Evidence for a colorectal cancer susceptibility locus on chromosome 3q21-q24 from a high-density SNP genome-wide linkage scan
Evidence for a colorectal cancer susceptibility locus on chromosome 3q21-q24 from a high-density SNP genome-wide linkage scan
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DOI：
10.1093/hmg/ddl231
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发表时间：
2006-10-01
影响因子：
3.5
通讯作者：
Houlston, Richard S.
中科院分区：
文献类型：
--
作者：
Kemp, Zoe;Carvajal-Carmona, Luis;Houlston, Richard S.
为了确定一个新的大肠癌（CRC）的易感基因，我们进行了全基因组连锁分析69个家系分离大肠癌，其中已知的基因座的参与已被排除在外，使用高密度单核苷酸多态性（SNP）阵列包含10 204个标记。采用非参数（无模型）和参数（基于模型）方法进行多点连锁分析。去除强连锁不平衡中的SNPs后，我们在染色体区域3q 21-q24获得了最大非参数连锁统计量3.40（P=0.0003）。相同的基因组位置也产生了最高的多点异质性LOD（HLOD）得分下的显性模型（HLOD=3.10，全基因组P=0.038）与62%的家庭连锁的基因座。我们提供了一个新的CRC易感基因的证据。需要进一步的研究来证实这一定位，并评估该位点对疾病发病率的贡献。
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.