Identification of consensus homozygous regions and their associations with growth and feed efficiency traits in American mink.

The recent chromosome-based genome assembly and the newly developed 70K single nucleotide polymorphism (SNP) array for American mink (Neogale vison) facilitate the identification of genetic variants underlying complex traits in this species. The objective of this study was to evaluate the association between consensus runs of homozygosity (ROH) with growth and feed efficiency traits in American mink. A subsample of two mink populations (n = 2,986) were genotyped using the Affymetrix Mink 70K SNP array. The identified ROH segments were included simultaneously, concatenated into consensus regions, and the ROH-based association studies were carried out with linear mixed models considering a genomic relationship matrix for 11 growth and feed efficiency traits implemented in ASReml-R version 4. In total, 298,313 ROH were identified across all individuals, with an average length and coverage of 4.16 Mb and 414.8 Mb, respectively. After merging ROH segments, 196 consensus ROH regions were detected and used for genome-wide ROH-based association analysis. Thirteen consensus ROH regions were significantly (P < 0.01) associated with growth and feed efficiency traits. Several candidate genes within the significant regions are known for their involvement in growth and body size development, including MEF2A, ADAMTS17, POU3F2, and TYRO3. In addition, we found ten consensus ROH regions, defined as ROH islands, with frequencies over 80% of the population. These islands harbored 12 annotated genes, some of which were related to immune system processes such as DTX3L, PARP9, PARP14, CD86, and HCLS1. This is the first study to explore the associations between homozygous regions with growth and feed efficiency traits in American mink. Our findings shed the light on the effects of homozygosity in the mink genome on growth and feed efficiency traits, that can be utilized in developing a sustainable breeding program for mink.

Characterization of runs of homozygosity islands in American mink using whole-genome sequencing data.

The genome-wide analysis of runs of homozygosity (ROH) islands can be an effective strategy for identifying shared variants within a population and uncovering important genomic regions related to complex traits. The current study performed ROH analysis to characterize the genome-wide patterns of homozygosity, identify ROH islands and annotated genes within these candidate regions using whole-genome sequencing data from 100 American mink (Neogale vison). After sequence processing, variants were called using GATK and Samtools pipelines. Subsequent to quality control, 8,373,854 bi-allelic variants identified by both pipelines remained for further analysis. A total of 34,652 ROH segments were identified in all individuals, among which shorter segments (0.3-1 Mb) were abundant throughout the genome, approximately accounting for 84.39% of all ROH. Within these segments, we identified 63 ROH islands housing 156 annotated genes. The genes located in ROH islands were associated with fur quality (EDNRA, FGF2, FOXA2 and SLC24A4), body size/weight (MYLK4, PRIM2, FABP2, EYS and PHF3), immune capacity (IL2, IL21, PTP4A1, SEMA4C, JAK2, CCNA2 and TNIP3) and reproduction (ADAD1, KHDRBS2, INSL6, PGRMC2 and HSPA4L). Furthermore, Gene Ontology and KEGG pathway enrichment analyses revealed 56 and 9 significant terms (FDR-corrected p-value < 0.05), respectively, among which cGMP-PKG signalling pathway, regulation of actin cytoskeleton, and calcium signalling pathway were highlighted due to their functional roles in growth and fur characteristics. This is the first study to present ROH islands in American mink. The candidate genes from ROH islands and functional enrichment analysis suggest possible signatures of selection in response to the mink breeding targets, such as increased body length, reproductive performance and fur quality. These findings contribute to our understanding of genetic characteristics, and provide complementary information to assist with implementation of breeding strategies for genetic improvement in American mink.

Genome-wide association studies for economically important traits in mink using copy number variation.

Copy number variations (CNVs) are structural variants consisting of duplications and deletions of DNA segments, which are known to play important roles in the genetics of complex traits in livestock species. However, CNV-based genome-wide association studies (GWAS) have remained unexplored in American mink. Therefore, the purpose of the current study was to investigate the association between CNVs and complex traits in American mink. A CNV-based GWAS was performed with the ParseCNV2 software program using deregressed estimated breeding values of 27 traits as pseudophenotypes, categorized into traits of growth and feed efficiency, reproduction, pelt quality, and Aleutian disease tests. The study identified a total of 10,137 CNVs (6968 duplications and 3169 deletions) using the Affymetrix Mink 70K single nucleotide polymorphism (SNP) array in 2986 American mink. The association analyses identified 250 CNV regions (CNVRs) associated with at least one of the studied traits. These CNVRs overlapped with a total of 320 potential candidate genes, and among them, several genes have been known to be related to the traits such as ARID1B, APPL1, TOX, and GPC5 (growth and feed efficiency traits); GRM1, RNASE10, WNT3, WNT3A, and WNT9B (reproduction traits); MYO10, and LIMS1 (pelt quality traits); and IFNGR2, APEX1, UBE3A, and STX11 (Aleutian disease tests). Overall, the results of the study provide potential candidate genes that may regulate economically important traits and therefore may be used as genetic markers in mink genomic breeding programs.

