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Objectives: This study investigated the association of MSX1 gene variants rs3821949 and rs12532 with nonsyndromic cleft lip and/or palate (NSCL/P) in the Pakistani population. Design: Comparative cross-sectional study. Setting: Multicenter of CL/P malformation. Patients/Participants: Unrelated Non-Syndromic cleft Lip/Palate patients and healthy controls were enrolled. Methods: One hundred (n = 100) subjects with NSCL/P and n = 50 unrelated healthy controls were enrolled in a multicenter comparative cross-sectional study. A tetra amplification refractory mutation system (ARMS) polymerase chain reaction (PCR) was performed to analyze MSXI gene single nucleotide variants (SNVs). Results: Among 100 NSCL/P subjects, the majority were males (56%; male: female = 1.27: 1). Most of the cases (74%) had cleft lip and palate (CLP) compared to isolated clefts. Genotyping of MSX1 gene variant rs3821949 showed an increased risk for NSCL/P in various genetic models (P < 0.0001), and the A allele exhibited a more than 4-fold increased risk among cases (OR = 4.22: 95% CI = 2.16–8.22; P < 0.0001). Our investigation found no significant difference between the rs12532 variation and NSCL/P. Conclusion: Our study findings suggest that MSX1 gene variants may increase predisposition to NSCL/P in the Pakistani population. Further studies comprising large samples are required to identify the genetic aetiology of NSCL/P among our people. [ABSTRACT FROM AUTHOR]

Introduction: Phosphorylation reactions highlight the essential role of protein kinases in sperm motility. TSSK6 protein is thought to play a crucial role in this process. Indeed, sperm obtained from mice with the Tssk6-/-genotype are unable to carry out fertilization and exhibit decreased motility. This leads us to investigate the causes of asthenozoospermia by searching for polymorphisms in the TSSK6 gene. Therefore, the objective of this study is to identify polymorphisms in the TSSK6 gene in men affected by asthenozoospermia. Material & Methods: The methodology involved direct sequencing of spermatozoa DNA. Thirty ejaculates were analyzed, including 20 from asthenozoospermic men and 10 from normozoospermic men. Spermograms were performed according to WHO procedures. DNA extraction was carried out using the phenol/chloroform method followed by conventional PCR. The amplicons were sequenced using the Sanger method, and the sequences were analyzed with BioEdit software. The data were analyzed using Fisher and Mann-Whitney tests. Results: The results revealed mutations in the TSSK6 gene in both normospermic and asthenozoospermic ejaculates. The synonymous mutations c.690T>C (p.Tyr230Tyr) and c.372C>A (p.Arg124Arg) were the most frequent, occurring at rates of 50% and 33.33%, respectively. Analysis of the mutations using PolyPhen-2 indicated that all mutations observed in normozoospermic samples are benign and would not affect sperm quality. However, only the mutations described in asthenozoospermic samples are predicted to be damaging to the protein. Conclusion: In conclusion, mutations in the TSSK6 gene were observed in infertile men. Deleterious mutations in the TSSK6 protein are associated with asthenozoospermia. [ABSTRACT FROM AUTHOR]

Simple Summary: This study aimed to identify and validate genes specific for the survival of patients with papillary renal cell carcinoma (PRCC) in the TCGA-KIRP and Korean-KIRP databases. Using machine learning with statistical analysis, 40 survival-specific genes were identified in TCGA-KIRP. Of them, 10 were verified as survival-specific genes for Korean-KIRP patients through next-generation sequencing. Among these, BAP1, PCSK2, and SPATA13 showed significant survival specificity in both overall survival and disease-free survival. Survival gene signatures, including PCSK2, which are commonly obtained from 40 gene signatures in TCGA and 10 gene signatures in Korean databases, are expected to provide insight into predicting the survival of PRCC patients and developing new treatments. Purpose: Papillary renal cell carcinoma (PRCC), the second most common kidney cancer, is morphologically, genetically, and molecularly heterogeneous with diverse clinical manifestations. Genetic variations of PRCC and their association with survival are not yet well-understood. This study aimed to identify and validate survival-specific genes in PRCC and explore their clinical utility. Materials and Methods: Using machine learning, 293 patients from the Cancer Genome Atlas-Kidney Renal Papillary Cell Carcinoma (TCGA-KIRP) database were analyzed to derive genes associated with survival. To validate these genes, DNAs were extracted from the tissues of 60 Korean PRCC patients. Next generation sequencing was conducted using a customized PRCC gene panel of 202 genes, including 171 survival-specific genes. Kaplan–Meier and Log-rank tests were used for survival analysis. Fisher's exact test was performed to assess the clinical utility of variant genes. Results: A total of 40 survival-specific genes were identified in the TCGA-KIRP database through machine learning and statistical analysis. Of them, 10 (BAP1, BRAF, CFDP1, EGFR, ITM2B, JAK1, NODAL, PCSK2, SPATA13, and SYT5) were validated in the Korean-KIRP database. Among these survival gene signatures, three genes (BAP1, PCSK2, and SPATA13) showed survival specificity in both overall survival (OS) (p = 0.00004, p = 1.38 × 10−7, and p = 0.026, respectively) and disease-free survival (DFS) (p = 0.00002, p = 1.21 × 10−7, and p = 0.036, respectively). Notably, the PCSK2 mutation demonstrated survival specificity uniquely in both the TCGA-KIRP (OS: p = 0.010 and DFS: p = 0.301) and Korean-KIRP (OS: p = 1.38 × 10−7 and DFS: p = 1.21 × 10−7) databases. Conclusions: We discovered and verified genes specific for the survival of PRCC patients in the TCGA-KIRP and Korean-KIRP databases. The survival gene signature, including PCSK2 commonly obtained from the 40 gene signature of TCGA and the 10 gene signature of the Korean database, is expected to provide insight into predicting the survival of PRCC patients and developing new treatment. [ABSTRACT FROM AUTHOR]

