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Plos Genetics : Inference of Relationships in Population Data Using Identity-by-descent and Identity-by-state, Volume 7

By Allison, David B.

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Book Id: WPLBN0003931688
Format Type: PDF eBook :
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Reproduction Date: 2015

Title: Plos Genetics : Inference of Relationships in Population Data Using Identity-by-descent and Identity-by-state, Volume 7  
Author: Allison, David B.
Volume: Volume 7
Language: English
Subject: Journals, Science, Genetics
Collections: Periodicals: Journal and Magazine Collection (Contemporary), PLoS Genetics
Publication Date:
Publisher: Plos


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Allison, D. B. (n.d.). Plos Genetics : Inference of Relationships in Population Data Using Identity-by-descent and Identity-by-state, Volume 7. Retrieved from

Description : It is an assumption of large, population-based datasets that samples are annotated accurately whether they correspond to known relationships or unrelated individuals. These annotations are key for a broad range of genetics applications. While many methods are available to assess relatedness that involve estimates of identity-by-descent (IBD) and/or identity-bystate (IBS) allele-sharing proportions, we developed a novel approach that estimates IBD0, 1, and 2 based on observed IBS within windows. When combined with genome-wide IBS information, it provides an intuitive and practical graphical approach with the capacity to analyze datasets with thousands of samples without prior information about relatedness between individuals or haplotypes. We applied the method to a commonly used Human Variation Panel consisting of 400 nominally unrelated individuals. Surprisingly, we identified identical, parent-child, and full-sibling relationships and reconstructed pedigrees. In two instances non-sibling pairs of individuals in these pedigrees had unexpected IBD2 levels, as well as multiple regions of homozygosity, implying inbreeding. This combined method allowed us to distinguish related individuals from those having atypical heterozygosity rates and determine which individuals were outliers with respect to their designated population. Additionally, it becomes increasingly difficult to identify distant relatedness using genomewide IBS methods alone. However, our IBD method further identified distant relatedness between individuals within populations, supported by the presence of megabase-scale regions lacking IBS0 across individual chromosomes. We benchmarked our approach against the hidden Markov model of a leading software package (PLINK), showing improved calling of distantly related individuals, and we validated it using a known pedigree from a clinical study. The application of this approach could improve genome-wide association, linkage, heterozygosity, and other population genomics studies that rely on SNP genotype data.


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