Multiple founder effects and geographical clustering of BRCA1 and BRCA2 families in Finland
Multiple founder effects and geographical clustering of BRCA1 and BRCA2 families in Finland
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DOI：
10.1038/sj.ejhg.5200529
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发表时间：
2000-10-01
影响因子：
5.2
通讯作者：
Nevanlinna, H
中科院分区：
文献类型：
--
作者：
Sarantaus, L;Huusko, P;Nevanlinna, H
在芬兰乳腺癌和卵巢癌家族中，发现了6个BRCA 1和5个BRCA 2突变。其中一些反复发生的突变在世界其他地方也有发现，而另一些则完全来自芬兰。对26个携带BRCA 1突变的芬兰家庭和20个携带BRCA 2突变的芬兰家庭进行的单倍型分析表明，每种复发突变的携带者都有共同的祖先。它们的共同祖先可以追溯到7-36代（150-800年）。这些创始人突变在芬兰的时间估计和地理聚类与该国的人口历史是一致的。对癌症表型的分析显示，BRCA 1基因5'和3'端携带突变的家族中卵巢癌表达存在差异，与BRCA 2突变的家族相比，BRCA 1突变的家族中卵巢癌发病年龄更早。在芬兰发现突出的和区域性的BRCA 1和BRCA 2创始人突变将对芬兰乳腺癌和卵巢癌家族的诊断产生重大影响。一个孤立的人口与已知的历史和多个地方的创始人在多基因疾病的影响可能提供独特的优势，也为映射新的易感基因。
In the Finnish breast and ovarian cancer families six BRCA1 and five BRCA2 mutations have been found recurrently. Some of these recurrent mutations have also been seen elsewhere in the world, while others are exclusively of Finnish origin. A haplotype analysis of 26 Finnish families carrying a BRCA1 mutation and 20 families with a BRCA2 mutation indicated that the carriers of each recurrent mutation have common ancestors. The common ancestors were estimated to trace back to 7-36 generations (150-800 years). The time estimates and the geographical clustering of these founder mutations in Finland are in concordance with the population history of this country. Analysis of the cancer phenotypes showed differential ovarian cancer expression in families carrying mutations in the 5' and 3' ends of the BRCA1 gene, and earlier age of ovarian cancer onset in families with BRCA1 mutations compared with families with BRCA2 mutations. The identification of prominent and regional BRCA1 and BRCA2 founder mutations in Finland will have significant impact on diagnostics in Finnish breast and ovarian cancer families. An isolated population with known history and multiple local founder effects in multigenic disease may offer distinct advantages also for mapping novel predisposing genes.