Genome-Wide Detection of Copy Number Variations in Ethiopia Indigenous Cattle using Whole-Genome Sequencing

In Ethiopia, cattle are the most economically and socio-culturally important livestock species. The country is endowed with a very large (70 million heads) and phenotypically diverse cattle population comprising over 28 traditional breeds. Apart from point mutations, such as single nucleotide polymorphisms (SNPs) and short insertions and deletions (InDels), structural variation is an important source of genetic variation. Typically, structural variants are identified as copy number variations (CNVs) and are known to be associated with economically important traits such as milk yield, milk composition, residual feed intake, body size, meat quality, disease susceptibility, reproduction, and adaptation. Moreover, structural genomic alterations are also related to breed domestication and formation. Recently, many studies have proposed that CNV can be used to study population genetics and show lineage-specific selection signatures in goats, sheep, and cattle. Despite the increasing importance of CNVs in cattle genomic analysis, genetic studies of Ethiopian cattle breeds have been limited to polymorphic variants such as RAPD, SNP, or microsatellite markers, with no CNV-based studies reported up to date. Genome-wide detection of CNVs in Ethiopia's indigenous cattle populations offers new insights into the genomic architecture of mosaic cattle breeds and facilitates unraveling the consequences of evolutionary forces playing a role in shaping the genomes of these unique genetic resources. Ethiopian indigenous cattle inhabit various climatic zones, exhibit diverse phenotypes, and adapt to heterogeneous landscapes. Therefore, detection of CNVs in Ethiopian cattle will help to uncover genomic regions and genes associated with production, reproduction, health, adaptation, and conformation traits. Moreover, the host institution has studied CNVs for many years and possesses a unique database on CNVs identified for various local European cattle breeds as well as for the Holstein-Friesian breed, the most advanced dairy breed worldwide in terms of milk production. We believe that the possibility of comparing the landscape of CNVs across the two resources (i.e., Ethiopian local breeds, European local breeds, and the Holstein-Friesian breed) is an important milestone in the understanding of cattle genetic diversity and its association with phenotypic diversity. In particular, whole-blood samples will be collected from 140 individuals representing four Ethiopian indicine cattle breeds: zebu (Borna, Begait, Arsi, Ogaden, Ambo, Guraghe, and Mursi), zenga (Horro, Fogera, and Arado), sanga (Raya-Azebo, Anuak, and Afar), and a taurine cattle breed (Sheko). The breeds were selected based on their geographic distribution (high vs. low altitude) and economic importance in Ethiopia. For all individuals, the whole-genome DNA sequence will be obtained using the Illumina technology, and the sequence preprocessing and CNV detection pipeline implemented at the host institution will be used to detect CNVs. The pipeline has been extensively tested and validated on cattle genomes representing various breeds. The final step will be to quantify within- and between-breed variation in CNV lengths and numbers, followed by the identification of CNV regions unique to each breed. Finally, the genomic and possibly functional annotation of those regions, expressed by metabolic pathways and gene ontology terms, will be carried out, with the expectation of identifying functional elements underpinning phenotypic differences between the breeds.