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Detection of genomic regions underlying resistance to gastrointestinal parasites in Australian sheep.

ABSTRACT: BACKGROUND:This study aimed at identifying genomic regions that underlie genetic variation of worm egg count, as an indicator trait for parasite resistance in a large population of Australian sheep, which was genotyped with the high-density 600 K Ovine single nucleotide polymorphism array. This study included 7539 sheep from different locations across Australia that underwent a field challenge with mixed gastrointestinal parasite species. Faecal samples were collected and worm egg counts for three strongyle species, i.e. Teladorsagia circumcincta, Haemonchus contortus and Trichostrongylus colubriformis were determined. Data were analysed using genome-wide association studies (GWAS) and regional heritability mapping (RHM). RESULTS:Both RHM and GWAS detected a region on Ovis aries (OAR) chromosome 2 that was highly significantly associated with parasite resistance at a genome-wise false discovery rate of 5%. RHM revealed additional significant regions on OAR6, 18, and 24. Pathway analysis revealed 13 genes within these significant regions (SH3RF1, HERC2, MAP3K, CYFIP1, PTPN1, BIN1, HERC3, HERC5, HERC6, IBSP, SPP1, ISG20, and DET1), which have various roles in innate and acquired immune response mechanisms, as well as cytokine signalling. Other genes involved in haemostasis regulation and mucosal defence were also detected, which are important for protection of sheep against invading parasites. CONCLUSIONS:This study identified significant genomic regions on OAR2, 6, 18, and 24 that are associated with parasite resistance in sheep. RHM was more powerful in detecting regions that affect parasite resistance than GWAS. Our results support the hypothesis that parasite resistance is a complex trait and is determined by a large number of genes with small effects, rather than by a few major genes with large effects.

SUBMITTER: Al Kalaldeh M

PROVIDER: S-EPMC6609385 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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Detection of genomic regions underlying resistance to gastrointestinal parasites in Australian sheep.

Al Kalaldeh Mohammad M Gibson John J Lee Sang Hong SH Gondro Cedric C van der Werf Julius H J JHJ

Genetics, selection, evolution : GSE 20190703 1

<h4>Background</h4>This study aimed at identifying genomic regions that underlie genetic variation of worm egg count, as an indicator trait for parasite resistance in a large population of Australian sheep, which was genotyped with the high-density 600 K Ovine single nucleotide polymorphism array. This study included 7539 sheep from different locations across Australia that underwent a field challenge with mixed gastrointestinal parasite species. Faecal samples were collected and worm egg counts ...[more]

PMID: 31269896

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Project description:BackgroundThe aim of this study was to estimate variance components and to identify genomic regions and pathways associated with resistance to gastrointestinal parasites, particularly Haemonchus contortus, in a breed of sheep adapted to tropical climate. Phenotypes evaluations were performed to verify resistance to gastrointestinal parasites, and were divided into two categories: i) farm phenotypes, assessing body condition score (BCS), degree of anemia assessed by the famacha chart (FAM), fur score (FS) and feces consistency (FC); and ii) lab phenotypes, comprising blood analyses for hematocrit (HCT), white blood cell count (WBC), red blood cell count (RBC), hemoglobin (HGB), platelets (PLT) and transformed (log10) egg per gram of feces (EPGlog). A total of 576 animals were genotyped with the Ovine SNP12k BeadChip (Illumina, Inc.), that contains 12,785 bialleleic SNP markers. The variance components were estimated using a single trait model by single step genomic BLUP procedure.ResultsThe overall linkage disequilibrium (LD) mean between pairs of markers measured by r2 was 0.23. The overall LD mean between markers considering windows up to 10 Mb was 0.07. The mean LD between adjacent SNPs across autosomes ranged from 0.02 to 0.10. Heritability estimates were low for EPGlog (0.11), moderate for RBC (0.18), PLT (0.17) HCT (0.20), HGB (0.16) and WBC (0.22), and high for FAM (0.35). A total of 22, 21, 23, 20, 26, 25 and 23 windows for EPGlog for FAM, WBC, RBC, PLT, HCT and HGB traits were identified, respectively. Among the associated windows, 10 were shown to be common to HCT and HGB traits on OAR1, OAR2, OAR3, OAR5, OAR8 and OAR15.ConclusionThe traits indicating gastrointestinal parasites resistance presented an adequate genetic variability to respond to selection in Santa Inês breed, and it is expected a higher genetic gain for FAM trait when compared to the others. The level of LD estimated for markers separated by less than 1 Mb indicated that the Ovine SNP12k BeadChip might be a suitable tool for identifying genomic regions associated with traits related to gastrointestinal parasite resistance. Several candidate genes related to immune system development and activation, inflammatory response, regulation of lymphocytes and leukocytes proliferation were found. These genes may help in the selection of animals with higher resistance to parasites.

