Runs Of Homozygosity Length Research Articles

Detectability of runs of homozygosity is influenced by analysis parameters and population-specific demographic history.

Wild populations are increasingly threatened by human-mediated climate change and land use changes. As populations decline, the probability of inbreeding increases, along with the potential for negative effects on individual fitness. Detecting and characterizing runs of homozygosity (ROHs) is a popular strategy for assessing the extent of individual inbreeding present in a population and can also shed light on the genetic mechanisms contributing to inbreeding depression. Here, we analyze simulated and empirical datasets to demonstrate the downstream effects of program selection and long-term demographic history on ROH inference, leading to context-dependent biases in the results. Through a sensitivity analysis we evaluate how various parameter values impact on ROH-calling results, highlighting its utility as a tool for parameter exploration. Our results indicate that ROH inferences are sensitive to factors such as sequencing depth and ROH length distribution, and with bias direction and magnitude varying with demographic history and the programs used. Estimation biases are particularly pronounced at lower sequencing depths, potentially leading to either underestimation or overestimation of inbreeding. These results are particularly important for the management of endangered species, as underestimating inbreeding signals in the genome can substantially undermine conservation initiatives. We also found that small true ROHs can be incorrectly lumped together and called as longer ROHs, leading to erroneous inference of recent inbreeding. To address these challenges, we suggest using a combination of ROH detection tools and ROH length-specific inferences, along with sensitivity analysis, to generate robust and context-appropriate population inferences regarding inbreeding history. We outline these recommendations for ROH estimation at multiple levels of sequencing effort, which are typical of conservation genomics studies.

Genetic Diversity in the Orenburg Goat Breed Revealed by Single-Nucleotide Polymorphism (SNP) Analysis: Initial Steps in Saving a Threatened Population

Background/Objectives: Orenburg goats are renowned for their soft down that acts as a substrate for warm clothing, particularly shawls that have an international reputation. As with many local livestock breeds, however, the Orenburg is presently at risk of extinction, an issue that can be addressed by assessing population genetic diversity and, thereafter, encouraging as much outbreeding as possible. Using single-nucleotide polymorphism (SNP)-based data, therefore, we analyzed the genetic diversity and population structure of modern Orenburg goats using samples collected from an expedition to Orenburg Oblast in 2024. Methods: We applied the Goat SNP50 BeadChip (Illumina, San Diego, CA, USA) for the genotyping of Orenburg goats from modern and archived populations. SNP genotypes of three Orenburg populations sampled in 2017 and 2019, Altai Mountain, Altai White, and Soviet Mohair breeds, were added to the dataset. Results: Principal component analysis and network and admixture analyses demonstrated that the genetic background inherent to the archived group of Orenburg goats was maintained in all modern populations. Values of genetic diversity indicators in modern populations were compatible with those obtained in comparison groups. Runs of homozygosity (ROH) were found in all the Orenburg goat populations (with a mean ROH length of 72.6–108.9 Mb and mean ROH number of 28–36). Genomic inbreeding based on ROH was low in all the Orenburg populations (FROH = 0.03–0.045). Conclusions: We showed that the ancestral background is retained in present-day Orenburg goats sampled in 2024. We provide the genetic basis through which certain breeder animals may be selected and bred traditionally or ex situ through a conservation program of gamete preservation.

Analyzing Runs of Homozygosity Reveals Patterns of Selection in German Brown Cattle.

