The genetics of pediatric inflammatory bowel disease:Towards precision medicine

Pediatric inflammatory bowel disease(IBD)is a chronic and heterogeneous disease.IBD is commonly classified into Crohn’s disease and ulcerative colitis.It is linked to serious symptoms and complications.The onset of IBD commonly occurs during adolescence.Despite the significant number of cases globally(~5 million),the causes of pediatric IBD,which constitutes 25%of IBD patients,are not yet fully understood.Apart from environmental factors,genetic factors contribute to a higher risk of developing IBD.The predisposition risk of IBD can be investigated using genetic testing.Genetic mechanisms of pediatric IBD are highly complex which resulted in difficulty in selecting effective treatment or patient management.Genetic variation of IBD would serve as a basis for precision medicine and allow for the discovery of more robust treatment avenues for this condition in pediatric patients.This review aims to discuss the genetics of pediatric IBD,and current development in the screening,diagnosis,and treatment based on genetic profiling of pediatric IBD subjects toward more personalized management of this disease.

Genetic insights in infectious diseases:Insights from a case report and implications for personalized medicine

The relationship between genetics and infectious diseases is important in shaping our understanding of disease susceptibility,progression,and treatment.Recent research shows the impact of genetic variations,such as heme-oxygenase promoter length,on diseases like malaria and sepsis,revealing both protective and inconclusive effects.Studies on vaccine responses highlight genetic markers like human leukocyte antigens,emphasizing the potential for personalized immunization strategies.The ongoing battle against drug-resistant tuberculosis(TB)illustrates the complexity of genomic variants in predicting resistance,highlighting the need for integrated diagnostic tools.Additionally,genome-wide association studies reveal antibiotic resistance mechanisms in bacterial genomes,while host genetic polymorphisms,such as those in solute carrier family 11 member 1 and vitamin D receptor,demonstrate their role in TB susceptibility.Advanced techniques like metagenomic next-generation sequencing promise detailed pathogen detection but face challenges in cost and accessibility.A case report involving a highly virulent Mycobacterium TB strain with the pks1 gene further highlights the need for genetic insights in understanding disease severity and developing targeted interventions.This evolving landscape emphasizes the role of genetics in infectious diseases,while also addressing the need for standardized studies and accessible technologies.

Mobile genetic elements facilitate the transmission of antibiotic resistance genes in multidrug-resistant Enterobacteriaceae from duck farms

Multidrug-resistant(MDR)Enterobacteriaceae critically threaten duck farming and public health.The phenotypes,genotypes,and associated mobile genetic elements(MGEs)of MDR Enterobacteriaceae isolated from 6 duck farms in Zhejiang Province,China,were investigated.A total of 215 isolates were identified as Escherichia coli(64.65%),Klebsiella pneumoniae(12.09%),Proteus mirabilis(10.23%),Salmonella(8.84%),and Enterobacter cloacae(4.19%).Meanwhile,all isolates were resistant to at least two antibiotics.Most isolates carried tet(A)(85.12%),blaTEM(78.60%)and sul1(67.44%)resistance genes.Gene co-occurrence analysis showed that the resistance genes were associated with IS26 and integrons.A conjugative IncFII plasmid pSDM004 containing all the above MGEs was detected in Proteus mirabilis isolate SDM004.This isolate was resistant to 18 antibiotics and carried the blaNDM-5 gene.MGEs,especially plasmids,are the primary antibiotic resistance gene transmission route in duck farms.These findings provide a theoretical basis for the rational use of antibiotics in farms which are substantial for evaluating public health and food safety.

