The hazards of genotype imputation in chromosomal regions under selection: A case study using the Lactase gene region.
Derived alleles
Lactase
haplotypes
imputation
selection
Journal
Annals of human genetics
ISSN: 1469-1809
Titre abrégé: Ann Hum Genet
Pays: England
ID NLM: 0416661
Informations de publication
Date de publication:
01 2022
01 2022
Historique:
revised:
15
07
2021
received:
15
05
2021
accepted:
11
08
2021
pubmed:
16
9
2021
medline:
22
1
2022
entrez:
15
9
2021
Statut:
ppublish
Résumé
Although imputation of missing SNP results has been widely used in genetic studies, claims about the quality and usefulness of imputation have outnumbered the few studies that have questioned its limitations. But it is becoming clear that these limitations are real-for example, disease association signals can be missed in regions of LD breakdown. Here, as a case study, using the chromosomal region of the well-known lactase gene, LCT, we address the issue of imputation in the context of variants that have become frequent in a limited number of modern population groups only recently, due to selection. We study SNPs in a 500 bp region covering the enhancer of LCT, and compare imputed genotypes with directly genotyped data. We examine the haplotype pairs of all individuals with discrepant and missing genotypes. We highlight the nonrandom nature of the allelic errors and show that most incorrect imputations and missing data result from long haplotypes that are evolutionarily closely related to those carrying the derived alleles, while some relate to rare and recombinant haplotypes. We conclude that bias of incorrectly imputed and missing genotypes can decrease the accuracy of imputed results substantially.
Substances chimiques
Lactase
EC 3.2.1.108
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
24-33Subventions
Organisme : Wellcome Trust
ID : 209106/Z/17/Z
Pays : United Kingdom
Informations de copyright
© 2021 The Authors. Annals of Human Genetics published by University College London (UCL) and John Wiley & Sons Ltd.
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