title: On the identification of disease mutations by the analysis of haplotype similarity and goodness of fit.
abstract: The observation that haplotypes from a particular region of the genome differ between affected and unaffected individuals or between chromosomes transmitted to affected individuals versus those not transmitted is sound evidence for a disease-liability mutation in the region. Tests for differentiation of haplotype distributions often take the form of either Pearson's chi(2) statistic or tests based on the similarity among haplotypes in the different populations. In this article, we show that many measures of haplotype similarity can be expressed in the same quadratic form, and we give the general form of the variance. As we describe, these methods can be applied to either phase-known or phase-unknown data. We investigate the performance of Pearson's chi(2) statistic and haplotype similarity tests through use of evolutionary simulations. We show that both approaches can be powerful, but under quite different conditions. Moreover, we show that the power of both approaches can be enhanced by clustering rare haplotypes from the distributions before performing a test.
authors.affiliation: Department of Statistics, Carnegie Mellon University, Pittsburgh, PA 15213, USA.
authors.forename: Jung-Ying
authors.initials: JY
authors.lastname: Tzeng
authors.forename: B
authors.initials: B
authors.lastname: Devlin
authors.forename: Larry
authors.initials: L
authors.lastname: Wasserman
authors.forename: Kathryn
authors.initials: K
authors.lastname: Roeder
mesh_terms: D002877:Chromosomes, Human / Q000235:genetics; D030342:Genetic Diseases, Inborn / Q000235:genetics*; D005819:Genetic Markers; D006239:Haplotypes; D006801:Humans; D008957:Models, Genetic; D015233:Models, Statistical; D009154:Mutation; D015203:Reproducibility of Results
chemical_list: D005819:Genetic Markers