Annals of Human Genetics最新文献

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Secondary findings in 443 exome sequencing data. 443 个外显子组测序数据的次要发现。
IF 1 4区 生物学
Annals of Human Genetics Pub Date : 2024-11-15 DOI: 10.1111/ahg.12586
Marija Branković, Heonjong Han, Milena Janković, Ana Marjanović, Nikola Andrejic, Ilija Gunjić, Vanja Virić, Aleksa Palibrk, Hane Lee, Stojan Peric
{"title":"Secondary findings in 443 exome sequencing data.","authors":"Marija Branković, Heonjong Han, Milena Janković, Ana Marjanović, Nikola Andrejic, Ilija Gunjić, Vanja Virić, Aleksa Palibrk, Hane Lee, Stojan Peric","doi":"10.1111/ahg.12586","DOIUrl":"https://doi.org/10.1111/ahg.12586","url":null,"abstract":"<p><p>Exome sequencing (ES) may identify and report secondary findings that are unrelated to the primary disease for which the patient underwent genetic testing, but are of potential value in patient care. In this study, we evaluated 81 American College of Medical Genetics (ACMG) medically actionable genes in 443 patients with various neurological disorders. The variants identified were classified and reported following the 2015 ACMG Standards and Guidelines for the interpretation of sequence variants and the ACMG recommendations for reporting secondary findings (v3.2). We detected a total of 17 variants in 17 patients across 9 different genes as secondary findings. Seven heterozygous variants were found in BRCA1, MSH2, and PALB2 which are part of the cancer phenotype category. Nine heterozygous variants were found in MYH7, TTN, LDLR, DSC2, and DSP which are part of the cardiovascular phenotype category. Finally, one heterozygous variant was found in TTR which is part of the miscellaneous phenotype category. Thirteen of above mentioned variants were classified as known pathogenic and four as expected pathogenic. The information collected in our study may lead to the prevention of severe morbidity and mortality and provides additional insight into the genetic background of the Serbian population.</p>","PeriodicalId":8085,"journal":{"name":"Annals of Human Genetics","volume":" ","pages":""},"PeriodicalIF":1.0,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142638061","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}
引用次数: 0
Gastroesophageal reflux disease increases predisposition to severe COVID-19: Insights from integrated Mendelian randomization and genetic analysis. 胃食管反流病增加了严重 COVID-19 的易感性:孟德尔随机化和遗传学综合分析的启示。
IF 1 4区 生物学
Annals of Human Genetics Pub Date : 2024-11-12 DOI: 10.1111/ahg.12584
Jingjing Pan, Jianhua Li
{"title":"Gastroesophageal reflux disease increases predisposition to severe COVID-19: Insights from integrated Mendelian randomization and genetic analysis.","authors":"Jingjing Pan, Jianhua Li","doi":"10.1111/ahg.12584","DOIUrl":"https://doi.org/10.1111/ahg.12584","url":null,"abstract":"<p><strong>Objective: </strong>This study aims to investigate the potential causal relationship, shared genomic loci, as well as potential molecular pathways and tissue-specific expression patterns between gastroesophageal reflux disease (GERD) and the risk of hospitalized/severe 2019 coronavirus disease (COVID-19).</p><p><strong>Methods: </strong>We employed linkage disequilibrium score regression and bidirectional Mendelian randomization (MR) analysis to explore potential genetic associations between GERD (N = 602,604) and hospitalized COVID-19 (N = 2095,324) as well as severe COVID-19 (N = 1086,211). Additionally, shared genomic loci were extracted from common pivotal regions, further confirmed through corresponding colocalization analyses. GERD-driven molecular pathway network was constructed using extensive literature data mining to understand the molecular-level impacts of GERD on COVID-19.