Biology subjects

Vander Jagt, C. J.

Publications and source records attributed to Vander Jagt, C. J..

4 recordsLinked to original sources

bioRxiv2020

Demographic history, cold adaptation, and recent NRAP recurrent convergent evolution at amino acid residue 100 in the world northernmost cattle from Russia

Native cattle breeds represent an important cultural heritage. They are a reservoir of genetic variation useful for properly responding to agriculture needs in light of ongoing climate changes. Evolutionary processes that occur in response to extreme environmental conditions could also be better understood using adapted local populations. Herein, different evolutionary histories for two of the world northernmost native cattle breeds from Russia were investigated. They highlighted Kholmogory as a typical taurine cattle, while Yakut cattle separated from European taurines ~5,000 years ago and contain numerous ancestral and some novel genetic variants allowing their adaptation to harsh conditions of living above the Polar Circle. Scans for selection signatures pointed to several common gene pathways related to adaptation to harsh climates in both breeds. But genes affected by selection from these pathways were mostly different. A Yakut cattle breed-specific missense mutation, H100Q, in a highly conserved NRAP gene, represents a unique example of a young amino acid residue convergent change shared with at least 16 species of hibernating/cold-adapted mammals from nine distinct phylogenetic orders. This suggests a convergent evolution event along the mammalian phylogenetic tree and fast fixation in a single isolated cattle population exposed to a harsh climate.

genomics↗

bioRxiv2019

Genome-wide profiling of microRNAs and prediction of mRNA targets in 17 bovine tissues

MicroRNAs regulate many eukaryotic biological processes in a temporal- and spatial-specific manner. Yet in cattle it is not fully known which microRNAs are expressed in each tissue, which genes they regulate, or which sites a given microRNA bind to within messenger RNAs. An improved annotation of tissue-specific microRNA network may in the future assist with the identification of causal variants affecting complex traits. Here, we report findings from analysing short RNA sequence from 17 tissues from a single lactating dairy cow. Using miRDeep2, we identified 699 expressed mature microRNA sequences. Using TargetScan, known (60%) and novel (40%) microRNAs were predicted to interact with 780,481 sites in bovine messenger RNAs homologous with human. Putative interactions between microRNA families and targets were significantly enriched for interactions from previous experimental and computational identification. Characterizing features of microRNAs and targets, we showed that (1) mature microRNAs derived from different arms of the same precursor targeted different genes in different tissues; (2) miRNA target sites preferentially occurred within gene regions marked with active histone modification; (3) variants within microRNAs and targets had lower allele frequencies than variants across the genome, as identified from 65 million whole genome sequence variants; (4) no significant correlation was found between the abundance of microRNAs and messenger RNAs differentially expressed in the same tissue; (5) microRNAs and target sites werent significantly associated with allelic imbalance of gene targets. This study contributes to the goals of Functional Annotation of Animal Genomes consortium to improve the annotation of genomes of domestic animals.

bioinformatics↗

bioRxiv2018

Putative bovine topological association domains and CTCF binding motifs can reduce the search space for causative regulatory variants of complex traits

BackgroundTopological association domains (TADs) are chromosomal domains characterised by frequent internal DNA-DNA interactions. The transcription factor CTCF binds to conserved DNA sequence patterns called CTCF binding motifs to either prohibit or facilitate chromosomal interactions. TADs and CTCF binding motifs control gene expression, but they are not yet well defined in the bovine genome. In this paper, we sought to improve the annotation of bovine TADs and CTCF binding motifs, and assess whether the new annotation can reduce the search space for cis-regulatory variants.\n\nResultsWe used genomic synteny to map TADs and CTCF binding motifs from humans, mice, dogs and macaques to the bovine genome. We found that our mapped TADs exhibited the same hallmark properties of those sourced from experimental data, such as housekeeping gene, tRNA genes, CTCF binding motifs, SINEs, H3K4me3 and H3K27ac. Then we showed that runs of genes with the same pattern of allele-specific expression (ASE) (either favouring paternal or maternal allele) were often located in the same TAD or between the same conserved CTCF binding motifs. Analyses of variance showed that when averaged across all bovine tissues tested, TADs explained 14% of ASE variation (standard deviation, SD: 0.056), while CTCF explained 27% (SD: 0.078). Furthermore, we showed that the quantitative trait loci (QTLs) associated with gene expression variation (eQTLs) or ASE variation (aseQTLs), which were identified from mRNA transcripts from 141 lactating cows white blood and milk cells, were highly enriched at putative bovine CTCF binding motifs. The most significant aseQTL and eQTL for each genic target were located within the same TAD as the gene more often than expected (Chi-Squared test P-value [≤] 0.001).\n\nConclusionsOur results suggest that genomic synteny can be used to functionally annotate conserved transcriptional components, and provides a tool to reduce the search space for causative regulatory variants in the bovine genome.

genomics↗

bioRxiv2017

Genome variants altering gene splicing in bovine are extensively shared between tissues

BackgroundMammalian phenotypes are shaped by numerous genome variants, many of which may regulate gene transcription or RNA splicing. To identify variants with regulatory functions in cattle, an important economic and model species, we used sequence variants to map a type of expression quantitative trait loci (expression QTLs) that are associated with variations in the RNA splicing, i.e., sQTLs. To further the understanding of regulatory variants, sQTLs were compare with other two types of expression QTLs, 1) variants associated with variations in gene expression, i.e., geQTLs and 2) variants associated with variations in exon expression, i.e., eeQTLs, in different tissues.\n\nResultsUsing whole genome and RNA sequence data from four tissues of over 200 cattle, sQTLs identified using exon inclusion ratios were verified by matching their effects on adjacent intron excision ratios. sQTLs contained the highest percentage of variants that are within the intronic region of genes and contained the lowest percentage of variants that are within intergenic regions, compared to eeQTLs and geQTLs. Many geQTLs and sQTLs are also detected as eeQTLs. Many expression QTLs, including sQTLs, were significant in all four tissues and had a similar effect in each tissue. To verify such expression QTL sharing between tissues, variants surrounding ({+/-}1Mb) the exon or gene were used to build local genomic relationship matrices (LGRM) and estimated genetic correlations between tissues. For many exons, the splicing and expression level was determined by the same cis additive genetic variance in different tissues. Thus, an effective but simple-to-implement meta-analysis combining information from three tissues is introduced to increase power to detect and validate sQTLs. sQTLs and eeQTLs together were more enriched for variants associated with cattle complex traits, compared to geQTLs. Several putative causal mutations were identified, including an sQTL at Chr6:87392580 within the 5th exon of kappa casein (CSN3) associated with milk production traits.\n\nConclusionsUsing novel analytical approaches, we report the first identification of numerous bovine sQTLs which are extensively shared between multiple tissue types. The significant overlaps between bovine sQTLs and complex traits QTL highlight the contribution of regulatory mutations to phenotypic variations.

genomics↗