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Title: Genetic variants of serum albumin in Americans and Japanese

Abstract

A collaborative search for albumin genetic variants (alloalbumins) was undertaken by cellulose acetate and agarose electrophoresis at pH 8.6 of the sera of patients at two major medical centers in the United States and of nearly 20,000 blood donors in Japan. Seventeen instances of alloalbuminemia were ascertained, and seven different alloalbumin types were characterized by structural study. Two previously unreported alloalbumin types were identified. All of the variants characterized in this study are point mutants, and the sites are spread throughout the albumin gene. However, about one-fourth of all known albumin mutations are clustered in the sequence segment from position 354 through 382.

Authors:
; ; ; ;  [1];  [2];  [3];  [4]; ;  [5]
  1. (Indiana Univ., Bloomington (United States))
  2. (Josai Univ., Saitama (Japan))
  3. (Univ. of Iowa, Iowa City (United States))
  4. (Mayo Clinic, Rochester, MN (United States))
  5. (Japanese Red Cross, Tokyo (Japan))
Publication Date:
OSTI Identifier:
5826515
Resource Type:
Journal Article
Resource Relation:
Journal Name: Proceedings of the National Academy of Sciences of the United States of America; (United States); Journal Volume: 88:21
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; ALBUMINS; AMINO ACID SEQUENCE; ARGININE; ASPARTIC ACID; BIOLOGICAL EVOLUTION; BLOOD SERUM; ELECTROPHORESIS; GENE MUTATIONS; HISTIDINE; HUMAN POPULATIONS; JAPAN; SCREENING; USA; AMINO ACIDS; ASIA; AZOLES; CARBOXYLIC ACIDS; DEVELOPED COUNTRIES; HETEROCYCLIC ACIDS; HETEROCYCLIC COMPOUNDS; IMIDAZOLES; MOLECULAR STRUCTURE; MUTATIONS; NORTH AMERICA; ORGANIC ACIDS; ORGANIC COMPOUNDS; ORGANIC NITROGEN COMPOUNDS; POPULATIONS; PROTEINS; 550200* - Biochemistry

