Reconstructing Evolutionary History of a Set of Haplotypes by a Tree Likelihood

• Activity Number: 337
• Type: Contributed
• Date/Time: Wednesday, August 6, 2003 : 8:30 AM to 10:20 AM
• Sponsor: Biopharmaceutical Section
• Author(s): Hoa Nguyen*+ and Kathryn M. Roeder and Bernie Devlin
• Companies: Carnegie Mellon University and Carnegie Mellon University and University of Pittsburgh
• Keywords: haplotype trees ; tree likelihood ; quasi-boundary procedure ; MAO haplotypes

Abstract

In the search for genetic variants affecting liability to complex diseases, haplotype data have received increasing recognition. When there are more than a few haplotypes, one way to study the association between disease status and haplotypes is to reconstruct an evolutionary tree which specifies the relative age of each haplotype. To achieve that goal, we combine information from two sources: (1) inferred network relating haplotypes; and (2) frequency and mutational history of each haplotype. The former resolves into a space of candidate trees while the latter entails probabilistic modeling to determine the absolute age of each haplotype. To maximize the "tree likelihood," or the joint likelihood of absolute ages of haplotypes for a given tree, we develop a quasi-boundary procedure that enables us to compare trees consistent with the inferred network. Such comparisons make explicit which trees are most likely to have generated the observed data. We evaluate these methods using data on MAO haplotypes from two ethnic backgrounds, African American and European American. Our results show that the trees exhibit consistency of relative ages among common haplotypes in the two ethnic groups.