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BACKGROUND: Psoriasis is strongly associated with insulin resistance (IR). Lipid profile disturbances and upregulation of enzymes crucial for fatty acid oxidation have been reported in patients with psoriasis. Mitochondrial ß-oxidation is altered in patients with IR. Common mitochondrial dysfunction may be involved in the origin of both diseases. OBJECTIVE: This study aimed to evaluate mitochondrial ß-oxidation, intermediary metabolism, and mitochondrial content in psoriatic patients with or without IR and compare them to healthy controls. METHODS: The participants were divided into three groups: (1) psoriasis and IR (n = 26); (2) psoriasis without IR (n = 17); and (3) healthy controls (n = 17). Quantification of amino acids and acylcarnitines (AC) by tandem mass spectrometry, determination of urinary organic acids by gas chromatography/mass spectrometry (GC/MS), and mitochondrial DNA quantification were performed in all groups. RESULTS: When comparisons were made between the two psoriatic groups, no differences were found between: C5DC + C6OH, C16:1, Met/Leu, Met/Phe, C16:1/C16, and C5DC + C6OH/C4DC + C5OH ratios. Nine analytes were different: phenylalanine, Cit/Phe, and Cit/Tyr ratios, C0, C3, C5, C6DC, C16, and C18:1OH. There were no correlations between psoriasis area and severity index (PASI), body mass index (BMI) and duration of disease with ACs. A higher proportion of patients with psoriasis showed increased urine levels of uric acid and hippuric acid (p = 0.01). The mtDNA content was significantly higher in cases than in controls, with no differences between IR and non-IR psoriatic patients. CONCLUSIONS: Psoriasis patients with and without IR have a different acylcarnitine profile reflecting impaired ß-oxidation. A distinctive profile of acylcarnitines suggests an involvement of mitochondrial function associated with an increase in stearoyl CoA desaturase (SCD) activity in psoriatic patients with and without IR.
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Resistência à Insulina , Psoríase , Humanos , Aminoácidos , MitocôndriasRESUMO
OBJECTIVE: Preeclampsia (PE) is a leading cause of pregnancy-associated maternal and neonatal morbidity and mortality. Detection of patients at risk before the clinical onset of PE is a priority. Proteomics have become a valuable tool for the discovery of new biomarkers; however, the understanding of the underlying mechanism is necessary. The aim of the study was to determine differences between proteomic serum profiles of PE and normotensive pregnancies using quantitative and qualitative approaches. STUDY DESIGN: Serum samples from pregnant women were taken at 10-12 weeks of gestation with follow-up to determine PE development. Samples were analyzed using nano 2-D liquid chromatography UPLC and qTOF-MS/MS. RESULTS: A total of 136 women were recruited, of which eight (5.9%) developed PE, and eight normotensive were randomly selected as a control group for comparison. A different profile was obtained between groups. Nine proteins showed quantitative differences with fold-change over 1.5: PRRC2C (217.02), HEATR5A (179.46), ATP6 (162.38), PRRC2B (83.09), RBM25 (5.36), NUP205 (3.38), HLA-I (2.27), ZC3H13 (2.15), and SREK1 (1.66); and two under 0.66: Importin-4 (0.55) and Cytochrome b (0.26). Using bilateral Fisher's exact test for the qualitative approach, LRRK1 had statistical significance (p = .044), while PRRC2B (p = .121), PRRC2C (p = .134), and NUP205 (p = .134) showed a tendency to be present in PE. CONCLUSION: The found proteins have plausibility with the early pathophysiological events that have been associated with this pathology. Further studies should be performed to confirm these findings and elucidate their specific roles.
