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

Z Kemp; L Carvajal-Carmona; S Spain; E Barclay; M Gorman; L Martin; E Jaeger; N Brooks; DT Bishop; H Thomas; I Tomlinson; E Papaemmanuil; E Webb; GS Sellick; W Wood; G Evans; A Lucassen; Eamonn Maher; RS Houlston

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

Z Kemp, L Carvajal-Carmona, S Spain, E Barclay, M Gorman, L Martin, E Jaeger, N Brooks, DT Bishop, H Thomas, I Tomlinson, E Papaemmanuil, E Webb, GS Sellick, W Wood, G Evans, A Lucassen, Eamonn Maher, RS Houlston

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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.

Original language	English
Pages (from-to)	2903-2910
Number of pages	8
Journal	Human Molecular Genetics
Volume	1
Issue number	15
Publication status	Published - 1 Jan 2006

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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, E., & 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, 1(15), 2903-2910.

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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.",

author = "Z Kemp and L Carvajal-Carmona and S Spain and E Barclay and M Gorman and L Martin and E Jaeger and N Brooks and DT Bishop and H Thomas and I Tomlinson and E Papaemmanuil and E Webb and GS Sellick and W Wood and G Evans and A Lucassen and Eamonn Maher and RS Houlston",

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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, E & 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. 1, no. 15, pp. 2903-2910.

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, Z

AU - Carvajal-Carmona, L

AU - Spain, S

AU - Barclay, E

AU - Gorman, M

AU - Martin, L

AU - Jaeger, E

AU - Brooks, N

AU - Bishop, DT

AU - Thomas, H

AU - Tomlinson, I

AU - Papaemmanuil, E

AU - Webb, E

AU - Sellick, GS

AU - Wood, W

AU - Evans, G

AU - Lucassen, A

AU - Maher, Eamonn

AU - Houlston, RS

PY - 2006/1/1

Y1 - 2006/1/1

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.

M3 - Article

SN - 1460-2083

VL - 1

SP - 2903

EP - 2910

JO - Human Molecular Genetics

JF - Human Molecular Genetics

IS - 15

ER -

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

Abstract

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