Comments on: I am free of rare homozygous recessives! (well, perhaps)

By: pconroy

pconroy — Tue, 02 Oct 2012 22:24:08 +0000

Just also noticed that my eldest daughter is Homozygous Recessive for this:

rs3218620 at Chr10b:90770373 gave ‘CT’ The minor allele is ‘T’ with a MAF = 0.00365
rs3218620 FAS Fas (TNF receptor superfamily, member 6)

Does that mean that her French Mom and I are related? I do know that we share one relative, this guy:
http://research.google.com/pubs/author37534.html

By: pconroy

pconroy — Tue, 02 Oct 2012 16:19:45 +0000

@5,

Just made an appointment today…

By: Justin Loe

Justin Loe — Tue, 02 Oct 2012 03:04:48 +0000

Apparently we have one rare snp that (to my knowledge) is absent from the current sample set entirely, i.e. everyone currently publicly participating in GEDMATCH or snpology, etc.

By: Sandgroper

Sandgroper — Mon, 01 Oct 2012 17:40:49 +0000

#4 – Paul – If you haven’t had one, I recommend having a colonoscopy ASAP, with follow ups at regular intervals, which is what I’m confident your doctor will suggest.

That’s actually not saying much – everyone over 55 should get screened at least once every 5 years.

If you do happen to get colon cancer, if it is caught early by screening, the 5 year survival rate is very high – better than 98%. It’s one of the very common causes of death that, with regular screening, is very successfully treatable.

By: pconroy

pconroy — Mon, 01 Oct 2012 17:09:04 +0000

Also, just looked at this rare allele I have:
rs2066459 at Chr2c:190708712 gave ‘AG’ The minor allele is ‘A’ with a MAF = 0.00868
rs2066459 PMS1 PMS1 postmeiotic segregation increased 1 (S. cerevisiae) - missense R202K

http://www.ncbi.nlm.nih.gov/gene/5378

Mutations in this gene cause hereditary nonpolyposis colorectal cancer type 3 (HNPCC3) either alone or in combination with mutations in other genes involved in the HNPCC phenotype, which is also known as Lynch syndrome

http://en.wikipedia.org/wiki/Hereditary_nonpolyposis_colorectal_cancer

Individuals with HNPCC have about an 80% lifetime risk for colon cancer.

It so happens that my father is one of 7 siblings, of which 4 – all females – have died of Colorectal Cancer by their early 50′s?! Yikes, that news is a real pain in the ass – must mention this to my doctor next visit!

By: Razib Khan

Razib Khan — Mon, 01 Oct 2012 16:28:14 +0000

Rare non-European SNPs will be unascertained, thus not on the chip in the first place.

fair enough. i had assumed that the ascertainment here was for variant SNPs…but then that begs the question about rare variants. can someone clarify?

By: pconroy

pconroy — Mon, 01 Oct 2012 15:15:35 +0000

I uploaded my results and Ian ran them. Seems I have no consanguinity reported either, even though my parents share a 4.5 cM segment with a few hundred SNP’s.

http://www.ianlogan.co.uk/23andme/open/paul%20conroy.htm

He notes: “The results show a mixed Eurpean pedigree – probably more Southern than Northern.” Which is kind of surprising, as most admixture analysis shows me as having more Scandinavian ancestry than the average Irish or British person?!

He says:
“The most interesting SNP is:
‘GT’ rs60831116 KRT14 keratin 14 – missense C18X”

I note that Razib and I share 2 rare alleles, as follows:
rs259729 LRRC63 leucine rich repeat containing 63
rs2892625 CYP2A6 cytochrome P450, family 2, subfamily A, polypeptide 6

By: Peter

Peter — Mon, 01 Oct 2012 09:46:47 +0000

I think you’re wrong on ascertainment bias. Yes, it’ll reduce the apparent variation, meaning you’ll have slightly elevated homozygosity – but homozygosity for common variants. Rare non-European SNPs will be unascertained, thus not on the chip in the first place.