</p><p><strong>Results: </strong>Our results revealed a significant positive genetic correlation between GERD and both hospitalized (r<sub>g</sub>  =  0.418) and severe COVID-19 (r<sub>g</sub>  =  0.314). Furthermore, the MR analysis demonstrated a unidirectional causal effect of genetic predisposition to GERD on COVID-19 outcomes, including hospitalized COVID-19 (odds ratio [OR]: 1.33, 95% confidence interval [CI]: 1.27-1.44, p = 9.17e - 12) and severe COVID-19 (OR: 1.27, 95% CI: 1.18-1.37, p = 1.20e - 05). Additionally, GERD and both COVID-19 conditions shared one genomic locus with lead-SNPs rs1011407 and rs1123573, corresponding to the transcription factor BCL11A. Colocalization analysis further demonstrated a significant positive correlation between genome-wide association study and expression quantitative trait locus (eQTL) abnormalities, including rs1011407 (eQTL_p = 2.35e - 07) and rs1123573 (eQTL_p = 2.74e - 05). Molecular pathway analysis indicated that GERD might promote the progression of COVID-19 by inducting immune-activated and inflammation-related pathways.</p><p><strong>Conclusion: </strong>These findings confirm that genetically determined GERD may increase the susceptibility to hospitalized/severe COVID-19. The shared genetic loci and the potential molecular pathways offer valuable insights into causal connections between GERD and COVID-19.</p>","PeriodicalId":8085,"journal":{"name":"Annals of Human Genetics","volume":" ","pages":""},"PeriodicalIF":1.0,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142613676","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}
引用次数: 0
Histone modification: Biomarkers and potential therapies in colorectal cancer 组蛋白修饰:大肠癌癌症的生物标志物和潜在疗法。
IF 1.9 4区 生物学
Annals of Human Genetics Pub Date : 2023-09-15 DOI: 10.1111/ahg.12528
Xin An, Xiaohua Lan, Zizhen Feng, Xiaohong Li, Qisheng Su
{"title":"Histone modification: Biomarkers and potential therapies in colorectal cancer","authors":"Xin An,&nbsp;Xiaohua Lan,&nbsp;Zizhen Feng,&nbsp;Xiaohong Li,&nbsp;Qisheng Su","doi":"10.1111/ahg.12528","DOIUrl":"10.1111/ahg.12528","url":null,"abstract":"<p>The complex mechanism of colorectal cancer development is closely associated with epigenetic modifications and is caused by overexpression and/or inactivation of oncogenes. Histone modifying enzymes catalyze histone modifications to alter gene expression, which plays a crucial role in the development and progression of colorectal cancer. Currently, there is more frequent study on histone acetylation, methylation, and phosphorylation, and their mechanisms in colorectal cancer development are clearer. This article elaborates on the role of histone modification in epigenetics in colorectal cancer development and discusses recent advances in using it as biomarkers and therapeutic targets for the treatment of colorectal cancer. The review aims to demonstrate the significant role of histone modification as a new therapeutic target in colorectal cancer and provides insights into the novel diagnostic and therapeutic options it offers.</p>","PeriodicalId":8085,"journal":{"name":"Annals of Human Genetics","volume":"87 6","pages":"274-284"},"PeriodicalIF":1.9,"publicationDate":"2023-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/ahg.12528","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10243763","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}
引用次数: 0
Genetic architecture of adiposity measures among Asians: Findings from GWAS 亚洲人肥胖测量的遗传结构:GWAS的研究结果。
IF 1.9 4区 生物学
Annals of Human Genetics Pub Date : 2023-09-06 DOI: 10.1111/ahg.12526
Tripti Agarwal, Tanica Lyngdoh, Rajesh Khadgawat, Dorairaj Prabhakaran, Giriraj Ratan Chandak, Gagandeep Kaur Walia
{"title":"Genetic architecture of adiposity measures among Asians: Findings from GWAS","authors":"Tripti Agarwal,&nbsp;Tanica Lyngdoh,&nbsp;Rajesh Khadgawat,&nbsp;Dorairaj Prabhakaran,&nbsp;Giriraj Ratan Chandak,&nbsp;Gagandeep Kaur Walia","doi":"10.1111/ahg.12526","DOIUrl":"10.1111/ahg.12526","url":null,"abstract":"<p>Adiposity has gradually become a global public threat over the years with drastic increase in the attributable deaths and disability adjusted life years (DALYs). Given an increased metabolic risk among Asians as compared to Europeans for any given body mass index (BMI) and considering the differences in genetic architecture between them, the present review aims to