We found a germline SNP in a pseudogene associated with several cancers. Why? Could the pseudogene be transcribed into noncoding RNA (ncRNA) and affect transcription of other genes?
Could it be associated by linkage disequilibrium to a nearby causal gene?
Hi Sergio,
Thanks so much for your comment. I'm not a big believer in LD for polygenic diseases (this one was a solid cancer). We have data for the ecNOS promoter about two SNPs 17 bp's apart (SNPs at -789 and -772). One SNP is tightly associated w/ NIDDM (p
I am really not an expert in pseudogenes, but I have read that some of them are transcribed and act as siRNA.
http://nar.oxfordjournals.org/content/early/2013/02/01/nar.gkt047
maybe because the SNP is in a trans regulatory region for another gene? maybe look for regulatory elements in the sequence nearby with any software like TFsearch will yield something. good luck!
As RNA Biologist, I would suggest that your SNP might be disturbing the function of some non-coding RNAs, either small, e.g. miRNA, siRNA, or long, e.g. lincRNAs or macro-ncRNAs. Advanced RNA-seq analysis of the locus should reveal if any ncRNAs are being transcribed there. For TF binging site you can look up available ChIP experiments. Finally, SNP may affect dynamics of the chromosome. Then, 3C experiments should be conducted.
This is my list of suggestions.
you could check by online tools,blast,secondary structure etc to see whether there is a conserved region or even pre-miRNA structure there surrounding that SNP.If the pseudogene is transcribed to a non-coding RNA u might be able to detect if lucky the expression of that specific region by RNA extraction and RT.
Pseudogenes can also be sinks for miRNAs. A SNP could change the miRNA recognition site, so that more miRNA might bind to the related (expressed) gene than would if the SNP were not present in the pseudogene. Have you checked to see whether the expression level of the related gene has changed?
Hi David, I attach you an article that deals with pseudogene in shrimps. Maybe from the discussion of the paper you can get out some conclusions that may give you a tip. We were recently faced with pseudogenes' problems in a marine invertebrate and I found an article, for me quite complicated to understand completely, but that may give you some hinds .
Thank you very much for all your answers. They're extremely helpful!
Here's the reference I should have supplied before: https://www.researchgate.net/publication/44799233_A_coding-independent_function_of_gene_and_pseudogene_mRNAs_regulates_tumour_biology?ev=srch_pub . It was also cited by https://www.researchgate.net/publication/235441738_pseudoMap_an_innovative_and_comprehensive_resource_for_identification_of_siRNA-mediated_mechanisms_in_human_transcribed_pseudogenes?ev=pub_cit_inc .
Article Poliseno L, Salmena L, Zhang J, Carver B, Haveman WJ, Pandol...
Article pseudoMap: An innovative and comprehensive resource for iden...
Hi David, is it possible that the link of the pseudogene with the disease is rather that the pseudogene might surpress the expression of the cancer? Here is an article that give you some ideas.
Transcribed pseudogene ψPPM1K generates endogenous siRNA to suppress oncogenic cell growth in hepatocellular carcinoma
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3616710/
I wonder if a population of an invasive species can suddenly "produce" many pseudogenes to surpress lethal genomic genes....
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