The c.1275A>G putative chronic pancreatitis-associated synonymous polymorphism in the glycoprotein 2 (GP2) gene decreases exon 9 inclusion

Molecular Genetics and Metabolism
Arnaud BoullingClaude Férec

Abstract

We have recently found that a common synonymous single nucleotide polymorphism (SNP), c.1275A>G, in exon 9 of the glycoprotein 2 (GP2) gene was significantly underrepresented in French idiopathic chronic pancreatitis patients 20years old or younger at disease onset than in the control population. To further investigate to this preliminary genetic finding, we characterized the functionality of c.1275A>G in the context of a minigene system. Bioinformatics analysis predicted that c.1275A>G could lead to disruption/generation of exonic splicing enhancer hexamers within exon 9 of the GP2 gene. Minigene analysis revealed that both the wild-type and mutant sequences expressed a full-length transcript and a short transcript lacking exon 9. Quantitation of the relative amount of the two transcripts indicated that the fraction of the full-length transcript derived from c.1275A>G is much lower than that derived from the wild-type (51.9% vs 77.4%). Extinction of two splicing factors (SF2/ASF and SC35) by RNA interference also affected c.1275A>G more seriously than the wild-type in terms of exon 9 skipping. Exon 9 skipping was presumed to cause a loss of GP2 function. This study represents the first detailed analysis of any variation in the...Continue Reading

References

Sep 3, 1998·The New England Journal of Medicine·N SharerJ Braganza
Sep 3, 1998·The New England Journal of Medicine·J A CohnP S Jowell
Jul 11, 2006·European Journal of Human Genetics : EJHG·Emmanuelle MassonClaude Férec
Oct 31, 2006·Nature Genetics·Cédric Le MaréchalClaude Férec
Dec 8, 2007·Clinical Gastroenterology and Hepatology : the Official Clinical Practice Journal of the American Gastroenterological Association·Emmanuelle MassonClaude Férec
Feb 28, 2008·Nature Reviews. Immunology·Donata Vercelli
May 8, 2008·Human Genetics·Emmanuelle MassonClaude Férec
Dec 9, 2008·The Biochemical Journal·Jennifer C Long, Javier F Caceres
May 21, 2009·Annual Review of Genomics and Human Genetics·Jian-Min Chen, Claude Férec
Mar 26, 2010·Pancreas·Emmanuelle MassonClaude Férec

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Citations

May 26, 2011·European Journal of Human Genetics : EJHG·Arnaud BoullingClaude Férec
Dec 18, 2014·World Journal of Gastroenterology : WJG·Sumit PaliwalGiriraj R Chandak
Dec 5, 2021·Genes and Environment : the Official Journal of the Japanese Environmental Mutagen Society·Yingsong LinShogo Kikuchi

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