Question: Can A Snp Have A Different Effect On Different Splice Variants?
3
gravatar for Andrea_Bio
8.7 years ago by
Andrea_Bio2.5k
Andrea_Bio2.5k wrote:

Hi

I recently asked a question as to whether exons can have different reading frames in the same gene. The answer was, surprisingly to me, yes. In this question I am assuming for simplicity that an exon has the same reading frame in all transcripts it features in.

Lets imagine a gene running from bases 1 to 200. Exon 1 is from bases 50 to 100 and exon 2 is from 125-150 and exon 3 is from 175-200.

Then lets say there is a splice variant (variant 1) containing exons 1 and 2 and another splice variant (variant 2) containing exons 1 and 3.

Then lets imagine there is a SNP in exon 1 at base 60. Could this SNP have a different effect in the different transcripts? For example is it possible that in variant 1 the exon is not translated at base 60 so the SNP is an an upstream untranslated region, but in variant 2 the SNP is in the translated region and causes a synonymous (or non-syn) amino acid change?

So another way of asking the question is this: if an exon appears in multiple transcripts, does it always play the same role in those transcripts? E.g is it always translated or not translated, and if it is translated, does translation start at the same place. I am assuming the answer to this will be 'no' because if an exon can have multiple reading frames in the same gene then all sorts of other scenarios are possible.

If what I describe does happen, roughly how common or uncommon is it?

Many thanks in advance

splicing snp • 2.7k views
ADD COMMENTlink modified 8.5 years ago by Pierre Lindenbaum121k • written 8.7 years ago by Andrea_Bio2.5k
2

Hope this recent paper from Butte Lab could be interesting to you: Non-Synonymous and Synonymous Coding SNPs Show Similar Likelihood and Effect Size of Human Disease Association: http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0013574

ADD REPLYlink written 8.7 years ago by Khader Shameer18k
11
gravatar for Pierre Lindenbaum
8.7 years ago by
France/Nantes/Institut du Thorax - INSERM UMR1087
Pierre Lindenbaum121k wrote:

I've piped the program I wrote for your previous question and described here: http://plindenbaum.blogspot.com/2010/10/where-are-alternative-reading-frames-in.html to cross the data with dbSNP/UCSC:

java BioStar3034  | head 1000 |  tr ":-" "," |\
awk -F ',' 'BEGIN { printf("select * from snp130 where chrom=\"_\" ");} {printf(" OR (chrom=\"%s\" and chromStart=%d)\n",$1,int($2)-1);} END {printf(";\n");}' |\
mysql  -h  genome-mysql.cse.ucsc.edu -A -u genome -D hg18

one of the result is rs1152725 http://genome.ucsc.edu/cgi-bin/hgTracks?db=hg18&position=chr1%3A1209324-1209324

if the alternate base is 'C' instead of ref='T'

  • transcript 1: codon CTC (L) -> CCC (Proline) (non-synonymous)
  • transcript 2: codon TCT(Serine) -> TCC (Serine) (synonymous)

some my anwser is YES: it happens :-)

ADD COMMENTlink written 8.7 years ago by Pierre Lindenbaum121k
1

Excellent answer Pierre.

ADD REPLYlink written 8.7 years ago by Khader Shameer18k

Hi. Thanks for your help. Could I email you about your script as i think it will be useful for me but I don't fully understand it?

ADD REPLYlink written 8.7 years ago by Andrea_Bio2.5k

Regarding this question, I'm not sure we're both on the same track which is probably my fault due to the wording in my question. I'm not asking whether exons can have different reading frames as you've already answered that question for me :) This is a simpler question. I'm asking, if an exon occurs in more than one transcript and has the same reading frame in those transcripts, is it possible that sometimes the exon is translated and sometimes it is not translated?

ADD REPLYlink written 8.7 years ago by Andrea_Bio2.5k

yes : plindenbaum at yahoo fr

ADD REPLYlink written 8.7 years ago by Pierre Lindenbaum121k

thats very kind of you. I'll be in touch.

ADD REPLYlink written 8.7 years ago by Andrea_Bio2.5k
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