Question: Synonymous Snps Not So Synonymous At All
7
gravatar for Stephan
8.2 years ago by
Stephan150
europe
Stephan150 wrote:

I've heard that even novel human synonymous snps could even be important because of the way the codons are read and/or instability of rna folding. because of the nucleotide change some codons would be more difficult to translate.

Is there someone experienced with these kind of snps?

Are there any prediction tools available?

prediction snp • 3.6k views
ADD COMMENTlink modified 4.1 years ago by Biostar ♦♦ 20 • written 8.2 years ago by Stephan150
21
gravatar for Larry_Parnell
8.2 years ago by
Larry_Parnell16k
Boston, MA USA
Larry_Parnell16k wrote:

Here are some articles on this topic:

Bratati Kahali, Surajit Basak, Tapash Chandra Ghosh. Reinvestigating the codon and amino acid usage of S. cerevisiae genome: A new insight from protein secondary structure analysis. Biochemical and Biophysical Research Communications 354 (2007) 693–699

Chava Kimchi-Sarfaty, Jung Mi Oh, In-Wha Kim, Zuben E. Sauna, Anna Maria Calcagno, Suresh V. Ambudkar, Michael M. Gottesman. A “Silent” Polymorphism in the MDR1 Gene Changes Substrate Specificity. Science 315:525-8.

A. G. Nackley, S. A. Shabalina, I. E. Tchivileva, K. Satterfield, O. Korchynskyi, S. S. Makarov, W. Maixner, L. Diatchenko. Human Catechol-O-Methyltransferase Haplotypes Modulate Protein Expression by Altering mRNA Secondary Structure. Science 314:1930-3.

Danxin Wang and Wolfgang Sadée. Searching for Polymorphisms That Affect Gene Expression and mRNA Processing: Example ABCB1 (MDR1). The AAPS Journal 2006; 8 (3) E515-E520.

I use the human codon frequency table at KEGG to ascertain allele-specific differences in codons of synonymous SNPs. The above papers then give some idea of effect size of the alleles.

Edit 1 Feb 2011: adding a new paper that has just come to my attention as this seems very neat. The synonymous SNP alters binding of a microRNA such that the protective allele is downregulated by the microRNA and the risk allele does not support binding of that microRNA. See details in this paper by Brest, Hofman, et al. on MIRN196, IRGM expression and Crohn's disease.

Edit 14 Dec 2011: There is a very nice news feature at Nature Medicine on this topic, written by Alla Katsnelson. The theme is "synonymous DNA changes can trigger disease in a number of ways."

ADD COMMENTlink modified 7.4 years ago • written 8.2 years ago by Larry_Parnell16k
1

I don't have an example off hand but synonymous snps can also affect the target sequences of intron splicing machinery and hence cause aberrant splicing. That might well be mentioned in the paper by Danxin Wang above as that mentions mRNA processing but I thought i'd mention it as another example just in case

ADD REPLYlink written 8.2 years ago by Mutated_Dater290

Larry, thanks a lot for the articles.

ADD REPLYlink written 8.2 years ago by Khader Shameer18k

thank you for the articles

ADD REPLYlink written 8.2 years ago by Stephan150

Indeed. There are exonic splice enhancers and intronic splice enhancers, either of which can be disrupted by a polymorphism like a SNP. Obviously, it is the ESEs that could be altered by a synonymous SNP.

ADD REPLYlink written 8.2 years ago by Larry_Parnell16k
1
gravatar for Pierre Lindenbaum
8.2 years ago by
France/Nantes/Institut du Thorax - INSERM UMR1087
Pierre Lindenbaum119k wrote:

See the well documented article in wikipedia: http://en.wikipedia.org/wiki/Silent_mutation

ADD COMMENTlink written 8.2 years ago by Pierre Lindenbaum119k
1
gravatar for Khader Shameer
8.2 years ago by
Manhattan, NY
Khader Shameer18k wrote:

Not specifically based on the mechanism that you explained, but a recent paper from Butte Lab showed that both synonymous and non-synonymous SNPs share similar likelihood and effect size of human disease associations. See the paper here.

ADD COMMENTlink written 8.2 years ago by Khader Shameer18k

Yes, this is an important point - effect size in terms of phenotype.

ADD REPLYlink written 8.2 years ago by Larry_Parnell16k
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