Background: More than 80 genes are involved in the pathogenesis of the most common single gene peripheral neuropathies denoted as Charcot-Marie-Tooth (CMT). Only a few studies have investigated the pathological molecular mechanisms of Iranian patients affected with CMT. The aim of this study is to identify the clinical manifestation, mutational spectrum and phenotypic correlation of a cohort of patients with Charcot-Marie-Tooth disease (CMT) in Iran. Methods: We conducted a comprehensive gene panel sequencing consisting of 80 genes in a cohort of 23 patients with CMT referred between January 2015 and March 2021. The recruited samples indicated almost an equal distribution of demyelinating and axonal types of CMT, with practically no difference between AD or AR patterns of inheritance. Results: Four novel mutations, including c.271C>T in LITAF and c.205+1delG in NDRG1, c.2455A>C in KIF1B and c.1728A>G in FIGF were detected in four patients affected with demyelinating CMT types (CMT1C and CMT4D), and characterized phenotypically. Conclusion: Our promising results unravel the complicated genetic architecture of Iranian CMT patients and help physicians and researchers achieve earlier diagnosis, better clinical management and recognizing high risk families. Further large-scale studies are needed to improve our understanding of CMT complex genetic architecture. [ABSTRACT FROM AUTHOR]

Background: Epilepsy comorbidities adversely affect the quality of life of patients. Women with epilepsy are at a high risk of comorbid endocrine disorders. Among them, the polycystic ovary syndrome (PCOS) has a threefold higher prevalence in women with epilepsy than in healthy women and is the main cause of infertility among the patients. Clinically, women with epilepsy show heterogeneity in the susceptibility to PCOS. This heterogeneity may be associated with genetic factor. Methods: To test this, we retrospectively collected clinical data from 45 female patients with epilepsy and divided them into three groups according to their susceptibility to PCOS. Groups A and B represented a high susceptibility to PCOS. Patients in Group A were diagnosed with PCOS before their first seizure, while patients in Group B were diagnosed with PCOS after a short period of monotherapy with a low dose of antiseizure medication (ASM) following the diagnosis of epilepsy. Patients in Group C did not develop PCOS despite a prolonged treatment with high-dose ASM. We compared the clinical data and genetic profiles among the three groups. Results: We found a clear trend of impaired metabolism in Group B patients and this may be associated with high-frequency mutations in MYO10 and ADGRL3. Conclusions: Our study suggests that women with epilepsy are heterogeneous in the susceptibility to PCOS and this is associated with mutations in specific genes. Therefore, genetic screening should be conducted to screen for women with epilepsy who are more likely to have comorbid PCOS, so that they can receive targeted interventions at an early stage to reduce the risk. [ABSTRACT FROM AUTHOR]

Genomics is foundational to precision oncology. Oncology nurses regularly review germline and somatic biomarker testing reports. The taxonomy and nomenclature of biomarker results have evolved. Accurate understanding and interpretation of germline and somatic genomic results are essential for safe patient care and patient education. This article reviews common variant nomenclature on genomic biomarker reports, including gene and variant location, coding data, information about protein function, and common DNA errors. This review includes examples of common variant types, such as insertions, deletions, duplications, and substitutions, and implications for nursing practice. [ABSTRACT FROM AUTHOR]

Objective Bladder cancer is one of the most common malignant tumors in urology in China. The analysis of gene mutation in bladder cancer and its relationship with clinical characteristics and prognosis will provide a basis for accurate treatment of bladder cancer. The aim of this study was to analyze the mutations and functional regions of bladder cancer–related genes based on high-throughput sequencing, and to explore the relationship between mutations and clinicopathological features, as well as its prognosis and clinical implication. Methods From April 2020 to October 2020, a total of 47 patients with bladder cancer in the Department of Urology, Affiliated Hospital of Chengde Medical College were studied. Gene sequencing was performed using Nextseq CN500 System, a high-throughput sequencing platform. The results of gene detection were described, and the relationship and clinical value of high frequency mutated genes with clinicopathological features and prognosis were systematically analyzed. Results A total of 29 mutation genes, 61 exons, and 95 mutation sites were identified in this study. The frequencies of TP53 , FGFR3 , PIK3CA , ERBB2 , MUC4 , and KRAS mutation are relatively high, accounting for 59.92 % of the total mutation frequency. The TP53 was significantly associated with muscle invasive bladder cancer, T2 stage, and progression-free survival, while FGFR3 was significantly associated with non-muscle invasive bladder cancer and T1 stage. Conclusion High-throughput sequencing technology provides a successful approach for detecting bladder cancer gene mutations. The TP53 , FGFR3 , PIK3CA , ERBB2 , MUC4 , and KRAS genes have high mutation frequencies in bladder cancer patients. The TP53 , FGFR3 and PIK3CA genes may play a predictive role in the prognosis of bladder cancer, which may hold certain guiding significance for in-depth study of the pathogenesis of bladder cancer and the development of targeted therapies. [ABSTRACT FROM AUTHOR]

