Genetics and Molecular Biology最新文献_第2页

Identifying genetically predisposed type 1 diabetes mellitus individuals in a Southern Brazilian population: The construction of a genetic risk score. 在巴西南部人群中识别遗传易感的1型糖尿病个体：遗传风险评分的构建

IF 1.7 4区生物学

Genetics and Molecular Biology Pub Date : 2025-04-18 eCollection Date: 2025-01-01 DOI: 10.1590/1678-4685-GMB-2023-0308

Felipe Mateus Pellenz, Mayara Souza de Oliveira, Guilherme Coutinho Kullmann Duarte, Natália Emerim Lemos, Cristine Dieter, Luís Henrique Canani, Taís Silveira Assmann, Daisy Crispim

{"title":"Identifying genetically predisposed type 1 diabetes mellitus individuals in a Southern Brazilian population: The construction of a genetic risk score.","authors":"Felipe Mateus Pellenz, Mayara Souza de Oliveira, Guilherme Coutinho Kullmann Duarte, Natália Emerim Lemos, Cristine Dieter, Luís Henrique Canani, Taís Silveira Assmann, Daisy Crispim","doi":"10.1590/1678-4685-GMB-2023-0308","DOIUrl":"https://doi.org/10.1590/1678-4685-GMB-2023-0308","url":null,"abstract":"Single nucleotide polymorphisms (SNPs) in the HLA DR/DQ region have the greatest impact on susceptibility to type 1 diabetes mellitus (T1DM). Non-HLA SNPs interact with the HLA, influencing the risk for T1DM. The aim of this study was to develop a genetic risk score (GRS) based on HLA DR/DQ and non-HLA SNPs to discriminate patients with T1DM. The sample comprised 466 patients with T1DM and 469 controls. The rs689/INS, rs2476601/PTPN22, rs231775/CTLA-4, rs2304256/TYK2, rs2292239/ERBB3, and HLA DR/DQ SNPs were genotyped using real-time PCR. The unweighted GRS (uGRS) was calculated by summing the risk alleles of each SNP and the weighted GRS (wGRS) by multiplying the risk alleles by their odds ratios. The uGRS was higher in T1DM patients than in non-diabetic controls (0.34 ± 0.14 vs. 0.26 ± 0.13, P <0.0001), being positively correlated with HbA1c levels (P <0.0001). wGRSs exhibited higher AUCs than uGRSs. The wGRS containing only HLA DR/DQ SNPs showed an AUC of 0.75 (95% CI 0.72 - 0.78). The wGRS containing both HLA DR/DQ and non-HLA SNPs, adjusted for race, demonstrated the best discriminative power [AUC 0.91 (95% CI 0.89 - 0.93)]. The race adjusted-wGRS, including all SNPs, seems to be a useful genetic tool for assessing individual's predisposition to T1DM.","PeriodicalId":12557,"journal":{"name":"Genetics and Molecular Biology","volume":"48 2","pages":"e20230308"},"PeriodicalIF":1.7,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11999062/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144005828","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

Mismatch uracil DNA glycosylase (Mug) is maintained in the Corynebacterium pseudotuberculosis genome and exhibits affinity for uracil but not other types of damage. 错配尿嘧啶DNA糖基酶（Mug）存在于假结核棒状杆菌基因组中，对尿嘧啶表现出亲和力，但对其他类型的损伤没有亲和力。

IF 1.7 4区生物学

Genetics and Molecular Biology Pub Date : 2025-04-14 eCollection Date: 2025-01-01 DOI: 10.1590/1678-4685-GMB-2023-0353

Bruno Carvalho Resende, Cássio Siqueira Souza Cassiano, Diego Lisboa Rios, Thalia Queiroz Ladeira, Vasco Ariston Carvalho Azevedo, Luciana Lara Dos Santos, Lucía Valenzuela-Pérez, Gonzalo Cabrera, Carlos Renato Machado, Débora de Oliveira Lopes

