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BMC Genomics

, 16:666

Human and rodent genomics


BackgroundAn understanding of linkage disequilibrium LD structures in the human genome underpins much of medical genetics and provides a basis for disease gene mapping and investigating biological mechanisms such as recombination and selection. Whole genome sequencing WGS provides the opportunity to determine LD structures at maximal resolution.

ResultsWe compare LD maps constructed from WGS data with LD maps produced from the array-based HapMap dataset, for representative European and African populations. WGS provides up to 5.7-fold greater SNP density than array-based data and achieves much greater resolution of LD structure, allowing for identification of up to 2.8-fold more regions of intense recombination. The absence of ascertainment bias in variant genotyping improves the population representativeness of the WGS maps, and highlights the extent of uncaptured variation using array genotyping methodologies. The complete capture of LD patterns using WGS allows for higher genome-wide association study GWAS power compared to array-based GWAS, with WGS also allowing for the analysis of rare variation. The impact of marker ascertainment issues in arrays has been greatest for Sub-Saharan African populations where larger sample sizes and substantially higher marker densities are required to fully resolve the LD structure.

ConclusionsWGS provides the best possible resource for LD mapping due to the maximal marker density and lack of ascertainment bias. WGS LD maps provide a rich resource for medical and population genetics studies. The increasing availability of WGS data for large populations will allow for improved research utilising LD, such as GWAS and recombination biology studies.

KeywordsLinkage disequilibrium map Population structure Whole-genome sequencing Recombination Next-generation sequencing AbbreviationsABGArray-based genotyping

CEUUtah Residents CEPH with Northern and Western European ancestry

GWASGenome-wide association study

LDLinkage disequilibrium

LDULinkage disequilibrium unit

MAFMinor-allele frequency

SNPSingle nucleotide polymorphism

WGSWhole-genome sequencing

YRIYoruba in Ibadan, Nigeria

Andrew Collins and Sarah Ennis contributed equally to this work.

Electronic supplementary materialThe online version of this article doi:10.1186-s12864-015-1854-0 contains supplementary material, which is available to authorized users.

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Autor: Reuben J. Pengelly - William Tapper - Jane Gibson - Marcin Knut - Rick Tearle - Andrew Collins - Sarah Ennis

Fuente: https://link.springer.com/

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