summarize the findings from genome-wide scans for various adiposity indices and related anthropometric measures from Asian populations. The search for related studies, published till February 2022, were made on PubMed and GWAS Catalog using search strategy built with relevant keywords joined by Boolean operators. It was recorded that out of a total of 47 identified studies, maximum studies are from Korean population (<i>n</i> = 14), followed by Chinese (<i>n</i> = 7), and Japanese (<i>n</i> = 6). Nearly 200 loci have been identified for BMI, 660 for height, 16 for weight, 28 for circumferences (waist and hip), 32 for ratios (waist hip ratio [WHR] and thoracic hip ratio [THR]), 5 for body fat, 16 for obesity, and 28 for adiposity-related blood markers among Asians. It was observed that though, most of the loci were unique for each trait, there were 3 loci in common to BMI and WHR. Apart from validation of variants identified in European setting, there were many novel loci discovered in Asian populations. Notably, 125 novel loci form Asian studies have been reported for BMI, 47 for height, 5 for waist circumference, and 2 for adiponectin level to the existing knowledge of the genetic framework of adiposity and related measures. It is necessary to examine more advanced adiposity measures, specifically of relevance to abdominal adiposity, a major risk factor for cardiometabolic disorders among Asians. Moreover, in spite of being one continent, there is diversity among different ethnicities across Asia in terms of lifestyle, climate, geography, genetic structure and consequently the phenotypic manifestations. Hence, it is also important to consider ethnic specific studies for identifying and validating reliable genetic variants of adiposity measures among Asians.</p>","PeriodicalId":8085,"journal":{"name":"Annals of Human Genetics","volume":"87 6","pages":"255-273"},"PeriodicalIF":1.9,"publicationDate":"2023-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/ahg.12526","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10164904","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}
引用次数: 0
A novel heterozygous truncating variant in the AGO1 gene in an Iranian family with schizophrenia as an unreported symptom 一个未报告症状为精神分裂症的伊朗家庭中AGO1基因的一个新的杂合截短变体。
IF 1.9 4区 生物学
Annals of Human Genetics Pub Date : 2023-08-17 DOI: 10.1111/ahg.12524
Atefeh Mir, Erfan Khorram, Yongjun Song, Hane Lee, Mohammad Amin Tabatabaiefar
{"title":"A novel heterozygous truncating variant in the AGO1 gene in an Iranian family with schizophrenia as an unreported symptom","authors":"Atefeh Mir,&nbsp;Erfan Khorram,&nbsp;Yongjun Song,&nbsp;Hane Lee,&nbsp;Mohammad Amin Tabatabaiefar","doi":"10.1111/ahg.12524","DOIUrl":"10.1111/ahg.12524","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 \u0000 <p>Intellectual disability (ID) and autism spectrum disorders (ASDs) are the most common developmental disorders in humans. Combined, they affect between 3% and 5% of the population. Although high-throughput genomic methods are rapidly increasing the pool of ASD genes, many cases remain idiopathic. <i>AGO1</i> is one of the less-known genes related to ID/ASD. This gene encodes a core member protein of the RNA-induced silencing complex, which suppresses mRNA expression through cleavage, degradation, and/or translational repression. Generally, patients with defects in the <i>AGO1</i> gene manifest varying degrees of ID, speech delay, and autistic behaviors. Herein, we used whole-exome sequencing (WES) to investigate an Iranian family with two affected members one of whom manifested ID and autism and the other showed borderline ID and schizophrenia. WES analysis identified a novel heterozygous truncating variant (NM_012199.5:c.1298G &gt; A, p.Trp433Ter) in the <i>AGO1</i> gene that co-segregated with the phenotypes using Sanger sequencing. Moreover, the structural analysis showed that due to this variant, two critical domains (Mid and PIWI) of the AGO1 protein have been lost, which has a detrimental effect on the protein's function and structure. To the best of our knowledge, schizophrenia has not been reported in patients with <i>AGO1</i> deficiency, which is a novel phenotypic finding that expands the <i>AGO1</i>-related behavioral disorders. Moreover, this study's findings determined that patients with the same variant in the <i>AGO1</i> gene may show heterogeneity in manifested phenotypes.