Higgs D R, Pressley L, Serjeant G R, Clegg J B, Weatherall D J
Br J Haematol. 1981 Jan;47(1):43-56. doi: 10.1111/j.1365-2141.1981.tb02760.x.
We have studied seven Jamaican Negro families in whom the genes for alpha thalassaemia and the sickle cell mutation (betas) were independently segregated. Using a combination of techniques we identified two alpha thalassaemia phenotypes which resemble the severe (alpha thalassaemia 1) and mild (alpha thalassaemia 2) determinants previously described in Orientals. This study has enabled us to clearly correlate the phenotype of alpha thalassaemia with the genotype in this population. Furthermore, since in each family alpha thalassaemia was present in association with the gene for the sickle cell mutation we have determined the proportion of Hb S in the peripheral blood of individuals with the alpha alpha/alpha alpha, -alpha/alpha alpha and -alpha/-alpha genotype who are also heterozygous for the betas mutation. Genetic analysis in these families shows that in each case subjects with the alpha thalassaemia 1 phenotype are homozygous for the alpha thalassaemia 2 defect (-alpha/-alpha). We have found no instances of the genotype --/alpha alpha in this population which may explain the rarity of the severe alpha thalassaemia syndromes in Jamaica. Restriction mapping data in the alpha thalassaemia 2 homozygotes from this population shows that the (-alpha/) haplotype results from a deletion of one of the linked pair of alpha globin genes and that this has probably arisen by an unequal crossover between non-homologous alpha genes.
我们研究了7个牙买加黑人家庭，其中α地中海贫血基因和镰状细胞突变（βS）基因是独立分离的。通过综合运用多种技术，我们识别出了两种α地中海贫血表型，它们类似于先前在东方人中所描述的严重型（α地中海贫血1）和轻型（α地中海贫血2）决定因素。这项研究使我们能够清楚地将该人群中α地中海贫血的表型与基因型关联起来。此外，由于在每个家庭中α地中海贫血都与镰状细胞突变基因同时存在，我们测定了αα/αα、-α/αα和-α/-α基因型且同时为βS突变杂合子的个体外周血中Hb S的比例。对这些家庭的遗传分析表明，在每种情况下，具有α地中海贫血1表型的个体对于α地中海贫血2缺陷（-α/-α）是纯合的。我们在该人群中未发现--/αα基因型的实例，这可能解释了牙买加严重α地中海贫血综合征的罕见性。来自该人群的α地中海贫血2纯合子的限制性图谱数据表明，（-α/）单倍型是由一对连锁的α珠蛋白基因中的一个缺失所致，并且这可能是由非同源α基因之间的不等交换产生的。
