Chamberlain J S, Boehnke M, Frank T S, Kiousis S, Xu J, Guo S W, Hauser E R, Norum R A, Helmbold E A, Markel D S
Department of Human Genetics, University of Michigan School of Medicine, Ann Arbor.
Am J Hum Genet. 1993 Apr;52(4):792-8.
Previous studies have demonstrated linkage between early-onset breast cancer and ovarian cancer and genetic markers on chromosome 17q21. These markers define the location of a gene (BRCA1) which appears to be inherited as an autosomal dominant susceptibility allele. We analyzed five families with multiple affected individuals for evidence of linkage to the BRCA1 region. Two of the five families appear to be linked to BRCA1. One apparently linked family contains critical recombinants, suggesting that the gene is proximal to the marker D17S579 (Mfd188). These findings are consistent with the maximum-likelihood position estimated by the Breast Cancer Linkage Consortium and with recombination events detected in other linked families. Linkage analysis was greatly aided by PCR-based analysis of paraffin-embedded normal breast tissue from deceased family members, demonstrating the feasibility and importance of this approach. One of the two families with evidence of linkage between breast cancer and genetic markers flanking BRCA1 represents the first such family of African-American descent to be reported in detail.
以往的研究已证实早发性乳腺癌与卵巢癌以及17号染色体q21区域的遗传标记之间存在连锁关系。这些标记确定了一个基因（BRCA1）的位置，该基因似乎作为常染色体显性易感等位基因进行遗传。我们分析了五个有多个患病个体的家族，以寻找与BRCA1区域连锁的证据。五个家族中有两个家族似乎与BRCA1连锁。一个明显连锁的家族包含关键重组体，这表明该基因位于标记D17S579（Mfd188）的近端。这些发现与乳腺癌连锁协会估计的最大似然位置以及在其他连锁家族中检测到的重组事件一致。基于聚合酶链反应（PCR）对已故家族成员石蜡包埋的正常乳腺组织进行分析，极大地辅助了连锁分析，证明了这种方法的可行性和重要性。两个显示乳腺癌与BRCA1侧翼遗传标记之间存在连锁证据的家族之一，是首个详细报道的非裔美国人后裔家族。
