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

Zoe Kemp; Luis Carvajal-Carmona; Sarah Spain; Ella Barclay; Margaret Gorman; Lynn Martin; Emma Jaeger; Neil Brooks; D. Timothy Bishop; Huw Thomas; Ian Tomlinson; Elli Papaemmanuil; Emily Webb; Gabrielle S Sellick; Wendy Wood; Gareth Evans; Anneke Lucassen; Eamonn R Maher; Richard S Houlston

doi:10.1093/hmg/ddl231

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

Zoe Kemp, Luis Carvajal-Carmona, Sarah Spain, Ella Barclay, Margaret Gorman, Lynn Martin, Emma Jaeger, Neil Brooks, D. Timothy Bishop, Huw Thomas, Ian Tomlinson, Elli Papaemmanuil, Emily Webb, Gabrielle S Sellick, Wendy Wood, Gareth Evans, Anneke Lucassen, Eamonn R Maher, Richard S Houlston

Aston Medical School

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Pages (from-to)	2903-2910
Number of pages	8
Journal	Human Molecular Genetics
Volume	15
Issue number	19
DOIs	https://doi.org/10.1093/hmg/ddl231
Publication status	Published - 1 Oct 2006

Keywords

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

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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., & 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. https://doi.org/10.1093/hmg/ddl231

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

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.",

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

author = "Zoe Kemp and Luis Carvajal-Carmona and Sarah Spain and Ella Barclay and Margaret Gorman and Lynn Martin and Emma Jaeger and Neil Brooks and Bishop, {D. Timothy} and Huw Thomas and Ian Tomlinson and Elli Papaemmanuil and Emily Webb and Sellick, {Gabrielle S} and Wendy Wood and Gareth Evans and Anneke Lucassen and Maher, {Eamonn R} and Houlston, {Richard S}",

year = "2006",

month = oct,

day = "1",

doi = "10.1093/hmg/ddl231",

language = "English",

volume = "15",

pages = "2903--2910",

journal = "Human Molecular Genetics",

issn = "0964-6906",

publisher = "Oxford University Press",

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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 2006, 'Evidence for a colorectal cancer susceptibility locus on chromosome 3q21-q24 from a high-density SNP genome-wide linkage scan', Human Molecular Genetics, vol. 15, no. 19, pp. 2903-2910. https://doi.org/10.1093/hmg/ddl231

TY - JOUR

T1 - Evidence for a colorectal cancer susceptibility locus on chromosome 3q21-q24 from a high-density SNP genome-wide linkage scan

AU - Kemp, Zoe

AU - Carvajal-Carmona, Luis

AU - Spain, Sarah

AU - Barclay, Ella

AU - Gorman, Margaret

AU - Martin, Lynn

AU - Jaeger, Emma

AU - Brooks, Neil

AU - Bishop, D. Timothy

AU - Thomas, Huw

AU - Tomlinson, Ian

AU - Papaemmanuil, Elli

AU - Webb, Emily

AU - Sellick, Gabrielle S

AU - Wood, Wendy

AU - Evans, Gareth

AU - Lucassen, Anneke

AU - Maher, Eamonn R

AU - Houlston, Richard S

PY - 2006/10/1

Y1 - 2006/10/1

N2 - 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.

AB - 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.

KW - Chromosome Mapping

KW - Chromosomes, Human, Pair 3/genetics

KW - Colorectal Neoplasms/genetics

KW - Female

KW - Genes, Dominant

KW - Genotype

KW - Humans

KW - Linkage Disequilibrium

KW - Lod Score

KW - Male

KW - Models, Genetic

KW - Pedigree

KW - Polymorphism, Single Nucleotide

KW - Risk Factors

UR - https://academic.oup.com/hmg/article/15/19/2903/630681

U2 - 10.1093/hmg/ddl231

DO - 10.1093/hmg/ddl231

M3 - Article

C2 - 16923799

SN - 0964-6906

VL - 15

SP - 2903

EP - 2910

JO - Human Molecular Genetics

JF - Human Molecular Genetics

IS - 19

ER -

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

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Keywords

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