Frontiers in Genetics最新文献

{"title":"Identification of key miRNAs and target genes in extracellular vesicles derived from low-intensity pulsed ultrasound-treated stem cells.","authors":"Xin Yin, Jialian Yi, Fugang Mao, Qisheng Tang, Xinyu Zhang, Xiaoyu Yang, Hongqing Xie, Linping Wang, Shuifen Sun, Xin Yu, Jie Liu, Lihong Jiang","doi":"10.3389/fgene.2024.1407671","DOIUrl":"https://doi.org/10.3389/fgene.2024.1407671","url":null,"abstract":"<p><strong>Objectives: </strong>This study aimed to investigate the impact of low-intensity pulsed ultrasound (LIPUS) treatment on the miRNA and mRNA profiles of stem cell-derived extracellular vesicles (EVs). Specifically, it sought to identify key miRNAs and their target mRNAs associated with enhanced therapeutic efficacy in LIPUS-treated stem cell-derived EVs.</p><p><strong>Methods: </strong>Utilizing miRNA deep-sequencing data from the Gene Expression Omnibus database, differential gene analysis was performed. MiRNA-mRNA target analysis, functional and pathway enrichment analysis, protein-protein interaction network construction, and hub gene identification were conducted. Validation of differentially expressed miRNAs was performed via RT-qPCR in human umbilical cord mesenchymal stem cells (hUC-MSCs) treated with LIPUS.</p><p><strong>Results: </strong>Ten differentially expressed miRNAs were identified, with six upregulated and four downregulated miRNAs in LIPUS-treated stem cell-derived EVs. Functional enrichment analysis revealed involvement in biological processes such as regulation of metabolic processes, cellular component organization, and response to stress, as well as signaling pathways like cell cycle, MAPK signaling, and Hippo signaling. Protein-protein interaction network analysis identified key hub genes including MYC, GAPDH, HSP90AA1, EP300, JUN, PTEN, DAC1, STAT3, HSPA8, and HIF1A associated with LIPUS treatment. RT-qPCR validation confirmed differential expression of selected miRNAs (hsa-miR-933, hsa-miR-3943, hsa-miR-4633-5p, hsa-miR-592, hsa-miR-659-5p, hsa-miR-4766-3p) in LIPUS-treated hUC-MSCs.</p><p><strong>Conclusion: </strong>This study sheds light on the potential therapeutic mechanisms underlying LIPUS-treated stem cell-derived EVs. The identified differentially expressed miRNAs and their potential target mRNAs offer valuable insights into the biological processes influenced by LIPUS treatment. While further investigation is necessary to validate their roles as therapeutic targets, this study lays the groundwork for future research on optimizing SC-EV therapy with LIPUS preconditioning.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"15 ","pages":"1407671"},"PeriodicalIF":2.8,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11774887/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143065156","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}

{"title":"Integrating single-cell RNA-seq and bulk RNA-seq to explore prognostic value and immune landscapes of methionine metabolism-related signature in breast cancer.","authors":"Yanxian Gao, Ziyu Feng, Hailong Zhao, Xinghai Liu, Muyu Zhu, Xiafei Yu, Xiaoan Liu, Xian Wu, Jing Tao","doi":"10.3389/fgene.2024.1521269","DOIUrl":"10.3389/fgene.2024.1521269","url":null,"abstract":"<p><strong>Background: </strong>Neoadjuvant, endocrine, and targeted therapies have significantly improved the prognosis of breast cancer (BC). However, due to the high heterogeneity of cancer, some patients cannot benefit from existing treatments. Increasing evidence suggests that amino acids and their metabolites can alter the tumor malignant behavior through reshaping tumor microenvironment and regulation of immune cell function. Breast cancer cell lines have been identified as methionine-dependent, and methionine restriction has been proposed as a potential cancer treatment strategy.</p><p><strong>Methods: </strong>We integrated transcriptomic and single-cell RNA sequencing (ScRNA-seq) analyses based on The Cancer Genome Atlas (TCGA) database and Gene Expression Omnibus (GEO) datasets. Then we applied weighted gene co-expression network analysis (WGCNA) and Cox regression to evaluate methionine metabolism-related genes (MRGs) in BC, constructing and validating a prognostic model for BC patients. Immune landscapes and immunotherapy were further explored. Finally, <i>in vitro</i> experiments were conducted to assess the expression and function of key genes APOC1.</p><p><strong>Results: </strong>In this study, we established and validated a prognostic signature based on eight methionine-related genes to predict overall survival (OS) in BC patients. Patients were further stratified into high-risk and low-risk groups according to prognostic risk score. Further analysis revealed significant differences between two groups in terms of pathway alterations, immune microenvironment characteristics, and immune checkpoint expression. Our study shed light on the relationship between methionine metabolism and immune infiltration in BC. APOC1, a key gene in the prognostic signature, was found to be upregulated in BC and closely associated with immune cell infiltration. Notably, APOC1 was primarily expressed in macrophages. Subsequent <i>in vitro</i> experiments demonstrated that silencing APOC1 reduced the generation of tumor-associated macrophages (TAMs) with an M2 phenotype while significantly decreasing the proliferation, invasion, and migration of MDA-MB-231 and MDA-MB-468 breast cancer cell lines.</p><p><strong>Conclusion: </strong>We established a prognostic risk score consisting of genes associated with methionine metabolism, which helps predict prognosis and response to treatment in BC. The function of APOC1 in regulating macrophage polarization was explored.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"15 ","pages":"1521269"},"PeriodicalIF":2.8,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11772272/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143058832","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}