Genetic and phenotypic correlations between Aleutian disease tests with body weight, growth, and feed efficiency traits in mink.

The ineffectiveness of vaccination, medicine, and culling strategy leads mink farmers to control Aleutian disease (AD) by selecting AD-resilient mink based on AD tests. However, the genetic background of AD tests and their correlations with economically important or AD-resilient traits are limited. This study estimated the genetic and phenotypic correlations between four AD tests and seven body weight (BW) traits, six growth parameters from the Richards growth model, and eight feed-related traits. Univariate models were used to test the significance (P < 0.05) of fixed effects (sex, color type, AD test year, birth year, and row-by-year), random effects (additive genetic, maternal genetic, and permanent environmental), and a covariate of age using ASReml 4.1. Likewise, pairwise bivariate analyses were conducted to estimate the phenotypic and genetic correlations among the studied traits. Both antigen- and virus capsid protein-based enzyme-linked immunosorbent assay tests (ELISA-G and ELISA-P) showed significant (P < 0.05) moderate positive genetic correlations (±SE) with maturation rate (from 0.36 ± 0.18 to 0.38 ± 0.19). ELISA-G showed a significant negative genetic correlation (±SE) with average daily gain (ADG, -0.37 ± 0.16). ELISA-P showed a significant positive moderate genetic correlation (±SE) with off-feed days (DOF, 0.42 ± 0.17). These findings indicated that selection for low ELISA scores would reduce the maturation rate, increase ADG (by ELISA-G), and minimize DOF (by ELISA-P). The iodine agglutination test (IAT) showed significant genetic correlations with DOF (0.73 ± 0.16), BW at 16 weeks of age (BW16, 0.45 ± 0.23), and BW at harvest (HW, -0.47 ± 0.20), indicating that selection for lower IAT scores would lead to lower DOF and BW16, and higher HW. These estimated genetic correlations suggested that the selection of AD tests would not cause adverse effects on the growth, feed efficiency, and feed intake of mink. The estimates from this study might strengthen the previous finding that ELISA-G could be applied as a reliable and practical indicator trait in the genetic selection of AD-resilient mink in AD-positive farms.

The selection of Aleutian disease-resistant individuals based on Aleutian disease (AD) tests is seen as a potential method to control AD effectively. However, the knowledge regarding the genetic background of AD tests is limited. This study estimated the genetic and phenotypic correlations between Aleutian disease tests and body weight, growth, and feed-related traits in mink. The estimates in this study indicated that the growth, feed efficiency, and feed intake of mink would not be adversely influenced by the selection of AD tests. In the meantime, the estimates further illustrate that the antigen-based enzyme-linked immunosorbent assay test could be applied as the most reliable and practical indicator trait to select AD-resilient mink in AD-positive farms.

Genome-wide detection of copy number variation in American mink using whole-genome sequencing.

BACKGROUND: Copy number variations (CNVs) represent a major source of genetic diversity and contribute to the phenotypic variation of economically important traits in livestock species. In this study, we report the first genome-wide CNV analysis of American mink using whole-genome sequence data from 100 individuals. The analyses were performed by three complementary software programs including CNVpytor, DELLY and Manta. RESULTS: A total of 164,733 CNVs (144,517 deletions and 20,216 duplications) were identified representing 5378 CNV regions (CNVR) after merging overlapping CNVs, covering 47.3 Mb (1.9%) of the mink autosomal genome. Gene Ontology and KEGG pathway enrichment analyses of 1391 genes that overlapped CNVR revealed potential role of CNVs in a wide range of biological, molecular and cellular functions, e.g., pathways related to growth (regulation of actin cytoskeleton, and cAMP signaling pathways), behavior (axon guidance, circadian entrainment, and glutamatergic synapse), lipid metabolism (phospholipid binding, sphingolipid metabolism and regulation of lipolysis in adipocytes), and immune response (Wnt signaling, Fc receptor signaling, and GTPase regulator activity pathways). Furthermore, several CNVR-harbored genes associated with fur characteristics and development (MYO5A, RAB27B, FGF12, SLC7A11, EXOC2), and immune system processes (SWAP70, FYN, ORAI1, TRPM2, and FOXO3). CONCLUSIONS: This study presents the first genome-wide CNV map of American mink. We identified 5378 CNVR in the mink genome and investigated genes that overlapped with CNVR. The results suggest potential links with mink behaviour as well as their possible impact on fur quality and immune response. Overall, the results provide new resources for mink genome analysis, serving as a guideline for future investigations in which genomic structural variations are present.

