Use of LINKAGE Programs for Linkage Analysis

Abstract This unit provides an introduction to human genetic linkage analysis for cases in which the genetic model is known (parametric or lod score linkage analysis). The LINKAGE computer package is used for computer analysis because it remains a training standard. The concepts presented for the LINKAGE programs, however, translate directly to other commonly used programs including the FASTLINK and VITESSE programs. This unit includes seven examples selected to illustrate many of the key concepts involved in performing linkage analysis. In Examples 1 through 4, a large pedigree segregating an autosomal dominant disease with reduced penetrance is studied for linkage to various markers. In Example 5, the effects of misspecification of the marker allele frequency on linkage analysis are demonstrated.