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Polycystic ovary syndrome (PCOS) is an endocrine and metabolic disorder with high prevalence in women around the world. The identification of single-nucleotide polymorphisms (SNPs) through genome-wide association studies has classified it as a polygenic disease. Most studies have independently evaluated the contribution of each SNP to the risk of PCOS. Few studies have assessed the effect of epistasis among the identified SNPs. Therefore, this exploratory study aimed to evaluate the interaction of 27 SNPs identified as risk candidates and their contribution to the pathogenesis of PCOS. The study population included 49 control women and 49 women with PCOS with a normal BMI. Genotyping was carried out through the MassARRAY iPLEX single-nucleotide polymorphism typing platform. Using the multifactor dimensionality reduction (MDR) method, the interaction between SNPs was evaluated. The analysis showed that the best interaction model (p < 0.0001) was composed of three loci (rs11692782-FSHR, rs2268361-FSHR, and rs4784165-TOX3). Furthermore, a tendency towards synergy was evident between rs2268361 and the SNPs rs7371084-rs11692782-rs4784165, as well as a redundancy in rs7371084-rs11692782-rs4784165. This pilot study suggests that epistasis may influence PCOS pathophysiology. Large-scale analysis is needed to deepen our understanding of its impact on this complex syndrome affecting thousands of women.

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The Cryptococcus genus comprises more than 100 species, of which C. neoformans and C. gattii are the leading cause of cryptococcosis. The distribution of C. gattii and C. neoformans species complexes has been extensively studied and widely reported globally. Other species such as Naganishia albida, Papiliotrema laurentii, and Papiliotrema flavescens have been reported as pathogenic yeasts. Since there are no reports of environmental isolation in the Boyacá region (Colombia), this study aimed to isolate and characterize Cryptococcus and Cryptococcus-like yeasts from pigeon feces, Eucalyptus, and olive trees distributed in the municipalities of Tunja and Ricaute Alto. The environmental data was recovered, and the isolations obtained were identified by microscopy, biochemical test, MALDI-TOF MS, URA5-RFLP, and sequencing of the ITS and LSU loci. For the 93 pigeon dropping samples collected in Tunja, 23 yielded to C. neoformans, 3 to N. globosa, 2 N. albida and 1 to P. laurentii. Of the 1188 samples collected from olive trees, 17 (1.43%) positive samples were identified as C. gattii species complex (4), C. neoformans species complex (2), P. laurentii (3), N. albida (2), N. globosa (5) and P. flavescens (1). Likewise, specimens of C. neoformans presented molecular type VNI and molecular type VNII; for C. gattii the molecular types found were VGIII and one VGIV by URA5-RFLP but VGIII by MALDI-TOF and sequencing of the ITS and LSU. Therefore, it can be concluded that the species of Cryptococcus, Naganishia and Papiliotrema genera, are present in the environment of Boyacá, and show a predilection for climate conditions that are typical of this region.

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Coronavirus disease (COVID-19) is an infectious disease caused by SARS-CoV-2. In Colombia, many commercial methods are now available to perform the RT-qPCR assays, and laboratories must evaluate their diagnostic accuracy to ensure reliable results for patients suspected of being positive for COVID-19. The purpose of this study was to compare four commercial RT-qPCR assays with respect to their ability to detect the SARS-CoV2 virus from nasopharyngeal swab samples referred to Laboratorio Carvajal IPS, SAS in Tunja, Boyacá, Colombia. We utilized 152 respiratory tract samples (Nasopharyngeal Swabs) from patients suspected of having SARS-CoV-2. The diagnostic accuracy of GeneFinderTM COVID-19 Plus RealAmp (In Vitro Diagnostics) (GF-TM), One-Step Real-Time RT-PCR (Vitro Master Diagnostica) (O-S RT-qPCR), and the Berlin modified protocol (BM) were assessed using the gold-standard Berlin protocol (Berlin Charité Probe One-Step RT-qPCR Kit, New England Biolabs) (BR) as a reference. Operational characteristics were estimated in terms of sensitivity, specificity, agreement, and predictive values. Using the gold-standard BR as a reference, the sensitivity/specificity of the diagnostic tests was found to be 100%/92.7% for GF-TM, 92.75%/67.47% for O-S RT-qPCR, and 100%/96.39% for the BM protocol. Using BR as a reference, the sensitivity/specificity for the diagnostic tests were found to be 100%/92.7% for the GF-TM assay, 92.72%/67.47% for the O-S RT-qPCR, and 100%/96.39% for BM. Relative to the BR reference protocol, the GF-TM and BM RT-PCR assays obtained similar results (k = 0.92 and k = 0.96, respectively), whereas the results obtained by O-S-RT-qPCR were only moderately similar. We conclude that the GF-TM and BM protocols offer the best sensitivity and specificity, with similar results in comparison to the gold-standard BR protocol. We recommend evaluating the diagnostic accuracy of the OS-RT-qPCR protocol in future studies with a larger number of samples.

