Global Medical Genetics最新文献

{"title":"Epigenetics of Hypogonadotropic Hypogonadism: Molecular Mimicry between Severe Acute Respiratory Syndrome Coronavirus 2 and KISSR.","authors":"Darja Kanduc","doi":"10.1055/s-0043-1770767","DOIUrl":"https://doi.org/10.1055/s-0043-1770767","url":null,"abstract":"<p><p>This study analyzed KISS1 and its receptor KISSR for peptide sharing with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It was found that SARS-CoV-2 shares numerous minimal immune pentapeptide determinants with KISSR only. The peptide sharing has a high immunologic potential since almost all the common peptides are present in 101 SARS-CoV-2-derived immunoreactive epitopes. Data are in favor of configuring molecular mimicry as an epigenetic factor that can alter KISSR thus causing the hypogonadotropic hypogonadism syndrome with which altered KISSR associates.</p>","PeriodicalId":40142,"journal":{"name":"Global Medical Genetics","volume":"10 2","pages":"129-132"},"PeriodicalIF":1.7,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10289852/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9717728","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Strong Association between Vitamin D Receptor Gene and Severe Acute Respiratory Syndrome coronavirus 2 Infectious Variants.","authors":"Begimai Mamurova, Gokce Akan, Evren Mogol, Ayla Turgay, Gulten Tuncel, Emine Unal Evren, Hakan Evren, Kaya Suer, Tamer Sanlidag, Mahmut Cerkez Ergoren","doi":"10.1055/s-0043-1761924","DOIUrl":"10.1055/s-0043-1761924","url":null,"abstract":"<p><p>A coronavirus disease 2019 (COVID-19) disease, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has created significant concern since December 2019 worldwide. The virus is known to be highly transmissible. Heterogenic clinical features even vary more among SARS-CoV-2 variants from asymptomatic forms to severe symptoms. Previous studies revealed an association between COVID-19 and vitamin D deficiency resulting from its low levels in COVID-19 patients. To our knowledge, there is no scientific investigation that evaluates the direct association between SARS-CoV-2 variants of concern and vitamin D receptor ( <i>VDR</i> ) gene markers in Cyprus. Thus, the present study aimed to identify the putative impact of <i>VDR</i> gene polymorphisms on SARS-CoV-2 infection among different variants. The nasopharyngeal swabs were taken from a total number of 600 patients who were admitted to Near East University Hospital COVID-19 Polymerase Chain Reaction (PCR) Diagnosis Laboratory for routine SARS-CoV-2 real-time quantitative reverse transcription PCR (RT-qPCR) test. The RT-qPCR negative resulting samples were taken as control samples ( <i>n</i>  = 300). On the contrary, the case group consisted of patients who were SARS-CoV-2 RT-qPCR positive, infected with either SARS-CoV-2 Alpha ( <i>n</i>  = 100), Delta ( <i>n</i>  = 100), or Omicron ( <i>n</i>  = 100) variants. Two <i>VDR</i> gene polymorphisms, <i>Taq</i> I-rs731236 T > C and <i>Fok</i> I-rs10735810 C > T, were genotyped by polymerase chain reaction-restriction fragment length polymorphism. The mean age of the COVID-19 patient's ± standard deviation was 46.12 ± 12.36 and 45.25 ± 12.71 years old for the control group ( <i>p</i>  > 0.05). The gender distribution of the patient group was 48.3% female and 51.7% male and for the control group 43% female and 57% male ( <i>p</i>  > 0.05). Significant differences were observed in genotype frequencies of <i>FokI</i> and <i>TaqI</i> variants between SARS-CoV-2 patients compared to the control group ( <i>p</i>  < 0.005). Furthermore, the risk alleles, <i>FokI</i> T allele and <i>TaqI</i> C, were found to be statistically significant (odds ratio [OR] = 1.80, 95% confidence interval [CI] = 1.42-2.29, OR = 1.62, 95% CI = 1.27-2.05, respectively) in COVID-19 patients. The highest number of patients with wild-type genotype was found in the control group, which is 52.9% compared with 17.5% in the case group. Moreover, most of the COVID-19 patients had heterozygous/homozygous genotypes, reaching 82.5%, while 47.1% of the control group patients had heterozygous/homozygous genotypes. Our results suggested that patients with <i>FokI</i> and <i>TaqI</i> polymorphisms might tend to be more susceptible to getting infected with SARS-CoV-2. Overall, findings from this study provided evidence regarding vitamin D supplements recommendation in individuals with vitamin D deficiency/insufficiency in the peri- or post-COVID-19 pandemic.