Parental genomes segregate into different blastomeres during multipolar zygotic divisions leading to mixoploid and chimeric blastocysts

The zygotic division enables two haploid genomes to segregate into two biparental diploid blastomeres. This fundamental tenet was challenged by the observation that blastomeres with different genome ploidy or parental genotypes can coexist within individual embryos. We hypothesized that whole parental genomes can segregate into distinct blastomere lineages during the first division through "heterogoneic division". Here, we map the genomic landscape of 82 blastomeres from 25 embryos that underwent multipolar zygotic division. The coexistence of androgenetic and diploid or polyploid blastomeres with or without anuclear blastomeres, and androgenetic and gynogenetic blastomeres within the same embryo proofs the existence of heterogoneic division. We deduced distinct segregation mechanisms and demonstrate these genome-wide segregation errors to persist to the blastocyst stage in both human and cattle. Genome-wide zygotic segregation errors contribute to the high incidence of embryonic arrest and provide an overarching paradigm for the development of mixoploid and chimeric individuals and moles.

Genome-Wide DNA Methylation and Hydroxymethylation Changes Revealed Epigenetic Regulation of Neuromodulation and Myelination in Yak Hypothalamus

Both 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) are important epigenetic modifications in neurodevelopment. However, there is little research examining the genome-wide patterns of 5mC and 5hmC in brain regions of animals under natural high-altitude conditions. We used oxidative reduced representation bisulfite sequencing (oxRRBS) to determine the 5mC and 5hmC sites in the brain, brainstem, cerebellum, and hypothalamus of yak and cattle. We reported the first map of genome-wide DNA methylation and hydroxymethylation in the brain, brainstem, cerebellum, and hypothalamus of yak (living at high altitudes) and cattle. Overall, we found striking differences in 5mC and 5hmC between the hypothalamus and other brain regions in both yak and cattle. Genome-wide profiling revealed that 5mC level decreased and 5hmC level increased in the hypothalamus than in other regions. Furthermore, we identified differentially methylated regions (DMRs) and differentially hydroxymethylated regions (DhMRs), most of which overlapped with each other. Interestingly, transcriptome results for these brain regions also showed distinctive gene levels in the hypothalamus. Finally, differentially expressed genes (DEGs) regulated by DMRs and DhMRs may play important roles in neuromodulation and myelination. Overall, our results suggested that mediation of 5mC and 5hmC on epigenetic regulation may broadly impact the development of hypothalamus and its biological functions.

Towards deciphering the structure of long homozygous stretches in cattle genome

p-to-day there is no as universally accepted software tool and threshold parameters to identify runs of homozygosity ( ROH ). The relative position of POH segments in the cattle genome has not been studied extensively. Specific objective of this study was to evaluate the effect of allowed missing and heterozygous SNPs in ROH on their number, on the estimate of inbreeding level, and on structure of ROH segments in the cattle genome. In this study 371 Holsteinized cows from six herds were genotyped with BovineSNP50 array. To identify ROH, the consecutive and sliding runs were carried out with detectRUNS and Plink tools. Neither effect was shown for missing SNPs genotype calls. Allowing even one heterozygous SNP resulted in significant bias of ROH data. Furthermore, the sliding runs identified less ROH than consecutive runs. The mean coefficient of inbreeding across herds was 0.111 ± 0.003 and 0.104 ± 0.003 based on consecutive and sliding runs respectively. It was shown how, using the heterozygous SNPs in ROH, may be possible to derive a distribution of ROH segments in the cow genome. We suggested it was similar to normal distribution. Furthermore, frequency of ROH in the chromosomes did not depend on their length. Of 29 chromosomes, the most abundant with ROH were BTA 14, BTA 7, and BTA 18. The result of this study confirmed more accurately identification of ROH with consecutive runs, uneven their distribution in the cattle genome, significant bias of the data due to allowing heterozygous SNPs in ROH.

Production of hornless dairy cattle from genome-edited blastocysts

Cattle of polled phenotype is convenient for breeders, as it decreases the risk of animals being hurt and ensures safety of workers. We developed the system for editing cattle genome using CRISPR/Cas9 which will allow production of animals with polled phenotype genetically based on any cattle breed without changing its main phenotypic traits.

Construction the first gene co-expression-based interactome in cattle

Integrating genomic information into cattle breeding is an important approach to exploring the molecular mechanism for complex traits related to diary and meat production. To assist with genomic-based selection, a reference map of interactome is needed to fully understand genotype-phenotype relationships. To this end we constructed a co-expression analysis of 92 tissues and this represents the first systematic exploration of gene-gene relationship in cattle. By using robust WGCNA (Weighted Gene Correlation Network Analysis), we described the gene co-expression network of 13,405 protein-coding genes from the cattle genome. Using the 5,000 genes with majority variations in expression across 92 tissues, we compiled a network with 72,306 co-associations and that provides functional insights into thousands of poorly characterized proteins. Further module identifications found 55 highly organized functional clusters representing diverse cellular activities. To demonstrate the re-use of our interaction for functional genomics analysis, we extracted a sub-network associated with DNA binding genes in cattle. The subnetwork was enriched within regulation of transcription from RNA polymerase II promoter representing central cellular functions. In addition, we identified 28 novel linker genes associated with more than 100 DNA binding genes. Our WGCNA-based co-expression network reconstruction will be a valuable resource for exploring the molecular mechanisms of incompletely characterized proteins and for elucidating larger-scale patterns of functional modulization in the cattle genome.

Construction the first gene co-expression-based interactome in cattle

Integrating genomic information into cattle breeding is an important approach to exploring the molecular mechanism for complex traits related to diary and meat production. To assist with genomic-based selection, a reference map of interactome is needed to fully understand genotype-phenotype relationships. To this end we constructed a co-expression analysis of 92 tissues and this represents the first systematic exploration of gene-gene relationship in cattle. By using robust WGCNA (Weighted Gene Correlation Network Analysis), we described the gene co-expression network of 13,405 protein-coding genes from the cattle genome. Using the 5,000 genes with majority variations in expression across 92 tissues, we compiled a network with 72,306 co-associations and that provides functional insights into thousands of poorly characterized proteins. Further module identifications found 55 highly organized functional clusters representing diverse cellular activities. To demonstrate the re-use of our interaction for functional genomics analysis, we extracted a sub-network associated with DNA binding genes in cattle. The subnetwork was enriched within regulation of transcription from RNA polymerase II promoter representing central cellular functions. In addition, we identified 28 novel linker genes associated with more than 100 DNA binding genes. Our WGCNA-based co-expression network reconstruction will be a valuable resource for exploring the molecular mechanisms of incompletely characterized proteins and for elucidating larger-scale patterns of functional modulization in the cattle genome.