Complete genome sequencing and characterization of a potential new genotype of Citrus tristeza virus in Iran.

Citrus tristeza virus (CTV) is one of the economically destructive viruses affecting citrus trees worldwide, causing significant losses in fruit production. Comparative genomic studies have shown genetic diversity in various regions of the genome of CTV isolates, which has classified the virus into several genotypes. In recent years, some orange citrumelo-tolerant rootstocks showed yellowing, decline, and vein clearing in northern Iran (Mazandaran province, Sari). We confirmed the presence of CTV in the symptomatic trees by reverse transcription PCR (RT-PCR). The complete genome of a Sari isolate of CTV (Sari isolate) was sequenced using next-generation sequencing (NGS) technology. In addition, phylogenetic analysis, differential gene expression of the virus and identification of its variants in a population were studied. We obtained the final contigs of the virus (nt) and annotated all genomes to viral ORFs, untranslated regions (UTRs), intergenic regions, and 5' and 3' ends of the genome. Phylogenetic analysis of the Sari isolate and other genotypes of CTV showed that the Sari isolates were placed in a distinct cluster without a sister group. Based on the number of specific transcripts (TPM) in CTV RNA -Seq, P13 was the most highly expressed gene related to the host range of the virus and its systemic infection. The ORFs of the polyprotein, P33, and P18 showed variation in a single population of the sari isolate. The CTV has a potential for variation in a population in a host, and these variations may contribute to the best fit of the CTV in different situations. In Iran, whole genome sequencing of the CTV was performed for the first time, and we gained new insights into CTV variation in a population.

Phase space nonclassicality and sub-Poissonianity of deformed photon-added nonlinear cat states: algebraic and group theoretical approach.

In this Letter, we introduce four distinct classes of f-deformed photon-added nonlinear cat state. This would be achieved by recalling a nonlinear coherent states approach, as well as a particular class of Gilmore-Perelomov-type of SU(1,1) coherent state and a class of SU(2) coherent state. We then examine the role of photon addition and nonlinearity functions in the phase space structure and sub-Poissonianity of even, odd, and Yurke-Stoler nonlinear cat states. The effect of photon addition, which results in a π phase shift at the origin of the Wigner function toward negativity, interestingly enhances the nonclassicality by means of the Wigner function and Mandel parameter. Furthermore, owing to photon addition, we can observe a deformation in the Gaussian shape of the Wigner function, which may be found to be potentially useful in quantum noise reduction. Moreover, the deformation function shows a remarkable role in revealing the nonclassical behavior and can increase the depth and the domain of nonclassicality.

Identification of Candidate Genes for Pigmentation in Camels Using Genotyping-by-Sequencing.

The coat color of dromedary is usually uniform and varies from black to white, although dark- to light-brown colors are the most common phenotypes. This project was designed to gain knowledge on novel color-related variants using genotyping-by-sequencing (GBS). The association between the SNPs and coat color was tested using MLM (mixed linear models) with kinship matrix. Three GWAS models including white color vs. non-white color, black vs. non-black color, and light-brown vs. dark-brown color were performed. There were no distinct genetic clusters detected based on the color phenotypes. However, admixture occurred among all individuals of the four different coat color groups. We identified nine significant SNPs associated with white color after Bonferroni correction, located close to ANKRD26, GNB1, TSPYL4, TEKT5, DEXI, CIITA, TVP23B, CLEC16A, TMPRSS13, FXYD6, MPZL3, ANKRD26, HFM1, CDC7, TGFBR3, and HACE1 genes in neighboring flanking regions. The 13 significant SNPs associated with black color and the candidate genes were: CAPN7, CHRM4, CIITA, CLEC16A, COL4A4, COL6A6, CREB3L1, DEXI, DGKZ, DGKZ, EAF1, HDLBP, INPP5F, MCMBP, MDK, SEC23IP, SNAI1, TBX15, TEKT5, TMEM189, trpS, TSPYL4, TVP23B, and UBE2V1. The SNAI1 gene interacted with MCIR, ASIP and KIT genes. These genes play a key role in the melanin biosynthetic and pigmentation biological process and melanogenesis biological pathway. Further research using a larger sample size and pedigree data will allow confirmation of associated SNPs and the identified candidate genes.