</p>","PeriodicalId":40142,"journal":{"name":"Global Medical Genetics","volume":"10 1","pages":"27-33"},"PeriodicalIF":1.2,"publicationDate":"2023-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9935054/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10764512","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sex and ABO Blood Differences in SARS-CoV-2 Infection Susceptibility.","authors":"Mahmut Cerkez Ergoren, Gokce Akan, Emrah Guler, Gulten Tuncel, Damla Akovalı, Emine Unal Evren, Hakan Evren, Huseyin Kaya Suer, Tamer Sanlidag","doi":"10.1055/s-0043-1761202","DOIUrl":"10.1055/s-0043-1761202","url":null,"abstract":"<p><p>Data consisting of millions of cases cannot still explain the immunopathogenesis mechanism between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and host cell for ongoing coronavirus disease 2019 (COVID-19) pandemics. Epidemiological studies among different populations suggested different impacts of ABO and Rh antibodies on the COVID-19 susceptibility. Thus, the ABO blood group and the SARS-CoV-2 infection paradox remain unclear. Therefore, the present retrospective case-control study aimed to investigate the possible association between ABO blood groups and Rh blood types on SARS-CoV-2 infection in the Turkish Cypriot population. A total of 18,639 Turkish Cypriot subjects (297 SARS-CoV-2 COVID-19 patients and 18,342 healthy) were included in this study. Personal and clinical characteristics including age, gender, SARS-CoV-2 infection status, the ABO blood group and Rh blood types were evaluated and compared between two groups. As a result, ABO blood group was shown to be associated with a higher risk of SARS-CoV-2 infection as well as with male sex ( <i>p</i>  = 0.018). There was no association between Rh blood type and COVID-19. Overall, this study is the first largest sample group study to show the distribution of ABO blood group and Rh blood types in the healthy Turkish Cypriot population. Based on the current evidence, there are insufficient data to guide public health policies regarding COVID-19 pathogenesis.</p>","PeriodicalId":40142,"journal":{"name":"Global Medical Genetics","volume":"10 1","pages":"22-26"},"PeriodicalIF":1.2,"publicationDate":"2023-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9886502/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10642154","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of a de novo Mutation in TMEM106B in a Saudi Child Causes Hypomyelination Leukodystrophy.","authors":"Lena Alotaibi,&nbsp;Amal Alqasmi","doi":"10.1055/s-0043-1764370","DOIUrl":"https://doi.org/10.1055/s-0043-1764370","url":null,"abstract":"<p><p>Hypomyelinating leukodystrophies are one of the white matter disorders caused by a lack of myelin deposition in the central nervous system (CNS). Here, we report the first case of hypomyelinating leukodystrophy in the Middle East and Saudi Arabia. This condition is caused by a mutation in the TMEM106B gene (HLD16; MIM 617964). Hypotonia, congenital nystagmus, delayed motor development, and delayed speech are the main clinical manifestations. The affected patient has mild pyramidal syndrome, a mild intellectual disability, ataxic gait, hyperreflexia, intention tremor, dysmetria, and other motor difficulties. Findings from neuroimaging reveal severe, ongoing, and diffuse hypomyelination identified via the whole exome sequencing, a harmful missense mutation in the TMEM106B gene that is heterozygous. The patient is the offspring of two unrelated persons. The protein's cytoplasmic domain contains a variation that is located in highly conserved residues. In an oligodendroglial cell line, the mutant protein significantly lowered the mRNA production of important myelin genes, decreased branching, and increased cell mortality. TMEM106B is abundantly expressed in neurons and oligodendrocytes in the CNS and is localized in the late endosome and lysosome compartments. TMEM106B levels can be controlled at the transcriptional level through chromatin modification, at the mRNA level through miRNAs, and at the protein level through lysosomal functions. Our findings reveal a novel role of zinc homeostasis in oligodendrocyte development and myelin production and show that variations in TMEM163 induce hypomyelination leukodystrophy.