The genetic basis and improvement of photosynthesis in tomato

Photosynthesis is one the most important chemical reaction in plants,and it is the ultimate energy source of any living organisms.The light and dark reactions are two essential phases of photosynthesis.Light reaction harvests light energy to synthesize ATP and NADPH through an electron transport chain,and as well as giving out O_(2);dark reaction fixes CO_(2) into six carbon sugars by utilizing NADPH and energy from ATP.Subsequently,plants convert optical energy into chemical energy for maintaining growth and development through absorbing light energy.Here,firstly,we highlighted the biological importance of photosynthesis,and hormones and metabolites,photosynthetic and regulating enzymes,and signaling components that collectively regulate photosynthesis in tomato.Next,we reviewed the advances in tomato photosynthesis,including two aspects of genetic basis and genetic improvement.Numerous genes regulating tomato photosynthesis are gradually uncovered,and the interaction network among those genes remains to be constructed.Finally,the photosynthesis occurring in fruit of tomato and the relationship between photosynthesis in leaf and fruit were discussed.Leaves and fruits are photosynthate sources and sinks of tomato respectively,and interaction between photosynthesis in leaf and fruit exists.Additionally,future perspectives that needs to be addressed on tomato photosynthesis were proposed.

A dual-RPA based lateral flow strip for sensitive,on-site detection of CP4-EPSPS and Cry1Ab/Ac genes in genetically modified crops

Traditional transgenic detection methods require high test conditions and struggle to be both sensitive and efficient.In this study,a one-tube dual recombinase polymerase amplification(RPA)reaction system for CP4-EPSPS and Cry1Ab/Ac was proposed and combined with a lateral flow immunochromatographic assay,named“Dual-RPA-LFD”,to visualize the dual detection of genetically modified(GM)crops.In which,the herbicide tolerance gene CP4-EPSPS and the insect resistance gene Cry1Ab/Ac were selected as targets taking into account the current status of the most widespread application of insect resistance and herbicide tolerance traits and their stacked traits.Gradient diluted plasmids,transgenic standards,and actual samples were used as templates to conduct sensitivity,specificity,and practicality assays,respectively.The constructed method achieved the visual detection of plasmid at levels as low as 100 copies,demonstrating its high sensitivity.In addition,good applicability to transgenic samples was observed,with no cross-interference between two test lines and no influence from other genes.In conclusion,this strategy achieved the expected purpose of simultaneous detection of the two popular targets in GM crops within 20 min at 37°C in a rapid,equipmentfree field manner,providing a new alternative for rapid screening for transgenic assays in the field.

Genetic factors that predict response and failure of biologic therapy in inflammatory bowel disease

Inflammatory bowel disease(IBD)represents a significant disease burden marked by chronic inflammation and complications that adversely affect patients’quality of life.Effective diagnostic strategies involve clinical assessments,endoscopic evaluations,imaging studies,and biomarker testing,where early diagnosis is essential for effective management and prevention of long-term complications,highlighting the need for continual advancements in diagnostic methods.The intricate interplay between genetic factors and the outcomes of biological therapy is of critical importance.Unraveling the genetic determinants that influence responses and failures to biological therapy holds significant promise for optimizing treatment strategies for patients with IBD on biologics.Through an indepth examination of current literature,this review article synthesizes critical genetic markers associated with therapeutic efficacy and resistance in IBD.Understanding these genetic actors paves the way for personalized approaches,informing clinicians on predicting,tailoring,and enhancing the effectiveness of biological therapies for improved outcomes in patients with IBD.

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.

Compiling molecular evidence from a tetraploid rose genome into a near-saturated map for the identification of pigment-related genes