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Pré-Eclâmpsia , Proteômica , Biomarcadores , Estudos de Casos e Controles , Feminino , Humanos , Recém-Nascido , Pré-Eclâmpsia/diagnóstico , Pré-Eclâmpsia/metabolismo , Gravidez , Primeiro Trimestre da Gravidez , Terceiro Trimestre da Gravidez , Fatores de Processamento de Serina-Arginina , Espectrometria de Massas em TandemRESUMO
BACKGROUND: Genitourinary disorders are the most frequent congenital defects in newborns; however, little is known about their etiology. Several studies have been carried out to find genetic risk factors in the development of these malformations. The expression of VAMP7 is found in testes, epididymis, seminal vesicles, prostatic tissues, penis, and urethra. Alterations in gene dose of VAMP7 were recently reported in a subset of male patients initially identified clinically by the presence of congenital genitourinary disorders. In 2016, the authors developed a diagnostic algorithm for early detection of sex chromosome aneuploidies by quantifying the SHOX, VAMP7, and SRY gene dose in newborns by qPCR using dried blood spot (DBS) samples. OBJECTIVE: Correlate the increased gene dose of VAMP7, obtained by qPCR using DBS, with genitourinary congenital defects attributable to disorders in virilization and verify the increased gene dose by microarrays. STUDY DESIGN: Samples that only presented increased VAMP7 gene dosage were selected from a previously analyzed group of 5088 males in which the early detection of sex chromosomes aneuploidies was performed. Eight males were found with an increased gene dose of VAMP7 (relative quantitation > 1.3) and were called in for a complete clinical evaluation aimed at the identification of genitourinary anomalies, qPCR and microarrays. RESULTS: Eight males from 5088 samples were identified with increased VAMP7 gene dosage of which six patients were clinically evaluated, of which 50% were identified with alterations in genital development (bilateral cryptorchidism, unilateral cryptorchidism, and glandular hypospadias) and speech delay, while the rest presented different types of atopy. DISCUSSION: Tannour-Louet et al. postulated on 2014 that the duplication of the Xq28 region, specifically of VAMP7, plays a role in the human masculinization disorders of the urogenital tract. The study was based on array comparative genomic hybridization (aCGH) results performed to 116 males with disorders of sexual differentiation. In the present study, the patients were initially selected due to an increased gene dose of VAMP7 detected by qPCR, then the clinical evaluation and the aCGH were performed, inverse to what was reported previously but with similar percentages between both studies. CONCLUSION: In this work, the authors report cases of cryptorchidism, hypospadias, language delay and atopy in male preschoolers initially identified because they have an increased gene dose of VAMP7.
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Criptorquidismo , Hipospadia , Hibridização Genômica Comparativa , Feminino , Dosagem de Genes , Humanos , Lactente , Recém-Nascido , Masculino , Proteínas R-SNARE/genética , VirilismoRESUMO
Aims: To explore the feasibility of detecting sex chromosome aneuploidies (SCAs) by means of gene copy number quantification of short stature homeobox (SHOX), vesicle-associated membrane protein 7 (VAMP7), and SRY in newborns. Materials and Methods: Gene doses of SHOX, VAMP7, and SRY were determined by quantitative polymerase chain reaction (qPCR) using DNA obtained from dried blood samples from newborns. Relative quantification values were obtained. An aneuploidy profile was established according to cutoff values. Samples with ≥2 gene doses (out of range) were reanalyzed, and those with aneuploidy profiles were confirmed by karyotyping. Sensitivity, specificity, and positive and negative predictive values were obtained. Results: A total of 10,033 samples were collected (4945 females and 5088 males). Of 244 (2.43%) samples with ≥2 gene doses that were retested, 20 cases were confirmed. The overall incidence of SCAs was 1 in 500 live newborns. There were six cases of Turner syndrome (1/824), 3 cases of XXX (1/1648), 7 cases of Klinefelter syndrome (1/726), and 4 cases of of XYY (1/1272). The sensitivity was 0.952 (95.42%); the specificity was 0.975 (97.56%); the positive predictive value was 0.909 (90.91%) and the negative predictive value was 0.987 (98.77%). Conclusions: Gene copy number analyses of the VAMP7, SHOX, and SRY genes by qPCR from blood samples spotted onto filter paper is a highly reliable method for the early detection of male and female SCAs.
