Resumen en Inglés:

Abstract Bardet-Biedl syndrome (BBS) is a rare ciliopathic disorder that segregates in an autosomal recessive manner. Genetic studies have so far identified 26 BBS-associated genes worldwide. This study analyzed a multiplex consanguineous Pakistani family with Bardet-Biedl syndrome. Genetic analysis was performed using whole-exome sequencing and Sanger sequencing. Additionally, in silico predictions were performed for functional characterization of the identified mutation. Whole exome analysis of this family identified a novel nonsense mutation [(NM_144596: exon11:c.C1047G: p.(Tyr349*)] in the 11th exon of TTC8 gene. The identified mutation presumably leads to removal of four TPR domains and C-terminus portion. Structural analyses of mutant TTC8 protein showed substantial morphologic and interactional variations, suggesting a defective role of the TTC8 protein in BBSome complex and thus its involvement in disease progression. Identification of novel mutation has expanded the mutational spectrum of TTC8. Moreover, these findings will help in genotype-phenotype association, prenatal diagnosis and genetic counseling of families at risk of BBS syndrome.

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Abstract Many countries lack their guidelines for best practices in genomic medicine, whether for clinical practice or research. For the construction of these national guidelines or institutional policies in human genomics research several key criteria must be observed. The determination of variant pathogenicity has become more refined, with specific global recommendations being adopted. A well-conducted consent process, managed by qualified professionals, ensures the protection of research participants’ rights. Pre-established sequencing and data analysis parameters are crucial for ensuring reliable results, and clear guidelines must be provided on whether or not to disclose findings to participants. Data storage remains a challenge due to both the size and sensitivity of the generated files. This work discusses these critical aspects and represents an initiative to propose the best practice recommendations for genomic medicine in human research. These recommendations were developed by a working group of experts and were further refined through discussions with members of the scientific community in genetics and genomic medicine.

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Abstract Cervical cancer is one of the most common types of carcinomas causing morbidity and mortality in women worldwide, primarily caused by high-risk human papillomavirus (hrHPV). However, some cervical tumors, particularly adenocarcinomas, may develop independently of HPV. Chronic cervicitis, often linked to bacterial infections, increases the risk of developing squamous low and high-grade intraepithelial lesions (LSIL and HSIL, respectively) and cervical cancer. Cancer-associated inflammation activates key signaling pathways (NF-κB, STAT, and FOXO), regulating orphan G protein-coupled receptors (oGPCRs) implicated in cancer. Notably, GPR161, GPR132, GPR20, and GPR139 play roles in various tumors. This study analyzed cervical tissue samples from 45 women undergoing colposcopy at UNEME Oncology in Mexicali, Baja California. Patient data, including reproductive history and lifestyle factors, were collected. The histopathological analysis identified 31.1% with cervicitis, 40% with LSIL, and 28.8% with HSIL. mRNA expression of orphan GPRs varied among groups, with GPR132 and GPR20 significantly elevated in LSIL samples (p < 0.05), while GPR139 expression was reduced in LSIL (p < 0.05). No significant difference was found for GPR161. The differential expression of oGPCRs in cervical tissue suggests their involvement in the progression of LSIL and HSIL, offering insights into novel therapeutic targets.

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Abstract Some patients with osteoporosis (OP) do not respond to treatment with bisphosphonates; pathways that stimulate osteoclatogenesis may be involved in this failure, such as the myddosome pathway. A total of 40 OP patients and 20 controls were included in the group study. Patients treated with sodium alendronate (SA) for two years were classified according to bone mineral density (BMD) variations of the lumbar spine, femoral neck, and total hip, measured by the method of dual-energy x-ray absorptiometry (DXA) as responsive patients (OP-R) (n = 20) and non-responders (OP-NR) (n = 20), to evaluate the impact of the myddosome pathway gene expression profile in postmenopausal women with OP. The gene expressions were measured through real-time relative quantitative PCR with Taqman® probes; relative quantification was normalized to GAPDH and RPLP0 reference genes. Non-responders showed increased expression levels of MYD88 and IRAK3 compared to responders Fold change (FC) = 2.86±1.54, p=0.0002 e FC= 3.62±0.46, p<0.0001 respectively. Our results demonstrate the influence of the myddosome on OP maintenance and response to sodium alendronate (SA) treatment, highlighting the importance of this pathway as a potential target for new therapeutic approaches in postmenopausal OP.

