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Groups - Bern - Computational Population Genetics - L. Excoffier
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Laurent Excoffier

Summary

The Computational and Molecular Population Genetics (CMPG) group is developing new methodologies for the simulation and analysis of molecular polymorphisms within species, with a particular focus on humans. It also develops and maintains the Arlequin software, a popular package for the analysis of multi-locus genetic diversity within and between populations.
 

Introduction

Data on DNA sequence variability within species is accumulating at an accelerating rate, particularly in model species like humans. A better characterization of this polymorphism is essential to understand the evolution of genomes, to demonstrate adaptation at the molecular level, and also to find the genetic determinants of inter-individual differences, including differential susceptibility to common diseases. However, the detection of the genomic regions under selection requires an accurate understanding of the evolutionary history of a population since past demographic events can mimic the action of selective events. The CMPG investigates new methodologies to estimate past demographic events from genetic data, provides computer software to analyse and visualize patterns of molecular diversity within species, and develops computer programs to simulate the effect on the genetic diversity of a population as it expands into new environments.
 

Projects and Services

Computer simulations to estimate demographic parameters

The past demography of a population needs to be known to make correct inferences about the selective processes that have shaped its molecular diversity. For instance, signals of positive selection at the molecular level can be mistaken for effects due to range expansions. The CMPG has therefore developed new approaches to estimate demographic parameters from genetic data based on massive computer simulations of the evolution of one or several populations. Within a Bayesian framework, observed diversity is compared to that simulated under arbitrarily complex scenarios, which allows the scientist to choose the most likely evolutionary scenario and to estimate the parameters of that model.

 

Arlequin: an integrated software package for population genetics data analysis

Arlequin is a popular software package with a user-friendly interface, which brings together a collection of population genetics methods for the analysis of genetic data within species. It can handle a large variety of data types and formats, and it computes various statistics of genetic diversity. It also estimates the level of genetic structure within and among populations, performs various tests of selection, estimates and measure levels of linkage disequilibrium (LD), and infers haplotypes from partially linked loci. A goal of the group is to enable Arlequin to deal with very large genomic data sets, to graphically visualize patterns of genetic diversity and LD across a genome, and to extend its ability to identify loci under selection. The CMPG also aims to extend it for the analysis of data produced from new large-scale sequencing platforms.
A graphical version of the software is available for Windows® , and command-line versions more suitable for the analysis of large data sets are available for Windows®,MacOSX, and Linux.

 

SPLATCHE: simulation of spatial genetic diversity

Most species, including humans, have undergone recent spatial expansions or contractions in response to climatic changes, and these spatial expansions have left specific traces at the molecular level. A spatially-explicit simulation program has been developed to simulate the genetic diversity of populations arranged on a two-dimensional lattice. The CMPG is working on ways to simulate selective events (positive or negative selection in different regions) to understand the joint effect of local adaptation and demographic expansions, or the spatial spread of disease genes.
 

Websites for Further Information

Computational Population Genetics Lab: http://www.cmpg.iee.unibe.ch/content/index_eng.html

Arlequin software: http://cmpg.unibe.ch/software/arlequin35/

SPLATCHE software: http://www.splatche.com/

 

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