Insights from homozygous signatures of cervus nippon revealed genetic architecture for components of fitness.

This study investigates the genomic landscape of Sika deer populations, emphasizing the detection and characterization of runs of homozygosity (ROH) and their contribution towards components of fitness. Using 85,001 high-confidence SNPs, the investigation into ROH distribution unveiled nuanced patterns of autozygosity across individuals especially in 2 out of the 8 farms, exhibiting elevated ROH levels and mean genome coverage under ROH segments. The prevalence of shorter ROH segments (0.5-4 Mb) suggests historical relatedness and potential selective pressures within these populations. Intriguingly, despite observed variations in ROH profiles, the overall genomic inbreeding coefficient (FROH) remained relatively low across all farms, indicating a discernible degree of genetic exchange and effective mitigation of inbreeding within the studied Sika deer populations. Consensus ROH (cROH) were found to harbor genes for important functions viz., EGFLAM gene which is involved in the vision function of the eye, SKP2 gene which regulates cell cycle, CAPSL involved in adipogenesis, SPEF2 which is essential for sperm flagellar assembly, DCLK3 involved in the heat stress. This first ever study on ROH in Sika deer, to shed light on the adaptive role of genes in these homozygous regions. The insights garnered from this study have broader implications in the management of genetic diversity in this vulnerable species.

Integration of ssGWAS and ROH analyses for uncovering genetic variants associated with reproduction traits in Large White pigs.

The low heritability of reproduction traits such as total number born (TNB), number born alive (NBA) and adjusted litter weight until 21 days at weaning (ALW) poses a challenge for genetic improvement. In this study, we aimed to identify genetic variants that influence these traits and evaluate the accuracy of genomic selection (GS) using these variants as genomic features. We performed single-step genome-wide association studies (ssGWAS) on 17 823 Large White (LW) pigs, of which 2770 were genotyped by 50K single nucleotide polymorphism (SNP) chips. Additionally, we analyzed runs of homozygosity (ROH) in the population and tested their effects on the traits. The genomic feature best linear unbiased prediction (GFBLUP) was then carried out in an independent population of 350 LW pigs using identified trait-related SNP subsets as genomic features. As a result, our findings identified five, one and four SNP windows that explaining more than 1% of genetic variance for ALW, TNB, and NBA, respectively and discovered 358 hotspots and nine ROH islands. The ROH SSC1:21814570-27186456 and SSC11:7220366-14276394 were found to be significantly associated with ALW and NBA, respectively. We assessed the genomic estimated breeding value accuracy through 20 replicates of five-fold cross-validation. Our findings demonstrate that GFBLUP, incorporating SNPs located in effective ROH (p-value < 0.05) as genomic features, might enhance GS accuracy for ALW compared with GBLUP. Additionally, using SNPs explaining more than 0.1% of the genetic variance in ssGWAS for NBA as genomic features might improve the GS accuracy, too. However, it is important to note that the incorporation of inappropriate genomic features can significantly reduce GS accuracy. In conclusion, our findings provide valuable insights into the genetic mechanisms of reproductive traits in pigs and suggest that the ssGWAS and ROH have the potential to enhance the accuracy of GS for reproductive traits in LW pigs.

The Association between the Abundance of Homozygous Deleterious Variants and the Morbidity of Dog Breeds.

It is well known that highly inbred dogs are more prone to diseases than less inbred or outbred dogs. This is because inbreeding increases the load of recessive deleterious variants. Using the genomes of 392 dogs belonging to 83 breeds, we investigated the association between the abundance of homozygous deleterious variants and dog health. We used the number of non-routine veterinary care events for each breed to assess the level of morbidity. Our results revealed a highly significant positive relationship between the number of homozygous deleterious variants located within the runs of homozygosity (RoH) tracts of the breeds and the level of morbidity. The dog breeds with low morbidity had a mean of 87 deleterious SNVs within the RoH, but those with very high morbidity had 187 SNVs. A highly significant correlation was also observed for the loss-of-function (LoF) SNVs within RoH tracts. The dog breeds that required more veterinary care had 2.3 times more homozygous LoF SNVs than those that required less veterinary care (112 vs. 50). The results of this study could be useful for understanding the disease burden on breed dogs and as a guide for dog breeding programs.