With their high economic value and cultural significance,modern roses are one of the most important ornamental plants.Because of their complicated genetic background and tetraploid nature,the creation of high-density genetic maps of roses has been a challenge that has slowed the pace of molecular breeding for modern roses.The current construction of tetraploid genetic maps based on existing diploid rose genomes could lead to inaccurate marker information and genotyping results.Therefore,we generated the first high-quality tetraploid genome of Rosa chinensis‘Yunzheng Xiawei.'Utilizing Illumina,PacBio,and Hi-C sequencing technologies,we assembled a genome of 858.59 Mb with 14pseudo-chromosomes.Mode of inheritance analysis using PolyOrigin indicated that modern roses show both quadrivalent and bivalent pairing.Based on this reference genome,high-density genetic maps were constructed using MSTmap with nearly saturated markers.Quantitative trait locus(QTL)analysis was conducted using WinQTLCart and R/qtl for flavonoids and carotenoids,and 11 QTL clusters were identified.By combining the genome annotation,phylogenetic analyses,and gene expression analyses,we were able to identify several key genes related to flavonoid and carotenoid biosynthesis.This study provides the basis for further genetic analyses of highly heterozygous tetraploid roses and could facilitate the progress of marker-assisted selection in modern roses.

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.

AAV-mediated expression of p65shRNA and bone morphogenetic protein 4 synergistically enhances chondrocyte regeneration

BACKGROUND:Adeno-associated virus(AAV)gene therapy has been proven to be reliable and safe for the treatment of osteoarthritis in recent years.However,given the complexity of osteoarthritis pathogenesis,single gene manipulation for the treatment of osteoarthritis may not produce satisfactory results.Previous studies have shown that nuclear factorκB could promote the inflammatory pathway in osteoarthritic chondrocytes,and bone morphogenetic protein 4(BMP4)could promote cartilage regeneration.OBJECTIVE:To test whether combined application of AAV-p65shRNA and AAV-BMP4 will yield the synergistic effect on chondrocytes regeneration and osteoarthritis treatment.METHODS:Viral particles containing AAV-p65-shRNA and AAV-BMP4 were prepared.Their efficacy in inhibiting inflammation in chondrocytes and promoting chondrogenesis was assessed in vitro and in vivo by transfecting AAV-p65-shRNA or AAV-BMP4 into cells.The experiments were divided into five groups:PBS group;osteoarthritis group;AAV-BMP4 group;AAV-p65shRNA group;and BMP4-p65shRNA 1:1 group.Samples were collected at 4,12,and 24 weeks postoperatively.Tissue staining,including safranin O and Alcian blue,was applied after collecting articular tissue.Then,the optimal ratio between the two types of transfected viral particles was further investigated to improve the chondrogenic potential of mixed cells in vivo.RESULTS AND CONCLUSION:The combined application of AAV-p65shRNA and AAV-BMP4 together showed a synergistic effect on cartilage regeneration and osteoarthritis treatment.Mixed cells transfected with AAV-p65shRNA and AAV-BMP4 at a 1:1 ratio produced the most extracellular matrix synthesis(P<0.05).In vivo results also revealed that the combination of the two viruses had the highest regenerative potential for osteoarthritic cartilage(P<0.05).In the present study,we also discovered that the combined therapy had the maximum effect when the two viruses were administered in equal proportions.Decreasing either p65shRNA or BMP4 transfected cells resulted in less collagen II synthesis.This implies that inhibiting inflammation by p65shRNA and promoting regeneration by BMP4 are equally important for osteoarthritis treatment.These findings provide a new strategy for the treatment of early osteoarthritis by simultaneously inhibiting cartilage inflammation and promoting cartilage repair.

Morgan’s Mistake Leads to a Revolution in Genetics

This paper reviews the authors research since 2018 on Mendels gene assumption. The main conclusion is that Morgans misreading of Mendels gene assumption would lead to the inevitable Copernican-like revolution (geocentrism replaced by heliocentrism) in genetics. The evidence for this judgment comes from written records in Morgans The Theory of the Gene. The result of Mendels experiment proposed the second question of genetics (template question), aim at which he assumed the gene was the element controlling individual specification. This led to dualistic genetics (two elements forming the germplasm). However, the gene located by Morgan was germplasm able to give rise to the individualthe answer to the first question of genetics. It ushered in gene-monistic genetics. The confirmation of the gene as DNA has opened a new era of physical verification of gene intension. The inability of DNA to build 3,5-phosphodiester bonds revealed that the gene has neither the ability to produce individuals nor is it self-replicating;consequently, the basis of gene monistic genetics completely collapsed. Instead, the universal fact that the eggs transcriptase initiates DNA (genome) transcription giving rise to the individual (unless accidents occur) confirms that Mendelian dualistic genetics is scientific genetics.

