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Topic:Genetics

Genetics in horses encompasses the study of hereditary traits and the genetic makeup that influences various characteristics and health conditions in equine populations. This field involves the analysis of genes and their functions, inheritance patterns, and the impact of genetic variations on traits such as coat color, performance ability, and susceptibility to diseases. Research in equine genetics employs techniques such as genome mapping, sequencing, and genetic testing to identify specific genes and mutations associated with these traits. This page gathers peer-reviewed research studies and scholarly articles that explore the genetic basis of equine traits, the methodologies used in genetic research, and the implications for breeding, health management, and conservation of horse breeds.
Corrigendum: Gene therapy approaches for equine osteoarthritis.
Frontiers in veterinary science    January 4, 2023   Volume 9 1117776 doi: 10.3389/fvets.2022.1117776
Thampi P, Samulski RJ, Grieger JC, Phillips JN, McIlwraith CW, Goodrich LR.[This corrects the article DOI: 10.3389/fvets.2022.962898.].
Immunogenicity analysis of BPV-1 positive equine sarcoid-derived cultured fibroblasts.
Veterinary immunology and immunopathology    January 4, 2023   Volume 256 110547 doi: 10.1016/j.vetimm.2023.110547
Gysens L, Depuydt E, Patruno M, Haspeslagh M, Spaas JH, Martens A.Sarcoids are the most common equine skin tumours Although they do not metastasize, they can be locally aggressive and cause significant clinical symptoms in affected horses. Despite being common, very little is known about the host immune response and the biological mechanisms underlying persistence and recurrence of equine sarcoids. The latter reflects the need for further research in this field. This in-vitro study used sarcoid explants from horses with naturally occurring sarcoids (n = 12) to evaluate the induction of a humoral immune response directed against equine sarcoid-derived bovin...
The complete ITS2 barcoding region for Strongylus vulgaris and Strongylus edentatus.
Veterinary research communications    January 4, 2023   Volume 47, Issue 3 1767-1771 doi: 10.1007/s11259-022-10067-w
Halvarsson P, Tydén E.Gastrointestinal nematode parasites are of major concern for horses, where Strongylus vulgaris is considered the most pathogenic among the Strongylus species. Diagnosis of S. vulgaris infections can be determined with next generation sequencing techniques, which are inherently dependent on reference sequences. The best marker for parasitic nematodes is internal transcribed spacer 2 (ITS2) and we provide the first complete ITS2 sequences from five morphologically identified S. vulgaris and additional sequences from two S. edentatus. These sequences have high similarity to already published part...
First sex modification case in equine cloning.
PloS one    January 4, 2023   Volume 18, Issue 1 e0279869 doi: 10.1371/journal.pone.0279869
Suvá M, Arnold VH, Wiedenmann EA, Jordan R, Galvagno E, Martínez M, Vichera GD.Somatic cell nuclear transfer (SCNT) is an asexual reproductive technique where cloned offspring contain the same genetic material as the original donor. Although this technique preserves the sex of the original animal, the birth of sex-reversed offspring has been reported in some species. Here, we report for the first time the birth of a female foal generated by SCNT of a male nuclear donor. After a single SCNT procedure, 16 blastocysts were obtained and transferred to eight recipient mares, resulting in the birth of two clones: one male and one female. Both animals had identical genetic prof...
Double and quadruple deletion mutant of EHV-1 is highly attenuated and induces optimal immune response.
Vaccine    January 4, 2023   Volume 41, Issue 5 1081-1093 doi: 10.1016/j.vaccine.2022.12.044
Balena V, Pradhan SS, Bera BC, Anand T, Sansanwal R, Khetmalis R, Madhwal A, Bernela M, Supriya K, Pavulraj S, Tripathi BN, Virmani N.Equid alphaherpesvirus 1 (EHV-1) infection causes significant health problems in equines. The EHV-1 infection leads to abortion storm in mares, respiratory disease and myeloencephalopathy. Despite the wide use of vaccines, the outbreaks of EHV-1 infections keep occurring globally, suggesting the need for the development of improved vaccines. Gene deletion attenuated mutant viruses could be a good candidate for the development of modified live vaccines. Here, we report the generation of mutant EHV-1 by deleting virulence (glycoprotein E & internal repeat 6; IR6) and immune evasive (pUL43 &a...
