致病变体揭示了前列腺癌的候选基因,对非洲血统的男性进行生殖基因检测
Kazzem Gheybi1, Pamela X Y Soh1, Jue Jiang1
1Ancestry & Health Genomics Laboratory, Charles Perkins Centre, School of Medical Sciences, Faculty of Medicine and Health, University of Sydney, Camperdown, NSW, Australia.
在非洲祖先人群中进行前列腺癌 (PCa) 的生殖基因检测,揭示了DNA修复和PCa基因中的新型致病变体. 这项研究确定了更具包容性的基因查的关键候选人,解决了当前的祖先限制.
科学领域:
- 遗传学 是一个遗传学.
- 在瘤学瘤学.
- 基因组医学是基因组医学.
背景情况:
- 前列腺癌 (PCa) 生殖基因检测受到祖先的限制,不成比例地排除了非洲人口.
- 现有的基因测试小组通常无法捕捉与非洲祖先群体相关的PCa相关变异的全部谱.
研究的目的:
- 在非洲祖先种群中识别DNA损伤修复 (DDR) 和PCa相关基因中的潜在致病性生殖系变异.
- 为突出新型基因候选人进行包括祖先的PCa生殖系检测.
主要方法:
- 整个基因组测序是在217名非洲血统的人身上进行的.
- 分析了变体的病原性,频率,功能,临床表现,以及与瘤匹配的双基失活.
- 基因根据病原性潜力和临床相关性进行排名.
主要成果:
- 在78个DDR或PCa相关基因中发现了172种潜在的致病变体.
- 已知显著变异的流行率低于非非洲人群,BRCA1,HOXB13,CDK12,MLH1,MSH2和BRIP1没有影响.
- 排名第一的候选人包括PREX2,POLE,FAT1,BRCA2,POLQ,LRP1B,ATM和Fanconi贫血基因 (FANCD2,FANCA,FANCG,ERCC4,FANCE,FANCI),以及DNA不匹配修复基因MSH3和PMS1.
结论:
- 这项研究阐明了非洲祖先人口中PCa相关的生殖系变异的风景.
- 已识别的变异和基因,特别是在DNA聚合酶和不匹配修复途径中,为开发更公平,更全面的PCa生殖系检测策略提供了关键目标.
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