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Deafness and DNA

Posted: 1366045349000
Classification: Query
Edited: 1366116799000
This is probably a shot in the dark but....

I uploaded my DNA to Promthease and received some interesting information but nothing about a specific gene that my family carries, which is Waardenburg Syndrome. This syndrome causes deafness, among other things. I have it and so do my mother, sister, aunt, grandaunt and possibly my grandpa's first cousin who was Deaf. Would anyone know what SNP I should look for for this specific gene, or direct me to someone who specialize in this kind of thing? We are really interested to find out where specifically this gene came from.

Re: Deafness

Posted: 1366050029000
Classification: Query
This post was deleted by a board administrator on 16 Apr 2013 12:58PM GMT
Posted: 1366050634000
Classification: Query
Edited: 1366050733000
Hello Dr. Turner,

Thanks for your response!

I believe we have Waardenburg Syndrome type II as the members of my family with the syndrome has sensorineural hearing loss, iris pigmentary abnormality and hair hypopigmentation but without dystopia canthorum.

I did some googling and found a list of SNPs that carry the MITF gene (that causes Waardenburg). I have one of the SNPs in my DNA: rs704246. Does this tell you anything?

I'm awaiting results from my grandparents' DNA testing which hopefully will tell me more.


Re: Deafness

Posted: 1366061402000
Classification: Query
The SNP you mentioned is a common variant and has no effect on the protein according to dbSNP. The dbSNP database is full of technical details, but you can see the distribution of the two possible alleles in different populations if you scroll down:

23andMe tests for 41 SNPs in the MITF gene, but none of them are listed in the allelic variants section at OMIM

The chips just look for somewhat common SNPs, and they're unlikely to cover the specific mutation in your family. It would take actual sequencing to learn what that might be. It could be unique to your close family, or it could come from a distant common ancestor.

However, you can use chip technology to see if the MITF gene might be implicated in your family. The gene is located on chromosome 3, positions 70014031-70016904.All the family members with the condition should match around that region, but none of the family members without the condition should match (except possibly siblings, who could match because of DNA they inherited from the unaffected parent).

AncestryDNA doesn't show where you match, but you can use your raw data with third party utilities for this purpose.

Although your query is about a specific medical condition, it illustrates how the same techniques used to identify cousins can be used to track any trait. I wrote a column about this for JoGG:

Re: Deafness and DNA

Posted: 1366119946000
Classification: Query
Edited: 1366120000000
This is a repost of my first response, which was deleted because it contained a link to a commercial site.


There are several different subtypes of Waardenburg Syndrome. If you know which type, I can tell you a little bit more.

I researched an autosomal dominant hearing impairment in my own family with a combination of genealogy and autosomal DNA testing at 23andMe. The gene was unknown in our case, but we think we have narrowed down the possibilities. I wrote about this on the 23andMe blog:

[link omitted -- you can find the post by Googling these keywords

turner "tracking down a trait" ]

It sounds like you might have enough family members to conduct similar research yourself.
Posted: 1366123997000
Classification: Query
Thanks for the information. I am awaiting results from my grandparents' DNA tests. Once I get them, I'll get the rest of my family tested. Hopefully we'll get to the bottom of the mystery of the origin of the MITF gene.

I have one more question. Do you know if there are any third-party sites that use chip technology and can tell me if the gene is implicated in my family?

Thank you!


Re: Deafness

Posted: 1366131133000
Classification: Query
You'll be able to use David Pike's utility to identify regions where you share DNA with your relatives

You will share quite a few regions with your grandparents, so this will be just a screening test to see if the results are *compatible* with the MITF hypothesis. If you test further relatives, the more distant ones will help narrow things down the most.

At a certain point, you may want to do "exome sequencing." The exome is just the small portion of your DNA (less than 2%) that codes for proteins. Sequencing (as opposed to scanning for particular rather common variants) can pick up mutations that have never been observed before. I can't post links to commercial websites, but there are some where you don't need a doctor's order.

Another alternative is to meet with a genetic counselor, who can advise you if there are clinical labs that will sequence just the MITF gene (or another plausible candidate) or research programs that might be interested in your family. If you haven't seen it already, this website has lots of links:
Posted: 1370465540000
Classification: Query
Hi Dr. Turner,

A few weeks ago, we discussed the Waardenburg Syndrome gene and how I could figure out which grandparent I got the gene from.

The Gedmatch website has an utility where you can do a search for Rare SNP (Minor Allele) in your DNA. I did that for all genes that cause Waardenburg Syndrome for myself and my grandparents which yielded interesting, yet confusing, results. It appears that I got a copy of the MITF gene from each grandparent. It also appears that I have the PAX3 gene as well, which I got from my grandfather. I was wondering if you could help further explain these results?

Myself (Kit No. A524104):

RSID, Chr, Position (B36), Genotype, %Occurrence, Gene

rs7623486, 3, 69991784, GG (both GG are mutations), 18.0446, MITF

rs1367370, 3, 69970346, aG (G is a mutation), 18.8722, MITF

rs4855447, 3, 69886018, Ag (A is a mutation), 19.6193, MITF

rs16863671, 2, 222942248, aG (G is a mutation), 11.2148, PAX3

The SNAI2 gene is absent
The SOX10 gene is absent

My grandfather (Kit No. A275138):

rs4855447, 3, 69886018, Ag (A is a mutation), 19.6193, MITF (my grandfather and I match on this one)

rs16863671, 2, 222942248, aG (G is a mutation), 11.2148, PAX3 (we also match here)

The SNAI2 gene is absent.

My grandmother (Kit No. A327547):

rs7623486, 3, 69991784, GG (both GG are mutations), 18.0446, MITF (my grandmother and I match on this one)

rs1367370, 3, 69970346, GG (both GG are mutations), 18.8722, MITF

rs4855447, 3, 69886018, AA (both AA are mutations), 19.6193, MITF

rs11774894, 8, 49995830, Ag (A is a mutation), 4.46515 SNAI2

The PAX3 gene is absent

Thank you!


Re: Deafness

Posted: 1370488601000
Classification: Query
Before I answer your questions, let me double check. You tested your mother's parents, but neither one of them exhibits signs of Waardenburg Syndrome? Exactly how are the aunt and grandaunt related?
Posted: 1370835610000
Classification: Query
My apologies for the late reply.

Right - neither of my grandparents show signs of Waardenburg Syndrome.

My aunt is my mother's sister. The grandaunt is my maternal grandfather's sister; however, we're not certain if the sign she has is contributed by the syndrome. She had a white forelock of hair when she was younger, but that is the only sign we are aware of. My aunt, on the other hand, has unusually bright blue eyes and her eyes are wideset, both characteristics that one of her daughters and my sister also exhibit.

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