Biology subjects

Meade, K. G.

Publications and source records attributed to Meade, K. G..

4 recordsLinked to original sources

bioRxiv2024

β-defensin gene copy number variation in cattle

{beta}-defensins are peptides with antimicrobial roles, characterized by a conserved tertiary structure. Beyond antimicrobial functions, they exhibit diverse roles in both the immune response and fertility, including involvement in sperm maturation and function. Copy number variation (CNV) of {beta}-defensin genes is extensive across mammals, including cattle, with possible implications for reproductive traits and disease resistance. In this study, we comprehensively catalogue 55 {beta}-defensin genes in cattle. By constructing a phylogenetic tree to identify human orthologues and lineage-specific expansions, we identify 1:1 human orthologues for 35 bovine {beta}-defensins. We also discover extensive {beta}-defensin gene CNV across breeds, with DEFB103 in particular showing extensive multiallelic CNV. By comparing {beta}-defensin expression levels in testis from calves and adult bulls, we find that 14 {beta}-defensins, including DEFB103, increase in expression during sexual maturation. Analysis of {beta}-defensin gene expression levels in the caput of adult bull epididymis, and {beta}-defensin gene copy number, in 94 matched samples shows expression level of four {beta}-defensins are correlated with genomic copy number, including DEFB103. We therefore demonstrate extensive copy number variation in bovine {beta}-defensin genes, in particular DEFB103, with potential functional consequences for fertility.

genetics↗

bioRxiv2024

Genome-wide local ancestry and the functional consequences of admixture in African and European cattle populations

Bos taurus (taurine) and Bos indicus (indicine) cattle diverged at least 150,000 years ago and, since that time, substantial genomic differences have evolved between the two lineages. During the last two millennia, genetic exchange in Africa has resulted in a complex tapestry of taurine-indicine ancestry, with most cattle populations exhibiting varying levels of admixture. Similarly, there are several Southern European cattle populations that also show evidence for historical gene flow from indicine cattle, the highest levels of which are found in the Central Italian White breeds. Here we use two different software tools (MOSAIC and ELAI) for local ancestry inference (LAI) with genome-wide high-and low-density SNP array data sets in hybrid African and Italian cattle populations and obtained broadly similar results despite critical differences in the two LAI methodologies used. Our analyses identified genomic regions with elevated levels of retained or introgressed ancestry from the African taurine, European taurine, Asian indicine lineages. Functional enrichment of genes underlying these ancestry peaks highlighted biological processes relating to immunobiology and olfaction, some of which may relate to differing susceptibilities to infectious diseases, including bovine tuberculosis, East Coast fever, and tropical theileriosis. Notably, for retained African taurine ancestry in admixed trypanotolerant cattle we observed enrichment of genes associated with haemoglobin and oxygen transport. This may reflect positive selection of genomic variants that enhance control of severe anaemia, a debilitating feature of trypanosomiasis disease, which severely constrains cattle agriculture across much of sub-Saharan Africa.

genomics↗

bioRxiv2024

Integrative genomics sheds light on the immunobiology of tuberculosis in cattle

Mycobacterium bovis causes bovine tuberculosis (bTB), an infectious disease of cattle that poses a zoonotic threat to humans. Research has shown that bTB susceptibility is a heritable trait, and that the peripheral blood (PB) transcriptome is perturbed during bTB disease. Hitherto, no study has integrated PB transcriptomic, genomic and GWAS data to study bTB disease, and little is known about the genomic architecture underpinning the PB transcriptional response to M. bovis infection. Here, we perform transcriptome profiling of PB from 63 control and 60 confirmed M. bovis infected animals and detect 2,592 differently expressed genes that perturb multiple immune response pathways. Leveraging imputed genome-wide SNP data, we characterise thousands of cis- and trans-expression quantitative trait loci (eQTLs) and show that the PB transcriptome is substantially impacted by intrapopulation genomic variation. We integrate our gene expression data with summary statistics from multiple GWAS data sets for bTB susceptibility and perform the first transcriptome-wide association study (TWAS) in the context of tuberculosis disease. From this TWAS, we identify 136 functionally relevant genes (including RGS10, GBP4, TREML2, and RELT) and provide important new omics data for understanding the host response to mycobacterial infections that cause tuberculosis in mammals.

genomics↗

bioRxiv2023

Preferential differential gene expression within the WC1.1+ γδ T cell compartment in cattle naturally infected with Mycobacterium bovis.

Bovine tuberculosis (bTB), caused by infection with Mycobacterium bovis, continues to cause significant issues for the global agriculture industry as well as for human health. An incomplete understanding of the host immune response contributes to the challenges of control and eradication of this zoonotic disease. In this study, high-throughput bulk RNA sequencing (RNA-seq) was used to characterize differential gene expression in {gamma}{delta} T cells - a subgroup of T cells that bridge innate and adaptive immunity and have known anti-mycobacterial response mechanisms. {gamma}{delta} T cell subsets are classified based on expression of a pathogen-recognition receptor known as Workshop Cluster 1 (WC1) and we hypothesised that bTB disease may alter the phenotype and function of specific {gamma}{delta} T cell subsets. Peripheral blood was collected from naturally M. bovis-infected (positive for single intradermal comparative tuberculin test (SICTT) and IFN-{gamma} ELISA) and age- and sex-matched, non-infected control Holstein-Friesian cattle. {gamma}{delta} T subsets were isolated using fluorescence activated cell sorting (n = 10-12 per group) and high-quality RNA extracted from each purified lymphocyte subset (WC1.1+, WC1.2+, WC1- and {gamma}{delta}-) was used to generate transcriptomes using bulk RNA-seq (n = 6 per group, representing a total of 48 RNA-seq libraries). Relatively low numbers of differentially expressed genes (DEGs) were observed between most cell subsets; however, 189 genes were significantly differentially expressed in the M. bovis-infected compared to the control groups for the WC1.1+ {gamma}{delta} T cell compartment (absolute log2 FC [≥] 1.5 and FDR Padj. [≤] 0.1). The majority of these DEGs (168) were significantly increased in expression in cells from the bTB+ cattle and included genes encoding transcription factors (TBX21 and EOMES), chemokine receptors (CCR5 and CCR7), granzymes (GZMA, GZMM, and GZMH) and multiple killer cell immunoglobulin-like receptor (KIR) proteins indicating cytotoxic functions. Biological pathway overrepresentation analysis revealed enrichment of genes with multiple immune functions including cell activation, proliferation, chemotaxis, and cytotoxicity of lymphocytes. In conclusion, WC1.1+ {gamma}{delta} T cells have been proposed as major regulatory cell subset in cattle, and we provide evidence for preferential differential activation of this specific subset in cattle naturally infected with M. bovis.

immunology↗