Korge B P, Gan S Q, McBride O W, Mischke D, Steinert P M
Laboratory of Skin Biology, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892.
Proc Natl Acad Sci U S A. 1992 Feb 1;89(3):910-4. doi: 10.1073/pnas.89.3.910.
Existing data suggest that the human keratin 10 intermediate filament protein is polymorphic in amino acid sequence and in size. To precisely define the nature of the polymorphism, we have used PCR amplification and sequence analyses on DNA from several individuals including five with documented size variations of the keratin 10 protein. We found no variation in the N-terminal or rod domain sequences. However, we observed many variations in the V2 subdomain near the C terminus in glycine-rich sequences with a variation of as much as 114 base pairs (38 amino acids), but all individuals had either one or two variants. Our results show that (i) the keratin 10 system is far more polymorphic than previously realized, (ii) the polymorphism is restricted to insertions and deletions of the glycine-rich quasipeptide repeats that form the glycine-loop motif in the C-terminal domain, (iii) the polymorphism can be accounted for by simple allelic variations that segregate by normal Mendelian mechanisms, and (iv) the differently sized PCR products most likely represent different alleles of a single-copy gene per haploid genome.
现有数据表明，人类角蛋白10中间丝蛋白在氨基酸序列和大小上具有多态性。为了精确界定这种多态性的本质，我们对来自多个个体的DNA进行了聚合酶链反应（PCR）扩增和序列分析，其中包括5名角蛋白10蛋白大小有记录差异的个体。我们发现N端或杆状结构域序列没有变异。然而，我们在靠近C端的V2亚结构域富含甘氨酸的序列中观察到许多变异，变异多达114个碱基对（38个氨基酸），但所有个体都有一个或两个变异体。我们的结果表明：（i）角蛋白10系统的多态性比之前认识到的要高得多；（ii）这种多态性仅限于在C端结构域形成甘氨酸环基序的富含甘氨酸的准肽重复序列的插入和缺失；（iii）这种多态性可以由通过正常孟德尔机制分离的简单等位基因变异来解释；（iv）大小不同的PCR产物很可能代表每个单倍体基因组中一个单拷贝基因的不同等位基因。
