Fine mapping of QTL and genomic prediction using allele-specific expression SNPs demonstrates that the complex trait of genetic resistance to Marek's disease is predominantly determined by transcriptional regulation.
BACKGROUND
Marek's disease (MD) is a lymphoproliferative disease of poultry induced by Marek's disease virus (MDV), a highly oncogenic alphaherpesvirus. Identifying the underlying genes conferring MD genetic resistance is desired for more efficacious control measures including genomic selection, which requires accurately identified genetic markers throughout the chicken genome.


METHODS
Hypothesizing that variants located in transcriptional regulatory regions are the main mechanism underlying this complex trait, a genome-wide association study was conducted by genotyping a ~1,000 bird MD resource population derived from experimental inbred layers with SNPs containing 1,824 previously identified allele-specific expression (ASE) SNPs in response to MDV infection as well as 3,097 random SNPs equally spaced throughout the chicken genome. Based on the calculated associations, genomic predictions were determined for 200 roosters and selected sires had their progeny tested for Marek's disease incidence.


RESULTS
Our analyses indicate that these ASE SNPs account for more than 83 % of the genetic variance and exhibit nearly all the highest associations. To validate these findings, 200 roosters had their genetic merit predicted from the ASE SNPs only, and the top 30 and bottom 30 ranked roosters were reciprocally mated to random hens. The resulting progeny showed that after only one generation of bidirectional selection, there was a 22 % difference in MD incidence and this approach gave a 125 % increase in accuracy compared to current pedigree-based estimates.


CONCLUSIONS
We conclude that variation in transcriptional regulation is the major driving cause for genetic resistance to MD, and ASE SNPs identify the underlying genes and are sufficiently linked to the causative polymorphisms that they can be used for accurate genomic prediction as well as help define the underlying molecular basis. Furthermore, this approach should be applicable to other complex traits.
USDA, ARS, Avian Disease and Oncology Laboratory, East Lansing, MI, 48823, USA. hans.cheng@ars.usda.gov.
Hans H
HH
Cheng
USDA, ARS, Avian Disease and Oncology Laboratory, East Lansing, MI, 48823, USA.|Microbiology & Molecular Genetics, Michigan State University, East Lansing, MI, 48824, USA.
Sudeep
S
Perumbakkam
USDA, ARS, Avian Disease and Oncology Laboratory, East Lansing, MI, 48823, USA.
Alexis Black
AB
Pyrkosz
USDA, ARS, Avian Disease and Oncology Laboratory, East Lansing, MI, 48823, USA.
John R
JR
Dunn
INRA, Animal Genetics, GenPhySE, Castanet Tolosan, 31326, France.
Andres
A
Legarra
Department of Animal Sciences, Purdue University, West Lafayette, IN, 47907, USA.
William M
WM
Muir
D000483:Alleles; D000818:Animals; D002645:Chickens / Q000235:genetics; D060467:Disease Resistance / Q000235:genetics*; D005260:Female; D015870:Gene Expression; D055106:Genome-Wide Association Study; D005838:Genotype; D008381:Herpesvirus 2, Gallid / Q000472:pathogenicity; D008297:Male; D008380:Marek Disease / Q000235:genetics* / Q000821:virology; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D040641:Quantitative Trait Loci / Q000235:genetics*; D050436:Regulatory Elements, Transcriptional / Q000235:genetics