Inferring Piecewise Ancestral History from Haploid Sequences

Abstract

Abstract. There has been considerable recent interest in the use of haplotype structure to aid in the design and analysis of case-control association studies searching for genetic predictors of human disease. The use of haplotype structure is based on the premise that genetic variations that are physically close on the genome will often be predictive of one another due to their frequent descent intact through recent evolution. Understanding these correlations between sites should make it possible to minimize the amount of redundant information gathered through assays or examined in association tests, improving the power and reducing the cost of the studies. In this work, we evaluate the potential value of haplotype structure in this context by applying it to two key subproblems: inferring hidden polymorphic sites in partial haploid sequences and choosing subsets of variants that optimally capture the information content of the full set of sequences. We develop methods for these approaches based on a prior method we developed for predicting piece-wise shared ancestry of haploid sequences. We apply these methods to a case study of two genetic regions with very different levels of sequence diversity. We conclude that haplotype correlations do have considerable potential for these problems, but that the degree to which they are useful will be strongly dependent on the population sizes available and the specifics of the genetic regions examined.

Efficient genome ancestry inference in complex pedigrees with inbreeding

“…To achieve high resolution, dense SNP markers are used (tens of thousands on each chromosome). Knowledge of genotype's ancestry is particularly useful in many problems such as studying the structure and history of haplotype blocks (Gabriel et al , 2002 ; Schwartz et al , 2004 ; Zhang et al , 2002 ), and mapping quantitative trait loci (QTLs; Mott et al , 2000 ; Valdar et al , 2006 ). In these studies, a probabilistic interpretation is favored over discrete solutions, due to the prevalence of ambiguities and measurement errors.…”

Minimum Mosaic Inference of a Set of Recombinants

“…An illustration is given in Figure 1. Finding recombination events has become a central problem in computational biology [2,3,4,1,5,6]. In most combinatorial models, a present population is assumed to be a descendent of a small number of specic sequences called founders.…”