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Triagem Neonatal/métodos , Transtornos do Cromossomo Sexual no Desenvolvimento Sexual/diagnóstico , Transtornos do Cromossomo Sexual no Desenvolvimento Sexual/genética , Aneuploidia , Cromossomos Humanos X , Variações do Número de Cópias de DNA/genética , Feminino , Dosagem de Genes , Humanos , Recém-Nascido , Cariotipagem/métodos , Síndrome de Klinefelter/diagnóstico , Masculino , México , Diagnóstico Pré-Natal/métodos , Proteínas R-SNARE/genética , Aberrações dos Cromossomos Sexuais , Cromossomos Sexuais/genética , Proteína da Região Y Determinante do Sexo/genética , Proteína de Homoeobox de Baixa Estatura/genética , Trissomia/diagnóstico , Síndrome de Turner/diagnósticoRESUMO
Hereditary breast and ovarian cancer (HBOC) syndrome is mainly caused by mutations in the BRCA1 and BRCA2 genes. The 3'UTR region allows for the binding of microRNAs, which are involved in genetic tune regulation. We aimed to identify allelic variants on 3'UTR miRNA-binding sites in the BRCA1 and BRCA2 genes in HBOC patients. Blood samples were obtained from 50 patients with HBOC and from 50 controls. The 3'UTR regions of BRCA1 and BRCA2 were amplified by PCR and sequenced to identify genetic variants using bioinformatics tools. We detected nine polymorphisms in 3'UTR, namely: four in BRCA1 (rs3092995 (C/G), rs8176318 (C/T), rs111791349 (G/A), and rs12516 (C/T)) and five in BRCA2 (rs15869 (A/C), rs7334543 (A/G), rs1157836 (A/G), and rs75353978 (TT/del TT)). A new variant in position c.*457 (A/C) on 3'UTR of BRCA2 was also identified. The following three variants increased the risk of HBOC in the study population: rs111791349-A, rs15869-C, and c.*457-C (odds ratio (OR) range 3.7-15.4; p < 0.05). Genetic variants into the 3'UTR of BRCA1 and BRCA2 increased the risk of HBOC between 3.7-15.4 times in the study population. The presence/absence of these polymorphisms may influence the loss/creation of miRNA binding sites, such as hsa-miR-1248 in BRCA1 3'UTR or the hsa-miR-548 family binding site in BRCA2. Our results add new evidence of miRNA participation in the pathogenesis of HBOC.
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INTRODUCTION: Molecular analysis in haemophilia is currently used in the diagnosis, treatment and prognosis of this disease. Hispanic populations in Latin America have been of interest to researchers due to the reportedly high prevalence of inhibitors in these patients. AIM: To perform next-generation sequencing (NGS) in a cohort of Mexican patients with HA and HB and correlate with clinical phenotypes. METHODS: Patients with Haemophilia A (HA) or haemophilia B (HB), were evaluated using NGS with an Ion AmpliSeq Custom Panel. Odds ratios (ORs) for associations between F8 variants and inhibitors were obtained. RESULTS: A total of 85 patients (60 with HA and 25 with HB) were included. Pathogenic variants in F8 were found in 93.3% of HA patients and in F9 in 96% of HB patients. Twelve novel potentially pathogenic variants were found. Inhibitors were observed in 20% of patients with severe HA. Four patients clinically diagnosed with HA were negative for F8 variants. CONCLUSION: Overall detection rate of pathogenic variants in F8 and F9 genes was 94.6%. We identified 12 non previously reported variants and pathogenic variants in other coagulation related genes. Molecular diagnosis of HA and HB permits better options for management, assessment and genetic counseling.
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Hemofilia A/genética , Hemofilia B/genética , Mutação , Estudos de Coortes , Fator VIII/química , Fator VIII/genética , Predisposição Genética para Doença , Hemofilia A/diagnóstico , Hemofilia A/epidemiologia , Hemofilia B/diagnóstico , Hemofilia B/epidemiologia , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , México/epidemiologia , Modelos MolecularesRESUMO
BACKGROUND: Pathogenic variants (PVs) of BRCA genes entail a lifetime risk of developing breast cancer in 50-85% of carriers. Their prevalence in different populations has been previously reported. However, there is scarce information regarding the most common PVs of these genes in Latin-Americans. This study identified BRCA1 and BRCA2 PV frequency in a high-risk female population from Northeastern Mexico and determined the association of these mutations with the patients' clinical and pathological characteristics. METHODS: Women were divided into three groups: aged ≤ 40 years at diagnosis and/or risk factors for hereditary breast cancer (n = 101), aged > 50 years with sporadic breast cancer (n = 22), and healthy women (n = 72). Their DNA was obtained from peripheral blood samples and the variants were examined by next-generation sequencing with Ion AmpliSeq BRCA1 and BRCA2 Panel using next-generation sequencing. RESULTS: PVs were detected in 13.8% group 1 patients (BRCA1, 12 patients; BRCA2, 2 patients). Only two patients in group 2 and none in group 3 exhibited BRCA1 PVs. Variants of uncertain significance were reported in 15.8% patients (n = 16). In group 1, patients with the triple-negative subtype, PV frequency was 40% (12/30). Breast cancer prevalence in young women examined in this study was higher than that reported by the National Cancer Institute Surveillance, Epidemiology (15.5% vs. 5.5%, respectively). CONCLUSIONS: The detected BRCA1 and BRCA2 PV frequency was similar to that reported in other populations. Our results indicate that clinical data should be evaluated before genetic testing and highly recommend genetic testing in patients with the triple-negative subtype and other clinical aspects.
