RPDOC - Retour Post-Doctorants

Functional admixture: genomic survey of metabolic adaption due to populations mix. – GENO-MIX

GENOMIX

Functional admixture: genomic survey of metabolic adaption due to population mix.

Background:

Genetic polymorphisms considered as disease risk factor in modern populations, are frequently relics of ancestral populations adaptation to new environments encounter during human migrations. This understanding has open a new appealing way to study pathologies called “evolutionary medicine”, which try to understand the past adaptive roles of today pathologic polymorphisms. However only few rare genetic diseases are caused by single mutations and at the opposite most of the diseases are caused by an accumulation of genetic and environmental risk factors, conversely selective constraints induce rarely the spread of only one polymorphism but instead select many polymorphisms. <br />In consequence, the next question rising is to understand how polymorphisms interact with each other and the environment to lead to adaptive or pathologic phenotype. One key difficulty of this challenge is that populations are more and more admixed. Indeed polymorphisms being neutral or advantageous in a particular genetic background might, by interacting with other polymorphisms, become deleterious in a new genetic background, and then could lead to disease predisposition. The role of polymorphism interactions and admixture on disease etiology is an upraising challenging question.

In order to gain a better understanding about the interaction between polymorphisms from different genetic background, we propose to perform a genome wide scan of the Malagasy population. Indeed this is a unique population resulting of a long-term admixture between populations coming from Indonesia and Africa. Because the genome background of original populations are very distinct, by understanding the mixing model and identifying selective signals it will be possible to characterize the beneficial and deleterious interactions between polymorphisms coming from such different genetic backgrounds.

Our approach is based on the study of genome wide scan of 600 individuals sampled following the highest ethical and anthropological standards over 20 geographic spots. Based on this knowledge of genetic diversity, we will:

(i) Uncover the migration and admixture scenario, which have lead to present Malagasy population.
(ii) Identify the genes that have been under selection and reveal the selective constraint encounter by African and Asiatic population during the island settlement.
(iii)Understand the consequences on the metabolism genes of the admixture (iv)Determine polymorphism compatibilities and incompatibilities.

Results will be published in jounal with brad impact in genetic and anthropologic field.

Genetic polymorphisms considered as disease risk factor in modern populations, are often relics of ancestral populations adaptation to new environments. This understanding has open a new appealing way to study pathologies called “evolutionary medicine” which try to understand the adaptive past of populations. However only few rare genetic diseases are caused by single mutations at the opposite most of the diseases are caused by an accumulation of genetic and environmental risk factors, conversely new selective constraints induce the spread of not only one but instead many polymorphisms.

In consequence, the next question rising is to understand how polymorphisms interact with each other plus the environment to lead to adaptive or pathologic phenotype. One key difficulty of this challenge is that populations are more and more admixed. Indeed polymorphisms being neutral or advantageous in a particular genetic background might, by interacting with other polymorphisms, become deleterious in a new genetic background, and then could lead to disease predisposition. The importance of polymorphism interactions and admixture on disease etiology is an upraising challenging question.

In order to gain a better understanding about the interaction between polymorphisms from different genetic background, we propose to perform a genome wide scan of the Malagasy population. Indeed this is a unique population resulting of a long-term admixture between populations coming from Indonesia and east Africa. Because the genome background of original populations are very distinct, by understanding the mixing model and identifying selective signals it will be possible to characterize the beneficial and deleterious interactions between polymorphisms coming from such different genetic backgrounds.

Our approach is based on the study of genome wide scan of 600 individuals sampled following the highest ethical and anthropological standards over 20 geographic spots. Based on this knowledge genetic diversity, we will :

(i) Uncover the migration and admixture scenario, which have lead to present Malagasy population.
(ii) Identify the genes that have been under selection and reveal the selective constraint encounter by African and Asiatic population during the island settlement.
(iii) Understand the consequences on the metabolism genes of the admixture
(iv) Study polymorphism compatibilities and incompatibilities.

Project coordinator

Université Paul Sabatier - Laboratoire d'Anthropologie Moléculaire et Imagerie de Synthèse (Laboratoire public)

The author of this summary is the project coordinator, who is responsible for the content of this summary. The ANR declines any responsibility as for its contents.

Partner

Université Paul Sabatier - Laboratoire d'Anthropologie Moléculaire et Imagerie de Synthèse

Help of the ANR 500,895 euros
Beginning and duration of the scientific project: January 2013 - 24 Months

Useful links