On the origin and spread of beta-thalassemia: recurrent observation of four mutations in different ethnic groups.
On the origin and spread of beta-thalassemia: recurrent observation of four mutations in different ethnic groups.
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关于β-地中海贫血的起源和传播：不同种族中四种突变的反复观察。
DOI：
10.1073/pnas.83.17.6529
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发表时间：
1986
影响因子：
11.1
通讯作者：
H. Kazazian
中科院分区：
文献类型：
--
作者：
C. Wong;S. Antonarakis;S. C. Goff;S. Orkin;C. Boehm;H. Kazazian
7个β-地中海贫血基因的特点后，他们被确定为候选人以前未描述的突变的基础上密切相关的β-珠蛋白基因簇中的DNA多态性单倍型与特定的种族突变。这些基因中有四个的分子缺陷是相同的，密码子41和42内的四个核苷酸（-CTTT）的移码缺失。该基因代表了老挝β地中海贫血基因[框架1（FR 1）]，越南人（FR 1）和两名中国患者（FR 3亚洲人和FR 1）共享的常见东南亚突变。该缺失先前已在中国人（FR 1）和亚洲印度人（FR 2）中观察到，并且是相同分子缺陷的独立起源、可能的等位基因间基因转换（如在中国人的两种不同β-珠蛋白基因框架上所见）和亚洲国家的突变基因迁移的实例。第二个突变基因迁移的例子是在一名伊朗患者中发现的，该患者在密码子8和9之间插入了一个核苷酸（G），与之前在同一染色体背景下的一名亚洲印度人中发现的突变相同。最后检测的两个基因代表了突变独立起源的进一步有力证据。亚洲印第安人-88位的C-到-T替换先前已在美洲黑人中在不同的β-珠蛋白基因框架上被鉴定，并且在美洲黑人中发现的间插序列2的核苷酸1处的G-到-A转换先前已在地中海人的不同染色体背景上被观察到。这项研究表明，没有多少常见的β地中海贫血突变有待发现。这也表明β-珠蛋白基因中的某些序列相对突变敏感。
Seven beta-thalassemia genes were characterized after they were identified as candidates for previously undescribed mutations based upon the close association of DNA polymorphism haplotypes in the beta-globin gene cluster with specific ethnic mutations. The molecular defect in four of these genes was identical, a frameshift deletion of four nucleotides (-CTTT) within codons 41 and 42. This gene represents a common Southeast Asian mutation shared by a Laotian beta-thalassemia gene, [framework 1 (FR1)], a Vietnamese (FR1), and two Chinese patients (FR3 Asian and FR1). The deletion has been observed previously in Chinese (FR1) and Asian Indians (FR2) and is an example of independent origins of the same molecular defect, possible interallelic gene conversion (as it is seen on two different beta-globin gene frameworks in Chinese), and mutant gene migration in the Asian countries. A second example of mutant gene migration was identified in an Iranian patient with a nucleotide insertion (G) between codons 8 and 9, the same mutation previously found in an Asian Indian in the same chromosomal background. The last two genes examined represent further strong evidence for independent origins of mutation. A C-to-T substitution at position -88 in an Asian Indian has been identified previously in an American Black on a different beta-globin gene framework, and a G-to-A transition at nucleotide 1 of intervening sequence 2 found in an American Black has been observed previously on a different chromosome background in Mediterraneans. This study suggests that there are not many common beta-thalassemia mutations remaining to be discovered. It also suggests that certain sequences in the beta-globin gene are relatively mutation sensitive.