</p>","PeriodicalId":40142,"journal":{"name":"Global Medical Genetics","volume":"10 1","pages":"38-41"},"PeriodicalIF":1.7,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10027483/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9166562","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of <i>GCK</i> (rs1799884), <i>GCKR</i> (rs780094), and <i>G6PC2</i> (rs560887) Gene Polymorphisms with Type 2 Diabetes among Malay Ethnics.","authors":"Neda Ansari,&nbsp;Vasudevan Ramachandran,&nbsp;Nur Afiqah Mohamad,&nbsp;Elnaz Salim,&nbsp;Patimah Ismail,&nbsp;Mohamad Hazmi,&nbsp;Liyana Najwa Inchee Mat","doi":"10.1055/s-0042-1760384","DOIUrl":"https://doi.org/10.1055/s-0042-1760384","url":null,"abstract":"<p><p><b>Background</b>  Type 2 diabetes mellitus (T2DM) is a complex metabolic disorder, and the underlying causes remain unknown and have not been fully elucidated. Several candidate genes have been associated with T2DM in various populations with conflicting results. The variations found in glucokinase ( <i>GCK</i> ), glucokinase regulatory protein ( <i>GCKR</i> ), and glucose-6-phosphatase 2 ( <i>G6PC2</i> ) genes were not well studied, particularly among Asians. <b>Aims</b>  The main objective of this study was to determine the candidate genetic polymorphisms of <i>GCK</i> (rs1799884), <i>GCKR</i> (rs780094), and <i>G6PC2</i> (rs560887) genes in T2DM among Malay ethnics. <b>Methods</b>  In this candidate gene association study, a total of 180 T2DM subjects and 180 control subjects were recruited to determine the genotypes using polymerase chain reaction-restriction fragment length polymorphism and <i>Taqman</i> probe assay methods. Genotype and allele frequencies in case and control samples were compared using the chi-squared test to determine a significant difference. <b>Results</b>  The body mass index, fasting blood glucose, hemoglobin A1c, systolic and diastolic blood pressure, and total cholesterol were significantly different ( <i>p</i>  < 0.05) between T2DM and control subjects. The genotypic and allelic frequencies of <i>GCK</i> (rs1799884), <i>GCKR</i> (rs780094), and <i>G6PC2</i> (rs560887) gene polymorphisms were significantly different between T2DM and controls ( <i>p</i>  < 0.05). <b>Conclusion</b>  Hence, rs1799884 of <i>GCK</i> gene and rs780094 of <i>GCKR</i> gene and rs560887 of the <i>G6PC2</i> gene are possible genetic biomarkers in T2DM development among Malay ethnics in Malaysia.</p>","PeriodicalId":40142,"journal":{"name":"Global Medical Genetics","volume":"10 1","pages":"12-18"},"PeriodicalIF":1.7,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9873477/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10626773","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular Mimicry between Respiratory Syncytial Virus F Antigen and the Human Proteome.","authors":"Darja Kanduc","doi":"10.1055/s-0043-1761489","DOIUrl":"https://doi.org/10.1055/s-0043-1761489","url":null,"abstract":"<p><p>This study examined respiratory syncytial virus (RSV) F glycoprotein (gp) antigen for molecular mimicry with the human proteome. It was found that the viral antigen presents an impressive number of pentapeptides (namely, 525 out of 570) in common with the human proteome, with viral sequences widely and repeatedly distributed among 3,762 human proteins implicated in crucial fundamental cellular functions. The data can have implications for anti-RSV vaccines. Indeed, the high level of molecular mimicry can lead to cross-reactivity and autoimmunity, and invites to follow safer vaccinal protocols based on pentapeptide sequences uniquely present in the viral antigen.</p>","PeriodicalId":40142,"journal":{"name":"Global Medical Genetics","volume":"10 1","pages":"19-21"},"PeriodicalIF":1.7,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9886499/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10696138","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic Analysis of the Single-Nucleotide Polymorphisms rs880810, rs545793, rs80094639, and rs13251901 in Nonsyndromic Oral Clefts: A Case-Parent Trio Study.","authors":"Mahamad Irfanulla Khan,&nbsp;Prashanth Cs,&nbsp;N Srinath,&nbsp;Praveen K Neela,&nbsp;Mohammed K Mohiuddin","doi":"10.1055/s-0043-1764399","DOIUrl":"https://doi.org/10.1055/s-0043-1764399","url":null,"abstract":"<p><p>Oral clefts, including cleft lip (CL), cleft palate (CP), and cleft lip and palate (CLP), are the most common types of congenital anomalies of the human face. Various genetic and environmental factors play a role in developing oral clefts. Several studies have shown the association of the <i>PAX7</i> gene and the 8q24 region with these oral clefts in different populations worldwide. However, there are