An increasing trend in ancestral and classical inbreeding coefficients as well as inbreeding depression for longevity were found in the German Brown population. In addition, the proportion of US Brown Swiss genes is steadily increasing in German Browns. Therefore, the aim of the present study was to analyze the presence and genomic localization of runs of homozygosity (ROH) in order to evaluate their associations with the proportion of US Brown Swiss genes and survival rates of cows to higher lactations. Genotype data were sampled in 2364 German Browns from 258 herds. The final data set included 49,693 autosomal SNPs. We identified on average 35.996 ± 7.498 ROH per individual with a mean length of 8.323 ± 1.181 Mb. The genomic inbreeding coefficient FROH was 0.122 ± 0.032 and it decreased to 0.074, 0.031 and 0.006, when genomic homozygous segments > 8 Mb (FROH>8), >16 Mb (FROH>16) and >32 Mb (FROH>32) were considered. New inbreeding showed the highest correlation with FROH>32, whereas ancestral inbreeding coefficients had the lowest correlations with FROH>32. The correlation between the classical inbreeding coefficient and FROH was 0.572. We found significantly lower FROH, FROH>4, FROH>8 and FIS for US Brown Swiss proportions <60% compared to >80%. Cows surviving to the 2nd, 4th, 6th, 8th, and 10th lactation had lower genomic inbreeding for FROH and up to FROH>32, which was due to a lower number of ROH and a shorter average length of ROH. The strongest ROH island and consensus ROH shared by 50% of the animals was found on BTA 6 at 85-88 Mb. The genes located in this genomic region were associated with longevity (NPFFR2 and ADAMTS3), udder health and morphology (SLC4A4, NPFFR2, GC and RASSF6), milk production, milk protein percentage, coagulation properties of milk and milking speed (CSN3). On BTA 2, a ROH island was detected only in animals with <60% US Brown Swiss genes. Genes within this region are predominantly important for dual-purpose cattle breeds including Original Browns. For cows reaching more than 9 lactations, an exclusive ROH island was identified on BTA 7 with genes assumed to be associated with longevity. The analysis indicated that genomic homozygous regions important for Original Browns are still present and also ROH containing genes affecting longevity may have been identified. The breeding of German Browns should prevent any further increase in genomic inbreeding and run a breeding program with balanced weights on production, robustness and longevity.

Determinants of Human Asymmetry: Does Asymmetrical Retinal Vasculature Predict Asymmetry Elsewhere in the Body?

The aim of this study was to explore retinal vasculature asymmetry (ReVA) patterns in subjects from the islands of Vis and Korcula and the city of Split, Croatia. Asymmetry estimates were based on topographic image analysis of non-mydriatic retinal fundus photographs and compared with nine ophthalmic measurements, three Doppler-based pressure indices and eight frequencies of audiometry. ReVA was also correlated to the genomic runs of homozygosity (ROHs) and used in a Cox regression survival model, where we adjusted for the effects of sex, age and comorbidity. In 1873 subjects, ReVA estimates were significantly correlated with most ophthalmic asymmetry measures, less strongly with the ankle-brachial pressure index and only modestly with higher-amplitude audiometry asymmetries (lowest p = 0.020). ReVA was significantly correlated with the number of ROHs (r = 0.229, p < 0.001) but less strongly with the ROH length (r = 0.101, p < 0.001). The overlap of asymmetries was low, with only 107 subjects (5.7% of the total sample) who had two or more instances in which they were among the top 10%. Multiple asymmetries did not affect survival (HR = 0.74, 95% confidence intervals 0.45-1.22). Retinal vasculature asymmetry is a poor predictor of asymmetry elsewhere in the body. Despite its existence and apparent association with comorbidities, the observed extent of retinal vasculature asymmetry did not affect the lifespan in this population.

Genetic diversity analysis of Inner Mongolia cashmere goats (Erlangshan subtype) based on whole genome re-sequencing

BackgroundInner Mongolia cashmere goat (IMCG), renowned for its superior cashmere quality, is a Chinese indigenous goat breed that has been developed through natural and artificial selection over a long period. However, recently, the genetic resources of IMCGs have been significantly threatened by the introduction of cosmopolitan goat breeds and the absence of adequate breed protection systems.ResultsIn order to assess the conservation effectiveness of IMCGs and efficiently preserve and utilize the purebred germplasm resources, this study analyzed the genetic diversity, kinship, family structure, and inbreeding of IMCGs utilizing resequencing data from 225 randomly selected individuals analyzed using the Plink (v.1.90), GCTA (v.1.94.1), and R (v.4.2.1) software. A total of 12,700,178 high-quality SNPs were selected through quality control from 34,248,064 SNP sites obtained from 225 individuals. The average minor allele frequency (MAF), polymorphic information content (PIC), and Shannon information index (SHI) were 0.253, 0.284, and 0.530, respectively. The average observed heterozygosity (Ho) and the average expected heterozygosity (He) were 0.355 and 0.351, respectively. The analysis of the identity by state distance matrix and genomic relationship matrix has shown that most individuals’ genetic distance and genetic relationship are far away, and the inbreeding coefficient is low. The family structure analysis identified 10 families among the 23 rams. A total of 14,109 runs of homozygosity (ROH) were identified in the 225 individuals, with an average ROH length of 1014.547 kb. The average inbreeding coefficient, calculated from ROH, was 0.026 for the overall population and 0.027 specifically among the 23 rams, indicating a low level of inbreeding within the conserved population.ConclusionsThe IMCGs exhibited moderate polymorphism and a low level of kinship with inbreeding occurring among a limited number of individuals. Simultaneously, it is necessary to prevent the loss of bloodline to guarantee the perpetuation of the IMCGs’ germplasm resources.

