Genome- wide analyses reveal population structure and identify candidate genes associated with tail fatness in local sheep from a semi- arid area

Under a climate change perspective, the genetic make-up of local livestock breeds showing adaptive traits should be explored and preserved as a priority. We used genotype data from the ovine 50 k Illumina BeadChip for assessing breed autozygosity based on runs of homozygosity (ROH) and fine-scale genetic structure and for detecting genomic regions under selection in 63 Tunis ia n sheep samples. The average genomic inbreeding coefficients based on ROH were estimated at 0.017, 0.021, and 0.024 for Barbarine (BAR, n = 26), Noire de Thibar (NDT, n = 23), and Queue fine de l'Ouest (QFO, n = 14) breeds, respectively. The genomic relationships among individuals based on identity by state (IBS) distance matrix highlighted a recent introgression of QFO into the BAR and a genetic differentiation of NDT samples, possibly explained by past introgression of Europe an gene pools. Genome-wide scan for ROH across breeds and within the BAR sample set identified an outstanding signal on chromosome 13 (46.58–49.61 Mbp). These results were confirmed using FST index, differentiating fat vs. thin-tailed individuals. Candidate genes under selection pressure (CDS2, PROKR1, and BMP2) were associated to lipid storage and probably preferentially selected in fat-tailed BAR animals. Our findings suggest paying more attention to preserve the genetic integrity and adaptive alleles of local sheep breeds

Genetic structure of Tunisian sheep breeds as inferred from genome-wide SNP markers

Assessing the status of genetic variability of native sheep breeds could provide important clues for research and policy makers to devise better strategies for the conservation and management of genetic resources. In this study, a genetic investigation of Tunisian sheep breeds using a genome-wide scan of approximately 50,000 SNPs was performed. To reconstruct genetic structure and relationships among four sheep breeds, 40 samples belonging to fat-tailed Barbarine, Queue Fine de l'Ouest, Noire de Thibar and D'Man breeds were genotyped using Illumina Ovine SNP50 BeadChip. Tunisian breeds averaged 96 % polymorphic loci with an expected heterozygosity (He = 0.36). Genetic analysis of relationship between breeds using Bayesian clustering, MDS and Neighbor-Network analysis, and estimation of FST genetic structure, highlighted the genetic differentiation of Noire de Thibar breed from the other local breeds, reflecting the effect of past events of introgression of European gene pool. The Queue Fine de l'Ouest breed showed a genetic heterogeneity and was close to Barbarine and D'Man breeds, as evidenced by MDS and the lowest level of differentiation with Barbarine breed (FST = 1.8 %). The D'Man breed shared a considerable gene flow with the thin-tailed Queue Fine de l'Ouest breed. Possible factors explaining the genetic patterns observed, such as considerable gene flow probably due to anthropogenic activities in the light of population management and conservation programs

The emerging roles of sphingosine 1-phosphate and SphK1 in cancer resistance: a promising therapeutic target

Abstract Cancer chemoresistance is a problematic dilemma that significantly restrains numerous cancer management protocols. It can promote cancer recurrence, spreading of cancer, and finally, mortality. Accordingly, enhancing the responsiveness of cancer cells towards chemotherapies could be a vital approach to overcoming cancer chemoresistance. Tumour cells express a high level of sphingosine kinase-1 (SphK1), which acts as a protooncogenic factor and is responsible for the synthesis of sphingosine-1 phosphate (S1P). S1P is released through a Human ATP-binding cassette (ABC) transporter to interact with other phosphosphingolipids components in the interstitial fluid in the tumor microenvironment (TME), provoking communication, progression, invasion, and tumor metastasis. Also, S1P is associated with several impacts, including anti-apoptotic behavior, metastasis, mesenchymal transition (EMT), angiogenesis, and chemotherapy resistance. Recent reports addressed high levels of S1P in several carcinomas, including ovarian, prostate, colorectal, breast, and HCC. Therefore, targeting the S1P/SphK signaling pathway is an emerging therapeutic approach to efficiently attenuate chemoresistance. In this review, we comprehensively discussed S1P functions, metabolism, transport, and signaling. Also, through a bioinformatic framework, we pointed out the alterations of SphK1 gene expression within different cancers with their impact on patient survival, and we demonstrated the protein–protein network of SphK1, elaborating its sparse roles. Furthermore, we made emphasis on different machineries of cancer resistance and the tight link with S1P. We evaluated all publicly available SphK1 inhibitors and their inhibition activity using molecular docking and how SphK1 inhibitors reduce the production of S1P and might reduce chemoresistance, an approach that might be vital in the course of cancer treatment and prognosis. Graphical Abstrac