Abstract

Background

There is evidence for an inherited contribution to primary brain cancer. Linkage analysis of high-risk brain cancer pedigrees has identified candidate regions of interest in which brain cancer predisposition genes are likely to reside.

Methods

Genome-wide linkage analysis was performed in a unique set of 11 informative, extended, high-risk primary brain cancer pedigrees identified in a population genealogy database, which include from 2 to 6 sampled, related primary brain cancer cases. Access to formalin-fixed paraffin embedded tissue samples archived in a biorepository allowed analysis of extended pedigrees.

Results

Individual high-risk pedigrees were singly informative for linkage at multiple regions. Suggestive evidence for linkage was observed on chromosomes 2, 3, 14, and 16. The chromosome 16 region in particular contains a promising candidate gene, pyridoxal-dependent decarboxylase domain-containing 1 (PDXDC1), with prior evidence for involvement with glioblastoma from other previously reported experimental settings, and contains the lead single nucleotide polymorphism (rs3198697) from the linkage analysis of the chromosome 16 region.

Conclusions

Pedigrees with a statistical excess of primary brain cancers have been identified in a unique genealogy resource representing the homogeneous Utah population. Genome-wide linkage analysis of these pedigrees has identified a potential candidate predisposition gene, as well as multiple candidate regions that could harbor predisposition loci, and for which further analysis is suggested.

中文翻译：

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高风险原发性脑癌谱系的全基因组分析将 PDXDC1 确定为候选脑癌易感基因

摘要

背景

有证据表明遗传因素对原发性脑癌有影响。高风险脑癌谱系的连锁分析已经确定了脑癌易感基因可能存在的候选感兴趣区域。

方法

在群体谱系数据库中确定的一组独特的 11 个信息丰富、扩展的高风险原发性脑癌谱系中进行了全基因组连锁分析，其中包括 2 至 6 个相关的原发性脑癌样本样本。通过获取生物样本库中存档的福尔马林固定石蜡包埋的组织样本，可以对扩展的谱系进行分析。

结果

个体高风险谱系对于多个区域的联系具有单独的信息。在 2、3、14 和 16 号染色体上观察到了连锁的提示性证据。16 号染色体区域特别包含一个有前途的候选基因，即吡哆醛依赖性脱羧酶结构域 1 (PDXDC1)，先前的证据表明其他区域与胶质母细胞瘤有关。先前报道的实验设置，并包含来自 16 号染色体区域连锁分析的先导单核苷酸多态性 (rs3198697)。

结论

在代表犹他州同质人群的独特家谱资源中，已经确定了原发性脑癌统计过量的家系。这些谱系的全基因组连锁分析确定了一个潜在的候选易感基因，以及可能含有易感位点的多个候选区域，并建议对其进行进一步分析。