Molecular Genetics and Genomics最新文献

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Diversity and potential functional role of phyllosphere-associated actinomycetota isolated from cupuassu (Theobroma grandiflorum) leaves: implications for ecosystem dynamics and plant defense strategies 从杯树叶中分离出的叶球相关放线菌的多样性和潜在功能作用:对生态系统动态和植物防御策略的影响
IF 3.1 3区 生物学
Molecular Genetics and Genomics Pub Date : 2024-07-27 DOI: 10.1007/s00438-024-02162-1
Jéssica Pereira de Matos, Dilson Fagundes Ribeiro, Ana Karla da Silva, Camila Henriques de Paula, Isabella Ferreira Cordeiro, Camila Gracyelle de Carvalho Lemes, Angélica Bianchini Sanchez, Lorrana Cachuite Mendes Rocha, Camila Carrião Machado Garcia, Nalvo F. Almeida, Rafael Moyses Alves, Vinicius A. C. de Abreu, Alessandro M. Varani, Leandro Marcio Moreira
{"title":"Diversity and potential functional role of phyllosphere-associated actinomycetota isolated from cupuassu (Theobroma grandiflorum) leaves: implications for ecosystem dynamics and plant defense strategies","authors":"Jéssica Pereira de Matos, Dilson Fagundes Ribeiro, Ana Karla da Silva, Camila Henriques de Paula, Isabella Ferreira Cordeiro, Camila Gracyelle de Carvalho Lemes, Angélica Bianchini Sanchez, Lorrana Cachuite Mendes Rocha, Camila Carrião Machado Garcia, Nalvo F. Almeida, Rafael Moyses Alves, Vinicius A. C. de Abreu, Alessandro M. Varani, Leandro Marcio Moreira","doi":"10.1007/s00438-024-02162-1","DOIUrl":"https://doi.org/10.1007/s00438-024-02162-1","url":null,"abstract":"<p>Exploring the intricate relationships between plants and their resident microorganisms is crucial not only for developing new methods to improve disease resistance and crop yields but also for understanding their co-evolutionary dynamics. Our research delves into the role of the phyllosphere-associated microbiome, especially Actinomycetota species, in enhancing pathogen resistance in <i>Theobroma grandiflorum</i>, or cupuassu, an agriculturally valuable Amazonian fruit tree vulnerable to witches’ broom disease caused by <i>Moniliophthora perniciosa</i>. While breeding resistant cupuassu genotypes is a possible solution, the capacity of the Actinomycetota phylum to produce beneficial metabolites offers an alternative approach yet to be explored in this context. Utilizing advanced long-read sequencing and metagenomic analysis, we examined Actinomycetota from the phyllosphere of a disease-resistant cupuassu genotype, identifying 11 Metagenome-Assembled Genomes across eight genera. Our comparative genomic analysis uncovered 54 Biosynthetic Gene Clusters related to antitumor, antimicrobial, and plant growth-promoting activities, alongside cutinases and type VII secretion system-associated genes. These results indicate the potential of phyllosphere-associated Actinomycetota in cupuassu for inducing resistance or antagonism against pathogens. By integrating our genomic discoveries with the existing knowledge of cupuassu’s defense mechanisms, we developed a model hypothesizing the synergistic or antagonistic interactions between plant and identified Actinomycetota during plant-pathogen interactions. This model offers a framework for understanding the intricate dynamics of microbial influence on plant health. In conclusion, this study underscores the significance of the phyllosphere microbiome, particularly Actinomycetota, in the broader context of harnessing microbial interactions for plant health. These findings offer valuable insights for enhancing agricultural productivity and sustainability.</p>","PeriodicalId":18816,"journal":{"name":"Molecular Genetics and Genomics","volume":"64 1","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141782269","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
Integrated analysis of methylation and transcriptome identifies a novel risk model for diagnosis, prognosis, and immune characteristics in head and neck squamous cell carcinoma. 甲基化和转录组的综合分析为头颈部鳞状细胞癌的诊断、预后和免疫特征确定了一个新的风险模型。
