A Restriction Fragment Length Polymorphism Results in a Nonconservative Amino Acid Substitution Encoded within the First Exon of the Human Lysyl Oxidase Gene

• Published in: Genomics (San Diego, Calif.) Vol. 16; no. 2; pp. 401 - 406
• Main Authors: Csiszar, Katalin, Mariani, Thomas J., Gosin, Jeffrey S., Deak, Susan B., Boyd, Charles D.
• Format: Journal Article
• Language: English
• Published: San Diego, CA Elsevier Inc 01.05.1993; Elsevier
• Subjects: Alleles; Amino Acid Sequence; Base Sequence; Biological and medical sciences; Classical genetics, quantitative genetics, hybrids; Consensus Sequence; DNA - genetics; DNA, Recombinant - genetics; Exons; Fundamental and applied biological sciences. Psychology; Genetics of eukaryotes. Biological and molecular evolution; Human; Humans; Lymphocytes; Molecular Sequence Data; Polymorphism, Restriction Fragment Length; Protein-Lysine 6-Oxidase - genetics; Human; Exon; Restriction fragment length polymorphism; Gene frequency; Gene; Nucleotide sequence; Enzyme; Protein-lysine 6-oxidase; Chromosome DNA; Nucleotide transition
• ISSN: 0888-7543; 1089-8646
• DOI: 10.1006/geno.1993.1203

A cDNA covering most of the coding sequence for human lysyl oxidase was used to screen, by Southern blot analysis, genomic DNA from circulating lymphocytes obtained from unrelated, apparently normal individuals. A heritable restriction fragment length polymorphism (RFLP) within a PstI restriction site was detected in 36% of individuals screened (a total of 72 chromosomes were analyzed). The major allele was represented as a 1.7-kb PstI restriction fragment. The minor allele was detected as 1.4 and 0.3kb restriction fragments. Lambda phage-DNA recombinants were isolated from a human lung fibroblast genomic DNA library using the human lysyl oxidase cDNA clone. DNA sequence analysis of several selected phage recombinants revealed that 83% of the coding sequence of lysyl oxidase was localized in four separate exons. Analysis of the coding sequence within exon 1, the most 5′ exon within the lysyl oxidase gene, revealed that the PstI RFLP was due to a G → A transition resulting in a nonconservative arginine to glutamine substitution proximal to a propeptide cleavage domain encoded by exon 1 of the lysyl oxidase gene.