Citation Formats

Madison, J., Sakamoto, Yasushi, Watkins, S., Davis, E., Putnam, F.W., Arai, Kunio, Feld, R.D., Kyle R.A., Matsuda, Yuhichi, and Amaki, Itta. Genetic variants of serum albumin in Americans and Japanese. United States: N. p., 1991. Web. doi:10.1073/pnas.88.21.9853.
Madison, J., Sakamoto, Yasushi, Watkins, S., Davis, E., Putnam, F.W., Arai, Kunio, Feld, R.D., Kyle R.A., Matsuda, Yuhichi, & Amaki, Itta. Genetic variants of serum albumin in Americans and Japanese. United States. doi:10.1073/pnas.88.21.9853.
Madison, J., Sakamoto, Yasushi, Watkins, S., Davis, E., Putnam, F.W., Arai, Kunio, Feld, R.D., Kyle R.A., Matsuda, Yuhichi, and Amaki, Itta. 1991. "Genetic variants of serum albumin in Americans and Japanese". United States. doi:10.1073/pnas.88.21.9853.
@article{osti_5826515,
title = {Genetic variants of serum albumin in Americans and Japanese},
author = {Madison, J. and Sakamoto, Yasushi and Watkins, S. and Davis, E. and Putnam, F.W. and Arai, Kunio and Feld, R.D. and Kyle R.A. and Matsuda, Yuhichi and Amaki, Itta},
abstractNote = {A collaborative search for albumin genetic variants (alloalbumins) was undertaken by cellulose acetate and agarose electrophoresis at pH 8.6 of the sera of patients at two major medical centers in the United States and of nearly 20,000 blood donors in Japan. Seventeen instances of alloalbuminemia were ascertained, and seven different alloalbumin types were characterized by structural study. Two previously unreported alloalbumin types were identified. All of the variants characterized in this study are point mutants, and the sites are spread throughout the albumin gene. However, about one-fourth of all known albumin mutations are clustered in the sequence segment from position 354 through 382.},
doi = {10.1073/pnas.88.21.9853},
journal = {Proceedings of the National Academy of Sciences of the United States of America; (United States)},
number = ,
volume = 88:21,
place = {United States},
year = 1991,
month =
}
  • Proalbumins are rare genetic variants of human serum albumin containing a basic propeptide that is not removed during post-transcriptional processing because of a mutation in the site of excision, an Arg-Arg sequence. The authors have identified the amino acid substitutions in three different types of proalbumins designated Gainesville, Taipei, and Takefu. The first two proalbumins are identical to previously described proalbumins of the Christchurch and Lille types, respectively, and exhibit the characteristic properties of susceptibility to tryptic cleavage and of lower metal-binding affinity. Takefu is a third type of proalbumin and resists tryptic cleavage because of the substitution Arg/sup -1/more » ..-->.. Pro. Each of the first two types of proalbumins has been identified in geographically separate, ethnically diverse populations and therefore must have arisen by independent mutations. There is some tendency for mutations in albumin to cluster in the propeptide sequence. Although the substitution His/sup 3/ ..-->.. Gln in the genetic variant albumin Nagasaki-3 decreases metal-binding affinity, mutations further down the polypeptide chain have no such effect, nor is there any reduction of cooper-binding affinity in albumin from patients with Wilson disease.« less
  • The structural changes in four genetic variants of human serum albumin were analyzed by tandem high-pressure liquid chromatography (HPLC) of the tryptic peptides, HPLC mapping and isoelectric focusing of the CNBr fragments, and amino acid sequence analysis of the purified peptides. Lysine-372 of normal (common) albumin A was changed to glutamic acid both in albumin Naskapi, a widespread polymorphic variant of North American Indians, and in albumin Mersin found in Eti Turks. The two variants also exhibited anomalous migration in NaDodSO/sub 4//PAGE, which is attributed to a conformational change. The identity of albumins Naskapi and Mersin may have originated throughmore » descent from a common mid-Asiatic founder of the two migrating ethnic groups, or it may represent identical but independent mutations of the albumin gene. In albumin Adana, from Eti Turks, the substitution site was not identified but was localized to the region from positions 447 through 548. The substitution of aspartic acid-550 by glycine was found in albumin Mexico-2 from four individuals of the Pima tribe. Although only single-point substitutions have been found in these and in certain other genetic variants of human albumin, five differences exist in the amino acid sequences inferred from cDNA sequences by workers in three other laboratories. However, our results on albumin A and on 14 different genetic variants accord with the amino acid sequence of albumin deduced from the genomic sequence. The apparent amino acid substitutions inferred from comparison of individual cDNA sequences probably reflect artifacts in cloning or in cDNA sequence analysis rather than polymorphism of the coding sections of the albumin gene.« less
  • A long-term electrophoretic survey of genetic variants of serum albumin has identified an alloalbumin in 589 unrelated individuals in Italy. The alloalbumins were classified electrophoretically into 17 types. The number of unrelated carriers for each type varied from 1 for several variants reported here to 103 for albumin B. The structural change in 8 of these types has previously been determined, and the amino acid substitutions in 3 additional types are reported here. The ability to distinguish so many alloalbumin types by electrophoresis at several pH values indicates that similar substitutions at different sites produce variants with different electrophoretic mobilities.more » Except for chain terminations in two Italian variants, all the mutations thus far determined for alloalbumins are attributable to a single-base change in the structural gene, and there is a preponderance of transitions and purine mutations. Seven alloalbumins for which the structural change has been established have been ascertained only in Italy. Several of these are clustered in specific geographic regions of Italy, which suggests an origin through a founder individual. Other variants that occur worldwide are nonetheless clustered in geographic regions within Italy. In these cases an independent mutation probably occurred at a hypermutable site such as a CpG dinucleotide.« less
  • The authors report an effort to determine the basis for the altered migration of seven inherited albumin variants detected by one-dimensional electrophoresis in population surveys involving tribal Amerindians and Japanese children. An amino acid substitution has thus far been determined for four of the variants. The randomness in the albumin polypeptide of these and the other sixteen independently ascertained amino acid substitutions of albumin and proalbumin thus far established was analyzed; the clustering of eight of these at two positions in the six-amino acid propeptide sequence seems noteworthy. By comparison with other proteins studied by electrophoresis, albumin exhibits average variability.more » It is a paradox that individuals who, for genetic reasons, lack albumin exhibit no obvious ill effects; yet, electrophoretic variants of albumin are no more numerous than are variants of proteins, the absence of which results in severe disease.« less
  • At least 35 allelic variants of human serum albumin have been sequenced at the protein level. All except two COOH-terminal variants, Catania and Venezia, are readily explainable as single-point substitutions. The two chain-termination variants are clustered in certain locations in Italy and are found in numerous unrelated individuals. In order to correlate the protein change in these variants with the corresponding DNA mutation, the two variant albumin genes have been cloned, sequenced, and compared to normal albumin genomic DNA. In the Catania variant, a single base deletion and subsequent frameshift leads to a shortened and altered COOH terminus. Albumin Veneziamore » is caused by a mutation that alters the first consensus nucleotide of the 5{prime} donor splice junction of intron 14 and the 3{prime} end of exon 14, which is shortened from 68 to 43 base pairs. This change leads to an exon skipping event resulting in direct splicing of exon 13 to exon 15. The predicted Venezia albumin product has a truncated amino acid sequence (580 residues instead of 585), and the COOH-terminal sequence is altered after Glu-571. The variant COOH terminus ends with the dibasic sequence Arg-Lys that is apparently removed through stepwise cleavage by serum carboxypeptidase B to yield several forms of circulating albumin.« less