Joint inference of identity by descent along multiple chromosomes from population samples

Journal of Computational Biology : a Journal of Computational Molecular Cell Biology
Chaozhi ZhengE A Thompson

Abstract

There has been much interest in detecting genomic identity by descent (IBD) segments from modern dense genetic marker data and in using them to identify human disease susceptibility loci. Here we present a novel Bayesian framework using Markov chain Monte Carlo (MCMC) realizations to jointly infer IBD states among multiple individuals not known to be related, together with the allelic typing error rate and the IBD process parameters. The data are phased single nucleotide polymorphism (SNP) haplotypes. We model changes in latent IBD state along homologous chromosomes by a continuous time Markov model having the Ewens sampling formula as its stationary distribution. We show by simulation that this model for the IBD process fits quite well with the coalescent predictions. Using simulation data sets of 40 haplotypes over regions of 1 and 10 million base pairs (Mbp), we show that the jointly estimated IBD states are very close to the true values, although the presence of linkage disequilibrium decreases the accuracy. We also present comparisons with the ibd_haplo program, which estimates IBD among sets of four haplotypes. Our new IBD detection method focuses on the scale between genome-wide methods using simple IBD models and comple...Continue Reading

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Citations

Mar 1, 1972·Theoretical Population Biology·W J Ewens
Aug 6, 2003·American Journal of Human Genetics·Anne-Louise LeuteneggerE A Thompson
Jul 29, 2005·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·Gilean A T McVean, Niall J Cardin
Mar 17, 2006·BMC Genetics·Paul Marjoram, Jeff D Wall
May 11, 2006·American Journal of Human Genetics·Sharon R Browning
Feb 20, 2008·Theoretical Population Biology·E A Thompson
Oct 31, 2008·Genome Research·Alexander GusevItsik Pe'er
Jan 24, 2009·Nature Genetics·Augustine KongKari Stefansson
Mar 23, 2010·American Journal of Human Genetics·Sharon R Browning, Brian L Browning
Jul 2, 2010·Genetics·Anders AlbrechtsenRasmus Nielsen
Dec 25, 2010·Genetic Epidemiology·Buhm HanEleazar Eskin
Feb 12, 2011·American Journal of Human Genetics·Brian L Browning, Sharon R Browning
Apr 14, 2012·Statistical Applications in Genetics and Molecular Biology·Chris Glazner, Elizabeth Alison Thompson

Related Concepts

Genome-Wide Association Study
In Silico
Genome
Dysequilibrium Syndrome
Genetics, Population
Genetic Markers
Genomics
Chromosomes
Monte Carlo Method
Linkage Disequilibrium

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