Sequence of DNA flanking the exons of the HEXA gene, and identification of mutations in Tay-Sachs disease

The rapid identification of mutations causing Tay-Sachs disease requires the capacity to readily screen the regions of the HEXA gene most likely to be affected by mutation. We have sequenced the portions of the introns flanking each of the 14 HEXA exons in order to specify oligonucleotide primers fo...

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Published inAmerican journal of human genetics Vol. 49; no. 5; pp. 1041 - 1054
Main Authors TRIGGS-RAINE, B. L, AKERMAN, B. R, CLARKE, J. T. R, GRAVAL, R. A
Format Journal Article
LanguageEnglish
Published Chicago, IL University of Chicago Press 01.11.1991
Subjects
Alleles
Base Sequence
beta -N-acetylhexosaminidase
beta-N-Acetylhexosaminidases - genetics
Biological and medical sciences
Blotting, Southern
Cell Line
Cloning, Molecular
DNA
Exons
genes
Genetic Testing
Hexosaminidase A
Humans
Medical sciences
Metabolic diseases
Molecular Sequence Data
Mutation
Nucleic Acid Heteroduplexes
Polymerase Chain Reaction
Polymorphism, Genetic
Tay-Sachs Disease - genetics
Chromosomal aberration
Human
Chromosome insertion
Pathogenesis
Deletion
Abnormal chromosome
Metabolic diseases
Mutation
Tay Sachs disease
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Summary:The rapid identification of mutations causing Tay-Sachs disease requires the capacity to readily screen the regions of the HEXA gene most likely to be affected by mutation. We have sequenced the portions of the introns flanking each of the 14 HEXA exons in order to specify oligonucleotide primers for the PCR-dependent amplification of each exon and splice-junction sequence. The amplified products were analyzed, by electrophoresis in nondenaturing polyacrylamide gels, for the presence of either heteroduplexes, derived from the annealing of normal and mutant DNA strands, or single-strand conformational polymorphisms (SSCP), derived from the renaturation of single-stranded DNA. Five novel mutations from Tay-Sachs disease patients were detected: a 5-bp deletion of TCTCC in IVS-9; a 2-bp deletion of TG in exon 5; G78 to A, giving a stop codon in exon 1; G533 to T in exon 5, producing the third amino acid substitution detected at this site; and G to C at position 1 of IVS-2, expected to produce abnormal splicing. In addition, two mutations, (G1496 to A in exon 13 and a 4-bp insertion in exon 11) that have previously been reported were identified.
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ISSN:0002-9297
1537-6605