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Human Molecular Genetics Advance Access originally published online on August 21, 2006
Human Molecular Genetics 2006 15(19):2903-2910; doi:10.1093/hmg/ddl231
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© The Author 2006. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

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

Zoe Kemp1,{dagger}, Luis Carvajal-Carmona1,{dagger}, Sarah Spain1,{dagger}, Ella Barclay1,{dagger}, Margaret Gorman1,2,{dagger}, Lynn Martin1,{dagger}, Emma Jaeger1,{dagger}, Neil Brooks3,{dagger}, D. Timothy Bishop4,{dagger}, Huw Thomas2,{dagger}, Ian Tomlinson1,2,*,{dagger}, Elli Papaemmanuil5,{ddagger}, Emily Webb5,{ddagger}, Gabrielle S Sellick5,{ddagger}, Wendy Wood5,{ddagger}, Gareth Evans6,{ddagger}, Anneke Lucassen7,{ddagger}, Eamonn R Maher8,{ddagger}, Richard S Houlston5,{ddagger},* and the ColoRectal tumour Gene Identification (CoRGI) Study Consortium

1 Molecular and Population Genetics Laboratory, Cancer Research UK, 44 Lincoln’s Inn Fields, London WC2A 3PX, UK, 2 Colorectal Cancer Unit, Cancer Research UK, St Mark’s Hospital, Watford Road, Harrow HA1 3UJ, UK, 3 Bioinformatics, Cancer Research UK, 44 Lincoln’s Inn Fields, London WC2A 3PX, UK, 4 Genetic Epidemiology Laboratory, Cancer Research UK, St James’s University Hospital, Beckett Street, Leeds, LS9 7TF, UK, 5 Institute of Cancer Research, 15 Cotswold Road, Sutton, Surrey, SM2 5NG, UK, 6 Medical Genetics, St Mary's Hospital, Manchester, Hathersage Road, Manchester, M13 0JH, UK, 7 Wessex Clinical Genetics Service, Princess Anne Hospital, Coxford Road, Southampton, SO16 5YA, UK and 8 Section of Medical and Molecular Genetics, University of Birmingham School of Medicine and West Midlands Genetics Service, Birmingham Women's Hospital, Edgbaston, Birmingham, B15 2TG, UK

* To whom correspondence should be addressed. Tel: +44 02072692884; Fax: +44 02072693093; Email: ian.tomlinson{at}cancer.org.ukor Tel: +44 208 722 4250; Email: r.houlston{at}icr.ac.uk

Received June 6, 2006; Accepted August 10, 2006

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.

{dagger} London Research Institute Group.

{ddagger} Institute of Cancer Research Group.

List of CoRGI Consortium collaborators available on request.


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