High-throughput imaging of ATG9A distribution as a diagnostic functional assay for adaptor protein complex 4-associated hereditary spastic paraplegia.

Adaptor protein complex 4-associated hereditary spastic paraplegia is caused by biallelic loss-of-function variants in AP4B1, AP4M1, AP4E1 or AP4S1, which constitute the four subunits of this obligate complex. While the diagnosis of adaptor protein complex 4-associated hereditary spastic paraplegia relies on molecular testing, the interpretation of novel missense variants remains challenging. Here, we address this diagnostic gap by using patient-derived fibroblasts to establish a functional assay that measures the subcellular localization of ATG9A, a transmembrane protein that is sorted by adaptor protein complex 4. Using automated high-throughput microscopy, we determine the ratio of the ATG9A fluorescence in the trans-Golgi-network versus cytoplasm and ascertain that this metric meets standards for screening assays (Z'-factor robust >0.3, strictly standardized mean difference >3). The 'ATG9A ratio' is increased in fibroblasts of 18 well-characterized adaptor protein complex 4-associated hereditary spastic paraplegia patients [mean: 1.54 ± 0.13 versus 1.21 ± 0.05 (standard deviation) in controls] and receiver-operating characteristic analysis demonstrates robust diagnostic power (area under the curve: 0.85, 95% confidence interval: 0.849-0.852). Using fibroblasts from two individuals with atypical clinical features and novel biallelic missense variants of unknown significance in AP4B1, we show that our assay can reliably detect adaptor protein complex 4 function. Our findings establish the 'ATG9A ratio' as a diagnostic marker of adaptor protein complex 4-associated hereditary spastic paraplegia.

Pre-Implantation Genetic Testing for Monogenic Disorders (PGT-M) in A Family with A Novel Mutation in DPAGT1 Gene.

Congenital disorders of glycosylation (CDG) are a heterogeneous group of systemic disorders characterized by defects in glycosylation of lipids and proteins. One of the rare subtypes of CDG is CDG-Ij (MIM # 608093), which is caused by pathogenic mutations in DPAGT1, a gene encoding UDP-N-acetylglucosaminedolichyl-phosphate N-acetylglucosaminephosphotransferase enzyme. This enzyme catalyzes the first step of oligosaccharide synthesis in glycoprotein biosynthesis pathway. Preimplantation genetic testing for monogenic disorders (PGT-M) is a diagnostic technique that can reveal the genetic profile of embryos before implantation phase of in vitro fertilization (IVF). Currently, this approach is performed using next generation sequencing (NGS) technology. Herein, with the help of whole-exome and Sanger sequencing, we detected a novel missense mutation (NM_001382, c.1217 A>G) in DPAGT1 gene in two families with consanguineous marriage. Using different online bioinformatics tools including MutationTaster, I-Mutant v2.0, T- Coffee, and CADD v1.0, this mutation was predicted pathogen. Finally, after performing PGT-M followed by successful pregnancy, a normal child was born in one of these families. In conclusion, we identified a novel pathogenic mutation in DPAGT1 in a family with multiple members affected by CDG, which extends the range of pathogenic variants associated with CDG and therefore facilitates early detection of the disease.

Genetic Testing in Various Neurodevelopmental Disorders Which Manifest as Cerebral Palsy: A Case Study From Iran.

