Search bioRxiv⌕ Search

bioRxiv · 10.1101/2023.10.08.561398

Ovine MyD88 have active role in host resistance against Haemonchus contortus infection

Abstract

Host resistance against parasitic infestation is quite important to study in current days, since till date no effective vaccines against parasites have been developed. Moreover, indiscrimate use of regular deworming as a practice may lead to the development of resistance to antihelmiths (as in case of antibiotic resistance against bacteria) or development of antihelminth resistant strains among dreadly parasites. In this present study, we attempt to explore immune response gene against Haemonchus contortus as dreadly parasite against sheep model. In our lab, we have already detected some of such promising genes, namely RIGI (earlier known antiviral in action), CD14, IL6 and IL10 (earlier known antibacterial in action). In this current publication, we have explored the role of MyD88 in mediating resistance against parasitic infestation. We have characterized ovine MyD88 molecule, identified important domain, analyzed molecular docking, identified the binding site with H. contortus through in silico studies, network and pathway analysis, followed by differential mRNA expression profiling, ultimate confirmation through immunohistochemistry. Identification of immune response genes against parasites may lead to immunomodulation, genomic selection, gene therapy or even development of disease resistant stock of sheep through gene editing approach.

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Banerjee, S., Pal, A., Chatterjee, J. K.. 2023-10-10. Ovine MyD88 have active role in host resistance against Haemonchus contortus infection. https://doi.org/10.1101/2023.10.08.561398

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

Structural variation in repeat elements is widespread in normal human tissues and in tumorigenesis

Somatic mosaicism contributes to genomic variation, yet postzygotic structural variants remain under-characterized. We performed long- and short-read WGS from multiple individuals (n=47 normal tissues; n=168 samples) and identified mosaic structural variants in all individuals and germ layers, impacting a median 285.2 kb/genome. Nearly half of breakpoints were independently validated, with tissue distributions reflecting both early and late developmental origins. Most mosaic variants were repeat-mediated and 8.3% overlapped functional elements, an enrichment compared to germline variants. To extend these analyses in samples where long-read sequencing is infeasible, we measured repeat alterations from short-read sequencing, recapitulating mosaic tissue-specific differences. We characterized tumor- and tissue- specific variation in repeats across 15 cancer types and found tumor-related repeat variation to be similar in scale to that of normal mosaic variation. Tracking repeat changes in cell-free DNA provided a noninvasive approach for tumor monitoring. Our analyses revealed widespread repeat-driven structural variation in health and disease.

genomics↗

RNA isoform-resolved multiplexed sequencing with bioorthogonal barcoding

RNA isoform dysregulation drives disease pathogenesis and is the target of FDA-approved splice-switching therapeutics. However, multiplexed sequencing methods discard splice junction information because only 3' termini are barcoded and counted. Here, we repurpose acylation and click chemistries to conjugate bioorthogonal barcodes (bobcodes) directly onto multiple internal positions along cellular RNAs. Bobcoded RNAs from multiple samples are pooled for multiplexed cDNA synthesis, during which reverse transcriptase switches from each RNA template onto its tethered bobcode with greater than 99% accuracy in species mixing experiments. Bobcode attachment intervals set cDNA insert sizes without a library fragmentation step, and priming with poly(dT) or random hexamers selects between 3'-end counting and full-length isoform capture. A bioorthogonal barcode-sequencing (BOB-seq v0.1) drug screen identifies transcriptome-wide on- and off-target RNA splicing effects and outperforms existing multiplexing RNA sequencing methods in workflow simplicity, sample-to-sample variability, and barcoding accuracy. Bobcodes add isoform resolution to scalable multiplexed RNA sequencing.

genomics↗

Structural polymorphism and population-variable coding capacity of HERV-K(HML-2) in human pangenomes

Approximately 8% of the human genome is derived from ancient retroviral infections. The most recently integrated of these endogenous retroviruses is the HERV-K(HML-2) clade, whose expression has been associated with cancer, amyotrophic lateral sclerosis, and embryogenesis. Studies of HERV expression, particularly HML-2, have relied predominantly on short-read sequencing. However, the high similarity among HML-2 proviruses prevents many short reads from being assigned uniquely to individual loci. We therefore compared haplotype-resolved long-read genome assemblies from 292 donors to resolve variation in proviral structure and coding capacity. Several loci previously thought to be fixed were structurally polymorphic. Tandem arrays occurred at 13 loci and contained up to six proviral copies in a single array. At 8q11.23, we identified a previously undescribed full-length provirus in one haplotype. All 583 other haplotypes carried a solo-LTR. We found that standard reference genomes failed to represent the coding capacity retained in many individuals, whose proviruses contained intact open reading frames despite disruptive mutations in the reference sequences. Short-read genotypes left 32.5% of the tested donor-variant pairs unresolved at sites associated with viral reading frames. These findings show why HML-2 expression must be interpreted in the context of the structural and coding alleles each individual carries.

genomics↗