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

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. 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. 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 111 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 regions with ROH islands were found to be associated with production traits. 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.

Multilocus pathogenic variants contribute to intrafamilial clinical heterogeneity: a retrospective study of sibling pairs with neurodevelopmental disorders

BackgroundMultilocus pathogenic variants (MPVs) are genetic changes that affect multiple gene loci or regions of the genome, collectively leading to multiple molecular diagnoses. MPVs may also contribute to intrafamilial phenotypic variability between affected individuals within a nuclear family. In this study, we aim to gain further insights into the influence of MPVs on a disease manifestation in individual research subjects and explore the complexities of the human genome within a familial context.MethodsWe conducted a systematic reanalysis of exome sequencing data and runs of homozygosity (ROH) regions of 47 sibling pairs previously diagnosed with various neurodevelopmental disorders (NDD).ResultsWe found siblings with MPVs driven by long ROH regions in 8.5% of families (4/47). The patients with MPVs exhibited significantly higher FROH values (p-value = 1.4e-2) and larger total ROH length (p-value = 1.8e-2). Long ROH regions mainly contribute to this pattern; the siblings with MPVs have a larger total size of long ROH regions than their siblings in all families (p-value = 6.9e-3). Whereas the short ROH regions in the siblings with MPVs are lower in total size compared to their sibling pairs with single locus pathogenic variants (p-value = 0.029), and there are no statistically significant differences in medium ROH regions between sibling pairs (p-value = 0.52).ConclusionThis study sheds light on the significance of considering MPVs in families with affected sibling pairs and the role of ROH as an adjuvant tool in explaining clinical variability within families. Identifying individuals carrying MPVs may have implications for disease management, identification of possible disease risks to different family members, genetic counseling and exploring personalized treatment approaches.

Inbreeding depression for producer-recorded udder, metabolic, and reproductive diseases in US dairy cattle

This study leveraged a growing dataset of producer-recorded phenotypes for mastitis, reproductive diseases (metritis and retained placenta), and metabolic diseases (ketosis, milk fever, and displaced abomasum) to investigate the potential presence of inbreeding depression for these disease traits. Phenotypic, pedigree, and genomic information were obtained for 354,043 and 68,292 US Holstein and Jersey cows, respectively. Total inbreeding coefficients were calculated using both pedigree and genomic information; the latter included inbreeding estimates obtained using a genomic relationship matrix and runs of homozygosity. We also generated inbreeding coefficients based on the generational inbreeding for recent and old pedigree inbreeding, for different run-of-homozygosity length classes, and for recent and old homozygous-by-descent segment-based inbreeding. Estimates on the liability scale revealed significant evidence of inbreeding depression for reproductive-disease traits, with an increase in total pedigree and genomic inbreeding showing a notable effect for recent inbreeding. However, we found inconsistent evidence for inbreeding depression for mastitis or any metabolic diseases. Notably, in Holsteins, the probability of developing displaced abomasum decreased with inbreeding, particularly for older inbreeding. Estimates of disease probability for cows with low, average, and high inbreeding levels did not significantly differ across any inbreeding coefficient and trait combination, indicating that although inbreeding may affect disease incidence, it likely plays a smaller role compared with management and environmental factors.

Genome-wide runs of homozygosity in Indian goat breeds reared under small holder production system

Small holder goat production system is often constrained by high inbreeding due to small herd size and uncontrolled breeding. Runs of homozygosity (ROH), the long stretches of homozygous genomic DNA is the most reliable measure of autozygosity. The objective of present study was to investigate the number and coverage of ROH in the genome and to estimate the genomic inbreeding coefficient (FROH) in two divergent Indian goat breeds viz; Attappady Black and Malabari goats farmed under small holder production system. The genome-wide single nucleotide polymorphism (SNP) marker data obtained by Illumina SNP50 goat BeadChip genotyping of 48 goats (24 each of Attappady Black and Malabari goats) sampled from farmers flock in their respective breeding tract was utilised for ROH detection. The ROH of > 1 Mb was defined as tracts of homozygous genotypes with at least 15 SNPs and less than five missing SNPs. The ROH detection was carried out with PLINK 1.9 version. The proportion of goats lacking ROH (per cent) was 66.67 in Attappady Black and 39.13 in Malabari goats. The mean number and length of ROH of 1 Mb or more was higher in Malabari goats (2.1304 ± 0.6369 and 6.0016 ± 0.5271 Mb) compared to Attappady Black goats (0.4583 ± 0.1343 and 4.0197 ± 0.3755 Mb). Mean ± S.E of sum of ROH coverage of genome per individual (SROH) was 1.8423 ± 0.05976 and 8.8236 ± 1.2785 Mb in Attappady Black and Malabari goats, respectively and differed among the two breeds significantly (p ≤ 0.05). Analysis of the distribution of ROH according to their length showed that majority of the detected ROH were < 8 Mb in length in both breeds with no ROH of > 8 Mb in Attappady Black goats. Mean ± S.E of genomic inbreeding coefficient (FROH≥1 Mb) in per cent was 0.519 ± 0.19 and 0.07480 ± 0.0243 in Malabari goats and Attappady Black goats, respectively. The pattern of ROH estimated in the present analysis indicates the inbreeding history of the goats farmed under small holder production system. Results of present study indicate that both breeds are less consanguineous and showed no evidence of recent inbreeding.

