibility may soon be more readily determined. Population studies and reference databases for control and disease-associated samples are required to provide an information resource about CNV frequencies and their relative contribution to phenotypic outcomes. The relatively high cost of screening individual samples has tended to limit the number of controls assayed, and use of the data has often been hampered by the variety of technology platforms and analysis techniques. As a result, there is still a paucity of data on population frequency and distribution of CNVs, particularly for those that are rare. Here, we provide an example of how to discover new CNVs from existing genotype data from large-scale genetic epidemiological studies. We also discuss the need to expand surveys of CNV in different population-based cohorts and to apply the information to studies of Human Variation and disease.
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structural Variation in the Human genome
Nature Reviews Genetics, 2006Co-Authors: Lars Feuk, Andrew R Carson, Stephen W SchererAbstract:The first wave of information from the analysis of the Human genome revealed SNPs to be the main source of genetic and phenotypic Human Variation. However, the advent of genome-scanning technologies has now uncovered an unexpectedly large extent of what we term 'structural Variation' in the Human genome. This comprises microscopic and, more commonly, submicroscopic variants, which include deletions, duplications and large-scale copy-number variants - collectively termed copy-number variants or copy-number polymorphisms - as well as insertions, inversions and translocations. Rapidly accumulating evidence indicates that structural variants can comprise millions of nucleotides of heterogeneity within every genome, and are likely to make an important contribution to Human diversity and disease susceptibility.
Andrea Manica - One of the best experts on this subject based on the ideXlab platform.
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Human Variation in the shape of the birth canal is significant and geographically structured
Proceedings of The Royal Society B: Biological Sciences, 2018Co-Authors: Lia Betti, Andrea ManicaAbstract:The Human birth canal shows a tight fit with the size of the neonate, which can lead to obstetric complications. This is not the case in other apes, and has been explained as the outcome of conflicting evolutionary pressures for bipedal locomotion and parturition of a highly encephalized fetus. Despite the suggested evolutionary constraints on the female pelvis, we show that women are, in fact, extremely variable in the shape of the bony birth canal, with Human populations having differently shaped pelvic canals. Neutral evolution through genetic drift and differential migration are largely responsible for the observed pattern of morphological diversity, which correlates well with neutral genetic diversity. Climatic adaptation might have played a role, albeit a minor one, with populations from colder regions showing a more transversally oval shape of the canal inlet. The significant extent of canal shape Variation among women from different regions of the world has important implications for modern obstetric practice in multi-ethnic societies, as modern medical understanding has been largely developed on studies of European women.
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Dataset.csv from Human Variation in the shape of the birth canal is significant and geographically structured
2018Co-Authors: Lia Betti, Andrea ManicaAbstract:The Human birth canal shows a tight fit with the size of the neonate, which can lead to obstetric complications. This is not the case in other apes, and has been explained as the outcome of conflicting evolutionary pressures for bipedal locomotion and parturition of a highly encephalized fetus. Despite the suggested evolutionary constraints on the female pelvis, we show that women are, in fact, extremely variable in the shape of the bony birth canal, with Human populations having differently shaped pelvic canals. Neutral evolution through genetic drift and differential migration are largely responsible for the observed pattern of morphological diversity, which correlates well with neutral genetic diversity. Climatic adaptation might have played a role, albeit a minor one, with populations from colder regions showing a more transversally oval shape of the canal inlet. The significant extent of canal shape Variation among women from different regions of the world has important implications for modern obstetric practice in multi-ethnic societies, as modern medical understanding has been largely developed on studies of European women
Donna K Arnett - One of the best experts on this subject based on the ideXlab platform.
