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

Genomics. 1994 May 15;21(2):364-70. doi: 10.1006/geno.1994.1278.


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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amidohydrolases / genetics*
  • Animals
  • Base Sequence
  • Biological Evolution*
  • Blotting, Southern
  • Canavan Disease / enzymology
  • Canavan Disease / genetics*
  • Cattle
  • Chickens
  • Chromosome Mapping
  • Chromosomes, Human, Pair 17*
  • Codon / genetics
  • Conserved Sequence
  • Dogs
  • Exons
  • Gene Expression Regulation, Enzymologic
  • Haplorhini
  • Humans
  • Hybrid Cells
  • In Situ Hybridization, Fluorescence
  • Introns
  • Mice
  • Molecular Sequence Data
  • RNA Splicing
  • Rabbits
  • Rats
  • Restriction Mapping
  • Saccharomyces cerevisiae / genetics
  • Sequence Homology, Nucleic Acid


  • Codon
  • Amidohydrolases
  • aspartoacylase

Associated data

  • GENBANK/S74726
  • GENBANK/S74727