Project description: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).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.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.

Project description:A total of 184 Djallonké lambs from Burkina Faso with phenotypes for packed-cell volume (PCV), log-transformed fecal egg count (lnFEC), and FAffa MAlan CHArt (FAMACHA©) eye scores were typed with the OvineSNP50 BeadChip of Illumina to contribute to the knowledge of the genetic basis of gastrointestinal (GIN) parasite resistance in sheep. Association analysis identified a total of 22 single-nucleotide polymorphisms (SNPs) related with PCV (6 SNPs), lnFEC (7), and FAMACHA scores (9) distributed among 14 Ovis aries chromosomes (OAR). The identified SNPs accounted for 18.76?% of the phenotypic variance for PCV, 21.24?% for lnFEC, and 34.38?% for FAMACHA scores. Analyses pointed out the importance of OAR2 for PCV, OAR3 for FAMACHA scores, and OAR6 for lnFEC. The 125?kb regions surrounding the identified SNPs overlapped with seven previously reported quantitative trait loci (QTLs) for the traits analyzed in the current work. The only chromosome harboring markers associated with the three traits studied was OAR2. In agreement with the literature, two different chromosomal areas on OAR2 can play a major role in the traits studied. Gene-annotation enrichment analysis allowed us to identify a total of 34 potential candidate genes for PCV (6 genes), lnFEC (4), and FAMACHA scores (24). Annotation analysis allowed us to identify one functional term cluster with a significant enrichment score (1.302). The cluster included five genes (TRIB3, CDK4, CSNK2A1, MARK1, and SPATA5) involved in immunity-related and cell-proliferation processes. Furthermore, this research suggests that the MBL2 gene can underlie a previously reported QTL for immunoglobulin A levels on OAR22 and confirms the importance of genes involved in growth and size (such as the ADAMTS17 gene on OAR18) for GIN resistance traits. Since association studies for the ascertainment of the genetic basis of GIN resistance may be affected by genotype-environment interactions, obtaining information from local sheep populations managed in harsh environments contributes to the identification of novel genomic areas of functional importance for GIN resistance for that trait.

Project description: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.

Project description:Ascochyta blight (AB), caused by a necrotrophic fungus, Ascochyta rabiei (syn. Phoma rabiei) has the potential to destroy the chickpea industry worldwide, due to limited sources of genetic resistance in the cultivated gene pool, high evolutionary potential of the pathogen and challenges with integrated disease management. Therefore, the deployment of stable genetic resistance in new cultivars could provide an effective disease control strategy. To investigate the genetic basis of AB resistance, genotyping-by-sequencing based DArTseq-single nucleotide polymorphism (SNP) marker data along with phenotypic data of 251 advanced breeding lines and chickpea cultivars were used to perform genome-wide association (GWAS) analysis. Host resistance was evaluated seven weeks after sowing using two highly aggressive single spore isolates (F17191-1 and TR9571) of A. rabiei. GWAS analyses based on single-locus and multi-locus mixed models and haplotyping trend regression identified twenty-six genomic regions on Ca1, Ca4, and Ca6 that showed significant association with resistance to AB. Two haplotype blocks (HB) on chromosome Ca1; HB5 (992178-1108145 bp), and HB8 (1886221-1976301 bp) were associated with resistance against both isolates. Nine HB on the chromosome, Ca4, spanning a large genomic region (14.9-56.6 Mbp) were also associated with resistance, confirming the role of this chromosome in providing resistance to AB. Furthermore, trait-marker associations in two F3 derived populations for resistance to TR9571 isolate at the seedling stage under glasshouse conditions were also validated. Eighty-nine significantly associated SNPs were located within candidate genes, including genes encoding for serine/threonine-protein kinase, Myb protein, quinone oxidoreductase, and calmodulin-binding protein all of which are implicated in disease resistance. Taken together, this study identifies valuable sources of genetic resistance, SNP markers and candidate genes underlying genomic regions associated with AB resistance which may enable chickpea breeding programs to make genetic gains via marker-assisted/genomic selection strategies.

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Detection of genomic regions underlying resistance to gastrointestinal parasites in Australian sheep.

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Detection of genomic regions underlying resistance to gastrointestinal parasites in Australian sheep.

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