{"title":"Mismatch uracil DNA glycosylase (Mug) is maintained in the Corynebacterium pseudotuberculosis genome and exhibits affinity for uracil but not other types of damage.","authors":"Bruno Carvalho Resende, Cássio Siqueira Souza Cassiano, Diego Lisboa Rios, Thalia Queiroz Ladeira, Vasco Ariston Carvalho Azevedo, Luciana Lara Dos Santos, Lucía Valenzuela-Pérez, Gonzalo Cabrera, Carlos Renato Machado, Débora de Oliveira Lopes","doi":"10.1590/1678-4685-GMB-2023-0353","DOIUrl":"https://doi.org/10.1590/1678-4685-GMB-2023-0353","url":null,"abstract":"The genome of Corynebacterium pseudotuberculosis, etiologic agent of Caseous Lymphadenitis (CLA), was sequenced to comprehend its genetics, pathogenicity, and virulence mechanisms due to its economic importance. A focus was placed on the G/U mismatch-specific DNA glycosylase (Mug), an enzyme vital for base excision repair in DNA that can play an important role in uracil repair, since the high G+C content of C. pseudotuberculosis makes it prone to deamination events, accentuating the potential significance of Mug. Through in silico and in vitro analyses, the Corynebacterium pseudotuberculosis Mug protein (CpMug) was characterized to confirm its DNA glycosylase activity and lesion affinity. The mug gene was identified in both pathogenic and non-pathogenic Corynebacterium species, lacking a discernible ancestry pattern. Bioinformatics analyses revealed the preservation of essential uracil DNA glycosylase catalytic residues in CpMug. The 3D structure of CpMug was constructed, and molecular docking analysis demonstrated its interaction with DNA containing uracil and other lesions. Comparative analyses revealed a higher affinity of CpMug's catalytic residues for uracil over other DNA lesions and enzymatic assays with purified CpMug affirmed its uracil DNA glycosylase activity, while it exhibited no activity on 8-oxoguanine, tetrahydrofuran, or thymine glycol, consistent with computational simulations.","PeriodicalId":12557,"journal":{"name":"Genetics and Molecular Biology","volume":"48 2","pages":"e20230353"},"PeriodicalIF":1.7,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12001322/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144063340","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

Ethnicity-specific associations between the promoter region G-308A polymorphism (rs1800629) of the TNF-α gene and the development of end-stage renal disease: An evidence-based meta-analysis and trial sequential analysis. TNF-α基因启动子区G-308A多态性（rs1800629）与终末期肾病发展之间的种族特异性关联：循证荟萃分析和试验序列分析

IF 1.7 4区生物学

Genetics and Molecular Biology Pub Date : 2025-02-24 eCollection Date: 2025-01-01 DOI: 10.1590/1678-4685-GMB-2024-0077

Suthiya Anumas, Amarit Tansawet, Pawin Numthavaj, Pattharawin Pattharanitima, Noel Pabalan, Hamdi Jarjanazi, Rungrawee Mongkolrob, Adis Tasanarong, Phuntila Tharabenjasin

{"title":"Ethnicity-specific associations between the promoter region G-308A polymorphism (rs1800629) of the TNF-α gene and the development of end-stage renal disease: An evidence-based meta-analysis and trial sequential analysis.","authors":"Suthiya Anumas, Amarit Tansawet, Pawin Numthavaj, Pattharawin Pattharanitima, Noel Pabalan, Hamdi Jarjanazi, Rungrawee Mongkolrob, Adis Tasanarong, Phuntila Tharabenjasin","doi":"10.1590/1678-4685-GMB-2024-0077","DOIUrl":"10.1590/1678-4685-GMB-2024-0077","url":null,"abstract":"Tumor necrosis factor-alpha (TNF-α), is partly attributed to pathogenesis of end-stage renal disease (ESRD). Inconsistency of reported associations between TNF-α G-308A polymorphism (rs1800629) and ESRD prompted a meta-analysis to obtain more precise estimates. Eleven case-control studies from 11 articles were included. Pooled odds ratios (OR) and 95% confidence intervals (95% CIs) were estimated to evaluate the association. Subgroup analysis was based on ethnicity (Caucasian and Asian). Multiple comparisons were Bonferroni-corrected. Trial sequential analysis (TSA) was implemented to ascertain the reliability of results. Sensitivity analyses and publication bias tests were performed on significant results. There were no significant association (pa >0.05) in the overall and ethnic subgroup. Indians, three significant pool ORs (pa < 0.01-0.03) showed increased susceptibility to ESRD in homozygous (OR, 6.57; 95% CI, 1.45 to 29.75; pa = 0.01), recessive (OR, 6.75; 95% CI, 1.44 to 31.56; pa = 0.02), and codominant (OR, 2.06; 95% CI, 1.08 to 3.94; pa = 0.03) models. TSA indicated the robustness of such association in the Indian population. The main outcomes were robust without evidence of publication bias. This study showed associations between TNF-α G-308A and ESRD are confined to Indians, which are susceptible to ESRD up to approximately 7 times.","PeriodicalId":12557,"journal":{"name":"Genetics and Molecular Biology","volume":"48 1","pages":"e20240077"},"PeriodicalIF":1.7,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11912548/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143572755","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

