Very interesting, Obed! I've recently been trying to do something similar with some low-coverage WGS results I have for myself. I have 23andMe results for three of my grandparents, so I can narrow down each heterozygous variant to two of my grandparents (one maternal and one paternal). One of the variants I have that I've been particularly interested in is a missense point mutation that a couple of studies have suggested might be a causative variant for malignant hyperthermia susceptibility. Malignant hyperthermia is a severe reaction to common general anesthesia. The studies in question are early-stage and far from conclusive and I've yet to undergo general anesthesia myself, but there are alternatives to these "triggering" anesthetics when there is knowledge or suspicion of a susceptibility to malignant hyperthermia, so I consider this a very "actionable" finding. Based on my 23andMe results, I've inherited the gene in question from my two grandfathers, neither of whom had any history of malignant hyperthermia. But even people with this susceptibility condition don't always experience a reaction during all anesthesia exposures. Also, there is the possibility that my result represents a recent de novo mutation. I'm currently thinking about ordering WGS for my parents through Full Genomes in order to try to pin this variant down further (as well as for more general use, including getting an mtDNA sequence for my father's maternal line and getting better coverage for my paternal chrY sequence). On Tue, Oct 27, 2015 at 10:44 AM, Obed W Odom via < genealogy-dna@rootsweb.com> wrote: > My whole-genome sequence showed me to be heterozygous for the G to A SNP > rs140578907 in the calicin gene at location 36170317 of chromosome 9, which > causes an arginine to glutamine change at position 273 of the calicin > protein. This SNP is very rare, the A allele having a frequency of less > than 0.1%. > > The calicin protein is said to be an integral protein of the head of a > sperm cell so I thought that perhaps the rarity of this mutation might > indicate that a sperm with this mutation might not be able to fertilize an > egg. If so, this mutation could only be inherited through the all-female > line, like mitochondrial DNA, except that, unlike mitochondrial DNA, this > mutation would only have a 50% chance of being inherited for each > transmission. > > To determine whether I inherited this SNP from my father or mother, I had > my 2 sons tested for it. Luckily, the 23andMe Relative Finder test had > already shown that one of my sons and I, but not the other son, match my > paternal first cousin for the region of the calicin gene. So one of my sons > inherited my paternal DNA in this region and the other son inherited my > maternal DNA. > > I just received the results of my sons' tests and, lo and behold, the son > who inherited my paternal DNA is positive for this SNP and the other son is > negative. This means that the SNP is on the DNA that I inherited from my > father, and a sperm with the A allele managed to fertilize an egg in 2 > transmission events, producing me and one of my sons. I conclude from this > that this SNP has little if any effect on sperm potency. The reason for the > rarity of the SNP is an open question, but perhaps it is just a relatively > recent SNP. It is mostly confined to people of European extraction, which > would tend to support this. > > ------------------------------- > To unsubscribe from the list, please send an email to > GENEALOGY-DNA-request@rootsweb.com with the word 'unsubscribe' without > the quotes in the subject and the body of the message >

Greg, is there an rsid for the variant you're interested in? I was wondering if imputation could be used for your grandfathers' genotype results from 23andMe. The imputed VCF file from http://dna.land has about 39,000,000 variants, but of course they are limited to ones with rsids. And thanks to you (and others) for your kind words about the GENEALOGY-DNA mailing list. Ann Turner On Wed, Oct 28, 2015 at 6:15 AM, G. Magoon via <genealogy-dna@rootsweb.com> wrote: > Very interesting, Obed! > I've recently been trying to do something similar with some low-coverage > WGS results I have for myself. I have 23andMe results for three of my > grandparents, so I can narrow down each heterozygous variant to two of my > grandparents (one maternal and one paternal). > > One of the variants I have that I've been particularly interested in is a > missense point mutation that a couple of studies have suggested might be a > causative variant for malignant hyperthermia susceptibility. Malignant > hyperthermia is a severe reaction to common general anesthesia. The studies > in question are early-stage and far from conclusive and I've yet to undergo > general anesthesia myself, but there are alternatives to these "triggering" > anesthetics when there is knowledge or suspicion of a susceptibility to > malignant hyperthermia, so I consider this a very "actionable" finding. > Based on my 23andMe results, I've inherited the gene in question from my > two grandfathers, neither of whom had any history of malignant > hyperthermia. But even people with this susceptibility condition don't > always experience a reaction during all anesthesia exposures. Also, there > is the possibility that my result represents a recent de novo mutation. > > I'm currently thinking about ordering WGS for my parents through Full > Genomes in order to try to pin this variant down further (as well as for > more general use, including getting an mtDNA sequence for my father's > maternal line and getting better coverage for my paternal chrY sequence). >