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Abstract Spinal muscular atrophy (SMA) is considered one of the most common autosomal recessive disorders, with an estimated incidence of 1 in 10,000 live births. Testing for SMA has been recommended for inclusion in neonatal screening (NBS) panels since there are several therapies available and there is evidence of greater efficacy when introduced in the pre/early symptomatic phases. In the present study, dried blood spot samples collected by the Reference Services of Neonatal Screening of the Brazilian states of Rio Grande do Sul, Sao Paulo, Mato Grosso and Bahia to perform the routine NBS panel were also screened for 5q-SMA, using real-time PCR (SALSA MC002 technique). In this study, samples from 80,000 newborns were analyzed, enabling the identification of 7 5q-SMA cases, which were confirmed by multiplex ligation-dependent probe amplification (MLPA). Considering our findings, Brazil has an incidence of 5q-SMA of 1 in 11,428 live births. This work expands regional knowledge about the incidence of SMA and is fundamental for planning the implementation of screening for this condition in Brazil.

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Abstract Brazil has two dog breeds recognized by the Fédération Cynologique Internationale: the Brazilian Terrier and the Brazilian Mastiff. The Brazilian Terrier is believed to descend from Jack Russell Terriers crossed with local strays and possibly Pinschers, while the Brazilian Mastiff is thought to have originated from crosses involving English Mastiffs, Bloodhounds, and English Bulldogs. Here, we partially sequenced the genomes of one pedigree-certified individual from each breed using Illumina HiSeq. We assembled and annotated their complete mitochondrial genomes and performed comparative phylogenomic analyses. The Brazilian Terrier showed the highest mitogenomic similarity to the Australian Shepherd, Miniature Dachshund, Rottweiler, Cairn Terrier, and Shetland Sheepdog. For the Brazilian Mastiff, the closest matches included the Schipperke, Walker Hound, Tibetan Spaniel, Bolognese, and Great Pyrenees. Analysis of the mitochondrial D-loop region confirmed these results with minor variations. Additionally, we analyzed a partial sequence of the MLPH gene in the Brazilian Terrier to document genetic variants associated with coat color dilution. Altogether, our findings indicate that the genetic origins of both Brazilian breeds are more complex than traditionally assumed. Future studies with broader sampling and nuclear sequencing will be essential to deepen our understanding of their ancestry and evolutionary relationships.

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Abstract Traditional morphological identification is challenging in large and diverse groups, such as the genus Scinax, which comprises about 78 species, and molecular taxonomy emerges as an efficient tool for species delimitation. We generated 164 new mitochondrial 16S rRNA sequences from Scinax individuals collected in north and central-west Brazil, covering the Amazon biome, Amazon-Cerrado transition zones, and the Pantanal. After comparison with all sequences available in GenBank, 22 references representing the closest lineages were selected for detailed analyses. These were examined through phylogenetic inferences, genetic distances, and species delimitation methods (ASAP, ABGD, GMYC, bPTP). The analyses confirmed the genetic identity of individuals belonging to Scinax acuminatus, S. boesemani, S. fuscomarginatus, S. fuscovarius, S. jolyi, S. madeirae, S. nasicus, S. nebulosus, S. proboscideus, S. similis, Scinax sp. 1, sp. 2, sp. 5, sp. 7, sp. 22, and sp. 27. This study also expanded the distribution of eight species, including described and undescribed taxa (S. jolyi, S. proboscideus, S. similis, Scinax sp. 2, Scinax sp. 5, Scinax sp. 7, Scinax sp. 21 and Scinax sp. 27), highlighting the importance of molecular approaches for clarifying biogeographic patterns. Our results reinforce the effectiveness of molecular taxonomy for Scinax identification and contribute to refining genus diversity knowledge, reducing distributional gaps in Neotropical amphibians.

