Annals of Human Genetics最新文献

{"title":"The dawn of a cure for sickle cell disease through CRISPR-based treatment: A critical test of equity in public health genomics.","authors":"Gerald Mboowa, Ivan Sserwadda, Stephen Kanyerezi, Stephen Tukwasibwe, Benson Kidenya","doi":"10.1111/ahg.12558","DOIUrl":"10.1111/ahg.12558","url":null,"abstract":"<p><p>Equity in access to genomic technologies, resources, and products remains a great challenge. This was evident especially during the coronavirus disease 2019 (COVID-19) pandemic when the majority of lower middle-income countries were unable to achieve at least 10% population vaccination coverage during initial COVID-19 vaccine rollouts, despite the rapid development of those vaccines. Sickle cell disease (SCD) is an inherited monogenic red blood cell disorder that affects hemoglobin, the protein that carries oxygen through the body. Globally, the African continent carries the highest burden of SCD with at least 240,000 children born each year with the disease. SCD has evolved from a treatable to a curable disease. Recently, the UK medical regulator approved its cure through clustered regularly interspaced short palindromic repeat (CRISPR)-based treatment, whereas the US Food and Drug Administration has equally approved two SCD gene therapies. This presents a remarkable opportunity to demonstrate equity in public health genomics. This CRISPR-based treatment is expensive and therefore, a need for an ambitious action to ensure that they are affordable and accessible where they are needed most and stand to save millions of lives.</p>","PeriodicalId":8085,"journal":{"name":"Annals of Human Genetics","volume":" ","pages":""},"PeriodicalIF":1.0,"publicationDate":"2024-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11416560/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140183556","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Using Drosophila amyloid toxicity models to study Alzheimer's disease","authors":"Elli Tsintzas,&nbsp;Teresa Niccoli","doi":"10.1111/ahg.12554","DOIUrl":"10.1111/ahg.12554","url":null,"abstract":"<p>Alzheimer's disease (AD) is the most prevalent form of dementia and is characterised by a progressive loss of neurons, which manifests as gradual memory decline, followed by cognitive loss. Despite the significant progress in identifying novel biomarkers and understanding the prodromal pathology and symptomatology, AD remains a significant unmet clinical need. Lecanemab and aducanumab, the only Food and Drug Administration approved drugs to exhibit some disease-modifying clinical efficacy, target Aβ amyloid, underscoring the importance of this protein in disease aetiology. Nevertheless, in the absence of a definitive cure, the utilisation of preclinical models remains imperative for the identification of novel therapeutic targets and the evaluation of potential therapeutic agents. <i>Drosophila melanogaster</i> is a model system that can be used as a research tool to investigate neurodegeneration and therapeutic interventions. The short lifespan, low price and ease of husbandry/rearing make <i>Drosophila</i> an advantageous model organism from a practical perspective. However, it is the highly conserved genome and similarity of <i>Drosophila</i> and human neurobiology which make flies a powerful tool to investigate neurodegenerative mechanisms. In addition, the ease of transgenic modifications allows for early proof of principle studies for future therapeutic approaches in neurodegenerative research. This mini review will specifically focus on utilising <i>Drosophila</i> as an in vivo model of amyloid toxicity in AD.</p>","PeriodicalId":8085,"journal":{"name":"Annals of Human Genetics","volume":"88 5","pages":"349-363"},"PeriodicalIF":1.0,"publicationDate":"2024-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/ahg.12554","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140183557","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Causal effect of severe and non-severe malaria on dyslipidemia in African Ancestry individuals: A Mendelian randomization study.","authors":"Mariam Traore, Harouna Sangare, Oudou Diabate, Abdoulaye Diawara, Cheickna Cissé, Oyekanmi Nashiru, Jian Li, Jeffrey Shaffer, Mamadou Wélé, Seydou Doumbia, Tinashe Chikowore, Opeyemi Soremekun, Segun Fatumo","doi":"10.1111/ahg.12555","DOIUrl":"10.1111/ahg.12555","url":null,"abstract":"<p><strong>Background: </strong>Dyslipidemia is becoming prevalent in Africa, where malaria is endemic. Observational studies have documented the long-term protective effect of malaria on dyslipidemia; however, these study designs are prone to confounding. Therefore, we used Mendelian randomization (MR, a method robust to confounders and reverse causation) to determine the causal effect of severe malaria (SM) and the recurrence of non-severe malaria (RNM) on lipid traits.