Individual Polymorphism of Albumin Gene Studied by Sequencing DNA

Amino acid substitutions in genetic variants of human serum albumin and in sequences inferred from molecular cloning.

“…None of the five substitutions inferred from cDNA sequence analysis accords with discrepancies in codon usage (silent mutations) noted in these studies (1)(2)(3)(4). Furthermore, when we used the computer program ENZYME to identify all possible sequence-specific sites for the restriction enzymes used in the study of albumin genetic polymorphism (5, 6), we found only two such sites in the albumin exons; neither was related to the apparent amino acid substitutions.…”

“…Two early structures obtained by protein sequencing had up to 10 discrepancies (21,22). The amino acid sequences later inferred from two well-documented cDNA sequences had only two discrepancies (2,3), but a preliminary report (4) listed three additional amino acid substitutions. Also, various groups studying cDNA sequence analysis (4), genomic sequence analysis (1), or restriction fragment length polymorphism (5,6) have concluded that the human albumin gene is highly polymorphic.…”

“…Although electrophoretically detectable mutations in serum albumin are very rare in most populations, an apparent amino acid substitution has been inferred for each of the five individual albumin clones for which the cDNA sequence has been reported (2-4), and the nucleotide variation has been estimated as >1 in 100 (4). Five of the nucleotide differences in the cDNA sequences would lead to an amino acid substitution (Table 1; Fig.…”

“…Although the human albumin gene is highly polymorphic (1)(2)(3)(4)(5)(6), the protein product of the gene is rarely so (7). Serum albumin polymorphism (alloalbuminemia) that is detectable by electrophoresis is very rare in most human populations but does occur with a prevalence of 1-25% in certain ethnic groups (7)(8)(9).…”

Molecular heterogeneity of human hereditary diseases and problems of their gene therapy

“…Следует однако отметить, что внедрение методологии рекомбинантных ДНК в медицинскую генетику (в частности, клонирование и секвенирование кДНК и анализ выведенных аминокислотных последовательностей кодируемых белков, а также изучение полиморфизма нуклеотидных последовательностей геномных генов) привело к существенному прогрессу и в этой области. Так, выявлено большое количество нейтральных (не ведущих к патологическому фенотипу) полиморфных вариантов сывороточного альбумина [59] и ряда других белков и показано, что нуклеотидные замены в геномных кодирующих последовательностях встречаются существенно чаще, чем замещения аминокислот в белках. Обнаружено большое количество точечных мутаций с патологическим фенотипом, что является дополнительным -свидетельством генетической гетерогенности наследственных болезней [60].…”