IF 2.3 3区 生物学
Molecular Genetics and Genomics Pub Date : 2024-07-20 DOI: 10.1007/s00438-024-02164-z
Jun-Wei Zhang, Xi-Lin Gao, Sheng Li, Shuang-Hao Zhuang, Qi-Wei Liang
{"title":"Integrated analysis of methylation and transcriptome identifies a novel risk model for diagnosis, prognosis, and immune characteristics in head and neck squamous cell carcinoma.","authors":"Jun-Wei Zhang, Xi-Lin Gao, Sheng Li, Shuang-Hao Zhuang, Qi-Wei Liang","doi":"10.1007/s00438-024-02164-z","DOIUrl":"https://doi.org/10.1007/s00438-024-02164-z","url":null,"abstract":"<p><strong>Background: </strong>DNA methylation is an important epigenetic modification that plays a crucial role in the development and progression of various tumors. However, the association between methylation‑driven genes and diagnosis, prognosis, and immune characteristics of head and neck squamous cell carcinoma (HNSCC) remains unclear.</p><p><strong>Methods: </strong>We obtained transcriptome, methylation, and clinical data from HNSCC patients in TCGA database, and used MethylMix algorithm to identify methylation-driven genes. A methylation driven gene-related risk model was constructed using Lasso regression analysis, and validated using data from GEO database. Immune infiltration and immune function analysis of the expression profiles were conducted using ssGSEA. Differences in immune checkpoint-related genes were analyzed, and the efficacy of immunotherapy was evaluated using TCIA database. Finally, a series of cell functional experiments were conducted to validate the results.</p><p><strong>Results: </strong>Five methylation-driven genes were identified and utilized to construct a prognostic risk model. Based on the median risk score, all patients were categorized into high-risk and low-risk groups. The K-M analysis revealed that patients in the high-risk group have a worse prognosis. Additionally, the risk model demonstrated better prognostic predictive value as indicated by ROC analysis. GSEA enrichment analysis indicated that gene sets in the high and low-risk groups were primarily enriched in pathways associated with tumor immunity and metabolism. Our subsequent investigations showed that high-risk patients exhibited more immunosuppressive phenotypes, while low-risk patients were more likely to respond positively to immunotherapy.</p><p><strong>Conclusion: </strong>These findings of our research have the potential to improve patient stratification, guide treatment decisions, and advance the development of personalized therapies for HNSCC.</p>","PeriodicalId":18816,"journal":{"name":"Molecular Genetics and Genomics","volume":"299 1","pages":"71"},"PeriodicalIF":2.3,"publicationDate":"2024-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141731350","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
A novel cancer-associated fibroblasts risk score model predict survival and immunotherapy in lung adenocarcinoma. 一种新型癌症相关成纤维细胞风险评分模型可预测肺腺癌患者的生存期和免疫疗法。
IF 2.3 3区 生物学
Molecular Genetics and Genomics Pub Date : 2024-07-17 DOI: 10.1007/s00438-024-02156-z
Fanhua Kong, Zhongshan Lu, Yan Xiong, Lihua Zhou, Qifa Ye
{"title":"A novel cancer-associated fibroblasts risk score model predict survival and immunotherapy in lung adenocarcinoma.","authors":"Fanhua Kong, Zhongshan Lu, Yan Xiong, Lihua Zhou, Qifa Ye","doi":"10.1007/s00438-024-02156-z","DOIUrl":"https://doi.org/10.1007/s00438-024-02156-z","url":null,"abstract":"<p><p>Lung adenocarcinoma (LUAD) is the leading cause of cancer-related death worldwide. Cancer-associated fibroblasts (CAFs) are a special type of fibroblasts, which play an important role in the development and immune escape of tumors. Weighted gene co-expression network analysis (WGCNA) was used to construct the co-expression module. In combination with univariate Cox regression and analysis of least absolute shrinkage operator (LASSO), characteristics associated