Genetics and Molecular Biology最新文献

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.

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.

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.

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.

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.

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.

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.

The deep sea environment is the largest environment and host some of the most extreme ecosystems on Earth, therefore, possessing a large and unique fish diversity that encompasses about 15% of all known species. Our knowledge about these fishes is still very limited in many biological fields basically due to the complexity to obtain specimens for research. In the present study, we describe the complete mitochondrial genome of Argentina brasiliensis, aiming a species characterization and the study of the phylogenetic relationships in the order Argentiniformes. The mitogenome is composed by 13 protein-coding genes, 2 rRNA genes, 22 tRNA genes, and a control region (D-loop), as found in other vertebrates. The phylogenetic results show that the order Argentiniformes is composed by two family groups the first formed by Argentinidae and Opisthoproctidae and the second formed by Bathylagidae and Microstomatidae. Additionally, we found that the genus Argentina is not monophyletic, and we suggest additional studies in the family Argentinidae to better investigate this question.

Sesame (Sesamum indicum L.), an important oilseed crop, has garnered considerable interest. The nuclear and chloroplast genomes of sesame have been extensively applied to sesame genetics and genomics research. The mitochondrial (mt) genome of sesame, however, has not been sequenced and annotated. In order to solve this issue, we reconstructed the first mt genome of sesame using third-generation sequencing data. The sesame mt genome was 724,998 bp in size and had 22 circular chromosomes. A total of 66 genes were annotated, including 37 protein-coding genes, 26 transfer RNAs, and three ribosomal RNAs. We investigated the codon usage patterns, simple sequence repeats, long tandem repeats, and dispersed repeats of the sesame mt genome. Furthermore, we investigated the DNA transfer from chloroplast to mitochondrion and compared the sesame mt genome to two other Lamiales mt genomes. Given the economic importance of this crop, our presented sesame mt genome is a valuable genomic resource and will allow for more comprehensive studies on sesame and related species.

Spondias mombin L. (Anacardiaceae) is an arboreal and allogamous fruit tree native from southern Mexico to southeastern Brazil, with great potential for economic exploitation. This study aimed to evaluate the structure and genomic diversity of yellow mombin accessions collected in nine locations in Brazil using Single Nucleotide Polymorphisms (SNP) markers. Significant genetic structure was observed in the discriminant analysis of principal components (DAPC) and dendrogram construction, in accordance with our hypotheses. The Mantel test identified a highly positive and significant correlation between geographic and genetic distances. The locations from the Amazon biome presented higher genetic diversity values when compared to those from the Atlantic Forest and Cerrado, which is expected considering the higher vulnerability of these biomes. However, although presenting greater genetic diversity, the Amazon biome showed positive inbreeding coefficients (F IS ) in three of the four locations, ranging from 0.0855 to 0.2421, indicating a potential risk of genetic erosion, possibly related to the increased degradation of this biome in recent decades. The results obtained contribute to the understanding of the distribution of genetic variation and conservation status of yellow mombin in Brazil. They could also be used as a subsidy for developing conservation strategies and the genetic improvement of this species.