Purpose: Cerebral palsy (CP) is a heterogeneous permanent disorder impacting movement and posture. Investigations aimed at diagnosing this disorder are expensive and time-consuming and can eventually inconclusive. This study aimed to determine the diagnostic yield of next generation sequencing in patients with atypical CP (ACP). Methods: Patient eligibility criteria included impaired motor function with onset at birth or within the first year of life, and one or more of the following conditions: severe intellectual disability, positive family history, brain imaging findings not typical for cerebral palsy, abnormal neurometabolic profile, intractable seizure, normal neuroimaging despite severe psychomotor disability, after pediatric neurologist assessment including neuroimaging and biochemical-metabolic study offered for genetic study. Results: Exome sequencing was done for 66 patients which revealed pathogenic, likely pathogenic, and variants of unknown significance in 36.2, 9, and 43.9%, respectively. We also found 10 new mutations and were able to suggest specific and personalized treatments for nine patients. We also found three different mutations with different phenotypical spectrum in one gene that have not been reported for cerebral palsy. Conclusion: An accurate history and physical examination and determination of patients with atypical cerebral palsy for doing exome sequencing result in improved genetic counseling and personalized management.

Investigating the association between common DRD2/ANKK1 genetic polymorphisms and schizophrenia: a meta-analysis.

Genetic factors play an important role in the pathogenesis of schizophrenia. Dysregulations in the dopaminergic system have long been known to play an influential role in the development of this disorder. Although a large number of studies have investigated the association between genetic polymorphisms in the genes involved in this system and the risk of schizophrenia, the results have been inconsistent. In this meta-analysis, we searched for publications in Ovid Medline, Embase, Web of Science (science citation index expanded), and PsycNET for articles published until January 2020. We identified case-control studies investigating the association between four common genetic polymorphisms (rs6277, rs1799732, rs1800497, and rs1801028) and the risk of schizophrenia. The studies were subsequently selected according to the predefined inclusion and exclusion criteria. The data extraction was conducted according to the PRISMA guidelines.We also assessed the quality of the studies and investigated publication bias using funnel plot and Egger's regression test. The association analysis was conducted in allelic, dominant, and recessive genetic models. Subsequently, bioinformatics analysis of the effect of the polymorphisms found to be significantly associated with schizophrenia on protein stability, posttranslational modifications, and 3D protein structure was conducted. This meta-analysis showed that Taq1A (allelic model: OR, 0.856, 95% CI, 0.734-0.998) has a protective effect against the development of schizophrenia. Further, it was found that this variant may decreaseANKK1protein stability. Further, this polymorphism was found to lead to the gain of modifications sites for ubiquitination (Ubi. score =-1.894) and methylation (Meth. score =-0.834). Several genetic factors contribute to the susceptibility of schizophrenia. The updated knowledge emerging from this meta-analysis showing the protective effect of rs1800497 polymorphism (Taq1A) can shed light on the role of Taq1A polymorphism in the susceptibility to schizophrenia and also pave way for further functional studies investigating the role of ANKK1 protein in the pathogenesis of schizophrenia.

A novel knockout mouse model of the noncoding antisense Brain-Derived Neurotrophic Factor (Bdnf) gene displays increased endogenous Bdnf protein and improved memory function following exercise.

Brain-derived neurotrophic factor (Bdnf) expression is tightly controlled at the transcriptional and post-transcriptional levels. Previously, we showed that inhibition of noncoding Bdnf antisense (Bdnf-AS) RNA upregulates Bdnf protein. Here, we generated a Bdnf-antisense knockout (Bdnf-AS KO) mouse model by deleting 6 kilobases upstream of Bdnf-AS. After verifying suppression of Bdnf-AS, baseline behavioral tests indicated no significant difference in knockout and wild type mice, except for enhanced cognitive function in the knockout mice in the Y-maze. Following acute involuntary exercise, Bdnf-AS KO mice were re-assessed and a significant increase in Bdnf mRNA and protein were observed. Following long-term involuntary exercise, we observed a significant increase in nonspatial and spatial memory in novel object recognition and Barnes maze tests in young and aged Bdnf-AS KO mice. Our data provides evidence for the beneficial effects of endogenous Bdnf upregulation and the synergistic effect of Bdnf-AS knockout on exercise and memory retention.

Biallelic variants in TMEM222 cause a new autosomal recessive neurodevelopmental disorder.