with CAFs were developed for a prognostic model. The migration and proliferation of lung cancer cells were evaluated in vitro. Finally, the expression levels of proteins were analyzed by Western blot. LASSO Cox regression algorithm was then performed to select hub genes. Finally, a total of 2 Genes (COL5A2, COL6A2) were obtained. We then divided LUAD patients into high- and low-risk groups based on CAFs risk scores. Survival analysis, CAFs score correlation analysis and tumor mutation load analysis showed that COL5A2 and COL6A2 were high-risk genes for LUAD. Human Protein Atlas (HPA), western blot and PCR results showed that COL5A2 and COL6A2 were up-regulated in LUAD tissues. When COL5A2 and COL6A2 were knocked down, the proliferation, invasion and migration of lung cancer cells were significantly decreased. Finally, COL5A2 can affect LUAD progression through the Wnt/β-Catenin and TGF-β signaling pathways. Our CAFs risk score model offers a new approach for predicting the prognosis of LUAD patients. Furthermore, the identification of high-risk genes COL5A2 and COL6A2 and drug sensitivity analysis can provide valuable candidate clues for clinical treatment of LUAD.</p>","PeriodicalId":18816,"journal":{"name":"Molecular Genetics and Genomics","volume":"299 1","pages":"70"},"PeriodicalIF":2.3,"publicationDate":"2024-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141627192","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
A novel homozygous missense TTC12 variant identified in an infertile Pakistani man with severe oligoasthenoteratozoospermia and primary ciliary dyskinesia. 在一名患有严重少精症和原发性睫状肌运动障碍的不育巴基斯坦男子体内发现了一种新型同卵错义 TTC12 变异体。
IF 2.3 3区 生物学
Molecular Genetics and Genomics Pub Date : 2024-07-12 DOI: 10.1007/s00438-024-02161-2
Imtiaz Ali, Haider Ali, Ahsanullah Unar, Fazal Rahim, Khalid Khan, Sobia Dil, Tanveer Abbas, Ansar Hussain, Aurang Zeb, Muhammad Zubair, Huan Zhang, Hui Ma, Xiaohua Jiang, Muzammil Ahmad Khan, Bo Xu, Wasim Shah, Qinghua Shi
{"title":"A novel homozygous missense TTC12 variant identified in an infertile Pakistani man with severe oligoasthenoteratozoospermia and primary ciliary dyskinesia.","authors":"Imtiaz Ali, Haider Ali, Ahsanullah Unar, Fazal Rahim, Khalid Khan, Sobia Dil, Tanveer Abbas, Ansar Hussain, Aurang Zeb, Muhammad Zubair, Huan Zhang, Hui Ma, Xiaohua Jiang, Muzammil Ahmad Khan, Bo Xu, Wasim Shah, Qinghua Shi","doi":"10.1007/s00438-024-02161-2","DOIUrl":"https://doi.org/10.1007/s00438-024-02161-2","url":null,"abstract":"<p><p>TTC12 is a cytoplasmic and centromere-localized protein that plays a role in the proper assembly of dynein arm complexes in motile cilia in both respiratory cells and sperm flagella. This finding underscores its significance in cellular motility and function. However, the wide role of TTC12 in human spermatogenesis-associated primary ciliary dyskinesia (PCD) still needs to be elucidated. Whole-exome sequencing (WES) and Sanger sequencing were performed to identify potentially pathogenic variants causing PCD and multiple morphological abnormalities of sperm flagella (MMAF) in an infertile Pakistani man. Diagnostic imaging techniques were used for PCD screening in the patient. Real-time polymerase chain reaction (RT‒PCR) was performed to detect the effect of mutations on the mRNA abundance of the affected genes. Papanicolaou staining and scanning electron microscopy (SEM) were carried out to examine sperm morphology. Transmission electron microscopy (TEM) was performed to examine the ultrastructure of the sperm flagella, and the results were confirmed by immunofluorescence staining. Using WES and Sanger sequencing, a novel homozygous missense variant (c.C1069T; p.Arg357Trp) in TTC12 was identified in a patient from a consanguineous family. A computed tomography scan of the paranasal sinuses confirmed the symptoms of the PCD. RT-PCR showed a decrease in TTC12 mRNA in the patient's sperm