Detection and replication of QTL underlying resistance to gastrointestinal nematodes in adult sheep using the ovine 50K SNP array

Abstract

Background: Persistence of gastrointestinal nematode (GIN) infection and the related control methods have major impacts on the sheep industry worldwide. Based on the information generated with the Illumina OvineSNP50 BeadChip (50 K chip), this study aims at confirming quantitative trait loci (QTL) that were previously identified by microsatellite-based genome scans and identifying new QTL and allelic variants that are associated with indicator traits of parasite resistance in adult sheep. We used a commercial half-sib population of 518 Spanish Churra ewes with available data for fecal egg counts (FEC) and serum levels of immunoglobulin A (IgA) to perform different genome scan QTL mapping analyses based on classical linkage analysis (LA), a combined linkage disequilibrium and linkage analysis (LDLA) and a genome-wide association study (GWAS).

Results: For the FEC and IgA traits, we detected a total of three 5 % chromosome-wise significant QTL by LA and 63 significant regions by LDLA, of which 13 reached the 5 % genome-wise significance level. The GWAS also revealed 10 significant SNPs associated with IgAt, although no significant associations were found for LFEC. Some of the significant QTL for LFEC that were detected by LA and LDLA on OAR6 overlapped with a highly significant QTL that was previously detected in a different half-sib population of Churra sheep. In addition, several new QTL and SNP associations were identified, some of which show correspondence with effects that were reported for different populations of young sheep. Other significant associations that did not coincide with previously reported associations could be related to the specific immune response of adult animals.

Discussion: Our results replicate a FEC-related QTL located on OAR6 that was previously reported in Churra sheep and provide support for future research on the identification of the allelic variant that underlies this QTL. The small proportion of genetic variance explained by the detected QTL and the large number of functional candidate genes identified here are consistent with the hypothesis that GIN resistance/susceptibility is a complex trait that is not determined by individual genes acting alone but rather by complex multi-gene interactions. Future studies that combine genomic variation analysis and functional genomic information may help elucidate the biology of GIN disease resistance in sheep.

Fig. 1

Results of linkage analysis (LA; a, b) and combined linkage disequilibrium and linkage analysis (LDLA; c, d) genome scans performed for the two indicator traits of parasite resistance analyzed. Analyzed traits: LFEC Log-transformed faecal egg count, IgA _t Box-Cox-transformed optical density ratio (ODR) values of immunoglobulin A activity. Likelihood ratio test (LRT) values obtained across the 26 ovine autosomes are represented. For those chromosomes that harbor significant QTL, the horizontal lines indicate the 5 % chromosome-wise significance threshold for LA (a, b) and the 5 % chromosome-wise significance threshold for LDLA (c, d)

Fig. 2

Results from the genome-wide association study (GWAS) performed for the two indicator traits of parasite resistance analyzed. Analyzed traits: LFEC Log-transformed faecal egg count, IgA _t Box-Cox-transformed optical density ratio (ODR) values of immunoglobulin A activity. The values of the log(1/P-value) are shown for all the 43,613 SNPs that passed the quality control. For the chromosomes that harbor significant SNP associations, the horizontal lines indicate the 5 % chromosome-wise significance threshold obtained by applying a Bonferroni correction considering the number of independent SNPs analyzed for each chromosome. The genome-wise significance threshold, considering the number of independent markers analyzed for the entire genome is also represented