A Comprehensive Genomic Analysis of Chinese Indigenous Ningxiang Pigs: Genomic Breed Compositions, Runs of Homozygosity, and Beyond.

Ningxiang pigs are a renowned indigenous pig breed in China, known for their meat quality, disease resistance, and environmental adaptability. In recent decades, consumer demand for meats from indigenous breeds has grown significantly, fueling the selection and crossbreeding of Ningxiang pigs (NXP). The latter has raised concerns about the conservation and sustainable use of Ningxiang pigs as an important genetic resource. To address these concerns, we conducted a comprehensive genomic study using 2242 geographically identified Ningxiang pigs. The estimated genomic breed composition (GBC) suggested 2077 pigs as purebred Ningxiang pigs based on a ≥94% NXP-GBC cut-off. The remaining 165 pigs were claimed to be crosses, including those between Duroc and Ningxiang pigs and between Ningxiang and Shaziling pigs, and non-Ningxiang pigs. Runs of homozygosity (ROH) were identified in the 2077 purebred Ningxiang pigs. The number and length of ROH varied between individuals, with an average of 32.14 ROH per animal and an average total length of 202.4 Mb per animal. Short ROH (1-5 Mb) was the most abundant, representing 66.5% of all ROH and 32.6% of total ROH coverage. The genomic inbreeding estimate was low (0.089) in purebred Ningxiang pigs compared to imported western pig breeds. Nine ROH islands were identified, pinpointing candidate genes and QTLs associated with economic traits of interest, such as reproduction, carcass and growth traits, lipid metabolism, and fat deposition. Further investigation of these ROH islands and candidate genes is anticipated to better understand the genomics of Ningxiang pigs.

Genome-wide scan for runs of homozygosity in South American Camelids

BackgroundAlpaca (Vicugna pacos), llama (Lama glama), vicugna (Vicugna vicugna) and guanaco (Lama guanicoe), are the camelid species distributed over the Andean high-altitude grasslands, the Altiplano, and the Patagonian arid steppes. Despite the wide interest on these animals, most of the loci under selection are still unknown. Using whole-genome sequencing (WGS) data we investigated the occurrence and the distribution of Runs Of Homozygosity (ROHs) across the South American Camelids (SACs) genome to identify the genetic relationship between the four species and the potential signatures of selection.ResultsA total of 37 WGS samples covering the four species was included in the final analysis. The multi-dimensional scaling approach showed a clear separation between the four species; however, admixture analysis suggested a strong genetic introgression from vicugna and llama to alpaca. Conversely, very low genetic admixture of the guanaco with the other SACs was found. The four species did not show significant differences in the number, length of ROHs (100-500 kb) and genomic inbreeding values. Longer ROHs (> 500 kb) were found almost exclusively in alpaca. Seven overlapping ROHs were shared by alpacas, encompassing nine loci (FGF5, LOC107034918, PRDM8, ANTXR2, LOC102534792, BSN, LOC116284892, DAG1 and RIC8B) while nine overlapping ROHs were found in llama with twenty-five loci annotated (ERC2, FZD9, BAZ1B, BCL7B, LOC116284208, TBL2, MLXIPL, PHF20, TRNAD-AUC, LOC116284365, RBM39, ARFGEF2, DCAF5, EXD2, HSPB11, LRRC42, LDLRAD1, TMEM59, LOC107033213, TCEANC2, LOC102545169, LOC116278408, SMIM15, NDUFAF2 and RCOR1). Four overlapping ROHs, with three annotated loci (DLG1, KAT6B and PDE4D) and three overlapping ROHs, with seven annotated genes (ATP6V1E1, BCL2L13, LOC116276952, BID, KAT6B, LOC116282667 and LOC107034552), were detected for vicugna and guanaco, respectively.ConclusionsThe signatures of selection revealed genomic areas potentially selected for production traits as well as for natural adaptation to harsh environment. Alpaca and llama hint a selection driven by environment as well as by farming purpose while vicugna and guanaco showed selection signals for adaptation to harsh environment. Interesting, signatures of selection on KAT6B gene were identified for both vicugna and guanaco, suggesting a positive effect on wild populations fitness. Such information may be of interest to further ecological and animal production studies.