Blood types and antibody profiles of Straight Egyptian Arabian horses in Qatar: Preliminary results.
Journal of equine veterinary science    January 3, 2023   Volume 122 104209 doi: 10.1016/j.jevs.2022.104209
Mattei D, Fenn MS, Caraguel C, Vinardell T.The characterization of the blood groups, antibody profiles, and its distribution pattern among different horse breeds and geographic locations, can be very useful in life-threatening situations where a blood transfusion is needed, and compatibility tests are not readily available. This study estimated the distribution of blood types and antibody profiles in Straight Egyptian Arabian horses from Qatar. A total of 20 Straight Egyptian Arabian horses, from multiple origins and genetic background were included. Venous blood from each horse was typed and screened for anti-red blood cell (RBC) hemo...
Lethal variants of equine pregnancy: is it the placenta or foetus leading the conceptus in the wrong direction?
Reproduction, fertility, and development    January 3, 2023   Volume 35, Issue 2 51-69 doi: 10.1071/RD22239
Shilton CA, Kahler A, Roach JM, Raudsepp T, de Mestre AM.Embryonic and foetal loss remain one of the greatest challenges in equine reproductive health with 5-10% of established day 15 pregnancies and a further 5-10% of day 70 pregnancies failing to produce a viable foal. The underlying reason for these losses is variable but ultimately most cases will be attributed to pathologies of the environment of the developing embryo and later foetus, or a defect intrinsic to the embryo itself that leads to lethality at any stage of gestation right up to birth. Historically, much research has focused on the maternal endometrium, endocrine and immune responses ...
A one-health lens offers new perspectives on the importance of endocrine disorders in the equine athlete.
Journal of the American Veterinary Medical Association    January 2, 2023   Volume 261, Issue 2 153-164 doi: 10.2460/javma.22.11.0485
Manfredi JM, Jacob S, Norton E.Endocrine disorders are associated with joint pain and tendon injury in humans, but the effects in the horse are only starting to be understood. Similar patterns of clinical signs and injury appear to affect horses and humans for both orthopedic and endocrine disorders, supporting the use of a one-health approach to tackle these issues. In this Currents in One Health, we will discuss common equine endocrinopathies, current testing recommendations, dietary management, genetic predispositions, and endocrine disorders' effects on performance. Our aim is to use a one-health lens to describe curren...
A New Intra-Breed Type, “Mamyr-Aktobe,” of the Kushum Breed of Horses of the Aktobe Population.
Archives of Razi Institute    December 31, 2022   Volume 77, Issue 6 2273-2279 doi: 10.22092/ARI.2022.360058.2539
The Kushum breed is one of the top breeds in the structure of horse breeds in the Aktobe region. In terms of numbers, it ranks third after the Kazakh and Mugalzhar breeds. The Kushum breed in the Aktobe region compares favorably with a number of horse-draft factory breeds in terms of early maturity, fertility, high meat, milk productivity, and economy of keeping. This article describes a new intra-breed type, the "Mamyr-Aktobe" type of the Kushum horse breed of the Aktobe population. The structure of the intra-breed type of Mamyr-Aktobe of the Kushum breed includes three factory lines of stall...
Antimicrobial Resistance and Genetic Diversity of Pseudomonas aeruginosa Strains Isolated from Equine and Other Veterinary Samples.
Pathogens (Basel, Switzerland)    December 30, 2022   Volume 12, Issue 1 64 doi: 10.3390/pathogens12010064
Pottier M, Castagnet S, Gravey F, Leduc G, Sévin C, Petry S, Giard JC, Le Hello S, Léon A. is one of the leading causes of healthcare-associated infections in humans. This bacterium is less represented in veterinary medicine, despite causing difficult-to-treat infections due to its capacity to acquire antimicrobial resistance, produce biofilms, and persist in the environment, along with its limited number of veterinary antibiotic therapies. Here, we explored susceptibility profiles to antibiotics and to didecyldimethylammonium chloride (DDAC), a quaternary ammonium widely used as a disinfectant, in 168 strains isolated from animals, mainly Equidae. A genomic study was performed on...
Proteomic Differences Between the Ovulatory and Anovulatory Sides of the Mare’s Follicular and Oviduct Fluid.
