Caio Santos Silva

Mitochondrial single-nucleotide variants (mtSNVs) can dysregulate cellular bioenergetics and have been increasingly implicated in susceptibility to Parkinson's disease (PD). These variants may impair oxidative metabolism and respiratory chain efficiency, thus contributing to neuronal dysfunction and degeneration. In peripheral blood, mtSNVs may also reflect systemic immunometabolic alterations associated with PD; however, this aspect remains poorly explored, particularly in admixed populations with significant indigenous ancestry. In this study, we analyzed the complete mtDNA of peripheral blood samples from 179 admixed individuals (104 with PD and 75 controls) from the Brazilian Amazon. Associations between mtSNVs and PD were assessed using adjusted logistic regression models, and functional annotation was performed using the Variant Effect Predictor. Furthermore, we proposed and calculated a heteroplasmy-weighted mitochondrial polygenic risk score (mtPRS). We observed a higher mtSNV burden in PD patients, predominantly in RNR2 gene and genes of Complexes I and IV. In total, 536 unique mitochondrial SNVs were identified (214 exclusive to PD, 321 shared between PD and controls, and one exclusive to controls). Four mitochondrial SNVs were associated with PD, including three novel variants (COX1: m.6630G>A, COX2: m.7613C>T, and RNR2: m.1996C>T) and one previously reported variant (ND4: m.12112C>T). Notably, the mitochondrial polygenic risk score (mtPRS) showed a strong association with increased PD risk (OR = 3.64; FDR = 1.12 x 10e-6). Taken together, these results suggest that mtSNVs may contribute to PD susceptibility in admixed Amazonian population, highlighting the relevance of mitochondrial genetic architecture in PD and emphasizing the importance of including underrepresented populations in genomic research.

The present study characterizes the complete mitochondrial genome of Potamotrygon leopoldi, commonly referred to as the “white blotched stingray”, a member of the Potamotrygonidae family that are a group of stingrays that live exclusively in freshwater environments. Potamotrygon leopoldi, endemic to the Xingu River in the Amazon region, are exploited by commercial fisheries for food and commonly exploited by the ornamental industry, and this has a significant impact on the populations. Here, newly assembled PacBio long-read sequencing assesses the complete mitogenome of P. leopoldi and performs a comparative investigation into the evolutionary connections to other extant taxa of elasmobranchs. The mitogenome has 17,504 bp, containing 13 protein-coding, 22 tRNA, and 2 rRNA genes. The mitogenome comprises A: 32.32%, T: 24.41%, C: 12.84%, and G: 30.42%, with an AT content of 56.73%. The values of AT and GC skewness were 0.13 and −0.40, respectively. Our phylogenetic analyses with mitogenome sequences of 40 elasmobranch species support the monophyly for the Potamotrygonidae family and indicate a close relationship to the Dasyatidae family and a sister relationship with Potamotrygon orbignyi and Potamotrygon falkneri. We also detected various amino acid sites in positive selection exclusively in P. leopoldi. This extensive comparative mitogenomic investigation offers novel and significant insights into the evolutionary lineage of neotropical freshwater stingrays and their closely related taxa. It is an indispensable resource for facilitating ongoing and prospective investigations into the molecular evolution of elasmobranchs.

Breast cancer (BC) is the type of neoplasm that most affects women worldwide. It is known that one of the hallmarks of cancer is the resistance to cell death with the evasion of apoptosis. Considering the relevance of TP53, BCL2, CASP3, and CASP9 genes for the occurrence of the intrinsic apoptosis, this study investigated the distribution of the genetic variants rs17880560 (TP53), rs11269260 (BCL2), rs4647655 (CASP3), rs4645982, and rs61079693 (CASP9), as well as genetic ancestry and clinical data, in a BC cohort from the Brazilian Amazon that other variants in these genes might play a role in this process. In the present study, 22 breast cancer tissues and 10 non-cancerous tissues were used, therefore, 32 samples from different patients were subjected to genotyping. We observed that breastfeeding and cancer history were factors that need to be considered for BC (p = 0.022). Therefore, this study contributed to a greater understanding of intrinsic apoptosis in BC, reinforcing previous data that suggest that the history of cancer might be a condition that affects the development of BC and that breastfeeding may act as a protective factor for this type of cancer. We recommend more studies on the genetic factors investigated here, aiming at a future with tools that can help in the early diagnosis.

Mitophagy is an important process that participates in mitochondrial quality control. Dysfunctions in this process can be caused by mutations in genes like PRKN and are associated with the development and progression of Parkinson’s Disease (PD). The most used drug in the treatment of PD is levodopa (LD), but it can cause adverse effects, such as dyskinesia. Currently, few studies are searching for biomarkers for an effective use of lLD for this disease, especially regarding mitophagy genetics. Thus, this work investigates the association of 14 variants of the PRKN gene with LD in the treatment of PD. We recruited 70 patients with PD undergoing treatment with LD (39 without dyskinesia and 31 with dyskinesia). Genotyping was based on Sanger sequencing. Our results reinforce that age at onset of symptoms, duration of PD, and treatment and dosage of LD can influence the occurrence of dyskinesia but not the investigated PRKN variants. The perspective presented here of variants of mitophagy-related genes in the context of treatment with LD is still underexplored, although an association has been indicated in previous studies. We suggest that other variants in PRKN or in other mitophagy genes may participate in the development of levodopa-induced dyskinesia in PD treatment.

