Accurate rare variant phasing of whole-genome and whole-exome sequencing data in the UK Biobank.
Détails
Télécharger: 37386248_BIB_EA0C8B7D22EF.pdf (6850.70 [Ko])
Etat: Public
Version: Final published version
Licence: CC BY 4.0
Etat: Public
Version: Final published version
Licence: CC BY 4.0
ID Serval
serval:BIB_EA0C8B7D22EF
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Accurate rare variant phasing of whole-genome and whole-exome sequencing data in the UK Biobank.
Périodique
Nature genetics
ISSN
1546-1718 (Electronic)
ISSN-L
1061-4036
Statut éditorial
Publié
Date de publication
07/2023
Peer-reviewed
Oui
Volume
55
Numéro
7
Pages
1243-1249
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Publication Status: ppublish
Résumé
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.
Mots-clé
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
Oui
Création de la notice
03/07/2023 14:39
Dernière modification de la notice
08/08/2024 6:42