Génétique humaine, maladies et évolution humaine
Vincent Plagnol (UCL Genetics Institute, London)
Michael Blum (TIMC-IMAG, Grenoble)
|After Genome Wide assocation study: Application of high-throughput DNA sequencing to the allele specific expression design (Vincent Plagnol)
|Genomic data and human evolution (Michael Blum)
After Genome Wide assocation study: Application of high-throughput DNA sequencing to the allele specific expression design
The widespread use of genome-wide association studies has enabled the identification of a large number of disease associated genetic variants. A key challenge is the design of functional assays to understand the molecular role of these risk alleles. Taking RNA as a first step, the typical expression quantitative trait locus (eQTL) experiment correlates gene expression with genotypes in large collections of samples. This design is not practical for samples that are difficult to collect on a large scale such as brain tissue or activated T cells. An alternative to measuring expression differences across individuals is to compare the relative expression of both chromosomes within the same individual. This is the purpose of the allele specific expression (ASE) design. Here, I describe how high throughput DNA sequencing enables to revisit ASE assays and how it can improve the accuracy of previous ASE experiments. This process is however challenging owing to the multiple biases associated with the sequencing step. Specific bioinformatic tools and statistical methods need to be constructed to account for these difficulties.
Genomic data and human evolution
Understanding the patterns of genetic variation for human population is of fundamental interest to anthropological sciences. Genetic data convey information about the demographic processes that occurred during the modern human colonization of the world. Here, I will show that genomic approaches shed new light on two important aspects of human demography: the relationships between demographic bottlenecks and ice ages; and the relationships between human migration and climatic gradients.