[This corrects the article doi: 10.1590/1678-4685-GMB-2023-0181].

Human reproduction goes through many challenges to its success and in many cases it fails. Cases of pregnancy loss are common outcomes for pregnancies, and implantation failures (IF) are common in assisted reproduction attempts. Although several risk factors have already been linked to adverse outcomes in reproduction, many cases remain without a definitive cause. Genetics of female reproduction is a field that may bring some pieces of this puzzle; however, there are no well-defined genes that might be related to the risk for recurrent pregnancy loss (RPL) and IF. Here, we present a literature review of the studies of genetic association in RPL and IF carried out in the Brazilian population and complemented with a database search to explore genes previously related to RPL and IF, where a search for genes previously involved in these conditions was performed in OMIM, HuGE, and CTD databases. Finally, we present the next steps for reproductive genetics investigation, through genomic sequencing analyses and discuss future plans in the study of RPL genetics. The combined strategy of looking for literature and databases is useful to raise hypotheses and to identify underexplored genes related to RPL and IF.

Effector proteins in Phakopsora pachyrhizi (Pp), the causative agent of Asian Soybean rust, are involved in the infection process. A previous study identified a rust effector Egh16-like family based expression profile during the interaction with soybean. Herein, we scrutinized available the Pp genomes to validate the predicted Egh16-like family of Pp and identify new family members. We described 22 members of the Egh16-like gene family in the Pp MT2006 genome and 18 in the UFV02 and K8108 genomes, highlighting a family expansion. Family members have a small signal peptide, conserved cysteine-rich R/Y/FxC motifs in the C-terminal region, and a virulence-related Egh16-like domain and were able to suppress PTI related responses in Benthamiana. Phylogenetic analysis placed the family members into eight clusters, with members induced during the early stages of rust infection. Members of clusters VI and VII are present in different copy numbers in Pp genomes and suppressed PAMP-related responses.

The genetic architecture of complex diseases affecting populations with Indigenous American ancestries is poorly understood due to their underrepresentation in genomics studies. While most of the genetic diversity associated with disease trait variation is shared among worldwide populations, a fraction of this component is expected to be unique to each continental group, including Indigenous Americans. Here, I describe the current state of knowledge from genome-wide association studies on Indigenous populations, as well as non-Indigenous populations with partial Indigenous ancestries from the American continent, focusing on disease susceptibility and anthropometric traits. While some studies identified risk alleles unique to Indigenous populations, their effects on trait variation are mostly small. I suggest that the associations rendered by many inter-population studies are probably inflated due to the absence of socio-cultural-economic covariates in the association models. I encourage the inclusion of admixed individuals in future GWAS studies to control for inter-ancestry differences in environmental factors. I suggest that some complex diseases might have arisen as trade-off costs of adaptations to past evolutionary selective pressures. Finally, I discuss how expanding panels with Indigenous ancestries in GWAS studies is key to accurately assess genetic risk in populations from the American continent, thus decreasing global health disparities.

Polyploidy is often related with phenotypic variation, as observed in Herbertia lahue, a geophyte species. This study examined the H. lahue polyploid series and departure in cytogenetic, morphometric, and pollen data. Diploids (2n=2x=14) present bimodal karyotype with two long and five short chromosome pairs, while hexaploids (2n=6x=42) and octoploids (2n=8x=56) present a gradual decrease in chromosome size. All cytotypes have CMA+/DAPI- bands co-localized with 18S rDNA sites in the satellite region (no DAPI+ bands in any cytotype). Unlike diploids and octoploids, 5S rDNA interstitial sites in hexaploids are not in a syntenic position with 18S rDNA sites. Genome size is effective as an indirect predictor of the cytotypes since 2C-values increased according to ploidy level. The reduction in the number of the rDNA sites in polyploids associated with their lower 1Cx-values compared to diploids may suggest a genome downsizing process. Morphometric analysis revealed significant differences among cytotypes, and discriminant analysis identified three morphometric groupings corresponding to the cytotypes. The phenotypic variation observed in pollen grains, bulbs, and ovary characters suggested the gigas effect. Concluding, remarkable differentiation was observed at both genomic and phenotypic characters in all the cytotypes analyzed, suggesting a possible ongoing speciation process in H. lahue.

