| Title: | Accurate rare variant phasing of whole-genome and whole-exome sequencing data in the UK Biobank |
| Journal: | Nature Genetics |
| Published: | 29 Jun 2023 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/37386248/ |
| DOI: | https://doi.org/10.1038/s41588-023-01415-w |
| URL: | https://www.nature.com/articles/s41588-023-01415-w.pdf |
Publication 7739
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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.4 Authors
- Robin J. Hofmeister
- Diogo M. Ribeiro
- Simone Rubinacci
- Olivier Delaneau
1 Application
| Application ID | Title |
|---|---|
| 66995 | Prediction of haplotypes, genotypes, parental-of-origin and applications in biobanks. |
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