Kemp, Z., Carvajal-Carmona, L., Spain, S., Barclay, E., Gorman, M., Martin, L., Jaeger, E., Brooks, N., Bishop, D.T., Thomas, H., Tomlinson, I., Papaemmanuil, E., Webb, E., Sellick, G.S., Wood, W., Evans, G., Lucassen, A., Maher, E.R. and Houlston, R.S. (2006) Evidence for a colorectal cancer susceptibility locus on chromosome 3q21-q24 from a high-density SNP genome-wide linkage scan. Human Molecular Genetics, 15 (19), 2903-2910. (doi:10.1093/hmg/ddl231).
Abstract
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
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