ASSIGNMENT OF THE ALPHA-1-ANTITRYPSIN GENE AND A SEQUENCE-RELATED GENE TO HUMAN CHROMOSOME-14 BY MOLECULAR HYBRIDIZATION

  • 1 January 1983
    • journal article
    • research article
    • Vol. 35  (3) , 385-392
Abstract
.alpha.1-Antitrypsin is a major plasma protease inhibitor synthesized in the liver. Genetic deficiency of this protein predisposes the affected individuals to development of infantile liver cirrhosis or chronic obstructive pulmonary emphysema. The human chromosomal .alpha.1-antitrypsin gene was cloned and shown to contain 3 introns in the peptide-coding region. When the cloned .alpha.1-antitrypsin gene was used as a hybridization probe to analyze Eco RI-digested genomic DNA from different individuals, 2 distinct bands of 9.6 kilobases (kb) and 8.5 kb in length were observed in every case. Further analysis using only labeled intronic DNA as the hybridization probe has indicated that the authentic .alpha.1-antitrypsin gene resides within the 9.6-kb fragment. The 8.5-kb fragment must contain another gene that is closely related in sequence to the .alpha.1-antitrypsin gene. Using a series of human-Chinese hamster somatic cell hybrids containing unique combinations of human chromosomes, the .alpha.1-antitrypsin gene as well as the sequence-related gene were assigned to human chromosome 14 by Southern hybridization and synteny analysis.