Clinical utility of regions of homozygosity (ROH) identified in exome sequencing: when to pursue confirmatory uniparental disomy testing for imprinting disorders?

OBJECTIVES: Regions of homozygosity (ROH) could implicate uniparental disomy (UPD) on specific chromosomes associated with imprinting disorders. Though the algorithms for ROH detection in exome sequencing (ES) have been developed, optimal reporting thresholds and when to pursue confirmatory UPD testing for imprinting disorders remain in ambiguity. This study used a data-driven approach to assess optimal reporting thresholds of ROH in clinical practice. METHODS: ROH analysis was performed using Automap in a retrospective cohort of 8,219 patients and a prospective cohort of 1,964 patients with ES data. Cases with ROH on imprinting-disorders related chromosomes were selected for additional methylation-specific confirmatory testing. The diagnostic yield, the ROH pattern of eventually diagnosed cases and optimal thresholds for confirmatory testing were analyzed. RESULTS: In the retrospective analysis, 15 true UPD cases of imprinting disorders were confirmed among 51 suspected cases by ROH detection. Pattern of ROH differed between confirmed UPD and non-UPD cases. Maximized yield and minimized false discovery rate of confirmatory UPD testing was achieved at the thresholds of >20 Mb or >25 % chromosomal coverage for interstitial ROH, and >5 Mb for terminal ROH. Current recommendation by ACMG was nearly optimal, though refined thresholds as proposed in this study could reduce the workload by 31 % without losing any true UPD diagnosis. Our refined thresholds remained optimal after independent evaluation in a prospective cohort. CONCLUSIONS: ROH identified in ES could implicate the presence of clinically relevant UPD. This study recommended size and coverage thresholds for confirmatory UPD testing after ROH detection in ES, contributing to the development of evidence-based reporting guidelines.

Automatized detection of uniparental disomies in a large cohort.

Uniparental disomy (UPD) is the inheritance of both homologues of a chromosome from only one parent. The detection of UPDs in sequencing data is not well established and a common gap in genetic diagnostics. We applied our in-house UPD detection pipeline to evaluate a cohort of 9212 samples, including multigene panels as well as exome sequencing data in a single, duo or trio constellation. We used the results to inform the design of our publicly available web app altAFplotter. UPDs categorized as heterodisomy, whole chromosome or segmental isodisomy were identified and validated with microsatellites, multiplex ligation-dependent probe amplification as well as Sanger sequencing. We detected 14 previously undiagnosed UPDs including nine isodisomies, four segmental isodisomies as well as one heterodisomy on chromosome 22. We characterized eight findings as potentially causative through homozygous pathogenic variants or imprinting disorders. Overall, our study demonstrates the utility of our UPD detection pipeline with our web app, altAFplotter, to reliably identify UPDs. This not only increases the diagnostic yield of cases with growth and metabolic disturbances, as well as developmental delay, but also enhances the understanding of UPDs that may be relevant for recurrence risks and genetic counseling.

Insights into the genomic homogeneity of Moroccan indigenous sheep breeds though the lens of runs of homozygosity.

Numerous studies have indicated that Morocco's indigenous sheep breeds are genetically homogenous, posing a risk to their survival in the challenging harsh climate conditions where they predominantly inhabit. To understand the genetic behind genetic homogeneity through the lens of runs of homozygosity (ROH), we analyzed the whole genome sequences of five indigenous sheep breeds (Beni Guil, Ouled Djellal, D'man, Sardi, Timahdite and Admixed).The results from principal component, admixture, Fst, and neighbour joining tree analyses consistently showed a homogenous genetic structure. This structure was characterized by an average length of 1.83 Mb for runs of homozygosity (ROH) segments, with a limited number of long ROH segments (24-48 Mb and > 48 Mb). The most common ROH segments were those ranging from 1-6 Mb. The most significant regions of homozygosity (ROH Islands) were mostly observed in two chromosomes, namely Chr1 and Chr5. Specifically, ROH Islands were exclusively discovered in the Ouled Djellal breed on Chr1, whereas Chr5 exhibited ROH Islands in all breeds. The analysis of ROH Island and iHS technique was employed to detect signatures of selection on Chr1 and Chr5. The results indicate that Chr5 had a high level of homogeneity, with the same genes being discovered across all breeds. In contrast, Chr1 displays some genetic variances between breeds. Genes identified on Chr5 included SLC39A1, IL23A, CAST, IL5, IL13, and IL4 which are responsible for immune response while genes identified on Chr1 include SOD1, SLAMF9, RTP4, CLDN1, and PRKAA2. ROH segment profile and effective population sizes patterns suggests that the genetic uniformity of studied breeds is the outcome of events that transpired between 250 and 300 generations ago. This research not only contributes to the understanding of ROH distribution across breeds but helps design and implement native sheep breeding and conservation strategies in Morocco. Future research, incorporating a broader sample size and utilizing the pangenome for reference, is recommended to further elucidate these breeds' genomic landscapes and adaptive mechanisms.

