selection signature

One of the principal and challenging animal studies in population genetics is to identify the signs of selection to improve economic traits and reduce diseases. Johne's disease is an incurable chronic bacterial infection that primarily affects the lower parts of the small intestine of ruminants, although its pathology and symptoms vary among species. The economic consequences of Johne's disease include reduced production, loss of genetic value, increased sensitivity to other diseases, increased interval between calving, weight loss, reduced carcass value, reduced fertility (due to reduced serum progesterone formation and corpus luteum), decreased quality and quantity of milk (decreasing fat and protein and increasing somatic cells in milk), and premature elimination. According to the results of new research, this bacterium may be a zoonotic pathogen that plays a role in causing Crohn's disease (a chronic inflammatory bowel disease (IBD)) in humans. Even after milk pasteurization, this pathogen remains alive and is therefore a threat to the health of society. This disease is one of the main diseases economically and one of the most prevalent diseases, causing great economic damage to the livestock industry worldwide. In this study, an extensive genome-wide scan was performed using single nucleotide polymorphisms (SNPs) to identify the signs of selection between populations of Holstein cows affected by Johne's disease and healthy animals.

In this study, 145 Holstein cows of the Feka cattle farm in Isfahan were genotyped based on Illumina 30K chips. Cows were grouped into two sick and healthy groups, with 45 and 100 cows, respectively. Quality control indicators included the animal read rate (mind), SNP read rate (geno), rare allele frequency (MAF), and Hardy-Weinberg equilibrium. To identify important metabolic pathways, ClueGo (version 2.5.6) was used in Cytoscape software, which provides biological interpretations of genes. In this study, two statistics, iHS and RSB, were used to identify the signs of selection.

Using iHS statistics, 63 and 70 genes were identified in the diseased and healthy populations of Holstein cows, respectively. The important genes identified by iHS statistics included HCN2, DOCK4, ITGA8, and STAG1 in the patient population, and CAV2, CNTNAP4, MIB1, and TTC23 in the healthy population. After examining the selected regions, 39 and 53 genes were identified in the diseased and healthy populations of Holstein cows with RSB statistics. The important genes identified by RSB statistics included GRID2, PPIP5K2, and CTNNA2 in the patient population, and  DOCK1, PCDH9, and AK1 in the healthy population.

In the present study, the results of the iHS statistics showed that 84 and 96 genomic regions were under selection in the healthy and patient populations, as well as 152 and 129 genomic regions in the healthy and patient populations using the RSB statistics. Most of the genes identified in this study were related to immunity, cancer, bacterial invasion of cells, cell aging, cell response, growth, and cell adhesion, which are among the important biological traits and characteristics of living organisms. By identifying possible candidate genes related to and resistance to Johne's disease in cattle, this information can be used in breeding programs (selection to reduce or increase the expression and frequency of important genes) for Holstein cows in Iran. However, due to the incomplete information related to the function of the genes in cattle species and the small population used in this study, more extensive studies with more samples and the analysis of several separate populations will provide a better understanding of candidate genes for Johne's disease in the cattle population.

Selective signatures provide information about the stages of evolution of different species, including sheep, which lead to changes in their genome over many years. The aim of this study was to detect signatures of selection in the genome of Iranian sheep in the highlands. A total of 58 sheep from 4 breeds, two breeds scattered in the highlands and two breeds scattered in the lowlands, were genotyped using Illumina ovine SNP600K BeadChip genomic arrays. Two statistical tests of unbiased FST (Theta) and hapFLK were used to identify the selection signatures. The results of Theta revealed 22 genomic regions and the results of hapFLK revealed 15 genomic regions. Bioinformatics analysis demonstrated that many of genes had important effects on adaptation to hypoxia conditions e.g. rheumatoid arthritis (TXNDC5), hematopoiesis (FANCA), immunity and fighting infection (LEF1, NMUR1, PTMA and COPS7B), regulating blood pressure and responding to pain and inflammation (NMUR1) and suppressing cancer (CD82, GAS8, PRMT1, B3GNT7). For example, TXNDC5 and FANCA functional genes, which are located on chromosome 13 and 14, were related to reacts to hypoxic conditions and hematopoiesis. Also, genes such as LEF1, NMUR1, PTMA and COPS7B are effective in immunogenicity and fighting infection. Study of the reported QTL in these regions of the sheep genome showed that they overlapped with QTL of economically important traits such as corpuscular hemoglobin concentration, hematocrit, traits related to meat, carcass, milk, body weight, bone density, and the total number of lambs born. Due to the fact that little research has been done regarding adaptation to altitude in sheep, the results of this research may facilitate the identification of genes affecting adaptation to altitude. However, it will be necessary to carry out more association and functional studies to demonstrate the implication of these genes.