{"title":"Improving prenatal diagnosis with combined karyotyping, CNV-seq and QF-PCR: a comprehensive analysis of chromosomal abnormalities in high-risk pregnancies.","authors":"Jia-Pei Liu, Shan-Bing Wang, Li Luo, Ya-Mei Guo","doi":"10.3389/fgene.2024.1517270","DOIUrl":"10.3389/fgene.2024.1517270","url":null,"abstract":"<p><strong>Objective: </strong>This study aims to assess the diagnostic efficacy of a combined approach integrating chromosomal karyotyping, copy number variation sequencing (CNV-seq), and quantitative fluorescence polymerase chain reaction (QF-PCR) in detecting chromosomal abnormalities in high-risk pregnancies.</p><p><strong>Methods: </strong>This retrospective study analyzed 617 high-risk pregnancies undergoing prenatal diagnosis from February 2023 to August 2024, with amniotic fluid samples concurrently analyzed using karyotyping, CNV-seq, and QF-PCR. We evaluated clinical characteristics, diagnostic yields, and inter-method concordance rates. Longitudinal follow-up assessed pregnancy outcomes and neonatal phenotypes, with particular emphasis on cases demonstrating diagnostic discrepancies or variants of uncertain clinical significance.</p><p><strong>Results: </strong>The integrated approach detected chromosomal abnormalities in 12.5% (77/617) of cases, significantly higher than the rates achieved by karyotyping alone (9.7%) and CNV-seq/QF-PCR alone (8.3%) (<i>p</i> < 0.05). Karyotyping showed full concordance with CNV-seq and QF-PCR in detecting major chromosomal aneuploidies, identifying 21 cases of trisomy 21 and 4 cases of trisomy 18. CNV-seq uniquely identified additional pathogenic copy number variations in 2.1% of cases and variants of uncertain significance (VUS) in 3.2% of cases, both undetectable by conventional karyotyping. Subjects with high-risk non-invasive prenatal testing (NIPT) results had the highest abnormality detection rate (57.6%, <i>p</i> < 0.05). Follow-up data revealed pregnancy termination in 44 of 97 cases with chromosomal abnormalities. Notably, neonates carrying pathogenic CNVs inherited from asymptomatic parents demonstrated normal phenotypes.</p><p><strong>Conclusion: </strong>The integration of karyotyping, CNV-seq, and QF-PCR provides superior diagnostic yield compared to individual testing strategies in high-risk pregnancies. Although karyotyping remains the gold standard for detecting major chromosomal aberrations, CNV-seq and QF-PCR enhance diagnostic precision through detection of submicroscopic variations. Multi-center studies with larger cohorts are needed to confirm these findings and clarify the clinical significance of uncertain variants.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"15 ","pages":"1517270"},"PeriodicalIF":2.8,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11770095/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143052334","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}