Genome-Wide Association Studies of Growth Trait Heterosis in Crossbred Meat Rabbits.

The application of heterosis can not only effectively improve the disease resistance and meat quality of livestock, but also significantly enhance the reproduction and growth of livestock and poultry. We conducted genome-wide association studies using data from F2 crossbred meat rabbits to screen out candidate genes with significant dominant effects associated with economic trait variation. High-throughput sequencing technology was used to obtain SNPs covering the whole genome to evaluate the homozygosity of the population genome, and analyze the number, length, frequency, and distribution of ROHs in the population. Candidate genes related to economic traits of meat rabbits were searched based on high-frequency ROH regions. After quality control filtering of genotype data, 380 F2 crossbred rabbits were identified with 78,579 SNPs and 42,018 ROHs on the autosomes. The fitting of the Logistic growth curve model showed that 49-day-old rabbits were a growth inflection point. Then, through genome-wide association studies, 10 SNP loci and seven growth trait candidate genes were found to be significantly related to body weight in meat rabbits at 84 days of age. In addition, we revealed the functional roles and locations of 20 candidate genes in the high-frequency ROH region associated with economic traits in meat rabbits. This study identified potential genes associated with growth and development in the high-frequency ROH region of meat rabbits. In this study, the identified candidate genes can be used as molecular markers for assisted selection in meat rabbits. At the same time, the inbreeding situation based on ROH assessment can provide reference for breeding and breeding preservation of meat rabbits.

Genomic Characterization of Local Croatian Sheep Breeds-Effective Population Size, Inbreeding & Signatures of Selection.

The Istrian (IS) and the Pag sheep (PS) are local Croatian breeds which provide significant income for the regional economy and have a cultural and traditional importance for the inhabitants. The aim of this study was to estimate some important population specific genetic parameters in IS (N = 1293) and PS (N = 2637) based on genome wide SNPs. Estimates of linkage disequilibrium effective population size (Ne) evidenced more genetic variability in PS (Ne = 838) compared to IS (Ne = 197), regardless of historical time (both recent and ancient genetic variability). The discrepancy in the recent genetic variability between these breeds was additionally confirmed by the estimates of genomic inbreeding (FROH), which was estimated to be notably higher in IS (FROH>2 = 0.062) than in PS (FROH>2 = 0.029). The average FROH2-4, FROH4-8, FROH8-16, and FROH>16 were 0.26, 1.65, 2.14, and 3.72 for IS and 0.22, 0.61, 0.75, and 1.58 for PS, thus evidencing a high contribution of recent inbreeding in the overall inbreeding. One ROH island with > 30% of SNP incidence in ROHs was detected in IS (OAR6; 34,253,440-38,238,124 bp) while there was no ROH islands detected in PS. Seven genes (CCSER1, HERC3, LCORL, NAP1L5, PKD2, PYURF, and SPP1) involved in growth, feed intake, milk production, immune responses, and resistance were associated with the found autozygosity. The results of this study represent the first comprehensive insight into genomic variability of these two Croatian local sheep breeds and will serve as a baseline for setting up the most promising strategy of genomic Optimum Contribution Selection.

Percutaneous removal of hardware after orthopedic surgery: Is it safe? and What are patients saying?

