Skip to main content
PMC home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1990 Nov;87(22):8721–8725. doi: 10.1073/pnas.87.22.8721

Mutations in genetic variants of human serum albumin found in Italy.

M Galliano 1, L Minchiotti 1, F Porta 1, A Rossi 1, G Ferri 1, J Madison 1, S Watkins 1, F W Putnam 1
PMCID: PMC55031  PMID: 2247440

Abstract

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. Albumin Varese has a substitution, -2 arginine to histidine (-2 Arg----His), the same as that reported for proalbumin Lille; albumin Torino has the substitution 60 Glu----Lys; and albumin Vibo Valentia has the substitution 82 Glu----Lys. 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. 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.

Full text

PDF
8721

Images in this article

8722Image
on p.8722

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Arai K., Ishioka N., Huss K., Madison J., Putnam F. W. Identical structural changes in inherited albumin variants from different populations. Proc Natl Acad Sci U S A. 1989 Jan;86(2):434–438. doi: 10.1073/pnas.86.2.434. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Arai K., Madison J., Huss K., Ishioka N., Satoh C., Fujita M., Neel J. V., Sakurabayashi I., Putnam F. W. Point substitutions in Japanese alloalbumins. Proc Natl Acad Sci U S A. 1989 Aug;86(16):6092–6096. doi: 10.1073/pnas.86.16.6092. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Arai K., Madison J., Shimizu A., Putnam F. W. Point substitutions in albumin genetic variants from Asia. Proc Natl Acad Sci U S A. 1990 Jan;87(1):497–501. doi: 10.1073/pnas.87.1.497. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Brennan S. O., Arai K., Madison J., Laurell C. B., Galliano M., Watkins S., Peach R., Myles T., George P., Putnam F. W. Hypermutability of CpG dinucleotides in the propeptide-encoding sequence of the human albumin gene. Proc Natl Acad Sci U S A. 1990 May;87(10):3909–3913. doi: 10.1073/pnas.87.10.3909. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Brennan S. O., Carrell R. W. A circulating variant of human proalbumin. Nature. 1978 Aug 31;274(5674):908–909. doi: 10.1038/274908a0. [DOI] [PubMed] [Google Scholar]
  6. Galliano M., Minchiotti L., Iadarola P., Ferri G., Zapponi M. C., Castellani A. A. The amino acid substitution in albumin Roma: 321 Glu----Lys. FEBS Lett. 1988 Jun 6;233(1):100–104. doi: 10.1016/0014-5793(88)81363-2. [DOI] [PubMed] [Google Scholar]
  7. Galliano M., Minchiotti L., Iadarola P., Stoppini M., Ferri G., Castellani A. A. The molecular defect of albumin Tagliacozzo: 313 Lys----Asn. FEBS Lett. 1986 Nov 24;208(2):364–368. doi: 10.1016/0014-5793(86)81050-x. [DOI] [PubMed] [Google Scholar]
  8. Galliano M., Minchiotti L., Iadarola P., Zapponi M. C., Ferri G., Castellani A. A. Structural characterization of a chain termination mutant of human serum albumin. J Biol Chem. 1986 Mar 25;261(9):4283–4287. [PubMed] [Google Scholar]
  9. Galliano M., Minchiotti L., Stoppini M., Tàrnoky A. L. A new proalbumin variant: albumin Jaffna (-1 Arg----Leu). FEBS Lett. 1989 Sep 25;255(2):295–299. doi: 10.1016/0014-5793(89)81109-3. [DOI] [PubMed] [Google Scholar]