Pinus thunbergii (P. thunbergii) is a gymnosperm with important economic and ecological value. In order to investigate the diagnosis and defense mechanism of P. thunbergii against Bursaphelenchus xylophilus (the pinewood nematode, PWN), the needles of P. thunbergii seedlings on the fifth day after being infected by PWN were taken as samples for transcriptome sequencing analysis. Compared with the control group, 647 genes were differentially expressed in the treatment group, of which 277 genes were upregulated and 370 genes were downregulated. Enrichment analysis showed that most of these differentially expressed genes were abundant in the biosynthesis of secondary metabolites, pathogen interaction and hormone signal transduction. In addition, among the differential genes, NBS-LRR genes, thiamine-metabolizing enzymes, phenylalanine ammonia lyase and acetaldehyde dehydrogenase were screened and analyzed. The analysis of the response of P. thunbergii to PWN stress and its disease resistance genes lays a foundation for the breeding of disease-resistant P. thunbergii in the future. [ABSTRACT FROM AUTHOR]

Simple Summary: Rotator cuff tear is the most common musculoskeletal disorders in the working population. Family members of patients with rotator cuff disease have a significant higher risk of tendon tears than general population. The etiology is multifactorial, and its pathogenesis is not completely understood. It is expected that multiple gene variants contribute to disease susceptibility but, in some instances, a few main rare variants can be responsible for the clinical manifestations. We performed exome sequencing on a family (4 members) to identify rare gene variants predisposing to the development of rotator cuff tears. Rare variants in common between the two affected subjects were selected. Using the predictions in silico tools, the candidate variants were segregated by Sanger sequencing. Based on the risk of being damaging and on the potential role in rotator cuff etiopathogenesis, three candidate genes for rotator cuff tears were prioritized: COL23A1, EMILIN3 and HDAC10. These findings suggest that performing exome sequencing in other rotator cuff tears families will possibly lead to the identification of major candidate genes for the disease. The genes identified in the present study could be confirmed in a larger cohort of patients with rotator cuff tears, even if they have no family history. Background: multiple gene variants seem to contribute to rotator cuff (RC) tear susceptibility. The aim of the study is to perform an exome sequencing analysis within a family to identify rare gene variants predisposing to the development of RC tear. Material and methods: the exome sequencing was conducted in a family consisting of four individuals, two healthy and the remaining ones with bilateral RC tears. Variants in common among the two affected subjects were selected, and those in common with the healthy subject and those with a frequency >1% were removed. The potential pathogenicity of the variants was investigated using the predictions of several in silico tools from VarSome. Results: the exome sequencing yielded approximately 600,000 variants per patient, subsequently filtered according to frequency <1% and absence of association with other diseases. Removing variants common with the healthy subject, 348 rare variants among 248 genes were identified. Based on the risk of damaging, three candidate genes for RC tear were found: COL23A1, EMILIN3, and HDAC10. Conclusion: this is the first whole-exome sequencing analysis within a family to explore genetic predisposition in RC tear. The results reveal the presence of common damaging variants among affected individuals in the COL23A1, EMILIN3, and HDAC10 genes. [ABSTRACT FROM AUTHOR]

Background: Genome-wide association studies for various hemorheological characteristics have not been reported. We aimed to identify genetic loci associated with hemorheological indexes in a cohort of healthy Chinese Han individuals. Methods: Genotyping was performed using Applied Biosystems Axiom™ Precision Medicine Diversity Array in 838 individuals, and 6,423,076 single nucleotide polymorphisms were available for genotyping. The relations were examined in an additive genetic model using mixed linear regression and combined with identical by descent matrix. Results: We identified 38 genetic loci (p < 5 × 10−6) related to hemorheological traits. In which, LOC102724502-OLIG2 rs28371438 was related to the levels of nd30 (p = 8.58 × 10−07), nd300 (p = 1.89 × 10−06), erythrocyte rigidity (p = 1.29 × 10−06), assigned viscosity (p = 6.20 × 10−08) and whole blood high cut relative (p = 7.30 × 10−08). The association of STK32B rs4689231 for nd30 (p = 3.85 × 10−06) and nd300 (p = 2.94 × 10−06) and GTSCR1-LINC01541 rs11661911 for erythrocyte rigidity (p = 9.93 × 10−09) and whole blood high cut relative (p = 2.09 × 10−07) was found. USP25-MIR99AHG rs1297329 was associated with erythrocyte rigidity (p = 1.81 × 10−06) and erythrocyte deformation (p = 1.14 × 10−06). Moreover, the association of TMEM232-SLC25A46 rs3985087 and LINC00470-METTL4 rs9966987 for fibrinogen (p = 1.31 × 10−06 and p = 4.29 × 10−07) and plasma viscosity (p = 1.01 × 10−06 and p = 4.59 × 10−07) was found. Conclusion: These findings may represent biological candidates for hemorheological indexes and contribute to hemorheological study. [ABSTRACT FROM AUTHOR]