Male aging in germ cells: What are we inheriting? 生殖细胞中的男性衰老：我们遗传了什么？

IF 1.7 4区生物学

Genetics and Molecular Biology Pub Date : 2025-02-18 eCollection Date: 2025-01-01 DOI: 10.1590/1678-4685-GMB-2024-0052

Arturo Elías-Llumbet, Sebastián Lira, Marcia Manterola

{"title":"Male aging in germ cells: What are we inheriting?","authors":"Arturo Elías-Llumbet, Sebastián Lira, Marcia Manterola","doi":"10.1590/1678-4685-GMB-2024-0052","DOIUrl":"10.1590/1678-4685-GMB-2024-0052","url":null,"abstract":"Aging is a significant risk factor for male fertility and can lead to severe developmental disorders in offspring. It disrupts testicular function and spermatogenesis, resulting in sperm abnormalities and DNA fragmentation. Male aging alters the genome and epigenome of germ cells due to persistent oxidative stress caused by the cumulative effects of environmental factors over a lifetime. At the molecular level, DNA damage occurs and is poorly repaired due to impaired DNA repair pathways, leading to unrepaired lesions and de novo mutations. Aging also creates distinct epigenetic landscapes that modify gene expression in germ cells, affect the DNA damage response, and generate de novo DNA and epigenetic mutations that are transmitted to the sperm and inherited by the offspring. This review discusses current knowledge on the age-associated effects on male germ cells and the genomic and epigenomic mechanisms contributing to altered male reproductive health and outcomes in progeny. We propose a male reproductive aging threshold, where cumulative exposure to risk factors leads to oxidative stress, impaired spermatogenesis, and altered reproductive outcomes. Finally, we discuss novel interventions to prevent premature testicular aging and emphasize the need for public health policies and counseling guidelines for men seeking paternity.","PeriodicalId":12557,"journal":{"name":"Genetics and Molecular Biology","volume":"47Suppl 1 Suppl 1","pages":"e20240052"},"PeriodicalIF":1.7,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11837248/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143448485","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

Van der Woude syndrome and amniotic band sequence: A clue to a common genetic etiology? A case report. Van der Woude综合征和羊膜带序列：共同遗传病因的线索？一份病例报告。

IF 1.7 4区生物学

Genetics and Molecular Biology Pub Date : 2025-02-17 eCollection Date: 2025-01-01 DOI: 10.1590/1678-4685-GMB-2024-0123

Ana Luiza Bossolani-Martins, Joanna Goes Castro Meira, Gerson Shigeru Kobayashi, Adriana Barbosa-Gonçalves, Maria Rita Passos-Bueno, Agnes Cristina Fett-Conte

{"title":"Van der Woude syndrome and amniotic band sequence: A clue to a common genetic etiology? A case report.","authors":"Ana Luiza Bossolani-Martins, Joanna Goes Castro Meira, Gerson Shigeru Kobayashi, Adriana Barbosa-Gonçalves, Maria Rita Passos-Bueno, Agnes Cristina Fett-Conte","doi":"10.1590/1678-4685-GMB-2024-0123","DOIUrl":"10.1590/1678-4685-GMB-2024-0123","url":null,"abstract":"Rare heterozygous variants in IRF6 (interferon regulatory factor-6) gene cause van der Woude syndrome 1 (VWS1) or Popliteal Pterygium syndrome, two forms of syndromic cleft lip/palate (CLP) that present with a variety of congenital malformations due to impairment ectodermal homeostasis. These malformations include, in addition to CLP, lip pits, pterygia, and intraoral and eyelid fibrous bands. Amniotic band sequence (ABS) is a rare condition of unknown genetic etiology that involves a range of congenital anomalies caused by the entanglement of fibrous bands, which disrupt fetal body parts. However, ABS co-occurs with CLP and other malformations that cannot be explained by this mechanism. Therefore, investigating the genetic relationship between ABS and CLP may provide clues regardind the genes involved in these conditions. Here, we report a case of a girl diagnosed with VWS1, autism, intellectual disability, and congenital right limb anomalies compatible with ABS. Molecular analysis revealed a novel, rare heterozygous missense variant in IRF6 (NM_006147.3:c.970T>C) located in exon 7, inherited from her father. This variant results in the replacement of serine by proline at position 324 of the IRF6 protein with potentially deleterious effects. This report expands the mutational landscape of IRF6 and provides further support for a possible link between the genetics of CLP and ABS.","PeriodicalId":12557,"journal":{"name":"Genetics and Molecular Biology","volume":"48 1","pages":"e20240123"},"PeriodicalIF":1.7,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11895807/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143623861","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

