مقایسه ژنومی دو نژاد گوسفند شیری کایاس و فریزارته از نظر شمار سلول‌های بدنی شیر با استفاده از روش‌های برآوردگر نااریب FST و hapFLK

The principal aim of the dairy sheep industry worldwide is to produce high-quality milk. Mastitis is an inflammatory disease in dairy animals that occurs in response to infectious factors and has substantial impacts on animal health, economic profitability. somatic cell count has been used as an indirect method to control mastitis. Genetic resistance to mastitis involves interconnected biological mechanisms that result from differences in the response to mastitis that activate and regulate different levels of the immune response. Over the last decade, interest in identifying genes or genomic regions targeted by selection has grown. Identifying selection signature can provide valuable insights into the genes or genomic regions that are or have been under selection pressure, which in turn leads to a better understanding of genotype-phenotype relationships. The aim of this study was to identify effective genes and genomic regions under positive selection in two sheep breeds using selection signature methods. For this purpose, FST and hapFLK analyzes were performed using the genome-wide single nucleotide polymorphisms (SNPs).
Material and Methods In this research, the information of 587 sheep of different from two breeds were used to identify genomic regions under selection associated with milk somatic cell count. To determine the genotype of the samples, Illumina ovine Bead Chip 50K were used. The genomic information of sheep breeds was extracted from Zenodo database. Quality control on genotyped samples was performed using PLINK v1.9. SNPs with a minor allele frequency (MAF) of less than 0.02 and those with a call rate of less than 0.97 were excluded. Additionally, individuals with more than 10% missing genotype data were removed. SNPs that did not conform to Hardy–Weinberg equilibrium (P value <10-6) were also eliminated. After these quality control measures, 41,673 SNPs from sheep SNP chip 50K from 587 sheeps remained for future analysis. To identify the signatures of selection, two statistical methods of FST and hapFLK were used under the software packages FST and hapFLK, respectively. Candidate genes were identified using Plink v1.9 software and the Illumina gene list in R by SNPs located in the 0.01 percentile of FST and hapFLK values. In addition, the latest published version of the animal genome database was used to define QTLs associated with economically important traits at identified loci. The GeneCards (http://www.genecards.org) and UniProtKB (http://www.uniprot.org) databases were also used to interpret the function of the obtained genes.
Results and Discussion: Using the FST approach, we identified nine genomic regions on chromosomes 2, 5, 7, 10, 11, 13 (two region), 17 and 22. The identified candidate genes associated with somatic cell count features in these genomic regions included IL11RA, CDC16, CARD14, BTRC, OTUD4, COL23A1, LACTB, and PRELID3B. Some of the genes located in the identified selection regions were associated with immune system, innate immune response, inflammation response, cancer disease and milk production. Some of these genes in the selected regions were consistent with previous studies. The investigation of reported QTLs showed that these regions are related to QTLs of important economic traits, including traits related to milk somatic cell count, Udder height and depth, clinical mastitis, bovine tuberculosis susceptibility and heat tolerance. Additionally, the results of hapFLK statistics in this research led to the identification of six genomic regions on chromosomes 3, 4, 5, 7, 10, and 13. The identified candidate genes associated with the somatic cell count in these genomic regions included FAM49A, CDK6 and DLGAP5. Bioinformatics analysis demonstrated that some of these genomic regions overlapped with known genes related to innate immune and various cancer.
Conclusion: Various/Different genes that emerged in these regions can be considered candidates for selection based on their function. By the way, various genes that were found within these regions can be considered as candidates under selection based on function. Most of the selected genes were found to be consistent with some previous studies and to be involved in production traits. However, to identify the exact function of the identified genes and QTLs, it is recommended to carry out more investigations. Also, these areas need to be confirmed in other independent studies with more samples. In general, the data of this research can be used in research related to genomic selection and genomic regions associated with mastitis in dairy sheeps., and additional reviews and evaluations to improve milk production in dairy sheep breeds.