Analysis of genetic diversity and genetic structure of Qinchuan cattle conservation population using whole-genome resequencing.

In the conservation of livestock and poultry resources, population genetic diversity and genetic structure of the conservation population are important factors affecting the effectiveness of conservation. In this study, whole-genome resequencing technology was used to detect genomic variation in 100 Qinchuan cattle (30 bulls and 70 cows). By analyzing population genetic diversity, runs of homozygosity (ROH) distribution features, kinship relationships, and family structure, the conservation effectiveness of Qinchuan cattle was comprehensively evaluated. The results showed that a total of 20,968,017 high-quality SNPs were detected in 100 Qinchuan cattle, the average minimum allele frequency was 0.191±0.124, the average polymorphic information content was 0.279±0.131, and the average observed heterozygosity was 0.275±0.131, the average expected heterozygosity is 0.279±0.131, indicating that the genetic diversity of the Qinchuan cattle conservation population is relatively rich. The average identity by state (IBS) distance of the Qinchuan conservation population was 0.243±0.020, with a value of 0.242±0.021 for the bulls. The results of the kinship G-matrix were consistent with the results of the IBS distance matrix, both showing that some individuals in the conservation population had close kinship. A total of 8258 genomic ROH were detected in 100 Qinchuan cattle, with a total length of 9.64 GB. The average length of ROH fragments was 1.167±1.203 Mb, 69.35% of the ROH were short ROH with a length of 0.5~1 Mb, and the average total length of ROH per individual was 96.40 Mb. The average inbreeding coefficient based on ROH was 0.039±0.039, with a value of 0.044±0.035 for the bulls, indicating that some bulls had a certain degree of inbreeding accumulation. The results of the phylogenetic tree combined with kinship analysis showed that the individuals in the Qinchuan cattle conservation population could be divided into eight families, including seven families with bulls and one family without bulls. This study demonstrated that the genetic diversity of the Qinchuan conservation population is relatively rich, with no significant inbreeding accumulation, but there is a risk of inbreeding among some individuals. Therefore, it is necessary to strengthen selection and mating to ensure the sustainable development of Qinchuan cattle resources.

Pedigree and genome-based patterns of homozygosity in the South African Ayrshire, Holstein, and Jersey breeds.

The erosion of genetic diversity limits long-term genetic gain and impedes the sustainability of livestock production. In the South African (SA) dairy industry, the major commercial dairy breeds have been applying estimated breeding values (EBVs) and/or have been participating in Multiple Across Country Evaluations (MACE). The transition to genomic estimated breeding values (GEBVs) in selection strategies requires monitoring of the genetic diversity and inbreeding of current genotyped animals, especially considering the comparatively small population sizes of global dairy breeds in SA. This study aimed to perform a homozygosity-based evaluation of the SA Ayrshire (AYR), Holstein (HST), and Jersey (JER) dairy cattle breeds. Three sources of information, namely 1) single nucleotide polymorphism (SNP) genotypes (3,199 animals genotyped for 35,572 SNPs) 2) pedigree records (7,885 AYR; 28,391 HST; 18,755 JER), and 3) identified runs of homozygosity (ROH) segments were used to quantify inbreeding related parameters. The lowest pedigree completeness was for the HST population reducing from a value of 0.990 to 0.186 for generation depths of one to six. Across all breeds, 46.7% of the detected ROH were between 4 megabase pairs (Mb) and 8Mb in length. Two conserved homozygous haplotypes were identified in more than 70% of the JER population on Bos taurus autosome (BTA) 7. The JER breed displayed the highest level of inbreeding across all inbreeding coefficients. The mean (± standard deviation) pedigree-based inbreeding coefficient (FPED) ranged from 0.051 (±0.020) for AYR to 0.062 (±0.027) for JER, whereas SNP-based inbreeding coefficients (FSNP) ranged from 0.020 (HST) to 0.190 (JER) and ROH-based inbreeding coefficients, considering all ROH segment coverage (FROH), ranged from 0.053 (AYR) to 0.085 (JER). Within-breed Spearman correlations between pedigree-based and genome-based estimates ranged from weak (AYR: 0.132 between FPED and FROH calculated for ROH <4Mb in size) to moderate (HST: 0.584 between FPED and FSNP). Correlations strengthened between FPED and FROH as the ROH length category was considered lengthened, suggesting a dependency on breed-specific pedigree depth. The genomic homozygosity-based parameters studied proved useful in investigating the current inbreeding status of reference populations genotyped to implement genomic selection in the three most prominent South African dairy cattle breeds.

