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Deafness and DNA

Replies: 11

Re: Deafness

Posted: 11 Jun 2013 6:00PM GMT
Classification: Query
OK, here we go, ready or not :) This is just some (rather complicated) educational background, and your best bet is to consult with a genetic counselor and/or a specialist familiar with Waardenburg Syndrome. WS is typically an autosomal dominant disorder, so it must have had "reduced penetrance" in whichever grandparent carried the mutation. The autosomal dominant pattern still holds, however, because of all the people affected in multiple generations.

The rare SNP utility isn't going to have much utility for your research. You're looking for a mutation that affects the gene function. There are many benign variants found in the general population that don't affect the function, and those probably include the ones you listed. The "rare" alleles aren't all that rare in absolute terms (ranging from 4 to 19%, far more common than WS). The SNP chips just have room for a limited number of variants.

You (and everyone) "have" two copies of the MITF gene, the SNAI2 gene, etc, one inherited from your mother's side (who got it from her mother OR her father) and the other from your father's side (who got it from his father OR his mother). Your genotype lists the two alleles (variations) for each marker (SNP) in an arbitrary order, so you can't tell which allele came from which parent. For rs4855447, your mother might have given you the A or the G (and your father would have given you the other allele). If she gave you the A, it could have come from either of her parents (her father has an A and so does her mother). Thus you can't really tell the source of a single allele.

However, you can look at another GEDmatch utility, the one-to-one comparison, and see what "chunks" of DNA you inherited from your maternal grandfather and grandmother. Then you can look up the location of the gene in question and see which chunk it falls within. There is a website called GeneCards. If you ask about MITF, one of the many items of information tells you that the gene goes from position 69,788,586 to 70,017,488 on chromosome 3. It looks like you inherited the MITF gene from your grandmother. If your grandfather's sister had WS, that sort of rules out the MITF gene. Note that your one-to-one comparisons to your grandfather and grandmother are like photographic negatives. If your grandfather didn't provide a certain chunk, then your grandmother did.

http://www.genecards.org/cgi-bin/carddisp.pl?gene=MITF

You can repeat the process for other genes that have been implicated in WS. Include the ones like SNAI2, where GEDmatch didn't list any "rare" SNPs. You could have the common version of all the SNPs on the chip, but your mutation will be so rare it's not even on the chip.

Your sister will also be informative. You can rule out any gene where you and your sister don't match. Your cousin will also be informative. You will be looking for a segment where all three of you match. It's even possible that none of the known genes explains the condition in your family.
SubjectAuthorDate Posted
Jason Gervase 15 Apr 2013 5:02PM GMT 
APTurner 15 Apr 2013 6:20PM GMT 
Jason Gervase 15 Apr 2013 6:30PM GMT 
APTurner 15 Apr 2013 9:30PM GMT 
Jason Gervase 16 Apr 2013 2:53PM GMT 
APTurner 16 Apr 2013 4:52PM GMT 
Jason Gervase 5 Jun 2013 8:52PM GMT 
APTurner 6 Jun 2013 3:16AM GMT 
Jason Gervase 10 Jun 2013 3:40AM GMT 
APTurner 12 Jun 2013 12:00AM GMT 
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