</p><p><strong>Method: </strong>We performed two-sample MR using genome wide association study (GWAS) summary statistics for recurrent non-severe malaria (RNM) from a Benin cohort (N = 775) and severe malaria from the MalariaGEN dataset (N = 17,000) and lipid traits from summary-level data of a meta-analyzed African lipid GWAS (MALG, N = 24,215) from the African Partnership for Chronic Disease Research (APCDR) (N = 13,612) and the Africa Wits-IN-DEPTH partnership for genomics studies (AWI-Gen) dataset (N = 10,603).</p><p><strong>Result: </strong>No evidence of significant causal association was obtained between RNM and high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), total cholesterol and triglycerides. However, a notable association emerged between severe malarial anaemia (SMA) which is a subtype of severe malaria and reduced HDL-C levels, suggesting a potential subtype-specific effect. Nonetheless, we strongly believe that the small sample size likely affects our estimates, warranting cautious interpretation of these results.</p><p><strong>Conclusion: </strong>Our findings challenge the hypothesis of a broad causal relationship between malaria (both severe and recurrent non-severe forms) and dyslipidemia. The isolated association with SMA highlights an intriguing area for future research. However, we believe that conducting larger studies to investigate the connection between malaria and dyslipidemia in Africa will enhance our ability to better address the burden posed by both diseases.</p>","PeriodicalId":8085,"journal":{"name":"Annals of Human Genetics","volume":" ","pages":""},"PeriodicalIF":1.0,"publicationDate":"2024-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140130579","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetically predicted retinal vascular occlusion in relation to cardiovascular diseases: A bidirectional two-sample Mendelian randomization analysis","authors":"Jun Zhang,&nbsp;Yiji Pan,&nbsp;Hongxia Yang,&nbsp;Shuqiong Hu,&nbsp;Sheng Zheng,&nbsp;Tao He","doi":"10.1111/ahg.12552","DOIUrl":"10.1111/ahg.12552","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Increasing evidence implicates retinal vascular occlusions as a susceptibility factor for cardiovascular diseases (CVDs), whereas inconsistent results on the relationship were reported in previous observational studies. This research using a bidirectional two-sample Mendelian randomization (MR) analysis aimed to investigate the potential association between genetically determined central/branch retinal artery and retinal vein occlusions (CRAO/BRAO/RVO) and the risk of CVD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Summary statistics of retinal vascular occlusions from the largest available genome-wide association study of European descent were used to investigate their relationship with CVDs, and vice versa. Primary analyses were conducted using the common inverse-variance weighted approach. Several complementary sensitivity analyses were performed to verify the reliability of our results.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Inverse variance weighted method showed suggestive effects of genetically determined RVO on ischemic stroke (IS) (odds ratio [OR] = 1.021, 95% confidence [CI] = 1.004–1.037, <i>p</i> = 0.012), a genetic liability to CRAO increased the risk of myocardial infarction (MI) (OR = 1.014, 95% CI = 1.006–1.023, <i>p</i> = 7.0 × 10−4). In addition, genetic predisposition to BRAO had a positive effect on stroke (OR = 1.008, 95% CI = 1.002–1.013, <i>p</i> = 0.011), IS (OR = 1.007, 95% CI = 1.001–1.014, <i>p</i> = 0.022), and cardioembolic stroke (CES) (OR = 1.018, 95% CI = 1.006–1.031, <i>p</i> = 0.004). The point estimates from sensitivity analyses were in the same direction. Reverse MR analyses found no significant evidence for the effect of CVDs on retinal vascular occlusions.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our MR study provides potential evidence that retinal vascular occlusions are causally linked to increased risk of CVDs including IS, MI, stroke, and CES. This supports the need for clinical CVD screening in individuals with retinal vascular occlusions. Further investigations are warranted to clarify the effects of CVDs on ocular comorbidities.