Putting IBD to bed


IBD plays a big part in my understanding of inheritance. I don’t mean inflammatory bowel disease. Nor do I mean isolation by distance. I’m talking identity by descent. Assuming your parents are “unrelated” then you are identical by descent with your sibling across some portion of your genome. You inherit identical segments from your parents, though due to recombination they will usually be non-identical at least across some part of the chromosome. Because of the law of segregation you should overlap 25% with your full sibling on the copy of the genes inherited from your mother and father (double that, and you get 50%). But this is an expected value. As it happens many siblings are not exactly 50% (e.g., I know of full siblings who share 40% of their genomes identical by descent from their parents). In the pre-genomic age this detail about variation was elided because usually you couldn’t precisely estimate the identity by descent. Rather, you just assume that you share 1/2 your genome with your full sibling, 1/4 with a half sibling or aunt/uncle or grandparent, 1/8 with your first cousin, and so forth.

Genomics has changed that. I can tell you for example that my son is ~20% identical by descent with one of his grandfathers. And, more surprisingly, he’s 18.9% identical by descent with one of his great-aunts! If expectation held his great-aunt should be 1/2 as related to him as his grandfather, but expectation did not hold. The figure above is from a review, Relatedness in the post-genomic era: is it still useful?:

Relatedness is a fundamental concept in genetics but is surprisingly hard to define in a rigorous yet useful way. Traditional relatedness coefficients specify expected genome sharing between individuals in pedigrees, but actual genome sharing can differ considerably from these expected values, which in any case vary according to the pedigree that happens to be available. Nowadays, we can measure genome sharing directly from genome-wide single-nucleotide polymorphism (SNP) data; however, there are many such measures in current use, and we lack good criteria for choosing among them. Here, we review SNP-based measures of relatedness and criteria for comparing them. We discuss how useful pedigree-based concepts remain today and highlight opportunities for further advances in quantitative genetics, with a focus on heritability estimation and phenotype prediction.

If you have academic access, you should read it. If you don’t, they seem to be proposing that we move beyond the confusing concept of identity by descent, and just think in terms of a coalescent framework. It does strike me that classical IBD-thinking is a historical contingency of genetics’ emergence in part in an age where pedigrees were very prevalent tools in interrogating patterns of inheritance. All for the good. But for non-geneticists I would suggest that these new methods which are able to pinpoint with fine precision patterns of genetic variation across pedigrees will allow us to explore in much more detail the nature of the heritability of many quantitative traits.

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