Glucose is a critical nutrient for energy metabolism. The SLC2A2 gene is essential for glucose sensing and homeostasis, as it encodes the facilitated glucose transporter GLUT2. During diabetes treatment, the C-allele of rs8192675 in SLC2A2 has been found to regulate the action of metformin and reduce the absolute level of HbA1c more effectively than the T-allele. In this study, stable HEK293T cell lines carrying the CC, CT, and TT genotypes of rs8192675 in SLC2A2 were generated using CRISPR/Cas9-mediated genome editing. GLUT2 mRNA and protein levels were elevated in cell clones with the TC genotype compared to those with the CC genotype but were reduced relative to the TT genotype. Additionally, high concentrations of glucose or fructose induced more GLUT2 protein production in CT-genotype cells than that induced in CC-genotype cells, yet less than that induced in TT-genotype cells. Metformin induced a greater increase in GLUT2 expression and a smaller increase in activated AMPK protein expression in CC-genotype cells than those induced in TT-genotype cells, resulting in a remarkable reduction in activated mTOR and S6 levels. This study directly supports the biological mechanism linking the C-allele of rs8192675 with improved treatment outcomes in metformin therapy for diabetes.

Chromosomal Microarray Analysis (CMA) has increased the comprehension of the mechanisms of copy number variation (CNV) formation, classification of these rearrangements, type of recurrence, and its origin, and has also been a powerful approach to identifying CNVs in individuals with intellectual disability. The aim of this study was to establish the parental origin of de novo pathogenic CNV in a cohort of patients with intellectual disability from the public health system of Goiás-Brazil. CMA was done in 76 trios and we identified 15 de novo pathogenic CNVs in 12 patients with intellectual disability. In a total of 15 de novo pathogenic CNV, 60% were derived from the maternal germline and 40% from the paternal germline. CNV flanked by low copy repeats (LCR) were identified in 46.7% and most of them were of maternal origin. No significant association was observed between paternal age and the mutation rate of de novo CNVs. The presence of high-identity LCRs increases the occurrence of CNV formation mediated by non-allelic homologous recombination and the majority of paternal CNVs are non-recurrent. The mechanism of formation of these CNV may have been by microhomology-mediated break-induced replication or non-homologous end joining.

ATP-binding cassette (ABC) transporters, including P-glycoproteins (PGP), have been implicated in drug resistance in different organisms including Haemonchus contortus. This study confirmed the resistance status of H. contortus isolates selected for ivermectin (IVM) and oxfendazole (OXF) resistances using the fecal egg count reduction test and evaluated the gene expression of seven ABC transporters using RT-qPCR for two biological scenarios: the effect of selection for anthelmintic resistance and the effect of drug exposure on gene expression. Gene expression results showed that selection for IVM resistance led to the significant upregulation of Hco-pgp-9a (1.5-fold), Hco-pgp-11 (3-fold) and Hco-haf-9 (1.5-fold) (p < 0.05). Similarly, selection for OXF resistance led to the significant upregulation of Hco-pgp-9a (3-fold), Hco-pgp-11 (4-fold) and Hco-haf-9 (2-fold) when comparing with the unselected ISE isolate (p < 0.05). Exposure of selected isolates to anthelmintics lead to no significant upregulation of the studied transporter genes. We also observed instances where there was strong intragroup variation regarding samples originating from parasites obtained from different individual hosts pointing that the interactions of the animal host with the tested anthelmintics may also play a role in the expression of the studied nematode genes.