Introduction[1]: Over the years, animals have been exposed to various factors such as natural selection, genetic drift, and multiple mutations, so such factors have caused changes between and within species. The genetic mutations that occur in the populations of domestic animals, will be added to the merits of animals who contain these genetic mutations and they will have more breeds. These mutations are also repeated in their breeds. If a new SNP in a population increases the competence of its carriers compared to other members of society, this choice will make the more deserving individual more involved in shaping the next generation. The most important statistical tests based on demographic differentiation are the FST statistics, which identify distinct positions under positive selection, which are of particular importance for economic characteristics. One of the best ways to understand physiological processes is to analyze gene regulation networks. Identification of genes involved in economic traits as molecular markers in breeding is of special importance. Gene regulation networks enable the researcher to study all of the genes together. The aim of this study was to identify selection signature regions and candidate genes related to economic traits. The necessary data for this research were acquired from two sources, namely NEXTGEN and HAPMAP. The dataset encompassed breeds such as Afshari (41 individuals), Ghezel (35 individuals), Moghani (35 individuals), and eight wild sheep. The initial objective was to assess data quality and perform filtration on raw data. For the remaining single nucleotide polymorphisms (SNPs), those not conforming to Hardy-Weinberg equilibrium were considered indicative of genotyping errors. A stringent probability level of 10⁻⁶, determined through Bonferroni correction, was applied. Various stages of quality control were meticulously executed using PLINK v1.9. Additionally, the study involved identifying animals positioned outside their respective groups, contributing to a comprehensive understanding of the population structure within the two groups. Principal component analysis (PCA) were done in R software. The FST index was proposed to study the distinction between subpopulations and identification of selection signature. the population structure of wild and domestic sheep breeds was analyzed. PCA analysis was performed using genotype information of the samples to investigate how the animals were grouped Investigation of identified genes using SNPs in the upper 1% range of FST were identified by Plink v1.9 software. In addition, the DAVID database (http://david.abcc.ncifcrf.gov) was used to determine biological routes. At this stage, it is assumed that genes that belong to a functional class can be considered as a group of genes that have some specific and common characteristics. GeneCards (http://www.genecards.org) and UniProtKB (http://www.uniprot.org) databases were also used to interpret the function of the obtained genes. The results showed that adjacent SNPs are highly dispersed in several genomic regions. From 34556 SNPs after filtration above 1%, SNPs with higher FST stabilization index (340 SNP) with FST range from 0.304 to 0.472 were selected. Selected SNPs consisted of 95 genomic regions on 23 chromosomes between domestic and wild sheep. Most regions were located on chromosomes 13 and 7 had 14 and 9 gene regions, respectively. Examination of the relationship between QTLs and important genes in selected areas showed that 95 genes related to economic traits were identified. QTLs with important economic characteristics including quality and quantity of meat, milk, fat, bone, immune system and parasite resistance were reported. Most QTLs were located on chromosomes 2, 3, 5, 6, and 7, indicating that the most positive mutations occurred on these chromosomes. Most of the identified biological pathways related to ion channels through cell membranes are neuromuscular processes, Brain and cerebellum growth, metencephalon growth, membrane ion membrane transport, and pathways involved in regulating ion transport in cell membranes. Genes identified in different genomic regions can be considered as selective candidates. A number of genes studied as selection signatures reported were consistent with previous studies. Important genes were included: GABRB1, GRM3, HERC1, HERC3 and KCND2. The study of genomic regions showed that these regions are directly and indirectly related to the quality and quantity of meat, milk, fat, bone, immune system and parasite resistance. Identifying important economic traits and locating parts of the genome that have changed as a result of selection could be used in sheep breeding programs. However, in this research we had limitations such as the incompleteness of information related to functional annotation of genes in sheep species and also the small sample size of this study. Therefore, in subsequent studies with more samples and more breeds of domestic and wild sheep in Iran, a better understanding of candidate genes for important economic traits in domestic and wild species would be achieved.

Identification of several genomic markers sequenced in farm animal enable us to study the structure of their genome. Samples from different parts of the world are usually used for sequencing genomic markers. Information on the sequence of specific markers of domestic animals of each geographical area will improve our knowledge about their genomic structure. The sequence of specific genome markers for Iranian native sheep were not yet identified. Present study aims to identify single-nucleotide polymorphism (SNPs) influencing important economic and physiological traits of Iranian domestic and wild sheep as candidate markers using selection signature.