OBJECTIVES: To analyze our patient's complication profile and rate after removal of hardware (ROH) surgery, and survey our patients to ask their overall status and improvement in symptomatology post-operatively. DESIGN: Retrospective chart review and survey. SETTING: Academic, tertiary referral center. PATIENTS/PARTICIPANTS: 173 patients with 314 pieces of hardware. Seventy-six patients (43.9%) responded to our survey. INTERVENTION: ROH surgery. MAIN OUTCOME MEASUREMENTS: Patient demographics and complications were recorded. All patients were sent a brief 3-question survey which asked: (1) Why did you get your hardware removed? (2) How did your overall status change after ROH? (3) How did the ROH affect your stiffness, pain, swelling, and mobility? RESULTS: There were 10 complications (5.5%): 5 infections, 2 with unresolved pain, 1 hematoma, 1 chronic regional pain syndrome exacerbation, and 1 recurrent deformity. All infections were treated with oral antibiotics and improved. All other complications resolved with treatment except for the patient who developed recurrent deformity. Patients underwent ROH surgery because their doctor suggested it (76.3%) and to improve mobility (39.5%). 86.9% reported their overall status improved after ROH. They improved regarding stiffness (73.7%), pain (73.6%), swelling (61.8%), and mobility (76.3%). Similar results were seen among different implants removed. CONCLUSIONS: The majority of patients who underwent percutaneous ROH were satisfied. They reported improvement in stiffness, pain, swelling and mobility (greatest improvement). The complication rate was low (5.5%). ROH can be a meaningful operation to patients allowing them to improve their quality of life with a low complication rate. LEVEL OF EVIDENCE: Level IV.

Evaluating genomic inbreeding of two Chinese yak (Bos grunniens) populations.

BACKGROUND: Yaks are a vital livestock in the Qinghai-Tibetan Plateau area for providing food products, maintaining sustainable ecosystems, and promoting cultural heritage. Because of uncontrolled mating, it is impossible to estimate inbreeding level of yak populations using the pedigree-based approaches. With the aims to accurately evaluate inbreeding level of two Chinese yak populations (Maiwa and Jiulong), we obtained genome-wide single nucleotide polymorphisms (SNPs) by DNA sequencing and calculated five SNP-by-SNP estimators ([Formula: see text], [Formula: see text], [Formula: see text], [Formula: see text], and [Formula: see text]), as well as two segment-based estimators of runs of homozygosity (ROH, [Formula: see text]) and homozygous-by-descent (HBD, [Formula: see text]). Functional implications were analyzed for the positional candidate genes located within the related genomic regions. RESULTS: A total of 151,675 and 190,955 high-quality SNPs were obtained from 71 Maiwa and 30 Jiulong yaks, respectively. Jiulong had greater genetic diversity than Maiwa in terms of allele frequency and nucleotide diversity. The two populations could be genetically distinguished by principal component analysis, with the mean differentiation index (Fst) of 0.0054. The greater genomic inbreeding levels of Maiwa yaks were consistently supported by all five SNP-by-SNP estimators. Based on simple proportion of homozygous SNPs ([Formula: see text]), a lower inbreeding level was indicated by three successfully sequenced old leather samples that may represent historical Maiwa yaks about five generations ago. There were 3304 ROH detected among all samples, with mean and median length of 1.97 Mb and 1.0 Mb, respectively. A total of 94 HBD segments were found among all samples, whereas 92 of them belonged to the shortest class with the mean length of 10.9 Kb. Based on the estimates of [Formula: see text] and [Formula: see text], however, there was no difference in inbreeding level between Maiwa and Jiulong yaks. Within the genomic regions with the significant Fst or enriched by ROH, we found several candidate genes and pathways that have been reported to be related to diverse production traits in farm animals. CONCLUSIONS: We successfully evaluated the genomic inbreeding level of two Chinese yak populations. Although different estimators resulted in inconsistent conclusions on their genomic inbreeding levels, our results may be helpful to implement the genetic conservation and utilization programs for the two yak populations.

Analysis of genetic diversity and structure of endangered Dengchuan cattle population using a single-nucleotide polymorphism chip.

