Accurate rare variant phasing of whole-genome and whole-exome sequencing data in the UK Biobank.
Nat Genet
; 55(7): 1243-1249, 2023 07.
Article
em En
| MEDLINE
| ID: mdl-37386248
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Genoma Humano
/
Bancos de Espécimes Biológicos
Limite:
Humans
País/Região como assunto:
Europa
Idioma:
En
Revista:
Nat Genet
Assunto da revista:
GENETICA MEDICA
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
Suíça