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Proteína BRCA1/genética , Proteína BRCA2/genética , Neoplasias da Mama/genética , Genes BRCA1 , Genes BRCA2 , Testes Genéticos , Adulto , Estudos de Casos e Controles , Éxons/genética , Feminino , Loci Gênicos , Mutação em Linhagem Germinativa , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , México , Pessoa de Meia-Idade , Taxa de MutaçãoAssuntos
Síndrome de Bloom/diagnóstico , Síndrome de Bloom/genética , Eritema/diagnóstico , Eritema/genética , Indígenas Norte-Americanos/genética , Síndrome de Bloom/complicações , Criança , Diagnóstico Diferencial , Eritema/complicações , Face/patologia , Humanos , Indígenas Norte-Americanos/etnologia , Masculino , México/etnologiaRESUMO
The enzyme myo-Inositol oxygenase (MIOX) is also termed ALDRL6. It is a kidney-specific member of the aldo-keto reductase family. MIOX catalyzes the first reaction involved in the myo-inositol metabolism signaling pathway and is fully expressed in mammalian tissues. MIOX catalyzes the oxidative cleavage of myo-Inositol and its epimer, D-chiro-Inositol to D-glucuronate. The dioxygen-dependent cleavage of the C6 and C1 bond in myo-Inositol is achieved by utilizing the Fe2+/Fe3+ binuclear iron center of MIOX. This enzyme has also been implicated in the complications of diabetes, including diabetic nephropathy. The MIOX gene was amplified with reverse transcription-polymerase chain reaction from baboon tissue samples, and the product was cloned and sequenced. MIOX expression in the baboon kidney is described in the present study. The percentages of nucleotide and amino acid similarities between baboons and humans were 95 and 96%, respectively. The MIOX protein of the baboon may be structurally identical to that of humans. Furthermore, the evolutionary changes, which have affected these sequences, have resulted from purifying forces.
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Objective: The purpose of this study is to establish the prevalence of vitamin D deficiency and their newborns and analyze the risk factors related to this deficiency. Methods: This is an observational, transversal, and prospective study. It included 191 puerperal women and their full-term newborns. Serum 25 hydroxyvitamin D values were analyzes by enzyme immunoassay. Results: 61% of the puerperal presented deficiency and 26% insufficiency of vitamin D. In the newborn group 98% showed deficiency and 66% of them presented severe deficiency. There is a positive correlation between the values of vitamin D in mothers and their newborns (r2 = 0.173 ng/ml; p = 0.017). The lowest levels were in autumn. (15.75 ng/mL mothers, 6 ng/mL newborns). There was no correlation between vitamin D levels in mothers and their dietary intake, maternal skin type, sun time exposure and prenatal body mass index. Conclusions: This is the first study that shows the existence of a high deficiency of vitamin D in Mexican mothers and their newborns.