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data for gaw20 genome wide dna sequence Variation and epigenome wide dna methylation before and after fenofibrate treatment in a family study of metabolic phenotypes
BMC Proceedings, 2018Co-Authors: Stella Aslibekyan, Laura Almasy, Michael A Province, Devin Absher, Donna K ArnettAbstract:GAW20 provided participants with an opportunity to comprehensively examine genetic and epigenetic Variation among related individuals in the context of drug treatment response. GAW20 used data from 188 families (N = 1105) participating in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) study (clinicaltrials.gov identifier NCT00083369), which included CD4+ T-cell DNA methylation at 463,995 cytosine-phosphate-guanine (CpG) sites measured before and after a 3-week treatment with fenofibrate, single-nucleotide Variation at 906,600 loci, metabolic syndrome components ascertained before and after the drug intervention, and relevant covariates. All GOLDN participants were of European descent, with an average age of 48 years. In addition, approximately half were women and approximately 40% met the diagnostic criteria for metabolic syndrome. Unique advantages of the GAW20data set included longitudinal (3 weeks apart) measurements of DNA methylation, the opportunity to explore the contributions of both genotype and DNA methylation to the interindividual variability in drug treatment response, and the familial relationships between study participants. The principal disadvantage of GAW20/GOLDN data was the spurious correlation between batch effects and fenofibrate effects on methylation, which arose because the pre- and posttreatment methylation data were generated and normalized separately, and any attempts to remove time-dependent technical artifacts would also remove biologically meaningful changes brought on by fenofibrate. Despite this limitation, the GAW20 data set offered informative, multilayered omics data collected in a large population-based study of common disease traits, which resulted in creative approaches to integration and analysis of inherited Human Variation.
Johan Den T Dunnen - One of the best experts on this subject based on the ideXlab platform.
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verifying nomenclature of dna variants in submitted manuscripts guidance for journals
Human Mutation, 2020Co-Authors: Jan Higgins, Johan Den T Dunnen, Raymond Dalgleish, Greg Barsh, Peter J Freeman, David Neil Cooper, Sara Cullinan, Kay E Davies, Huw DorkinsAbstract:Documenting Variation in our genomes is important for research and clinical care. Accuracy in the description of DNA variants is therefore essential. To address this issue, the Human Variome Project convened a committee to evaluate the feasibility of requiring authors to verify that all variants submitted for publication complied with a widely accepted standard for description. After a pilot study at two journals, the committee agreed that requiring authors to verify that variants complied with Human Genome Variation Society nomenclature is a reasonable step toward standardizing the worldwide inventory of Human Variation. This article is protected by copyright. All rights reserved.
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development of nipbl locus specific database using lovd from novel mutations to further genotype phenotype correlations in cornelia de lange syndrome
Human Mutation, 2010Co-Authors: Jorge Oliveira, Cristina Dias, Egbert J W Redeker, Eurico Costa, Joao Silva, M Lima, Johan Den T Dunnen, Rosario SantosAbstract:The establishment of Locus Specific Databases (LSDB) is a crucial aspect for the Human Genetics field and one of the aims of the Human Variation Project. We report the development of a publicly accessible LSDB for the NIPBL gene (http://www.lovd.nl/NIPBL) implicated in Cornelia de Lange Syndrome (CdLS). This rare disorder is characterized by developmental and growth retardation, typical facial features, limb anomalies, and multiple organ involvement. Mutations in the NIPBL gene, the product of which is involved in control of the cohesion complex, account for over half of the patients currently characterized. The NIPBL LSDB adopted the Leiden Open Variation database (LOVD) software platform, which enables the comprehensive Web-based listing and curation of sequence Variations and associated phenotypical information. The NIPBL-LOVD database contains 199 unique mutations reported in 246 patients (last accessed April 2010). Information on phenotypic characteristics included in the database enabled further genotype–phenotype correlations, the most evident being the severe form of CdLS associated with premature termination codons in the NIPBL gene. In addition to the NIPBL LSDB, 50 novel mutations are described in detail, resulting from a collaborative multicenter study. Hum Mutat 31:1216–1222, 2010. © 2010 Wiley-Liss, Inc.