Journal of equine veterinary science    December 30, 2022   Volume 121 104207 doi: 10.1016/j.jevs.2022.104207
Shen Y, Ulaangerel T, Ren H, Davshilt T, Yi M, Li X, Xing J, Du M, Bai D, Dugarjav M, Bou G.The follicular fluid and oviduct fluid play major roles in oocyte maturation, sperm activation, and fertilization. To better understand the physiological environments for equine oocyte maturation and fertilization, here we conducted the proteome analysis and comparison on follicular fluids and oviduct fluids from the ovulatory side and the anovulatory side. The results showed that there is no significant difference between two side oviduct fluids, but a total of 71 differential abundance proteins (DAPs) were identified between two side follicular fluids, of which 9 are up-regulated and 62 are ...
Results of a Clinical Trial Showing Changes to the Faecal Microbiome in Racing Thoroughbreds after Feeding a Nutritional Supplement.
Veterinary sciences    December 30, 2022   Volume 10, Issue 1 27 doi: 10.3390/vetsci10010027
Adams VJ, LeBlanc N, Penell J.Next-generation sequencing (NGS) has been used to evaluate the effect of various interventions on the equine microbiome. The aim of this randomised blinded clinical trial was to determine if a prebiotic nutritional supplement would result in a change from baseline in the faecal microbiome composition of racing Thoroughbred horses in training being fed a high concentrate/grain-based diet to be more similar to that found in forage fed/pasture grazed horses. Thirty-two horses on one training yard were randomised to either receive the supplement or not. Faecal samples were collected at baseline, 6...
The Enrichment of Specific Hair Follicle-Associated Cell Populations in Plucked Hairs Offers an Opportunity to Study Gene Expression Underlying Hair Traits.
International journal of molecular sciences    December 29, 2022   Volume 24, Issue 1 561 doi: 10.3390/ijms24010561
Naboulsi R, Cieślak J, Headon D, Jouni A, Negro JJ, Andersson G, Lindgren G.Gene expression differences can assist in characterizing important underlying genetic mechanisms between different phenotypic traits. However, when population-dense tissues are studied, the signals from scarce populations are diluted. Therefore, appropriately choosing a sample collection method that enriches a particular type of effector cells might yield more specific results. To address this issue, we performed a polyA-selected RNA-seq experiment of domestic horse () plucked-hair samples and skin biopsies. Then, we layered the horse gene abundance results against cell type-specific marker ge...
Genetic diversity analysis and parentage verification of Taishu horses using 31 microsatellites.
Journal of equine science    December 28, 2022   Volume 33, Issue 4 63-69 doi: 10.1294/jes.33.63
Yoshihara T, Kikuchi M, Akiba Y, Horiguchi M, Takasu M, Tozaki T.The Taishu horse in Tsushima is one of eight Japanese native breeds. The breed is on the verge of extinction due to a rapid decrease in numbers since the 1960s owing to motorization in Japan. In this study, we aimed to confirm the pedigree information of 52 horses by genotyping 31 microsatellites in order to avoid inbreeding. Parentage verification failed to identify genetic contradictions among trios (sires, dams, and foals) registered with the Japan Equine Affairs Association (JEAA). Pedigree information registered at the JEAA was obtained and adequately understood. Additionally, the genetic...
Integrating genome-wide methylation and transcriptome-wide analyses to reveal the genetic mechanism of milk traits in Kazakh horses.
Gene    December 24, 2022   Volume 856 147143 doi: 10.1016/j.gene.2022.147143
Liu L, Zhang Y, Ma H, Cao H, Liu W.Horse Milk has important quantitative characteristics and high economic value. However, the DNA methylation regulators involved in horse milk traits have not been clarified. To explore the important role of genome-wide DNA methylation in regulating equine milk yield, this study systematically investigated the genome-wide DNA methylation profiles of Kazakh horse blood by comparing a high-production group (HP, average daily milk yield of 7.5 kg) and low-production group (LP, average daily milk yield of 3.2 kg) using deep whole-genome bisulfite sequencing. First, both groups showed similar prop...
Follicle Selection in Mares as a Model for Illustrating the Many Hormonal and Biochemical Interactions That Drive a Single Physiological Mechanism.
