Identification and analysis of polymorphisms in miRNA genes and associated targets in Bos taurus and Bos primigenius for genomic selection in cattle
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Cattle production is of high economic importance to agriculture in Ireland. For more than a decade, significant effort focused on the improvement of the selection of economically important traits in beef and dairy breeds. The application of genomics technologies has greatly improved our ability to detect genetic markers related to important traits. This study identified novel Single nucleotide polymorphisms (SNP) between aurochs and cattle in micro-RNAs (miRNA) and miRNA-binding sites. This study also identified SNPs in miRNAs then SNPs in miRNA 3¢ untranslated region (3¢UTR) targets between cattle breeds. One polymorphic miRNA gene active region and 1606 polymorphic miRNA target genes have been identified between aurochs and modern cattle. These polymorphic miRNA and miRNA-binding sites, which arose since domestication, showed associations with important functions such as neurodevelopment and food metabolism that could have been selected by humans. These polymorphisms may represent potential DNA based biomarkers for improving these specific traits in cattle. The screening of SNPs in miRNA between cattle breeds identified 89 miRNAs, which have different sequences compared to the reference miRNAs. Out of these 89, 25 had SNPs in their miRNA binding region. The analysis of change of targets and their related function highlighted three candidates of interest: mir-2419, mir-449b and mir- 29e. These three candidate miRNAs have polymorphisms, which modify their binding properties to target genes, related to milk production. Some of these miRNA SNPs have been included into an association study on 914 Holsteins for which the traits of their 50,000 daughters had been quantified. However, only one SNP has been weakly associated with milk traits. This SNP is located in mir-2419-3p and is weakly associated with rear udder height. The screening of polymorphisms in 3' UTR of cattle breeds allowed the identification of 726 genes containing 1097 different SNPs in their miRNA-binding sites. The analysis of these genes showed links with various functions of economic importance in cattle. The SNPs identified in the 3' UTRs of TARBP1, GUCA2B and CYP3A5 were associated with milk production traits in a candidate genes association study on Holstein breed. Furthermore, a SNP in the 3' UTR of PRKAG1 was identified, which created a change in a miRNA-binding site. This could have implications for milk xi Abstract production, considering that PRKAG1 was previously shown to be associated with this trait. Moreover, three other polymorphic miRNA-binding target genes, BTS2B, GIMAP1 and LAMTOR2 have been related to immune response in cattle. These SNPs identified in miRNA-binding sites warrant further investigation. Analysis of miRNA-related polymorphisms in the aurochs ancestor and the commonly used beef and dairy breeds of cattle facilitated the discovery of candidate DNA markers useful for the better understanding and the improvement of traits in beef and dairy breeds. These novel SNPs could, (following validation on very large population of cattle) contribute to the national genome selection of beef and dairy breeding programme. These SNPs have been included on previous version of the International Dairy and Beef SNP-Chip (1 and 2) as well as the latest version (v3), used for the national genomic evaluations of beef and dairy herds in Ireland.