Linked Life Data

11689490

Source:http://linkedlifedata.com/resource/pubmed/id/11689490

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
21
pubmed:dateCreated
2001-11-5
pubmed:databankReference
pubmed:abstractText
Spinocerebellar ataxia 2 (SCA2) is an autosomal dominant neurodegenerative disorder that results from the expansion of a cryptic CAG repeat within the exon 1 of the SCA2 gene. The CAG repeat in normal individuals varies in length from 14 to 31 repeats and is frequently interrupted by one or more CAA triplets, whereas the expanded alleles contain a pure uninterrupted stretch of 34 to 59 CAG repeats. We have previously reported the presence of a limited pool of 'ancestral' or 'at risk' haplotypes for the expanded SCA2 alleles in the Indian population. We now report the identification of two novel single nucleotide polymorphisms (SNPs) in exon 1 of the SCA2 gene and their characterization in 215 normal and 64 expanded chromosomes. The two biallelic SNPs distinguished two haplotypes, GT and CC, each of which formed a predominant haplotype associated with normal and expanded SCA2 alleles. All the expanded alleles segregated with CC haplotype, which otherwise was associated with only 29.3% of the normal chromosomes. CAA interspersion analysis revealed that majority of the normal alleles with CC haplotype were either pure or lacked the most proximal 5' CAA interruption. The repeat length variation at SCA2 locus also appeared to be polar with changes occurring mostly at the 5' end of the repeat. Our results demonstrate that CAA interruptions play an important role in conferring stability to SCA2 repeat and their absence predisposes alleles towards instability and pathological expansion. Our study also provides new haplotypes associated with SCA2 that should prove useful in further understanding the mutational history and mechanism of repeat instability at the SCA2 locus.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0964-6906
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
10
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2437-46
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:11689490-Alleles, pubmed-meshheading:11689490-Animals, pubmed-meshheading:11689490-Cercopithecidae, pubmed-meshheading:11689490-DNA, pubmed-meshheading:11689490-DNA Mutational Analysis, pubmed-meshheading:11689490-Evolution, Molecular, pubmed-meshheading:11689490-Female, pubmed-meshheading:11689490-Genetic Variation, pubmed-meshheading:11689490-Gorilla gorilla, pubmed-meshheading:11689490-Haplotypes, pubmed-meshheading:11689490-Humans, pubmed-meshheading:11689490-Macaca mulatta, pubmed-meshheading:11689490-Macaca radiata, pubmed-meshheading:11689490-Male, pubmed-meshheading:11689490-Microsatellite Repeats, pubmed-meshheading:11689490-Molecular Sequence Data, pubmed-meshheading:11689490-Nerve Tissue Proteins, pubmed-meshheading:11689490-Pan troglodytes, pubmed-meshheading:11689490-Papio, pubmed-meshheading:11689490-Point Mutation, pubmed-meshheading:11689490-Polymorphism, Single Nucleotide, pubmed-meshheading:11689490-Proteins, pubmed-meshheading:11689490-Spinocerebellar Degenerations, pubmed-meshheading:11689490-Trinucleotide Repeat Expansion, pubmed-meshheading:11689490-Trinucleotide Repeats
pubmed:year
2001
pubmed:articleTitle
CAG repeat instability at SCA2 locus: anchoring CAA interruptions and linked single nucleotide polymorphisms.
pubmed:affiliation
Functional Genomics Unit, Centre for Biochemical Technology (CSIR), Mall Road, Delhi, India.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't