A recent Chinese genome-wide association study found evidence for 58 out of the 128 schizophrenia-associated variants previously discovered in Western samples by the Schizophrenia Working Group of the Psychiatric Genomics Consortium (PGC). However, the functional impact of these trans-ancestry genome-wide single-nucleotide polymorphisms (SNPs) is not clear. In the current study, we examined the roles of trans-ancestry SNPs in cognitive and neural plasticity. We first performed a behavioral study of 547 healthy volunteers, who received month-long working memory training, and working memory capability assessment both before and after the training. A separate sample of 101 subjects received the same training and received fMRI scans during a working memory task, both before and after the training. The behavioral study found a significant association between the polygenic risk score (PRS) and behavioral plasticity, with higher schizophrenia risk scores being linked to less plasticity. At the SNP level, rs36068923 showed a significant signal, with the risk allele being associated with less plasticity. The fMRI study further found that the PRS and rs36068923 polymorphism were associated with training-induced changes in striatal activation, with higher PRS and the risk allele of rs36068923 being linked to less brain plasticity. In sum, this study found that a high genetic risk for schizophrenia was associated with less plasticity at both behavioral and neural levels. These results provide new insights into the neural and cognitive mechanisms linking genes to schizophrenia. [ABSTRACT FROM AUTHOR]

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Efficient tools for data management and integration are essential for many aspects of high-throughput biology. In particular, annotations of genes and human genetic variants are commonly used but highly fragmented across many resources. Here, we describe MyGene.info and MyVariant.info, high-performance web services for querying gene and variant annotation information. These web services are currently accessed more than three million times permonth. They also demonstrate a generalizable cloud-based model for organizing and querying biological annotation information. MyGene.info and MyVariant.info are provided as high-performance web services, accessible at http://mygene.info and http://myvariant.info . Both are offered free of charge to the research community.

Background: Congenital hypofibrinogenemia is characterized by proportional decreases in fibrinogen activity and immunoreactive fibrinogen levels. Here, we describe a new case with the bleeding risk identified in our hospital. Methods: The proband was cut and bled for 3 h. Coagulation testing, gene analysis, thrombelastogram, sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS‐PAGE), in vitro plasmid construction, and functional analyses were performed to explore the pathogenic mechanism. Results: Coagulation testing of the male proband revealed low levels of fibrinogen detected by two methods (the Clauss method and the PT‐derived method); his two sons had normal coagulation results. DNA sequencing of the proband revealed a heterozygous point mutation in exon 8 of the FGB gene causing Trp→Stop substitution and a polymorphic site (p.Leu92Phe). Human Trp433 was found to be highly conserved. SDS‐PAGE showed that the fibrinogen level of the proband was markedly lower than that of healthy controls. Using high‐performance liquid chromatography‐mass spectrometry, a mutated Bβ chain was not detected in circulation. In vitro expression analyses indicated that the mutation affected the secretion of fibrinogen. The TEG results indicated that the proband had a prolonged K time, a lower CI value, and a lower angle value. Conclusion: We report a new case with a novel nonsense mutation that resulted in hypofibrinogenemia. The results indicate that the nonsense mutation may cause misfolding of the D domain, which then affects the secretion of fibrinogen. [ABSTRACT FROM AUTHOR]

Study Design: A genetic case-control study.Objectives: To investigate whether the variants in BOC, SEC16B, and SH2D1B are sex-specifically and functionally associated with the susceptibility of adolescent idiopathic scoliosis (AIS) in Chinese Han population.Summary Of Background Data: A recent genome-wide association study identified three female-specific susceptibility loci of AIS in Japanese population. However, the association of these genes with AIS in other populations remains unclear. Further investigation of the functional role of the three genes was warranted.Methods: SNPs rs73235136, rs545608, and rs142502288 were genotyped in 1599 AIS patients and 2985 controls. Paraspinal muscle collected from 40 AIS and 30 lumber disc herniation patients during surgical interventions was used for gene expression analysis. The difference regarding genotype and allele frequency between patients and controls was analyzed by chi-square analysis. Expression of BOC and SEC16B was compared between AIS and lumber disc herniation patients by the Student t test. Pearson correlation analysis was performed to evaluate the relationship between gene expression level and clinical phenotypes.Results: SNPs rs73235136 of BOC and rs545608 of SEC16B were found to be remarkably associated with AIS only in females. Allele C of rs73235136 and allele G of rs545608 could significantly add to the risk of female AIS patients, with an odds ratio of 1.087 and 1.033, respectively. However, there was no significant difference between the male patients and controls regarding genotype or allele frequency of rs73235136 and rs545608. No polymorphism at rs142502288 was detected in either patients or controls, and all the subjects had genotype of AA. Moreover, tissue expression of BOC and SEC16B was significantly lower in AIS patients compared with controls. BOC expression was positively associated with bone mineral contents, and expression of SEC16B was negatively correlated with curve severity in AIS patients.Conclusion: Female-specific variants in BOC and SEC16B were associated with AIS. Expression of BOC and SEC16B was significantly lower in AIS patients. The role of BOC and SEC16B in the development of AIS is worthy of further investigation.Level of Evidence: 3. [ABSTRACT FROM AUTHOR]