This study aimed to evaluate the genetic diversity and structure within the Dengchuan cattle population and effectively protect and utilize their germplasm resources. Herein, the single-nucleotide polymorphisms (SNPs) of 100 Dengchuan cattle (46 bulls and 54 cows) were determined using the GGP Bovine 100K SNP Beadchip. The results showed that among the Dengchuan cattle, a total of 101,220 SNPs were detected, and there were 83,534 SNPs that passed quality control, of which 85.7% were polymorphic. The average genetic distance based on identity-by-state (IBS) within the conservation population of Dengchuan cattle was 0.26 ± 0.02. A total of 3,999 genome-length runs of homozygosity (ROHs) were detected in the Dengchuan cattle, with ROH lengths primarily concentrated in the range of 1-5 Mb, accounting for 87.02% of the total. The average inbreeding coefficient based on ROHs was 4.6%, within the conservation population of Dengchuan cattle, whereas it was 4.9% for bulls, and the Wright inbreeding coefficient (FIS) value was 2.4%, demonstrating a low level of inbreeding within the Dengchuan cattle population. Based on neighbor-joining tree analysis, the Dengchuan cattle could be divided into 16 families. In summary, the conservation population of Dengchuan cattle displays relatively abundant diversity and a moderate genetic relationship. Inbreeding was observed among a few individuals, but the overall inbreeding level of the population remained low. It is important to maintain this low level of inbreeding when introducing purebred bloodlines to expand the core group. This approach will ensure the long-term conservation of Dengchuan cattle germplasm resources and prevent loss of genetic diversity.

Runs of homozygosity analysis for selection signatures in the Yellow Korean native chicken.

Objective: Yellow Korean native chicken (KNC-Y) is one of the five pure Korean indigenous chicken breeds that were restored through a government project in 1992. KNC-Y is recognized for its superior egg production performance compared to other KNC lines. In this study, we performed runs of homozygosity (ROH) analysis to discover selection signatures associated with egg production traits in the KNC-Y population. Methods: A total of 675 DNA samples from KNC-Y were genotyped to generate single nucleotide polymorphism (SNP) data using custom 60K Affymetrix SNP chips. ROH analysis was performed using PLINK software, with predefined parameters set for the analysis. The threshold of ROH island was defined as the top 1% frequency of SNPs withing the ROH among the population. Results: In the KNC-Y population, a total of 29,958 runs of homozygosity (ROH) fragments were identified. The average total length of ROH was 120.84 Mb, with each ROH fragment having an average length of 2.71 Mb. The calculated ROH-based inbreeding coefficient (FROH) was 0.13. Furthermore, we revealed the presence of ROH islands on chromosomes 1, 2, 4, 5, 7, 8, and 11. Within the identified regions, a total of 113 genes were annotated, and among them were genes related to economic traits, including PRMT3, ANO5, HDAC4, LSS, PLA2G4A, and PTGS2. Most of the overlapping quantitative trait locus (QTL) regions with ROH islands were found to be associated with production traits. Conclusion: This study conducted a comprehensive analysis of ROH in the KNC-Y population. Notably, among the findings, the PTGS2 gene is believed to play a crucial role in influencing the laying performance of KNC-Y.

Characterisation of runs of homozygosity and inbreeding coefficients in the red-brown Korean native chickens.

OBJECTIVE: The analysis of runs of homozygosity (ROH) has been applied to assess the level of inbreeding and identify selection signatures in various livestock species. The objectives of this study were to characterize the ROH pattern, estimate the rate of inbreeding, and identify signatures of selection in the red-brown Korean native chickens. METHODS: The Illumina 60K single nucleotide polymorphism chip data of 651 chickens was used in the analysis. Runs of homozygosity were analysed using the PLINK v1.9 software. Inbreeding coefficients were estimated using the GCTA software and their correlations were examined. Genomic regions with high levels of ROH were explored to identify selection signatures. RESULTS: A total of 32,176 ROH segments were detected in this study. The majority of the ROH segments were shorter than 4 Mb. The average ROH inbreeding coefficients (FROH) varied with the length of ROH segments. The means of inbreeding coefficients calculated from different methods were also variable. The correlations between different inbreeding coefficients were positive and highly variable (r = 0.18-1). Five ROH islands harbouring important quantitative trait loci were identified. CONCLUSION: This study assessed the level of inbreeding and patterns of homozygosity in Red-brown native Korean chickens. The results of this study suggest that the level of recent inbreeding is low which indicates substantial progress in the conservation of red-brown Korean native chickens. Additionally, Candidate genomic regions associated with important production traits were detected in homozygous regions.

