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

By Razib Khan | September 30, 2012 4:11 pm

I got a notification today from Ian Logan that he set up a page on my genotype using a method which detects rare homozygous SNPs in the ~1 million markers I put up from my 23andMe results. My raw data is online, so anyone can analyze it. Here is the summary of my results:

The program finds about 50 ‘rare/uncommon’ SNPs from the 900,000+ tested by 23andMe.

The are no ‘homozygous-recessive’ results (surprisingly, as 1-2 might be expected).

There are a list other individuals, and sure enough most of them do have a rare recessive homozygous locus or two. I assume that ascertainment bias (the technology finding variation in Europeans better than non-Europeans in most cases) wouldn’t result in my case, because I should have less variation, not more (less variation would presumably result in more homozygous recessives). So I am thinking it may simply be that because I’m from a population with greater genetic variation (South Asians) I am less likely to yield a homozygous recessive.

In most cases population substructure doesn’t yield benefits for South Asians in terms of their genetic variation, because of intra-caste marriage (so the useful scope of ‘population’ is much smaller than the geographic one), or cousin-marriage among some South Indian Hindus and Muslims generally. But my family background is highly mixed, so I am an appropriately reshuffled Bengali (I have analyzed runs of homozygosity and genome-wide heteozygosity, and I have less than the typical Eurasian of the former and more than the typical Eurasian of the latter).

I only point this out to encourage more people to release their genotypes. This is arguably altruistic, as the more genotypes there are, the fewer will be interested in my own results. Though over the long term more data in the public domain, analyzable by interested researchers and motivated enthusiasts, will mean greater gains of understanding.

CATEGORIZED UNDER: Personal Genomics
MORE ABOUT: Personal genomics

Comments (8)

  1. Peter

    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.

  2. pconroy

    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.


    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

  3. 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?

  4. pconroy

    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


    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


    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!

  5. Sandgroper

    #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.

  6. Justin Loe

    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.

  7. pconroy


    Just made an appointment today…

  8. pconroy

    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:


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About Razib Khan

I have degrees in biology and biochemistry, a passion for genetics, history, and philosophy, and shrimp is my favorite food. In relation to nationality I'm a American Northwesterner, in politics I'm a reactionary, and as for religion I have none (I'm an atheist). If you want to know more, see the links at http://www.razib.com


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