Abstract
The α1-protease inhibitor, or α-antitrypsin (AAT), a major plasma inhibitor of leukocyte elastase and bacterial proteases, is encoded at the PI locus on chromosome 14 (14q24.3–q32.1)1. A deficiency of AAT in individuals homozygous for the PI Z allele occurs in about 1 in 2,000–8,000 Caucasians2 and is associated with an increased risk of early adult onset emphysema3 and liver disease in childhood4. We have now used DNA polymorphisms associated with the AAT gene to investigate the origin of the PI Z allele. Using two genomic probes5 extending into the 5′ and 3′ flanking regions, respectively, we have identified eight polymorphic restriction sites. Extensive linkage disequilibrium occurs throughout the probed region with the PI Z allele, but not with normal PI M alleles. The Z allele occurs mainly with one haplotype, indicating a single, relatively recent, origin in Caucasians.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 51 print issues and online access
$199.00 per year
only $3.90 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Cox, D. W., Markovic, V. D. & Teshima, I. E. Nature 297, 428–430 (1982).
Fagerhol, M. K. & Cox, D. W. Adv. hum. Genet. 11, 1–62 (1981).
Laurell, C.-B. & Eriksson, S., J. clin. Lab. Invest. 15, 132–140 (1963).
Sharp, H. L., Bridges, R. A., Krivit, W. & Frier, E. F. J Lab. clin. Med. 73, 934–939 (1969).
Leicht, M. et al. Nature 297, 655–659 (1982).
Cox, D. W. Am. J. hum. Genet. 33, 354–365 (1981).
Kidd, V. J., Wallace, R. B., Itakura, K. & Woo, S. L. C. Nature 304, 230–234 (1983).
Long, G. L., Chandra, T., Kurachi, K., Woo, S. L. C. & Davie, E. W. Biochemistry 23, 4828–4837 (1984).
Fisher, R. A. in Statistical Methods for Research Workers, 78–97 (Oliver and Boyd, Edinburgh, (1944).
Jeppson, J.-O. FEBS Lett. 65, 195–197 (1976).
Yoshida, L., Lieberman, J., Gaidulis, L. & Ewing, C. Proc. natn. Acad. Sci. U.S.A. 73, 1324–1328 (1976).
Kan, Y. W. & Dozy, A. M. Lancet ii, 910–911 (1978).
Pagnier, J. et al. Proc. natn. Acad. Sci. U.S.A. 81, 1771–1773 (1984).
Orkin, S. H. et al. Nature 296, 627–631 (1982).
Kurnit, D. M. Lancet i, 104 (1979).
Antonarakis, S. E., Boehm, C. D., Giardina, P. J. V. & Kazazian, H. H., Proc. natn. Acad. Sci. U.S.A. 79, 137–141 (1982).
Bech-Hansen, N. T., Linsley, P. S. & Cox, D. W. Proc. natn. Acad. Sci. U.S.A. 80, 6952–6956 (1983).
Fagerhol, M. K. in Proc. IVth int. Congr. hum. Genet., Paris (eds de Grouchy, J., Ebling, F. J. G. & Henderson, I. W.) 277–285 (Excerpta Medica, Amsterdam, 1971).
Kueppers, F. . in Pulmonary Emphysema and Proteolysis (ed. Mittman, C.) 133–137 (Academic, New York, 1972).
Cox, D. W. & Mansfield, T. Lancet i, 230 (1985).
Botstein, D., White, R.L., Skolnick, M. & Davis, R. W. Am. J. hum. Genet. 32,314–331 (1980).
Cox, D. W. & Huber, O. Clin. Genet. 17, 153–160 (1980).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Cox, D., Woo, S. & Mansfield, T. DNA restriction fragments associated with α1-antitrypsin indicate a single origin for deficiency allele PI Z. Nature 316, 79–81 (1985). https://doi.org/10.1038/316079a0
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/316079a0
This article is cited by
-
The prevalence of alpha-1 antitrypsin deficiency in Ireland
Respiratory Research (2011)
-
Polymorphisms in the HPC/ELAC-2 and alpha 1-antitrypsin genes that correlate with human diseases in a North Indian population
Molecular Biology Reports (2011)
-
Molecular linkage of the human αl-antitrypsin and corticosteroid-binding globulin genes on Chromosome 14q32.1
Mammalian Genome (1997)
-
Highly variable clinical course in severeα 1-antitrypsin deficiency — Use of polymerase chain reaction for the detection of rare deficiency alleles
Klinische Wochenschrift (1990)
Comments
By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.