sample. Papanicolaou staining, SEM, and TEM analysis revealed a significant change in shape and a disorganized axonemal structure in the sperm flagella of the patient. Immunostaining assays revealed that TTC12 is distributed throughout the flagella and is predominantly concentrated in the midpiece in normal spermatozoa. In contrast, spermatozoa from patient deficient in TTC12 showed minimal staining intensity for TTC12 or DNAH17 (outer dynein arms components). This could lead to MMAF and result in male infertility. This novel TTC12 variant not only illuminates the underlying genetic causes of male infertility but also paves the way for potential treatments targeting these genetic factors. This study represents a significant advancement in understanding the genetic basis of PCD-related infertility.</p>","PeriodicalId":18816,"journal":{"name":"Molecular Genetics and Genomics","volume":"299 1","pages":"69"},"PeriodicalIF":2.3,"publicationDate":"2024-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141590801","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
Population dynamics and genetic isolation in the Central Himalayan region: insights from Sikkim population, India. 喜马拉雅中部地区的种群动态和遗传隔离:印度锡金种群的启示。
IF 2.3 3区 生物学
Molecular Genetics and Genomics Pub Date : 2024-07-09 DOI: 10.1007/s00438-024-02160-3
Gaurav Priyank, Avinash Vahinde, Penny H Niranjan, Vivek Sahajpal, Deepika Bhandari, Ajay S Rana, Satish Kumar, Malay Shukla, Sweta Nidhi, Abhishek Singh
{"title":"Population dynamics and genetic isolation in the Central Himalayan region: insights from Sikkim population, India.","authors":"Gaurav Priyank, Avinash Vahinde, Penny H Niranjan, Vivek Sahajpal, Deepika Bhandari, Ajay S Rana, Satish Kumar, Malay Shukla, Sweta Nidhi, Abhishek Singh","doi":"10.1007/s00438-024-02160-3","DOIUrl":"10.1007/s00438-024-02160-3","url":null,"abstract":"<p><p>India's rich diversity encompasses individuals from varied geographical, cultural, and ethnic backgrounds. In the field of population genetics, comprehending the genetic diversity across distinct populations plays a crucial role. This study presents significant findings from genetic data obtained from the Sikkimese population of India. Autosomal markers were crucial for evaluating forensic parameters, with a combined paternity index of 1 × 10<sup>9</sup>. Notably, Penta E emerged as a distinguishing marker for individual identification in the Sikkim population. Fst genetic distance values revealed insights into genetic isolation among different groups, enhancing our understanding of population dynamics in the central Himalayan region. The NJ-based phylogenetic tree highlighted close genetic relationships, of the Sikkim population with the Nepalese population surrounding neighbouring Himalayan populations providing glimpses into common ancestry. In summary, this study contributes valuable data to population genetics and underscores the importance of genetic variation in comprehending population dynamics and forensic applications.</p>","PeriodicalId":18816,"journal":{"name":"Molecular Genetics and Genomics","volume":"299 1","pages":"67"},"PeriodicalIF":2.3,"publicationDate":"2024-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141559267","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
Delineation of the phenotypes and genotypes of PIK3CA-related overgrowth spectrum in East asians. 划定东亚人与 PIK3CA 相关的过度生长谱系的表型和基因型。
IF 2.3 3区 生物学
Molecular Genetics and Genomics Pub Date : 2024-07-09 DOI: 10.1007/s00438-024-02159-w
Hongrui Chen, Bin Sun, Hongyuan Liu, Wei Gao, Yajing Qiu, Chen Hua, Xiaoxi Lin
