Two-Locus Linkage Analysis in Multiple Sclerosis (MS)
P.J. Tienari, T.D. Terwilliger, J. Ott, J. Palo, L. Peltonen,
Genomics , 19(2), 320--325 (1994 Jan 15)
Abstract
One of the major challenges in genetic linkage analyses is the study
of complex diseases. We demonstrate here the use of two-locus
linkage analysis in multiple sclerosis (MS), a multifactorial
disease with a complex mode of inheritance. In a set of Finnish
multiplex families, we have previously found evidence for linkage
between MS susceptibility and two independent loci, the myelin basic
protein gene (MBP) on chromosome 18 and the HLA complex on
chromosome 6. This set of families provides a unique opportunity to
perform linkage analysis conditional on two loci contributing to the
disease. In the two-trait-locus/two-marker-locus analysis, the
presence of another disease locus is parametrized and the analysis
more appropriately treats information from the unaffected family
members than single-disease-locus analysis. As exemplified here in
MS, the two-locus analysis can be a powerful method for
investigating susceptibility loci in complex traits, best suited for
analysis of specific candidate genes, or for situations in which
preliminary evidence for linkage already exists or is suggested.
