Annals of Human Genetics最新文献

{"title":"Increased prevalence of the null allele of the p.Arg577Ter variant in the ACTN3 gene in Brazilian long-distance athletes: A retrospective study","authors":"João Paulo Limongi França Guilherme,&nbsp;Edilamar Menezes Oliveira","doi":"10.1111/ahg.12571","DOIUrl":"10.1111/ahg.12571","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>The phenotypic consequences of the p.Arg577Ter variant in the α-actinin-3 (<i>ACTN3</i>) gene are suggestive of a trade-off between performance traits for speed and endurance sports. Although there is a consistent association of the c.1729C allele (aka R allele) with strength/power traits, there is still a debate on whether the null allele (c.1729T allele; aka X allele) influences endurance performance. The present study aimed to test the association of the <i>ACTN3</i> p.Arg577Ter variant with long-distance endurance athlete status, using previously published data with the Brazilian population.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Genotypic data from 203 long-distance athletes and 1724 controls were analysed in a case–control approach.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The frequency of the X allele was significantly higher in long-distance athletes than in the control group (51.5% vs. 41.4%; <i>p </i>= 0.000095). The R/X and X/X genotypes were overrepresented in the athlete group. Individuals with the R/X genotype instead of the R/R genotype had a 1.6 increase in the odds of being a long-distance athlete (<i>p</i> = 0.012), whereas individuals with the X/X genotype instead of the R/R genotype had a 2.2 increase in the odds of being a long-distance athlete (<i>p</i> = 0.00017).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The X allele, mainly the X/X genotype, was associated with long-distance athlete status in Brazilians.</p>\u0000 </section>\u0000 </div>","PeriodicalId":8085,"journal":{"name":"Annals of Human Genetics","volume":"88 6","pages":"414-422"},"PeriodicalIF":1.0,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141465804","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":"Population-genetic and comparative interpopulation studies of the 15 autosomal STR markers in the population living in the Northwest of Iran","authors":"Saeed Ghadimi Haddadan,&nbsp;Esmaeil Babaei,&nbsp;Mehrdad Setareh","doi":"10.1111/ahg.12564","DOIUrl":"10.1111/ahg.12564","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Iran, a country in the Middle East, has several ethnic and ethno-religious groups and needs its own ethnic-specific databases for the forensic statistical parameters and allele frequency of STR markers.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We have investigated 600 unrelated Turk individuals from four northwestern provinces of Iran using the Identifiler™ system (TPOX, FGA, vWA, TH01, CSF1PO, D2S1338, D3S1358, D5S818, D7S820, D8S1179, D13S317, D16S539, D18S51, D19S433, and D21S11). Furthermore, STR allelic frequencies were compared to previously population-based data.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results and conclusion</h3>\u0000 \u0000 <p>After Bonferroni correction, deviation from Hardy-Weinberg equilibrium (HWE) was observed in the FGA, TPOX, VWA, and D19S433 loci (<i>P</i> value &lt; 0.05). The combined power of discrimination (CPD) and exclusion (CPE) values for all 15 STR loci were 0.9999999999999999999984 and 0.9999999, respectively. In comparison with Azerbaijani and Turkish populations, there were no significant differences on all STR markers. However, in the Chinese Han population, differences at 13 STR loci were detected. Additionally, comparisons of Fischer genetic distance indices (FST) <i>P</i>-values did not reveal any statistically significant difference between Northwestern Iran, Azerbaijan and Iran (Fars) populations. PCA and PCoA analyses showed that our population was grouped with different populations in different quarters, showing a positive and negative correlation, respectively. In the NJ and UPGMA phylogenetic trees, Iranian populations were grouped together. These results demonstrated that the given set of STR markers can be confidently used for all identification tests in Northwestern Iran.