Genome-Wide Analysis of Milk Production Traits and Selection Signatures in Serbian Holstein-Friesian Cattle.

To improve the genomic evaluation of milk-related traits in Holstein-Friesian (HF) cattle it is essential to identify the associated candidate genes. Novel SNP-based analyses, such as the genetic mapping of inherited diseases, GWAS, and genomic selection, have led to a new era of research. The aim of this study was to analyze the association of each individual SNP in Serbian HF cattle with milk production traits and inbreeding levels. The SNP 60 K chip Axiom Bovine BovMDv3 was deployed for the genotyping of 334 HF cows. The obtained genomic results, together with the collected phenotypic data, were used for a GWAS. Moreover, the identification of ROH segments was performed and served for inbreeding coefficient evaluation and ROH island detection. Using a GWAS, a polymorphism, rs110619097 (located in the intron of the CTNNA3 gene), was detected to be significantly (p < 0.01) associated with the milk protein concentration in the first lactation (adjusted to 305 days). The average genomic inbreeding value (FROH) was 0.079. ROH islands were discovered in proximity to genes associated with milk production traits and genomic regions under selection pressure for other economically important traits of dairy cattle. The findings of this pilot study provide useful information for a better understanding of the genetic architecture of milk production traits in Serbian HF dairy cows and can be used to improve lactation performances in Serbian HF cattle breeding programs.

Signatures of positive selection after the introduction of genomic selection in the Finnish Ayrshire population.

The Finnish Ayrshire (FAY) belongs to the Nordic Red breeds and is characterized by high milk yield, high milk components, good fertility, and functional conformation. The FAY breeding program is based on genomic selection. Despite the benefits of selection on breeding values, autozygosity in the genome may increase due to selection, and increased autozygosity may cause inbreeding depression in selected traits. However, there is lack of studies concerning selection signatures in the FAY after genomic selection introduction. The aim of this study was to identify signatures of selection in FAY after the introduction of genomic selection. Genomic data included 45,834 SNPs. The genotyped animals were divided into 2 groups: animals born before genomic selection introduction (6,108 cows) and animals born after genomic selection introduction (47,361 cows). We identified the selection signatures using 3 complementary methods: 2 based on identification of selection signatures from runs of homozygosity (ROH) islands and one based on the decay of site-specific extended haplotype between populations at SNP sites (Rsb). In total, we identified 34 ROH islands on chromosomes 1, 3, 6, 8, 12-15, 17, 19, 22, and 26 in FAY animals born before genomic selection (between 1980 and 2011) and 30 ROH islands on chromosomes 1-3, 13-17, 22, and 25-26 in FAY animals born after genomic selection introduction (between 2015 and 2020). We additionally detected 22 ΔROH islands on chromosomes 2-3, 11, 13, 14, 16, 18, 20, and 25-26. Finally, a total of 31 Rsb regions on chromosomes 2, 3, 14, 18, 20, and 25 were identified. Based on the results, genomic selection has favored certain alleles and haplotypes on genomic regions related to traits relevant in the FAY breeding program: milk production, fertility, growth, beef production traits, and feed efficiency. Several genes related to these traits (e.g., PLA2G4A, MECR, CHUK, COX15, RICTOR, SHISA9, and SEMA4G) overlapped or partially overlapped the observed selection signature regions. The association of genotypes within these regions and their effects on traits relevant in the FAY breeding program should be studied and genetic regions undergoing selection monitored in the FAY population.

Genome-wide runs of homozygosity signatures in diverse Indian goat breeds.

