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.

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.

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. (MTHFR metabolism TP TP5 integrity date CT C T rs rs180113 ProArg Pro Arg rs104252 antagonist (PsA n=114 n114 n 114 (n=114 n=100 n100 100 (n=100 RFLPPCR. RFLPPCR RFLP PCR. PCR RFLP-PCR i (i genotyping Tallele allele 40% 40 (40 22% 22 OR231 OR 2 31 OR=2.31 95 CI=1.104.88, CI110488 CI CI=1.10 4.88, 1 10 4 88 CI=1.10-4.88 p=0.0379. p00379 p p=0.0379 . 0 0379 p=0.0379) CTTT TT 11.70 1170 11 70 (11.7 5.328.80 532880 5.3 28.80 5 3 28 80 (5.3-28.80 mgmL mg mL 740 7 7.4 5.0015.05 5001505 5.00 15.05 00 15 05 (5.00-15.05 p=0.0355. p00355 p=0.0355 0355 p=0.0355) similar ii (ii Argallele 42% 42 (42 29% 29 OR175 75 OR=1.75 CI=1.072.86, CI107286 CI=1.07 2.86, 07 86 CI=1.07-2.86 p=0.0275. p00275 p=0.0275 0275 p=0.0275) conclusion rs18011 rs10425 n=11 n11 (n=11 n=10 n10 (n=10 (4 OR23 OR=2.3 9 104 CI=1.104.88 CI11048 CI110 CI=1.1 488 4.88 8 CI=1.10-4.8 p0037 p=0.037 037 11.7 117 (11. 328 5.328.8 53288 53 5. 2880 28.8 (5.3-28.8 74 7. 0015 5.0015.0 500150 500 5.0 1505 15.0 (5.00-15.0 p0035 p=0.035 035 OR17 OR=1.7 072 CI=1.072.86 CI10728 CI107 CI=1.0 286 2.86 CI=1.07-2.8 p0027 p=0.027 027 rs1801 rs1042 n=1 n1 (n=1 ( OR2 OR=2. CI=1.104.8 CI1104 CI11 CI=1. 48 4.8 CI=1.10-4. p003 p=0.03 03 11. (11 32 5.328. 5328 288 28. (5.3-28. 001 5.0015. 50015 50 150 15. (5.00-15. OR1 OR=1. CI=1.072.8 CI1072 CI10 2.8 CI=1.07-2. p002 p=0.02 02 rs180 rs104 n= (n= OR=2 CI=1.104. CI1 CI=1 4. CI=1.10-4 p00 p=0.0 (1 5.328 532 (5.3-28 5.0015 5001 (5.00-15 OR=1 CI=1.072. 2. CI=1.07-2 rs18 rs10 (n OR= CI=1.104 CI= CI=1.10- p0 p=0. 5.32 (5.3-2 5.001 (5.00-1 CI=1.072 CI=1.07- rs1 p=0 (5.3- (5.00- p= (5.3 (5.00 (5. (5.0 (5