Journal of equine veterinary science    December 22, 2022   Volume 121 104196 doi: 10.1016/j.jevs.2022.104196
Ginther OJ.The mechanism for selection of the future dominant or ovulatory follicle in mares involves a relatively abrupt separation in growth rates between the future dominant follicle and several subordinate follicles and is termed diameter deviation. The event is used to illustrate that a coordinated complex of many follicular, hormonal, and biochemical factors interact and interbalance during a single physiological mechanism. For example, a positive effect of follicle stimulating hormone (FSH) on development of all follicles during the growing phase can later involve a positive effect of luteinizing ...
Mitochondrial Genomes of the American Dog Tick (Dermacentor variabilis) Isolated from Horses in the Midwestern United States.
Microbiology resource announcements    December 21, 2022   Volume 12, Issue 1 e0033022 doi: 10.1128/mra.00330-22
Reynolds S, Hedberg M, Herrin B, Jesudoss Chelladurai JRJ.Here, we report two complete and three partial mitochondrial genome sequences of Dermacentor variabilis specimens collected from horses in the United States. The complete genomes are 14,837 bp long and contain 13 protein-coding genes, 2 rRNA genes, and 22 tRNA genes. The sequences have been deposited under GenBank accession numbers ON052120 to ON052124.
Maternal allogeneic cancellous bone graft for the treatment of osteitis along the physeal scar of the proximal metatarsus in a foal.
Veterinary surgery : VS    December 21, 2022   Volume 52, Issue 3 467-477 doi: 10.1111/vsu.13926
Sauer FJ, Verhaar N, Geburek F.To describe the treatment and outcome of a foal with a fresh allogenic cancellous bone graft after surgical debridement of a traumatic septic osteitis. Methods: A neonatal Quarter Horse foal. Methods: Case report. Methods: The foal sustained a traumatic laceration exposing the proximal third metatarsal bone. One week after surgical debridement and closure, radiographic signs of septic osteitis were noted along the physeal scar. The lesion was debrided, and antimicrobial therapy was implemented. The infection resolved but left a large defect in the metaphysis and epiphysis. Grafting was indic...
Whole-Genome Sequence Analysis Reveals the Origin of the Chakouyi Horse.
Genes    December 19, 2022   Volume 13, Issue 12 doi: 10.3390/genes13122411
Li Y, Liu Y, Wang M, Lin X, Li Y, Yang T, Feng M, Ling Y, Zhao C.The Chakouyi horse is an ancient Chinese indigenous horse breed distributed in Gansu Province in northwestern China, and is also one of the key breeds protected by the government. However, the origin of the Chakouyi horse remains unclear. As it is distributed in a key region of the Silk Road, it was speculated that the origin of the Chakouyi horse might involve the foreign horse breeds found along this ancient commercial artery. In this study, whole-genome resequencing data of 12 horse breeds, including both indigenous and foreign horses, were applied to reveal the genetic relationships betwee...
Analysis of Proteins and Peptides of Highly Purified CD9+ and CD63+ Horse Milk Exosomes Isolated by Affinity Chromatography.
International journal of molecular sciences    December 17, 2022   Volume 23, Issue 24 16106 doi: 10.3390/ijms232416106
Sedykh SE, Purvinsh LV, Burkova EE, Dmitrenok PS, Ryabchikova EI, Nevinsky GA.Exosomes are nanovesicles with a 40-150 nm diameter and are essential for communication between cells. Literature data suggest that exosomes obtained from different sources (cell cultures, blood plasma, urea, saliva, tears, spinal fluid, milk) using a series of centrifugations and ultracentrifugations contain hundreds and thousands of different protein and nucleic acid molecules. However, most of these proteins are not an intrinsic part of exosomes; instead, they co-isolate with exosomes. Using consecutive ultracentrifugation, gel filtration, and affinity chromatography on anti-CD9- and anti-C...
Common protein-coding variants influence the racing phenotype in galloping racehorse breeds.
Communications biology    December 13, 2022   Volume 5, Issue 1 1320 doi: 10.1038/s42003-022-04206-x
Han H, McGivney BA, Allen L, Bai D, Corduff LR, Davaakhuu G, Davaasambuu J, Dorjgotov D, Hall TJ, Hemmings AJ, Holtby AR, Jambal T, Jargalsaikhan B....Selection for system-wide morphological, physiological, and metabolic adaptations has led to extreme athletic phenotypes among geographically diverse horse breeds. Here, we identify genes contributing to exercise adaptation in racehorses by applying genomics approaches for racing performance, an end-point athletic phenotype. Using an integrative genomics strategy to first combine population genomics results with skeletal muscle exercise and training transcriptomic data, followed by whole-genome resequencing of Asian horses, we identify protein-coding variants in genes of interest in galloping ...
