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Dernière mise à jour : Mai 2018

Menu Logo Principal AgroParisTech Université Paris-Saclay

INRA GABI Unit

GABI : Génétique Animale et Biologie IntégrativeUnité Mixte de Recherche INRA - AgroParisTech

Large-scale and high-throughput characterization of genetic diversity of the Major Histocompatiblity Complex (MHC) in chickens

Large-scale and high-throughput characterization of genetic diversiy of the MHC in chickens
© Inra
The large-scale and high-throughput characterization of the MHC in chickens with two types of complementary genotyping techniques has allowed identifying more than 80 different alleles in this 250 kb region along with evolutionary relationships between alleles. The data obtained are reference genetic resources for future studies.

Context and stakes

The MHC (Major Histocompatiblity Complex) is a genomics region which, in vertebrates and in chickens in particular, plays a central functional role in the immune response to pathogens by the intermediary notably of genes implicated in the presentation of antigens to lymphocytes. It is a complex locus whose variations explain a large part of the differences observed for response to pathogens in mammals. The study of the MHC is a subject for which the GIS team has much expertise. This dense region in chickens (250kb for approximately 40 genes in chickens) presents an exceptionnal allelic diversity and requires specific molecular characterization methods to replace the traditionnal serology techniques that are limited to experimental populations. The long-term objective is to predict animal performance to an immune stress (pathogene or vaccine) without previous seriological knowledge.

Resultats

Two complementary approaches were used for the genotyping of the MHC in different samples: in-depth characterization by sequencing of a VNTR complex marker (LEI0258) and the development and then use of a panel of SNP intended for high-throughput genotyping. These studies were carried out mainly as part of the doctoral studies of Olympe CHAZARA.

The sequencing of 534 alleles of the marker LEI0258, isolated from 80 populations of different origins, allowed the identification of 80 unique alleles including 52 that have not yet been identified, which represents a good evaluation of the genetic diversity of the MHC. For an economically important population (generally either experimental or commercial), genotyping of a marker of this type will provide an excellent characterization of this locus at a low cost. But the rapid dynamics of the LEI0258 marker will not allow establishing a specific relation with the serological data already known for all the populations.

A panel of 79 SNP of the MHC was developed using preexisting polmorphism data and by complementary sequencing of the target regions. The genotyping of these 79 SNP on 1861 samples from many populations allowed the identification of 84 different haplotypes from only homozygous samples (the phasing of the genotyped heterozygotes is problematic due to this important haplotypic diversity). Almost no correlation was observed between the SNP, which were on average only 2.2 kb apart, indicating that the density of the genotyped SNP in the region is still insufficient to capture all the variability.

The two genotyping approaches will help improve our understanding of the evolutionary relations between haplotypes of the MHC observed. The SNP genotyping notably showed that the haplotypic diversification is the consequence of rare recombinations between haplotypes belonging to the three main groups.

Even though this study is by far the most complete on the characterization of the variability of the MHC in the chicken, many alleles identified in this study only represent a small part of those that can be found in world populations, probably including several hundreds of alleles for this region of only 250 kb. This important diversity is the consequence of an equilibrating selection that occurs at this locus, due to its role in the response of the animal to changing pathogenic environments.

Perspectives

The use of the LE10258 marker or the SNP panel are complementary approaches allowing the fine characterization of genetic diversity of the MHC as part of studies on the polymorphism of this region in relation with traits that depend on the MHC, like vaccine response. The data obtained through this project are important genetic reference resources for future studies. The genotyping and the identification of routine MHC are in fact important activities of this research team.

Concerning the MHC in pangenomic appoaches, the SNP study has shown that the density of the Illumina 57K array is not sufficient to capture the complete variability of the locus. A sufficient SNP density is potentially reached with the HD Affymetrix 580K array, but the high number of haplotypes in this region necessitate a specific approach for the identification of these haplotypes.

The characterization of the MHC will be continued at a resolution higher than that using resequencing of the different identified haplotypes.

Valorization 

Large-scale characterization of the MHC using the marker LEI0258 was published in the journal Immunogenetics.

Bibliography

Chazara O, Chang CS, Bruneau N, Benabdeljelil K, Kayang BK, Loukou NE, Osei-Amponsah R, Yapi-Gnaore V, Youssao IAK, Chen CF, Pinard-van der Laan MH, Tixier-Boichard M, Bed'Hom B. Diversity and evolution of the highly polymorphic tandem repeat LEI0258 in the chicken MHC-B region. Immunogenetics 65:447-459, 2013

Bed’Hom B, Fulton J, Juul-Madsen H, Chazara O. Large scale analysis of MHC variability in chicken using a dedicated SNP panel. 10th International Veterinary Immunology Symposium, Milan, Italy, August 28th-September 1st 2013 (p.218)