Razib Khan One-stop-shopping for all of my content

January 19, 2011

The rise of genetic architecture

In science, like most things, one prefers simple over complex whenever possible. You keep adding variables until the explanatory juice starts hitting diminishing marginal returns. So cystic fibrosis is due to a mutation at one gene, and the disease expresses recessively at that locus. The reality is that one mutation accounts for ~65-70% of cystic fibrosis cases around the world, and there are nearly ~1,400 known mutations on the CFTR locus. How about skin color? Mutations on a dozen genes can probably explain ~90% of the variance in the trait value across the world between populations. In fact, one single mutation on one base pair can explain ~30-40% of the trait value difference between Europeans and Africans. This is a more complex story that cystic fibrosis; you have not just many mutations, but many mutations across many genes. But, the number of genes and mutations are manageable. You can keep track of most of them in your head (e.g., I can tell you that SLC24A5, SLC45A2, KITLG, and HERC2, can explain most of the trait value difference between Africans and Europeans without looking it up).


January 18, 2011

Synthetic associations and all that

Filed under: Genetics,Genomics,GWAS,synthetic associations — Razib Khan @ 2:28 pm

PLoS Biology has four items of great interest out today:

Synthetic Associations Created by Rare Variants Do Not Explain Most GWAS Results
Synthetic Associations Are Unlikely to Account for Many Common Disease Genome-Wide Association Signals
The Importance of Synthetic Associations Will Only Be Resolved Empirically
Common Disease: Are Causative Alleles Common or Rare?

These are a response to last year’s paper on synthetic associations from the Goldstein lab. Here’s a critique of that that paper. I plan on reviewing the first in the list above soon. #3 is a response to #1 and #2 from David Goldstein, while #4 is a summation more aimed at the general audience.

Powered by WordPress