In order to identify significant genetic variants under selection in domestic and wild sheep, the whole genome sequence of 20 domestic (Ovis aries) and 14 wild sheep (Ovis orientalis) obtained from the Next Gene project was used. After doing quality control, variant under selection were detected using statistical methods consisting iHS and XP-EHH. Genetic variance for identified variants were estimated. The genetic variance of known variants in Merino, Suffolk, texel and Afshari were also estimated. The threshold for selecting variants based on iHS and XP-EHH methods were considerd to be 99.9% in domestic sheep and 99.9% and 0.001% in wild sheep, respectively. Finally, variants with genetic variances higher than 0.25, were identified and suggested as candidate markers.

In present study, 170 genomic variants with iHS and XP-EHH values higher than 3.83 and 3.44 in domestic sheep and 150 genomic variants with iHS values higher than 3.05 and XP-EHH values lower than -4.43 in wild sheep were identified and suggested as candidate markers. Genetic variance of these variants were 0.27 to 0.50 and the genetic variance of known variants in Merino, Suffolk, Texel and Afshari were from 0.02 to 0.50. This comparison shows the importance of identified variants in Iranian domestic and wild sheep. Most of identified variants in domestic and wild sheep associated with economically important traits including carcass, milk and wool related traits. The ontology of genes related to identified variants showed that these variants are located near genes related to metabolic process of production and reproduction traits

Present results showed that there are many significant genetic variants associated with economic traits in domestic and wild Iranian sheep which are not included in the commercial sheep arrays available in the market. Identification of new SNPs related to economic traits in domestic and wild sheep may help to improve the studies related to genomic structure of Iranian sheep. These results together with similar studies could be efficiently used for producing SNP arrays designed for Iranian native sheep.

The principal aim of the sheep industry worldwide is to produce high-quality meat. In addition to the meat, milk, and wool production are the economic traits in sheep breeding programs. Wool production is one of the most important economic characteristics of sheep with a complex physiological and biochemical process that is influenced by genetics, environment, and nutrition. Almost all Iranian sheep breeds are double-coated and produce carpet wool. Therefore, considering the role of wool on the country's economy, it is necessary to conduct a study to identify the genetic factors affecting this trait. Identifying the genomic regions under selection is effective in understanding the processes involved in the evolution of the genome and also in identifying the genomic regions involved in the emergence of economic traits. Selective signatures in the whole genome can help us to understand the mechanisms of selection and to identify the genomic regions that have been under natural or artificial selection for many years. Since Selective signatures are usually associated with major effect genes and important economic traits, they can provide suitable information sources to improve the performance of selection programs in the future. The objective of this study was to identify the genomic regions that have been under selection in skin and wool sheep breeds.

 In the present study, Illumina ovine SNP600K BeadChip genomic arrays of 80 sheep from six breeds were used, three breeds were bred for their skin (Karakul, SiahKabud, and Gray Shiraz) and three breeds were bred for their wool (Sanjabi, Kermani and Baluchi). Unbiased methods of Weir and Cockerham’s FST (Theta) and hapFLK were used to detect the selection signatures. Also, to check the genes and QTLs in the selected regions, the Biomart database, OAR 3.1 version of the sheep genome, was used, and the function of the identified genes was analyzed through a wide search in different databases such as Genecards and OMIM. Finally, the list of genes related to the selected regions was reported. For this purpose, the chromosomal position of SNPs with high numerical values of theta and hapFLK, as well as the 250 kbp region around these markers, were further investigated. Then, the DAVID database online search was used to investigate the biological and functional processes of genes and to study the ontology. Finally, Cytoscape software was used to determine gene networks.Then, DAVID database online search was used to investigate the biological and functional processes of genes and to study the ontology.سپس از جستجوی آنلاین پایگاه داده DAVID برای بررسی فرآیندهای بیولوژیکی و عملکردی ژن ها و مطالعه هستی شناسی استفاده شد.Then, to investigate the biological and functional processes of genes and to study the ontology, DAVID database was used to search online. سپس برای بررسی فرآیندهای بیولوژیکی و عملکردی ژن ها و مطالعه هستی شناسی از پایگاه داده DAVID برای جستجوی آنلاین استفاده شد. Can't load full results Try again Retrying…

