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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

Human molecular genetics

Publication Date

10/2006

Volume

15

Pages

2903 - 2910

Addresses

Molecular and Population Genetics Laboratory, Cancer Research UK, London, UK.

Keywords

ColoRectal tumour Gene Identification (CoRGI) Study Consortium, Chromosomes, Human, Pair 3, Humans, Colorectal Neoplasms, Risk Factors, Chromosome Mapping, Pedigree, Genotype, Genes, Dominant, Linkage Disequilibrium, Lod Score, Polymorphism, Single Nucleotide, Models, Genetic, Female, Male