{"title":"Delineation of the phenotypes and genotypes of PIK3CA-related overgrowth spectrum in East asians.","authors":"Hongrui Chen, Bin Sun, Hongyuan Liu, Wei Gao, Yajing Qiu, Chen Hua, Xiaoxi Lin","doi":"10.1007/s00438-024-02159-w","DOIUrl":"10.1007/s00438-024-02159-w","url":null,"abstract":"<p><p>PIK3CA-related overgrowth spectrum (PROS) is an umbrella term to describe a diverse range of developmental disorders. Research to date has predominantly emerged from Europe and North America, resulting in a notable scarcity of studies focusing on East Asian populations. Currently, the prevalence and distribution of PIK3CA variants across various genetic loci and their correlation with distinct phenotypes in East Asian populations remain unclear. This study aims to elucidate the phenotype-genotype correlations of PROS in East Asian populations. We presented the phenotypes and genotypes of 82 Chinese patients. Among our cohort, 67 individuals carried PIK3CA variants, including missense, frameshift, and splice variants. Six patients presented with both PIK3CA and an additional variant. Seven PIK3CA-negative patients exhibited overlapping PROS manifestations with variants in GNAQ, AKT1, PTEN, MAP3K3, GNA11, or KRAS. An integrative review of the literature pertaining to East Asian populations revealed that specific variants are uniquely associated with certain PROS phenotypes. Some rare variants were exclusively identified in cases of megalencephaly and diffuse capillary malformation with overgrowth. Non-hotspot variants with undefined oncogenicity were more common in CNS phenotypes. Diseases with vascular malformation were more likely to have variants in the helical domain, whereas phenotypes involving adipose/muscle overgrowth without vascular abnormalities predominantly presented variants in the C2 domain. Our findings underscore the unique phenotype-genotype patterns within the East Asian PROS population, highlighting the necessity for an expanded cohort to further elucidate these correlations. Such endeavors would significantly facilitate the development of PI3Kα selective inhibitors tailored for the East Asian population in the future.</p>","PeriodicalId":18816,"journal":{"name":"Molecular Genetics and Genomics","volume":"299 1","pages":"66"},"PeriodicalIF":2.3,"publicationDate":"2024-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141559266","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
Understanding the role of P-type ATPases in regulating pollen fertility and development in pigeonpea. 了解 P 型 ATP 酶在调节鸽子豆花粉育性和发育中的作用。
IF 2.3 3区 生物学
Molecular Genetics and Genomics Pub Date : 2024-07-09 DOI: 10.1007/s00438-024-02155-0
Rishu Jain, Harsha Srivastava, Kuldeep Kumar, Sandhya Sharma, Anandita Singh, Kishor Gaikwad
{"title":"Understanding the role of P-type ATPases in regulating pollen fertility and development in pigeonpea.","authors":"Rishu Jain, Harsha Srivastava, Kuldeep Kumar, Sandhya Sharma, Anandita Singh, Kishor Gaikwad","doi":"10.1007/s00438-024-02155-0","DOIUrl":"https://doi.org/10.1007/s00438-024-02155-0","url":null,"abstract":"<p><p>The P-type ATPase superfamily genes are the cation and phospholipid pumps that transport ions across the membranes by hydrolyzing ATP. They are involved in a diverse range of functions, including fundamental cellular events that occur during the growth of plants, especially in the reproductive organs. The present work has been undertaken to understand and characterize the P-type ATPases in the pigeonpea genome and their potential role in anther development and pollen fertility. A total of 59 P-type ATPases were predicted in the pigeonpea genome. The phylogenetic analysis classified the ATPases into five subfamilies: eleven P1B, eighteen P2A/B, fourteen P3A, fifteen P4, and one P5. Twenty-three pairs of P-type ATPases were tandemly duplicated, resulting in their expansion in the pigeonpea genome during evolution. The orthologs of the reported anther development-related genes were searched in the pigeonpea genome, and the expression profiling studies of specific genes via qRT-PCR in the pre- and post-meiotic anther stages of AKCMS11A (male sterile), AKCMS11B (maintainer) and AKPR303 (fertility restorer) lines of pigeonpea was done. Compared to the restorer and maintainer lines, the down-regulation of CcP-typeATPase22 in the post-meiotic anthers of the male sterile line might have played a role in pollen sterility. Furthermore, the strong expression of CcP-typeATPase2 in the post-meiotic anthers of restorer line and CcP-typeATPase46, CcP-typeATPase51, and CcP-typeATPase52 in the maintainer lines, respectively, compared to the male sterile line, clearly indicates their potential role in developing male reproductive organs in pigeonpea.