 The results of the Theta analysis revealed 26 genomic regions on 1, 2, 6, 19, and 24 chromosomes, and the results of hapFLK revealed seven genomic regions on 6 and 19 chromosomes. Bioinformatics analysis demonstrated that some of these genomic regions overlapped with known genes related to pigment traits and characteristics of wool (KIT on chr 6, MITF on chr 19, IGSF10 on chr 1, PDGFRA on chr 6), muscles (MICALL2 on chr 24), vasodilation and immune response (P2RY on chr 1) and cancer (MIR339 on chr 24, ELFN1 on chr 24, MAD1L1 on chr 24, GPR87 on chr 1). The investigation of reported QTLs showed that these regions are related to QTLs of important economic traits, including traits related to meat, carcass, milk, body weight, bone density, and the total number of lambs born. Also, the analysis of Gene Ontology and Enriched pathway terms in regions under positive selection were related to the pathways involved in the differentiation of melanocytes and pigments, differentiation of stem cells, cellular processes, development of the immune system, blood system, reproductive and cellular processes. The results of the gene networks with the information obtained from Theta and hapFLK statistics showed that the genes identified were significantly active in the development and morphogenesis networks of the embryonic digestive tract, the networks related to pigment and melanocyte differentiation, and the networks related to Purine and G protein. However, to identify the exact function of the identified genes and QTLs, it is recommended to carry out more investigations.نتایج شبکه های ژنی با اطلاعات به دست آمده از آمار تتا و hapFLK نشان داد که ژن های شناسایی شده به طور معنی داری در شبکه های رشد و مورفوژنز دستگاه گوارش جنینی، شبکه های مربوط به تمایز رنگدانه و ملانوسیت و شبکه های مربوط به The results of the gene networks with the information obtained from theta and hapFLK statistics showed that the genes identified were significantly in the development and morphogenesis networks of the embryonic digestive system, the networks related to the differentiation of pigment and melanocytes and the networks related to نتایج شبکه های ژنی با اطلاعات به دست آمده از آمار تتا و hapFLK نشان داد که ژن های شناسایی شده به طور معنی داری در شبکه های رشد و مورفوژنز دستگاه گوارش جنینی، شبکه های مربوط به تمایز رنگدانه ها و ملانوسیت ها و شبکه های مربوط بهCan't load full results Try again Retrying…

 The results of the present study and the identified genomic regions can play an important role in the study of the effect of the selection on population differentiation in two sheep breeds that bred for skin and sheep production. Subsequently, this would direct us to identify the genomic regions associated with traits that differentiate these groups. However, 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, design of mating systems, and additional reviews and evaluations to improve skin and wool production in sheep.

Tail in sheep is a valuable energy source. However, in modern intensive and semi-intensive sheep industry the lean-tailed sheep breeds have more desirable and marketable. Therefore, due to the negative effect of tail size on production efficiency, researchers are looking for methods to eliminate this trait. Identification of genes involved in the process of fat deposition in tail is necessary for reducing tail size in sheep. Several genomic methods such as genome-wide association and selection signature studies or gene expression analysis for describing a possible genetic background for deposition of fat in various fat-tail breeds have been used. The aim of this study was to identify effective genes in fat-tailed sheep breeds (Afshari and Sunite) compared to breeds without tail (Dorper and German Mutton) using selection signature and gene ontology methods.

In this study, genotype information of 366 sheep (37 Afshari, 69 Sunite, 99 Dorper and 161 German Mutton) genotyped with Illumina Ovine SNP50K BeadChip genome arrays, were used. The XP-EHH method using R software package version 1.9 was used to identify selection signature. Genomic version Oar_v4.0 database NCBI was used for detecting the genomic position of SNPs in sheep genome. Candidate genes were identified by SNPs located at 1% upper range of XP-EHH using Plink v1.9 software and gene list of Illumina in R. Additionally, the latest published version of Animal genome database was used for defining QTLs associated with fat deposition traits in identified locations.