Reconstruction of the Major Maternal and Paternal Lineages in the Feral New Zealand Kaimanawa Horses.
Animals : an open access journal from MDPI    December 12, 2022   Volume 12, Issue 24 3508 doi: 10.3390/ani12243508
Sharif MB, Fitak RR, Wallner B, Orozco-terWengel P, Frewin S, Fremaux M, Mohandesan E.New Zealand has the fourth largest feral horse population in the world. The Kaimanawas (KHs) are feral horses descended from various domestic horse breeds released into the Kaimanawa ranges in the 19th and 20th centuries. Over time, the population size has fluctuated dramatically due to hunting, large-scale farming and forestry. Currently, the herd is managed by an annual round-up, limiting the number to 300 individuals to protect the native ecosystem. Here, we genotyped 96 KHs for uniparental markers (mitochondrial DNA, Y-chromosome) and assessed their genetic similarity with respect to other...
Garrano Horses Perceive Letters of the Alphabet on a Touchscreen System: A Pilot Study.
Animals : an open access journal from MDPI    December 12, 2022   Volume 12, Issue 24 3514 doi: 10.3390/ani12243514
Schubert CL, Ryckewaert B, Pereira C, Matsuzawa T.This study aimed to use a computer-controlled touchscreen system to examine visual discrimination in Garrano horses (), an endangered breed of pony belonging to the Iberian horse family. This pilot study focused on the perceptual similarity among letters of the alphabet. We tested five horses in a one-male unit (OMU) living permanently in a semi-free enclosure near their natural habitat in Serra d'Arga, northern Portugal. Horses were trained to nose-touch black circles that appeared on the screen. Then, they were tested for discrimination of five letters of the Latin alphabet in Arial font, na...
Prevalence and genetic characterization of Theileria equi and Babesia caballi in grazing horses in Xinjiang, northwestern China.
Parasitology research    December 12, 2022   Volume 122, Issue 2 387-394 doi: 10.1007/s00436-022-07749-4
Wu J, Cui Y, Yu F, Muhatai G, Tao D, Zhao A, Ning C, Qi M.Piroplasmosis is a disease that negatively affects equine health worldwide. Hence, 324 blood samples were collected from grazing horses in ten sites in Xinjiang and testing them for the presence of Theileria equi and Babesia caballi by PCR of the EMA-1 gene and BC48 gene, respectively. Of the 324 blood samples, 161 (49.7%) were positive for equine piroplasms. The prevalence of T. equi was 38.9% (126/324), while that of B. caballi was 30.2% (98/324). The T. equi and B. caballi co-infection rate was 19.4% (63/324). From the 126 EMA-1 gene sequences and 98 BC48 gene sequences we obtained, 21 and ...
Identification of Copy Number Variations in Four Horse Breed Populations in South Korea.
Animals : an open access journal from MDPI    December 12, 2022   Volume 12, Issue 24 3501 doi: 10.3390/ani12243501
Kim YM, Ha SJ, Seong HS, Choi JY, Baek HJ, Yang BC, Choi JW, Kim NY.In this study, genome-wide CNVs were identified using a total of 469 horses from four horse populations (Jeju horses, Thoroughbreds, Jeju riding horses, and Hanla horses). We detected a total of 843 CNVRs throughout all autosomes: 281, 30, 301, and 310 CNVRs for Jeju horses, Thoroughbreds, Jeju riding horses, and Hanla horses, respectively. Of the total CNVRs, copy number losses were found to be the most abundant (48.99%), while gains and mixed CNVRs accounted for 41.04% and 9.96% of the total CNVRs, respectively. The length of the CNVRs ranged from 0.39 kb to 2.8 Mb, while approximately 7.2% ...
Investigation of MicroRNA Biomarkers in Equine Distal Interphalangeal Joint Osteoarthritis.
