Jacobson D R, Alves I L, Saraiva M J, Thibodeau S N, Buxbaum J N
Department of Medicine, New York University School of Medicine, NY.
Hum Genet. 1995 Mar;95(3):308-12. doi: 10.1007/BF00225199.
Transthyretin (TTR) Ser 6 was originally described in a Scottish kindred without amyloidosis. This variant, arising from a G-->A transition in codon 6 that destroys an MspI site and creates a BsrI site, was present in none of 50 controls, and was therefore thought to be rare. This variant has subsequently been found in a normal human cDNA liver library and in two unrelated patients with familial amyloidosis and other TTR variants, raising the question whether it is actually a common polymorphism. To address this question, we performed PCR and restriction digestion of 574 DNA samples from people without evidence of amyloidosis or a known family history of amyloidosis. The TTR Ser 6 allele frequency was 33/558 (.060) in Caucasians (including 8/192 (.04) in North American Ashkenazic Jews, 16/218 (.07) in North American non-Jews, and 9/148 (.06) in Portuguese), 3(242 (.01) in African Americans, 0/140 in Africans, and 0/208 in Asians. These data are most suggestive of a single Caucasian founder and the known 25% admixture of "Caucasian" genes in the African-American population. Alternatively, as this variant arose from a transition at a CG dinucleotide "hot spot," it may have arisen on multiple occasions. These data indicate that TTR Ser 6 is a common non-amyloidogenic population polymorphism in Caucasians.
转甲状腺素蛋白（TTR）的Ser 6最初是在一个没有淀粉样变性的苏格兰家族中被描述的。这种变体是由密码子6中的G→A转换产生的，它破坏了一个MspI位点并产生了一个BsrI位点，在50名对照者中均未出现，因此被认为是罕见的。随后在一个正常人类cDNA肝脏文库以及两名患有家族性淀粉样变性和其他TTR变体的无关患者中发现了这种变体，这就引发了一个问题，即它实际上是否是一种常见的多态性。为了解决这个问题，我们对574份没有淀粉样变性证据或已知淀粉样变性家族史的人的DNA样本进行了PCR和限制性消化。在白种人中，TTR Ser 6等位基因频率为33/558（0.060）（包括北美阿什肯纳兹犹太人中的8/192（0.04）、北美非犹太人中的16/218（0.07）以及葡萄牙人中的9/148（0.06）），非裔美国人中为3/242（0.01），非洲人中为0/140，亚洲人中为0/208。这些数据最能表明存在一个单一的白种人奠基者，以及非裔美国人中已知的25%的“白种人”基因混合情况。或者，由于这种变体是由CG二核苷酸“热点”处的转换产生的，它可能已经多次出现。这些数据表明，TTR Ser 6是白种人中一种常见的非淀粉样变性群体多态性。