Genetic diversity and population genetic structure of Paeonia suffruticosa by chloroplast DNA simple sequence repeats(cpSSRs)

Paeonia suffruticosa Andr.is an endemic shrub flower in China with 2n=10.This study used 228 cultivars from four populations,i.e.,Jiangnan,Japan,Northwest,and Zhongyuan,as materials to explore the genetic diversity levels among different populations of tree peony varieties.The results showed that 34 bands were amplified using five pairs of cp SSR primers,with an average of 6.8 bands per primer pair.The average number of different alleles(N_(a)),effective alleles(N_(e)),Shannon's information index(I),diversity(H),and polymorphic information content(PIC)were 3.600,2.053,0.708,0.433,and 0.388,respectively.The PIC value was between 0.250 and 0.500,indicating a moderate level of polymorphism for the five cp SSR primer pairs.The genetic diversity levels of peony cultivars varied among different populations,with the Northwest population showing relatively lower levels(I=0.590,H=0.289,and PIC=0.263).A total of 52 haplotypes were identified in the four examined populations,and the number of haplotypes per population ranged from 11 to 22.Forty-four private haplotypes were detected across populations,and the Northwest population exhibiting the highest count of private haplotypes with 17.The mean number of effective number of haplotypes(N_(eh)),haplotypic richness(R_h),and diversity(H)were 8.351,6.824,and 0.893,respectively.Analysis of molecular variance indicated that genetic variation within tree peony germplasm was greater than that between germplasm resources,and the main variation was found within individuals of peony germplasm.Cluster analysis,principal coordinate analysis,and genetic structure analysis classified tree peonies from different origins into two groups,indicating a certain degree of genetic differentiation among these four tree peony cultivation groups.This study provides a theoretical basis for the exploration,utilization,and conservation of peony germplasm resources,as well as for research on the breeding of excellent varieties.

Impact of Genetic Diversity of Uropathogenic Escherichia coli and Klebsiella pneumoniae Strains on the Dissemination of Extended Spectrum Beta-Lactam Resistance Genes in Côte d’Ivoire

The increase and spread of bacterial resistance to extended-spectrum beta-lactam antibiotics are reported in many infections and are a real public health problem worldwide. Drug pressure is a factor that favors the emergence of a population of better adapted bacteria. However, there is no literature highlighting the genetic diversity and evolutionary structure of E. coli and K. pneumoniae in an environment with high selection pressure in Côte d’Ivoire. The objective of this study was to evaluate the genetic diversity of E. coli and K. pneumoniae strains circulating at the HKB Hospital in Abobo and at the Daloa Regional Hospital and its impact on the dissemination of extended spectrum beta-lactam resistance genes. A total of 39 strains isolated from the urinary tract of infected patients, including 30 strains of E. coli and 9 strains of K. pneumoniae were studied. A total of 39 strains isolated from the urinary tract of infected patients, including 30 strains of E. coli and 9 strains of K. pneumoniae were studied. From genomic DNA extracts, ESBL resistance genes were amplified by PCR and sequenced, in addition to genetic typing by ERIC-PCR. The data obtained were submitted to genetic and bioinformatics analyses. The results have shown a genetic diversity important in E. coli and K. pneumoniae with diversity indexs (SID) ranging from 0.5 to 0.77. The genetic structure of the bacterial species studied has shown a clonal distribution of strains with clones expressing TEM-9 and CTX-M-15 variants. Also, this clonal structure was correlated with the spread of resistance genes in E. coli and K. pneumoniae. The spread of resistant clones is a factor that might limit the fight against antibiotic resistance.

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.

