Combining information within and between pedigrees for mapping complex traits.

Abstract

This paper is concerned with efficient strategies for gene mapping using pedigrees containing small numbers of affecteds and identity-by-descent data from closely spaced markers throughout the genome. Particular attention is paid to additive traits involving phenocopies and/or locus heterogeneity. For a sample of pedigrees containing a particular configuration of affecteds, e.g., pairs of siblings together with a first cousin, we use a likelihood analysis to find 1-df statistics that are very efficient over a broad range of penetrances and allele frequencies. We identify configurations of affecteds that are particularly powerful for detecting linkage, and we show how pedigrees containing different numbers and configurations of affecteds can be efficiently combined in an overall test statistic.