Canavan disease: Genomic organization and localization of human ASPA to 17p13-ter and conservation of the ASPA gene during evolution

Journal Article · Sun May 15 00:00:00 EDT 1994 · Genomics; (United States)

DOI:https://doi.org/10.1006/geno.1994.1278· OSTI ID:6949867

Kaul, R; Balamurugan, K; Gao, G P; Matalon, R ^[1]

---

1. Research Institute, Miami, FL (United States)

Canavan disease, or spongy degeneration of the brain, is a severe leukodystrophy caused by the deficiency of aspartoacylase (ASPA). Recently, a missense mutation was identified in human ASPA coding sequence from patients with Canavan disease. The human ASPA gene has been cloned and found to span 29 kb of the genome. Human aspartoacylase is coded by six exons intervened by five introns. The exons vary from 94 (exon III) to 514 (exon VI) bases. The exon/intron splice junction sites follow the gt/ag consensus sequence rule. Southern blot analysis of genomic DNA from human/mouse somatic cell hybrid cell lines localized ASPA to human chromosome 17. The human ASPA locus was further mapped in the 17p13-ter region by fluorescence in situ hybridization. The bovine aspa gene has also been cloned, and its exon/intron organization is identical to that of the human gene. The 500-base sequence upstream of the initiator ATG codon in the human gene and that in the bovine gene are 77% identical. Human ASPA coding sequences cross-hybridize with genomic DNA from yeast, chicken, rabbit, cow, dog, mouse, rat, and monkey. The specificity of cross-species hybridization of coding sequences suggests that aspartoacylase has been conserved during evolution. It should now be possible to identify mutations in the noncoding genomic sequences that lead to Canavan disease and to study the regulation of ASPA. 45 refs., 4 figs., 1 tab.

• OSTI ID: 6949867
• Journal Information: Genomics; (United States), Vol. 21:2; ISSN 0888-7543
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
BRAIN
HEREDITARY DISEASES
CYCLASES
GENES
HUMAN CHROMOSOME 17
GENETIC MAPPING
DNA SEQUENCING
DNA-CLONING
GENE MUTATIONS
BODY
CENTRAL NERVOUS SYSTEM
CHROMOSOMES
CLONING
DISEASES
DNA HYBRIDIZATION
ENZYMES
HUMAN CHROMOSOMES
HYBRIDIZATION
LYASES
MAPPING
MUTATIONS
NERVOUS SYSTEM
ORGANIC COMPOUNDS
ORGANS
PROTEINS
STRUCTURAL CHEMICAL ANALYSIS
550400* - Genetics