Carcinoma of the stomach: A review of epidemiology, pathogenesis, molecular genetics and chemoprevention

Carcinoma of the stomach is still the second most common cause of cancer death worldwide, although the incidence and mortality have fallen dramatically over the last 50 years in many regions. The incidence of gastric cancer varies in different parts of the world and among various ethnic groups. Despite advances in diagnosis and treatment, the 5-year survival rate of stomach cancer is only 20 per cent. Stomach cancer can be classified into intestinal and diffuse types based on epidemiological and clinicopathological features. The etiology of gastric cancer is multifactorial and includes both dietary and nondietary factors. The major diet-related risk factors implicated in stomach cancer development include high content of nitrates and high salt intake. Accumulating evidence has implicated the role of Helicobacter pylori (H. pylori) infection in the pathogenesis of gastric cancer. The development of gastric cancer is a complex, multistep process involving multiple genetic and epigenetic alterations of oncogenes, tumor suppressor genes, DNA repair genes, cell cycle regulators, and signaling molecules. A plausible program for gastric cancer prevention involves intake of a balanced diet containing fruits and vegetables, improved sanitationand hygiene, screening and treatment of H. pylori infection, and follow-up of precancerous lesions. The fact that diet plays an important role in the etiology of gastric cancer offers scope for nutritional chemoprevention. Animal models have been extensively used to analyze the stepwise evolution of gastric carcinogenesis and to test dietary chemopreventive agents. Development of multitargeted preventive and therapeutic strategies for gastric cancer is a major challenge for the future.

The Practice and Exploration of Applying EBM to Bilingual Teaching of Medical Genetics at OSBCM

In the process of teaching medical genetics of undergraduate clinical medicine, the practice and exploration of applying EBM to the bilingual teaching of OSBCM medical genetics are carried out. Using CBL and PBL as the carrier can make up for the shortcomings of a single teaching mode, synthesize the advantages of multiple teaching modes. It starts from integrating the basic theoretical knowledge of medicine and clinical practice knowledge, improving students’ bilingual level of medical genetics, cultivating students’ literature retrieval ability, and promoting early clinical, multi-clinical and repeated clinical consciousness for medical students. Therefore, it is more conducive to cultivate students’ ability to learn independently, accurately analyze and solve problems, improve medical students’ clinical thinking ability and scientific research awareness, improve medical students’ ability of international communication, and lay a solid foundation for improving medical students’ future post competence, innovative spirit and lifelong learning ability.

Gallbladder cancer epidemiology, pathogenesis and molecular genetics: Recent update

Gallbladder cancer is a malignancy of biliary tract which is infrequent in developed countries but common in some specific geographical regions of developing countries. Late diagnosis and deprived prognosis are major problems for treatment of gallbladder carcinoma. The dramatic associations of this orphan cancer with various genetic and environmental factors are responsible for its poorly defined pathogenesis. An understanding to the relationship between epidemiology, molecular genetics and pathogenesis of gallbladder cancer can add new insights to its undetermined pathophysiology. Present review article provides a recent update regarding epidemiology, pathogenesis, and molecular genetics of gallbladder cancer. We systematically reviewed published literature on gallbladder cancer from online search engine Pub Med(http://www.ncbi.nlm.nih.gov/pubmed). Various keywords used for retrieval of articles were Gallbladder, cancer Epidemiology, molecular genetics and bullion operators like AND, OR, NOT. Cross references were manually searched from various online search engines(http://www.ncbi.nlm.nih.gov/pubmed,https://scholar.google.co.in/, http://www.medline.com/home.jsp). Most of the articles published from 1982 to 2015 in peer reviewed journals have been included in this review.

