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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.

Original publication

DOI

10.1093/hmg/ddl231

Type

Journal article

Journal

Hum Mol Genet

Publication Date

01/10/2006

Volume

15

Pages

2903 - 2910

Keywords

Chromosome Mapping, Chromosomes, Human, Pair 3, Colorectal Neoplasms, Female, Genes, Dominant, Genotype, Humans, Linkage Disequilibrium, Lod Score, Male, Models, Genetic, Pedigree, Polymorphism, Single Nucleotide, Risk Factors