Based on the results of XP-EHH, 18 common genes were identified from comparing Afshari population with German Mutton and Dorper breeds, in which five genes (LOC114116389, LOC114118754, KCMF1, TCF7L1 and RASSF2) were associated with QTLs related to fat deposition including carcass fat percentage, internal fat amount and fat tail deposition. 15 common genes were also identified from comparing Sunite population with German Mutton and Dorper populations, in which two genes (SEMA5B and CDH9) were associated with QTLs related to fat deposition. The results of gene ontology showed that some of these genes play effective roles in signaling Wnt, growth, development and morphology of cells.

based on the results of selection signature using XP-EHH method in Afshari and Sunite breeds, RASSF2 gene was identified as a selection signature in Afshari breeds. This gene was also related to tail fat storage QTL, which was identified for the first time in this study. LOC11411689 and LOC114118754 genes related to carcass fat percentage QTL, KCMF1 and TCF7L1 genes related to the QTL of internal fat amount in Afshari breed were also identified. In addition, the SEMA5B gene associated with the QTL of carcass fat percentage and the CDH9 gene associated with of subcutaneous fat weight were identified in the Sunite breed. The results of this study could be used in sheep breeding programs to reduce fat deposition in tail, especially for Afshari breed.

Selection to increase the frequency of new mutations useful only in some subpopulations leaves markers at the genome level. Most of these regions are related to genes and QTLs associated with significant economic traits. The aim of this study was to identify selection traits related to functional traits in the number of world's sheep using modern methods. For this purpose, genotyping files were used using genomic chips related to 1591 sheep from different breeds of the world, (Dryad ،Frontiresin ،Zenodo ،Animal Genom، Hapmap( including 52 breeds from 20 countries on all continents, and 13 studies were stored in various genomic databases. First, to determine the population mixing between different breeds from regions with different climatic conditions, population structure analysis or population stratification was carried out. Fst, hapflk, iHs, Rsb, XpEHH tests were used to identify the selection signatures, and finally, a meta-analysis of the above methods was used. The population was divided into three groups by PCA analysis: AIT: Asian, Turkish and African breeds, AUNZ: Australian and New Zealand breeds, and EU: European breeds. Based on the meta-analysis test, 10 genus regions were identified on chromosomes 2, 3, 4, 5, 6, 7, 9, 12, 20, 22. For example, the MC1R gene is associated with skin color, the DSG2 gene with the quality and quantity of wool, and the AICDA gene with the production of immunoglobulin. Bioinformatics analysis showed that some of these gene regions are directly and indirectly associated with genes affecting environmental adaptation (ADAMTS9), reproduction (GNAQ), melanocyte regulation (KITLG), and immunoglobulin production (BATF, TNFSF13, AICDA, MZB1), Cell differentiation (TNFSF13, TGFB1), Immune process (AGBL5, ATG7, PRDX1, CCL26, IL17RC, TNFSF12, TGFB2, PTGS1), Cellular response to external stimulation, NKK1, PRF3 (PR) Interferon alpha (DDX58), defense response process (CCL24, FAM13B, LDLR, CLDN7), cellular homeostasis (BAMBI, DVL2), regulation of mitogen-activated protein kinase (PLCE1) and regulation of stress response (FXR2, HSPH1). Comparative analysis of meta-analysis of selection cues based on bioinformatics databases can identify selected genomic regions for traits of economic and biological importance in sheep.

The aim of this study was to find the footprint of selection in native Sarabi and Taleshi cattle breeds 296 cattle from two breeds were sampled and genotyped. by 40 k microarray of illumine company. 43 animals were removed because their ACR was below 0.09. Markers were filtered with minor allele frequency (MAF) equal 0.01 and Hardy-Weinberg equilibrium test (10-6). After filtering, 28782 markers remained. To study the genetic structure of population and sub-population principal component analysis (PCA) was used. To identify selective signals for Sarabi and Taleshi pure population theta parameter was calculated. To reduce error theta values was averaged with near marker and Manhattans graph were obtained by haploview software. Chromosomes 2, 5, 6, 7, 10, 22, 25 and 27 had selection signatures. To searching for selection signatures in both population, extended haplotype homozygosity statistics (EHH) was calculated using R software. In addition, for each chromosome LD erosion rate for ancestral and mutant alleles were calculated. To study of positions that showed signature selection, bioinformatics web site were searched. EIF4G3 gene was identified on chromosome 2. This gene have fundamental role in transfering RNA from nucleus to the cytoplasm and gene expression. ANK2 gene was identified on chromosome 6 which encodes polypeptide ankirin B expressed in all tissues. On chromosome 7 the gene ARHGAP26 was found which is a tumor suppressor genes. On chromosome 10, a gene identified that encodes protein SYNJ2BP that suppress activing protein. On chromosome 22, FAM3D protein coding gene detected that plays a role in cyto sckeleton actin biochemical pathway. This gene is expressed in the placenta and plays a role in biological functions such as migration and function of leukocyte, temperature regulation, cell survival and hematopoiesis differentiation.