Surrey S, Ohene-Frempong K, Rappaport E, Atwater J, Schwartz E
Proc Natl Acad Sci U S A. 1980 Aug;77(8):4885-9. doi: 10.1073/pnas.77.8.4885.
We have studied the inheritance of the alpha-chain hemoglobin variant Hb G-Philadelphia (alpha 2(68 Asn leads to Lys)Beta 2) in two African-American families. Expression of the alpha-globin loci was monitored by the percentage of Hb G in these individuals. The variant represented approximately 33% of the total adult hemoglobin in some and 50% in others. alpha-Globin gene fragments were analyzed by using restricton endonucleases that cleave outside (EcoRI), within (HindIII), and between (Bgl II) the normal duplicated alpha-globin loci (alpha alpha/alpha alpha). Individuals having 33% variant lack one functioning alpha gene (alpha G/alpha alpha); those with 50% variant lack two genes, one missing on each chromosome (alpha G/alpha). Inheritance of alpha G was therefore linked to that of a chromosome with only one functional alpha-globin gene locus. This locus is probably the result of a nonhomologous crossover. Our results also suggest equal expression of the alpha-globin loci in humans because the percentages of the variant could be explained solely on the basis of the total number of alpha genes present. The percentages of Hb G as well as other hematologic data all were consistent with the number of alpha-globin genes identified by restriction endonuclease mapping. Gene mapping yields a more precise determination of the number of alpha-globin genes than does study of globin synthesis.
我们研究了两个非裔美国家庭中α链血红蛋白变体Hb G - 费城（α2(68 Asn→Lys)β2）的遗传情况。通过这些个体中Hb G的百分比来监测α珠蛋白基因座的表达。在一些个体中，该变体约占成人血红蛋白总量的33%，而在另一些个体中占50%。使用限制性内切酶分析α珠蛋白基因片段，这些酶分别在正常重复的α珠蛋白基因座（αα/αα）外侧（EcoRI）、内部（HindIII）和之间（Bgl II）进行切割。含有33%变体的个体缺少一个有功能的α基因（αG/αα）；含有50%变体的个体缺少两个基因，每条染色体上各缺失一个（αG/α）。因此，αG的遗传与仅带有一个功能性α珠蛋白基因座的染色体的遗传相关。这个基因座可能是一次非同源交叉的结果。我们的结果还表明人类α珠蛋白基因座存在等量表达，因为变体的百分比仅根据所存在的α基因总数就能得到解释。Hb G的百分比以及其他血液学数据均与通过限制性内切酶图谱鉴定的α珠蛋白基因数量一致。与珠蛋白合成研究相比，基因图谱能更精确地确定α珠蛋白基因的数量。
