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2.
Twin Res Hum Genet ; 23(4): 259-263, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32744204

RESUMO

It is likely that genetic factors play a role in the susceptibility to, and recovery from, COVID-19. A survey of ongoing twin research could produce findings likely to help in the prevention and management of this pandemic. This survey is followed by a review of research comparing selected features of asthmatic and nonasthmatic twins, links between twin mammals and COVID-19, and relationships between twin delivery and the three 'Rs'. The final section of this article presents newsworthy twin-related items, some associated with COVID-19. They include a summary of the Rainman Twins film, a study of anal prints, the 'Twins' Irish pub, newborn twins 'Covid and Corona', the death of a surgeon who separated conjoined twins, and Twinco, a twin-based supply company.


Assuntos
Infecções por Coronavirus/genética , Suscetibilidade a Doenças , Doenças em Gêmeos/genética , Pneumonia Viral/genética , Betacoronavirus/patogenicidade , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/terapia , Infecções por Coronavirus/virologia , Doenças em Gêmeos/epidemiologia , Doenças em Gêmeos/terapia , Doenças em Gêmeos/virologia , Humanos , Pandemias , Pneumonia Viral/epidemiologia , Pneumonia Viral/terapia , Pneumonia Viral/virologia
3.
Dent Med Probl ; 57(2): 207-211, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32609956

RESUMO

Due to the special circumstances and the pre-natal environment in twin gestations, disruptions in the development of the embryo are more frequently observed in twin births as compared to singleton births. Twin research provides an excellent model to explore the etiology of disruptions in craniofacial biology. Mirror imaging (MI) is a special manifestation of twinning, and the elucidation of the etiology of this phenomenon is important to understand the biological mechanisms which underlie congenital defects, like orofacial clefts, and to provide insight into left-right asymmetry. The aim of this paper was, therefore, to present 3 pairs of Turkish monozygotic (MZ) twins with MI dental features, and to contribute to the knowledge of the MI phenomenon in the literature. We examined 2 male and 1 female MZ twin pairs clinically and radiographically in terms of their MI features. Mirrorimage features in dental and other ectodermal structures were detected in all the twins. Understanding the biological mechanisms of MI provides broad insight into preventive measures and treatment protocols. Furthermore, the presence of MI features may lead to the detection of other MI pathologies in twins.


Assuntos
Fenda Labial , Fissura Palatina , Gravidez de Gêmeos , Fenda Labial/diagnóstico por imagem , Fenda Labial/genética , Fissura Palatina/diagnóstico por imagem , Fissura Palatina/genética , Doenças em Gêmeos/diagnóstico por imagem , Doenças em Gêmeos/genética , Feminino , Humanos , Masculino , Gêmeos Monozigóticos
4.
Nutr Metab Cardiovasc Dis ; 30(10): 1609-1621, 2020 09 24.
Artigo em Inglês | MEDLINE | ID: mdl-32682747

RESUMO

BACKGROUND AND AIMS: Studies of twins can reduce confounding and provide additional evidence about the causes of disease, due to within-pair matching for measured and unmeasured factors. Although findings from twin studies are typically applicable to the general population, few studies have taken full advantage of the twin design to explore the developmental origins of cardiometabolic health outcomes. We aimed to systematically review the evidence from twin studies and generate pooled estimates for the effects of early-life risk factors on later-life cardiometabolic health. METHODS AND RESULTS: An initial search was conducted in March 2018, with 55 studies of twins included in the review. Risk of bias was assessed using the Newcastle-Ottawa Scale, and eligible studies were included in a meta-analysis, where pooled estimates were calculated. Twenty-six studies analysed twins as individuals, and found that higher birthweight was associated with lower SBP (ß = -2.02 mmHg, 95%CI: -3.07, -0.97), higher BMI (ß = 0.52 kg/m2, 95%CI: 0.20, 0.84) and lower total cholesterol (ß = -0.07 mmol/L, 95%CI: -0.11, -0.04). However, no associations were reported in studies which adjusted for gestational age. Few of the included studies separated their analyses into within-pair and between-pair associations. CONCLUSIONS: Early-life risk factors were associated with cardiometabolic health outcomes in twin studies. However, many estimates from studies in this review were likely to have been confounded by gestational age, and few fully exploited the twin design to assess the developmental origins of cardiometabolic health outcomes.