</p>\u0000 </section>\u0000 </div>","PeriodicalId":8085,"journal":{"name":"Annals of Human Genetics","volume":"88 6","pages":"402-413"},"PeriodicalIF":1.0,"publicationDate":"2024-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141417482","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":"RETRACTED: Investigating the effectiveness of forensic genetics and population genetic diversity using a multi-InDel system in Chinese Hezhou and Southern Shaanxi Han populations","authors":"Xi Wang,&nbsp;Qiong Lan,&nbsp;Yifeng Lin,&nbsp;Xi Yuan,&nbsp;Shuyan Mei,&nbsp;Fanzhang Lei,&nbsp;Bonan Dong,&nbsp;Ming Zhao,&nbsp;Meiming Cai,&nbsp;Chunmei Shen,&nbsp;Bofeng Zhu","doi":"10.1111/ahg.12553","DOIUrl":"10.1111/ahg.12553","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Multiple insertion-deletion (multi-InDel) has greater potential in forensic genetics than InDel, and its efficacy in kinship testing, individual identification, DNA mixture detection and ancestry inference remains to be explored.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Consequently, we designed an efficient and robust system consisting of 41 multi-InDels to evaluate its efficacy in forensic applications in Chinese Hezhou Han (HZH) and Southern Shaanxi Han (SNH) populations and explore the genetic relationships between the SNH, HZH, and 26 reference populations.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results and conclusion</h3>\u0000 \u0000 <p>The obtained results showed that 38 out of the 41 multi-InDels had fairly high genetic variations. The the cumulative probability of discrimination and exclusion values of the multi-InDels (except MI38) in HZH and SNH populations both exceeded 1-e⁻²⁵ and 1-e⁻⁶, correspondingly. The genetic compositions of HZH and SNH individuals were similar to that of East Asians and the Naive Bayes model could well distinguish East Asians, Africans and Americans. These results indicated that the multi-InDel systerm can serve as an effective tool to provide important evidence for the development of multi-InDels in forensic practice and better analyse the genetic background of the Han Chinese populations.</p>\u0000 </section>\u0000 </div>","PeriodicalId":8085,"journal":{"name":"Annals of Human Genetics","volume":"89 2-3","pages":"e1-e13"},"PeriodicalIF":1.0,"publicationDate":"2024-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141064923","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":"NanoImprint: A DNA methylation tool for clinical interpretation and diagnosis of common imprinting disorders using nanopore long-read sequencing","authors":"Caroline Hey Bækgaard,&nbsp;Emilie Boye Lester,&nbsp;Steffen Møller-Larsen,&nbsp;Mathilde Faurholdt Lauridsen,&nbsp;Martin Jakob Larsen","doi":"10.1111/ahg.12556","DOIUrl":"10.1111/ahg.12556","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Long-read whole genome sequencing like Oxford Nanopore Technology, is increasingly being introduced in clinical settings. With its ability to simultaneously call sequence variation and DNA modifications including 5-methylcytosine, nanopore is a promising technology to improve diagnostics of imprinting disorders.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Currently, no tools to analyze DNA methylation patterns at known clinically relevant imprinted regions are available. Here we present NanoImprint, which generates an easily interpretable report, based on long-read nanopore sequencing, to use for identifying clinical relevant abnormalities in methylation levels at 14 imprinted regions and diagnosis of common imprinting disorders.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results and conclusion</h3>\u0000 \u0000 <p>NanoImprint outputs a summarizing table and visualization plots displays methylation frequency (%) and chromosomal positions for all regions, with phased data color-coded for the two alleles. We demonstrate the utility of NanoImprint using three imprinting disorder samples from patients with Beckwith-Wiedemann syndrome (BWS), Angelman syndrome (AS) and Prader-Willi syndrome (PWS). NanoImprint script is available from https://github.com/carolinehey/NanoImprint.</p>\u0000 </section>\u0000 </div>","PeriodicalId":8085,"journal":{"name":"Annals of Human Genetics","volume":"88 5","pages":"392-398"},"PeriodicalIF":1.0,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/ahg.12556","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140829932","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":"Epithelial–mesenchymal transition dysregulation in prostate cancer: Insights from molecular unraveling and epidemiological analyses in Tunisia, North Africa","authors":"Rahma Said,&nbsp;Javier Hernández-Losa,&nbsp;Rosa Somoza Lopez de Haro,&nbsp;Teresa Moline,&nbsp;Skander Zouari,&nbsp;Ahlem Blel,&nbsp;Soumaya Rammeh,&nbsp;Amine Derouiche,&nbsp;Slah Ouerhani","doi":"10.1111/ahg.12563","DOIUrl":"10.1111/ahg.12563","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>The progression of prostate cancer (PCa) has been linked worldwide, including in African populations, to the dysregulation of the epithelial–mesenchymal transition (EMT).