Genome-wide analysis of runs of homozygosity in Pakistani controls with no history of speech or language-related developmental phenotypes

Background Runs of homozygosity (ROHs) analysis of controls provide a convenient resource to minimize the association of false positive results of disease-associated ROHs and genetic variants for simple and complex disorders in individuals from the same population. Evidence for the value of ROHs to speech or language-related traits is restricted due to the absence of population-matched behaviourally defined controls and limited family-based studies. Aim This study aims to identify common ROHs in the Pakistani population, focussing on the total length and frequency of ROHs of variable sizes, shared ROHs, and their genomic distribution. Subjects and methods We performed homozygosity analysis (in PLINK) of 86 individuals (39 males, 47 females) with no history of speech or language-related phenotypes (controls) who had been genotyped with the Illumina Infinium QC Array-24. Results ROHs of 1-<4 megabases (Mb) were frequent in unrelated individuals. We observed ROHs over 20 Mb among six individuals. Over 30 percent of the identified ROHs were shared among several individuals, indicating consanguinity’s effect on the Pakistani population. Conclusion Our findings serve as a foundation for family-based genetic studies of consanguineous families with speech or language-related disorders to ultimately narrow the homozygosity regions of interest to identify pathogenic variants.

Estimates of genomic inbreeding and identification of candidate regions in Beijing-You chicken populations.

Runs of homozygosity (ROHs) has become an effective method for analysing inbreeding in livestock populations. Moreover, ROHs is well-suited to detect signatures of selection via ROH islands. This study aimed to investigate the occurrence and distribution of ROHs, compare the genomic inbreeding coefficients and identify the genomic regions with high ROH frequencies in different Beijing-You chicken (BY) populations, including a random conservation population (BY_R), a pedigree conservation population (BY_P), and a commercial population obtained from the market (BY_C). Among them, BY_R in 2010 and 2019 were BY_R1 and BY_R2 respectively. A total of 27 916 ROHs were identified. The average number of ROHs per individual across the three BY populations ranged from 213 (BY_P) to 161 (BY_C), and the average length of ROHs ranged from 0.432Mb (BY_R2) to 0.451Mb (BY_P). The highest inbreeding coefficient calculated based on ROHs (FROH ) was 0.1 in BY_P, whereas the lowest FROH was 0.0743 in BY_C. In addition, the inbreeding coefficient of BY_R2 (FROH =0.0798) was higher than that of BY_R1 (FROH =0.0579). Furthermore, the highest proportion of long ROH fragments (>4 Mb) was observed in BY_P and BY_C. This study showed the top 10 ROH islands of each population, and these ROH islands harboured 53 genes, some of which were related to limb development, body size and immune response. These findings contribute to the understanding of genetic diversity and population demography, and might help improve breeding and conservation strategies for BY populations.

Genomic characterization of autozygosity and recent inbreeding trends in all major breeds of US dairy cattle.