Neuroblastoma (NB) is a solid tumor that accounts for 15% of all pediatric oncological deaths, and much is due to the low response to therapy in relapsed tumors. High-risk NB may present deletions in chromosome 11q, which may be associated with other chromosomal alterations and a poor response to therapy, but this association is still poorly understood. Using a systems biology network approach, we studied three patients with high-risk NB with deleted 11q stage 4 to highlight the connections between treatment resistance and copy number alterations in distinct cases. We built different protein-protein interaction networks for each patient based on protein-coding genes mapped at the cytobands pre- and post-chemotherapy from distinct copy number alterations data. In the post-chemotherapy networks, we identified five common regulatory nodes corresponding to the gained region located in ch17q:BIRC5, BRCA1, PRKCA, SUMO2, andGPS1. A crosslink between DNA damage and chromatin remodeling proteins was also found - a connection still poorly understood in NB. We identified a potential connection between XPB gain and chemoresistance of NB. The findings help elucidate the molecular profiles of high-risk NB with 11q deletion in pre- and post-chemotherapy tumor samples, which may reflect unique profiles in poor response to treatment.

Pedicularis L., a generally bothersome genus of hemiparasitic plants, is primarily native to southwestern China. The phylogenetic relationship and evolutionary history of this genus have not yet been fully resolved. In this study, we sequenced and assembled chloroplast genomes of three Pedicularis species, P. chinensis, P. melampyriflora, and P. striata using high-throughput Illumina sequencing. The assembled plastomes were 142,059 bp (P. chinensis) to 152,146 bp (P. striata) in size, containing 110 (P. chinensis) to 117 (P. striata) genes. Moreover, we identified 13-15 pseudogenes within the three plastomes, nine of which were pseudogenized in all three species. The three plastomes exhibited a similar codon usage pattern. Moreover, the plastomes contained abundant simple sequence repeats and long repeats, which showed slight variations between the three species. A maximum likelihood analysis was performed to elucidate the phylogenetic positions of the three species within the Pedicularis genus. The plastomes presented in our study can be used as valuable genomic resources for further genetic and genomic studies of the Pedicularis genus.

Regulated cell death by a non-apoptotic pathway known as parthanatos is increasingly recognised as a central player in pathological processes, including ischaemic tissue damage and neurodegenerative diseases. Parthanatos is activated under conditions that induce high levels of DNA damage, leading to hyperactivation of the DNA damage sensor PARP1. While this strict dependence on PARP1 activation is a defining feature of parthanatos that distinguishes it from other forms of cell death, the molecular events downstream of PARP1 activation remain poorly understood. In this mini-review, we highlight a number of important questions that remain to be answered about this enigmatic form of cell death.

Neotropical fishes emerge as an extremely diverse group of vertebrates where genomic strategies to evaluate structural and functional features are still beginning. Here, we present a second draft genome of Apareiodon sp. (2n=54, ZZ/ZW), adding PacBio technology whole genome sequencing, and assembling by combining two technologies (long and short reads). Using a detailed strategy for genome assembly with fish genomes of Pygocentrus nattereri, Carassius auratus, and Astyanax mexicanus as references, the final assembly of the Apareiodon sp. genome generated 93 scaffolds, an N50 of 37,200,078 bases, and a size estimate considering 28 scaffolds (26 autosomes+ZW) of ~945 Mb. In Apareiodon sp., this second genome draft confirmed that ~36% of the genome is composed of repetitive DNA. Furthermore, the new draft genome has improved genomic quality assessments, allowing the annotation of 36,290 genes and 15,683 proteins, which presented similarities to reference genomes. The second draft genome of Apareiodon sp. will be useful for research on integrative cytogenetic and genomic data. It will open perspectives for analyzing sex-determining genes in Neotropical fish with a ZZ/ZW sex chromosome system.

The catalytic, regulatory and structural properties of RNA, combined with their extraordinary ubiquity in cellular processes, are consistent with the proposal that this molecule played a much more conspicuous role in heredity and metabolism during the early stages of biological evolution. This review explores the pivotal role of RNA in the earliest life forms and its relevance in modern biological systems. It examines current models that study the early evolution of life, providing insights into the primordial RNA world and its legacy in contemporary biology.