Abstract Transplantation of stem cells derived from donors with CCR5Δ32 homozygous genotype is a potential strategy to achieve both the control of malignant hematological disease as well as sustained remission of the HIV infection, and researchers in different countries are looking for CCR5Δ32 homozygous donors to replicate such a ‘double-target’ strategy. We determined the frequency of the CCR5Δ32 variant in a sample of 1,398 bone marrow donors from Rio Grande do Sul State, Brazil. This study also evaluated whether HLA-A, HLA-B and HLA-DRB1 genotypes are homogeneously distributed between CCR5Δ32 carriers and non-carriers in a population characterized by a significant genetic admixture. The CCR5Δ32 allele frequency was 7.4% (CI0.95 6.4-8.4%), and the frequency of the Δ32/Δ32 homozygous genotype was 0.72% (CI0.95 0.34-1.31%). In general, HLA genotypes are homogeneously distributed between CCR5Δ32 carriers and non-carriers. Considering the large number of bone marrow donors in Brazil and the high CCR5Δ32 allele frequency observed in our study, our results clearly indicate the existence of a considerable amount of potential CCR5Δ32 homozygous bone marrow donors in southern Brazil, suggesting that an active search for these donors is not only feasible but an attractive and promising strategy towards effective HIV infection control and treatment. CCRΔ CCR Δ CCR5Δ3 ‘doubletarget doubletarget ‘double target double ‘double-target 1398 1 398 1,39 State HLAA, HLAA A, A HLA-A HLAB B HLADRB1 HLADRB DRB1 DRB HLA-DRB noncarriers non admixture 74 7 4 7.4 CI0.95 CI095 CI CI0 95 (CI0.9 6.48.4%, 6484 6.4 8.4% , 6 8 6.4-8.4%) Δ32Δ32 ΔΔ Δ32 Δ32/Δ3 072 0 72 0.72 0.341.31%. 034131 0.34 1.31% . 34 31 0.34-1.31%) general noncarriers. carriers. treatment CCR5Δ 139 39 1,3 7. CI0.9 CI09 9 (CI0. 48 6.48.4% 648 64 6. 84 8.4 6.4-8.4% Δ32Δ3 Δ3 Δ32/Δ 07 0.7 341 0.341.31% 03413 034 0.3 131 1.31 3 0.34-1.31% 13 1, CI0. (CI0 6.48.4 8. 6.4-8.4 Δ32Δ 0. 0.341.31 0341 03 1.3 0.34-1.31 (CI 6.48. 6.4-8. 0.341.3 1. 0.34-1.3 6.48 6.4-8 0.341. 0.34-1. 6.4- 0.341 0.34-1 0.34-

Abstract 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. Pp, , (Pp) process Egh16like Eghlike Egh16 like Egh soybean Herein 2 MT MT200 1 UFV UFV0 K K810 expansion peptide cysteinerich cysteine rich RYFxC R Y FxC Cterminal C terminal region virulencerelated virulence Benthamiana PAMPrelated PAMP (Pp Egh1 MT20 K81 MT2 K8

Abstract 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. (CMA (CNV rearrangements recurrence GoiásBrazil. GoiásBrazil Goiás Brazil. Brazil Goiás-Brazil 7 1 60 40 LCR (LCR 467 46 46.7 highidentity high identity nonallelic non allelic nonrecurrent. nonrecurrent recurrent. recurrent non-recurrent microhomologymediated microhomology breakinduced break induced nonhomologous joining 6 4 46.

Abstract Butyrate is a promising candidate for an antitumoral drug, as it promotes cancer cell apoptosis and reduces hormone receptor activity, while promoting differentiation and proliferation in normal cells. However, the effects of low-dose butyrate on breast cancer cell cultures are unclear. We explored the impact of sub-therapeutic doses of butyrate on estrogen receptor alpha (ERα) transcriptional activity in MCF-7 cells, using RT-qPCR, Western blot, wound-healing assays, and chromatin immunoprecipitation. Our results showed that sub-therapeutic doses of sodium butyrate (0.1 - 0.2 mM) increased the transcription of ESR1, TFF1, and CSTD genes, but did not affect ERα protein levels. Moreover, we observed an increase in cell migration in wound-healing assays. ChIP assays revealed that treatment with 0.1 mM of sodium butyrate resulted in estrogen-independent recruitment of ERα at the pS2 promoter and loss of NCoR. Appropriate therapeutic dosage of butyrate is essential to avoid potential adverse effects on patients’ health, especially in the case of estrogen receptor-positive breast tumors. Sub-therapeutic doses of butyrate may induce undesirable cell processes, such as migration due to low-dose butyrate-mediated ERα activation. These findings shed light on the complex effects of butyrate in breast cancer and provide insights for research in the development of antitumoral drugs. drug cells However lowdose low dose unclear subtherapeutic sub (ERα MCF7 MCF 7 MCF- RTqPCR, RTqPCR RT qPCR, qPCR RT-qPCR blot woundhealing wound healing immunoprecipitation 01 0 1 (0. 02 2 0. ESR1 ESR TFF1 TFF genes levels Moreover estrogenindependent independent pS NCoR patients health receptorpositive positive tumors Subtherapeutic Sub processes butyratemediated mediated activation drugs (0 (

