A synonymous SNP of the corneodesmosin gene leads to increased mRNA stability and demonstrates association with psoriasis across diverse ethnic groups

Human Molecular Genetics
Francesca CaponRichard Trembath

Abstract

Psoriasis is a chronic skin disorder with multifactorial aetiology. Genome-wide scans have provided unambiguous evidence for a major disease susceptibility locus on chromosome 6p21 (PSORS1). A minimal PSORS1 interval has been defined which encompasses three genes (HLA-C, HCR and CDSN) carrying psoriasis-associated SNPs. On the basis of this genetic evidence, we have undertaken an assessment of CDSN allele functional impact. A comparison of CDSN intragenic haplotypes showed that SNPs exclusive to disease-associated chromosomes are located in regions implicated in the stabilization of RNA transcripts. As CDSN is over-expressed in psoriatic lesions, we hypothesised that disease-associated intragenic SNPs may alter the rate of its mRNA decay. Here, we demonstrate that mRNAs transcribed from a CDSN risk haplotype present a 2-fold increase in stability, compared with those transcribed from a neutral haplotype (t-test P=0.004). Site-directed mutagenesis revealed that a single synonymous SNP (CDSN*971T) accounts for the observed increase in RNA stability. CDSN*971T maps to a RNA stability motif and UV cross-linking analysis demonstrated that the SNP affects the transcript affinity for a 39 kDa RNA binding protein. Association analyses ...Continue Reading

References

Mar 1, 1988·The Journal of Cell Biology·P BoukampN E Fusenig
May 20, 1998·European Journal of Cell Biology·D BreitkreutzN E Fusenig
Feb 17, 1999·The Journal of Dermatology·J N Barker
May 20, 1999·Lancet·M H AllenJ N Barker
Sep 1, 1999·The Journal of Investigative Dermatology·N BalendranR C Trembath
Oct 3, 1999·The Journal of Investigative Dermatology·E MallonC B Bunker
May 10, 2000·American Journal of Human Genetics·R P NairJ T Elder
Nov 9, 2000·The Journal of Investigative Dermatology·S GonzalezC López-Larrea
Jul 17, 2001·Laboratory Investigation; a Journal of Technical Methods and Pathology·M AllenJ Barker
Dec 12, 2001·The Journal of Biological Chemistry·Nathalie JoncaGuy Serre
Feb 8, 2002·American Journal of Human Genetics·Rosa Di PaolaVincenzo Trischitta
Mar 5, 2002·Human Molecular Genetics·Kati AsumalahtiUNKNOWN Psoriasis Consortium
May 2, 2002·The Journal of Investigative Dermatology·Francesca CaponRichard Trembath
Jul 10, 2003·American Journal of Human Genetics·UNKNOWN International Psoriasis Genetics Consortium
Mar 5, 2004·Human Molecular Genetics·Anne M Bowcock, William O C M Cookson

❮ Previous
Next ❯

Citations

Feb 21, 2009·Breast Cancer Research and Treatment·Rongxi YangBarbara Burwinkel
Mar 26, 2010·Molecular Biology Reports·Yanxin LiuGenlin Wang
Jun 19, 2013·Immunology Letters·Hongjun SunXiaotian Chang
Apr 26, 2008·Proceedings of the National Academy of Sciences of the United States of America·Mitsuru MatsumotoDavid D Chaplin
May 23, 2012·Bioinformatics·Mingxiang TengYunlong Liu
Oct 5, 2012·Genome Biology and Evolution·Yang DingJoshua B Plotkin
Jan 8, 2009·Molecular Human Reproduction·E FitzpatrickE K Moses
May 10, 2006·Nucleic Acids Research·Svetlana A ShabalinaNikolay A Spiridonov
Sep 24, 2009·Nucleic Acids Research·Hamed Shateri NajafabadiReza Salavati
Dec 4, 2008·European Journal of Neurology : the Official Journal of the European Federation of Neurological Societies·Y-J LiouI-C Lai
May 31, 2012·Genome Génome / Conseil National De Recherches Canada·Jiajie SunHong Chen
Aug 30, 2005·Annual Review of Genomics and Human Genetics·Anne M Bowcock
May 5, 2011·Journal of Biomedicine & Biotechnology·Isabelle Benz-de BretagneChantal Le Guellec
Nov 6, 2009·BMC Medical Genetics·Marilene PavanJosé Xavier-Neto
Jul 21, 2007·BMC Medical Genetics·Richard G Del MastroRandall D Little
Dec 16, 2010·European Journal of Medical Research·U H FreyN H Brockmeyer
Dec 31, 2009·PLoS Genetics·Marina SirotaAtul J Butte
Sep 20, 2007·PloS One·Fabienne LesueurJudith Fischer
Feb 27, 2010·PloS One·Arne B GjuvslandStig W Omholt
Apr 21, 2009·Pharmacogenomics·Grace S Y PangCaroline G L Lee
Jan 15, 2014·Theoretical Biology & Medical Modelling·Mohammad-Hadi Foroughmand-AraabiMehdi Sadeghi

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.