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Abstract Soybean like other commodities brings important income to producer countries. In Brazil, the picture is not different. Thus, due to its economic significance and considering all field challenges, that impose abiotic and biotic constraints to improve yield, research efforts have focused on solving problems by applying biotechnological tools. In this review, a description of genetic engineering being developed in Brazil for soybean crop is addressed, including research in tolerance to abiotic conditions such as drought; to biotic factors such as insects, nematodes and fungal among other categories; as well as the use of soybean as bio-factories. All commercially available soybean events in Brazil and South American countries, for insect resistance and herbicide tolerance are also discussed. An overview of the Brazilian regulatory framework and South American countries for Biotech products is presented as well as the future perspectives for soybean genetic engineering in Brazil. In addition, a list of papers, from 2008 to the present, showing the state of the art of genetic engineering of soybean and by-products in Brazil is made available. The same search on the literature for South American countries did not return papers published on the genetic engineering of soybean and by-products. Although South American countries did not develop science on GM soybean, a search on GM varieties being sowed indicated that these countries adopted GM technology, due to all the advantages that these lines offer.

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Abstract Entomopathogenic filamentous fungi from the Order Hypocreales are studied for biological pest control due to their ability to infect arthropods. Their biotechnological potential lies in the production of secondary metabolites (SMs), encoded by biosynthetic gene clusters (BGCs), which are crucial for the fungal life cycle and infection. Due to the different roles played by SMs in fungi, the in-depth study of these molecules has increased over the last years. Considering the proven biotechnological importance of species of the genus Beauveria have already shown, we performed an in-silico analysis of BGCs of the species from the order Hypocreales to uncover potential conserved pathways and find new candidates for biological pest control. A total of 295 genome sequences were analyzed using antiSMASH, allowing the identification of 12,968 BGCs. Conservation analysis was performed using BiG-SCAPE, which could group these BGCs into 2,127 biosynthetic gene families. Despite the presence of conserved gene clusters, especially within the same genus, when the comparison of BGCs was performed within the order, a large part of them is orphaned, highlighting the great diversity of BGCs and consequently the chemodiversity of fungal species. Our approach helps to uncover new molecules that may provide new biotechnological tools.

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Abstract Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) and CRISPR-associated (Cas) system constitutes a crucial adaptive defense mechanism in prokaryotes against foreign genetic elements. Although CRISPR-Cas systems have been characterized in numerous bacteria, the architecture and function of these systems in the Haemophilus genus remain poorly understood. This study aims to analyze CRISPR-Cas systems in 138Haemophilusstrains and investigate their function, particularly in relation to virulence factors. Results revealed that CRISPR-Cas systems were identified in 31.88% of the Haemophilusstrains. Subtype I-C was the most prevalent, followed by subtypes II-C and III-A. Repeat sequences and thecas1gene were highly conserved within the same subtype. 29.62% of spacer sequences exhibited homology to plasmids or bacteriophages. phiMHaA1 was an important target of the CRISPR-Cas system in Haemophilusgenus. The protospacer adjacent motif sequences (PAM) were determined to be 5′-TTC-3′ for subtype I-C and 5′-TTT-3′ for subtype II-C. Comparative analysis of virulence genes showed that CRISPR-positive strains carried more ompP2 than CRISPR-negative strains, while the distribution of hmw2C and hmw1C exhibited an opposite trend. These findings provide novel insights into the diversity and function of CRISPR-Cas systems inHaemophilusgenus and propose potential strategies for attenuating the impact ofHaemophilusvirulence factors.

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Abstract Xanthomonas citri is a phytopathogenic species with a wide host range that harbors subspecies and pathovars such as citri, mangiferaeindicae, viticola, and malvacearum which cause citrus canker, bacterial canker of the mango, bacterial blight of cotton, and grapevine bacterial canker, respectively. In this work, 32 genomes belonging to these four pathovars were sequenced, two of which were from X. citri subsp. citri, one from X. citri pv. mangiferaeindicae, 13 from X. citri pv. viticola, and 16 from X. citri subsp. malvacearum. The genome size, N50, and GC content ranged from 4,978,419 to 5,256,019 bp, 67,322 to 727,867 bp, and 64.32% and 64.79%, respectively. All strains presented values of dDDH and ANIm greater than 77.3% and 96.1%, when compared to each other, and above 93% and 99%, when compared in relation to their respective pathotype strains. Maximum likelihood analysis of 1,298 core genes grouped the strains and their respective pathotype type with a 100% bootstrap. CRISPR sequences and genes from the Xop family (XopX, XopA, and XopV) and transcription activator-like effectors (TALE) were detected in all analyzed strains. The genomes sequenced in this study will help to understand the biology of these plant pathogens, enabling the development of more effective and precise management strategies and the prevention of disease outbreaks.