Chalcopteryx rutilans Rambur, 1842 (Polythoridae, Odonata) is a species widely distributed in central Amazonia. Due to its sensitivity to environmental changes, it is a bioindicator species used to evaluate the environmental conditions of streams in federally protected areas. By sequencing C. rutilans mitogenome, we report the first whole mitogenome from the Polythoridae family and the first from an Odonata species endemic to South America. The entire mitogenome has 15,653 bp and contains 13 protein-coding, 22 tRNA, and two rRNA genes. The nucleotide composition of the mitogenome is 42.7%, T: 25.5%, C: 19.4%, and G: 12.4%. The AT and GC skews of the mitogenome sequence were 0.249 and −0.220, respectively. C. rutilans was recovered as a sister to Pseudolestes mirabilis Kirby, 1900 (Pseudolestidae), demonstrating the absence of mitogenomes of species from multiple families in the current literature. Mitogenome data from this study will provide useful information for further studies on the phylogeny and conservation of Polythoridae.

Hyphessobrycon heterorhabdus (Ulrey, 1894), popularly known as ‘Flag Tetra’ in English speaking countries, belongs to the genus Hyphessobrycon of the family Characidae, and is widely present in the eastern Amazon basin. Here, using Illumina sequencing, we report the complete mitogenome sequence of H. heterorhabdus. Overall, the mitogenome has 17,021 bp, containing 13 protein-coding, 22 tRNA, and 2 rRNA genes. Non-ambiguous nucleotide compositions of the H. heterorhabdus mitogenome are A: 29.2%, T: 29.4%, G: 15.6%, and C: 25.8%. As recently indicated, the phylogenetic analyses did not support four separate genera (Hemigrammus, Hyphessobrycon, Moenkhausia, and Psalidodon) of Characidae. Understanding the H. heterorhabdus mitogenome is important for taxonomic purposes as well as for the molecular characterization of environmental pollutants. Thus, the mitogenome described here will be a valuable resource for studies on environmental changes, evolutionary genetics, species delimitation, and phylogenetic analyses in Characidae.

Vitamin D has been considered a strong contributing factor to type 1 diabetes mellitus (T1DM). Many studies have investigated polymorphisms in the VDR gene in association with T1DM in different populations, but there are still conflicting findings. This study aimed to evaluate the association of four variants in the VDR gene (rs7975232, rs1544410, rs731236, and rs2228570) with T1DM risk and vitamin D levels within a population from North Region, Brazil, as well as the influence of genomic ancestry on T1DM. A total of 65 T1DM patients and 83 non-T1DM patients were enrolled in this study. VDR gene polymorphisms were assessed using Sanger sequencing analysis. Genomic ancestry was analyzed using a set of 61 ancestry-informative markers. T1DM patients showed higher European genomic contribution and lower Native American genomic contribution when compared to non-T1DM patients. T1DM patients with AA genotype in rs1544410 or CC genotype in rs731236 had significantly lower 25(OH)D levels compared to the other two genotypes (p = 0.013 and p = 0.02, respectively), while T1DM with TT genotype in rs2228570 had higher 25(OH)D levels compared to CC + TC in the same polymorphism (p = 0.011). Our findings suggest that the association between 25(OH)D and T1DM may be modified by VDR variants, possibly influencing the development of this autoimmune disease.

The objective this work was to evaluate genetically the buffaloes populations using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in the leptin and stearoyl-CoA desaturase (SCD) genes, and associate the genotypes with milk production. Sixty-nine samples of Bubalus bubalis - 38 Murrah breed, 18 Mediterranean and 13 mixed-breed of the Murrah with Mediterranean - were evaluated. Allele and genotype frequencies, the heterozygosity observed and expected, the inbreeding coefficients (FIS), the probabilities of the Hardy-Weinberg equilibrium, the F statistic for population differentiation and Shannon index were calculated using GENEPOP and GenALEx programs. The associations of the different genotypes with a role in milk production were tested by Analysis of Variance (ANOVA) and t-test. We reported the leptin and SCD allele contribution to genetic variability in buffaloes herds in the Brazilian Amazonian region. The A allele was more representative in leptin and SCD genes for all breed groups. No significant effects between genotypes and milk production were found in the present study, but there is an indicative that AA genotype in leptin gene affects milk production in Murrah breed.

The Amazonian symbol fish Arapaima gigas is the only living representative of the Arapamidae family. Environmental pressures and illegal fishing threaten the species’ survival. To protect wild populations, a national regulation must be developed for the management of A. gigas throughout the Amazon basin. Moreover, the reproductive genetic management and recruitment of additional founders by aquaculture farms are needed to mitigate the damage caused by domestication. To contribute to the sustainable development, we investigated the genetic diversity of wild and cultivated populations of A. gigas and developed a panel composed by 12 microsatellite markers for individual and population genetic tracing. We analyzed 368 samples from three wild and four farmed populations. The results revealed low rates of genetic diversity in all populations, loss of genetic diversity and high inbreeding rates in farmed populations, and genetic structuring among wild and farmed populations. Genetic tracing using the 12 microsatellite markers was effective, and presented a better performance in identifying samples at the population level. The 12-microsatellite panel is appliable to the legal aspects of the trade of the A. gigas, such as origin discrimination, reproductive genetic management by DNA profiling, and evaluation and monitoring of genetic diversity.