Progress Towards Genetics and Breeding for Minor Genes Based Resistance to Ug99 and Other Rusts in CIMMYT High-Yielding Spring Wheat

Wheat rusts continue to cause significant losses worldwide despite major efforts given to their genetic control. This is due to frequent evolution and selection of virulence in pathogen overcoming the deployed race-specific resistance genes. Although the life of effective race-specific resistance genes can be prolonged by using gene combinations, an alternative approach being implemented at CIMMYT is to deploy varieties that posses adult plant resistance （APR） based on combinations of minor, slow rusting genes. When present alone, the APR genes do not confer adequate resistance especially under high disease pressure; however, combinations of 4 or 5 minor genes usually result in ＂near-immunity＂ or a high level of resistance. Although only a few APR genes are catalogued, various APR QTLs are now known and could lead to further characterization of additional genes. Four characterized genes have pleiotropic effects in conferring partial APR to all 3 rusts and powdery mildew, thus simplifying the task of breeding wheat varieties that are resistant to multiple diseases. Significant progress was made recently in developing high-yielding wheat germplasm that possesses high levels of APR to all three rusts by implementing a Mexico- Kenya shuttle breeding scheme. Parents with APR to Ug99 were hybridized with high-yielding parents that had adequate to high levels of APR to leaf rust and yellow rust. Segregating populations and advanced lines from these crosses were selected under high rust pressures in Mexico （leaf rust and yellow rust） and Kenya （Ug99 stem rust and yellow rust） to identify high- yielding progenies that possess high to adequate APR to all three rusts. International distribution of these high-yielding wheats is underway through CIMMYT intemational yield trials and screening nurseries. It is expected that several wheat varieties with APR to three rusts will be released and grown in various countries in the near-future that will allow determining the durability of resistance.

Holistic paradigm in carcinogenesis:Genetics,epigenetics,immunity,inflammation and oral infections

Recent debate among the experts of cancer research regarding the main causes of carcinogenesis encouraged us to review the etiology of cancer pathogenesis. The somatic mutation theory attributes carcinogenesis to random errors in DNA multiplication while the tissue organization field theory ascribes causation to environmental factors. We recognize complexity in cancer pathogenesis and accept the premise of both DNA multiplication errors and environmental factors in cancer development. Furthermore, it should also be noted that the combination of these factors and the relative importance of the each differ in various types of cancers. For example, in some cancers, genetics plays a prominent role while in others environment such as obesity plays a much stronger role. Additionally, the cancer mitigating factors should also be considered. The balance of cancer-enhancing and cancer-suppressing forces determines the cancer incidence. Ultimately, identifying the lifestyle factors that revise somatic mutations or epigenetic alterations will lead to a clear understanding of pathogenic mechanisms of cancer and to the optimal preventive strategies. This narrative review evaluates the published evidence on carcinogenesis pertaining to the whole organism(thus, holistic) incorporating genetics, epigenetics, immunology, inflammation and infections with emphasis on oral infections.

Current understandings of the pathogenesis of type 1 diabetes:Genetics to environment

Type 1 diabetes(T1D)is an autoimmune disease that usually strikes early in life,but can affect individuals at almost any age.It is caused by autoreactive T cells that destroy insulin-producing beta cells in the pancreas.Epidemiological studies estimate a prevalence of 1 in 300 children in the United States with an increasing incidence of 2%-5%annually worldwide.The daily responsibility,clinical management,and vigilance required to maintain blood sugar levels within normal range and avoid acute complications(hypoglycemic episodes and diabetic ketoacidosis)and long term micro-and macro-vascular complications significantly affects quality of life and public health care costs.Given the expansive impact of T1D,research work has accelerated and T1D has been intensively investigated with the focus to better understand,manage and cure this condition.Many advances have been made in the past decades in this regard,but key questions remain as to why certain people develop T1D,but not others,with the glaring example of discordant disease incidence among monozygotic twins.In this review,we discuss the field’s current understanding of its pathophysiology and the role of genetics and environment on the development of T1D.We examine the potential implications of these findings with an emphasis on T1D inheritance patterns,twin studies,and disease prevention.Through a better understanding of this process,interventions can be developed to prevent or halt it at early stages.