Dichrocephala benthamii C. B. Clarke has long been used as traditional Chinese medicine. However, the chloroplast (cp) genome of D. benthamii is poorly understood so far. In this study, we sequenced and analyzed the cp genome of D. benthamii. The results showed that the cp genome is 152,350 bp in length, with a pair of inverted repeat regions (IRa and IRb, each 24,982 bp), a large single-copy (LSC) region comprising 84,136 bp, and a small single-copy (SSC) region comprising 18,250 bp. The GC content of the cp genome was 37.3%. A total of 134 genes were identified, including 87 protein-coding genes (CDS), 38 tRNA genes, 8 rRNA genes, and 1 pseudogene (ycf1). Expansion or contraction of IR regions were detected in D. benthamii and other species of the tribe Astereae. Additionally, our analyses showed the types of sequence repeats and the highly variable regions discovered by analyzing the border regions, sequence divergence, and hot spots. The phylogenetic analysis revealed D. benthamii is the basal group of Astereae. The results of this study will be a significant contribution to the genetics and species identification related to D. benthamii.

Melon (Cucumis melo L.) is an economically important horticultural crop. Spotted rind at maturity is an important appearance quality trait in melons. However, the gene controlling this trait remains unknown. In this study, the inheritance pattern of this trait was explored, and the candidate gene underlying this trait was also successfully identified. Genetic analysis showed that a single dominant gene, Cucumis melo Spotted Rind (CmSR), regulates the spotted rind trait. A preliminary genetic mapping analysis was conducted based on a BSA-seq approach. The CmAPRR2 gene was identified to be linked with the spotted rind trait and was located on the short arm of chromosome 4. It harbored two single-nucleotide mutations (chr4: 687014 G/A and chr4: 687244 C/A) in the non-spotted line 'Yellow 2', which may result in the alternative splicing of the transcript and an amino acid change in the respective protein, from proline to glutamine, respectively. Moreover, marker SNP687014-G/A was developed and co-segregated with the spotted rind trait. Therefore, it is speculated that the CmAPRR2 gene may be involved in the regulation of the spotted rind trait in melon. This study provides a theoretical foundation for further research on the gene regulatory mechanism of the rind color in melon.

In South America, Tambaqui (Colossoma macropomum) stands as the primary target for aquaculture, yet breeding programs for this Amazon native species are in their early stages. While high-density single nucleotide polymorphism (SNP) arrays are pivotal for aquaculture breeding, their costs can be prohibitive for non- or semi-industrial species. To overcome this, a cost-effective approach involves developing low-density SNP arrays followed by genotype imputation to higher densities. In this study, a 1K SNP array for tambaqui was created and validated, offering a balance between SNP quantity and genome representativity. The imputation accuracy from various SNP densities to a medium-density array was evaluated, with the 1K density demonstrating the best trade-off (accuracy of 0.93). This subset was further utilized to construct a commercial array through Agriseq™ targeted genotyping-by-sequencing, validated in 192 DNA samples, affirming its high quality for genotyping tambaqui. The low-density SNP array, with genome-wide coverage and high polymorphism, emerges as an effective tool for exploring genetic variation within diverse populations. Population analyses using the 1K panel proved to be an efficient tool for genetic characterization of sampled broodstocks, making it a valuable resource for genetic improvement programs targeting this Amazon native species.

The review explores parasitic plants' evolutionary success and adaptability, highlighting their widespread occurrence and emphasizing the role of an invasive organ called haustorium in nutrient acquisition from hosts. It discusses the genetic and physiological adaptations that facilitate parasitism, including horizontal gene transfer, and the impact of environmental factors like climate change on these relationships. It addresses the need for further research into parasitic plants' genomes and interactions with their hosts to better predict environmental changes' impacts.