Maintaining a genetically diverse dairy cattle population is critical to preserving adaptability to future breeding goals and avoiding declines in fitness. This study characterized the genomic landscape of autozygosity and assessed trends in genetic diversity in 5 breeds of US dairy cattle. We analyzed a sizable genomic data set containing 4,173,679 pedigreed and genotyped animals of the Ayrshire, Brown Swiss, Guernsey, Holstein, and Jersey breeds. Runs of homozygosity (ROH) of 2 Mb or longer in length were identified in each animal. The within-breed means for number and the combined length of ROH were highest in Jerseys (62.66 ± 8.29 ROH and 426.24 ± 83.40 Mb, respectively; mean ± SD) and lowest in Ayrshires (37.24 ± 8.27 ROH and 265.05 ± 85.00 Mb, respectively). Short ROH were the most abundant, but moderate to large ROH made up the largest proportion of genome autozygosity in all breeds. In addition, we identified ROH islands in each breed. This revealed selection patterns for milk production, productive life, health, and reproduction in most breeds and evidence for parallel selective pressure for loci on chromosome 6 between Ayrshire and Brown Swiss and for loci on chromosome 20 between Holstein and Jersey. We calculated inbreeding coefficients using 3 different approaches, pedigree-based (FPED), marker-based using a genomic relationship matrix (FGRM), and segment-based using ROH (FROH). The average inbreeding coefficient ranged from 0.06 in Ayrshires and Brown Swiss to 0.08 in Jerseys and Holsteins using FPED, from 0.22 in Holsteins to 0.29 in Guernsey and Jerseys using FGRM, and from 0.11 in Ayrshires to 0.17 in Jerseys using FROH. In addition, the effective population size at past generations (5-100 generations ago), the yearly rate of inbreeding, and the effective population size in 3 recent periods (2000-2009, 2010-2014, and 2015-2018) were determined in each breed to ascertain current and historical trends of genetic diversity. We found a historical trend of decreasing effective population size in the last 100 generations in all breeds and breed differences in the effect of the recent implementation of genomic selection on inbreeding accumulation.

Comparative analysis of genomic inbreeding parameters and runs of homozygosity islands in several fancy and meat rabbit breeds.

Runs of homozygosity (ROH) are defined as long stretches of DNA homozygous at each polymorphic position. The proportion of genome covered by ROH and their length are indicators of the level and origin of inbreeding. In this study, we analysed SNP chip datasets (obtained using the Axiom OrcunSNP Array) of a total of 702 rabbits from 12 fancy breeds and four meat breeds to identify ROH with different approaches and calculate several genomic inbreeding parameters. The highest average number of ROH per animal was detected in Belgian Hare (~150) and the lowest in Italian Silver (~106). The average length of ROH ranged from 4.001 ± 0.556Mb in Italian White to 6.268 ± 1.355Mb in Ermine. The same two breeds had the lowest (427.9 ± 86.4 Mb, Italian White) and the highest (921.3 ± 179.8 Mb, Ermine) average values of the sum of all ROH segments. More fancy breeds had a higher level of genomic inbreeding (as defined by ROH) than meat breeds. Several ROH islands contain genes involved in body size, body length, pigmentation processes, carcass traits, growth, and reproduction traits (e.g.: AOX1, GPX5, IFRD1, ITGB8, NELL1, NR3C1, OCA2, TRIB1, TRIB2). Genomic inbreeding parameters can be useful to overcome the lack of information in the management of rabbit genetic resources. ROH provided information to understand, to some extent, the genetic history of rabbit breeds and to identify signatures of selection in the rabbit genome.

Genetic diversity and population structure of Tongcheng pigs in China using whole-genome SNP chip.

Tongcheng (TC) pigs, distinguished by their superior meat quality, are a Chinese indigenous pig breed. Recently, the genetic resources of TC pigs are under tremendous threat due to the introduction of cosmopolitan pig breeds and African swine fever disease. To promote their management and conservation, the present study assessed genetic diversity and population structure of TC pigs using single nucleotide polymorphism (SNP) markers. A total of 26, 999 SNPs were screened from 51, 315 SNPs in 68 TC pigs. The multi-dimensional scaling (MDS) analysis and neighbor-joining tree revealed that all 68 pigs were from a purebred population. The effective population size decreased over time, and it was 96 prior to generation 20. Both linkage disequilibrium (LD) and neutrality test indicated a low selection of TC pigs with average LD value of 0.15 ± 0.23. Genetic diversity results exhibited a minor allele frequency (MAF) of 0.23, observed heterozygosity (HO) of 0.32, expected heterozygosity (He) of 0.31, and nucleotide diversity (Pi) of 0.31. All these parameters indicated a remarkably high genetic diversity of TC pigs. Additionally, 184 runs of homozygosity (ROH) segments were detected from the whole genome of TC pigs with an average ROH length of 23.71Mb, ranging from 11.26Mb to 69.02 Mb. The highest ROH coverage was found on chromosome 1 (10.12%), while the lowest was on chromosome 18 (1.49%). The average inbreeding coefficients based on ROH (FROH) was 0.04%. Fourteen ROH islands containing 240 genes were detected on 9 different autosomes. Some of these 240 genes were overlapped with the genes related to biological processes such as immune function, reproduction, muscular development, and fat deposition, including FFAR2, FFAR4, MAPK8, NPY5R, KISS1, and these genes might be associated with such traits as meat quality and disease resistance in TC pigs. Taken together, population structure and genetic diversity results suggested that the TC pig represented a valuable genetic resource. However, TC pig breed conservation program remains to be further optimized to ensure adequate genetic diversity and avoid inbreeding depression. Our findings provide theoretical basis for formulating management and conservation strategies for TC pigs.

