Yi-Tao Z, Headlee M E, Henson J, Lam H, Wilson J B, Huisman T H
Biochim Biophys Acta. 1982 Oct 5;707(2):206-12. doi: 10.1016/0167-4838(82)90352-1.
Two alpha-chain variants, Hb G-Philadelphia and Hb Matsue-Oki, were present in members of a relatively large black family from South Carolina. The four Hb G-Philadelphia heterozygotes averaged 35.6% Hb G, suggesting the presence of an alpha-thalassemia-2 condition in cis to the Hb G mutation, which was confirmed by DNA structural analysis. The seven Hb Matsue-Oki heterozygotes averaged 22.2% Hb MO and likely have four active alpha-chain genes. One infant was a compound heterozygote for the two Hb variants which could not be separated from each other. The quantity of Hb G plus Hb MO was 58% by DEAE-cellulose chromatography and 69% by chain analyses. These results and the family data indicate that this child had three active alpha-chain genes, of which one regulated the synthesis of the normal alpha chain, one was mutated to give the alpha G chain, and one to give the alpha MO chain. The amino acid substitutions in Hb G-Philadelphia and Hb Matsue-Oki are located in the tryptic peptide alpha T-9, which is 29 amino acid residues long. Structural analyses of these abnormalities made use of high-pressure liquid chromatography for the separation of both tryptic and thermolytic peptides and of a highly sensitive ultra-micro sequencing procedure. Although the alpha 68 Asn replaced by Lys substitution is readily demonstrable in Hb G-Philadelphia the elucidation of the alpha 75 Asp replaced by Asn replacement in Hb Matsue-Oki was greatly facilitated by the use of these microprocedures.
来自南卡罗来纳州的一个相对较大的黑人家庭的成员中存在两种α链变体，即Hb G - 费城变体和Hb松江 - 冲变体。4名Hb G - 费城杂合子平均含有35.6%的Hb G，提示在Hb G突变的顺式位置存在α地中海贫血2型情况，这一点通过DNA结构分析得到证实。7名Hb松江 - 冲杂合子平均含有22.2%的Hb MO，可能有4个活性α链基因。一名婴儿是这两种Hb变体的复合杂合子，二者无法彼此分离。通过DEAE - 纤维素色谱法测定，Hb G加Hb MO的含量为58%，通过链分析测定为69%。这些结果以及家族数据表明，这名儿童有3个活性α链基因，其中一个调控正常α链的合成，一个发生突变产生αG链，另一个产生αMO链。Hb G - 费城变体和Hb松江 - 冲变体中的氨基酸替换位于胰蛋白酶肽αT - 9中，该肽段长29个氨基酸残基。对这些异常情况的结构分析利用高压液相色谱法分离胰蛋白酶肽和热解肽，并采用了高度灵敏的超微量测序程序。虽然在Hb G - 费城变体中α68位天冬酰胺被赖氨酸替换很容易得到证实，但通过使用这些微量程序，极大地促进了对Hb松江 - 冲变体中α75位天冬氨酸被天冬酰胺替换的阐明。