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>To clarify the connection among EMT markers, clinicopathological parameters, and epidemiological factors, we analyzed 35 PCa specimens from patients in Tunisia, a country in North Africa, arranged by stages. We also carried out extensive molecular and epidemiological analyses.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Significant dysregulation of EMT genes was found, with an overexpression of <i>ZEB-1</i>, <i>Twist</i>, <i>Snail-1</i>, and <i>Vimentin</i> (<i>p</i> &lt; 0.05) and underexpression of <i>E-cadherin</i> and <i>β-catenin</i> (<i>p &lt;</i> 0.05). Positive correlations were observed between transcription factors and the mesenchymal marker <i>Vimentin</i> (<i>p</i> &lt; 0.001, <i>r</i> = 0.574; <i>p</i> = 0.029, <i>r</i> = 0.411; and <i>p</i> &lt; 0.001; <i>r</i> = 0.506) according to Spearman correlation analyses, whereas negative correlations were found between epithelial markers (<i>E-cadherin, β-catenin</i>) and <i>Vimentin</i> (<i>p</i> &lt; 0.05; <i>r</i> &lt; 0). Higher PSA, Gleason scores, and metastasis were all correlated with the dysregulation of EMT (<i>p</i> &lt; 0.05). Notably, there was a positive correlation between higher consumption of tobacco (≥20 Packets per year) and <i>Vimentin</i> expression (<i>p</i> &lt; 0.001, <i>r</i> = 0.854), suggesting a relationship between smoking and EMT activation in the Tunisian population. Moreover, <i>Twist</i> showed a positive correlation with diabetes (<i>p</i> &lt; 0.001, <i>r</i> = 0.385), whereas no significant correlations were found between EMT markers and comorbidities such as hypertension and coronary insufficiency. These results demonstrate the intricate connection between molecular changes, epidemiological factors, and disease progression, and they emphasize the crucial role that EMT plays in promoting PCa aggressiveness in African populations, particularly in Tunisia.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>In summary, understanding these correlations could help develop focused treatment plans and enhance patient outcomes for PCa management in African settings.</p>\u0000 </section>\u0000 </div>","PeriodicalId":8085,"journal":{"name":"Annals of Human Genetics","volume":"89 4","pages":"169-177"},"PeriodicalIF":1.0,"publicationDate":"2024-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140656883","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":"Attention-deficit/hyperactivity disorder and dopamine receptor D4 (DRD4) exon 3 variable number of tandem repeats (VNTR) 2-repeat allele","authors":"Larry Baum,&nbsp;Chi Chiu Lee,&nbsp;Rui Ye,&nbsp;Yuanxin Zhong,&nbsp;Se Fong Hung,&nbsp;Chun Pan Tang,&nbsp;Ting Pong Ho,&nbsp;James M Swanson,&nbsp;Robert K Moyzis,&nbsp;Pak-Chung Sham,&nbsp;Patrick Wing-Leung Leung","doi":"10.1111/ahg.12560","DOIUrl":"10.1111/ahg.12560","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 \u0000 <p>To investigate the association of attention-deficit/hyperactivity disorder (ADHD) with the 48-base pair (bp) variable number of tandem repeats (VNTR) in exon 3 of the dopamine receptor D4 (DRD4) gene, we genotyped 240 ADHD patients and their parents from Hong Kong. The 4R allele was most common, followed by 2R. We examined association between the 2R allele (relative to 4R) and ADHD by Transmission Disequilibrium Test (TDT). The odds ratio (OR) (95% confidence interval) was 0.90 (0.64–1.3). The <i>p</i>-value was 0.6. Examining subgroups revealed nominally significant association of 2R with inattentive ADHD: OR = 0.33 (0.12–0.92) and <i>p</i> = 0.03. Because our study used TDT analysis, we meta-analyzed the association of 2R with ADHD in Asians (1329 patient alleles), revealing results similar to ours: OR = 0.97 (0.80–1.2) and <i>p</i> = 0.8. To examine the association of 2R with inattentive ADHD, we meta-analyzed all studies (regardless of analysis type or ethnicity, in order to increase statistical power): 702 patient alleles, 1420 control alleles, OR = 0.81 (0.57–1.1) and <i>p</i> = 0.2. Overall, there is no evidence of association between ADHD and the 2R allele, but the suggestive association with the inattentive type warrants further investigation.