Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1101073 | ENA |
REPOSITORIES: ENA
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Project description:Structural and functional impacts of copy number variations (CNVs) on livestock genomes are not yet well understood. In this study, we have identified 1853 CNV regions (CNVRs) using population-scale sequencing data generated from 75 cattle of 8 breeds (Holstein, Angus, Jersey, Limousin, Romagnola, Brahman, Gir and Nelore). Individual genome sequence coverage ranged from 4 to 30 fold, with a mean of 11.8 fold. A total of 3.1% (87.5 Mb) of the cattle genome is predicted to be copy number variable, representing a substantial increase over the previous estimates (~2%). This dataset was highly correlated with array CGH data (r2 = 0.761) and was validated to be accurate with an estimated 12% false positive rate and a 19% false negative rate based on qPCR and array CGH, respectively. Hundreds of CNVs were found to be either breed specific or differentially variable across breeds, including the RICTOR gene in dairy breeds and the PNPLA3 gene in the beef breeds. In contrast, clusters of the PRP and PAG genes are duplicated in all sequenced animals, implicating that subfunctionalization, neofunctionalization or overdominance play a role in diversifying these fertility related genes. Further population-genetic analyses based on CNVs revealed the population structures of these taurine and indicine breeds and uncovered hundreds of positively selected CNV candidates near important functional genes. These CNV results provide a new glimpse of diverse selections during cattle speciation, domestication, breed formation, and recent genetic improvement.
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Project description:Animal African trypanosomosis, caused by blood protozoan parasites transmitted mainly by tsetse flies, represents a major constraint for millions of cattle in sub-Saharan Africa. Exposed cattle include West African taurine breeds called trypanotolerant according to their ability to control parasite development and to survive and grow in enzootic areas, and indicine breeds that are trypanosusceptible to the disease. Until now the genetic basis of trypanotolerance remains unclear. Here, we improved knowledge in the biological processes involved in trypanotolerance by identifying bovine genes differentially expressed during an experimental infection by Trypanosoma congolense and their biological functions. To this end, whole blood genome-wide transcriptome profiling by RNA sequencing was performed on five West African cattle breeds, three trypanotolerant taurine breeds (N'Dama, Lagune and Baoulé), one susceptible zebu (Zebu Fulani) and one African taurine x zebu admixed breed (Borgou), at four dates, one before and three during infection. As expected, infection had a major impact on cattle blood transcriptome whatever the breed. The functional analysis of differentially expressed genes over time in each breed confirmed an early activation of the innate immune response, followed by an activation of the humoral response and an inhibition of T cells functions at the chronic stage of infection. More importantly, we highlighted overlooked features, as a strong disturbance in host metabolism and cell production energy that differentiate trypantolerant and trypanosusceptible breeds. N'Dama breed showed the earliest regulation of immune response, associated with a strong activation of cellular energy production, this last feature being also shared with Lagune, and to a lesser extent with Baoulé. Susceptible Zebu Fulani breed was distinguished from other breeds by the strongest modification in lipid metabolism regulation. Lastly, basal differences in gene expression reflected the structuration of cattle genetic diversity, and could have consequences on the tolerant or susceptible phenotype. Overall, it would be of value to deeper investigate interactions between immune response and cell metabolism that likely impact disease outcome.
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Project description:Genomic structural variation is an important and abundant source of genetic and phenotypic variation. Here we describe the first systematic and genome-wide analysis of copy number variations (CNVs) in modern domesticated cattle using array comparative genomic hybridization (array CGH), quantitative PCR (qPCR) and fluorescent in situ hybridization (FISH). The array CGH panel included 90 animals from 11 Bos taurus, 3 Bos indicus and 3 composite breeds for beef, dairy or dual purpose. We identified over 200 candidate CNV regions (CNVRs) in total and 177 within known chromosomes, which harbor or are adjacent to gains or losses. These 177 high-confidence CNVRs cover 28.1 mega bases or ~1.07% of the genome. Over 50% of the CNVRs (89/177) were found in multiple animals or breeds and analysis revealed breed-specific frequency differences and reflected aspects of the known ancestry of these cattle breeds. Selected CNVs were further validated by independent methods using qPCR and FISH. Approximately 67% of the CNVRs (119/177) completely or partially span cattle genes and 61% of the CNVRs (108/177) directly overlap with segmental duplications. The CNVRs span about 400 annotated cattle genes that are significantly enriched for specific biological functions such as immunity, lactation, reproduction and rumination. Multiple gene families, including ULBP, have gone through ruminant lineage-specific gene amplification. We detected and confirmed marked differences in their CNV frequencies across diverse breeds, indicating that some cattle CNVs are likely to arise independently in breeds and contribute to breed differences. Our results provide a valuable resource beyond microsatellites and single nucleotide polymorphisms to explore the full dimension of genetic variability for future cattle genomic research.
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