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Polycystic ovary syndrome (PCOS) is a multifactorial and polygenic endocrine-metabolic disorder in women of reproductive age. SNPs in the THADA gene have been identified as PCOS risk loci. In this study, we evaluated the frequency of five polymorphisms in a sample of Colombian women with PCOS, and their association with clinical and endocrine-metabolic parameters. Forty-nine women with PCOS and forty-nine healthy women were included. Allelic discrimination was performed in the THADA gene by iPLEX and the MassARRAY system (Agena Bioscience). Haploview software was conducted to analyze the linkage disequilibrium (LD) and haplotypes of polymorphisms. There was an association between the genotypes TT of rs12468394, CC + AA of rs12468394, and GG of rs6544661 and an increase in the levels of free testosterone. The CC + AA of rs12468394 genotype also was associated with an increase of androstenedione levels. THADA gene SNPs were not associated with PCOS risk. There was very strong LD among the SNPs. No significant differences in the frequency of haplotypes between groups were observed. The statistical power of this analysis is low because of the small number of samples analyzed. Additional studies involving large populations of Colombian women with PCOS are needed to verify the role of the THADA gene in this disorder.

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Pesticides are a group of environmental pollutants widely used in agriculture to protect crops, and their indiscriminate use has led to a growing public awareness about the health hazards associated with exposure to these substances. In fact, exposure to pesticides has been associated with an increased risk of developing diseases, including cancer. In a study previously published by us, we observed the induction of specific chromosomal alterations and, in general, the deleterious effect of pesticides on the chromosomes of five individuals exposed to pesticides. Considering the importance of our previous findings and their implications in the identification of cytogenetic biomarkers for the monitoring of exposed populations, we decided to conduct a new study with a greater number of individuals exposed to pesticides. Considering the above, the aim of this study was to evaluate the type and frequency of chromosomal alterations, chromosomal variants, the level of chromosomal instability and the clonal heterogeneity in a group of thirty-four farmers occupationally exposed to pesticides in the town of Simijacá, Colombia, and in a control group of thirty-four unexposed individuals, by using Banding Cytogenetics and Molecular Cytogenetics (Fluorescence in situ hybridization). Our results showed that farmers exposed to pesticides had significantly increased frequencies of chromosomal alterations, chromosomal variants, chromosomal instability and clonal heterogeneity when compared with controls. Our results confirm the results previously reported by us, and indicate that occupational exposure to pesticides induces not only chromosomal instability but also clonal heterogeneity in the somatic cells of people exposed to pesticides. This study constitutes, to our knowledge, the first study that reports clonal heterogeneity associated with occupational exposure to pesticides. Chromosomal instability and clonal heterogeneity, in addition to reflecting the instability of the system, could predispose cells to acquire additional instability and, therefore, to an increased risk of developing diseases.