The present study analyzed ROH and consensus ROH regions in 102 animals of eleven diverse Indian goat (Capra hircus) breeds using whole genome sequencing. A total of 51,705 ROH and 21,271 consensus regions were identified. The mean number of ROH per animal was highest in the meat breed, Jharkhand Black (2693) and lowest in the pashmina breed, Changthangi (60). The average length of ROH (ALROH) was maximum in Kanniadu (974.11 Kb) and minimum in Tellicherry (146.98 Kb). Long ROH is typically associated with more recent inbreeding, whereas short ROH is connected to more ancient inbreeding. The overall ROH-based genomic inbreeding (FROH) was highest for Jharkhand Black (0.602) followed by Kanniadu (0.120) and Sangamneri (0.108) among all breeds. FROH of Jharkhand Black was higher than Kanniadu  up to 5 Mb ROH length category. However, in > 20 Mb ROH length category, Kanniadu (0.98)  exhibited significantly higher FROH than Jharkhand Black (0.46). This  implies that Kanniadu had higher levels of recent inbreeding than Jharkhand Black. Despite this, due to the presence of both recent and ancient inbreeding, Jharkhand Black  demonstrated higher overall FROH compared to Kanniadu. ROH patterns revealed dual purpose (meat and dairy) and pashmina breeds as less consanguineous while recent inbreeding was apparent in meat breeds. Analysis of ROH consensus regions identified selection sweeps in key genes governing intramuscular fat deposition, meat tenderisation, lean meat production and carcass weight (CDK4, ALOX15, CASP9, PRDM16, DVL1) in meat breeds; milk fat percentage and mammary gland development (POLD1, NOTCH2, ARHGAP35) in dual purpose (meat and dairy) breeds; while cold adaptation and hair follicle development (APOBEC1, DNAJC3, F2RL1, FGF9) in pashmina breed. MAPK, RAS, BMP and Wnt signaling pathways associated with hair follicle morphogenesis in Changthangi were also identified. PCA analysis based on ROH consensus regions revealed that meat breeds are more diverse than other goat breeds/populations. Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-024-03921-y.

Assessment of runs of homozygosity, heterozygosity-rich regions and genomic inbreeding estimates in a subpopulation of Guzerá (Bos indicus) dual-purpose cattle.

For decades, inbreeding in cattle has been evaluated using pedigree information. Nowadays, inbreeding coefficients can be obtained using genomic information such as runs of homozygosity (ROH). The aims of this study were to quantify ROH and heterozygosity-rich regions (HRR) in a subpopulation of Guzerá dual-purpose cattle, to examine ROH and HRR islands, and to compare inbreeding coefficients obtained by ROH with alternative genomic inbreeding coefficients. A subpopulation of 1733 Guzerá animals genotyped for 50k SNPs was used to obtain the ROH and HRR segments. Inbreeding coefficients by ROH (FROH ), by genomic relationship matrix based on VanRaden's method 1 using reference allele frequency in the population (FGRM ), by genomic relationship matrix based on VanRaden's method 1 using allele frequency fixed in 0.5 (FGRM_0.5 ), and by the proportion of homozygous loci (FHOM ) were calculated. A total of 15,660 ROH were identified, and the chromosome with the highest number of ROH was BTA6. A total of 4843 HRRs were identified, and the chromosome with the highest number of HRRs was BTA23. No ROH and HRR islands were identified according to established criteria, but the regions closest to the definition of an island were examined from 64 to 67 Mb of BTA6, from 36 to 37 Mb of BTA2 and from 0.50 to 1.25 Mb of BTA23. The genes identified in ROH islands have previously been associated with dairy and beef traits, while genes identified on HRR islands have previously been associated with reproductive traits and disease resistance. FROH was equal to 0.095 ± 0.084, and its Spearman correlation with FGRM was low (0.44) and moderate-high with FHOM (0.79) and with FGRM_0.5 (0.80). The inbreeding coefficients determined by ROH were higher than other cattle breeds' and higher than pedigree-based inbreeding in the Guzerá breed obtained in previous studies. It is recommended that future studies investigate the effects of inbreeding determined by ROH on the traits under selection in the subpopulation studied.

Characterization of runs of Homozygosity revealed genomic inbreeding and patterns of selection in indigenous sahiwal cattle.