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Mães/estatística & dados numéricos , Deficiência de Vitamina D/epidemiologia , Vitamina D/análogos & derivados , Adolescente , Adulto , Estudos Transversais , Feminino , Humanos , Técnicas Imunoenzimáticas , Recém-Nascido , Prevalência , Estudos Prospectivos , Fatores de Risco , Estações do Ano , Índice de Gravidade de Doença , Vitamina D/sangue , Deficiência de Vitamina D/etnologia , Adulto JovemRESUMO
BACKGROUND: The olfactomedin-like domain (OLFML) is present in at least four families of proteins, including OLFML2A and OLFML2B, which are expressed in adult rat retina cells. However, no expression of their orthologous has ever been reported in human and baboon. OBJECTIVE: The aim of this study was to investigate the expression of OLFML2A and OLFML2B in ocular tissues of baboons (Papio hamadryas) and humans, as a key to elucidate OLFML function in eye physiology. METHODS: OLFML2A and OLFML2B cDNA detection in ocular tissues of these species was performed by RT-PCR. The amplicons were cloned and sequenced, phylogenetically analyzed and their proteins products were confirmed by immunofluorescence assays. RESULTS: OLFML2A and OLFML2B transcripts were found in human cornea, lens and retina and in baboon cornea, lens, iris and retina. The baboon OLFML2A and OLFML2B ORF sequences have 96% similarity with their human's orthologous. OLFML2A and OLFML2B evolution fits the hypothesis of purifying selection. Phylogenetic analysis shows clear orthology in OLFML2A genes, while OLFML2B orthology is not clear. CONCLUSIONS: Expression of OLFML2A and OLFML2B in human and baboon ocular tissues, including their high similarity, make the baboon a powerful model to deduce the physiological and/or metabolic function of these proteins in the eye.
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Proteínas da Matriz Extracelular/metabolismo , Olho/metabolismo , Glicoproteínas/metabolismo , Proteínas de Membrana/metabolismo , Animais , Código de Barras de DNA Taxonômico , Evolução Molecular , Proteínas da Matriz Extracelular/análise , Proteínas da Matriz Extracelular/genética , Olho/química , Imunofluorescência/métodos , Glicoproteínas/análise , Glicoproteínas/genética , Humanos , Proteínas de Membrana/análise , Proteínas de Membrana/genética , Fenômenos Fisiológicos Oculares , Papio , Valores de Referência , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transcrição Reversa , Análise de Sequência de ProteínaRESUMO
PURPOSE: The aim of this study was to evaluate the usefulness of urine concentrations of 12 proteins as a risk parameter for developing preeclampsia (PE). METHODS: A nested case-control study was designed to determine protein concentrations in urine from women predicted to develop PE (WPD-PE) and normotensive pregnancies (controls). Protein profiles were determined at 12, 16 and 20 gestational weeks (GW) using the Bio-Plex Pro human kidney toxicity Panel 1 and Panel 2 (Bio-Rad). Receiver operating characteristic (ROC) curve analyses were performed. Correlations between proteins and clinical parameters at the time of PE diagnosis were also assessed. RESULTS: Significant differences were observed in urine cystatin C (Cys C) levels at 16 and 20 GW and clusterin at 20 GW between WPD-PE and controls (P < 0.05). ROC analysis revealed that Cys C at 16 GW had the highest area under the ROC curve (0.758). At 16 GW, patients with urine Cys C levels above 73.7 ng/mL had eightfold increased odds for developing PE (odds ratio 7.92; 95 % CI 1.3-47.5; P = 0.027). A positive correlation was found between urinary Cys C (at 16 and 20 GW) and leukocyte counts, total proteins, aspartate aminotransferase, alanine aminotransferase, bilirubin and lactate dehydrogenase at the time of PE diagnosis (P value < 0.05). CONCLUSIONS: Urinary Cys C and clusterin showed predictive value for PE development in our cohort. Further studies are needed to validate their use as predictive biomarkers for PE and/or their participation in PE pathogenesis.
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Clusterina/urina , Cistatina C/urina , Pré-Eclâmpsia , Adulto , Biomarcadores/urina , Estudos de Casos e Controles , Feminino , Idade Gestacional , Humanos , México/epidemiologia , Pré-Eclâmpsia/diagnóstico , Pré-Eclâmpsia/epidemiologia , Pré-Eclâmpsia/urina , Valor Preditivo dos Testes , Gravidez , Prognóstico , Curva ROC , Medição de Risco , Urinálise/métodosRESUMO
BACKGROUND: The olfactomedin-like domain (OLFML) is present in at least four families of proteins, including OLFML2A and OLFML2B, which are expressed in adult rat retina cells. However, no expression of their orthologous has ever been reported in human and baboon. OBJECTIVE: The aim of this study was to investigate the expression of OLFML2A and OLFML2B in ocular tissues of baboons (Papio hamadryas) and humans, as a key to elucidate OLFML function in eye physiology. METHODS: OLFML2A and OLFML2B cDNA detection in ocular tissues of these species was performed by RT-PCR. The amplicons were cloned and sequenced, phylogenetically analyzed and their proteins products were confirmed by immunofluorescence assays. RESULTS: OLFML2A and OLFML2B transcripts were found in human cornea, lens and retina and in baboon cornea, lens, iris and retina. The baboon OLFML2A and OLFML2B ORF sequences have 96% similarity with their human's orthologous. OLFML2A and OLFML2B evolution fits the hypothesis of purifying selection. Phylogenetic analysis shows clear orthology in OLFML2A genes, while OLFML2B orthology is not clear. CONCLUSIONS: Expression of OLFML2A and OLFML2B in human and baboon ocular tissues, including their high similarity, make the baboon a powerful model to deduce the physiological and/or metabolic function of these proteins in the eye.
