Canavan Disease: Genomic Organization and Localization of Human ASPA to 17p13-ter and Conservation of the ASPA Gene during Evolution

Rajinder Kaul, K. Balamurugan, Guang P. Gao, Reuben Matalon

Research output: Contribution to journalArticle

52 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)364-370
Number of pages7
JournalGenomics
Volume21
Issue number2
DOIs
StatePublished - May 15 1994
Externally publishedYes

Fingerprint

Canavan Disease
Exons
Genes
Introns
Hybrid Cells
Species Specificity
Chromosomes, Human, Pair 17
Initiator Codon
aspartoacylase
DNA
Consensus Sequence
Human Chromosomes
Missense Mutation
Southern Blotting
Fluorescence In Situ Hybridization
Haplorhini
Chickens
Yeasts
Genome
Dogs

ASJC Scopus subject areas

  • Genetics

Cite this

Canavan Disease : Genomic Organization and Localization of Human ASPA to 17p13-ter and Conservation of the ASPA Gene during Evolution. / Kaul, Rajinder; Balamurugan, K.; Gao, Guang P.; Matalon, Reuben.

In: Genomics, Vol. 21, No. 2, 15.05.1994, p. 364-370.

Research output: Contribution to journalArticle

@article{63b9513a5c2b4df8862b8d43e5d1e7f9,
title = "Canavan Disease: Genomic Organization and Localization of Human ASPA to 17p13-ter and Conservation of the ASPA Gene during Evolution",
abstract = "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.",
author = "Rajinder Kaul and K. Balamurugan and Gao, {Guang P.} and Reuben Matalon",
year = "1994",
month = "5",
day = "15",
doi = "10.1006/geno.1994.1278",
language = "English (US)",
volume = "21",
pages = "364--370",
journal = "Genomics",
issn = "0888-7543",
publisher = "Academic Press Inc.",
number = "2",

}

TY - JOUR

T1 - Canavan Disease

T2 - Genomic Organization and Localization of Human ASPA to 17p13-ter and Conservation of the ASPA Gene during Evolution

AU - Kaul, Rajinder

AU - Balamurugan, K.

AU - Gao, Guang P.

AU - Matalon, Reuben

PY - 1994/5/15

Y1 - 1994/5/15

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=0028178607&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0028178607&partnerID=8YFLogxK

U2 - 10.1006/geno.1994.1278

DO - 10.1006/geno.1994.1278

M3 - Article

C2 - 8088831

AN - SCOPUS:0028178607

VL - 21

SP - 364

EP - 370

JO - Genomics

JF - Genomics

SN - 0888-7543

IS - 2

ER -