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Human polymorphic sites database? - to compare if two patients have the same alelle (Jun/01/2007 )

Hi, we have this case.

I found a rare mutation in a gene in two assumed-unrelated patients. I'd like to investigate, whether it is the same allele, inherited from a single ancestor, or if it was two separate hits.
I'm pretty new to this, so I was trying to find some haplotyping database, and find there a polymorfic region or repeat near the target gene, and then examine both of the samples. It seemed to me, that SNPs is no use, because they are not very polymorphic (i.e. I would need to screen many SNPs to tell if it's the same haplotype for sure as I understood). So I googled..

I found HapMap, but I understood it only contains a SNPs and with a ratio of occurence in certain populations, so that's not what I need.
I found STRbase which have what I was looking for, but only shows a few polymorphic repeats, and only one on my target chromosome, I would need something closer to my gene.
And I found some UniSTS markers in Ensembl inside and near my gene, but I assume they are only for a mapping analysis, and are not polymorphic, right?

My boss keeps telling me, that he knows there is a database for haplotyping, being often cited in Nature Genetics (but don't remembers the address), but so far I'm not lucky with finding it. I'm a bit lost in all this unsure.gif

Is my approach good at all? Or could I just found some repeat region in my gene and try to find if it's polymorphic enough? Has anyone an experience how to do this?
It would really help me a lot, thanks.


So you are trying to find out if indeed your patients are distantly related and have the same gene or if it is two ocurrences of a spontaneous SNP?

HapMap I think is what you want. You look in HapMap and it tells you whether or not a site is polymorphic and if it is how polymorphic is it (ie are most people homozygous recessive or homozygous dominant etc.) See if HapMap has your allele, see if it is already identified in the Entrez SNP database, once you get an RS number it will be easier to search...

HTH and good luck


Yes. Only it's not a simple SNP, but it's a causative of a disease.

I don't want to know the polymorphic status of that mutation (which is obviously very low, only occurs in diseased people), but rather look for a whole gene/flanking regions informative polymorphisms.
And in HapMap, all I can find are SNPs and frequencies. And particulary in my gene of interes are only two adjacent SNPs with very low polymorficity (and basically usually you can have either e.g. C or G, so in same frequencies 50% of people will have C and 50% G, that is too little to tell if they have the same haplotype). So that won't help me.

Mini and microsatellites are much more polymorphic (in size and sequence) and different from person to person. So if I test some of those and will be same or different in my two samples (and different in all controls) I can tell if they're related or not. IMHO.

I'm not sure whether I'm explaining it right, maybe what I'm looking for is not called a "haplotype" but rather checking identity of small chromosome portion or something.


I am just curious, how could you possibly know, based on two people, that this SNP is causative of your disease?


maybe you could get like one of those forensic kits to test relationdip by rflp??


QUOTE (beccaf22 @ Jun 5 2007, 08:38 PM)
I am just curious, how could you possibly know, based on two people, that this SNP is causative of your disease?

It's not a first occurence of that mutation, functional studies have already been published.

QUOTE (beccaf22 @ Jun 5 2007, 08:40 PM)
maybe you could get like one of those forensic kits to test relationdip by rflp??

Problem is that a genome-wide fingerprinting could tell me if they are related somehow, but doesn't tell me if those alleles are the same, that's what I need to know. They can be related, but still have this particular gene different.


You can do a "mutation dating" experiment. Use VNTRs or SNPs and build haplotypes. You can tell a lot about their common ancestor (if there is one!).