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Humanos , Animais , Glicoproteínas/metabolismo , Proteínas da Matriz Extracelular/metabolismo , Olho/metabolismo , Proteínas de Membrana/metabolismo , Papio , Valores de Referência , Glicoproteínas/análise , Glicoproteínas/genética , Proteínas da Matriz Extracelular/análise , Proteínas da Matriz Extracelular/genética , Imunofluorescência/métodos , Evolução Molecular , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Análise de Sequência de Proteína , Transcrição Reversa , Olho/química , Código de Barras de DNA Taxonômico , Proteínas de Membrana/análise , Proteínas de Membrana/genética , Fenômenos Fisiológicos OcularesRESUMO
BACKGROUND: Free amino acids and acylcarnitines circulating in the blood can be used for diagnosis for metabolic illness and imbalances. To date, the normal reference ranges of amino acids and acylcarnitines in horse peripheral blood have not been established. In this study, the concentrations of 12 amino acids and 26 acylcarnitines were determined by tandem mass spectrometry in complete blood from 100 healthy horses (50 Quarter horses (QH) [23 males and 27 females] and 50 American Miniature horses (AMH) [15 males and 35 females]) with no signs of metabolic disease. The means and standard deviations were determined and data statistically analyzed. FINDINGS: Concentrations of short, medium, and long chain acylcarnitines were significantly higher in male AMH than in male QH. The concentrations of the amino acids alanine, arginine, glycine, proline (glycogenic), and leucine (ketogenic) were higher in the QH than in the AMH. Female AMH had higher concentrations of propionylcarnitine, leucine, proline, arginine, and ornithine than female QH. CONCLUSIONS: Normal reference ranges of amino acids and acylcarnitines were established for AMH and QH. Significant differences were found in concentration of these compounds between breeds and gender.
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Aminoácidos/sangue , Carnitina/análogos & derivados , Cavalos/sangue , Cavalos/metabolismo , Animais , Carnitina/sangue , Feminino , Cavalos/genética , Masculino , México , Valores de Referência , Espectrometria de Massas em Tandem/veterináriaRESUMO
BACKGROUND: Chemerin, encoded by the retinoic acid receptor responder 2 (RARRES2) gene is an adipocytesecreted protein with autocrine/paracrine functions in adipose tissue, metabolism and inflammation with a recently described function in vascular tone regulation, liver, steatosis, etc. This molecule is believed to represent a critical endocrine signal linking obesity to diabetes. There are no data available regarding evolution of RARRES2 in non-human primates and great apes. Expression profile and orthology in RARRES2 genes are unknown aspects in the biology of this multigene family in primates. Thus; we attempt to describe expression profile and phylogenetic relationship as complementary knowledge in the function of this gene in primates. To do that, we performed A RT-PCR from different tissues obtained during necropsies. Also we tested the hypotheses of positive evolution, purifying selection, and neutrality. And finally a phylogenetic analysis was made between primates RARRES2 protein. RESULTS: RARRES2 transcripts were present in liver, lung, adipose tissue, ovary, pancreas, heart, hypothalamus and pituitary tissues. Expression in kidney and leukocytes were not detectable in either species. It was determined that the studied genes are orthologous. CONCLUSIONS: RARRES2 evolution fits the hypothesis of purifying selection. Expression profiles of the RARRES2 gene are similar in baboons and chimpanzees and are also phylogenetically related.
