Linkage Disequilibrium Estimation in Low Coverage High-Throughput Sequencing Data

Genetics: A Periodical Record of Investigations Bearing on Heredity and Variation

Timothy P. Bilton^1¹ 

[1] AgResearch, Invermay Agricultural Centre, Mosgiel 9053, New Zealand^1

关键词: genotyping-by-sequencing;    linkage disequilibrium;    maximum likelihood;    allelic dropout;    low coverage;   

DOI  :  10.1534/genetics.118.300831

学科分类：医学（综合）

来源: Genetics Society of America

【 摘 要 】

High-throughput sequencing methods that multiplex a large number of individuals have provided a cost-effective approach for discovering genome-wide genetic variation in large populations. These sequencing methods are increasingly being utilized in population genetic studies across a diverse range of species. Two side-effects of these methods, however, are (1) sequencing errors and (2) heterozygous genotypes called as homozygous due to only one allele at a particular locus being sequenced, which occurs when the sequencing depth is insufficient. Both of these errors have a profound effect on the estimation of linkage disequilibrium (LD) and, if not taken into account, lead to inaccurate estimates. We developed a new likelihood method, GUS-LD, to estimate pairwise linkage disequilibrium using low coverage sequencing data that accounts for undercalled heterozygous genotypes and sequencing errors. Our findings show that accurate estimates were obtained using GUS-LD, whereas underestimation of LD results if no adjustment is made for the errors.

【 授权许可】

CC BY