</p>\u0000 </section>\u0000 </div>","PeriodicalId":8085,"journal":{"name":"Annals of Human Genetics","volume":"87 6","pages":"295-301"},"PeriodicalIF":1.9,"publicationDate":"2023-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10011777","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}
引用次数: 1
Novel GALT variations and genetic spectrum in Turkish population with the correlation of genotype and phenotype 土耳其人群中GALT的新变异和遗传谱与基因型和表型的相关性。
IF 1.9 4区 生物学
Annals of Human Genetics Pub Date : 2023-08-11 DOI: 10.1111/ahg.12523
Irem Kalay, Cagri Gulec, Mehmet Cihan Balcı, Guven Toksoy, Gulden Gokcay, Seher Basaran, Mubeccel Demirkol, Zehra Oya Uyguner
{"title":"Novel GALT variations and genetic spectrum in Turkish population with the correlation of genotype and phenotype","authors":"Irem Kalay,&nbsp;Cagri Gulec,&nbsp;Mehmet Cihan Balcı,&nbsp;Guven Toksoy,&nbsp;Gulden Gokcay,&nbsp;Seher Basaran,&nbsp;Mubeccel Demirkol,&nbsp;Zehra Oya Uyguner","doi":"10.1111/ahg.12523","DOIUrl":"10.1111/ahg.12523","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <p>Classic galactosemia (OMIM#230400) is an autosomal recessive inborn error of carbohydrate metabolism caused by a deficiency of the galactose-1-phosphate-uridyl-transferase enzyme encoded by the <i>GALT</i> gene. Even though a galactose-restricted diet efficiently resolves the acute complications, it is insufficient to prevent long-term complications regarding speech defects, intellectual functioning, premature ovarian failure, cataract, hepatomegaly, dysarthria, ataxia, and tremor. Seventy-seven patients who were genetically diagnosed with classic galactosemia were included in this cohort. Identified novel variants were classified based on their predicted effect on the GALT function. Further, potential genotype–phenotype correlations were investigated via statistical analysis. In total, 18 different sequence variants were identified, including four novels (c.200delG/p.(Arg67Profs<sup>*</sup>19), c.533T&gt;G/ p.(Met178Arg), c.708_709delGT/p.(Ser236Argfs<sup>*</sup>30), c.467C&gt;A/p.(Ser156<sup>*</sup>)). Jaundice was the most common short-term finding with 80% (61/77). Even with early diagnosis, intellectual disability is encountered with 36% (27/74) of the long-term complications. Patients with biallelic missense variants have a significantly higher prevalence of cataracts (OR: 17.9). Longitudinal observations showed attenuation of cataracts and hepatomegaly. This study has shown the <i>GALT</i> variation spectrum of the Turkish population with a 30-year retrospective cohort, submitting a significant contribution to the genotype/phenotype correlation in galactosemia. This study also highlights the cost-effective importance of Sanger sequencing in the diagnosis of single-gene metabolic diseases.</p>\u0000 </section>\u0000 </div>","PeriodicalId":8085,"journal":{"name":"Annals of Human Genetics","volume":"87 6","pages":"285-294"},"PeriodicalIF":1.9,"publicationDate":"2023-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9977277","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}
引用次数: 0
Reassessing the association of MUC5B with survival in idiopathic pulmonary fibrosis 重新评估MUC5B与特发性肺纤维化患者生存的关系
IF 1.9 4区 生物学
Annals of Human Genetics Pub Date : 2023-08-03 DOI: 10.1111/ahg.12522
Siyang Cai, Richard J. Allen, Louise V. Wain, Frank Dudbridge