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OBJECTIVE: Prenatal cytogenetic evaluation is a key tool for identifying alterations in pregnant women with high risk for fetal chromosomal abnormalities (CA). In Colombia, there are not large-scale reports about the prevalence and pattern of CA in prenatal cytogenetic analysis. METHOD: A descriptive study was performed from registers of prenatal cytogenetic analysis on amniotic fluid (AF), chorionic villus biopsy (CVS), and fetal blood (FB) samples sent to the specialized laboratory of the Clínica Universitaria Colombia between 2013 and 2019. RESULTS: The prevalence of CA was 20.9%. The trisomies 21, 18, 13, and monosomy X were the most frequent aneuploidies, and the derivative chromosomes were the most frequent structural abnormalities. Although the rate of CA was higher in women over the age of 35 years old; monosomy X, unbalanced rearrangements, and microduplications were associated with the group of women under the age of 35 (p < .05). Trisomies 21 and 18 were the most common aneuploidies identified by FISH and were found to be altered in 52% of the aCGH studies. Ultrasonographic markers associated with CA were the most frequent clinical indication. CONCLUSION: In Colombia, the invasive prenatal cytogenetic analysis continues being an important diagnostic tool available for pregnant women with high risk for fetal CA.

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The genus Cryptococcus comprises more than 80 species, including C. neoformans and C. gattii, which are pathogenic to humans, mainly affecting the central nervous system. The two species differ in geographic distribution and environmental niche. C. neoformans has a worldwide distribution and is often isolated from bird droppings. On the contrary, C. gattii is reported in tropical and subtropical regions and is associated with Eucalyptus species. This review aims to describe the distribution of environmental isolates of the Cryptococcus neoformans species complex and the Cryptococcus gattii species complex in Colombia. A systematic investigation was carried out using different databases, excluding studies of clinical isolates reported in the country. The complex of the species of C. gattii is recovered mainly from trees of the genus Eucalyptus spp., while the complex of the species of C. neoformans is recovered mainly from avian excrement, primarily Columba livia (pigeons) excrement. In addition, greater positivity was found at high levels of relative humidity. Likewise, an association was observed between the presence of the fungus in places with little insolation and cold or temperate temperatures compared to regions with high temperatures.

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Polycystic ovary syndrome (PCOS) is one of the most common endocrine-metabolic disorders in women of reproductive age. It is characterized by an increase in the biosynthesis of androgens, anovulation, and infertility. PCOS has been reported as a polygenic entity in which multiple single nucleotide polymorphisms (SNPs) are associated with the clinical features of the pathology. Herein, we describe the common polymorphic variants in genes related to PCOS, their role in its pathogenesis, and etiology. Whole-genome association studies have been focused on women from Asian and European populations. The most common genes associated with PCOS are DENND1A, THADA, FSHR, and LHCGR. However, other genes have been associated with PCOS such as AMH, AMHR2, ADIPOQ, FTO, HNF1A, CYP19, YAP1, HMGA2, RAB5B, SUOX, INSR, and TOX3. Nevertheless, the relationship between the biological functions of these genes and the development of the pathology is unclear. Studies in each gene in different populations do not always comply with a general pattern, so researching these variants is essential for better understanding of this polygenic syndrome. Future population studies should be carried out to evaluate biological processes, incidence rates, allelic and genotypic frequencies, and genetic susceptibility factors that predispose PCOS.

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The clonal basis of relapse in B-cell precursor acute lymphoblastic leukemia (BCP-ALL) is complex and not fully understood. Next-generation sequencing (NGS), array comparative genomic hybridization (aCGH), and multiplex ligation-dependent probe amplification (MLPA) were carried out in matched diagnosis-relapse samples from 13 BCP-ALL patients to identify patterns of genetic evolution that could account for the phenotypic changes associated with disease relapse. The integrative genomic analysis of aCGH, MLPA and NGS revealed that 100% of the BCP-ALL patients showed at least one genetic alteration at diagnosis and relapse. In addition, there was a significant increase in the frequency of chromosomal lesions at the time of relapse (p = 0.019). MLPA and aCGH techniques showed that IKZF1 was the most frequently deleted gene. TP53 was the most frequently mutated gene at relapse. Two TP53 mutations were detected only at relapse, whereas the three others showed an increase in their mutational burden at relapse. Clonal evolution patterns were heterogeneous, involving the acquisition, loss and maintenance of lesions at relapse. Therefore, this study provides additional evidence that BCP-ALL is a genetically dynamic disease with distinct genetic profiles at diagnosis and relapse. Integrative NGS, aCGH and MLPA analysis enables better molecular characterization of the genetic profile in BCP-ALL patients during the evolution from diagnosis to relapse.