Applying Machine Learning Algorithms for the Classification of Mink Infected with Aleutian Disease Using Different Data Sources.

American mink (Neogale vison) is one of the major sources of fur for the fur industries worldwide, whereas Aleutian disease (AD) is causing severe financial losses to the mink industry. A counterimmunoelectrophoresis (CIEP) method is commonly employed in a test-and-remove strategy and has been considered a gold standard for AD tests. Although machine learning is widely used in livestock species, little has been implemented in the mink industry. Therefore, predicting AD without using CIEP records will be important for controlling AD in mink farms. This research presented the assessments of the CIEP classification using machine learning algorithms. The Aleutian disease was tested on 1157 individuals using CIEP in an AD-positive mink farm (Nova Scotia, Canada). The comprehensive data collection of 33 different features was used for the classification of AD-infected mink. The specificity, sensitivity, accuracy, and F1 measure of nine machine learning algorithms were evaluated for the classification of AD-infected mink. The nine models were artificial neural networks, decision tree, extreme gradient boosting, gradient boosting method, K-nearest neighbors, linear discriminant analysis, support vector machines, naive bayes, and random forest. Among the 33 tested features, the Aleutian mink disease virus capsid protein-based enzyme-linked immunosorbent assay was found to be the most important feature for classifying AD-infected mink. Overall, random forest was the best-performing algorithm for the current dataset with a mean sensitivity of 0.938 ± 0.003, specificity of 0.986 ± 0.005, accuracy of 0.962 ± 0.002, and F1 value of 0.961 ± 0.088, and across tenfold of the cross-validation. Our work demonstrated that it is possible to use the random forest algorithm to classify AD-infected mink accurately. It is recommended that further model tests in other farms need to be performed and the genomic information needs to be used to optimize the model for implementing machine learning methods for AD detection.

Genetic and phenotypic parameters for feed efficiency and component traits in American mink.

Feed cost is the largest expense of mink production systems, and, therefore, improvement of feed efficiency (FE) through selection for high feed-efficient mink is a practical way to increase the mink industry's sustainability. In this study, we estimated the heritability, phenotypic, and genetic correlations for different FE measures and component traits, including harvest weight (HW), harvest length (HL), final body length (FBL), final body weight (FBW), average daily gain (ADG), daily feed intake (DFI), feed conversion ratio (FCR), residual feed intake (RFI), residual gain (RG), residual intake and gain (RIG), and Kleiber ratio (KR), using data from 2,288 American mink (for HW and HL), and 1,038 to 1,906 American mink (for other traits). Significance (P < 0.05) of fixed effects (farm, sex, and color type), a covariate (age of animal), and random effects (additive genetic, maternal, and common litter) were evaluated through univariate models implemented in ASReml-R version 4. Genetic parameters were estimated via fitting a set of bivariate models using ASReml-R version 4. Estimates of heritabilities (±SE) were 0.28 ± 0.06, 0.23 ± 0.06, 0.28 ± 0.10, 0.27 ± 0.11, 0.25 ± 0.09, 0.26 ± 0.09, 0.20 ± 0.09, 0.23 ± 0.09, 0.21 ± 0.10, 0.25 ± 0.10, and 0.26 ± 0.10 for HW, HL, FBL, FBW, ADG, DFI, FCR, RFI, RG, RIG, and KR, respectively. RIG had favorable genetic correlations with DFI (-0.62 ± 0.24) and ADG (0.58 ± 0.21), and nonsignificant (P > 0.05) genetic correlations with FBW (0.14 ± 0.31) and FBL (-0.15 ± 0.31). These results revealed that RIG might be a superior trait as it guarantees reduced feed intake with faster-growing mink yet with no negative impacts on body weight and length. In addition, the strong positive genetic correlations (±SE) between KR with component traits (0.88 ± 0.11 with FBW, 0.68 ± 0.17 with FBL, and 0.97 ± 0.02 with ADG) suggested KR as an applicable indirect measure of FE for improvement of component traits as it did not require the individual feed intake to be measured. Overall, our results confirmed the possibility of including FE traits in mink breeding programs to effectively select feed-efficient animals.

