3-Hydroxy-3-methylglutaryl CoA lyase (HL): Mouse and human HL gene (HMGCL) cloning and detection of large gene deletions in two unrelated HL-deficient patients
Abstract
3-hydroxy-3-methylglutaryl CoA lyase (HL, EC 4.1.3.4) catalyzes the cleavage of 3-hydroxy-3-methylglutaryl CoA to acetoacetic acid and acetyl CoA, the final reaction of both ketogenesis and leucine catabolism. Autosomal-recessive HL deficiency in humans results in episodes of hypoketotic hypoglycemia and coma. Using a mouse HL cDNA as a probe, we isolated a clone containing the full-length mouse HL gene that spans about 15 kb of mouse chromosome 4 and contains nine exons. The promoter region of the mouse HL gene contains elements characteristic of a housekeeping gene: a CpG island containing multiple Sp1 binding sites surrounds exon 1, and neither a TATA nor a CAAT box are present. We identified multiple transcription start sites in the mouse HL gene, 35 to 9 bases upstream of the translation start codon. We also isolated two human HL genomic clones that include HL exons 2 to 9 within 18 kb. The mouse and human HL genes (HGMW-approved symbol HMGCL) are highly homologous, with identical locations of intron-exon junctions. By genomic Southern blot analysis and exonic PCR, was found 2 of 33 HL-deficient probands to be homozygous for large deletions in the HL gene. 26 refs., 4 figs., 2 tabs.
- Authors:
-
- Hopital Sainte-Justine, Quebec (Canada); and others
- Publication Date:
- OSTI Identifier:
- 465929
- Resource Type:
- Journal Article
- Journal Name:
- Genomics
- Additional Journal Information:
- Journal Volume: 33; Journal Issue: 1; Other Information: PBD: 1 Apr 1996
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 55 BIOLOGY AND MEDICINE, BASIC STUDIES; GENE MUTATIONS; DETECTION; PATIENTS; HEREDITARY DISEASES; METABOLIC DISEASES; LYASES; DNA-CLONING; GENETIC MAPPING; STRUCTURE-ACTIVITY RELATIONSHIPS; TRANSCRIPTION; DNA SEQUENCING; LEUCINE; CATABOLISM; CHROMOSOMES; RECESSIVE MUTATIONS; AMINO ACIDS; POLYMERASE CHAIN REACTION; MICE; DNA HYBRIDIZATION; KETONES
Citation Formats
Wang, S P, Robert, M F, and Mitchell, G A. 3-Hydroxy-3-methylglutaryl CoA lyase (HL): Mouse and human HL gene (HMGCL) cloning and detection of large gene deletions in two unrelated HL-deficient patients. United States: N. p., 1996.
Web. doi:10.1006/geno.1996.0164.
Wang, S P, Robert, M F, & Mitchell, G A. 3-Hydroxy-3-methylglutaryl CoA lyase (HL): Mouse and human HL gene (HMGCL) cloning and detection of large gene deletions in two unrelated HL-deficient patients. United States. https://doi.org/10.1006/geno.1996.0164
Wang, S P, Robert, M F, and Mitchell, G A. 1996.
"3-Hydroxy-3-methylglutaryl CoA lyase (HL): Mouse and human HL gene (HMGCL) cloning and detection of large gene deletions in two unrelated HL-deficient patients". United States. https://doi.org/10.1006/geno.1996.0164.
@article{osti_465929,
title = {3-Hydroxy-3-methylglutaryl CoA lyase (HL): Mouse and human HL gene (HMGCL) cloning and detection of large gene deletions in two unrelated HL-deficient patients},
author = {Wang, S P and Robert, M F and Mitchell, G A},
abstractNote = {3-hydroxy-3-methylglutaryl CoA lyase (HL, EC 4.1.3.4) catalyzes the cleavage of 3-hydroxy-3-methylglutaryl CoA to acetoacetic acid and acetyl CoA, the final reaction of both ketogenesis and leucine catabolism. Autosomal-recessive HL deficiency in humans results in episodes of hypoketotic hypoglycemia and coma. Using a mouse HL cDNA as a probe, we isolated a clone containing the full-length mouse HL gene that spans about 15 kb of mouse chromosome 4 and contains nine exons. The promoter region of the mouse HL gene contains elements characteristic of a housekeeping gene: a CpG island containing multiple Sp1 binding sites surrounds exon 1, and neither a TATA nor a CAAT box are present. We identified multiple transcription start sites in the mouse HL gene, 35 to 9 bases upstream of the translation start codon. We also isolated two human HL genomic clones that include HL exons 2 to 9 within 18 kb. The mouse and human HL genes (HGMW-approved symbol HMGCL) are highly homologous, with identical locations of intron-exon junctions. By genomic Southern blot analysis and exonic PCR, was found 2 of 33 HL-deficient probands to be homozygous for large deletions in the HL gene. 26 refs., 4 figs., 2 tabs.},
doi = {10.1006/geno.1996.0164},
url = {https://www.osti.gov/biblio/465929},
journal = {Genomics},
number = 1,
volume = 33,
place = {United States},
year = {Mon Apr 01 00:00:00 EST 1996},
month = {Mon Apr 01 00:00:00 EST 1996}
}