July 29, 2014

Lethal mutations quantified

A very interesting new preprint on the arXiv (so it can be freely read). The founder population is the Hutterites. The key sentence:
Our approach indicates that on average, one in every two humans carries a recessive lethal allele on the autosomes that lead to lethality after birth and before reproductive age or to complete sterility.

arXiv:1407.7518 [q-bio.PE]

An estimate of the average number of recessive lethal mutations carried by humans

Ziyue Gao, Darrel Waggoner, Matthew Stephens, Carole Ober, Molly Przeworski

The effects of inbreeding on human health depend critically on the number and severity of recessive, deleterious mutations carried by individuals. In humans, existing estimates of these quantities are based on comparisons between consanguineous and non-consanguineous couples, an approach that confounds socioeconomic and genetic effects of inbreeding. To circumvent this limitation, we focused on a founder population with almost complete Mendelian disease ascertainment and a known pedigree. By considering all recessive lethal diseases reported in the pedigree and simulating allele transmissions, we estimated that each haploid set of human autosomes carries on average 0.29 (95% credible interval [0.10, 0.83]) autosomal, recessive alleles that lead to complete sterility or severe disorders at birth or before reproductive age when homozygous. Comparison to existing estimates of the deleterious effects of all recessive alleles suggests that a substantial fraction of the burden of autosomal, recessive variants is due to single mutations that lead to death between birth and reproductive age. In turn, the comparison to estimates from other eukaryotes points to a surprising constancy of the average number of recessive lethal mutations across organisms with markedly different genome sizes.



Black Taylor said...

As far as I can tell it's been 10 years to the day since your first blog post. I've been an almost daily reader since summer 2004 and wanted to thank you for the time and energy you've put into shedding light on so many topics within anthropology and genetics. There aren't many people who make as significant a contribution to these fields across so wide and varied an audience, so consistently and across that type of time span. Maybe one day we'll get to know more about you as an individual, but the main thing is that you keep that brain of yours protected by a good quality helmet whenever you're biking, walking down the street or just sitting under trees or shelves or whatever could dump heavy objects on you. Keep the insights coming and all the best to you. Happy 10 year blogging anniversary!

terryt said...

@ Black Taylor:

I agree with every word. Congratulations Dienekes.

Va_Highlander said...

Indeed. Congratulations!

Unknown said...

Yes, congratulations, Dienekes!

And BTW this paper you posted here is a bit of a shocker. Trojan horse, lethal recessive alleles. Once again showing just how fragile the thin lines of human genetic descent are. And how important diversity is to group survival. It's like the paper that says that 90% of LBK remains show some effect of tuberculosis. Human history has been a tightrope walk and you never know what's going to cut the rope.

Ten more years, Dienekes!