The decline of inbreeding, written in our genes

Nalls, M., Simon-Sanchez, J., Gibbs, J., Paisan-Ruiz, C., Bras, J., Tanaka, T., Matarin, M., Scholz, S., Weitz, C., Harris, T., Ferrucci, L., Hardy, J., & Singleton, A. (2009). Measures of Autozygosity in Decline: Globalization, Urbanization, and Its Implications for Medical Genetics PLoS Genetics, 5 (3) DOI: 10.1371/journal.pgen.1000415


i-5ab121aeaed1696575410a70c30029b5-polydactyly.jpgA new study indicates that increases in mobility, urbanisation, and cross-population mating over the last century have substantially reduced inbreeding, and left a distinctive trace in the genome of modern Americans.

The study, published in the latest issue of PLoS Genetics, used genome-wide patterns of genetic variation in 809 unrelated American males to explore changes in the degree of inbreeding in the North American population over the last century. Inbreeding leaves a characteristic signature in the genome: long tracts of autozygosity, meaning regions in which an individual has inherited the same sets of genetic variants from both parents. The more closely-related an individual's parents are the more of these regions they will carry and the longer such regions will be.

The authors of this study took advantage of a set of healthy individuals collected by the Coriell Institute as a generic control group, sampled so as to be broadly representative of the North American population of varied European descent. The cohort contained individuals ranging from 19 to 99 years of age, essentially providing a sliding window of patterns of genetic change over the last century. Because the cohort was used as a control in genome-wide association studies the researchers had access to information from over half a million genetic variants scattered throughout the genome of each participant.

That dataset allowed the authors to directly measure the levels of autozygosity and estimate changes in the level of inbreeding over the last hundred years. Here's the money shot:

i-bcf5ce140deba143002f1182fc1702cf-inbreeding_coefficient_1900-2000.png

The graph shows a steady decline in estimated inbreeding levels across the studied time span, consistent with an increased tendency for individuals to find mates far from the place they were born - something made a lot easier by mechanised transport and increased urbanisation, and something that (barring civilisational catastrophe) seems set to continue for the foreseeable future.

The authors note the obvious upside of this process: "decreasing autozygosity and less homozygosity genome-wide may help to
slightly reduce the burden of rare recessive diseases in the future."

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That's weirdly fascinating to me. I'm going to go read it.

But I wonder if it is a regional thing. Or not so much regional, but the slope might be different in places other than North America. Most of us got here in the last 300 years or so. I can remember being astonished at the DNA analysis of some prehistoric British skeleton and they had actually found a guy nearby who was related....This is the one: http://query.nytimes.com/gst/fullpage.html?sec=health&res=9807EEDB133BF…

But this is the clever kind of experiment that can be done with the resources in hand from another set of work and can build from it. Very neat.

Maybe they address that region thing. I'm going to read now.

Actually one might realize that inbreeding may be the cause of the high age of some of the studied individuals. Homozygoty can enhance longevity, as it can also enhance a shorter lifespan, but those 'inbred' individuals with a short lifespan die young and would never be observed within studies like these.

The bulk of the 'oldest ever' people came from isolated regions with small to none new genetic input. I recall some old French and Swiss women from Alpvalleys, oldies from the Balkan Mnts., some old Japanese people from isolated valleys and some Icelandic oldies. All from regions with low genetic variation (= inbreeding).