Journal Article

Evidence for a colorectal cancer susceptibility locus on chromosome 3q21–q24 from a high-density SNP genome-wide linkage scan

Zoe Kemp, Luis Carvajal-Carmona, Sarah Spain, Ella Barclay, Margaret Gorman, Lynn Martin, Emma Jaeger, Neil Brooks, D. Timothy Bishop, Huw Thomas, Ian Tomlinson, Elli Papaemmanuil, Emily Webb, Gabrielle S Sellick, Wendy Wood, Gareth Evans, Anneke Lucassen, Eamonn R Maher and Richard S Houlston

in Human Molecular Genetics

Volume 15, issue 19, pages 2903-2910
Published in print October 2006 | ISSN: 0964-6906
Published online August 2006 | e-ISSN: 1460-2083 | DOI: http://dx.doi.org/10.1093/hmg/ddl231
Evidence for a colorectal cancer susceptibility locus on chromosome 3q21–q24 from a high-density SNP genome-wide linkage scan

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To identify a novel susceptibility gene for colorectal cancer (CRC), we conducted a genome-wide linkage analysis of 69 pedigrees segregating colorectal neoplasia in which involvement of known loci had been excluded, using a high-density single nucleotide polymorphism (SNP) array containing 10 204 markers. Multipoint linkage analyses were undertaken using both non-parametric (model-free) and parametric (model-based) methods. After the removal of SNPs in strong linkage disequilibrium, we obtained a maximum non-parametric linkage statistic of 3.40 (P=0.0003) at chromosomal region 3q21–q24. The same genomic position also yielded the highest multipoint heterogeneity LOD (HLOD) score under a dominant model (HLOD=3.10, genome-wide P=0.038) with 62% of families linked to the locus. We provide evidence for a novel CRC susceptibility gene. Further studies are needed to confirm this localization and to evaluate the contribution of this locus to disease incidence.

Journal Article.  4374 words.  Illustrated.

Subjects: Genetics and Genomics

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