{"title":"Reassessing the association of MUC5B with survival in idiopathic pulmonary fibrosis","authors":"Siyang Cai,&nbsp;Richard J. Allen,&nbsp;Louise V. Wain,&nbsp;Frank Dudbridge","doi":"10.1111/ahg.12522","DOIUrl":"10.1111/ahg.12522","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 \u0000 <p>A variant in the mucin 5B gene (<i>MUC5B</i>) is strongly associated with the risk of idiopathic pulmonary fibrosis. However, the same variant is associated with increased survival time. Previous work suggested that this may be explained by index event bias, with the true effect being to decrease survival. Here, we reassessed this claim using more recent methods and datasets. We found that the statistical assumptions of the previous analysis did not hold, and instead, we applied recent methods of corrected weighted least squares, MR-RAPS and Slope-hunter to both the previous data and an updated consortium meta-analysis. However, these analyses did not yield robust evidence for increased or decreased survival. In simulations of a true effect of decreased survival, we did not observe any realistic scenario in which index event bias led to an observed effect of increased survival. We therefore regard as unsafe the claim that <i>MUC5B</i> has a true effect of decreased survival. Alternative explanations should be sought to explain the observed association with increased survival.</p>\u0000 </section>\u0000 </div>","PeriodicalId":8085,"journal":{"name":"Annals of Human Genetics","volume":"87 5","pages":"248-253"},"PeriodicalIF":1.9,"publicationDate":"2023-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/ahg.12522","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10053687","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}
引用次数: 0
Functional characterization of a rare pathogenic variant c.875G > A, p.(Cys292Tyr) in COMP COMP中一种罕见致病变异Cys292Tyr的功能特征
IF 1.9 4区 生物学
Annals of Human Genetics Pub Date : 2023-07-18 DOI: 10.1111/ahg.12521
Lan Yin, Yingchuan Zhu, Wenhao Jiang, Yue Song, Yilu Lu, Dachang Tao, Yunqiang Liu, Yongxin Ma
{"title":"Functional characterization of a rare pathogenic variant c.875G > A, p.(Cys292Tyr) in COMP","authors":"Lan Yin,&nbsp;Yingchuan Zhu,&nbsp;Wenhao Jiang,&nbsp;Yue Song,&nbsp;Yilu Lu,&nbsp;Dachang Tao,&nbsp;Yunqiang Liu,&nbsp;Yongxin Ma","doi":"10.1111/ahg.12521","DOIUrl":"10.1111/ahg.12521","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The protein encoded by the cartilage oligomeric matrix protein (<i>COMP</i>) gene is a noncollagenous extracellular matrix (ECM) protein that is important for chondrocyte formation and growth. Variations in the <i>COMP</i> gene cause pseudoachondroplasia (PSACH), which is mainly characterized by short-limbed dwarfing in the clinic.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>To characterize the function of a rare pathogenic variant in the <i>COMP</i> gene (c.875G &gt; A, p.Cys292Tyr).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials &amp; Methods</h3>\u0000 \u0000 <p>We performed 3D structural analysis, in vitro expression analysis, and immunofluorescence to characterize the effects of the variant on protein structure, expression, and cellular localization respectively.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Variation modeling showed that the interactions between amino acids were changed after the variation, and there were 31 changes in the secondary structure of mutant COMP (MT-COMP). Western blot showed that the intracellular quantity of MT-COMP was higher than the wild-type COMP (WT-COMP). Cellular immunofluorescence results showed that WT-COMP was less abundant and homogenously distributed in cells, while the MT-COMP accumulated in the cytoplasm.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Discussion</h3>\u0000 \u0000 <p>Herein, we report a variant of <i>COMP</i> in a Chinese family with PSACH. We have shown that the rare missense variant, <i>COMP</i> c.875G &gt; A, previously reported in ClinVar and identified in our patient, results in excessive accumulation of mutant protein in the cytoplasm, and is therefore pathogenic.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Through in silico and experimental analyses, we provide evidence that <i>COMP</i> c.875G &gt; A is the likely cause of PSACH in a Chinese family.</p>\u0000 </section>\u0000 </div>","PeriodicalId":8085,"journal":{"name":"Annals of Human Genetics","volume":"87 5","pages":"241-247"},"PeriodicalIF":1.9,"publicationDate":"2023-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10046593","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}