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BACKGROUND: Assisted reproduction techniques (ARTs) and the preimplantation genetic test for aneuploidies (PGT-A) help couples with fertility problems to achieve a healthy live birth around the world. The aim of this study was to determine the rate of whole chromosomal copy number variations in embryos from couples undergoing ART and PGT-A, associations of chromosomal variations with embryo morphological parameters, and their relationship to maternal age. METHODS: This study included a retrospective analysis of the number of whole chromosomal copies identified by aCGH in embryos from couples undergoing ART. RESULTS: Seventy-six embryos from 29 couples using their own gametes were analyzed, of which 25 (32.9%) were chromosomally normal, and 51 (67.1%) were abnormal. Eleven embryos were evaluated from the group of couples with donated gametes, of which 5 (45.4%) embryos were chromosomally normal, and 6 (54.5%) embryos were abnormal. The main aneuploidies observed were trisomy X (7.8%), trisomy 21 (5.9%), trisomy 9 (3.9%), monosomy 11 (3.9%), monosomy 13 (3.9%) and monosomy X (3.9%), and the principal chromosomes affected were 19, X and 13. A significant association was found between the quality of the embryo and the genetic condition: embryos with euploidy and aneuploidy (p=0.046). CONCLUSION: The rate of aneuploidies from couples with their own gametes was 67.1% (51/76) and from couples with donated eggs and/or sperm was 54.5% (6/11). The quality of the embryo determinated by the morphological parameters was not associated with the embryo genetic status, and also there was no association between maternal age and aneuploidy rate.

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INTRODUCTION: An important economic activity in Colombia is agricultural production and farmers are frequently exposed to pesticides. Occupational exposure to pesticides is associated with an increased incidence of various diseases, including cancer, Parkinson's disease, Alzheimer's disease, reproductive disorders, and birth defects. However, although high genotoxicity is associated with these chemicals, information about the type and frequency of specific chromosomal alterations (CAs) and the level of chromosomal instability (CIN) induced by exposure to pesticides is scarce or absent. METHODS: In this study, CAs and CIN were assessed in peripheral blood lymphocytes (PBLs) from five farmers occupationally exposed to pesticides and from five unexposed individuals using GTG-banding and molecular cytogenetic analysis. RESULTS: A significant increase in clonal and non-clonal chromosomal alterations was observed in pesticide-exposed individuals compared with unexposed individuals (510±12,2 vs 73±5,7, respectively; p<0.008). Among all CAs, monosomies and deletions were more frequently observed in the exposed group. Also, a high frequency of fragilities was observed in the exposed group. CONCLUSION: Together, these findings suggest that exposure to pesticides could be associated with CIN in PBLs and indicate the need for the establishment of educational programs on safety precautions when handling pesticides, such as wearing gloves, masks and boots, changing clothes and maintaining proper hygiene, among others. Further evaluation in other similar studies that include a greater number of individuals exposed to pesticides is necessary.

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The 22q11.2 deletion syndrome (22q11.2DS) is present in approximately 5 to 8% of patients with cleft lip, palate, or both (CL/P) and 75 to 80% of patients with congenital heart disease (CHD). In a literature review, we consider this association of 22q11.2DS in pediatric patients with CL/P and CHD. Early diagnosis of 22q11.2DS in pediatric patients with CL/P and CHD helps to optimize a multidisciplinary treatment approach for 22q11DS. Early diagnosis, thereby, can improve quality of life for these patients and awareness of other potential clinical implications that may require attention throughout the patient's life.

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Recurrent pregnancy loss (RPL) is a reproductive disorder defined as two or more successive and spontaneous pregnancy losses (before 20 weeks of gestation), which affects approximately 1-2% of couples. At present, the causes of RPL remain unknown in a considerable number of cases, leading to complications in treatment and high levels of stress in couples. Idiopathic recurrent pregnancy loss (iRPL) has become one of the more complicated reproductive problems worldwide due to the lack of information about its etiology, which limits the counseling and treatment of patients. For that reason, iRPL requires further study of novel factors to provide scientific information for determining clinical prevention and targeted strategies. The aim of this study is to describe the most recent and promising progress in the identification of potential genetic and epigenetic risk factors for iRPL, expanding the genetic etiology of the disease.

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