</p>\u0000 </section>\u0000 </div>","PeriodicalId":8085,"journal":{"name":"Annals of Human Genetics","volume":"88 4","pages":"336-348"},"PeriodicalIF":1.9,"publicationDate":"2024-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139899254","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The systematic identification of survival-related alternative splicing events and splicing factors in glioblastoma","authors":"Tao Peng,&nbsp;Zhe Liu,&nbsp;Yu Zhang,&nbsp;Xudong Liu,&nbsp;Lijun Zhao,&nbsp;Ying Ma,&nbsp;Jinke Fan,&nbsp;Xinqiang Song,&nbsp;Lei Wang","doi":"10.1111/ahg.12550","DOIUrl":"10.1111/ahg.12550","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 \u0000 <p>Glioblastoma multiforme (GBM) is the most common and aggressive primary brain tumor, making it one of the most life-threatening human cancers. Nevertheless, research on the mechanism of action between alternative splicing (AS) and splicing factor (SF) or biomarkers in GBM is limited. AS is a crucial post-transcriptional regulatory mechanism. More than 95% of human genes undergo AS events. AS can diversify the expression patterns of genes, thereby increasing the diversity of proteins and playing a significant role in the occurrence and development of tumors. In this study, we downloaded 599 clinical data and 169 transcriptome analysis data from The Cancer Genome Atlas (TCGA) database. Besides, we collected AS data about GBM from TCGA-SpliceSeq. The overall survival (OS) related AS events in GBM were determined through least absolute shrinkage and selection operator (Lasso) and Cox analysis. Subsequently, the association of these 1825 OS-related AS events with patient survival was validated using the Kaplan–Meier survival analysis, receiver operating characteristic curve, risk curve analysis, and independent prognostic analysis. Finally, we depicted the AS–SF regulatory network, illustrating the interactions between splicing factors and various AS events in GBM. Additionally, we identified three splicing factors (<i>RNU4-1</i>, <i>SEC31B</i>, and <i>CLK1</i>) associated with patient survival. In conclusion, based on AS occurrences, we developed a predictive risk model and constructed an interaction network between GBM-related AS events and SFs, aiming to shed light on the underlying mechanisms of GBM pathogenesis and progression.</p>\u0000 </section>\u0000 </div>","PeriodicalId":8085,"journal":{"name":"Annals of Human Genetics","volume":"88 4","pages":"320-335"},"PeriodicalIF":1.9,"publicationDate":"2024-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139899255","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of blood lipid profiles and asthma: A bidirectional two-sample Mendelian randomization study","authors":"Yi-Shian Liu,&nbsp;Yu-Chun Lin,&nbsp;Meng-Chih Lin,&nbsp;Chao-Chien Wu,&nbsp;Tsu-Nai Wang","doi":"10.1111/ahg.12545","DOIUrl":"10.1111/ahg.12545","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Observational studies and meta-analyses have indicated associations between blood lipid profiles and asthma. However, the causal association is unknown. Therefore, this study investigated the causal relationship between blood lipid profiles and asthma using bidirectional Mendelian randomization analysis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods and materials</h3>\u0000 \u0000 <p>Our analyses were performed using individual data from the Taiwan Biobank and summary statistics from the Asian Genetic Epidemiology Network (AGEN). The causal estimates between all genetic variants, exposures of interest and asthma were calculated using an inverse-variance weighted method based on Taiwan Biobank data from 24,853 participants (mean age, 48.8 years; 49.8% women). Sensitivity analyses, including the weighted median, MR Egger regression, MR-PRESSO, mode-based estimate, contamination mixture methods, and leave-one-out analysis, were applied to validate the results and detect pleiotropy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In the inverse-variance weighted (IVW) analyses, we found evidence of a significant causal effect of an increased level of low-density lipoprotein cholesterol on asthma risk (<i>β</i>_IVW = 1.338, <i>p</i> = 0.001). A genetically decreased level of high-density lipoprotein cholesterol was also associated with asthma risk (<i>β</i>_IVW = −0.338, <i>p</i> = 0.01). We also found that an increased level of total cholesterol was associated with an increased risk of asthma (<i>β</i>_IVW = 1.343, <i>p</i> = 0.001). Several sensitivity analyses generated consistent findings. We did not find evidence to support the causality between asthma and blood lipid profiles in either direction.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our results supported the causal relationship between higher levels of LDL cholesterol and total cholesterol and lower levels of HDL cholesterol with an increased risk of asthma.