PURPOSE: To elucidate the novel molecular cause in families with a new autosomal recessive neurodevelopmental disorder. METHODS: A combination of exome sequencing and gene matching tools was used to identify pathogenic variants in 17 individuals. Quantitative reverse transcription polymerase chain reaction (RT-qPCR) and subcellular localization studies were used to characterize gene expression profile and localization. RESULTS: Biallelic variants in the TMEM222 gene were identified in 17 individuals from nine unrelated families, presenting with intellectual disability and variable other features, such as aggressive behavior, shy character, body tremors, decreased muscle mass in the lower extremities, and mild hypotonia. We found relatively high TMEM222 expression levels in the human brain, especially in the parietal and occipital cortex. Additionally, subcellular localization analysis in human neurons derived from induced pluripotent stem cells (iPSCs) revealed that TMEM222 localizes to early endosomes in the synapses of mature iPSC-derived neurons. CONCLUSION: Our findings support a role for TMEM222 in brain development and function and adds variants in the gene TMEM222 as a novel underlying cause of an autosomal recessive neurodevelopmental disorder.

Genomic prediction for growth using a low-density SNP panel in dromedary camels.

For thousands of years, camels have produced meat, milk, and fiber in harsh desert conditions. For a sustainable development to provide protein resources from desert areas, it is necessary to pay attention to genetic improvement in camel breeding. By using genotyping-by-sequencing (GBS) method we produced over 14,500 genome wide markers to conduct a genome- wide association study (GWAS) for investigating the birth weight, daily gain, and body weight of 96 dromedaries in the Iranian central desert. A total of 99 SNPs were associated with birth weight, daily gain, and body weight (p-value < 0.002). Genomic breeding values (GEBVs) were estimated with the BGLR package using (i) all 14,522 SNPs and (ii) the 99 SNPs by GWAS. Twenty-eight SNPs were associated with birth weight, daily gain, and body weight (p-value < 0.001). Annotation of the genomic region (s) within ± 100 kb of the associated SNPs facilitated prediction of 36 candidate genes. The accuracy of GEBVs was more than 0.65 based on all 14,522 SNPs, but the regression coefficients for birth weight, daily gain, and body weight were 0.39, 0.20, and 0.23, respectively. Because of low sample size, the GEBVs were predicted using the associated SNPs from GWAS. The accuracy of GEBVs based on the 99 associated SNPs was 0.62, 0.82, and 0.57 for birth weight, daily gain, and body weight. This report is the first GWAS using GBS on dromedary camels and identifies markers associated with growth traits that could help to plan breeding program to genetic improvement. Further researches using larger sample size and collaboration of the camel farmers and more profound understanding will permit verification of the associated SNPs identified in this project. The preliminary results of study show that genomic selection could be the appropriate way to genetic improvement of body weight in dromedary camels, which is challenging due to a long generation interval, seasonal reproduction, and lack of records and pedigrees.

Role of IgG against N-protein of SARS-CoV2 in COVID19 clinical outcomes.

The Nucleocapsid Protein (N Protein) of severe acute respiratory syndrome Coronavirus 2 (SARS-CoV2) is located in the viral core. Immunoglobulin G (IgG) targeting N protein is detectable in the serum of infected patients. The effect of high titers of IgG against N-protein on clinical outcomes of SARS-CoV2 disease has not been described. We studied 400 RT-PCR confirmed SARS-CoV2 patients to determine independent factors associated with poor outcomes, including Medical Intensive Care Unit (MICU) admission, prolonged MICU stay and hospital admissions, and in-hospital mortality. We also measured serum IgG against the N protein and correlated its concentrations with clinical outcomes. We found that several factors, including Charlson comorbidity Index (CCI), high levels of IL6, and presentation with dyspnea were associated with poor clinical outcomes. It was shown that higher CCI and higher IL6 levels were independently associated with in-hospital mortality. Anti-N protein IgG was detected in the serum of 55 (55%) patients at the time of admission. A high concentration of antibodies, defined as signal to cut off ratio (S/Co) > 1.5 (75 percentile of all measurements), was found in 25 (25%) patients. The multivariable logistic regression models showed that between being an African American, higher CCI, lymphocyte counts, and S/Co ratio > 1.5, only S/Co ratio were independently associated with MICU admission and longer length of stay in hospital. This study recommends that titers of IgG targeting N-protein of SARS-CoV2 at admission is a prognostic factor for the clinical course of disease and should be measured in all patients with SARS-CoV2 infection.

