Argininosuccinic Aciduria: Assignment of the Argininosuccinate Lyase Gene to the pter→ q22 Region of Human Chromosome 7 by Bioautography

• Published in: Proceedings of the National Academy of Sciences - PNAS 1978-12, Vol.75 (12), p.6159-6162
• Main Authors: Naylor, S. L., Klebe, R. J., Shows, T. B.
• Format: Article
• Language: English
• Subjects: Amino Acid Metabolism, Inborn Errors - genetics; Arginine - analogs & derivatives; Argininosuccinate Lyase - analysis; Argininosuccinate Lyase - genetics; Argininosuccinic Acid - urine; Argininosuccinic Aciduria; Chromosome Mapping; Chromosomes; Chromosomes, Human, 6-12 and X; Electrophoresis - methods; Enzymes; Genes; Human chromosomes; Human genetics; Humans; Hybrid Cells; Hybridity; Lyases - genetics; Medical genetics; Segregation; Somatic cells
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.75.12.6159

Argininosuccinic aciduria, an autosomal recessive disorder of the urea cycle in humans, is associated with a deficiency of argininosuccinate lyase (ASL; L-argininosuccinate arginine-lyase, EC 4.3.2.1). ASL activity was visualized on gels after electrophoresis by a new method, termed bioautography. Bioautography involves the use of mutant bacteria to visualize the location of mammalian enzymes after zone electrophoresis. By this technique, human ASL migrated to a position different from mouse ASL, while a survey of mouse strains, tissues, and tissue culture cell extracts demonstrated the same electrophoretic form and no genetic variants of mouse ASL. Identifying human ASL by bioautography in human-mouse somatic cell hybrids has made it possible to regionally locate the ASL gene on human chromosome 7. The human ASL phenotype segregated concordantly with the human enzyme β -glucuronidase (GUS; β -D-glucuronide glucuronosohydrolase, EC 3.2.1.31) in cell hybrids, but showed discordant segregation with 32 other enzyme markers representing 23 linkage groups. The gene for GUS has been assigned to chromosome 7 in humans, and cosegregation (synteny) of ASL and GUS demonstrates the assignment of ASL to chromosome 7. Regional location of ASL and GUS to the pter→ q22 region of chromosome 7 was achieved in hybrids segregating a 7/9 translocation.