👤 Imtiaz A S Randhawa

Thousands of years of natural and artificial selection since the domestication of the horse has shaped the distinctive genomes of Chinese Mongolian horse populations. Consequently, genomic signatures of selection can provide insights into the human-mediated selection history of specific traits and evolutionary adaptation to diverse environments. Here, we used genome-wide SNPs from five distinct Chinese Mongolian horse populations to identify genomic regions under selection for the population-specific traits, gait, black coat colour, and hoof quality. Other global breeds were used to identify regional-specific signatures of selection. We first identified the most significant selection peak for the Wushen horse in the region on ECA23 harbouring DMRT3, the major gene for gait. We detected selection signatures encompassing several genes in the Baicha Iron Hoof horse that represent good biological candidates for hoof health, including the CSPG4, PEAK1, EXPH5, WWP2 and HAS3 genes. In addition, an analysis of regional subgroups (Asian compared to European) identified a single locus on ECA3 containing the ZFPM1 gene that is a marker of selection for the major domestication event leading to the DOM2 horse clade. Genomic variation at these loci in the Baicha Iron Hoof may be leveraged in other horse populations to identify animals with superior hoof health or those at risk of hoof-related pathologies. The overlap between the selection signature in Asian horses with the DOM2 selection peak raises questions about the nature of horse domestication events, which may have involved a prehistoric clade other than DOM2 that has not yet been identified. Show less

Though cholesterol accumulation is an established hallmark of a tumor cell, the relationship between the two is still not clear. Previously, we identified 3-Hydroxy-3-Methylglutaryl-CoA Reductase (HMGCR), Sterol Regulatory Element BindingTranscription Factor 2 (SREBF2), Nuclear Receptor Subfamily 1 Group H Member 3 (NR1H3), and Nuclear Receptor Subfamily 1 Group H Member 2 (NR1H2) as the key cholesterol homeostasis genes involved in colorectal cancer (CRC). In the present study, we aimed to identify microRNAs regulating these key genes in CRC. miR-18a-5p, miR-144-3p, and miR-663b were selected as the miRNAs targeting NR1H2, HMGCR, and SREBF2, respectively, based on the bioinformatic prediction tools and literature review. Their expression was evaluated in the local and The Cancer Genome Atlas (TCGA) cohorts. Receiver Operating Characteristic Curves and Kaplan Meier analysis were performed to elucidate their diagnostic and prognostic potential. Pearson or Spearman's correlations were used to evaluate the relationship between miRNAs and their target genes. Protein-protein interaction networks and Gene Ontology analyses were performed to investigate the potential molecular mechanism of these miRNAs. Deregulated expression of miR-18a-5p, miR-144-3p, and miR-663b was associated with various clinicopathological features. miR-18a-5p exhibited an inverse correlation with NR1H2. miR-18a-5p and miR-144-3p also had a significant direct correlation with miR-33a-5p, an important modulator of cholesterol homeostasis. These miRNAs also exhibited high centrality in the mirna-protein interaction network. miR-144-3p and miR-663b exhibited the potential to be used as diagnostic biomarkers. miR-18a-5p and miR-144-3p exhibited the potential to modulate cholesterol homeostasis in CRC. miR-663b is an interesting candidate in CRC pathophysiology. Show less