Abstract Mucopolysaccharidosis type IIIB (MPS IIIB) is caused by deficiency of alpha-N-acetylglucosaminidase, leading to storage of heparan sulphate. The disease is characterized by intellectual disability and hyperactivity, among other neurological and somatic features. Here we studied retrospective data from a total of 19 MPS IIIB patients from Brazil, aiming to evaluate disease progression. Mean age at diagnosis was 7.2 years. Speech delay was one of the first symptoms to be identified, around 2-3 years of age. Behavioral alterations include hyperactivity and aggressiveness, starting around age four. By the end of the first decade, patients lost acquired abilities such as speech and ability to walk. Furthermore, as disease progresses, respiratory, cardiovascular and joint abnormalities were found in more than 50% of the patients, along with organomegaly. Most common cause of death was respiratory problems. The disease progression was characterized in multiple systems, and hopefully these data will help the design of appropriate clinical trials and clinical management guidelines. alphaNacetylglucosaminidase, alphaNacetylglucosaminidase alpha N acetylglucosaminidase, acetylglucosaminidase alpha-N-acetylglucosaminidase sulphate features 1 Brazil 72 7 2 7. identified 23 3 2- aggressiveness four decade walk Furthermore progresses 50 organomegaly problems systems guidelines 5

Abstract Group I introns are small RNAs (250-500 nt) capable of catalyzing their own splicing from the precursor RNA. They are widely distributed across the tree of life and have intricate relationships with their host genomes. In this work, we review its basic structure, self-splicing and its mechanisms of gene mobility. As they are widely found in unicellular eukaryotes, especially fungi, we gathered information regarding their possible impact on the physiology of fungal cells and the possible application of these introns in medical mycology. 250500 250 500 (250-50 nt RNA genomes work structure selfsplicing self mobility eukaryotes fungi mycology 25050 25 50 (250-5 2505 2 5 (250- (250 (25 (2 (

Abstract Latin America (LatAm) has a rich and historically significant role in delineating both novel and well-documented genetic disorders. However, the ongoing advancements in the field of human genetics pose challenges to the relatively slow adaption of LatAm in the field. Here, we describe past and present contributions of LatAm to the discovery of novel genetic disorders, often referred as novel gene-disease associations (NGDA). We also describe the current methodologies for discovery of NGDA, taking into account the latest developments in genomics. We provide an overview of opportunities and challenges for NGDA research in LatAm considering the steps currently performed to identify and validate such associations. Given the multiple and diverse needs of populations and countries in LatAm, it is imperative to foster collaborations amongst patients, indigenous people, clinicians and scientists. Such collaborative effort is essential for sustaining and enhancing the LatAm´s contributions to the field of NGDA. (LatAm welldocumented well documented disorders However Here genedisease gene disease . (NGDA) genomics patients people scientists LatAms s (NGDA

