Assessment of the genomic variation in a cattle population by re-sequencing of key animals at low to medium coverage

BMC Genomics

Research Article

Sandra Jansen¹  Michal Wysocki¹  Hubert Pausch¹  Ruedi Fries¹  Bernhard Aigner¹  Thomas Wieland²  Sebastian Eck²  Anna Benet-Pagès²  Elisabeth Graf²  Thomas Meitinger³  Tim M Strom³ 

[1] Chair of Animal Breeding, Technische Universität München, Liesel-Beckmann-Strasse 1, 85354, Freising, Germany;Institute of Human Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, 85764, Neuherberg, Germany;Institute of Human Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, 85764, Neuherberg, Germany;Institute of Human Genetics, Technische Universität München, 81675, Munich, Germany;

关键词: Next-generation sequencing;    Low-coverage;    Genotyping by sequencing;    Variant annotation;   

DOI  :  10.1186/1471-2164-14-446

 received in 2013-03-05, accepted in 2013-06-19,  发布年份 2013

来源: Springer

【 摘 要 】

BackgroundGenome- and population-wide re-sequencing would allow for most efficient detection of causal trait variants. However, despite a strong decrease of costs for next-generation sequencing in the last few years, re-sequencing of large numbers of individuals is not yet affordable. We therefore resorted to re-sequencing of a limited number of bovine animals selected to explain a major proportion of the population's genomic variation, so called key animals, in order to provide a catalogue of functional variants and a substrate for population- and genome-wide imputation of variable sites.ResultsForty-three animals accounting for about 69 percent of the genetic diversity of the Fleckvieh population, a cattle breed of Southern Germany and Austria, were sequenced with coverages ranging from 4.17 to 24.98 and averaging 7.46. After alignment to the reference genome (UMD3.1) and multi-sample variant calling, more than 17 million variant positions were identified, about 90 percent biallelic single nucleotide variants (SNVs) and 10 percent short insertions and deletions (InDels). The comparison with high-density chip data revealed a sensitivity of at least 92 percent and a specificity of 81 percent for sequencing based genotyping, and 97 percent and 93 percent when a imputation step was included. There are 91,733 variants in coding regions of 18,444 genes, 46 percent being non-synonymous exchanges, of which 575 variants are predicted to cause premature stop codons. Three variants are listed in the OMIA database as causal for specific phenotypes.ConclusionsLow- to medium-coverage re-sequencing of individuals explaining a major fraction of a population's genomic variation allows for the efficient and reliable detection of most variants. Imputation strongly improves genotype quality of lowly covered samples and thus enables maximum density genotyping by sequencing. The functional annotation of variants provides the basis for exhaustive genotype imputation in the population, e.g., for highest-resolution genome-wide association studies.

【 授权许可】

Unknown   
© Jansen et al.; licensee BioMed Central Ltd. 2013. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.