Molecular diagnostic assays for COVID-19: an overview.

The coronavirus disease 2019 (COVID-19) pandemic has highlighted the cardinal importance of rapid and accurate diagnostic assays. Since the early days of the outbreak, researchers with different scientific backgrounds across the globe have tried to fulfill the urgent need for such assays, with many assays having been approved and with others still undergoing clinical validation. Molecular diagnostic assays are a major group of tests used to diagnose COVID-19. Currently, the detection of SARS-CoV-2 RNA by reverse transcription polymerase chain reaction (RT-PCR) is the most widely used method. Other diagnostic molecular methods, including CRISPR-based assays, isothermal nucleic acid amplification methods, digital PCR, microarray assays, and next generation sequencing (NGS), are promising alternatives. In this review, we summarize the technical and clinical applications of the different COVID-19 molecular diagnostic assays and suggest directions for the implementation of such technologies in future infectious disease outbreaks.

Cytokine Gene Expression Alterations in Human Macrophages Infected by Leishmania major.

OBJECTIVE: Leishmaniasis is caused by members of the Leishmania species and constitute a group of infective diseases that range from cutaneous lesions to lethal visceral forms. In infected persons, macrophages recognize and eliminate the parasites via phagocytosis. In order to change a hostile environment into an environment adequate for survival and reproduction, the engulfed Leishmania species needs to modulate the function of its host macrophage. The expression patterns of cytokine genes such as interleukin-12 (IL-12), tumour necrosis factor-alpha (TNF-α), IL-1, and interferon-gamma (IFNγ) represent the immune response. In this study, we employed an RNA-seq approach for human monocyte-derived macrophages infected with Leishmania major (L. major) to decipher cytokine gene expression alterations in host macrophages. MATERIALS AND METHODS: In this descriptive study, human monocytes were isolated by magnetic activated cell sorting (MACS) and cultured in the presence of monocyte colony stimulating factor (M-CSF) to obtain the macrophages. Monocyte-derived macrophages were then co-cultured with metacyclic promastigotes of L. major for 4 hours. RNA isolation was performed using TRIzol reagent. RNA sequencing was performed using the Illumina sequencing platforms. Gene expression analysis was performed using a Bioconductor DESeq2 package. RESULTS: Our data revealed significant changes in immune response gene expressions in macrophages infected with L. major, with an up-regulation of cytokines and mostly down-regulation of their receptors. CONCLUSION: The obtained data could shed more light on the biology of L. major and how the host cell responds to leishmaniasis.

Potential voriconazole associated posterior reversible leukoencephalopathy in children with malignancies: Report of two cases.

INTRODUCTION: The fungal infection has become severe morbidity amongst patients with malignancy. Voriconazole, a new generation of triazole, has shown excellent results in treating invasive fungal infections. CASE REPORT: Herein, we report two cases of posterior reversible encephalopathy syndrome (PRES), which induced after voriconazole exposure.Management and outcome: Magnetic resonance imaging, and the serum level of voriconazole were investigated in both patients to assess toxicity. The role of methotrexate, as one of the possible causes of PRES, is weakened significantly through precise assessing diffusion-weighted images on magnetic resonance imaging. DISCUSSION: These unique cases emphasize that voriconazole can induce PRES even at therapeutic levels. Therefore, in the case of neurotoxicity, PRES must be considered, and voriconazole should discontinue. The prognosis seemed promising when voriconazole stopped immediately after clinical suspicion.

Biallelic TMEM251 variants in patients with severe skeletal dysplasia and extreme short stature.

