Accurate rare variant phasing of whole-genome and whole-exome sequencing data in the UK Biobank.
Details
Serval ID
serval:BIB_EA0C8B7D22EF
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Accurate rare variant phasing of whole-genome and whole-exome sequencing data in the UK Biobank.
Journal
Nature genetics
ISSN
1546-1718 (Electronic)
ISSN-L
1061-4036
Publication state
Published
Issued date
07/2023
Peer-reviewed
Oui
Volume
55
Number
7
Pages
1243-1249
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Publication Status: ppublish
Abstract
Phasing involves distinguishing the two parentally inherited copies of each chromosome into haplotypes. Here, we introduce SHAPEIT5, a new phasing method that quickly and accurately processes large sequencing datasets and applied it to UK Biobank (UKB) whole-genome and whole-exome sequencing data. We demonstrate that SHAPEIT5 phases rare variants with low switch error rates of below 5% for variants present in just 1 sample out of 100,000. Furthermore, we outline a method for phasing singletons, which, although less precise, constitutes an important step towards future developments. We then demonstrate that the use of UKB as a reference panel improves the accuracy of genotype imputation, which is even more pronounced when phased with SHAPEIT5 compared with other methods. Finally, we screen the UKB data for loss-of-function compound heterozygous events and identify 549 genes where both gene copies are knocked out. These genes complement current knowledge of gene essentiality in the human genome.
Keywords
Humans, Biological Specimen Banks, Exome Sequencing, Sequence Analysis, DNA/methods, Genotype, Haplotypes, Genome, Human/genetics, United Kingdom, Polymorphism, Single Nucleotide/genetics
Pubmed
Web of science
Open Access
Yes
Create date
03/07/2023 14:39
Last modification date
08/08/2024 6:42