Targeted Parametric Linkage Analysis in Eight Families with Non-BRCA1/BRCA2 Breast Cancer

Azra Kurbasic

Centre for Mathematical Sciences
Mathematical Statistics
Lund University,
2000

Abstract:

Breast cancer is known to have an inherited component, consistent in some families with autosomal dominant inheritance. Two major genes, BRCA1 and BRCA2, responsible for inherited breast cancer have been discovered 1990 and 1995 respectively. These two genes explain less than 50 % of familial breast cancer, which is not a significant proportion. Hunting for BRCA3, BRCA4, etc. has been in progress for many years. This Master's thesis reports the results of a linkage study involving eight breast cancer families. Twenty-one markers, spanning approximately 25 cM (centiMorgan) on chromosome 13, and five control markers (three on chromosome 13 and two on chromosome 17) were typed in the families. The aim of the study was to extract all available inheritance information from pedigrees. Some evidence for linkage among some markers and a disease locus was found, but not a significant one. Small evidence for heterogeneity within the lod scores was found for some markers. Both evidence for linkage and for heterogeneity were confirmed by Monte Carlo simulation.

Key words:

Linkage analysis, recombination, lod score, heterogeneity.