no reported studies on the possible connection between the <i>PAX7</i> gene and the 8q24 region nucleotide variants and the risk of developing nonsyndromic oral clefts (NSOC) in the Indian population. Hence, this study aimed to test the possible association between <i>PAX7</i> gene single-nucleotide polymorphisms (SNPs) rs880810, rs545793,rs80094639, and rs13251901 of the 8q24 region using a case-parent trio design. Forty case-parent trios were selected from the CLP center. Genomic DNA was isolated from the cases and their parents. The rs880810, rs545793, rs80094639, and rs13251901 were genotyped by the MassARRAY technique. PLINK software was used for statistical analysis. All the SNPs were tested for Hardy-Weinberg equilibrium. No statistical significance was found with any SNPs, as none of the genotyped SNPs showed a <i>p</i> -value of less than 0.05. Hence, the rs880810, rs545793, and rs80094639 of the <i>PAX7</i> gene, and rs13251901 of the 8q24 region are not associated with NSOC in the Indian population.</p>","PeriodicalId":40142,"journal":{"name":"Global Medical Genetics","volume":"10 1","pages":"34-37"},"PeriodicalIF":1.7,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10049805/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9577744","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Maternal Transmission of the <i>PAX7</i> Single Nucleotide Polymorphisms among Indian Cleft Trios.","authors":"Mahamad Irfanulla Khan,&nbsp;Prashanth C S,&nbsp;Mohammed S Mustak,&nbsp;Sheikh Nizamuddin","doi":"10.1055/s-0042-1760383","DOIUrl":"https://doi.org/10.1055/s-0042-1760383","url":null,"abstract":"<p><p>Cleft lip and/or cleft palate (CL/P) is one of the most common congenital anomalies of the human face with a complex etiology involving multiple genetic and environmental factors. Several studies have shown the association of the paired box 7 ( <i>PAX7</i> ) gene with CL/P in different populations worldwide. However, the current literature reveals no reported case-parent trio studies to evaluate the association between the <i>PAX7</i> gene and the risk of nonsyndromic cleft lip and/or palate (NSCL/P) in the Indian population. Hence, the purpose of this study was to assess the <i>PAX7</i> gene single nucleotide polymorphisms (SNPs) in the etiology of NSCL/P among the Indian cleft trios. Forty Indian case-parent trios of NSCL/P were included. The cases and their parents' genomic DNA were extracted. The SNPs rs9439714, rs1339062, rs6695765, rs742071, and rs618941of the <i>PAX7</i> gene were genotyped using the Agena Bio MassARRAY analysis. The allelic transmission disequilibrium test was performed using PLINK software while pair-wise linkage disequilibrium by the Haploview program. The SNP rs9439714 showed evidence of association ( <i>p</i> -value = 0.02, odds ratio = 3) with NSCL/P. Considering the parent-of-origin effects, the SNPs rs9439714 and rs618941 showed an excess maternal transmission of allele C at rs9439714 ( <i>p</i> -value = 0.05) and G allele at rs618941 ( <i>p</i> -value = 0.04). The results of the present study suggested that the SNPs rs9439714 and rs618941 showed an excess maternal transmission of alleles suggestive of the possible role of the <i>PAX7</i> gene involvement in the etiology of NSCL/P in the Indian population.</p>","PeriodicalId":40142,"journal":{"name":"Global Medical Genetics","volume":"10 1","pages":"6-11"},"PeriodicalIF":1.7,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9873478/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10680947","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>PMS2</i> Pathogenic Variant in Lynch Syndrome-Associated Colorectal Cancer with Polyps.","authors":"Henriette Poaty,&nbsp;Lauria Batamba Bouya,&nbsp;Aimé Lumaka,&nbsp;Arnaud Mongo-Onkouo,&nbsp;Deby Gassaye","doi":"10.1055/s-0042-1759888","DOIUrl":"https://doi.org/10.1055/s-0042-1759888","url":null,"abstract":"<p><p><b>Background</b>  Lynch syndrome (LS) is an autosomal dominant condition due to the germline mutation in the mismatch repair (MMR) genes including <i>MLH1</i> , <i>MSH2</i> , <i>MSH6,</i> and <i>PMS2</i> (post-meiotic segregation increased 2). The MMR mutation carriers have high risk for cancers. Pathogenic <i>PMS2</i> variants are rarely reported in LS-associated colorectal cancer (CRC) with colorectal polyps. The aim of the study was to investigate the genetic etiology of CRC in an individual with CRC with multiple colorectal polyps and a family history of cancers. <b>Patients and