</p>\u0000 </section>\u0000 </div>","PeriodicalId":8085,"journal":{"name":"Annals of Human Genetics","volume":"88 5","pages":"382-391"},"PeriodicalIF":1.0,"publicationDate":"2024-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/ahg.12560","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140578458","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":"Genetic variations in CYP2A6, CYP2E1, GSTM1, GSTT1 genes and the risk of Nasopharyngeal carcinoma in North African population","authors":"Imane EL Alami,&nbsp;Wafa Khaali,&nbsp;Majida Jalbout,&nbsp;Amina Gihbid,&nbsp;Wided Ben Ayoub,&nbsp;Abdellatif Benider,&nbsp;Selma Mohamed Brahim,&nbsp;Mokhtar Hamdi Cherif,&nbsp;Nadia Benchakroun,&nbsp;Mohammed El Mzibri,&nbsp;El Khalil Ben Driss,&nbsp;Khalid Belghmi,&nbsp;Marilys Corbex,&nbsp;Meriem Khyatti","doi":"10.1111/ahg.12562","DOIUrl":"10.1111/ahg.12562","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Nasopharyngeal carcinoma (NPC) is a multifactorial malignancy associated with both genetic and environmental factors. Polymorphic deletions of the phase I and phase II genes involved in the detoxification of potential carcinogens may be a risk factor for nasopharyngeal carcinoma. In this study, we investigated the relationship between <i>CYP2E1</i> (rs3813867), <i>CYP2A6, GSTM1</i>(rs1183423000) and <i>GSTT1</i>(rs1601993659) gene variations and NPC risk in North African countries with the highest incidence of NPC (Morocco, Algeria and Tunisia). and the evaluation of the potential use of these variants as potential biomarkers for NPC management.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A total of 600 NPC cases and 545 controls frequency-matched on ethnicity, sex, age and childhood household type, were recruited from three North African countries (Morocco, Algeria and Tunisia) and analysed. Genotyping of <i>CYP2A6</i> and <i>CYP2E1</i>(rs3813867) was performed by polymerase chain reaction restriction (PCR)-fragment length polymorphism (RFLP) analysis and the <i>GSTM1</i> (rs1183423000) and <i>GSTT1</i>(rs1601993659) genetic variations were evaluated using the PCR technique.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The genotype distributions of <i>CYP2E1</i>(rs3813867)<i>, CYP2A6, GSTM1</i>(rs1183423000) and <i>GSTT1</i>(rs1601993659) genotypes did not differ significantly among NPC cases and controls (<i>p</i> &gt; 0.05). Furthermore, our data did not reveal any association with smoking and the studied variants, even when the samples were stratified by the duration period of smoking.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>In this large studied North African population, our findings suggest that the functional <i>CYP2E1</i>, <i>CYP2A6, GSTM1</i> and <i>GSTT1</i> variations did not influence NPC susceptibility.</p>\u0000 </section>\u0000 </div>","PeriodicalId":8085,"journal":{"name":"Annals of Human Genetics","volume":"89 4","pages":"158-168"},"PeriodicalIF":1.0,"publicationDate":"2024-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140578488","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":"Need of the hour? Genetic and genomic testing referrals from primary healthcare centers with inclusion of precision medicine in Pakistan","authors":"Muhammad Osama Siddiqui,&nbsp;Rabeet Tariq,&nbsp;Raman Kumar,&nbsp;Saira Mansoor","doi":"10.1111/ahg.12561","DOIUrl":"10.1111/ahg.12561","url":null,"abstract":"","PeriodicalId":8085,"journal":{"name":"Annals of Human Genetics","volume":"88 6","pages":"399-401"},"PeriodicalIF":1.0,"publicationDate":"2024-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140608475","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 historical perspective on Lionel Penrose: Scientist, geneticist and dedicated opponent of eugenics","authors":"Maria Kiladi","doi":"10.1111/ahg.12551","DOIUrl":"10.1111/ahg.12551","url":null,"abstract":"<p>The paper explores Lionel Penrose's scientific work. Penrose investigated the causes of mental disorders from clinical and genetic points of view. His investigations on phenylketonuria and Down syndrome helped to demonstrate the heterogenous character of mental disorders, whose causes can range from genetic with high penetrance, to largely environmental. He was specifically selected by JBS Haldane to become University College London's third Galton Chair as a result of his Colchester survey investigations. He became the first Galton Chair who had medical training. He never concealed his distaste for anything related to eugenics. As well as using his scientific work to reject eugenic ideas such as suggestions on sterilisation measures or the existence of a social problem group, he campaigned successfully to rename the Department of Eugenics, Biometry and Genetics to Department of Human Genetics and Biometry. With his work, he discredited prejudiced eugenic ideas on mental disorders and became an advocate for those with mental disabilities.