Abstract Growth differentiation factor 11 (GDF11) and myostatin (MSTN/GDF8) are closely related members of the transforming growth factor β (TGFβ) superfamily, sharing structural homology. Despite these structural similarities, recent research has shed light on the distinct roles these ligands play within muscle tissue. This study aims to uncover both the differences and similarities in gene expression at the transcriptome level by utilizing RNA sequencing. We conducted experiments involving five distinct groups, each with three biological replicates, using C2C12 cell cultures. The cells were subjected to high-throughput profiling to investigate disparities in gene expression patterns following preconditioning with either GDF11 or MSTN at concentrations of 1 nM and 10 nM, respectively. In addition, control groups were established. Our research revealed concentration-dependent gene expression patterns, with 38 genes showing significant differences when compared to the control groups. Notably, GADD45, SMAD7, EGR-1, and HOXA3 exhibited significant differential expression. We also conducted an over-representation analysis, highlighting the activation of MAPK and JNK signaling pathways, along with GO-terms related to genes that negatively regulate metabolic processes, biosynthesis, and protein phosphorylation. This study unveiled the activation of several genes not previously discussed in existing literature whose full biological implications are yet to be determined in future research. GDF (GDF11 MSTN/GDF8 MSTNGDF8 MSTNGDF GDF8 (MSTN/GDF8 TGFβ (TGFβ superfamily homology tissue sequencing replicates CC C C2C1 cultures highthroughput high throughput GDF1 respectively addition established concentrationdependent concentration dependent 3 Notably GADD45 GADD SMAD7 SMAD EGR1, EGR1 EGR 1, EGR-1 HOXA overrepresentation over representation analysis pathways GOterms GO terms processes biosynthesis phosphorylation (GDF1 MSTN/GDF (MSTN/GDF C2C GADD4 EGR- (GDF

Abstract Major histocompatibility complex (MHC) allelic polymorphism is critically important for mediating antigen presentation in vertebrates. Presently, there are insufficient studies of MHC genetic diversity in domestic Anseriform birds. In this study, we analyzed the expression profile of MHC I genes and screened for MHC I exon 2 polymorphism in one domestic goose population from China using Illumina MiSeq sequencing. The results showed that four MHC I alleles (Ancy-IE2*09/*11/*13/*21) in one goose were identified based on cDNA cloning and sequencing using four primer combinations, and the varying number of cDNA clones implied that these four classical sequences showed differential expression patterns. Through next-generation sequencing, 27 alleles were obtained from 68 geese with 3-10 putative alleles per individual, indicating at least the existence of 5 MHC I loci in the goose. The marked excess of the non-synonymous over the synonymous substitution in the peptide-binding region (PBR) along 27 alleles and five positively selected sites (PSSs) detected around the PBR indicated that balancing selection might be the major force in shaping high MHC variation in the goose. Additionally, IA alleles displaying lower polymorphism were subject to less positive selection pressure than non-IA alleles with a higher level of polymorphism. (MHC vertebrates Presently birds study AncyIE2*09/*11/*13/*21 AncyIE209111321 AncyIE Ancy IE2*09/*11/*13/*21 IE2 09 11 13 21 IE (Ancy-IE2*09/*11/*13/*21 combinations patterns nextgeneration next generation 6 310 3 10 3-1 individual nonsynonymous non peptidebinding peptide binding (PBR PSSs (PSSs Additionally nonIA AncyIE2 AncyIE2*09/*11/*13/*2 AncyIE20911132 IE209111321 IE2*09/*11/*13/*2 0 1 (Ancy-IE2*09/*11/*13/*2 31 3- AncyIE2*09/*11/*13/* AncyIE2091113 IE20911132 IE2*09/*11/*13/* (Ancy-IE2*09/*11/*13/* AncyIE2*09/*11/*13/ AncyIE209111 IE2091113 IE2*09/*11/*13/ (Ancy-IE2*09/*11/*13/ AncyIE2*09/*11/*13 AncyIE20911 IE209111 IE2*09/*11/*13 (Ancy-IE2*09/*11/*13 AncyIE2*09/*11/*1 AncyIE2091 IE20911 IE2*09/*11/*1 (Ancy-IE2*09/*11/*1 AncyIE2*09/*11/* AncyIE209 IE2091 IE2*09/*11/* (Ancy-IE2*09/*11/* AncyIE2*09/*11/ AncyIE20 IE209 IE2*09/*11/ (Ancy-IE2*09/*11/ AncyIE2*09/*11 IE20 IE2*09/*11 (Ancy-IE2*09/*11 AncyIE2*09/*1 IE2*09/*1 (Ancy-IE2*09/*1 AncyIE2*09/* IE2*09/* (Ancy-IE2*09/* AncyIE2*09/ IE2*09/ (Ancy-IE2*09/ AncyIE2*09 IE2*09 (Ancy-IE2*09 AncyIE2*0 IE2*0 (Ancy-IE2*0 AncyIE2* IE2* (Ancy-IE2* (Ancy-IE2 (Ancy-IE