Improvement of feed efficiency (FE) in American mink is highly beneficial, as feed costs comprise the largest expense of mink production systems. The present study estimated the heritability, phenotypic and genetic correlations for different FE measures and component traits in mink. The residual intake and gain can be applied as FE measurement in selection programs as it will guarantee faster-growing mink with reduced feed intake, yet without negative impacts on growth traits. In addition, Kleiber ratio had strong positive genetic correlations with component traits, which made this trait an appealing indirect FE trait for mink breeding programs, knowing the fact that this trait was not dependent on feed intake records. Overall, our results suggested that including FE traits can assist mink breeding programs to develop an index for the selection of feed-efficient mink and, therefore, reduce the cost of mink production.

Application of Genetic, Genomic and Biological Pathways in Improvement of Swine Feed Efficiency.

Despite the significant improvement of feed efficiency (FE) in pigs over the past decades, feed costs remain a major challenge for producers profitability. Improving FE is a top priority for the global swine industry. A deeper understanding of the biology underlying FE is crucial for making progress in genetic improvement of FE traits. This review comprehensively discusses the topics related to the FE in pigs including: measurements, genetics, genomics, biological pathways and the advanced technologies and methods involved in FE improvement. We first provide an update of heritability for different FE indicators and then characterize the correlations of FE traits with other economically important traits. Moreover, we present the quantitative trait loci (QTL) and possible candidate genes associated with FE in pigs and outline the most important biological pathways related to the FE traits in pigs. Finally, we present possible ways to improve FE in swine including the implementation of genomic selection, new technologies for measuring the FE traits, and the potential use of genome editing and omics technologies.

Emerging Roles of Non-Coding RNAs in the Feed Efficiency of Livestock Species.

A global population of already more than seven billion people has led to an increased demand for food and water, and especially the demand for meat. Moreover, the cost of feed used in animal production has also increased dramatically, which requires animal breeders to find alternatives to reduce feed consumption. Understanding the biology underlying feed efficiency (FE) allows for a better selection of feed-efficient animals. Non-coding RNAs (ncRNAs), especially micro RNAs (miRNAs) and long non-coding RNAs (lncRNAs), play important roles in the regulation of bio-logical processes and disease development. The functions of ncRNAs in the biology of FE have emerged as they participate in the regulation of many genes and pathways related to the major FE indicators, such as residual feed intake and feed conversion ratio. This review provides the state of the art studies related to the ncRNAs associated with FE in livestock species. The contribution of ncRNAs to FE in the liver, muscle, and adipose tissues were summarized. The research gap of the function of ncRNAs in key processes for improved FE, such as the nutrition, heat stress, and gut-brain axis, was examined. Finally, the potential uses of ncRNAs for the improvement of FE were discussed.

Shared Ancestry and Signatures of Recent Selection in Gotland Sheep.

Gotland sheep, a breed native to Gotland, Sweden (an island in the Baltic Sea), split from the Gute sheep breed approximately 100 years ago, and since, has probably been crossed with other breeds. This breed has recently gained popularity, due to its pelt quality. This study estimates the shared ancestors and identifies recent selection signatures in Gotland sheep using 600 K single nucleotide polymorphism (SNP) genotype data. Admixture analysis shows that the Gotland sheep is a distinct breed, but also has shared ancestral genomic components with Gute (~50%), Karakul (~30%), Romanov (~20%), and Fjällnäs (~10%) sheep breeds. Two complementary methods were applied to detect selection signatures: A Bayesian population differentiation FST and an integrated haplotype homozygosity score (iHS). Our results find that seven significant SNPs (q-value < 0.05) using the FST analysis and 55 significant SNPs (p-value < 0.0001) using the iHS analysis. Of the candidate genes that contain significant markers, or are in proximity to them, we identify several belongings to the keratin genes, RXFP2, ADCY1, ENOX1, USF2, COX7A1, ARHGAP28, CRYBB2, CAPNS1, FMO3, and GREB1. These genes are involved in wool quality, polled and horned phenotypes, fertility, twining rate, meat quality, and growth traits. In summary, our results provide shared founders of Gotland sheep and insight into genomic regions maintained under selection after the breed was formed. These results contribute to the detection of candidate genes and QTLs underlying economic traits in sheep.

A genome-wide scan of copy number variants in three Iranian indigenous river buffaloes.