International journal of molecular sciences    December 8, 2022   Volume 23, Issue 24 15526 doi: 10.3390/ijms232415526
Baker ME, Lee S, Clinton M, Hackl M, Castanheira C, Peffers MJ, Taylor SE.Osteoarthritis of the equine distal interphalangeal joint is a common cause of lameness. MicroRNAs from biofluids are promising biomarkers and therapeutic candidates. Synovial fluid samples from horses with mild and severe equine distal interphalangeal joint osteoarthritis were submitted for small RNA sequencing. The results demonstrated that miR-92a was downregulated in equine synovial fluid from horses with severe osteoarthritis and there was a significant increase in COMP, COL1A2, RUNX2 and SOX9 following miR-92a mimic treatment of equine chondrocytes in monolayer culture. This is the first...
Genetic characterization of three recently discovered parvoviruses circulating in equines in China.
Frontiers in veterinary science    December 8, 2022   Volume 9 1033107 doi: 10.3389/fvets.2022.1033107
Ou J, Li J, Wang X, Zhong L, Xu L, Xie J, Lu G, Li S.The family comprises many major viral pathogens that can infect humans and multiple other species, causing severe diseases. However, knowledge of parvoviruses that infect equids is limited. In the present study, we found that three equine parvoviruses (EqPVs), namely, equine parvovirus-hepatitis (EqPV-H), equine parvovirus-cerebrospinal fluid (EqPV-CSF) and equine copivirus (EqCoPV) cocirculated among horses in China. We examined the prevalence of these three EqPVs in 225 horse serum samples in China and found EqPV-H, EqPV-CSF and EqCoPV viremia in 7.6% (17/225), 2.7% (6/225) and 2.2% of samp...
Identification of putative orthologs of clinically relevant antimicrobial peptides in the equine ocular surface and amniotic membrane.
Veterinary ophthalmology    December 7, 2022   Volume 26 Suppl 1, Issue Suppl 1 125-133 doi: 10.1111/vop.13042
Hisey EA, Martins BC, Donnelly CG, Cassano JM, Katzman SA, Murphy CJ, Thomasy SM, Leonard BC.This study aimed to define the antimicrobial peptide (AMP) expression pattern of the equine ocular surface and amniotic membrane using a targeted qPCR approach and 3'Tag-sequencing. It will serve as a reference for future studies of ocular surface innate immunity and amniotic membrane therapies. Methods: A targeted qPCR approach was used to investigate the presence of orthologs for three of the most highly expressed beta-defensins (DEFB1, DEFB4B, and DEFB103A) of the human ocular surface and amniotic membrane in equine corneal epithelium, conjunctiva, and amniotic membrane. 3'Tag-sequencing wa...
Conditionally immortalised equine skeletal muscle cell lines for in vitro analysis.
Biochemistry and biophysics reports    December 5, 2022   Volume 33 101391 doi: 10.1016/j.bbrep.2022.101391
Rooney MF, Neto NGB, Monaghan MG, Hill EW, Porter RK.Thoroughbred racehorse performance is largely influenced by a major quantitative trait locus at the () gene which determines aptitude for certain race distances due to a promoter region insertion mutation influencing functional phenotypes in skeletal muscle. To develop an system for functional experiments we established three novel equine skeletal muscle cell lines reflecting the variation in phenotype associated with genotype (CC/II, CT/IN and TT/NN for SNP g.66493737C > T/SINE insertion 227 bp polymorphism). Primary equine skeletal muscle myoblasts, isolated from Thoroughbred horse , we...
Molecular diagnostics for gastrointestinal helminths in equids: Past, present and future.
Veterinary parasitology    December 5, 2022   Volume 313 109851 doi: 10.1016/j.vetpar.2022.109851
Ghafar A, Abbas G, Beasley A, Bauquier J, Wilkes EJA, Jacobson C, McConnell E, El-Hage C, Carrigan P, Cudmore L, Tennent-Brown B, Hurley J....This review is aimed to (i) appraise the literature on the use of molecular techniques for the detection, quantification and differentiation of gastrointestinal helminths (GIH) of equids, (ii) identify the knowledge gaps and, (iii) discuss diagnostic prospects in equine parasitology. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines for systematic reviews, we retrieved 54 studies (horses: 50/54; donkeys and zebras: 4/54) from four databases. Polymerase chain reaction (PCR) was employed in all of the studies whereas PCR amplicons were sequenced...
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