Assuntos
Doenças Cardiovasculares/etiologia , Doenças em Gêmeos/etiologia , Doenças Metabólicas/etiologia , Gêmeos , Adiposidade , Adolescente , Adulto , Idoso , Biomarcadores/sangue , Peso ao Nascer , Glicemia/metabolismo , Pressão Sanguínea , Índice de Massa Corporal , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/genética , Doenças Cardiovasculares/fisiopatologia , Criança , Pré-Escolar , Colesterol/sangue , Doenças em Gêmeos/sangue , Doenças em Gêmeos/genética , Doenças em Gêmeos/fisiopatologia , Feminino , Idade Gestacional , Nível de Saúde , Humanos , Insulina/sangue , Masculino , Doenças Metabólicas/sangue , Doenças Metabólicas/genética , Doenças Metabólicas/fisiopatologia , Pessoa de Meia-Idade , Estudos Observacionais como Assunto , Fatores de Risco , Estudos em Gêmeos como Assunto , Adulto Jovem
5.
DNA Cell Biol ; 39(8): 1449-1457, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32609007

RESUMO

Kearns-Sayre Syndrome (KSS) is a severe mitochondrial disorder involving the central nervous system, eyes, ears, skeletal muscles, and heart. The mitochondrial DNA (mtDNA) rearrangements, especially the deletions, are present in almost all KSS patients and considered as the disease-causing factor. However, the size and position of mtDNA deletions are distinct in different individuals. In this study, we report the case of a pair of Chinese twins with KSS. The twin patients revealed typical KSS clinical symptoms, including heart block, bilateral sensorineural hearing loss, progressive external ophthalmoplegia, exercise intolerance, proximal limb weakness, and endocrine disorders. Using long-range polymerase chain reactions (long-range PCR) and next-generation sequencing (NGS), the genetic features of the twin patients were investigated. A large 6600 bp mtDNA deletion, ranging from position 8702 to 15,302, was detected in both patients. To our knowledge, this kind of mtDNA deletion has never been described previously. Our study enriched the mutation spectrum of KSS and showed that NGS is a powerful tool for detecting mtDNA large variants.


Assuntos
DNA Mitocondrial/genética , Doenças em Gêmeos/genética , Síndrome de Kearns-Sayre/genética , Oftalmoplegia Externa Progressiva Crônica/genética , Sistema Nervoso Central/patologia , Criança , Cromossomos/genética , Doenças em Gêmeos/patologia , Orelha/patologia , Olho/patologia , Deleção de Genes , Predisposição Genética para Doença , Coração/fisiopatologia , Humanos , Síndrome de Kearns-Sayre/patologia , Masculino , Músculo Esquelético/metabolismo , Músculo Esquelético/patologia , Mutação/genética , Oftalmoplegia Externa Progressiva Crônica/patologia , Fenótipo
6.
Taiwan J Obstet Gynecol ; 59(1): 123-126, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32039779

RESUMO

OBJECTIVE: We present the prenatal diagnosis of a class II 1q21.1 microdeletion in monozygotic (MZ) twins with discordant phenotypes. CASE REPORT: A monochorionic diamniotic twin pair presented with discordant ultrasound anomalies; twin A had cardiovascular abnormalities, while twin B did not. No specific complications were noted in the twins during pregnancy. A single nucleotide polymorphism array revealed an identical class II 1q21.1 microdeletion inherited from a phenotypically normal mother and identified the twins as MZ. The deleted region encompassed both the proximal 1q21.1 thrombocytopenia absent radius syndrome region and the distal 1q21.1 recurrent microdeletion region. No other rare copy number variants (CNVs) were identified, and concordance was observed in the CNVs between the twins. CONCLUSION: Discordant cardiovascular abnormalities may occur in MZ twins carrying the same class II 1q21.1 microdeletion. Further studies involving discordant MZ twins are needed to determine the modifying factors of the phenotypic heterogeneity of the microdeletion.


