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
- Hopital Sainte-Justine, Quebec (Canada); and others
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.
- OSTI ID:
- 465929
- Journal Information:
- Genomics, Vol. 33, Issue 1; Other Information: PBD: 1 Apr 1996
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
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