Bovine papillomavirus (BPV) infects cattle cells worldwide, leading to hyperproliferative lesions and the potential development of cancer, driven by E5, E6, and E7 oncoproteins along with other cofactors. E6 oncoprotein binds experimentally to various proteins, primarily paxillin and MAML1, as well as hMCM7 and CBP/p300. However, the molecular and structural mechanisms underlying BPV-induced malignant transformation remain unclear. Therefore, we have modeled the E6 oncoprotein structure from non-oncogenic BPV-5 and compared them with oncogenic BPV-1 to assess the relationship between structural features and oncogenic potential. Our analysis elucidated crucial structural aspects of E6, highlighting both conserved elements across genotypes and genotype-specific variations potentially implicated in the oncogenic process, particularly concerning primary target interactions. Additionally, we predicted the location of the hMCM7 binding site on the N-terminal of BPV-5 E6. This study enhances our understanding of the structural characteristics of BPV E6 oncoproteins and their interactions with host proteins, clarifying structural differences and similarities between high and low-risk BPVs. This is important to understand better the mechanisms involved in cell transformation in BPV infection, which could be used as a possible target for therapy.

Down syndrome (DS), affecting 1 in 700 live births, is the most prevalent chromosomal disorder among newborns. Recognizable by classical clinical features, patients with DS are susceptible to various immunological misbalances. Inflammasome is (mis)activated in several immune-mediated diseases, however studies on individuals with DS are lacking. The present study evaluated the gene expression of NLRP1, NLRP3 and IL-1β in individuals with DS, aiming to understand their susceptibility to immune-mediated diseases. In addition, we assessed whether the individuals with DS present a differential inflammatory response after in vitro infection using PBMCs. For the gene expression assay, 20 individuals with DS and 15 healthy individuals for the control group (CT) were included, while the in vitro infection assay included 10 subjects. mRNA levels from individuals with DS group showed 1.9-fold change (FC) downregulation for NLRP1 (p=0.0001), but no differences for NLRP3 and IL1β. We did not observe significant differences between lipopolysaccharide (LPS)-treated and untreated cells in our in vitro assays. The differential expression of NLRP1 in individuals with DS suggests a potential association with susceptibility to the development of immune-mediated diseases, but further analysis is needed to confirm this relationship.

Bladder cancer is the tenth most frequently diagnosed cancer globally. Classification of high- or low-grade tumors is based on cytological differentiation and is an important prognostic factor. LncRNAs regulate gene expression and play critical roles in the occurrence and development of cancer, however, there are few reports on their diagnostic value and co-expression levels with genes, which may be useful as specific biomarkers for prognosis and therapy in bladder cancer. Thus, we performed a marker lesion study to investigate whether gene/lncRNA expression in urothelial carcinoma tissues may be useful in differentiating low-grade and high-grade tumors. RT-qPCR was used to evaluate the expression of the JHDM1D gene and the lncRNAs CTD-2132N18.2, SBF2-AS1, RP11-977B10.2, CTD-2510F5.4, and RP11-363E7.4 in 20 histologically diagnosed high-grade and 10 low-grade tumors. A protein-to-protein interaction network between genes associated with JHDM1D gene was constructed using STRING website. The results showed a moderate (positive) correlation between CTD-2510F5.4 and CTD2132N18.2. ROC curve analyses showed that combined JHDM1D and RP11-363E7.4 predicted tumor grade with an AUC of 0.826, showing excellent accuracy. In conclusion, the results indicated that the combined expression of JHDM1D and RP11-363E7.4 may be a prognostic biomarker and a promising target for urothelial tumor therapy.

Iron oxide nanoparticles (FeO-NPs) are widely used in scientific and technological fields. Environmental concerns have been raised about residual FeO-NPs levels as their toxicity and bioaccumulative potential are not well understood. Oreochromis niloticus were exposed to nanoparticles of γ-Fe2O3 and Fe3O4. Micro-CT 3D image and grayscale graphic assessments revealed the accumulation of radiopaque material in the digestive tract of fish exposed to FeO-NPs. Histological analysis showed the presence of such NPs in the hepatopancreas, gills, kidneys, and muscles. No genotoxicity occurred, through micronucleus test and comet assay in peripheral erythrocytes. Body clearance was confirmed by iron-content reduction in organisms exposed to FeO-NPs after recovery period. No tissue injuries were observed in the exposed animals which may be attributed to the absence or low toxicity of iron oxide nanoparticles under the study conditions. O. niloticus showed tolerance to sublethal exposures to FeO-NPs.