Genomewide Linkage Analysis of Chronic Lymphocytic Leukemia by Use of a High-Density Single Nucleotide Polymorphism Assay Containing 11,555 Markers.

A genetic basis for chronic lymphocytic leukemia (CLL) is indicated by studies demonstrating that the lifetime risk of developing the disease increases by a factor of seven when at least one first-degree relative is affected. Significant familial aggregation of CLL has been demonstrated, but the mode of inheritance is unknown. To date no genes which when mutated have unequivocally been shown to confer susceptibility to the disease. We have collected clinical data and biospecimens from 370 families comprising of at least two affected family members with CLL. Of these, samples from two or more individuals from 100 families were informative for linkage analysis. To identify a predisposition locus for CLL a high-density single nucleotide polymorphism (SNP)-based genomewide linkage search was conducted using the GeneChip Mapping 10k Xba array containing 11,555 SNP markers (Affymetrix Inc., Santa Clara, CA). Multipoint LOD scores were calculated, assuming both dominant and recessive inheritance and allowing for increased penetrance with age and genetic heterogeneity. Non-parametric linkage scores were also calculated. The results from these analyses will be presented.