Genetic diversity of the alpha-1-antitrypsin gene in Africans identified using a novel genotyping assay

Hum Mutat. 2003 Jul;22(1):59-66. doi: 10.1002/humu.10231.


The highly polymorphic human alpha-1-antitrypsin (AAT) gene, more recently named SERPINA1, codes for the most abundant circulating plasma serine protease inhibitor, protease inhibitor 1 (PI). Most studies determining AAT haplotype frequencies have been restricted first by the limited accuracy of the phenotypic method used and secondly by the analysis of predominantly Caucasian populations. Limited studies have been performed on African-based populations. Here a new comprehensive assay for genotyping the entire coding region, including splice junctions, of the AAT gene was designed. This assay, based on denaturing gradient gel electrophoresis (DGGE), allows for the complete analysis of a single individual in two lanes on a gel. Application of the assay resulted in the identification of nine known AAT variants as well as 13 novel sequence variants, five of which are single nucleotide polymorphisms (SNPs), occurring exclusively in the African-based populations. This is the first comprehensive analysis of the genetic diversity of the AAT gene in a cohort from sub-Saharan Africa.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Africa South of the Sahara
  • Amino Acid Substitution / genetics
  • Asians / genetics
  • Blacks / genetics
  • China / ethnology
  • DNA Mutational Analysis / methods
  • Electrophoresis, Polyacrylamide Gel / methods
  • Europe / ethnology
  • Gene Frequency / genetics
  • Genetic Variation*
  • Genetics, Population / methods*
  • Genotype
  • Humans
  • India / ethnology
  • Polymorphism, Single Nucleotide / genetics
  • RNA Splice Sites / genetics
  • Whites / genetics
  • alpha 1-Antitrypsin / genetics*
  • alpha 1-Antitrypsin Deficiency / genetics


  • RNA Splice Sites
  • alpha 1-Antitrypsin