The pattern of runs of homozygosity, heterozygosity and genomic inbreeding in the population of sensitive and resistant sheep to footrot

Document Type : Research Paper

Authors

• Fatemeh Ebrahimi ¹
• Mohsen Gholizadeh ²
• Ayoub Farhadi ¹

¹ Department of Animal Science, Faculty of Animal Science and Fisheries, Sari Agricultural Sciences and Natural Resources University, Sari-Iran

² Department of Animal Science, Faculty of Animal Science and Fisheries, Sari Agricultural Sciences and Natural Resources University, SARI-IRAN

Abstract

Keywords

• runs of homozygosity
• runs of heterozygosity
• genomic inbreeding coefficient
• Alpine sheep

Main Subjects

• Animal Breeding and Genetics

Extended Abstract

Introduction

  The present study aimed to estimate the genomic inbreeding coefficient based on runs of homozygosity (F_ROH), to identify runs of homozygosity (ROH), and heterozygosity (ROHet), and to map selection signatures in the relevant genomic regions in Swiss white Alpine sheep.

Materials and Methods

  Swiss White Alpine sheep were genotyped using 600K single nucleotide polymorphism (SNP) arrays, and a case-control study was conducted in the form of 154 healthy controls versus 76 severe cases. For the quality control, SNPs that could not be assigned a position on the ARS-UI_Ramb_v2.0, and duplicate SNPs were discarded from further analysis. Individuals with missing genotypes larger than 0.05 were excluded. Also, SNPs with a call rate less than 0.05, a minor allele frequency (MAF) less than 0.05, and a significant deviation from Hardy-Weinberg equilibrium (HWE) (P < 1×10^-6) were eliminated. 229 sheep and, a total of 461195 SNPs and 459100 SNPs, respectively, in the healthy and case groups met the desired criteria and were subsequently included in the final analysis.

Results and discussion

  F_ROH estimates ranged from 0.03 to 0.13, with an average of 0.09 for the entire genome. Chromosome 2 (85.5% by 65 counts) and 1 (84.3% by 129 counts) had the highest F_ROH percentage and chromosome 8 (0.65% by 1 count) had the lowest F_ROH percentage. In the healthy population, 68959 ROH and 731026 ROHet were observed, while in the case population, 34569 ROH and 364125 ROHet were detected. Based on the run lengths for the ROH and ROHet, five classes have been considered for each population (0-6, 6-12,12-24, 24-48, and >48 Mbp). Using ROH, the highest percentage of observations for healthy population was detected for the 0-6 Mbp class (98.79%,) and the lowest percentage of observations was for the class >48 Mbp, (0.01%). On the other hand, the highest percentage of observations in the case population was for the class 0-6 Mbp (98.81%), and the lowest percentage of observations was for the class 24-48 Mbp (0.01%). In the 0-6 Mbp class for the healthy population, there were 68128 ROH with an average size of 0.671 Mbp. For the case population, there were 34157 ROH with an average size of 0.680 Mbp. On the other hand, in the >48 Mbp class, the average size for the 7 ROH in the healthy population was 97.212 Mbp, and in the case population was 103.804 Mbp. For both healthy and severely case populations, chromosomes 1 and 26 had the highest and lowest number of ROH, respectively. The highest and lowest number of ROHet for both healthy and case populations were on chromosomes 1 and 24, respectively. There were 17 and 10 representative regions in ROH islands with frequencies >70% in the healthy and case populations, respectively. By ROHet, 6 and 19 regions presented frequencies of >60% in the healthy and the case populations, respectively. Using ROH analysis, the genes identified for healthy animals were distributed on chromosomes 1, 2, 8, 13, 15, 18, and 22, and for case animals on chromosomes 2, 4, 6, 8, 13, and 18. According to ROHet analysis, 527 genes had a known function and were distributed on chromosome 24 for both healthy and diseased populations. In total, 553 candidate genes were identified using ROH and ROHet analyses within the selection signatures. ROH islands had genes associated with reproductive traits (FSIP2), production traits (POPDC3), immune system (RAB39A), adaptation (PTPN9, LDB1), milk production (SIN3A), mastitis (MAN2C1) and disease resistance (COMMD4). ROHet islands had genes related to the immune system (MAPK8IP, ADCY9, IL32), inflammatory response (TNFRSF12A), adaptation (CLCN7, E4F1, CLDN9, HMOX2, ZNF598, PAQR4), body size (TRAF7, SEC14L5), body weight and body structure traits (GLIS2, VASN, TFAP4), litter size (NUDT16L1, ANKS3, ZNF500), milk traits (AMDHD2), calf birth weight (ZNF75A), lactation continuity (EEF2KMT, ALG1, SEC14L5, RBFOX1, NAGPA) ), growth traits (SOX8, SSTR5, IGFALS, NPW) and meat quality (RPL3L, SLC9A3R2). Using the ROH method, some of these genes identified in the healthy population were also identified in the case population such as FSIP2 on chromosome 2, POPDC3 on chromosome 8, and PTPN9, SIN3A, MAN2C1, and COMMD4 on chromosome 18. By the ROHet method, some of the genes identified in the healthy population in this study were consistent with the candidate genes reported in previous studies. including TEKT4, MGRN1, ROGDI, GLYR1, UBN1, PPL, UNKL, CCDC154, IFT140, DNAJA3, NMRAL1, HCFC1R1, THOC6, CLDN9, CLDN6, TNFRSF12A, BICDL2 and MMP25, MAPK8IP3, ADCY9, IL32, TNFRSF12A, CLCN7, E4F1, CLDN9, ZNF598, HMOX2, PAQR4, PTX4, TRAF7, SEC14L5, AMDHD2, ZNF75A, NAA60, NLRC3, TFAP4, GLIS2, VASN, NUDT16L1, ANKS3, ZNF500, EEF2KMT, ALG1, SEC14L5, RBFOX1, NAGPA, ADRA1D, SOX8 , SSTR5, IGFALS, NPW, RPL3L, SLC9A3R2 and RNF151, which were all located on chromosome 24. In the case population, GNG1 was detected. The results of the gene ontology (GO) showed that the most enriched terms identified in cellular components, molecular function, and KEGG pathway were related to the Apicolateral plasma membrane, Metal ion binding, and Fanconi anemia pathway, respectively.

Conclusion

  The results of the present study revealed that the healthy population of Swiss White Alpine sheep exhibited ancient inbreeding, a greater number of ROH and ROHet, and a higher average length of ROHet compared to the case population. The number of islands detected using the ROH was higher in the healthy population compared to the case population, whereas the ROHet method identified more islands in the case population than in the healthy population. According to the comparison made between two groups of case and healthy sheep, this research provides a new insight in understanding the mechanism of resistance to footrot in sheep.

Author Contributions

Conceptualization, M.G.; methodology, M.G. and F.E.; software, M.G. and F.E.; formal analysis, M.G. and F.E.; writing—original draft preparation, F.E.; writing—review and editing, M.G. and A.F.; supervision, M.G. and A.F. All authors have read and agreed to the published version of the manuscript.

Data Availability Statement

The data that support the findings of this study can be retrieved at https://www.animalgenome.org/repository/pub/BERN2017.0821/.

Acknowledgements

We used genotyping data retrieved at public database (https://www.animalgenome). The authors are grateful for access to the data.

Ethical considerations

The study was approved by the Ethics Committee of the University of Sari Agricultural Sciences and Natural Resources University (Ethical code: SANRU.1403.03). The authors avoided data fabrication, falsification, plagiarism, and misconduct.