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首页> 外文期刊>Human Molecular Genetics >Dense genome-wide SNP linkage scan in 301 hereditary prostate cancer families identifies multiple regions with suggestive evidence for linkage.
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Dense genome-wide SNP linkage scan in 301 hereditary prostate cancer families identifies multiple regions with suggestive evidence for linkage.

机译：在301个遗传性前列腺癌家族中进行的全基因组SNP紧密连锁扫描发现了多个具有连锁暗示的区域。

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The search for susceptibility loci in hereditary prostate cancer (HPC) has proven challenging due to genetic and disease heterogeneity. Multiple risk loci have been identified to date, however few loci have been replicated across independent linkage studies. In addition, most previous analyses have been hampered by the relatively poor information content provided by microsatellite scans. To overcome these issues, we have performed linkage analyses on members of 301 HPC families genotyped using the Illumina SNP linkage panel IVb. The information content for this panel, averaged over all pedigrees and all chromosomes, was 86% (range 83-87% over chromosomes). Analyses were also stratified on families according to disease aggressiveness, age at diagnosis and number of affected individuals to achieve more genetically homogeneous subsets. Suggestive evidence for linkage was identified at 7q21 (HLOD = 1.87), 8q22 (KCLOD = 1.88) and 15q13-q14 (HLOD = 1.99) in 289 Caucasian families, and nominal evidence for linkage was identified at 2q24 (LOD = 1.73) in 12 African American families. Analysis of more aggressive prostate cancer phenotypes provided evidence for linkage to 11q25 (KCLOD = 2.02), 15q26 (HLOD = 1.99) and 17p12 (HLOD = 2.13). Subset analyses according to age at diagnosis and number of affected individuals also identified several regions with suggestive evidence for linkage, including a KCLOD of 2.82 at 15q13-q14 in 128 Caucasian families with younger ages at diagnosis. The results presented here provide further evidence for a prostate cancer susceptibility locus on chromosome 15q and demonstrate the power of utilizing high information content SNP scans in combination with homogenous collections of large prostate cancer pedigrees.
机译：由于遗传和疾病的异质性，在遗传性前列腺癌（HPC）中寻找易感基因座已被证明具有挑战性。迄今为止，已经确定了多个风险基因座，但是在独立的连锁研究中几乎没有重复的基因座。此外，以前的大多数分析都因微卫星扫描提供的相对较差的信息内容而受阻。为了克服这些问题，我们对使用Illumina SNP连锁面板IVb基因型分型的301个HPC家族的成员进行了连锁分析。该面板的信息含量（在所有谱系和所有染色体上平均）为86％（在染色体上为83-87％）。还根据疾病的侵袭性，诊断时的年龄和受影响个体的数量对家庭进行了分层，以实现更多的遗传同质子集。在289个白种人家庭中，有迹象表明在7q21（HLOD = 1.87），8q22（KCLOD = 1.88）和15q13-q14（HLOD = 1.99）之间存在联系的暗示证据，在12q24（LOD = 1.73）中确定了有联系的名义证据非裔美国人家庭。对更具侵略性的前列腺癌表型的分析提供了与11q25（KCLOD = 2.02），15q26（HLOD = 1.99）和17p12（HLOD = 2.13）连锁的证据。根据诊断时的年龄和受影响个体的数量进行亚集分析，还发现了几个具有相关性的暗示证据，包括在128个年龄较小的白种人家庭中，在15q13-q14时KCLOD为2.82。此处提供的结果为15q号染色体上的前列腺癌易感基因座提供了进一步的证据，并证明了结合使用高信息量SNP扫描和大型前列腺癌谱系的同质集合的能力。

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