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Mutation and Recombination in the Cattle Germline: Genomic Analysis and Impact on Fertility

Objective

Mutation and recombination are fundamental biological processes that determine adaptability of populations. The mutation rate reflects the equilibrium between the need to adapt, the burden of mutation load, the “cost of fidelity”, and random drift that determines a lower limit in achievable fidelity. Recombination fulfills an essential mechanistic role during meiosis, ensuring proper chromosomal segregation. Recombination affects the rate of creation and loss of favorable haplotypes, imposing 2nd-order selection pressure on modifiers of recombination.

It is becoming apparent that recombination and mutation rates vary between individuals, and that these differences are in part inherited. Both processes are therefore “evolvable”, and amenable to genomic analysis. Identifying genetic determinants underlying these differences will provide insights in the regulation of mutation and recombination. The mutational load, and in particular the number of lethal equivalents per individual, remains poorly defined as epidemiological and molecular data yield estimates that differ by one order of magnitude. A relationship between recombination and fertility has been reported in women but awaits confirmation.

Population structure (small effective population size; large harems), phenotypic data collection (systematic recording of > 50 traits on millions of cows), and large-scale SNP genotyping (for genomic selection), make cattle populations uniquely suited for genetic analysis. DAMONA proposes to exploit these unique resources, combined with recent advances in next generation sequencing and genotyping, to:

(i) quantify and characterize inter-individual variation in male and female mutation and recombination rates,
(ii) map, fine-map and identify causative genes underlying QTL for these four phenotypes,
(iii) test the effect of loss-of-function variants on >50 traits including fertility, and
(iv) study the effect of variation in recombination on fertility.

Call for proposal

ERC-2012-ADG_20120314
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Host institution

UNIVERSITE DE LIEGE
EU contribution
€ 2 258 000,00
Address
PLACE DU 20 AOUT 7
4000 Liege
Belgium

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Region
Région wallonne Prov. Liège Arr. Liège
Activity type
Higher or Secondary Education Establishments
Administrative Contact
Isabelle Halleux (Dr.)
Principal investigator
Michel Alphonse Julien Georges (Prof.)
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Total cost
No data

Beneficiaries (1)