</p>","PeriodicalId":18816,"journal":{"name":"Molecular Genetics and Genomics","volume":"299 1","pages":"68"},"PeriodicalIF":2.3,"publicationDate":"2024-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141559268","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
Unveiling novel genetic variants in 370 challenging medically relevant genes using the long read sequencing data of 41 samples from 19 global populations. 利用来自全球 19 个人群的 41 个样本的长读测序数据,揭示 370 个具有挑战性的医学相关基因中的新型基因变异。
IF 2.3 3区 生物学
Molecular Genetics and Genomics Pub Date : 2024-07-07 DOI: 10.1007/s00438-024-02158-x
Yanfeng Ji, Junfan Zhao, Jiao Gong, Fritz J Sedlazeck, Shaohua Fan
{"title":"Unveiling novel genetic variants in 370 challenging medically relevant genes using the long read sequencing data of 41 samples from 19 global populations.","authors":"Yanfeng Ji, Junfan Zhao, Jiao Gong, Fritz J Sedlazeck, Shaohua Fan","doi":"10.1007/s00438-024-02158-x","DOIUrl":"10.1007/s00438-024-02158-x","url":null,"abstract":"<p><strong>Background: </strong>A large number of challenging medically relevant genes (CMRGs) are situated in complex or highly repetitive regions of the human genome, hindering comprehensive characterization of genetic variants using next-generation sequencing technologies. In this study, we employed long-read sequencing technology, extensively utilized in studying complex genomic regions, to characterize genetic alterations, including short variants (single nucleotide variants and short insertions and deletions) and copy number variations, in 370 CMRGs across 41 individuals from 19 global populations.</p><p><strong>Results: </strong>Our analysis revealed high levels of genetic variants in CMRGs, with 68.73% exhibiting copy number variations and 65.20% containing short variants that may disrupt protein function across individuals. Such variants can influence pharmacogenomics, genetic disease susceptibility, and other clinical outcomes. We observed significant differences in CMRG variation across populations, with individuals of African ancestry harboring the highest number of copy number variants and short variants compared to samples from other continents. Notably, 15.79% to 33.96% of short variants were exclusively detectable through long-read sequencing. While the T2T-CHM13 reference genome significantly improved the assembly of CMRG regions, thereby facilitating variant detection in these regions, some regions still lacked resolution.</p><p><strong>Conclusion: </strong>Our results provide an important reference for future clinical and pharmacogenetic studies, highlighting the need for a comprehensive representation of global genetic diversity in the reference genome and improved variant calling techniques to fully resolve medically relevant genes.</p>","PeriodicalId":18816,"journal":{"name":"Molecular Genetics and Genomics","volume":"299 1","pages":"65"},"PeriodicalIF":2.3,"publicationDate":"2024-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11955097/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141545043","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
Catalyzing precision: unraveling the diagnostic conundrum of tunisian familial hypophosphatasia case through integrative clinical and molecular approaches. 精准催化:通过综合临床和分子方法揭开突尼斯家族性低磷血症病例的诊断难题。
IF 2.3 3区 生物学
Molecular Genetics and Genomics Pub Date : 2024-06-23 DOI: 10.1007/s00438-024-02157-y