Conservation status and historical relatedness of South African communal indigenous goat populations using a genome-wide single-nucleotide polymorphism marker.

Indigenous goats form the majority of populations in smallholder, low input, low output production systems and are considered an important genetic resource due to their adaptability to different production environments and support of communal farming. Effective population size (N e ), inbreeding levels, and the runs of homozygosity (ROHs) are effective tools for exploring the genetic diversity and understanding the demographic history in efforts to support breeding strategies to use and conserve genetic resources. Across populations, the current N e of Gauteng was the lowest at 371 animals, while the historical N e across populations suggests that the ancestor N e has decreased by 53.86%, 44.58%, 42.16%, and 41.16% in Free State (FS), North West (NW), Limpopo (LP), and Gauteng (GP), respectively, over the last 971 generations. Genomic inbreeding levels related to ancient kinship (F ROH > 5 Mb) were highest in FS (0.08 ± 0.09) and lowest in the Eastern Cape (EC) (0.02 ± 0.02). A total of 871 ROH island regions which include important environmental adaptation and hermo-tolerance genes such as IL10RB, IL23A, FGF9, IGF1, EGR1, MTOR, and MAPK3 were identified (occurring in over 20% of the samples) in FS (n = 37), GP (n = 42), and NW (n = 2) populations only. The mean length of ROH across populations was 7.76 Mb and ranged from 1.61 Mb in KwaZulu-Natal (KZN) to 98.05 Mb (GP and NW). The distribution of ROH according to their size showed that the majority (n = 1949) of the detected ROH were > 5 Mb in length compared to the other categories. Assuming two hypothetical ancestral populations, the populations from KZN and LP are revealed, supporting PC 1. The genomes of KZN and LP share a common origin but have substantial admixture from the EC and NW populations. The findings revealed that the occurrence of high N e and autozygosity varied largely across breeds in communal indigenous goat populations at recent and ancient events when a genome-wide single-nucleotide polymorphism (SNP) marker was used. The use of Illumina goat SNP50K BeadChip shows that there was a migration route of communal indigenous goat populations from the northern part (LP) of South Africa to the eastern areas of the KZN that confirmed their historical relatedness and coincides with the migration periods of the Bantu nation.

Runs of homozygosity in Sable Island feral horses reveal the genomic consequences of inbreeding and divergence from domestic breeds

BackgroundUnderstanding inbreeding and its impact on fitness and evolutionary potential is fundamental to species conservation and agriculture. Long stretches of homozygous genotypes, known as runs of homozygosity (ROH), result from inbreeding and their number and length can provide useful population-level information on inbreeding characteristics and locations of signatures of selection. However, the utility of ROH for conservation is limited for natural populations where baseline data and genomic tools are lacking. Comparing ROH metrics in recently feral vs. domestic populations of well understood species like the horse could provide information on the genetic health of those populations and offer insight into how such metrics compare between managed and unmanaged populations. Here we characterized ROH, inbreeding coefficients, and ROH islands in a feral horse population from Sable Island, Canada, using ~41 000 SNPs and contrasted results with those from 33 domestic breeds to assess the impacts of isolation on ROH abundance, length, distribution, and ROH islands.ResultsROH number, length, and ROH-based inbreeding coefficients (FROH) in Sable Island horses were generally greater than in domestic breeds. Short runs, which typically coalesce many generations prior, were more abundant than long runs in all populations, but run length distributions indicated more recent population bottlenecks in Sable Island horses. Nine ROH islands were detected in Sable Island horses, exhibiting very little overlap with those found in domestic breeds. Gene ontology (GO) enrichment analysis for Sable Island ROH islands revealed enrichment for genes associated with 3 clusters of biological pathways largely associated with metabolism and immune function.ConclusionsThis study indicates that Sable Island horses tend to be more inbred than their domestic counterparts and that most of this inbreeding is due to historical bottlenecks and founder effects rather than recent mating between close relatives. Unique ROH islands in the Sable Island population suggest adaptation to local selective pressures and/or strong genetic drift and highlight the value of this population as a reservoir of equine genetic variation. This research illustrates how ROH analyses can be applied to gain insights into the population history, genetic health, and divergence of wild or feral populations of conservation concern.