Tag Archive for 'natural selection'

Looking closer at natural selection in inflammatory bowel disease

19/11/2012
Categories: Analysis
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As I mentioned a few weeks ago, we recently published a large study into the genetics of inflammatory bowel disease (IBD), which included a number of analyses digging into the biology and evolutionary history of IBD genetic risk. Gratifyingly, our paper has stimulated a lot of discussion among other scientists, which has generated several ideas about future directions for this work. One question that was raised by several population-genetics experts at ASHG was about our natural selection analysis, and in particular our claim to discover an enrichment of balancing selection in IBD loci. In the paper, we found clear signals of natural selection on IBD loci, a subset of which we interpreted as balancing selection. In this post I will set out how I came to this conclusion, but then outline another explanation that could explain the results: recent local positive selection in Europeans.

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Identifying targets of natural selection in human and dog evolution

07/03/2012
Categories: Analysis
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Over the course of the past year or so, I’ve been working (with Jonathan Pritchard) on a statistical method for learning about the history of a set of populations from genetic data. Much of this work is described in a paper we recently made available as a preprint [1]. However, as many readers will know, writing a paper involves deciding which results are important to the main point (and worth fleshing out in detail), and which aren’t. In this post, I’m going to describe some results and thoughts that didn’t quite make the cut, but which I think merit a small note. In particular, I’m going to discuss how having a demographic model for a large number of populations might be used to identify genes important in adaptation, and describe results from humans and dogs.

Background

Imagine you have genome-wide genetic data (from SNP arrays, genome sequencing, or whatever) from a number of populations in a species. A common way to visualize the relationship between your populations is to use a tree. For example, below I’ve built a tree of the 53 human populations from the Human Genome Diversity Panel (using the data from Li et al. [2]).

HGDP Tree

Maximum likelihood tree of 53 human populations built using TreeMix.

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Detecting positive natural selection from genetic data

16/09/2010
Categories: Background
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As humans expanded out of Africa into the rest of the world, they adapted to a whole host of new habitats, pathogens, and food sources. In recent years, there has been an explosion of interest in identifying the specific genetic loci underlying these adaptations using whole genome genotyping (and now sequencing). In this post, I’ll outline some of the basic principles of how these methods work.

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