Yaravirus brasiliense genomic structure analysis and its possible influence on the metabolism. 巴西Yaravirus基因组结构分析及其对代谢的可能影响。

IF 1.7 4区生物学

Genetics and Molecular Biology Pub Date : 2025-02-07 eCollection Date: 2025-01-01 DOI: 10.1590/1678-4685-GMB-2024-0139

Ana Karoline Nunes-Alves, Jônatas Santos Abrahão, Sávio Torres de Farias

{"title":"Yaravirus brasiliense genomic structure analysis and its possible influence on the metabolism.","authors":"Ana Karoline Nunes-Alves, Jônatas Santos Abrahão, Sávio Torres de Farias","doi":"10.1590/1678-4685-GMB-2024-0139","DOIUrl":"10.1590/1678-4685-GMB-2024-0139","url":null,"abstract":"Here we analyze the Yaravirus brasiliense, an amoeba-infecting 80-nm-sized virus with a 45-kbp dsDNA, using structural molecular modeling. Almost all of its 74 genes were previously identified as ORFans. Considering its unprecedented genetic content, we analyzed Yaravirus genome to understand its genetic organization, its proteome, and how it interacts with its host. We reported possible functions for all Yaravirus proteins. Our results suggest the first ever report of a fragment proteome, in which the proteins are separated in modules and joined together at a protein level. Given the structural resemblance between some Yaravirus proteins and proteins related to tricarboxylic acid cycle (TCA), glyoxylate cycle, and the respiratory complexes, our work also allows us to hypothesize that these viral proteins could be modulating cell metabolism by upregulation. The presence of these TCA cycle-related enzymes specifically could be trying to overcome the cycle's control points, since they are strategic proteins that maintain malate and oxaloacetate levels. Therefore, we propose that Yaravirus proteins are redirecting energy and resources towards viral production, and avoiding TCA cycle control points, \"unlocking\" the cycle. Altogether, our data helped understand a previously almost completely unknown virus, and a little bit more of the incredible diversity of viruses.","PeriodicalId":12557,"journal":{"name":"Genetics and Molecular Biology","volume":"48 1","pages":"e20240139"},"PeriodicalIF":1.7,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11803573/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143363939","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 variant W chromosome in Centromochlus heckelii (Siluriformes, Auchenipteridae) and the role of repeated DNA in its heteromorphism. 黑斑拟中央蝽W染色体的变异及重复DNA在其异型性中的作用。

IF 1.7 4区生物学

Genetics and Molecular Biology Pub Date : 2025-01-27 eCollection Date: 2025-01-01 DOI: 10.1590/1678-4685-GMB-2024-0071

Chrystian Aparecido Grillo Haerter, Patrik Ferreira Viana, Fábio Hiroshi Takagui, Sandro Tonello, Vladimir Pavan Margarido, Daniel Rodrigues Blanco, Josiane Baccarin Traldi, Roberto Laridondo Lui, Eliana Feldberg

{"title":"A variant W chromosome in Centromochlus heckelii (Siluriformes, Auchenipteridae) and the role of repeated DNA in its heteromorphism.","authors":"Chrystian Aparecido Grillo Haerter, Patrik Ferreira Viana, Fábio Hiroshi Takagui, Sandro Tonello, Vladimir Pavan Margarido, Daniel Rodrigues Blanco, Josiane Baccarin Traldi, Roberto Laridondo Lui, Eliana Feldberg","doi":"10.1590/1678-4685-GMB-2024-0071","DOIUrl":"10.1590/1678-4685-GMB-2024-0071","url":null,"abstract":"Centromochlus heckelii has the lowest diploid chromosome number (2n = 46) and the only described heteromorphic sex chromosome system in Auchenipteridae. This study presents a population of C. heckelii from the Central Amazon basin with subtle variations in the karyotype composition and a variant W chromosome with distinct morphology and increased C-positive heterochromatin content. In this population, the W chromosome is subtelocentric, whereas the only previous study on C. heckelii reported a metacentric W chromosome. Constitutive heterochromatin (CH) and accumulation of microsatellite motifs have significantly contributed to this W chromosome enlargement. Notably, this population exhibits numerous interstitial telomeric sites (ITSs). Some of these ITSs might represent genuine chromosomal fusion points due to the reduced 2n; however, additional mechanisms, such as chromosomal inversions, translocations, transpositions, or association with satellite DNA, are likely responsible for this unusual pattern. The 18S rDNA sites were found in both the Z and W chromosomes of all individuals. However, two individuals exhibited an additional 18S rDNA site in a single homologous of the chromosome pair 20, characterizing an intrapopulation polymorphism. The 5S rDNA sites were found in two chromosome pairs, distinguishing this population from other Centromochlinae species and further supporting it as one of the most efficient cytotaxonomic markers within the subfamily.","PeriodicalId":12557,"journal":{"name":"Genetics and Molecular Biology","volume":"48 1","pages":"e20240071"},"PeriodicalIF":1.7,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11789463/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143052286","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