Purpose: It is unknown why some athletes develop patellar tendinopathy and others do not, even when accounting for similar workloads between individuals. Genetic differences between these two populations may be a contributing factor. The purpose of this work was to screen the entire genome for genetic markers associated with patellar tendinopathy. Methods: Genome-wide association (GWA) analyses were performed utilizing data from the Kaiser Permanente Research Board (KPRB) and the UK Biobank. Patellar tendinopathy cases were identified based on electronic health records from KPRB and UK Biobank. GWA analyses from both cohorts were tested for patellar tendinopathy using a logistic regression model adjusting for sex, height, weight, age, and race/ethnicity using allele counts for single nucleotide polymorphisms. The data from the two GWA studies (KPRB and UK Biobank) were combined in a meta-analysis. Results: There were a total of 1670 cases of patellar tendinopathy and 293,866 controls within the two cohorts. Two single nucleotide polymorphisms located in the intron of the cytochrome c oxidase assembly factor 1 (COA1) gene showed a genome-wide significant association in the meta-analysis. Conclusions: Genetic markers in COA1 seem to be associated with patellar tendinopathy and are potential risk factors for patellar tendinopathy that deserve further validation regarding molecular mechanisms. [ABSTRACT FROM AUTHOR]

Background: Genetic kidney disease is well established as an important cause of pediatric kidney failure, and genetic testing might increase diagnostic accuracy, but evidence is limited. This study was conducted to determine the diagnostic yield and clinical impact of genetic testing for children with kidney failure. Methods: Patients who were diagnosed with kidney failure before 19 years of age at Children's Hospital of Fudan University from 2009 to 2018 and received next-generation sequencing (NGS) were enrolled. The results for likely pathogenic variants in genes known to cause chronic kidney disease (CKD) were analyzed. Results: A molecular diagnosis was identified in 39.9% (75/188) of children with kidney failure. Specific subtype of clinical category was discerned in 54 (72.0%) patients, kidney disease was reclassified in 7 (9.3%) patients, the unknown etiology of 5 (6.7%) patients was molecularly diagnosed, and the clinical diagnoses of the other 9 (12.0%) patients were confirmed. In addition, genetic diagnosis was considered to have contributed to clinical management, including negating the need for kidney biopsy (26/75, 34.7%), avoiding immunosuppressive therapy (24/75, 32.0%), changing surveillance (48/75, 64.0%), guiding specific treatment (21/75, 28.0%), and guiding peri-transplant management and options for kidney transplantation (12/75, 16.0%). Furthermore, cascade testing was subsequently offered to 34.7% (26/75) of families. Conclusions: Genetic testing identified a molecular diagnosis in nearly 40% of children with kidney failure. Our results confirm that in children with kidney failure, genetic testing can not only establish a specific molecular diagnosis, but has a significant impact on clinical management. [ABSTRACT FROM AUTHOR]

With the completion of the Human Genome Project and advances in genomic sequencing technologies, the use of clinical molecular diagnostics has grown tremendously over the last decade. Next-generation sequencing (NGS) has overcome many of the practical roadblocks that had slowed the adoption of molecular testing for routine clinical diagnosis. In endocrinology, targeted NGS now complements biochemical testing and imaging studies. The goal of this review is to provide clinicians with a guide to the application of NGS to genetic testing for endocrine conditions, by compiling a list of established gene mutations detectable by NGS, and highlighting key phenotypic features of these disorders. As we outline in this review, the clinical utility of NGS-based molecular testing for endocrine disorders is very high. Identifying an exact genetic etiology improves understanding of the disease, provides clear explanation to families about the cause, and guides decisions about screening, prevention and/or treatment. To illustrate this approach, a case of hypophosphatasia with a pathogenic mutation in the ALPL gene detected by NGS is presented.

Multiple sclerosis (MS) is a chronic inflammatory autoimmune disease, which leads to neurodegenerative processes that cause neuron demyelination. MS is multifactorial with uncertain etiology, where interactions between genetic makeup of an individual and environmental factors influence disease risk. More than 200 risk variants have been implicated in MS, each contributed to understanding the etiology of MS through providing meaningful clues of the functional mechanisms underlying the development of this disease. This study aimed to identify genetic variants associated with MS in the Jordanian population. We performed whole exome sequencing for eight pairs of related patients from eight different families including one pair of discordant monozygotic twins, to determine the shared genetic information and genetic variants, and their correlation to MS. We identified rare exonic missense and frame shift variants segregating in all patients in MUC6, MUC16, and MUC19 genes, which are involved in innate immunity, in addition to ZNF717 gene. Moreover, variants in two of the previously described MS genes (HLA-DRB1, HLA- DRQ1) were also segregating in most patients. These molecular genetic details require further validation and functional analysis, to be implicated in the clinical diagnosis process of MS. This is the first attempt to characterize the genetic factors associated with MS in the Jordanian population. [ABSTRACT FROM AUTHOR]

Objective: To perform the genetic characterization of a cohort with familial parkinsonism and cognitive-behavioral syndrome.Methods: A Next Generation Sequencing - based targeted sequencing of 32 genes associated to various neurodegenerative phenotypes, plus a screening for SNCA Copy Number Variations and C9orf72 repeat expansion, was applied in a cohort of 85 Italian patients presenting with parkinsonism and cognitive and/or behavioral syndrome and a positive familial history for any neurodegenerative disorder (i.e., dementia, movement disorders, amyotrophic lateral sclerosis).Results: Through this combined genetic approach, we detected potentially relevant genetic variants in 25.8% of patients with familial parkinsonism and cognitive and/or behavioral syndrome. Peculiar phenotypes are described (Cortico-basal syndrome with APP, Posterior Cortical Atrophy with GBA, Progressive Supranuclear Palsy-like with GRN, Multiple System Atrophy with TARDBP). The majority of patients presented a rigid-bradykinetic parkinsonian syndrome, while rest tremor was less common. Myoclonic jerks, pyramidal signs, dystonic postures and vertical gaze disturbances were more frequently associated with the presence of a pathogenic variant in one of the tested genes.Conclusions: Given the syndromic approach adopted in our study, we were able to provide a detailed clinical description of patients beyond the boundaries of specific clinical diagnoses and describe peculiar phenotypes. This observation further supports the knowledge that genetic disorders present phenotypic overlaps across different neurodegenerative syndromes, highlighting the limitations of current clinical diagnostic criteria defining sharp boundaries between distinct conditions. [ABSTRACT FROM AUTHOR]

Sequencing 16S rRNA gene amplicons is the gold standard to uncover the composition of prokaryotic communities. The presence of multiple copies of this gene makes the community abundance data distorted and gene copy normalization (GCN) necessary for correction. Even though GCN of 16S data provided a picture closer to the metagenome before, it should also be compared with communities of known composition due to the fact that library preparation is prone to methodological biases. Here, we process 16S rRNA gene amplicon data from eleven simple mock communities with DADA2 and estimate the impact of GCN. In all cases, the mock community composition derived from the 16S sequencing differs from those expected, and GCN fails to improve the classification for most of the analysed communities. Our approach provides empirical evidence that GCN does not improve the 16S target sequencing analyses in real scenarios. We therefore question the use of GCN for metataxonomic surveys until a more comprehensive catalogue of copy numbers becomes available. [ABSTRACT FROM AUTHOR]

The chicken Insulin-like growth factor 1 (IGF1) is a candidate gene for growth, body composition and metabolism, skeletal characteristics and growth of adipose tissue and fat deposition in chickens. It is mapped to 165.95 cM on chromosome 1 and composed of four exons and three introns, spanning more than 50 kb. Genomic DNA was extracted from blood samples collected from the experimental birds using Qiagen DNA extraction kits. Polymersae chain reaction (PCR) was carried out using established primers. The PCR amplicon involving 5'untranslated region were sequenced. The sequences were analysed to identify polymorphisms, their genetic diversities and evolutionary relationships among three strains of Nigerian indigenous chickens [Frizzle Feathered (7), Normal Feathered (19) and Naked Neck (19), and the Arbor Acre broiler chicken (17)]. Nucleotide sequences generated were edited and aligned using Codon Code Aligner. Diversity analysis was done using DnaSp while MEGA6 software was used to plot phylogenetic tree using maximum likelihood method. A total of nineteen single nucleotide polymorphisms (SNPs) were detected from 560 bp portions of the 5'UTR among the four chicken populations studied with none detected in the Frizzle feathered chicken. The Naked neck chicken had the highest number of SNP's (13), haplotypes (6), haplotype diversity (0.778), nucleotide diversity (0.00487), average number of nucleotide differences (2.725), highest number of polymorphic (segregating) sites (13), parsimony informative site (5) and singleton variable site (8). The Naked neck chicken therefore had the highest rate of mutation and degree of allelic variation compared to other chicken strains used in this study. The phylogenetic tree showed that small genetic differentiation exists among the chicken populations studied. Some of the SNPs are newly discovered; hence, association between these alleles and productive traits in Nigerian native chickens is desirable in future studies. [ABSTRACT FROM AUTHOR]

Sour rot, caused by Geotrichum citri-aurantii , is a major postharvest disease of citrus，and it causes serious economic losses. In this study, a high-quality genome sequence of G. citri-aurantii was obtained by Single Molecule Real-Time Sequencing (SMRT). Approximately 5.43 Gb of clean data were obtained and a total of 27.94-Mb genomic sequence was mapped to 10 chromosome groups after high-through chromosome conformation capture (Hi-C) assembly. In addition, three polygalacturonase genes which were related to pathogenicity in G. citri-aurantii genome were discovered. And transcriptome data of guazatine-resistance had been analyzed, the results showed that the guazatine-resistance of G. citri-aurantii was related to two ATP-binding cassette (ABC) transporter family genes, six major facilitator superfamily (MFS) transporter family genes and two multidrug and toxic compound extrusion (MATE) transporter family genes. In summary, our research may provide novel insights into the effective control of this pathogen. • A high-quality genome sequence of G. citri-aurantii was obtained by SMRT for the first time. • Three polygalacturonase (PG) genes and twelve genes related to pathogenicity were identified. • Two ABC transporter family genes, six MFS transporter family genes and two MATE transporter family genes were identified. [ABSTRACT FROM AUTHOR]

Background: Alzheimer's disease, frontotemporal lobar degeneration, dementia with Lewy bodies, and Parkinson's disease (PD) overlap in clinical characteristics, neuropathology, and genetics.Objective: The aim of this study was to evaluate the role of pathogenic mutations and rare variants in genes associated with PD among early-onset dementia (EOD) patients.Methods: Rare non-synonymous variants (MAF < 0.01) in ten genes (SNCA, PARK2, PARK7, LRRK2, PINK1, ATP13A2, UCHL1, HTRA2, GBA, and SNCAIP) and low-frequency (MAF < 0.05) GBA variants were screened using a targeted next-generation sequencing panel in a strictly defined cohort of 37 early-onset (age at onset (AAO) <65 years) dementia patients presenting with atypical features (e.g., myoclonia or spasticity), rapidly progressive course of the disease or with a family history of dementia. The identified variations were further screened in a larger cohort of EOD (n = 279, mean AAO 57, range 36-65) patients.Results: No pathogenic mutations were found, but we identified seven possible risk variants for neurodegeneration (LRRK2 p.Arg793Met, PARK2 p.Ala82Glu, SNCAIP p.Arg240Gln, SNCAIP p.Phe369Leu, GBA p.Asn409Ser, GBA p.Glu365Lys, GBA p.Thr408Met).Discussion: Altogether, the frequency of these variants was two times higher in the first selected cohort compared to the whole cohort. This suggests that specific rare variants in the genes associated with PD might play a role also especially in familial EOD. [ABSTRACT FROM AUTHOR]

Background and Aims: Periodontitis is one of the most common causes of damage to the gums and retaining structures of the teeth. Matrix protein, a metalloproteinase, is known as intermediate collagenase and the enzyme collagenase fibroblast, which is encoded in humans by the MMP-1 gene. The aim of this study was to investigate 1G/2G polymorphism in the MMP-1 gene and its association with the periodontal disease in the Iranian patients. Materials and Methods: In this study, 50 patients with periodontal disease and 50 patients were selected as the control group in Kerman city. DNA was extracted from a person's blood sample using a kit. The desired primers were controlled by the NCBI site. Then, with the Tetra arms PCR technique, the desired polymorphism was multiplied. In the next step, the samples were transferred to electrophoresis gel and examined. The results were analyzed with SPSS software using T-test or Squer Chi-(X2). Results: The percentage of 1G/1G genotype in the patients group was 8% and for the controls group was 0%. The percentage of 2G/2G genotype for the patients group was 24% and for the controls group was 18%. In addition, the 1G/2G genotype frequency was 68% for the patients group, and for the controls group was 82% (P=0.83). The results of Tetra-arms PCR genotyping of the samples were confirmed by sequencing. Conclusion: The findings indicated that in Iranian patients, MMP-1 -1607 1G/2G (rs1799750) was not significantly associated with periodontal disease. It is recommended to take more samples from different parts of Iran to confirm the results. [ABSTRACT FROM AUTHOR]

Background There is increasing evidence that certain genetic variants increase the risk of schizophrenia and other neurodevelopmental disorders. Exome sequencing has been shown to have a high diagnostic yield for developmental disability and testing for copy number variants has been advocated for schizophrenia. The diagnostic yield for exome sequencing in schizophrenia is unknown. Method A sample of 591 exome-sequenced schizophrenia cases and their parents were screened for disruptive and damaging variants in autosomal genes listed in the Genomics England panels for intellectual disability and other neurological disorders. Results Previously reported disruptive de novo variants were noted in SETD1A , POGZ , SCN2A, and ZMYND11. Although the loss of function of ZMYND11 is a recognized cause of intellectual disability, it has not previously been noted as a risk factor for schizophrenia. A damaging de novo variant of uncertain significance was noted in NRXN1. A previously reported homozygous damaging variant in BLM is predicted to cause Bloom syndrome in 1 case and 1 case was homozygous for a damaging variant in MCPH1 , a result of uncertain significance. There were more than 400 disruptive and damaging variants in the target genes in cases but similar numbers were seen among untransmitted parental alleles and none appeared to be clinically significant. Conclusions The diagnostic yield from exome sequencing in schizophrenia is low. Disruptive and damaging variants seen in known neuropsychiatric genes should not be automatically assumed to have an etiological role if observed in a patient with schizophrenia. [ABSTRACT FROM AUTHOR]

Rice stripe virus (RSV) is one of the major constraints in rice production which is transmitted by the small brown plant hopper, Laodelphax striatellus. Identifying new resistance genes from diverse sources is important for rice breeding programs to enhance the resistance level and/or to overcome the breakdown of resistance genes. This study was conducted to identify novel sources of resistance against RSV. We used five RSV resistant varieties that do not harbor Stv-bi . The presence of known genes for RSV resistance was identified using the InDel7 marker for Stv-bi , two Indel (Sid primer set) markers for Stv-b, and DNA sequence analysis for OsSOT1. We revealed that two varieties, 02428 (IT236925) and Tung Ting Wan Hien 1, are novel RSV resistance sources. [ABSTRACT FROM AUTHOR]

It is increasingly common in oncology practice to perform tumour sequencing using large cancer panels. For pathogenic sequence variants in cancer susceptibility genes identified on tumour-only sequencing, it is often unclear whether they are of somatic or constitutional (germline) origin. There is wide-spread disparity regarding both the extent to which systematic 'germline-focussed analysis' is carried out upon tumour sequencing data and for which variants follow-up analysis of a germline sample is carried out. Here we present analyses of paired sequencing data from 17 152 cancer samples, in which 1494 pathogenic sequence variants were identified across 65 cancer susceptibility genes. From these analyses, the European Society of Medical Oncology Precision Medicine Working Group Germline Subgroup has generated (i) recommendations regarding germline-focussed analyses of tumour-only sequencing data, (ii) indications for germline follow-up testing and (iii) guidance on patient information-giving and consent. [ABSTRACT FROM AUTHOR]

Manganese (Mn) is one of the most abundant transitional metals in the crust of the Earth and Mn contamination is occurring in groundwater worldwidely. The removal of manganese is mainly achieved by catalytic oxidation of manganese-oxidizing bacteria. As a result, biological Mn-removal technology has attracted increased attention due to its high efficiency and convenience. Several species of bacteria, including Bacillus and Pseudomonas , have the ability to oxidize Mn. A bacterial strain MK-1 from Lysinibacillus , capable of oxidizing 98% of Mn under optimal conditions (1mmol/L of Mn(II), pH 7.0, 3days), was obtained from a mine located in Hunan province, and a gene, mokA , putatively encoding a manganese oxidase, was identified. The MokA enzyme produced by mok A is a CotA-like multicopper oxidase (MCO) that exhibited significantly different expression profiles in medium with and without Mn(II). Sequence analysis of MokA revealed that it is structurally similar to previously reported manganese oxidases. The results of this study broaden the taxonomic range manganese-oxidizing bacteria. Based on these results, our findings suggested that MK-1 might be applied for the treatment of Mn(II)-contaminated water. [ABSTRACT FROM AUTHOR]

Objective: Microtia is a congenital malformation of the external ear. Great progress about the genetic of microtia has been made in recent years. This article was to prioritize the potential candidate pathogenic genes of microtia based on existing studies and reports, with the purpose of narrowing the range of following study scientifically and quickly. Method: A computational tool called Phenolyzer (phenotype-based gene analyzer) was used to prioritize microtia genes. Microtia, as a query term, was input in the interface of Phenolyzer. After several steps, including disease match, gene query, gene score system, seed gene growth, and gene ranking, the final results about genetic information of microtia were provided. Then we tracked details of the top 10 genes ranked by Phenolyzer on the basis of previous reports. Results: We detected 10 348 genes associated with microtia or related syndromes, and 78 genes of those genes belonged to seed genes. Every gene was given a score, and the gene with higher scores was more likely influence microtia. The top 10 ranked genes included HOXA2, CHD7, CDT1, ORC1, ORC4, ORC6, CDC6, MED12, TWIST1, and GLI3. Otherwise, four gene-gene interactions were displayed. Conclusion: This article prioritized candidate genes of microtia for the first time. High-throughput methods provide tens of thousands of single-nucleotide variants, indels, and structural variants, and only a handful are relevant to microtia or associated syndromes. Combine the ranked potential pathogenic genes list from Phenolyzer with the results of samples provided by high-throughput methods, and more precise research directions are presented. [ABSTRACT FROM AUTHOR]

Purpose: Molecular analysis of different types of thumb duplication and identification of new suspected gene mutations.Materials and methods: In a series of patients operated for polydactyly, DNA was extracted from blood samples collected preoperatively. Among these, the samples of two patients with thumb duplication (Wassel types III and IV) were initially selected for molecular analysis. The method of Clinical Exome Solution was used for the study of the phenotype-involved genes. Next-generation sequencing (NGS) was performed on a NextSeq-500 Platform (Illumina), and Sophia DDM® SaaS algorithms were used for the bioinformatics analysis of the data.Results: In total, 8—including 4 new—mutations were detected in CEP290 (1 mutation), RPGRIP1 (2 mutations), TMEM216 (2 mutations), FBN1 (1 mutation), CEP164 (1 mutation), and MEGF8 (1 mutation) genes. NGS revealed 3 mutated genes in the patient with Wassel III thumb duplication and 5 mutated genes in the patient with Wassel IV duplication. The molecular analysis revealed that the patients had 2 mutated genes in common, but they only shared one common mutation.Conclusion: The new detected mutations are most probably associated with thumb duplication, as they belong to genes with already described mutations causing ciliopathies, often including polydactyly in their phenotype. Recognition of these mutations will be helpful to prenatal diagnosis, operative treatment strategy prediction, and possible future experimental applications in gene therapy. [ABSTRACT FROM AUTHOR]