Genomewide linkage analysis of bipolar disorder by use of a high-density single-nucleotide-polymorphism (SNP) genotyping assay: a comparison with microsatellite marker assays and finding of significant linkage to chromosome 6q22.

摘要: We performed a linkage analysis on 25 extended multiplex Portuguese families segregating for bipolar disorder, by use of high-density single-nucleotide–polymorphism (SNP) genotyping assay, the GeneChip Human Mapping 10K Array (HMA10K). Of these families, 12 were used direct comparison HMA10K with traditional 10-cM microsatellite marker set and more dense 4-cM set. This comparative indicated presence significant peaks in SNP assay chromosomal regions characterized poor coverage low information content assays. The provided consistently high enhanced throughout regions. Across entire genome, had an average 0.842 0.21-Mb intermarker spacing. In 12-family set, HMA10K-based detected two genomewide chromosomes 6q22 11p11; both failed to meet this strict threshold full 25-family collection further strengthened findings chromosome 6q22, achieving significance maximum nonparametric (NPL) score 4.20 LOD 3.56 at position 125.8 Mb. addition highly finding, several other suggestive have also been identified data including 2 (57 Mb, NPL = 2.98; 145 3.09), as well 4 (91 2.97), 16 (20 2.89), 20 (60 2.99). conclude that least some we may largely undetected previous whole-genome scans disorder because insufficient or content, particularly 11p11.