</p>\u0000 </section>\u0000 </div>","PeriodicalId":8085,"journal":{"name":"Annals of Human Genetics","volume":"88 4","pages":"307-319"},"PeriodicalIF":1.9,"publicationDate":"2024-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139668876","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ABCA1 variant rs9282541 is associated with metabolic syndrome in Maya children","authors":"Barbara I. Peña-Espinoza,&nbsp;Emmanuel Torre-Horta,&nbsp;María G. Ortiz-López,&nbsp;Marta Menjivar","doi":"10.1111/ahg.12546","DOIUrl":"10.1111/ahg.12546","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Metabolic syndrome (MetS) is a metabolic disorder encompassing risk factors for cardiovascular disease and type 2 diabetes (T2D). In Mexico, the MetS is a national health problem in adults and children. Environmental and genetic factors condition the MetS. However, studies to elucidate the contribution of genetic factors to MetS in Mexico are scarce. A recent study showed that variant rs9282541 (A-allele) in ATP-binding cassette transporter A1 (<i>ABCA1</i>) was associated with T2D in the Maya population in addition to low levels of high-density lipoprotein cholesterol (HDL-C). Thus, this study aimed to determine whether the genetic variant of <i>ABCA1</i> A-allele (rs9282541, NM_005502.4:c.688C &gt; T, NP_005493.2:p.Arg230Cys) is associated with MetS and its components in Mexican Maya children.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The study was conducted in 508 children aged 9–13 from the Yucatán Peninsula. MetS was identified according to the de Ferranti criteria. Genotyping was performed using TaqMan assay by real-time PCR. Evaluation of genetic ancestry group was included.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The frequency of MetS and overweight–obesity was 45.9% and 41.6%, respectively. The genetic variant rs9282541 was associated with low HDL-C and high glucose concentrations. Remarkably, for the first time, this study showed the association of <i>ABCA1</i> rs9282541 with MetS in Maya children with an OR of 3.076 (95% CI = 1.16–8.13 <i>p</i> = 0.023). Finally, this study reveals a high prevalence of MetS and suggests that variant rs9282541 of the <i>ABCA1</i> gene plays an important role in the developing risk of MetS in Maya children.</p>\u0000 </section>\u0000 </div>","PeriodicalId":8085,"journal":{"name":"Annals of Human Genetics","volume":"88 4","pages":"279-286"},"PeriodicalIF":1.9,"publicationDate":"2024-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139401562","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigation of the association between the Toll-like receptor 1 rs4833095 variation and gastric adenocarcinoma recurrence","authors":"Yuan Dang,&nbsp;Jingyun Huang,&nbsp;Chen Lin,&nbsp;Shaohua Xu","doi":"10.1111/ahg.12548","DOIUrl":"10.1111/ahg.12548","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Toll-like receptors (TLRs) are a family of transmembrane receptors that play key roles in identifying invading pathogens and activating innate immunity. TLR1 has been reported to be associated with the risk of gastric cancer (GC) but that was based on only a simple statistical analysis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We genotyped the TLR1 in 526 GC patients to investigate the association between the variation and gastric cancer survival by the multiplex polymerase chain reaction and sequencing method. The rs4833095 variation (chr4:38798089 [GRCh38. p14], T &gt; C) in the <i>TLR1</i> gene was genotyped in 526 patients who underwent GC resection. The associations between genotype, survival, and recurrence were investigated. The potential role of TLR1 in stomach cancer was investigated using clinical data from formalin-fixed, paraffin-embedded tissue samples.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Patients with the T/C and C/C genotypes of rs4833095 had a lower risk of recurrence than those with the T/T genotype. Recurrence-free periods were substantially longer in patients with the T/C or C/C genotypes (22.6 and 22.3 months, respectively) than in those with the T/T genotype (20.7 months). Patients with the T/C or C/C genotype, low expression levels of <i>VEGF1</i>, high expression levels of <i>ERBB2</i> and <i>ERCC1</i>, the absence of cancer nodules, a tumor size of less than 5 cm, and poor differentiation had a considerably reduced risk of recurrence.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p><i>TLR1</i> rs4833095 was correlated with the postresection prognosis of patients with gastric cancer, suggesting that TLR1 may have a role in the onset or progression of gastric cancer.