Reconstructing Ancestral Haplotypes with a Dictionary Model

We propose a dictionary model for haplotypes. According to the model, a haplotype is constructed by randomly concatenating haplotype segments from a given dictionary of segments. A haplotype block is defined as a set of haplotype segments that begin and end with the same pair of markers. In this framework, haplotype blocks can overlap, and the model provides a setting for testing the accuracy of simpler models invoking only nonoverlapping blocks. Each haplotype segment in a dictionary has an assigned probability and alternate spellings that account for genotyping errors and mutation. The model also allows for missing data, unphased genotypes, and prior distribution of parameters. Likelihood evaluations rely on forward and backward recurrences similar to the ones encountered in hidden Markov models. Parameter estimation is carried out with an EM algorithm. The search for the optimal dictionary is particularly difficult because of the variable dimension of the model space. We define a m...

• Type: Journal
• Year: 2006
• Where: JCB
• Authors: Kristin L. Ayers, Chiara Sabatti, Kenneth Lange
• Keywords: Haplotype, Haplotype Blocks, Haplotype Segment, JCB 2006