Skeletal dysplasias are a heterogeneous group of disorders ranging from mild to lethal skeletal defects. We investigated two unrelated families with individuals presenting with a severe skeletal disorder. In family NMD02, affected individuals had a dysostosis multiplex-like skeletal dysplasia and severe short stature (<-8.5 SD). They manifested increasingly coarse facial features, protruding abdomens, and progressive skeletal changes, reminiscent of mucopolysaccharidosis. The patients gradually lost mobility and the two oldest affected individuals died in their twenties. The affected child in family ID01 had coarse facial features and severe skeletal dysplasia with clinical features similar to mucopolysaccharidosis. She had short stature, craniosynostosis, kyphoscoliosis, and hip-joint subluxation. She died at the age of 5 years. Whole-exome sequencing identified two homozygous variants c.133C>T; p.(Arg45Trp) and c.215dupA; p.(Tyr72Ter), respectively, in the two families, affecting an evolutionary conserved gene TMEM251 (NM_001098621.1). Immunofluorescence and confocal studies using human osteosarcoma cells indicated that TMEM251 is localized to the Golgi complex. However, p.Arg45Trp mutant TMEM251 protein was targeted less efficiently and the localization was punctate. Tmem251 knockdown by small interfering RNA induced dedifferentiation of rat primary chondrocytes. Our work implicates TMEM251 in the pathogenesis of a novel disorder and suggests its potential function in chondrocyte differentiation.

Molecular mechanisms of long non-coding RNAs in anaplastic thyroid cancer: a systematic review.

BACKGROUND: anaplastic thyroid cancer (ATC) is one of the most lethal and aggressive cancers. Evidence has shown that the tumorigenesis of ATC is a multistep process involving the accumulation of genetic and epigenetic changes. Several studies have suggested that long non-coding RNAs (lncRNAs) may play an important role in the development and progression of ATC. In this article, we have collected the published reports about the role of lncRNAs in ATC. METHODS: "Scopus", "Web of Science", "PubMed", "Embase", etc. were systematically searched for articles published since 1990 to 2020 in English language, using the predefined keywords. RESULTS: 961 papers were reviewed and finally 33 papers which fulfilled the inclusion and exclusion criteria were selected. Based on this systematic review, among a lot of evidences on examining the function of lncRNAs in thyroid cancer, there are only a small number of studies about the role of lncRNAs and their molecular mechanisms in the pathogenesis of ATC. CONCLUSIONS: lncRNAs play a crucial role in regulation of different processes involved in the development and progression of ATC. Currently, just a few lncRNAs have been identified in ATC that may serve as prognosis markers such as GAS5, MIR22HG, and CASC2. Also, because of the dysregulation of Klhl14-AS, HOTAIRM1, and PCA3 during ATC development and progression, they may act as therapeutic targets. However, for most lncRNAs, only a single experiment has evaluated the expression profile in ATC tissues/cells. Therefore, further functional studies and expression profiling is needed to resolve this limitation and identify novel and valid biomarkers.

A Neurite Outgrowth Assay and Neurotoxicity Assessment with Human Neural Progenitor Cell-Derived Neurons.

Neurite outgrowth assay and neurotoxicity assessment are two major studies that can be performed using the presented method herein. This protocol provides reliable analysis of neuronal morphology together with quantitative measurements of modifications on neurite length and synaptic protein localization and abundance upon treatment with small molecule compounds. In addition to the application of the presented method in neurite outgrowth studies, neurotoxicity assessment can be performed to assess, distinguish and rank commercial chemical compounds based on their potential developmental neurotoxicity effect. Even though cell lines are nowadays widely used in compound screening assays in neuroscience, they often differ genetically and phenotypically from their tissue origin. Primary cells, on the other hand, maintain important markers and functions observed in vivo. Therefore, due to the translation potential and physiological relevance that these cells could offer neurite outgrowth assay and neurotoxicity assessment can considerably benefit from using human neural progenitor cells (hNPCs) as the primary human cell model. The presented method herein can be utilized to screen for the ability of compounds to induce neurite outgrowth and neurotoxicity by taking advantage of the human neural progenitor cell-derived neurons, a cell model closely representing human biology."

