Akerman B R, Fujiwara T M, Lancaster G A, Morgan K, Scriver C R
Department of Biology, McGill University, Montreal, Quebec, Canada.
Am J Med Genet. 1990 May;36(1):76-84. doi: 10.1002/ajmg.1320360115.
We obtained blood samples in a screening program designed to detect beta-thalassemia heterozygotes in Montreal; additional samples were obtained from referred persons. We analyzed DNA for variant numbers of alpha-globin genes, notably the alpha-thalassemia2 (-alpha/), alpha-thalassemia1, (- -/), and triplicated alpha-globin gene (alpha alpha alpha/) haplotypes using restriction enzymes and probes for alpha-globin and zeta-globin gene sequences. We estimated the numbers of Montreal residents of Italian and Greek ethnic origin with -alpha/alpha alpha genotype. Thus, 4.3% of Italians and 1.5% of Greeks, or about 7,500 persons, are estimated to be alpha-thalassemia2, trait (silent carriers), largely (80%) in the -alpha 3.7/type I form. The triplicated alpha-globin gene haplotype was also found. The risk of a severe (alpha-thalassemia1) phenotype associated with inheritance of - -/alpha alpha or -alpha/-alpha genotypes was low and was found predominantly in this study, in persons of Asian ethnic origin. The sample of Asians was too small to estimate carrier frequencies; however, based on results from the beta-thalassemia screening program, we estimated that about 4% of Asians (about 1,300 persons) in Montreal are alpha-thalassemia carriers. We identified persons heterozygous for both beta-thalassemia and alpha-thalassemia mutations. In these double heterozygotes, the effect of the triplicated alpha-globin gene was to make the erythrocyte parameters used for screening (MCV and %HbA2) more deviant from normal whereas deletion of 2 alpha-globin genes tended to normalize the erythrocyte values. These findings have implications for the screening program and reproductive counseling.
我们在一项旨在检测蒙特利尔β地中海贫血杂合子的筛查项目中采集了血样；另外的样本则取自转诊人员。我们使用针对α珠蛋白和ζ珠蛋白基因序列的限制性内切酶及探针，分析了α珠蛋白基因数量变异的DNA，尤其是α地中海贫血2（-α/）、α地中海贫血1（--/）和α珠蛋白基因三倍体（ααα/）单倍型。我们估算了蒙特利尔意大利和希腊族裔中-α/αα基因型居民的数量。因此，据估计，4.3%的意大利人和1.5%的希腊人，约7500人，为α地中海贫血2性状（沉默携带者），其中大部分（80%）为-α3.7/Ⅰ型。还发现了α珠蛋白基因三倍体单倍型。与--/αα或-α/-α基因型遗传相关的严重（α地中海贫血1）表型风险较低，且在本研究中主要见于亚洲族裔人群。亚洲人的样本量过小，无法估算携带者频率；不过，根据β地中海贫血筛查项目的结果，我们估计蒙特利尔约4%的亚洲人（约1300人）为α地中海贫血携带者。我们鉴定出了同时携带β地中海贫血和α地中海贫血突变的杂合子。在这些双重杂合子中，α珠蛋白基因三倍体的作用是使用于筛查的红细胞参数（平均红细胞体积和HbA2百分比）更偏离正常范围，而缺失2个α珠蛋白基因则倾向于使红细胞值恢复正常。这些发现对筛查项目和生殖咨询具有重要意义。