Yessine Amri, Rym Dabboubi, Monia Khemiri, Elham Jebabli, Sondess Hadj Fredj, Sarra Ben Ahmed, Yosr Jouini, Faida Ouali, Taieb Messaoud
{"title":"Catalyzing precision: unraveling the diagnostic conundrum of tunisian familial hypophosphatasia case through integrative clinical and molecular approaches.","authors":"Yessine Amri, Rym Dabboubi, Monia Khemiri, Elham Jebabli, Sondess Hadj Fredj, Sarra Ben Ahmed, Yosr Jouini, Faida Ouali, Taieb Messaoud","doi":"10.1007/s00438-024-02157-y","DOIUrl":"https://doi.org/10.1007/s00438-024-02157-y","url":null,"abstract":"<p><p>Familial Hypophosphatasia presents a complex diagnostic challenge due to its wide-ranging clinical manifestations and genetic heterogeneity. This study aims to elucidate the molecular underpinnings of familial Hypophosphatasia within a Tunisian family harboring a rare c.896 T > C mutation in the ALPL gene, offering insights into genotype-phenotype correlations and potential therapeutic avenues. The study employs a comprehensive approach, integrating biochemical examination, genetic analysis, structural modeling, and functional insights to unravel the impact of this rare mutation. Genetic investigation revealed the presence of the p.Leu299Pro mutation within the ALPL gene in affected family members. This mutation is strategically positioned in proximity to both the catalytic site and the metal-binding domain, suggesting potential functional consequences. Homology modeling techniques were employed to predict the 3D structure of TNSALP, providing insights into the structural context of the mutation. Our findings suggest that the mutation may induce conformational changes in the vicinity of the catalytic site and metal-binding domain, potentially affecting substrate recognition and catalytic efficiency. Molecular dynamics simulations were instrumental in elucidating the dynamic behavior of the tissue-nonspecific alkaline phosphatase isozyme (TNSALP) in the presence of the p.Leu299Pro mutation. The simulations indicated alterations in structural flexibility near the mutation site, with potential ramifications for the enzyme's overall stability and function. These dynamic changes may influence the catalytic efficiency of TNSALP, shedding light on the molecular underpinnings of the observed clinical manifestations within the Tunisian family. The clinical presentation of affected individuals highlighted significant phenotypic heterogeneity, underscoring the complex genotype-phenotype correlations in familial Hypophosphatasia. Variability in age of onset, severity of symptoms, and radiographic features was observed, emphasizing the need for a nuanced understanding of the clinical spectrum associated with the p.Leu299Pro mutation. This study advances our understanding of familial Hypophosphatasia by delineating the molecular consequences of the p.Leu299Pro mutation in the ALPL gene. By integrating genetic, structural, and clinical analyses, we provide insights into disease pathogenesis and lay the groundwork for personalized therapeutic strategies tailored to specific genetic profiles. Our findings underscore the importance of comprehensive genetic and clinical evaluation in guiding precision medicine approaches for familial Hypophosphatasia.</p>","PeriodicalId":18816,"journal":{"name":"Molecular Genetics and Genomics","volume":"299 1","pages":"64"},"PeriodicalIF":2.3,"publicationDate":"2024-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141440690","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
Correction: Genetic evidence for a single founding population of the Lakshadweep Islands. 更正:拉克沙德韦普群岛单一始祖种群的遗传证据。
IF 2.3 3区 生物学
Molecular Genetics and Genomics Pub Date : 2024-06-21 DOI: 10.1007/s00438-024-02154-1
Sachin Kumar, Prajjval Pratap Singh, Nagarjuna Pasupuleti, Shivanand S Shendre, Jaison Jeevan Sequeira, Idrees Babu, Mohammed S Mustak, Niraj Rai, Gyaneshwer Chaubey
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