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.
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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
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DOI: https://doi.org/10.1038/316079a0
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