{"title":"Genetic variation in patent foramen ovale: a case-control genome-wide association study.","authors":"Bosi Dong, Yajiao Li, Fandi Ai, Jia Geng, Ting Tang, Wan Peng, Yusha Tang, Hui Wang, Zixuan Tian, Fengxiao Bu, Lei Chen","doi":"10.3389/fgene.2024.1523304","DOIUrl":"10.3389/fgene.2024.1523304","url":null,"abstract":"<p><strong>Background: </strong>Patent foramen ovale (PFO) is a congenital defect between the atria, resulting in abnormal hemodynamics. We conducted a genome-wide association study (GWAS) to identify common genetic variants associated with PFO.</p><p><strong>Methods: </strong>We performed a whole genome sequencing in a discovery cohort of 3,227 unrelated Chinese participants screened for PFO via contrast transthoracic echocardiography (cTTE). Single-nucleotide polymorphisms (SNPs) associated with PFO were further validated by Sanger sequencing and subsequently were evaluated in a validation cohort. Expression quantitative trait loci (eQTL) analysis was conducted using the GTEx database. Single-cell sequencing analyses with pseudotime trajectory modeling were employed to evaluate their expression in human fetal hearts.</p><p><strong>Results: </strong>The case-control GWAS of discovery cohort ultimately included 517 cases and 517 demographically matched controls. Of the 7,040,407 variants assessed, we identified rs1227675732 (OR = 2.903; 95% CI, 1.961 to 4.297; <i>p</i> = 3.05 × 10^-8), rs62206790 (OR = 2.780; 95% CI, 1.864 to 4.146; <i>p</i> = 2.02 × 10^-7), rs879176184 (OR = 2.724; 95% CI, 1.822 to 4.073; <i>p</i> = 4.30 × 10^-7) and rs13115019 (OR = 2.437; 95% CI, 1.702 to 3.488; <i>p</i> = 5.80 × 10^-7) as high-risk variants for PFO, while rs57922961 (OR = 0.5081; 95% CI, 0.388 to 0.666; <i>p</i> = 6.82 × 10^-7) was identified as protective variant. These variations were replicated in the validation cohort (111 cases and 152 controls). Single-cell sequencing showed that <i>CNOT2</i>, <i>KCNMB4</i>, <i>MLLT10</i>, <i>IGBP1</i>, and <i>FRG1</i> were highly expressed with significant changes during heart development.</p><p><strong>Conclusion: </strong>The identification of susceptible loci for PFO might provide insights into the pathogenesis of PFO and contribute to understanding heart development.</p><p><strong>Clinical trial registration: </strong>https://www.chictr.org.cn/showproj.html?proj=40590, identifier ChiCTR1900024623.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"15 ","pages":"1523304"},"PeriodicalIF":2.8,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11769951/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143052333","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}

{"title":"Uncovering somatic mosaic variants of <i>PIK3CA</i>-related overgrowth disorders - three cases with different clinical presentations.","authors":"M Tooming, P Mertsina, T Kahre, R Teek, I Vainumäe, S Lilles, M H Wojcik, P Ilves, K Õunap","doi":"10.3389/fgene.2024.1484651","DOIUrl":"10.3389/fgene.2024.1484651","url":null,"abstract":"<p><strong>Introduction: </strong><i>PIK3CA</i> related disorders (PRD, OMIM: *171834) are genetic disorders resulting from pathogenic somatic mosaic variants in the <i>PIK3CA</i> gene, which encodes a protein crucial for regulating cell growth and division. PRD typically manifest during the post-zygotic phase, leading to a broad spectrum of overgrowth and vascular malformations affecting various body regions.</p><p><strong>Methods: </strong>Conventional diagnostic methods struggle to detect and confirm pathogenic PIK3CA gene variants due to the mosaic nature of these disorders and the limited accessibility of affected tissues. In this study, we conducted comprehensive genomic profiling on a cohort of individuals with PRD to address these diagnostic challenges.</p><p><strong>Results: </strong>Our analysis revealed significant diagnostic challenges posed by somatic mosaicism in PRD. The comprehensive genomic profiling allowed for the meticulous evaluation of potentially pathogenic gene variants in affected individuals and their corresponding tissues.</p><p><strong>Discussion: </strong>Our findings advocate for the adoption of comprehensive genomic profiling in clinical practice to improve the detection and management of PRD. This approach can enhance patient care by providing a more accurate diagnosis and better understanding of the genetic underpinnings of PRD.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"15 ","pages":"1484651"},"PeriodicalIF":2.8,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11769973/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143052335","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}