BACKGROUND: In Iran, river buffalo is of great importance. It plays an important role in the economy of the Country, because its adaptation to harsh climate conditions and long productive lifespan permitting its farming across the Country and to convert low-quality feed into valuable milk. The genetic variability in Iranian buffalo breeds have been recently studied using SNPs genotyping data, but a whole genome Copy Number Variants (CNVs) mapping was not available. The aim of this study was to perform a genome wide CNV scan in 361 buffaloes of the three Iranian river breeds (Azeri, Khuzestani and Mazandarani) through the analysis of data obtained using the Axiom® Buffalo Genotyping Array 90 K. RESULTS: CNVs detection resulted in a total of 9550 CNVs and 302 CNVRs identified in at least 5% of samples within breed, covering around 1.97% of the buffalo genome. and A total of 22 CNVRs were identified in all breeds and a different proportion of regions were in common among the three populations. Within the more represented CNVRs (n = 302) mapped a total of 409 buffalo genes, some of which resulted associated with morphological, healthy, milk, meat and reproductive traits, according to Animal Genome Cattle database. CONCLUSIONS: This work provides a step forward in the interpretation of genomic variation within and among the buffalo populations, releasing a first map of CNVs and providing insights about their recent selection and adaptation to environment. The presence of the set of genes and QTL traits harbored in the CNVRs could be possibly linked with the buffalo's natural adaptive history together to a recent selection for milk used as primary food source from this species.

Signatures of selection reveal candidate genes involved in economic traits and cold acclimation in five Swedish cattle breeds.

BACKGROUND: Thousands of years of natural and artificial selection have resulted in indigenous cattle breeds that are well-adapted to the environmental challenges of their local habitat and thereby are considered as valuable genetic resources. Understanding the genetic background of such adaptation processes can help us design effective breeding objectives to preserve local breeds and improve commercial cattle. To identify regions under putative selection, GGP HD 150 K single nucleotide polymorphism (SNP) arrays were used to genotype 106 individuals representing five Swedish breeds i.e. native to different regions and covering areas with a subarctic cold climate in the north and mountainous west, to those with a continental climate in the more densely populated south regions. RESULTS: Five statistics were incorporated within a framework, known as de-correlated composite of multiple signals (DCMS) to detect signatures of selection. The obtained p-values were adjusted for multiple testing (FDR < 5%), and significant genomic regions were identified. Annotation of genes in these regions revealed various verified and novel candidate genes that are associated with a diverse range of traits, including e.g. high altitude adaptation and response to hypoxia (DCAF8, PPP1R12A, SLC16A3, UCP2, UCP3, TIGAR), cold acclimation (AQP3, AQP7, HSPB8), body size and stature (PLAG1, KCNA6, NDUFA9, AKAP3, C5H12orf4, RAD51AP1, FGF6, TIGAR, CCND2, CSMD3), resistance to disease and bacterial infection (CHI3L2, GBP6, PPFIBP1, REP15, CYP4F2, TIGD2, PYURF, SLC10A2, FCHSD2, ARHGEF17, RELT, PRDM2, KDM5B), reproduction (PPP1R12A, ZFP36L2, CSPP1), milk yield and components (NPC1L1, NUDCD3, ACSS1, FCHSD2), growth and feed efficiency (TMEM68, TGS1, LYN, XKR4, FOXA2, GBP2, GBP5, FGD6), and polled phenotype (URB1, EVA1C). CONCLUSIONS: We identified genomic regions that may provide background knowledge to understand the mechanisms that are involved in economic traits and adaptation to cold climate in cattle. Incorporating p-values of different statistics in a single DCMS framework may help select and prioritize candidate genes for further analyses.

Linkage disequilibrium and within-breed genetic diversity in Iranian Zandi sheep.

This research aimed to measure the extent of linkage disequilibrium (LD), effective population size ( N e ), and runs of homozygosity (ROHs) in one of the major Iranian sheep breeds (Zandi) using 96 samples genotyped with Illumina Ovine SNP50 BeadChip. The amount of LD ( r 2 ) for single-nucleotide polymorphism (SNP) pairs in short distances (10-20 kb) was 0.21 ± 0.25 but rapidly decreased to 0.10 ± 0.16 by increasing the distance between SNP pairs (40-60 kb). The N e of Zandi sheep in past (approximately 3500 generations ago) and recent (five generations ago) populations was estimated to be 6475 and 122, respectively. The ROH-based inbreeding was 0.023. We found 558 ROH regions, of which 37 % were relatively long ( > 10  Mb). Compared with the rate of LD reduction in other species (e.g., cattle and pigs), in Zandi, it was reduced more rapidly by increasing the distance between SNP pairs. According to the LD pattern and high genetic diversity of Zandi sheep, we need to use an SNP panel with a higher density than Illumina Ovine SNP50 BeadChip for genomic selection and genome-wide association studies in this breed.