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Evolução Molecular , Pan troglodytes/genética , Papio/genética , Receptores do Ácido Retinoico/genética , Animais , Sequência de Bases , Feminino , Masculino , Dados de Sequência Molecular , Filogenia , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
Turner Syndrome (TS) is an unfavorable genetic condition with a prevalence of 1:2500 in newborn girls. Prompt and effective diagnosis is very important to appropriately monitor the comorbidities. The aim of the present study was to propose a feasible and practical molecular diagnostic tool for newborn screening by quantifying the gene dosage of the SHOX, VAMP7, XIST, UBA1, and SRY genes by quantitative polymerase chain reaction (qPCR) in individuals with a diagnosis of complete X monosomy, as well as those with TS variants, and then compare the results to controls without chromosomal abnormalities. According to our results, the most useful markers for these chromosomal variants were the genes found in the pseudoautosomic regions 1 and 2 (PAR1 and PAR2), because differences in gene dosage (relative quantification) between groups were more evident in SHOX and VAMP7 gene expression. Therefore, we conclude that these markers are useful for early detection in aneuploidies involving sex chromosomes.
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Genes Ligados ao Cromossomo X , Testes Genéticos/métodos , Proteínas de Homeodomínio/genética , Triagem Neonatal/métodos , Proteínas R-SNARE/genética , Reação em Cadeia da Polimerase em Tempo Real/métodos , Síndrome de Turner/diagnóstico , Cromossomos Humanos X/genética , Diagnóstico Precoce , Feminino , Dosagem de Genes , Perfilação da Expressão Gênica , Genes sry , Humanos , Recém-Nascido , Cariotipagem , Masculino , México/epidemiologia , Monossomia , RNA Longo não Codificante/genética , Proteína de Homoeobox de Baixa Estatura , Síndrome de Turner/epidemiologia , Síndrome de Turner/genética , Enzimas Ativadoras de Ubiquitina/genéticaRESUMO
BACKGROUND: Chemerin, encoded by the retinoic acid receptor responder 2 (RARRES2) gene is an adipocytesecreted protein with autocrine/paracrine functions in adipose tissue, metabolism and inflammation with a recently described function in vascular tone regulation, liver, steatosis, etc. This molecule is believed to represent a critical endocrine signal linking obesity to diabetes. There are no data available regarding evolution of RARRES2 in non-human primates and great apes. Expression profile and orthology in RARRES2 genes are unknown aspects in the biology of this multigene family in primates. Thus; we attempt to describe expression profile and phylogenetic relationship as complementary knowledge in the function of this gene in primates. To do that, we performed A RT-PCR from different tissues obtained during necropsies. Also we tested the hypotheses of positive evolution, purifying selection, and neutrality. And finally a phylogenetic analysis was made between primates RARRES2 protein. RESULTS: RARRES2 transcripts were present in liver, lung, adipose tissue, ovary, pancreas, heart, hypothalamus and pituitary tissues. Expression in kidney and leukocytes were not detectable in either species. It was determined that the studied genes are orthologous. CONCLUSIONS: RARRES2 evolution fits the hypothesis of purifying selection. Expression profiles of the RARRES2 gene are similar in baboons and chimpanzees and are also phylogenetically related.
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Animais , Masculino , Feminino , Papio/genética , Pan troglodytes/genética , Receptores do Ácido Retinoico/genética , Evolução Molecular , Filogenia , Dados de Sequência Molecular , Sequência de Bases , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
OBJECTIVES: Mutations in the DFNB1 locus are the most common cause of autosomal-recessive nonsyndromic hearing loss (ARNSHL) worldwide. The aim of this study was to identify the most frequent mutations in patients with ARNSHL who reside in Northeastern Mexico. METHODS: We determined the nucleotide sequence the coding region of GJB2 of 78 patients with ARNSHL. Polymerase chain reaction assays were used to detect the GJB2 IVS1+1G>A mutation and deletions within GJB6. RESULTS: GJB2 mutations were detected in 9.6% of the alleles, and c.35delG was the most frequent. Six other less-frequent mutations were detected, including an extremely rare variant (c.645_648delTAGA), a novel mutation (c.35G>A), and one of possible Mexican origin (c.34G>T). GJB6 deletions and GJB2 IVS1+1G>A were not detected. CONCLUSIONS: These data suggest that mutations in the DFNB1 locus are a rare cause of ARNSHL among the population of Northeastern Mexico. This confirms the genetic heterogeneity of this condition and indicates that further research is required to determine the other mechanisms of pathogenesis of ARNSHL in Mexicans.