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


Kemp, Z; Carvajal-Carmona, L; Spain, S; Barclay, E; Gorman, M; Martin, L; Jaeger, E; Brooks, N; Bishop, DT; Thomas, H; Tomlinson, I; Papaemmanuil, E; Webb, E; Sellick, GS; Wood, W; Evans, G; Lucassen, A; Maher, ER; Houlston, RS; ColoRectal tumour Gene Identification (CoRGI) Study Consortium, ; (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). pp. 2903-10. ISSN 0964-6906 DOI: https://doi.org/10.1093/hmg/ddl231

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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.

Item Type: Article
Faculty and Department: Faculty of Epidemiology and Population Health > Dept of Infectious Disease Epidemiology
PubMed ID: 16923799
Web of Science ID: 240696100007
URI: http://researchonline.lshtm.ac.uk/id/eprint/2426

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