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Leveraging Identity-by-Descent for Accurate Genotype Inference in Family Sequencing Data

Li, B and Wei, Q and Zhan, X and Zhong, X and Chen, W and Li, C and Haines, J (2015) Leveraging Identity-by-Descent for Accurate Genotype Inference in Family Sequencing Data. PLoS Genetics, 11 (6). ISSN 1553-7390

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Sequencing family DNA samples provides an attractive alternative to population based designs to identify rare variants associated with human disease due to the enrichment of causal variants in pedigrees. Previous studies showed that genotype calling accuracy can be improved by modeling family relatedness compared to standard calling algorithms. Current family-based variant calling methods use sequencing data on single variants and ignore the identity-by-descent (IBD) sharing along the genome. In this study we describe a new computational framework to accurately estimate the IBD sharing from the sequencing data, and to utilize the inferred IBD among family members to jointly call genotypes in pedigrees. Through simulations and application to real data, we showed that IBD can be reliably estimated across the genome, even at very low coverage (e.g. 2X), and genotype accuracy can be dramatically improved. Moreover, the improvement is more pronounced for variants with low frequencies, especially at low to intermediate coverage (e.g. 10X to 20X), making our approach effective in studying rare variants in cost-effective whole genome sequencing in pedigrees. We hope that our tool is useful to the research community for identifying rare variants for human disease through family-based sequencing.


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Item Type: Article
Status: Published
CreatorsEmailPitt UsernameORCID
Li, B
Wei, Q
Zhan, X
Zhong, X
Chen, Wwei.chen@pitt.eduWEC47
Li, C
Haines, J
ContributionContributors NameEmailPitt UsernameORCID
Date: 1 July 2015
Date Type: Publication
Access Restriction: No restriction; Release the ETD for access worldwide immediately.
Journal or Publication Title: PLoS Genetics
Volume: 11
Number: 6
DOI or Unique Handle: 10.1371/journal.pgen.1005271
Institution: University of Pittsburgh
Schools and Programs: School of Medicine > Pediatrics
Refereed: Yes
ISSN: 1553-7390
Date Deposited: 05 Jul 2016 20:37
Last Modified: 07 Dec 2021 12:55


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