Truncated SPAG9 as a novel candidate gene for a new syndrome: Coarse facial features, albinism, cataract and developmental delay (CACD syndrome). 截断的SPAG9作为一种新综合征的新候选基因：面部粗糙，白化病，白内障和发育迟缓（ccd综合征）。

IF 1.7 4区生物学

Genetics and Molecular Biology Pub Date : 2025-01-20 eCollection Date: 2025-01-01 DOI: 10.1590/1678-4685-GMB-2024-0094

Majid Alfadhel, Bashayr S Alhubayshi, Muhammad Umair, Ahmed Alfaidi, Deemah Alwadaani, Essra Aloyouni, Safdar Abbas, Abdulkareem Al Abdulrahman, Mohammed Aldrees, Abeer Al Tuwaijri, Ruaa S Alharithy, Abdulaziz Alajlan, Abdulrahman Alswaid, Saad Almohrij, Sultan Al-Khenaizan

{"title":"Truncated SPAG9 as a novel candidate gene for a new syndrome: Coarse facial features, albinism, cataract and developmental delay (CACD syndrome).","authors":"Majid Alfadhel, Bashayr S Alhubayshi, Muhammad Umair, Ahmed Alfaidi, Deemah Alwadaani, Essra Aloyouni, Safdar Abbas, Abdulkareem Al Abdulrahman, Mohammed Aldrees, Abeer Al Tuwaijri, Ruaa S Alharithy, Abdulaziz Alajlan, Abdulrahman Alswaid, Saad Almohrij, Sultan Al-Khenaizan","doi":"10.1590/1678-4685-GMB-2024-0094","DOIUrl":"10.1590/1678-4685-GMB-2024-0094","url":null,"abstract":"Sperm-associated antigen 9 (SPAG9) is a member of cancer-testis antigen, having characteristics of a scaffold protein, which is involved in the c-Jun N-terminal kinase JNK signaling pathway, suggesting its key involvement in different physiological processes, such as survival, apoptosis, tumorigenesis, and cell proliferation. We identified two families (A and B) having multisystem features like coarse facial features, albinism, cataracts, skeletal abnormalities, and developmental delay. Whole genome sequencing (WGS) in families A and B revealed a homozygous frameshift variant (c.903del; p.Phe301Leufs*2) in the SPAG9 gene. Sanger sequencing of both families revealed perfect segregation of the identified variant in all family members. 3D protein modeling revealed substantial changes in the protein's secondary structure. Furthermore, RT-qPCR revealed a substantial reduction of SPAG9 gene expression at the mRNA level in the affected individuals of both families, thus supporting the pathogenic nature of the identified variant. For the first time in the literature, biallelic SPAG9 gene variation was linked to multisystem-exhibiting features like coarse facial features, albinism, cataracts, skeletal abnormalities, and developmental delay. Thus, this data supports the notion that SPAG9 plays an important role in a multisystemic disorder in humans.","PeriodicalId":12557,"journal":{"name":"Genetics and Molecular Biology","volume":"48 1","pages":"e20240094"},"PeriodicalIF":1.7,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11773325/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143022684","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

MTHFR C677T rs1801133 and TP53 Pro72Arg rs1042522 gene variants in South African Indian and Caucasian psoriatic arthritis patients. 南非印度和高加索银屑病关节炎患者的MTHFR C677T rs1801133和TP53 Pro72Arg rs1042522基因变异