</p>","PeriodicalId":8085,"journal":{"name":"Annals of Human Genetics","volume":"89 5","pages":"285-292"},"PeriodicalIF":1.2,"publicationDate":"2024-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/ahg.12551","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140578413","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":"An exploration of the genetics of the mutant Huntingtin (mHtt) gene in a cohort of patients with chorea from different ethnic groups in sub-Saharan Africa","authors":"Mendi J Muthinja,&nbsp;Carlos Othon Guelngar,&nbsp;Maouly Fall,&nbsp;Fatumah Jama,&nbsp;Huda Aldeen Shuja,&nbsp;Jamila Nambafu,&nbsp;Daniel Gams Massi,&nbsp;Oluwadamilola O. Ojo,&nbsp;Njideka U. Okubadejo,&nbsp;Funmilola Tolulope Taiwo,&nbsp;Alassane Mamadou Diop,&nbsp;Coudjou J. D. G. de Chacus,&nbsp;Fodé Abass Cissé,&nbsp;Amara Cissé,&nbsp;Juzar Hooker,&nbsp;Dilraj Sokhi,&nbsp;Henry Houlden,&nbsp;Mie Rizig","doi":"10.1111/ahg.12557","DOIUrl":"10.1111/ahg.12557","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Background&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Africans are underrepresented in Huntington's disease (HD) research. A European ancestor was postulated to have introduced the mutant &lt;i&gt;Huntingtin&lt;/i&gt; (&lt;i&gt;mHtt&lt;/i&gt;) gene to the continent; however, recent work has shown the existence of a unique &lt;i&gt;Htt&lt;/i&gt; haplotype in South-Africa specific to indigenous Africans.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Objective&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;We aimed to investigate the CAG trinucleotide repeats expansion in the &lt;i&gt;Htt&lt;/i&gt; gene in a geographically diverse cohort of patients with chorea and unaffected controls from sub-Saharan Africa.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Methods&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;We evaluated 99 participants: 43 patients with chorea, 21 asymptomatic first-degree relatives of subjects with chorea, and 35 healthy controls for the presence of the &lt;i&gt;mHtt&lt;/i&gt;. Participants were recruited from 5 African countries. Additional data were collected from patients positive for the &lt;i&gt;mHtt&lt;/i&gt; gene; these included demographics, the presence of psychiatric and (or) cognitive symptoms, family history, spoken languages, and ethnic origin. Additionally, their pedigrees were examined to estimate the number of people at risk of developing HD and to trace back the earliest account of the disease in each region.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Results&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;HD cases were identified in all countries. Overall, 53.4% of patients with chorea were carriers for the &lt;i&gt;mHTT&lt;/i&gt;; median tract size was 45 CAG repeats. Of the asymptomatic relatives, 28.6% (6/21) were carriers for the &lt;i&gt;mHTT;&lt;/i&gt; median tract size was 40 CAG. No homozygous carries were identified. Median CAG tract size in controls was 17 CAG repeats. Men and women were equally affected by HD. All patients with HD—bar three who were juvenile onset of &lt;21 years—were defined as adult onset (median age of onset was 40 years). HD transmission followed an autosomal dominant pattern in 84.2% (16/19) of HD families. In familial cases, maternal transmission was higher 52.6% (10/19) than paternal transmission 36.8% (7/19). The number of asymptomatic individuals at risk of developing HD was estimated at ten times more than the symptomatic patients. HD could be traced back to the early 1900s in most African sites. HD cases spread over seven ethnic groups belonging to two distinct linguistic lineages separated from each other approximately 54–16 kya ago: Nilo-Sahara and Niger-Congo.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Conclusion&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;This is the first study examining","PeriodicalId":8085,"journal":{"name":"Annals of Human Genetics","volume":"89 4","pages":"149-157"},"PeriodicalIF":1.0,"publicationDate":"2024-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/ahg.12557","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140334515","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}