A novel stop-gain mutation in DPYS gene causing Dihidropyrimidinase deficiency, a case report.

BACKGROUND: Dihidropyrimidinase (DHP) deficiency is an inherited inborn error of pyrimidine metabolism with a variable clinical presentation and even asymptomatic subjects. Dihydropyrimidinase is encoded by the DPYS gene, thus pathogenic mutations in this gene can cause DHP deficiency. To date, several variations in the DPYS gene have been reported but only 23 of them have been confirmed to be pathogenic. Therefore, the biochemical, clinical and genetic aspects of this disease are still unclear. CASE PRESENTATION: Here, we report a 22-year-old woman with DHP deficiency. To identify the genetic cause of DHP deficiency in this patient, Whole Exome Sequencing (WES) was performed, which revealed a novel homozygote stop gain mutation (NM_001385: Exon 9, c.1501 A > T, p.K501X) in the DPYS gene. Sanger sequencing was carried out on proband and other family members in order to confirm the identified mutation. According to the homozygote genotype of the patient and heterozygote genotype of her parents, the autosomal recessive pattern of inheritance was confirmed. In addition, bioinformatics analysis of the identified variant using Mutation Taster and T-Coffee Multiple Sequence Alignment showed the pathogenicity of mutation. Moreover, mRNA expression level of DPYS gene in the proband's liver biopsy showed about 6-fold reduction compared to control, which strongly suggested the pathogenicity of the identified mutation. CONCLUSIONS: This study identified a novel pathogenic stop gain mutation in DPYS gene in a DHP deficient patient. Our findings can improve the knowledge about the genetic basis of the disease and also provide information for accurate genetic counseling for the families at risk of these types of disorders.

Genome-Wide Diversity, Population Structure and Demographic History of Dromedaries in the Central Desert of Iran.

The development of camel husbandry for good production in a desert climate is very important, thus we need to understand the genetic basis of camels and give attention to genomic analysis. We assessed genome-wide diversity, linkage disequilibrium (LD), effective population size (Ne) and relatedness in 96 dromedaries originating from five different regions of the central desert of Iran using genotyping-by-sequencing (GBS). A total of 14,522 Single Nucleotide Polymorphisms (SNPs) with an average minor allele frequency (MAF) of 0.19 passed quality control and filtering steps. The average observed heterozygosity in the population was estimated at 0.25 ± 0.03. The mean of LD at distances shorter than 40 kb was low (r2 = 0.089 ± 0.234). The camels sampled from the central desert of Iran exhibited higher relatedness than Sudanese and lower than Arabian Peninsula dromedaries. Recent Ne of Iran's camels was estimated to be 89. Predicted Tajima's D (1.28) suggested a bottleneck or balancing selection in dromedary camels in the central desert of Iran. A general decrease in effective and census population size poses a threat for Iran's dromedaries. This report is the first SNP calling report on nearly the chromosome level and a first step towards understanding genomic diversity, population structure and demography in Iranian dromedaries.

Reporting one very rare pathogenic variation c.1106G>A in POMT2 gene.

Dystroglycan (DG) is a major cell membrane glycoprotein, which is encoded by the DAG1 gene. α-DG is one of DG subunits, belongs to O-mannosylated protein of mammals and was identified in brain, peripheral nerves and muscle. Dystroglycanopathies are a group of heterogeneous congenital muscular dystrophies, which can result from defective α-DG mannosylation. First line of α-DG glycosylation is catalyzed by protein O-mannosyltransferase family (PMT). In this study, the mutation was identified in the POMT2 gene, which encodes O-mannosyltransferase 2 protein and its mutations can be contributed to dystroglycanopathies. A very rare missense mutation in the POMT2 gene (NM_013382: exon9: c. 1106G>A) was identified by next generation sequencing (NGS) and was subsequently confirmed using Sanger sequencing in both affected siblings. There was no report of this mutation in the literature, therefore, the significance was uncertain. Our findings confirmed the pathogenicity of mutation and expanded the mutation spectrum of POMT2, which will be helpful in further molecular evaluations of muscular diseases.