{"title":"Comprehensive analysis of ferroptosis-related genes reveals potential therapeutic targets in osteoporosis patients: a computational analysis and <i>in vitro</i> experiments.","authors":"Sihui Chen, Yi Jiang, Guoqin Xie, Peng Wu, Jinyu Zhu","doi":"10.3389/fgene.2024.1522809","DOIUrl":"10.3389/fgene.2024.1522809","url":null,"abstract":"<p><strong>Background: </strong>Ferroptosis-related genes have been reported to play important roles in many diseases, but their molecular mechanisms in osteoporosis have not been elucidated.</p><p><strong>Methods: </strong>Based on two independent GEO datasets (GSE35956 and GSE35958), and GSE35959 as the validation dataset, we comprehensively elucidated the pathological mechanism of ferroptosis-related genes in osteoporosis by GO analyses, KEGG analyses and a PPI network. Then, We used Western Blot (WB) and Quantitative real-time polymerase chain reaction (qPCR) to verify the expression level of KMT2D, a ferroptosis-related hub gene, in clinical samples. Subsequently, we predicted the upstream miRNA of KMT2D gene and analyzed the mechanism of KMT2D in osteoporosis, the potential prognostic value and its immune invasion of KMT2D in pan-cancer.</p><p><strong>Results: </strong>This study identified KMT2D and MYCN, TP63, RELA, SOX2, and CDKN1A as key ferroptosis-related genes in osteoporotic cell aging. The independent dataset validated that the expression level of KMT2D was significantly upregulated in osteoporosis samples. The experimental verification results of qPCR and WB indicate that KMT2D is highly expressed in patients with osteoporosis. Further analysis revealed that the hsa-miR-204-5p-KMT2D axis may play an important role in the aging of osteoporotic cells. The analysis of KMT2D reveals that KMT2D may mainly play a role in the aging of osteoporotic cells through epigenetics and the value in pan-cancer.</p><p><strong>Conclusion: </strong>The study provides a theoretical basis for the treatment of osteoporosis.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"15 ","pages":"1522809"},"PeriodicalIF":2.8,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11757248/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143046394","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}

{"title":"Depression-related innate immune genes and pan-cancer gene analysis and validation.","authors":"Yakun Yang, Wei Han, Xiaoyu Zhang, Hao Yuan, Ran Wang, Jia Yang, Cuixia An, Dongyang Huang","doi":"10.3389/fgene.2024.1521238","DOIUrl":"10.3389/fgene.2024.1521238","url":null,"abstract":"<p><strong>Background: </strong>Depression, a prevalent chronic mental disorder, presents complexities and treatment challenges that drive researchers to seek new, precise therapeutic targets. Additionally, the potential connection between depression and cancer has garnered significant attention.</p><p><strong>Methods: </strong>This study analyzed depression-related gene expression data from the GEO database. Using data normalization, differential expression analysis, WGCNA, and machine learning, we identified core genes strongly associated with depression. These genes were validated in depression patients through q-PCR and examined for expression patterns and potential roles across various cancers.</p><p><strong>Results: </strong>We identified six core genes (GRB10, TDRD9, BCL7A, GPR18, KLRG1, and THEM4) significantly associated with depression and cancer. In depression, GRB10 and TDRD9, involved in cell growth and stress responses, exhibited elevated expression, while BCL7A, GPR18, KLRG1, and THEM4, linked to immune regulation and apoptosis, showed reduced expression, suggesting dysregulated cellular signaling and impaired immune function. In cancer, these genes displayed altered expression patterns across tumor types, influencing tumor progression, prognosis, and immune microenvironment modulation. Shared molecular pathways, such as immune dysregulation and apoptosis, highlight their potential as biomarkers and therapeutic targets for both depression and cancer.</p><p><strong>Conclusion: </strong>This study integrates bioinformatics and machine learning to uncover key molecular pathways and targets for depression, introducing innovative therapeutic prospects that may enhance precision treatment for depression. Furthermore, by revealing shared mechanisms between depression and cancer, we have identified six core genes with significant functional roles in immune regulation, apoptosis, and cellular signaling. These findings not only deepen our understanding of the molecular overlap between these conditions but also lay the groundwork for developing dual-targeted therapeutic strategies. This study uniquely contributes to bridging mental health and oncology research, offering new insights and hope for improving patient outcomes in both fields.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"15 ","pages":"1521238"},"PeriodicalIF":2.8,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11757255/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143046395","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}