</p>\u0000 </section>\u0000 </div>","PeriodicalId":8085,"journal":{"name":"Annals of Human Genetics","volume":"88 4","pages":"287-299"},"PeriodicalIF":1.9,"publicationDate":"2024-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139401572","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nonsense suppression induces read-through of a novel BMPR1A variant in a Chinese family with hereditary colorectal cancer","authors":"Zhaokun Wang,&nbsp;Jiaying Shi,&nbsp;Dachang Tao,&nbsp;Shengyu Xie,&nbsp;Yuan Yang,&nbsp;Yunqiang Liu","doi":"10.1111/ahg.12549","DOIUrl":"10.1111/ahg.12549","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>BMPR1A-mediated signaling transduction plays an essential role in intestinal growth. Variations of <i>BMPR1A</i> lead to a rare autosomal dominant inherited juvenile polyposis syndrome (JPS) with high probability of developing into colorectal cancer (CRC). Nonsense and frameshift variations, generating premature termination codons (PTCs), are the most pathogenic variants in the <i>BMPR1A</i> gene.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>This study aimed to investigate the molecular genetic etiology in a Chinese family with three generations of CRC.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Pathogenic variants of 18 known CRC susceptibility genes were examined in a Chinese CRC family through multigene panel testing using the next-generation sequencing platform. The candidate gene variant was validated in the family members by Sanger sequencing. Potential biological functions of the gene variant were further investigated in the RKO colon cancer cell line.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A novel nonsense variant (c.1114A &gt; T, p.Lys372*) of <i>BMPR1A</i> was identified in the CRC family. This variant generated a PTC at the kinase domain and caused nonsense-mediated mRNA decay. Read-through inducing reagents G418 and PTC124 partially restored BMPR1A expression and its following signaling pathway.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The identification of the novel <i>BMPR1A</i> variant enriched the genotype–phenotype spectrum of <i>BMPR1A</i>. Meanwhile, our finding also provided support for future PTC-targeting therapy for BMPR1A-mediated JPS and CRC.</p>\u0000 </section>\u0000 </div>","PeriodicalId":8085,"journal":{"name":"Annals of Human Genetics","volume":"88 4","pages":"300-306"},"PeriodicalIF":1.9,"publicationDate":"2024-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139401573","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A comprehensive review of HVS-I mitochondrial DNA variation of 19 Iranian populations","authors":"Motahareh Amjadi,&nbsp;Zahra Hayatmehr,&nbsp;Balázs Egyed,&nbsp;Mahmood Tavallaei,&nbsp;Anna Szécsényi-Nagy","doi":"10.1111/ahg.12544","DOIUrl":"10.1111/ahg.12544","url":null,"abstract":"<p>Iran is located along the Central Asian corridor, a natural artery that has served as a cross-continental route since the first anatomically modern human populations migrated out of Africa. We compiled and reanalyzed the HVS-I (hypervariable segment-I) of 3840 mitochondrial DNA (mtDNA) sequences from 19 Iranian populations and from 26 groups from adjacent countries to give a comprehensive review of the maternal genetic variation and investigate the impact of historical events and cultural factors on the maternal genetic structure of modern Iranians. We conclude that Iranians have a high level of genetic diversity. Thirty-six haplogroups were observed in Iran's populations, and most of them belong to widespread West-Eurasian haplogroups, such as H, HV, J, N, T, and U. In contrast, the predominant haplogroups observed in most of the adjacent countries studied here are H, M, D, R, U, and C haplogroups. Using principal component analysis, clustering, and genetic distance-based calculations, we estimated moderate genetic relationships between Iranian and other Eurasian groups. Further, analyses of molecular variance and comparing geographic and genetic structures indicate that mtDNA HVS-I sequence diversity does not exhibit any sharp geographic structure in the country. Barring a few from some culturally distinct and naturally separated minorities, most Iranian populations have a homogenous maternal genetic structure.</p>","PeriodicalId":8085,"journal":{"name":"Annals of Human Genetics","volume":"88 3","pages":"259-277"},"PeriodicalIF":1.9,"publicationDate":"2023-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/ahg.12544","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139071378","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}