Source:http://linkedlifedata.com/resource/pubmed/id/20650818
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
5
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| pubmed:dateCreated |
2010-7-23
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| pubmed:abstractText |
The +1169A allele of the A/T single nucleotide polymorphism (SNP; rs2665802), located within intron 4 of the human growth hormone 1 ( GH1 ) gene, has been associated with reduced levels of circulating GH and insulin-like growth factor 1, a reduced risk of colorectal cancer and a predisposition to osteoporosis. Whether this intronic SNP is itself the functional polymorphism responsible for exerting a direct effect on GH1 gene expression, however, or whether it is instead in linkage disequilibrium with the functional SNP, has been an open question. The evolutionary conservation of the +1169T allele (and the surrounding intronic sequence) in the bovine genome, as well as in primate genomes, is, however, suggestive of its functionality. Although a potential alternative splice site spans the location of the +1169 SNP, polymerase chain reaction-based assays failed to yield any evidence for alternative splicing associated with either allele. To determine whether the +1169 SNP, in different allelic combinations with SNPs at -278 (G/T), -57 (T/G) and +2103 (C/T), exerts a direct effect on gene expression and/or GH secretion, we performed a series of transfections of various GH1 haplotype-expressing constructs into rat GC (somatotroph) cells. The results obtained provided evidence to support the contention that the +1169A allele contributes directly to the observed reduction in both GH1 gene expression and GH secretion. Part of the apparent influence of the +1169A-bearing allele on GH1 gene expression and GH secretion may still, however, be attributable to alleles of additional SNPs in cis to +1169A and located within either the promoter or the 3'-flanking region.
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| pubmed:commentsCorrections | |
| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical | |
| pubmed:status |
MEDLINE
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| pubmed:month |
Jun
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| pubmed:issn |
1479-7364
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| pubmed:author | |
| pubmed:issnType |
Electronic
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| pubmed:volume |
4
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
289-301
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| pubmed:meshHeading |
pubmed-meshheading:20650818-3' Flanking Region,
pubmed-meshheading:20650818-Alleles,
pubmed-meshheading:20650818-Alternative Splicing,
pubmed-meshheading:20650818-Animals,
pubmed-meshheading:20650818-Base Sequence,
pubmed-meshheading:20650818-Cell Line,
pubmed-meshheading:20650818-Conserved Sequence,
pubmed-meshheading:20650818-European Continental Ancestry Group,
pubmed-meshheading:20650818-Evolution, Molecular,
pubmed-meshheading:20650818-Gene Expression Regulation,
pubmed-meshheading:20650818-Haplotypes,
pubmed-meshheading:20650818-Human Growth Hormone,
pubmed-meshheading:20650818-Humans,
pubmed-meshheading:20650818-Introns,
pubmed-meshheading:20650818-Linkage Disequilibrium,
pubmed-meshheading:20650818-Molecular Sequence Data,
pubmed-meshheading:20650818-Polymorphism, Single Nucleotide,
pubmed-meshheading:20650818-Promoter Regions, Genetic,
pubmed-meshheading:20650818-RNA Splice Sites,
pubmed-meshheading:20650818-Rats,
pubmed-meshheading:20650818-Sequence Homology, Nucleic Acid,
pubmed-meshheading:20650818-Somatotrophs
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| pubmed:year |
2010
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| pubmed:articleTitle |
Characterisation of a functional intronic polymorphism in the human growth hormone (GH1) gene.
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| pubmed:affiliation |
Institute of Medical Genetics, Cardiff University, Heath Park, UK. millar@cardiff.ac.uk
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| pubmed:publicationType |
Journal Article
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