{"title":"Single-cell RNA sequencing elucidates cellular plasticity in esophageal small cell carcinoma following chemotherapy treatment.","authors":"Qinkai Zhang, Ziyu Gao, Ru Qiu, Jizhao Cao, Chunxiao Zhang, Wei Qin, Meiling Yang, Xinyue Wang, Ciqiu Yang, Jie Li, Dongyang Yang","doi":"10.3389/fgene.2024.1477705","DOIUrl":"10.3389/fgene.2024.1477705","url":null,"abstract":"<p><p>Small cell carcinoma of the esophagus (SCCE) is a rare and aggressively progressing malignancy that presents considerable clinical challenges.Although chemotherapy can effectively manage symptoms during the earlystages of SCCE, its long-term effectiveness is notably limited, with theunderlying mechanisms remaining largely undefined. In this study, weemployed single-cell RNA sequencing (scRNA-seq) to analyze SCCE samplesfrom a single patient both before and after chemotherapy treatment. Our analysisrevealed significant cellular plasticity and alterations in the tumormicroenvironment's cellular composition. Notably, we observed an increase intumor cell diversity coupled with reductions in T cells, B cells, and myeloid-likecells. The pre-treatment samples predominantly featured carcinoma cells in amiddle transitional state, while post-treatment samples exhibited an expandedpresence of cells in terminal, initial-to-terminal (IniTerm), and universally alteredstates. Further analysis highlighted dynamic interactions between tumor cells andimmune cells, with significant changes detected in key signaling pathways, suchas TIGIT-PVR and MDK-SDC4. This study elucidates the complex dynamics of cellplasticity in SCCE following chemotherapy, providing new insights and identifyingpotential therapeutic targets to enhance treatment efficacy.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"15 ","pages":"1477705"},"PeriodicalIF":2.8,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11754407/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143028339","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}

{"title":"Variability of <i>PRDM9</i> in buffaloes.","authors":"Luca Godoi Rocha Santana, Jackeline Santos Alves, Fabieli Loise Braga Feitosa, Victoria Camilla Parente Rocha, Humberto Tonhati, Raphael Bermal Costa, Gregório Miguel Ferreira de Camargo","doi":"10.3389/fgene.2024.1479287","DOIUrl":"10.3389/fgene.2024.1479287","url":null,"abstract":"<p><p>The buffalo population raised in Brazil tend to show loss of genetic variability over generations, with significant estimates of inbreeding depression. Besides mating genetically distant individuals, other tools can be used to maintain/increase the genetic variability of the population, such as the use of <i>PRDM9</i> genotypes. The <i>PRDM9</i> gene promotes the creation of crossing-over points across the genome, with each allele promoting the creation of a different hotspot. Thus, increasing the frequency of less frequent alleles in the population, allows the emergence of new haplotypes and increases genetic variability. So, this study aimed to characterize the alleles of the <i>PRDM9</i> gene circulating in the Murrah, Jaffarabadi, and Mediterranean breeds and verify their potential impact on genetic diversity management within the populations. The three alleles (B, C and D) were found in the three breeds at different frequencies, as well as the genotypic frequencies. The mating of different homozygous genotypes and genotypes carrying less frequent alleles may increase recombination rates and population variability. Four described variants and one new variant for allele D were found by sequencing. It was verified that it is possible to mate sires and dams with different <i>PRDM9</i> genotypes in order to try to increase genetic variability in buffalo populations, improving the matings choices in buffalo breeding, helping to maintain production levels.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"15 ","pages":"1479287"},"PeriodicalIF":2.8,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11754284/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143028362","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}

{"title":"A family with normal sperm motility carrying a sY86 deletion in AZFa region and partial deletion in AZFc region.","authors":"Yuhong Zhao, Weiwei Zhi, Dongsheng Xiong, Ningjing Li, Xinrong Du, Jiuzhi Zeng, Guohui Zhang, Weixin Liu","doi":"10.3389/fgene.2024.1519774","DOIUrl":"10.3389/fgene.2024.1519774","url":null,"abstract":"<p><strong>Introduction: </strong>Usually, patients with sY84 or sY86 deficiency present with azoospermia, but recent studies have shown that some males with partial AZFa deletions, including sY84 or sY86, exhibit normal fertility. Here, we reported a rare case of AZF deletion in a family, where both father and son exhibited a deletion at the sY86 site in the AZFa region and a partial deletion in the AZFc region.</p><p><strong>Methods and results: </strong>Detection was performed using classical multiplex polymerase chain reaction and the \"Male AZF Full-region Detection\" Panel, revealing specific deletions in AZFa: Yq11.21 (14,607,372-14,637,973), 30.6 kb; AZFc: Yq11.223-11.23 (25,848,831-27,120,665), 1.3 M for the father; and Yq11.223-11.23 (25,505,378-27,120,665), 1.6 M for the son. Notably, although the son's sperm motility parameters showed no significant abnormalities, there was a history of failed pregnancies for twice, with sperm exhibiting a high rate of head defect.</p><p><strong>Discussion: </strong>Given the complexities of the reproductive phenotype following AZF region deletions, additional extended genetic testing is necessary when partial deletions in the AZF region are detected, thus providing more accurate predictions of the spermatogenesis in patient. This study provides valuable insights and guidance for clinical decision-making and the implementation of assisted reproductive technologies in such cases.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"15 ","pages":"1519774"},"PeriodicalIF":2.8,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11754199/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143028576","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}