引用次数: 0
Uncovering cilia function in glial development 揭示纤毛在神经胶质发育中的功能。
IF 1.9 4区 生物学
Annals of Human Genetics Pub Date : 2023-07-10 DOI: 10.1111/ahg.12519
Rachel M. Bear, Tamara Caspary
{"title":"Uncovering cilia function in glial development","authors":"Rachel M. Bear,&nbsp;Tamara Caspary","doi":"10.1111/ahg.12519","DOIUrl":"10.1111/ahg.12519","url":null,"abstract":"<p>Primary cilia play critical roles in regulating signaling pathways that underlie several developmental processes. In the nervous system, cilia are known to regulate signals that guide neuron development. Cilia dysregulation is implicated in neurological diseases, and the underlying mechanisms remain poorly understood. Cilia research has predominantly focused on neurons and has overlooked the diverse population of glial cells in the brain. Glial cells play essential roles during neurodevelopment, and their dysfunction contributes to neurological disease; however, the relationship between cilia function and glial development is understudied. Here we review the state of the field and highlight the glial cell types where cilia are found and the ciliary functions that are linked to glial development. This work uncovers the importance of cilia in glial development and raises outstanding questions for the field. We are poised to make progress in understanding the function of glial cilia in human development and their contribution to neurological diseases.</p>","PeriodicalId":8085,"journal":{"name":"Annals of Human Genetics","volume":"88 1","pages":"27-44"},"PeriodicalIF":1.9,"publicationDate":"2023-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/ahg.12519","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9754660","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}
引用次数: 0
Pitfalls of predicting age-related traits by polygenic risk scores 通过多基因风险评分预测年龄相关特征的陷阱
IF 1.9 4区 生物学
Annals of Human Genetics Pub Date : 2023-07-07 DOI: 10.1111/ahg.12520
Valentina Escott-Price, Karl Michael Schmidt
{"title":"Pitfalls of predicting age-related traits by polygenic risk scores","authors":"Valentina Escott-Price,&nbsp;Karl Michael Schmidt","doi":"10.1111/ahg.12520","DOIUrl":"10.1111/ahg.12520","url":null,"abstract":"<p>Polygenic risk scores (PRS) are a method increasingly used to capture the combined effect of genome-wide significant variants and those which individually do not show genome-wide significant association but are likely to contribute to the risk of developing diseases. However, their practical use incurs complications and inconsistencies that so far limit their clinical applicability. The aims of the present review are to discuss the PRS for age-related diseases and to highlight pitfalls and limitations of PRS prediction accuracy due to ageing and mortality effects. We argue that the PRS is widely used but the individual's PRS values differ substantially depending on the number of genetic variants included, the discovery GWAS and the method employed to generate them. Moreover, for neurodegenerative disorders, although an individual's genetics do not change with age, the actual score depends on the age of the sample used in the discovery GWAS and is likely to reflect the individual's disease risk at this particular age. Improvement of PRS prediction accuracy for neurodegenerative disorders will come from two sides, both the precision of clinical diagnoses, and a careful attention to the age distribution in the underlying samples and validation of the prediction in longitudinal studies.</p>","PeriodicalId":8085,"journal":{"name":"Annals of Human Genetics","volume":"87 5","pages":"203-209"},"PeriodicalIF":1.9,"publicationDate":"2023-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/ahg.12520","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10053150","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}
引用次数: 2
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