%0 Journal Article
%T Genomewide high-density SNP linkage analysis of non-BRCA1/2 breast cancer families identifies various candidate regions and has greater power than microsatellite studies
%A Anna Gonzalez-Neira
%A Juan Rosa-Rosa
%A Ana Osorio
%A Emilio Gonzalez
%A Melissa Southey
%A Olga Sinilnikova
%A Henry Lynch
%A Rogier A Oldenburg
%A Christi J van Asperen
%A Nicoline Hoogerbrugge
%A Guillermo Pita
%A Peter Devilee
%A David Goldgar
%A Javier Benitez
%J BMC Genomics
%D 2007
%I BioMed Central
%R 10.1186/1471-2164-8-299
%X In order to evaluate the power improvement provided by using SNP markers in a real situation, we have performed a whole genome screen of 19 non-BRCA1/2 breast cancer families using 4720 genomewide SNPs with Illumina technology (Illumina's Linkage III Panel), with an average distance of 615 Kb/SNP. We identified six regions on chromosomes 2, 3, 4, 7, 11 and 14 as candidates to contain genes involved in breast cancer susceptibility, and additional fine mapping genotyping using microsatellite markers around linkage peaks confirmed five of them, excluding the region on chromosome 3. These results were consistent in analyses that excluded SNPs in high linkage disequilibrium. The results were compared with those obtained previously using a 10 cM microsatellite scan (STR-GWS) and we found lower or not significant linkage signals with STR-GWS data compared to SNP data in all cases.Our results show the power increase that SNPs can supply in linkage studies.Genomewide linkage scans have traditionally been performed using low-density maps of microsatellite markers with a spacing of about 10 cM across the genome [1]. However, the recent development of new high-throughput technologies for SNP genotyping has opened up the possibility of taking a genome-wide approach to study polymorphisms quickly and economically. Moreover, several studies have demonstrated that a map of very closely spaced SNP markers could offer many advantages over the low density maps of microsatellite markers, mainly by increasing the power to detect linkage and consequently more precisely identify the disease locus [2-7]. Although these biallelic markers have lower heterozygosity, they are at a higher density in the genome and they are associated with lower genotyping error rates [8,9]. Additionally, SNP assays are more amenable to multiplexing and are easier to automate, and over 6 million validated human SNPs have been stored in public databases to date.Genomewide linkage scans have become a widely used t
%U http://www.biomedcentral.com/1471-2164/8/299