Abstract
BackgroundGastroinestinal nematodes (GIN) are one of the major health problem in grazing sheep. Although genetic variability of the resistance to GIN has been documented, traditional selection is hampered by the difficulty of recording phenotypes, usually fecal egg count (FEC). To identify causative mutations or markers in linkage disequilibrium (LD) to be used for selection, the detection of quantitative trait loci (QTL) for FEC based on linkage disequilibrium-linkage analysis (LDLA) was performed on 4097 ewes (from 181 sires) all genotyped with the OvineSNP50 Beadchip. Identified QTL regions (QTLR) were imputed from whole-genome sequences of 56 target animals of the population. An association analysis and a functional annotation of imputed polymorphisms in the identified QTLR were performed to pinpoint functional variants with potential impact on candidate genes identified from ontological classification or differentially expressed in previous studies.ResultsAfter clustering close significant locations, ten QTLR were defined on nine Ovis aries chromosomes (OAR) by LDLA. The ratio between the ANOVA estimators of the QTL variance and the total phenotypic variance ranged from 0.0087 to 0.0176. QTL on OAR4, 12, 19, and 20 were the most significant. The combination of association analysis and functional annotation of sequence data did not highlight any putative causative mutations. None of the most significant SNPs showed a functional effect on genes’ transcript. However, in the most significant QTLR, we identified genes that contained polymorphisms with a high or moderate impact, were differentially expressed in previous studies, contributed to enrich the most represented GO process (regulation of immune system process, defense response). Among these, the most likely candidate genes were: TNFRSF1B and SELE on OAR12, IL5RA on OAR19, IL17A, IL17F, TRIM26, TRIM38, TNFRSF21, LOC101118999, VEGFA, and TNF on OAR20.ConclusionsThis study performed on a large experimental population provides a list of candidate genes and polymorphisms which could be used in further validation studies. The expected advancements in the quality of the annotation of the ovine genome and the use of experimental designs based on sequence data and phenotypes from multiple breeds that show different LD extents and gametic phases may help to identify causative mutations.
Highlights
Gastroinestinal nematodes (GIN) are one of the major health problem in grazing sheep
The laboriousness of fecal egg counting on a large scale makes markerassisted selection potentially more profitable in terms of cost benefits
The ten significant markers identified in our study and already available on the commercial Illumina arrays explain an important portion of the genetic variation in our large population
Summary
Gastroinestinal nematodes (GIN) are one of the major health problem in grazing sheep. The inclusion of GIN resistance in current breeding schemes is hampered by the difficulty to record FEC on a large scale since its measure is too laborious and costly in field conditions For this reason, several studies have been carried out to dissect the genetic determinism of GIN resistance with the final aim of setting up breeding schemes that are based on molecular information rather than large-scale recording for progeny testing. Several studies have been carried out to dissect the genetic determinism of GIN resistance with the final aim of setting up breeding schemes that are based on molecular information rather than large-scale recording for progeny testing Such studies have followed the development of the molecular biology and omic sciences and the concomitant advancement of the statistical methodologies. The availability of high-throughput sequencing technologies and increasingly accurate genome annotations may allow the discovery of new polymorphisms in DNA or RNA sequences and the classification of their effects on genes that are more and more well-known in terms of functions
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