Whole genome sequences are required to fully resolve the linkage disequilibrium structure of human populations

BMC Genomics
Reuben J PengellySarah Ennis

Abstract

An 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. We 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 sub...Continue Reading

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Citations

Nov 9, 2016·Nature Communications·Ke CaoLirong Wang
May 6, 2019·European Journal of Human Genetics : EJHG·Alejandra Vergara-LopeAndrew Collins
Oct 3, 2019·Heredity·M Reza JabalameliAndrew Collins
Sep 26, 2019·PloS One·Andréa Carla Bastos AndradeFabyano Fonseca E Silva
Jul 28, 2018·Briefings in Bioinformatics·Clare HorscroftAndrew Collins
Nov 8, 2017·Journal of the Neurological Sciences·Mayowa OwolabiBruce Ovbiagele

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Methods Mentioned

BETA
genotyping

Software Mentioned

VCFtools
PLINK
LDMAP

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