Abstract The breast microbiome presents a diverse microbial community that could affects health and disease states, in the context of breast cancer. Sequencing technologies have allowed describing the diversity and abundance of microbial communities among individuals. The complex tumoral microenvironment that includes the microbial composition could influence tumor growth. The imbalance of diversity and abundance inside the microbial community, known as dysbiosis plays a crucial role in this context. One the most prevalent bacterial genera described in breast invasive carcinoma are Bacillus, Pseudomonas, Brevibacillus, Mycobacterium, Thermoviga, Acinetobacter, Corynebacterium, Paenibacillus, Ensifer, and Bacteroides. Paenibacills genus shows a relation with patient survival. When the Paenibacills genus increases its abundance in patients with breast cancer, the survival probability decreases. Within this dysbiotic environment, various bacterial metabolites could play a pivotal role in the progression and modulation of breast cancer. Key bacterial metabolites, such as cadaverine, lipopolysaccharides (LPS), and trimethylamine N-oxide (TMAO), have been found to exhibit potential interactions within breast tissue microenvironments. Understanding the intricate relationships between dysbiosis and these metabolites in breast cancer may open new avenues for diagnostic biomarkers and therapeutic targets. Further research is essential to unravel the specific roles and mechanisms of these microbial metabolites in breast cancer progression. states individuals growth Bacillus Pseudomonas Brevibacillus Mycobacterium Thermoviga Acinetobacter Corynebacterium Paenibacillus Ensifer Bacteroides decreases environment cadaverine LPS, LPS , (LPS) Noxide N oxide TMAO, TMAO (TMAO) microenvironments targets (LPS (TMAO

Abstract Distinguishing between environmental adaptations and neutral processes poses a challenge in population genetics and evolutionary studies, particularly when phenomena can be explained by both processes. Clines are genotypic or phenotypic characters correlated with environmental variables, because of that correlation, they are used as examples of spatially varying selection. At the same time, many genotypic clines can be explained by demographic history, like isolation by distance or secondary contact zones. Clines have been extensively studied in Drosophila melanogaster, especially in North America and Australia, where they are attributed to both differential selection and various demographic processes. This review explores existing literature supporting this conclusion and suggests new approaches to better understand the influence of these processes on clines. These innovative approaches aim to shed light on the longstanding debate regarding the importance of natural selection versus neutral processes in maintaining variation in natural populations. studies variables correlation time history zones melanogaster Australia populations

Abstract Oral squamous cell carcinoma (OSCC) has a poor prognosis and the treatment employed generates significant physical deformity in patients. In recent years, an increase in the incidence of cases of OSCC has been observed in adult patients up to 45 years old in several genetic underrepresented and underserved countries. The increase in OSCC cases in young people is very relevant because it shows that OSCC does not make exceptions and hereditarily must play an important role. This fact has not been associated with an evident biological basis, and a large majority of these patients do not present the classic principal risk factors association. OSCC is the result of accumulation of genetic and epigenetic alterations and this information is still fragmented in the literature, mainly in the young group. Conducting studies with a comprehensive analysis of genetic and epigenetic data is crucial, to provide greater understanding of the underlying biology of OSCC, because this information can be decisive to determine targets for therapeutic treatment. We review the main germline and somatic aspects of genetic and genomic variation in OSCC considering the absence of genomic data from developing countries such as Chile and the rest of Hispano-America. (OSCC 4 role basis association literature group crucial HispanoAmerica. HispanoAmerica Hispano America. America Hispano-America