  10. Huss K., Madison J., Ishioka N., Takahashi N., Arai K., Putnam F. W. The same substitution, glutamic acid----lysine at position 501, occurs in three alloalbumins of Asiatic origin: albumins Vancouver, Birmingham, and Adana. Proc Natl Acad Sci U S A. 1988 Sep;85(18):6692–6696. doi: 10.1073/pnas.85.18.6692. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Iadarola P., Minchiotti L., Galliano M. Localization of the amino acid substitution site in a fast migrating variant of human serum albumin. FEBS Lett. 1985 Jan 21;180(1):85–88. doi: 10.1016/0014-5793(85)80237-4. [DOI] [PubMed] [Google Scholar]
  12. Minchiotti L., Galliano M., Iadarola P., Meloni M. L., Ferri G., Porta F., Castellani A. A. The molecular defect in a COOH-terminal-modified and shortened mutant of human serum albumin. J Biol Chem. 1989 Feb 25;264(6):3385–3389. [PubMed] [Google Scholar]
  13. Minchiotti L., Galliano M., Iadarola P., Stoppini M., Ferri G., Castellani A. A. Structural characterization of two genetic variants of human serum albumin. Biochim Biophys Acta. 1987 Dec 18;916(3):411–418. doi: 10.1016/0167-4838(87)90187-7. [DOI] [PubMed] [Google Scholar]
  14. Minchiotti L., Galliano M., Iadarola P., Zepponi E., Ferri G. The molecular defect of albumin Castel di Sangro: 536 Lys----Glu. Biochim Biophys Acta. 1990 Jun 19;1039(2):204–208. doi: 10.1016/0167-4838(90)90187-k. [DOI] [PubMed] [Google Scholar]
  15. Minghetti P. P., Ruffner D. E., Kuang W. J., Dennison O. E., Hawkins J. W., Beattie W. G., Dugaiczyk A. Molecular structure of the human albumin gene is revealed by nucleotide sequence within q11-22 of chromosome 4. J Biol Chem. 1986 May 25;261(15):6747–6757. [PubMed] [Google Scholar]
  16. Neel J. V., Satoh C., Goriki K., Asakawa J., Fujita M., Takahashi N., Kageoka T., Hazama R. Search for mutations altering protein charge and/or function in children of atomic bomb survivors: final report. Am J Hum Genet. 1988 May;42(5):663–676. [PMC free article] [PubMed] [Google Scholar]
  17. Rochu D., Fine J. M., Putnam F. W. Variants génétiques de l'albumine humaine: caractérisation structurale des allotypes utilisés comme références dans la classification électrophorétique. Rev Fr Transfus Immunohematol. 1988 Dec;31(5):725–733. doi: 10.1016/s0338-4535(88)80080-1. [DOI] [PubMed] [Google Scholar]
  18. Takahashi N., Takahashi Y., Blumberg B. S., Putnam F. W. Amino acid substitutions in genetic variants of human serum albumin and in sequences inferred from molecular cloning. Proc Natl Acad Sci U S A. 1987 Jul;84(13):4413–4417. doi: 10.1073/pnas.84.13.4413. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Takahashi N., Takahashi Y., Isobe T., Putnam F. W., Fujita M., Satoh C., Neel J. V. Amino acid substitutions in inherited albumin variants from Amerindian and Japanese populations. Proc Natl Acad Sci U S A. 1987 Nov;84(22):8001–8005. doi: 10.1073/pnas.84.22.8001. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Takahashi N., Takahashi Y., Putnam F. W. Structural changes and metal binding by proalbumins and other amino-terminal genetic variants of human serum albumin. Proc Natl Acad Sci U S A. 1987 Nov;84(21):7403–7407. doi: 10.1073/pnas.84.21.7403. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Tárnoky A. L. Genetic and drug-induced variation in serum albumin. Adv Clin Chem. 1980;21:101–146. doi: 10.1016/s0065-2423(08)60087-6. [DOI] [PubMed] [Google Scholar]
  22. Weitkamp L. R., McDermid E. M., Neel J. V., Fine J. M., Petrini C., Bonazzi L., Ortali V., Porta F., Tanis R., Harris D. J. Additional data on the population distribution of human serum albumin genes; three new variants. Ann Hum Genet. 1973 Oct;37(2):219–226. doi: 10.1111/j.1469-1809.1973.tb01829.x. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES