Genetic variants in C1GALT1 are associated with gastric cancer risk by influencing immune infiltration

Core 1 synthase glycoprotein-N-acetylgalactosamine 3-β-galactosyltransferase 1(C1GALT1)is known to play a critical role in the development of gastric cancer,but few studies have elucidated associations between genetic variants in C1GALT1 and gastric cancer risk.By using the genome-wide association study data from the database of Genotype and Phenotype(dbGAP),we evaluated such associations with a multivariable logistic regression model and identified that the rs35999583 G>C in C1GALT1 was associated with gastric cancer risk(odds ratio,0.83;95% confidence interval[CI],0.75-0.92;P=3.95×10^(-4)).C1GALT1 mRNA expression levels were significantly higher in gastric tumor tissues than in normal tissues,and gastric cancer patients with higher C1GALT1 mRNA levels had worse overall survival rates(hazards ratio,1.33;95%CI,1.05-1.68;P_(log-rank)=1.90×10^(-2)).Furthermore,we found that C1GALT1 copy number differed in various immune cells and that C1GALT1 mRNA expression levels were positively correlated with the infiltrating levels of CD4^(+)T cells and macrophages.These results suggest that genetic variants of C1GALT1 may play an important role in gastric cancer risk and provide a new insight for C1GALT1 into a promising predictor of gastric cancer susceptibility and immune status.

Genetic Analysis of Two Novel GPI Variants Disrupting H Bonds and Localization Characteristics of 55 Gene Variants Associated with Glucose-6-phosphate Isomerase Deficiency

Objective:Glucose-6-phosphate isomerase(GPI)deficiency is a rare hereditary nonspherocytic hemolytic anemia caused by GPI gene variants.This disorder exhibits wide heterogeneity in its clinical manifestations and molecular characteristics,often posing challenges for precise diagnoses using conventional methods.To this end,this study aimed to identify the novel variants responsible for GPI deficiency in a Chinese family.Methods:The clinical manifestations of the patient were summarized and analyzed for GPI deficiency phenotype diagnosis.Novel compound heterozygous variants of the GPI gene,c.174C>A(p.Asn58Lys)and c.1538G>T(p.Trp513Leu),were identified using whole-exome and Sanger sequencing.The AlphaFold program and Chimera software were used to analyze the effects of compound heterozygous variants on GPI structure.Results:By characterizing 53 GPI missense/nonsense variants from previous literature and two novel missense variants identified in this study,we found that most variants were located in exons 3,4,12,and 18,with a few localized in exons 8,9,and 14.This study identified novel compound heterozygous variants associated with GPI deficiency.These pathogenic variants disrupt hydrogen bonds formed by highly conserved GPI amino acids.Conclusion:Early family-based sequencing analyses,especially for patients with congenital anemia,can help increase diagnostic accuracy for GPI deficiency,improve child healthcare,and enable genetic counseling.

Integration between Genomic and Computational Statistical Surveys for the Screening of SNP Genetic Variants in Inflammatory Bowel Disease (IBD) Pediatric Patients*

Inflammatory bowel diseases (IBD) are complex multifactorial disorders that include Crohn’s disease (CD) and ulcerative colitis (UC). Considering that IBD is a genetic and multifactorial disease, we screened for the distribution dynamism of IBD pathogenic genetic variants (single nucleotide polymorphisms;SNPs) and risk factors in four (4) IBD pediatric patients, by integrating both clinical exome sequencing and computational statistical approaches, aiming to categorize IBD patients in CD and UC phenotype. To this end, we first aligned genomic read sequences of these IBD patients to hg19 human genome by using bowtie 2 package. Next, we performed genetic variant calling analysis in terms of single nucleotide polymorphism (SNP) for genes covered by at least 20 read genomic sequences. Finally, we checked for biological and genomic functions of genes exhibiting statistically significant genetic variant (SNPs) by introducing Fitcon genomic parameter. Findings showed Fitcon parameter as normalizing IBD patient’s population variability, as well as inducing a relative good clustering between IBD patients in terms of CD and UC phenotypes. Genomic analysis revealed a random distribution of risk factors and as well pathogenic SNPs genetic variants in the four IBD patient’s genome, claiming to be involved in: i) Metabolic disorders, ii) Autoimmune deficiencies;iii) Crohn’s disease pathways. Integration of genomic and computational statistical analysis supported a relative genetic variability regarding IBD patient population by processing IBD pathogenic SNP genetic variants as opposite to IBD risk factor variants. Interestingly, findings clearly allowed categorizing IBD patients in CD and UC phenotypes by applying Fitcon parameter in selecting IBD pathogenic genetic variants. Considering as a whole, the study suggested the efficiency of integrating clinical exome sequencing and computational statistical tools as a right approach in discriminating IBD phenotypes as well as improving inflammatory bowel disease (IBD) molecular diagnostic process.

Progress in clinical diagnosis and treatment of colorectal cancer with rare genetic variants

Targeted therapy is crucial for advanced colorectal cancer(CRC) positive for genetic drivers. With advances in deep sequencing technology and new targeted drugs, existing standard molecular pathological detection systems and therapeutic strategies can no longer meet the requirements for careful management of patients with advanced CRC. Thus, rare genetic variations require diagnosis and targeted therapy in clinical practice. Rare gene mutations, amplifications, and rearrangements are usually associated with poor prognosis and poor response to conventional therapy. This review summarizes the clinical diagnosis and treatment of rare genetic variations, in genes including erb-b2 receptor tyrosine kinase 2(ERBB2), B-Raf proto-oncogene, serine/threonine kinase(BRAF), ALK receptor tyrosine kinase/ROS proto-oncogene 1, receptor tyrosine kinase(ALK/ROS1), neurotrophic receptor tyrosine kinases(NTRKs), ret proto-oncogene(RET), fibroblast growth factor receptor 2(FGFR2), and epidermal growth factor receptor(EGFR), to enhance understanding and identify more accurate personalized treatments for patients with rare genetic variations.

Genome-wide investigation to assess copy number variants in the Italian local chicken population

Background Copy number variants(CNV)hold significant functional and evolutionary importance.Numerous ongoing CNV studies aim to elucidate the etiology of human diseases and gain insights into the population structure of livestock.High-density chips have enabled the detection of CNV with increased resolution,leading to the identification of even small CNV.This study aimed to identify CNV in local Italian chicken breeds and investigate their distribution across the genome.Results Copy number variants were mainly distributed across the first six chromosomes and primarily associated with loss type CNV.The majority of CNV in the investigated breeds were of types 0 and 1,and the minimum length of CNV was significantly larger than that reported in previous studies.Interestingly,a high proportion of the length of chromosome 16 was covered by copy number variation regions(CNVR),with the major histocompatibility complex being the likely cause.Among the genes identified within CNVR,only those present in at least five animals across breeds(n=95)were discussed to reduce the focus on redundant CNV.Some of these genes have been associated to functional traits in chickens.Notably,several CNVR on different chromosomes harbor genes related to muscle development,tissue-specific biological processes,heat stress resistance,and immune response.Quantitative trait loci(QTL)were also analyzed to investigate potential overlapping with the identified CNVR:54 out of the 95 gene-containing regions overlapped with 428 QTL associated to body weight and size,carcass characteristics,egg production,egg components,fat deposition,and feed intake.Conclusions The genomic phenomena reported in this study that can cause changes in the distribution of CNV within the genome over time and the comparison of these differences in CNVR of the local chicken breeds could help in preserving these genetic resources.

Genetic variant in a BaP-activated super-enhancer increases prostate cancer risk by promoting AhR-mediated FAM227A expression

Genetic variants in super-enhancers(SEs)are increasingly implicated as a disease risk-driving mechanism.Previous studies have reported an associations between benzo[a]pyrene(BaP)exposure and some malignant tumor risk.Currently,it is unclear whether BaP is involved in the effect of genetic variants in SEs on prostate cancer risk,nor the associated intrinsic molecular mechanisms.In the current study,by using logistic regression analysis,we found that rs5750581T>C in 22q-SE was significantly associated with prostate cancer risk(odds ratio=1.26,P=7.61×10^(-5)).We also have found that the rs6001092T>G,in a high linkage disequilibrium with rs5750581T>C(r^(2)=0.98),is located in a regulatory aryl hydrocarbon receptor(AhR)motif and may interact with the FAM227A promoter in further bioinformatics analysis.We then performed a series of functional and BaP acute exposure experiments to assess biological function of the genetic variant and the target gene.Biologically,the rs6001092-G allele strengthened the transcription factor binding affinity to AhR,thereby upregulating FAM227A,especially upon exposure to BaP,which induced the malignant phenotypes of prostate cancer.The current study highlights that AhR acts as an environmental sensor of BaP and is involved in the SE-mediated prostate cancer risk,which may provide new insights into the etiology of prostate cancer associated with the inherited SE variants under environmental carcinogen stressors.

Genetic Analysis of Variants of the MYH6 Gene Promoter in Congenital Atrial Septal Defects

Background:Atrial septal defect(ASD)is one of the common congenital heart diseases.The MYH6 gene has a critical role in cardiac development but the role of MYH6 promoter variants in patients with ASD has not been explored.Methods:In 613 subjects including 320 ASD patients,we investigated the MYH6 gene promoter variants and verified the effect on gene expression by using cellular functional experiments and bioinformatics analysis.Results:Eleven variants were identified in the MYH6 gene promoter,of which four variants were found only in ASD patients,and two variants(g.3434G>C and g.4524C>T)were identified for the first time.Cellular functional experiments indicated that all four variants reduced the transcriptional activity of the MYH6 gene promoter(p<0.05).Subsequent analysis through the JASPAR(A database of transcription factor binding profiles)suggests that these variants may alter transcription factor binding sites,which may in turn lead to changes in myocardin subunit expression and ASD formation.Conclusions:Our study for the first time focuses on variants in the promoter region of the MYH6 gene in Chinese patients with ASD and the discovered variants have functional significance.The study provides new insights in the role of the MYH6 gene promoter region to better understand the genetic basis of ASD formation and facilitates clinical diagnosis.

An efficient method for constructing a random insertional mutant library for forward genetics in Nannochloropsis oceanica

Insertional mutation,phenotypic evaluation,and mutated gene cloning are widely used to clone genes from scratch.Exogenous genes can be integrated into the genome during non-homologous end joining(NHEJ)of the double-strand breaks of DNA,causing insertional mutation.The random insertional mutant library constructed using this method has become a method of forward genetics for gene cloning.However,the establishment of a random insertional mutant library requires a high transformation efficiency of exogenous genes.Many microalgal species show a low transformation efficiency,making constructing random insertional mutant libraries difficult.In this study,we established a highly efficient transformation method for constructing a random insertional mutant library of Nannochloropsis oceanica,and tentatively tried to isolate its genes to prove the feasibility of the method.A gene that may control the growth rate and cell size was identified.This method will facilitate the genetic studies of N.oceanica,which should also be a reference for other microalgal species.

A new rhombohedral phase and its 48 variants inβtitanium alloy

A new rhombohedral phase(termed R′)in a solution-aging-treated titanium alloy(Ti-4.5Al-6.5Mo-2Cr-2Nb-1V-1Sn-1Zr,wt.%)was identified.Its accurate Bravais lattice parameters were determined by a novel unit cell reconstruction method based on conventional selected-area electron diffraction(SAED)technique.The orientation relationship between R'phase and BCC phase was revealed.The results show that the R′phase is found to have 48crystallographically equivalent variants,resulting in rather complicated SAED patterns with high-order reflections.A series of in-situ SAED patterns were taken along both low-and high-index zone axes,and all weak and strong reflections arising from the 48 variants were properly explained and directly assigned with self-consistent Miller indices,confirming the presence of the rhombohedral phase.Additionally,some criteria were also proposed for evaluating the indexed results,which together with the Bravais lattice reconstruction method shed light on the microstructure characterization of even unknown phases in other alloys.

Contribution of Genomic Surveillance in the Detection and Monitoring of SARS-CoV-2 Variants during the 6 Pandemic Waves in the Central African Republic from 2020 to 2023

Objective: The COVID-19 pandemic has highlighted the need to strengthen diagnosis and genomic surveillance capacities. In 2021, Central African managed five waves of COVID-19 by integrating genomic surveillance into their health monitoring system. This study sought to report surveillance data from the National Laboratory of Clinical Biology and Public Health and describe the circulation of SARS-CoV-2 variants. Materials and Methods: This retrospective, descriptive observational study spans three years, from April 2020 to November 2023. It was conducted on a population of consenting volunteers from across the Central African Republic, who were tested using RT-PCR on nasopharyngeal samples. Data with sufficient information were obtained from the National Laboratory of Clinical Biology and Public Health (LNBCSP) databases. Sequencing was largely carried out at the National Institute of Biomedical Research (INRB) in Kinshasa until May 2023, and subsequently at the LNBCSP. Results and Discussion: Out of 97,864 RT-PCR tests performed, 9,764 were positive, resulting in a prevalence of 9.98%. The average age of the patients was 39.97 years ± 13.76, and the male-to-female sex ratio was 2.12. RT-PCR test positivity was significantly associated with age (p = 0.001), sex (p = 0.013) and clinical manifestations. Ten variants circulated during the five recorded waves, with Omicron (B.1.1.529), Delta (B.1.617.2) variants being predominant. Notably, the B.1.620 and B.640 variants were prominent during the second wave. Conclusion: This retrospective study provides key insights into the COVID-19 pandemic in the CAR. It identifies risk factors and details the circulation of various SARS-CoV-2 variants. Enhancing national genomic surveillance capacities would enable the country to better respond to future pandemic challenges.

New recessive compound heterozygous variants of RP1L1 in RP1L1 maculopathy

AIM:To identify a maculopathy patient caused by new recessive compound heterozygous variants in RP1L1.METHODS:Comprehensive retinal morphological and functional examinations were evaluated for the patient with RP1L1 maculopathy.Targeted sequence capture array technique was used to screen potential pathologic variants.Polymerase chain reaction and Sanger sequencing were used to confirm the screening results.RESULTS:Fundus examination showed round macular lesions appeared in both eyes.Optical coherence tomography showed that the inner segment/outer segment continuity was disorganized and disruptive in the left eye,but it was uneven and slightly elevated in the right eye.Fundus autofluorescence showed patchy hyper-autofluorescence in the macula.Visual field examination indicates central defects in both eyes.Electroretinogram(ERG)and multifocal ERG showed no obvious abnormalities.Fundus fluorescein angiography in the macula showed obviously irregular hyper-fluorescence in the right eye and slightly hyper-fluorescence in the left eye.We found that the proband carried a missense variant(c.1972C>T)and a deletion variant(c.4717_4718del)of RP1L1,which were originated from the parents and formed compound heterozygous variants.Both variants are likely pathogenic according to the ACMG criteria.Multimodal imaging,ERG and detailed medical history are important diagnostic tools for differentiating between acquired and inherited retinal disorders.CONCLUSION:A maculopathy case with detailed retinal phenotype and new recessive compound heterozygous variants of RP1L1 is identified in a Chinese family,which expands the understanding of phenotype and genotype in RP1L1 maculopathy.

Sex Determination in Homo sapiens as a Multi-Step Process: Potential for Development of Variants and Sex Differences in Disease Risk

Reproduction via cis-binary mechanisms appears to have evolved fairly early in the evolution of complex organisms, and a system committed to prior to evolution of humans. While the evolution of a chromosomal-specific approach has been a successful strategy for survival of a large variety of species including humans, the fidelity of sex determination leading to 100% cis-binary outcomes is not achieved in many species, with evidence for homosexual or bisexual behaviour evident in more than 1500 species. Thus, such outcomes indicates that sex determination is a multi-step process and not a single event, and as such, could lead to the appearance of variants during the process which developed much earlier than humans. Variants could arise either due to intrinsic variation in the steps of determination, or also be influenced by environmental factors of a biological or psychological nature. In contrast to homosexual variants which do not require interventions such as hormone therapy or surgery, expression of gender dysphoria, is more based in psychology, but also has biological underpinnings and can be influenced by such hormonal interventions and surgery. While the numbers of those with gender dysphoria is small (~0.6% - 1.0% of population), the attention given to this issue raises the possibility of biological and psychological environmental factors impacting the emergence of some of those expressing gender dysphoria. Furthermore, transitioning from male-to-female or female-to-male can have consequences regarding disease risks latter in life, including the appearance of autoimmune diseases. This review will attempt to review some of the evidence regarding sex determination, discuss why the system has potentially not been improved upon during evolution, how a potential role for sex chromosome function on neurodevelopment may be central to variation in humans, and how commitment to the current strategy is likely integrated into other sex-related events such as puberty, pregnancy, and menopause to ensure species survival. It will also discuss how variants in sex determination could contribute to sex differences in disease risk and how epigenetic modifications could play a role in such risk. .

Lab results of COVID-19 patients:Omicron vs delta variants

BACKGROUND The coronavirus disease 2019(COVID-19)virus has been a world-known pan-demic since February 2020.Multiple variances had been established;the most common variants in Israel were omicron and delta.AIM To analyze and compare laboratory values in the"omicron"and"delta"variants of the coronavirus by conducting follow-up examinations and laboratory audits on COVID-19 patients admitted to our institution.METHODS A retrospective study,two groups,50 patients in each group.Patients examined positive for COVID-19 were divided into groups according to the common variant at the given time.We reviewed demographic data and laboratory results such as complete blood count and full chemistry,including electrolytes and coagulation parameters.RESULTS The mean age was 52%,66.53±21.7 were female.No significance was found comparing laboratory results in the following disciplines:Blood count,hemo-globin,and lymphocytes(P=0.41,P=0.87,P=0.97).Omicron and delta variants have higher neutrophil counts,though they are not significantly different(P=0.38).Coagulation tests:Activated paritial thromoplastin test and international normalized ratio(P=0.72,P=0.68).We found no significance of abnormality for all electrolytes.CONCLUSION The study compares laboratory results of blood tests between two variants of the COVID-19 virus–omicron and delta.We found no significance between the variants.Our results show the need for further research with larger data as well as the need to compare all COVID-19 variants.

Functional analysis of the novel mitochondrial tRNA^(Trp)and tRNA^(Ser(AGY))variants associated with type 2 diabetes mellitus

BACKGROUND Mutations in mitochondrial tRNA(mt-tRNA)genes that result in mitochondrial dysfunction play important roles in type 2 diabetes mellitus(T2DM).We previously reported a large Chinese pedigree with maternally inherited T2DM that harbors novel mt-tRNA^(Trp)A5514G and tRNA^(Ser(AGY))C12237T variants,however,the effects of these mt-tRNA variants on T2DM progression are largely unknown.AIM To assess the potential pathogenicity of T2DM-associated m.A5514G and m.C12237T variants at genetic,molecular,and biochemical levels.METHODS Cytoplasmic hybrid(cybrid)cells carrying both m.A5514G and m.C12237T variants,and healthy control cells without these mitochondrial DNA(mtDNA)variants were generated using trans-mitochondrial technology.Mitochondrial features,including mt-tRNA steady-state level,levels of adenosine triphosphate(ATP),mitochondrial membrane potential(MMP),reactive oxygen species(ROS),mtDNA copy number,nicotinamide adenine dinucleotide(NAD+)/NADH ratio,enzymatic activities of respiratory chain complexes(RCCs),8-hydroxy-deoxyguanine(8-OhdG),malondialdehyde(MDA),and superoxide dismutase(SOD)were examined in cell lines with and without these mt-tRNA variants.RESULTS Compared with control cells,the m.A5514G variant caused an approximately 35%reduction in the steady-state level of mt-tRNA^(Trp)(P<0.0001);however,the m.C12237T variant did not affect the mt-tRNA^(Ser(AGY))steady-state level(P=0.5849).Biochemical analysis revealed that cells with both m.A5514G and m.C12237T variants exhibited more severe mitochondrial dysfunctions and elevated oxidative stress than control cells:ATP,MMP,NAD+/NADH ratio,enzyme activities of RCCs and SOD levels were markedly decreased in mutant cells(P<0.05 for all measures).By contrast,the levels of ROS,8-OhdG and MDA were significantly increased(P<0.05 for all measures),but mtDNA copy number was not affected by m.A5514G and m.C12237T variants(P=0.5942).CONCLUSION The m.A5514G variant impaired mt-tRNA^(Trp)metabolism,which subsequently caused mitochondrial dysfunction.The m.C12237T variant did not alter the steady-state level of mt-tRNA^(Ser(AGY)),indicating that it may be a modifier of the m.A5514G variant.The m.A5514G variant may exacerbate the pathogenesis and progression of T2DM in this Chinese pedigree.

Interaction between diet and genetics in patients with inflammatory bowel disease

In this editorial,we comment on the article by Marangoni et al,published in the recent issue of the World Journal of Gastroenterology 2023;29:5618-5629,about“Diet as an epigenetic factor in inflammatory bowel disease”.The authors emphasized the role of diet,especially the interaction with genetics,in promoting the inflam-matory process in inflammatory bowel disease(IBD)patients,focusing on DNA methylation,histone modifications,and the influence of microRNAs.In this editorial,we explore the interaction between genetics,gut microbiota,and diet,in an only way.Furthermore,we provided dietary recommendations for patients with IBD.The Western diet,characterized by a low fiber content and deficiency the micronutrients,impacts short-chain fatty acids production and may be related to the pathogenesis of IBD.On the other hand,the consumption of the Mediter-ranean diet and dietary fibers are associated with reduced risk of IBD flares,particularly in Crohn’s disease(CD)patients.According to the dietary guidance from the International Organization for the Study of Inflammatory Bowel Diseases(IOIBD),the regular consumption of fruits and vegetables while reducing the consumption of saturated,trans,dairy fat,additives,processed foods rich in maltodextrins,and artificial sweeteners containing sucralose or saccharine is recommended to CD patients.For patients with ulcerative colitis,the IOIBD recommends the increased intake of natural sources of omega-3 fatty acids and follows the same restrictive recommendations aimed at CD patients,with the possible inclusion of red meats.In conclusion,IBD is a complex and hetero-geneous disease,and future studies are needed to elucidate the influence of epigenetics on diet and microbiota in IBD patients.

Whole exome sequencing identifies risk variants associated with intracranial epidermoid cyst deterioration:A case report

BACKGROUND Intracranial epidermoid cyst(IEC)transformation to malignant squamous cell carcinoma(SCC)is extremely rare,and its etiology is yet unknown.Currently,SCC is treated by performing surgery,followed by a combination of radiotherapy and chemotherapy.It is crucial to identify efficient and trustworthy therapeutic targets for SCC to improve its diagnosis,prognosis,and treatment.CASE SUMMARY In this study,we report the case of a 47-year-old female patient with SCC,which progressed from IEC in the left internal capsule region.The patient was sought treatment at our hospital for severe diplopic vision,accompanied with speech disorder and memory loss.Based on the clinical and postoperative pathology,this patient was finally diagnosed with SCC.To identify disease-causing variants,whole exome sequencing(WES)was performed on the proband.WES revealed two pathogenic missense mutations on Gap junction protein beta 2(GJB2)(c.257C>T)and Toll-like receptor 2(TLR2)(c.1039A>G),respectively.CONCLUSION This study provided the first clinical evidence for demonstrating the role of GJB2 and TLR2 in IEC development and treatment.We further confirmed WES as a robust and reliable technique for underlying rare and complex disease-related genetic factor identification.

Clinicopathological features and medium-term outcomes of histologic variants of primary focal segmental glomerulosclerosis in adults:A retrospective study

BACKGROUND The Columbia classification identified five histological variants of focal segmental glomerulosclerosis(FSGS).The prognostic significance of these variants remains controversial.AIM To evaluate the relative frequency,clinicopathologic characteristics,and medium-term outcomes of FSGS variants at a single center in Pakistan.METHODS This retrospective study was conducted at the Department of Nephrology,Sindh Institute of Urology and Transplantation,Karachi,Pakistan on all consecutive adults(≥16 years)with biopsy-proven primary FSGS from January 1995 to December 2017.Studied subjects were treated with steroids as a first-line therapy.The response rates,doubling of serum creatinine,and kidney failure(KF)with replacement therapy were compared between histological variants using ANOVA or Kruskal Wallis,and Chi-square tests as appropriate.Data were analyzed by SPSS version 22.0.P-value≤0.05 was considered significant.RESULTS A total of 401 patients were diagnosed with primary FSGS during the study period.Among these,352(87.7%)had a designated histological variant.The not otherwise specified(NOS)variant was the commonest,being found in 185(53.9%)patients,followed by the tip variant in 100(29.1%)patients.Collapsing(COL),cellular(CEL),and perihilar(PHI)variants were seen in 58(16.9%),6(1.5%),and 3(0.7%)patients,respectively.CEL and PHI variants were excluded from further analysis due to small patient numbers.The mean follow-up period was 36.5±29.2 months.Regarding response rates of variants,patients with TIP lesions achieved remission more frequently(59.5%)than patients with NOS(41.8%)and COL(24.52%)variants(P<0.001).The hazard ratio of complete response among patients with the COL variant was 0.163[95%confidence interval(CI):0.039-0.67]as compared to patients with NOS.The TIP variant showed a hazard ratio of 2.5(95%CI:1.61-3.89)for complete remission compared to the NOS variant.Overall,progressive KF was observed more frequently in patients with the COL variant,43.4%(P<0.001).Among these,24.53%of patients required kidney replacement therapy(P<0.001).The hazard ratio of doubling of serum creatinine among patients with the COL variant was 14.57(95%CI:1.87-113.49)as compared to patients with the TIP variant.CONCLUSION In conclusion,histological variants of FSGS are predictive of response to treatment with immunosuppressants and progressive KF in adults in our setup.

A Theory of Bio-Quantum Genetics

The physical mechanism of heredity or inheritance of genes is a quantum mechanical and/or quantum computational process. A theory of bio-quantum genetics is established in this paper. Principle of Bio-quantum Genetics is suggested. I propose and define the soft-genes of genetics controlling the processes of heredity or inheritance of genes. This research deals with the quantum mechanisms of Mendel plant heredity and family inheritance as examples of bio-quantum genetics, deepening our understanding of heredity or inheritance. I believe that more contributions will be made to promote researches of bio-quantum genetics or quantum biology at large.

A computational framework for improving genetic variants identification from 5,061 sheep sequencing data

Background Pan-genomics is a recently emerging strategy that can be utilized to provide a more comprehensive characterization of genetic variation.Joint calling is routinely used to combine identified variants across multiple related samples.However,the improvement of variants identification using the mutual support information from mul-tiple samples remains quite limited for population-scale genotyping.Results In this study,we developed a computational framework for joint calling genetic variants from 5,061 sheep by incorporating the sequencing error and optimizing mutual support information from multiple samples’data.The variants were accurately identified from multiple samples by using four steps:(1)Probabilities of variants from two widely used algorithms,GATK and Freebayes,were calculated by Poisson model incorporating base sequencing error potential;(2)The variants with high mapping quality or consistently identified from at least two samples by GATK and Freebayes were used to construct the raw high-confidence identification(rHID)variants database;(3)The high confidence variants identified in single sample were ordered by probability value and controlled by false discovery rate(FDR)using rHID database;(4)To avoid the elimination of potentially true variants from rHID database,the vari-ants that failed FDR were reexamined to rescued potential true variants and ensured high accurate identification variants.The results indicated that the percent of concordant SNPs and Indels from Freebayes and GATK after our new method were significantly improved 12%-32%compared with raw variants and advantageously found low frequency variants of individual sheep involved several traits including nipples number(GPC5),scrapie pathology(PAPSS2),sea-sonal reproduction and litter size(GRM1),coat color(RAB27A),and lentivirus susceptibility(TMEM154).Conclusion The new method used the computational strategy to reduce the number of false positives,and simulta-neously improve the identification of genetic variants.This strategy did not incur any extra cost by using any addi-tional samples or sequencing data information and advantageously identified rare variants which can be important for practical applications of animal breeding.

Alternative polyadenylation-related genetic variants contribute to bladder cancer risk

Aberrant alternative polyadenylation(APA)events play an important role in cancers,but little is known about whether APA-related genetic variants contribute to the susceptibility to bladder cancer.Previous genome-wide association study performed APA quantitative trait loci(apaQTL)analyses in bladder cancer,and identified 17955 single nucleotide polymorphisms(SNPs).We found that gene symbols of APA affected by apaQTL-associated SNPs were closely correlated with cancer signaling pathways,high mutational burden,and immune infiltration.Association analysis showed that apaQTL-associated SNPs rs34402449 C>A,rs2683524 C>T,and rs11540872 C>G were significantly associated with susceptibility to bladder cancer(rs34402449:OR=1.355,95%confidence interval[CI]:1.159-1.583,P=1.33×10^(−4);rs2683524:OR=1.378,95%CI:1.164-1.632,P=2.03×10^(−4);rs11540872:OR=1.472,95%CI:1.193-1.815,P=3.06×10^(−4)).Cumulative effect analysis showed that the number of risk genotypes and smoking status were significantly associated with an increased risk of bladder cancer(P_(trend)=2.87×10^(−12)).We found that PRR13,being demonstrated the most significant effect on cell proliferation in bladder cancer cell lines,was more highly expressed in bladder cancer tissues than in adjacent normal tissues.Moreover,the rs2683524 T allele was correlated with shorter 3′untranslated regions of PRR13 and increased PRR13 expression levels.Collectively,our findings have provided informative apaQTL resources and insights into the regulatory mechanisms linking apaQTL-associated variants to bladder cancer risk.