Bunn H F, Schmidt G J, Haney D N, Dluhy R G
Proc Natl Acad Sci U S A. 1975 Sep;72(9):3609-13. doi: 10.1073/pnas.72.9.3609.
An asymptomatic woman was found to have a compensated hemolytic state due to an unstable hemoglobin variant, comprising 35% of the total. Peptide maps of tryptic digests of the abnormal beta chain were identical to those of beta A except that tryptic peptide 15 (Tyr-His-COOH) was absent and a new peptide was detected, containing equivalent amounts of Ser, Ile, Thr, and Lys. Its sequence was determined by manual Edman degradation. An additional hydrophobic peptide isolated by counter-current distribution contained: Asx, Ser, Ala, Tyr, 2 Phe, and 3 Leu. Its sequence was determined on an automatic solid phase sequencer. Digestion with carboxypeptidase A confirmed the C-terminal sequence. Hemoglobin Cranston has an elongated beta chain with the following structure: (see article). This variant is the first "adult" human hemoglobin known to contain isoleucine. It is likely that hemoglobin Cranston arose because of a nonhomologous crossover of two normal beta chain genes, probably during meiosis, with the insertion of two nucleotides (AG) at position 144, resulting in a frame shift. Hemoglobin Cranston provides new information on the structure of the beta chain gene as well as an explanation of both the structure and genetic basis of hemoglobin Tak, the only other elongated beta chain variant that has been described.
一名无症状女性被发现由于一种不稳定的血红蛋白变异体而处于代偿性溶血状态，该变异体占总量的35%。异常β链胰蛋白酶消化产物的肽图与βA的肽图相同，只是缺少胰蛋白酶肽15（酪氨酸-组氨酸-COOH），并检测到一种新肽，其含有等量的丝氨酸、异亮氨酸、苏氨酸和赖氨酸。通过手动埃德曼降解法确定了其序列。通过逆流分配法分离出的另一种疏水肽含有：天冬氨酸、丝氨酸、丙氨酸、酪氨酸、2个苯丙氨酸和3个亮氨酸。在自动固相测序仪上确定了其序列。用羧肽酶A消化证实了C末端序列。克兰斯顿血红蛋白具有以下结构的延长β链：（见文章）。这种变异体是已知的第一种含异亮氨酸的“成人”人类血红蛋白。克兰斯顿血红蛋白很可能是由于两个正常β链基因在减数分裂期间可能发生的非同源交叉，在第144位插入了两个核苷酸（AG），导致移码而产生的。克兰斯顿血红蛋白为β链基因的结构提供了新信息，同时也解释了已描述的另一种延长β链变异体——塔克血红蛋白的结构和遗传基础。
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