Transcriptional profiling ofOvis ariesidentifiesOvar-DQA1allele frequency differences between nematode-resistant and susceptible selection lines

Abstract

Gastrointestinal nematodes are a major cause of disease in grazing livestock; however, individual animals differ in their response to infection. To identify genes whose expression correlates with resistance status, transcriptional profiling of resistant and susceptible sheep was undertaken. Transcription profiles were taken at three time points during the growth of lambs. The number of genes differentially expressed increased as animals were exposed to longer nematode challenge. Almost 300 genes, with a variety of functions, were differentially expressed overall, although genes more highly expressed in resistant animals typically had major histocompatibility complex (MHC) II, free radical scavenging or smooth muscle-specific functions. The Ovar-DQA1 gene was 8.4-fold more highly expressed in resistant animals. This was due in part to a higher frequency of DQA1 null alleles in susceptible animals. The null allele of DQA1 was also associated with susceptibility in a separate selection flock, presenting the hypothesis that failure to present parasite antigens to immune cells led to nematode susceptibility. To test this hypothesis, commercial rams from three breeds were genotyped for the null allele of DQA1. The homozygous null allele was associated with susceptibility in only one of the three breeds tested indicating that the null allele does not cause susceptibility to intestinal parasites per se but is probably in linkage disequilibrium with additional polymorphisms in the MHC region. A combination of these polymorphisms may contribute to susceptibility in some populations. The extent of linkage disequilibrium between polymorphisms may vary from breed to breed or population to population.

Transcriptional profiling of the ovine abomasal lymph node reveals a role for timing of the immune response in gastrointestinal nematode resistance

“…A number of previous studies have been undertaken to characterise the duodenal (Diez-Tascon et al, 2005;Keane et al, 2007;Keane et al, 2006), abomasal mucosal (Knight et al, 2011;Rowe et al, 2009) and lymph node and lymph fluid transcriptome (Andronicos et al, 2010;Gossner et al, 2013;Knight et al, 2010;MacKinnon et al, 2009) and have led to the identification of genes and biological processes associated with the host response to GIN. As a result of these studies, a number of pathways have been postulated to be involved in the development of a resistant phenotype; however, no clear consensus has emerged.…”

Genetic markers to gastrointestinal nematode resistance in sheep: a review

“…Microarrays have identified from 100 (Diez-Tascon et al, 2005) to 300 (Keane et al, 2007) differential gene expression patterns between sheep genetically resistant and those that are susceptible to parasitic nematodes. In resistant animals more highly expressed were genes associated with cell morphology, cellular development, and the immune and lymphatic system development and function.…”

“…In resistant animals more highly expressed were genes associated with cell morphology, cellular development, and the immune and lymphatic system development and function. While in susceptible animals higher expression is displayed by stress response genes and those which are involved in gene regulation and DNA binding (Keane et al, 2007). In Diez-Tascon et al (2005) two genes highly expressed in resistant animals coded for two smooth muscle proteins: transgelin (TAGLIN) and actin-γ2 (ACTG2).…”

“…In Diez-Tascon et al (2005) two genes highly expressed in resistant animals coded for two smooth muscle proteins: transgelin (TAGLIN) and actin-γ2 (ACTG2). To these genes Keane et al (2007) have added other genes expressed in the intestinal smooth muscle, these are Wiskott-Aldrich syndrome family gene 2 (WASF2), myosin light chain kinase (MYLK) and desmin (DES). The explanation of contradictory effect of association of MHC gene polymorphism with FEC reduction has been found using microarray approaches.…”

“…The explanation of contradictory effect of association of MHC gene polymorphism with FEC reduction has been found using microarray approaches. Dies-Tascon et al (2005) have suggested that expression of MHC class II genes in the resistant lambs may only be effective in reducing parasite infection if combined with a set of certain MHC alleles, Keane et al (2007) indicated that the crucial role in this process lay in the presence or lack DQA1 alleles. This explained why in some reports an association between MHC alleles and FEC reductions has been pointed out (Schwaiger et al, 1995;Buitkamp et al, 1996), while this relationship in another studies has been not observed (Cooper et al, 1989;Crawford et al, 1997).…”