IF 1.7 4区生物学

Genetics and Molecular Biology Pub Date : 2025-01-10 eCollection Date: 2025-01-01 DOI: 10.1590/1678-4685-GMB-2023-0325

Pragalathan Naidoo, Ajesh B Maharaj, Terisha Ghazi, Anil A Chuturgoon

{"title":"MTHFR C677T rs1801133 and TP53 Pro72Arg rs1042522 gene variants in South African Indian and Caucasian psoriatic arthritis patients.","authors":"Pragalathan Naidoo, Ajesh B Maharaj, Terisha Ghazi, Anil A Chuturgoon","doi":"10.1590/1678-4685-GMB-2023-0325","DOIUrl":"10.1590/1678-4685-GMB-2023-0325","url":null,"abstract":"Methylenetetrahydrofolate reductase (MTHFR) gene is involved in homocysteine and folic acid metabolism. Tumour suppressor protein TP53 gene maintains cellular and genetic integrity. To date, no studies associated the MTHFR C677T rs1801133 and TP53 Pro72Arg rs1042522 with CRP levels and methotrexate (a folic acid antagonist) treatment outcomes in psoriatic arthritis (PsA) patients. The present study aimed to investigate whether the MTHFR rs1801133 and TP53 rs1042522 gene variants influences CRP levels and methotrexate treatment outcomes in South African Indian and Caucasian PsA patients. PsA patients (n=114) and healthy controls (n=100) were genotyped for the rs1801133 and rs1042522 using RFLP-PCR. (i) Results for rs1801133 genotyping: Caucasian patients had a higher frequency of the variant T-allele versus healthy Caucasian controls (40% versus 22%; OR=2.31, 95% CI=1.10-4.88, p=0.0379). Patients with the variant CT+TT genotypes had higher median CRP levels at baseline versus wildtype CC genotypes (11.70 (5.3-28.80) mg/mL versus 7.40 (5.00-15.05) mg/mL, p=0.0355). After 6 months of methotrexate treatment median CRP levels between genotypes reduced and remained similar. (ii) Results for rs1042522 genotyping: Indian patients had a higher frequency of the variant Arg-allele versus healthy Indian controls (42% versus 29%; OR=1.75, 95% CI=1.07-2.86, p=0.0275). In conclusion, patients with the MTHFR rs1801133 variant T-allele have elevated CRP levels, which can be ameliorated with methotrexate.","PeriodicalId":12557,"journal":{"name":"Genetics and Molecular Biology","volume":"48 1","pages":"e20230325"},"PeriodicalIF":1.7,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11721215/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142946718","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

Re-evaluating evidence for giant genomes in amoebae. 重新评估阿米巴巨型基因组的证据。

IF 1.7 4区生物学

Genetics and Molecular Biology Pub Date : 2024-12-20 eCollection Date: 2024-01-01 DOI: 10.1590/1678-4685-GMB-2024-0092

Daniel Barzilay, João P B Alcino, Giulia M Ribeiro, Alfredo L P Sousa, Daniel J G Lahr

{"title":"Re-evaluating evidence for giant genomes in amoebae.","authors":"Daniel Barzilay, João P B Alcino, Giulia M Ribeiro, Alfredo L P Sousa, Daniel J G Lahr","doi":"10.1590/1678-4685-GMB-2024-0092","DOIUrl":"10.1590/1678-4685-GMB-2024-0092","url":null,"abstract":"Here we reassess available evidence for the long-held misconception of amoebae possessing exceptionally large genomes. Traditionally, estimates relied on inaccurate methods like DNA weight measurements, leading to inflated sizes. These methods failed to account for contaminating DNA from prey, endosymbionts, and intrinsic genomic features like ribosomal operon amplification. Modern sequencing techniques unveil a different picture. Fully sequenced amoebozoa genomes range from 14.4 to 52.37 mega basepairs, well within the typical single-celled eukaryote expectation. While the whole genome of the historically relevant Amoeba proteus has not yet been fully sequenced, we provide here a statistical analysis using protein-coding genes from transcriptomic data, suggesting that the genome size is consistent with this range, far smaller than previously claimed. The misconception likely originated in the early 21st century and perpetuated through popular science materials. We conclude that there is no longer reason to reaffirm that amoeba genomes are giant.","PeriodicalId":12557,"journal":{"name":"Genetics and Molecular Biology","volume":"47Suppl 1 Suppl 1","pages":"e20240092"},"PeriodicalIF":1.7,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11773323/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143052205","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}

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