Själander A, Birgander R, Kivelä A, Beckman G
Department of Medical Genetics, Umeå University, Sweden.
Hum Hered. 1995 May-Jun;45(3):144-9. doi: 10.1159/000154275.
Three different p53 polymorphisms (a codon 72 BstUI RFLP, a 16-bp duplication in intron 3 and an MspI RFLP in intron 6) and haplotype combinations were studied in three northern European populations, viz. Finns, Swedes and Swedish Saamis. Significant ethnic differences were found in the codon 72 and 16-bp polymorphisms. The three polymorphisms were in strong linkage disequilibria, all of which were highly significant (p < 1 x 10(-18)), and ethnic differences with respect to linkage disequilibria were observed. Estimates of the frequencies of extended haplotypes showed that the most common ('wild-type') haplotype in the three populations was 2-1-2, viz, the codon 72 Arg allele linked to absence of the 16-bp duplication and presence of the MspI site. There were two additional common haplotypes, 1-1-2 and 1-2-1, and five rare haplotypes with a combined frequency of about 0.03. The present results indicate that extended haplotypes would be more informative in studies of population differences and associations between p53 germline mutations and cancer.
在三个北欧人群，即芬兰人、瑞典人和瑞典萨米人中，研究了三种不同的p53基因多态性（密码子72 BstUI限制性片段长度多态性、内含子3中的16 bp重复序列和内含子6中的MspI限制性片段长度多态性）以及单倍型组合。在密码子72和16 bp多态性中发现了显著的种族差异。这三种多态性处于强连锁不平衡状态，所有这些都具有高度显著性（p < 1×10^(-18)），并且观察到了连锁不平衡方面的种族差异。扩展单倍型频率的估计表明，这三个人群中最常见的（“野生型”）单倍型是2-1-2，即密码子72的精氨酸等位基因与不存在16 bp重复序列和存在MspI位点相关联。还有另外两种常见单倍型，1-1-2和1-2-1，以及五种罕见单倍型，其合并频率约为0.03。目前的结果表明，扩展单倍型在研究p53种系突变与癌症之间的人群差异和关联方面将提供更多信息。