Runs of homozygosity (ROH) are contiguous genomic regions, homozygous across all sites which arise in an individual due to the parents transmitting identical haplotypes to their offspring. The genetic improvement program of Sahiwal cattle after decades of selection needs re-assessment of breeding strategy and population phenomena. Hence, the present study was carried out to optimize input parameters in PLINK for ROH estimates, to explore ROH islands and assessment of pedigree and genome-based inbreeding in Sahiwal cattle. The sliding window approach with parameters standardized to define ROH for the specific population under study was used for the identification of runs. The optimum maximum gap, density, window-snp and window-threshold were 250 Kb, 120 Kb/SNP, 10, 0.05 respectively and ROH patterns were also characterized. ROH islands were defined as the short homozygous genomic regions shared by a large proportion of individuals in a population, containing significantly higher occurrences of ROH than the population specific threshold level. These were identified using the -homozyg-group function of the PLINK v1.9 program. Our results indicated that the Islands of ROH harbor a few candidate genes, ACAD11, RFX4, BANP, UBA5 that are associated with major economic traits. The average FPED (Pedigree based inbreeding coefficient), FROH (Genomic inbreeding coefficient), FHOM (Inbreeding estimated as the ratio of observed and expected homozygous genotypes), FGRM (Inbreeding estimated on genomic relationship method) and FGRM0.5 (Inbreeding estimated from the diagonal of a GRM with allele frequencies near to 0.5) were 0.009, 0.091, 0.035, -0.104 and -0.009, respectively. Our study revealed the optimum parameter setting in PLINK viz. maximal gaps between two SNPs, minimal density of SNPs in a segment (in kb/SNP) and scanning window size to identify ROH segments, which will enable ROH estimation more efficient and comparable across various SNP genotyping-based studies. The result further emphasized the significant role of genomics in unraveling population diversity, selection signatures and inbreeding in the ongoing Sahiwal breed improvement programs.

Genome-Wide Association Studies and Runs of Homozygosity to Identify Reproduction-Related Genes in Yorkshire Pig Population.

Reproductive traits hold considerable economic importance in pig breeding and production. However, candidate genes underpinning the reproductive traits are still poorly identified. In the present study, we executed a genome-wide association study (GWAS) and runs of homozygosity (ROH) analysis using the PorcineSNP50 BeadChip array for 585 Yorkshire pigs. Results from the GWAS identified two genome-wide significant and eighteen suggestive significant single nucleotide polymorphisms (SNPs) associated with seven reproductive traits. Furthermore, we identified candidate genes, including ELMO1, AOAH, INSIG2, NUP205, LYPLAL1, RPL34, LIPH, RNF7, GRK7, ETV5, FYN, and SLC30A5, which were chosen due to adjoining significant SNPs and their functions in immunity, fertilization, embryonic development, and sperm quality. Several genes were found in ROH islands associated with spermatozoa, development of the fetus, mature eggs, and litter size, including INSL6, TAF4B, E2F7, RTL1, CDKN1C, and GDF9. This study will provide insight into the genetic basis for pig reproductive traits, facilitating reproduction improvement using the marker-based selection methods.

Genomic signatures of selection, local adaptation and production type characterisation of East Adriatic sheep breeds.

BACKGROUND: The importance of sheep breeding in the Mediterranean part of the eastern Adriatic has a long tradition since its arrival during the Neolithic migrations. Sheep production system is extensive and generally carried out in traditional systems without intensive systematic breeding programmes for high uniform trait production (carcass, wool and milk yield). Therefore, eight indigenous Croatian sheep breeds from eastern Adriatic treated here as metapopulation (EAS), are generally considered as multipurpose breeds (milk, meat and wool), not specialised for a particular type of production, but known for their robustness and resistance to certain environmental conditions. Our objective was to identify genomic regions and genes that exhibit patterns of positive selection signatures, decipher their biological and productive functionality, and provide a "genomic" characterization of EAS adaptation and determine its production type. RESULTS: We identified positive selection signatures in EAS using several methods based on reduced local variation, linkage disequilibrium and site frequency spectrum (eROHi, iHS, nSL and CLR). Our analyses identified numerous genomic regions and genes (e.g., desmosomal cadherin and desmoglein gene families) associated with environmental adaptation and economically important traits. Most candidate genes were related to meat/production and health/immune response traits, while some of the candidate genes discovered were important for domestication and evolutionary processes (e.g., HOXa gene family and FSIP2). These results were also confirmed by GO and QTL enrichment analysis. CONCLUSIONS: Our results contribute to a better understanding of the unique adaptive genetic architecture of EAS and define its productive type, ultimately providing a new opportunity for future breeding programmes. At the same time, the numerous genes identified will improve our understanding of ruminant (sheep) robustness and resistance in the harsh and specific Mediterranean environment.