Methods</b>  The index patient was an African male affected by CRC with multiple colorectal polyps. The clinical diagnostic for LS was based on the Amsterdam II criteria and pedigree. Next-generation sequencing with inherited cancer genes panel was used to detect the pathogenic variant. <b>Results</b>  The patient fulfilled the Amsterdam II criteria and the pedigree revealed a family history of recurrent CRC. A deleterious <i>PMS2</i> germline heterozygous mutation c.2192_2196delTAACT was detected. <b>Conclusion</b>  Our study supports the notion that LS may be associated with polyps and shows the predisposition of <i>PMS2</i> heterozygous mutation in LS-associated CRC at young age.</p>","PeriodicalId":40142,"journal":{"name":"Global Medical Genetics","volume":"10 1","pages":"1-5"},"PeriodicalIF":1.7,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9833889/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10536395","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mystery Behind Barrett's Esophagus: The Origin and Malignant Transformation of Esophageal Adenocarcinoma.","authors":"Xiayao Diao","doi":"10.1055/s-0042-1758764","DOIUrl":"10.1055/s-0042-1758764","url":null,"abstract":"Esophageal cancer (EC) is the eighth most common cancer in the world, with an estimated 604,100 new cases in 2020, accounting for 3.1% of all cancer cases.1 Esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC) are the two main histologic subtypes of EC. ESCC predominantly affects developing countries and accounts for more than 88.8% in Chinese EC patients,2,3 while EAC predominantly affects developed countries and accounts for 80.1% in EC patients from United States.4,5 Multiple risk factors, such as Barrett’s esophagus, are associated with EC development. Barrett’s esophagus is a typical metaplastic disease that begins at the gastroesophageal junctions with proximal displacement of the squamocolumnar junctions. Intestinal metaplasia increases the propensity for ECs, especially EACs, and may result from transcriptional switches within gastric cell types or products of intestinal cell types, but the exact origin is unclear. However, half of EAC patients were not observed to have Barrett’s esophagus at the time of diagnosis.6,7 Therefore, we cannot help but ask the following question: does Barrett’s esophagus increase the risk of EAC? This question can be answered by determining the origin of Barrett’s esophagus. Most scientists believe that Barrett’s esophagus originates from many sources, such as various specific cell populations in the gastroesophageal junctions and esophageal submucosal glands. Lineage tracing studies in mouse models is the primary method for exploring Barrett’s esophagus origin. However, the squamous pregastric keratinization and lack of esophageal submucosal glands make this animal model unable to fully mimic human gastroesophageal physiology. Additionally, isolation of esophageal submucosal glands from fresh human tissue is particularly difficult. All of these have become the major obstacles to lineage tracing studies. In a study recently published in Science, titled “Molecular phenotyping reveals the identity of Barrett’s esophagus and its malignant transition,” Nowicki-Osuch et al8 successfully harvested the tissue samples across the gastroesophageal junction and isolated esophageal submucosal glands from patients and healthy individuals to explore the exact source of Barrett’s esophagus. These tissue samples were analyzed by single-cell transcriptomic profiling, in silico lineage tracing of methylation, and somatic mutation/open chromatin array. The functional validation was performed in organoid models. In brief, the authors immuno-stained pan-epithelial tissues, squamous tissues, columnar tissues, and esophageal submucosal glands of fresh human esophagus tissue with cadherin 1 (CDH1), keratin 5 (KRT5), keratin 8 (KRT8), and keratin 7 (KRT7) antibodies, respectively, and then used the three-dimensional confocal microscopy to identify and isolate the ductal cells, oncocytes, mucous cells, and myoepithelial cells. Theyobserved a population of P63þKRT5þKRT7þ cells (transitional basal progenitor) in ","PeriodicalId":40142,"journal":{"name":"Global Medical Genetics","volume":"9 4","pages":"287-289"},"PeriodicalIF":1.7,"publicationDate":"2022-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9771686/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10435826","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}