Assuntos
Anormalidades Múltiplas/diagnóstico , Anormalidades Cardiovasculares/diagnóstico , Doenças em Gêmeos/diagnóstico , Megalencefalia/diagnóstico , Diagnóstico Pré-Natal/métodos , Gêmeos Monozigóticos/genética , Anormalidades Múltiplas/genética , Adulto , Anormalidades Cardiovasculares/genética , Deleção Cromossômica , Cromossomos Humanos Par 1/genética , Variações do Número de Cópias de DNA , Doenças em Gêmeos/genética , Feminino , Humanos , Megalencefalia/genética , Fenótipo , Gravidez , Gravidez de Gêmeos/genética
7.
J Stroke Cerebrovasc Dis ; 29(4): 104652, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32033901

RESUMO

The COL4A1 mutation is a very rare monogenic cause of small vessel disease related to recurrent intracerebral hemorrhage. We report a family in which the index case presented with two intracerebral hemorrhages in the basal ganglia with severe periventricular leukoaraiosis and a cataract and vascular tortuosity in the ophthalmological study. His twin brother also had severe leukoaraiosis and multiple subcortical microhemorrhages as well as a congenital cataract and vascular tortuosity in the retina. The older sister had a porencephalic cyst and involvement of the periventricular white matter and intracerebral hemorrhage. In single-gene testing, all three were found to have the same COL4A1 mutation. Intracerebral subcortical hemorrhages or microhemorrhages and severe subcortical leukoaraiosis in familial cases may be related to COL4 mutations.


Assuntos
Hemorragia Cerebral/genética , Colágeno Tipo IV/genética , Doenças em Gêmeos/genética , Mutação , Catarata/diagnóstico , Catarata/genética , Hemorragia Cerebral/diagnóstico , Doenças em Gêmeos/diagnóstico , Feminino , Predisposição Genética para Doença , Humanos , Leucoaraiose/diagnóstico , Leucoaraiose/genética , Masculino , Pessoa de Meia-Idade , Linhagem , Fenótipo , Recidiva
8.
Gene ; 738: 144461, 2020 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-32057927

RESUMO

Down syndrome is one of the most common chromosomal disorders and yet our understanding about the dysregulated genes in this disease is limited. Through this case study, we investigated the gene expression profile of primary amniotic fluid mesenchymal stem cells (AFMSCs) isolated from the amniotic sac of monozygotic twins discordant for trisomy 21 with one fetal hydrops at 17 weeks of gestation. AFMSCs were cultured to analyze the gene expression profiles for the human transcriptome array. Gene ontology was used to evaluate dysregulated gene functions. Total 25,799 genes were identified such that 65 were up-regulated (0.25%) and 111 were down-regulated (0.43%) with a log2 fold change trisomy 21/euploidy (log2 [FC]) > 1, p < 0.01). 16 genes were selected and verified by qRT-PCR, which showed compatible result with transcriptome array. At the chromosome level, chromosome 21 was found to carry the highest percentage of up-regulated genes (2.13%, 7/329 genes) with the highest mean log2 [FC] (0.23, p < 10-5), particularly on 21q22.3. There were eight segments with significant mean log2 [FC] on chromosomes 1, 6, 11, and 21 for upregulation, and on chromosomes 16, 17, and 19 for downregulation, indicating a pattern of dysregulated genes clustering in domains along the genome. Gene ontology showed the identified genes associated with extracellular matrix organization (11 genes, p = 5.1 × 10-6) and central nervous system development (8 genes, p = 6.0 × 10-5). Using transcriptome analysis of the AFMSCs of monozygotic twins discordant for trisomy 21, we report the dysregulated genes involved in Down syndrome, their predominance on chromosome 21, and the cluster pattern on the whole genome.


Assuntos
Síndrome de Down/genética , Perfilação da Expressão Gênica/métodos , Análise em Microsséries/métodos , Líquido Amniótico , Transtornos Cromossômicos/genética , Doenças em Gêmeos/genética , Feminino , Ontologia Genética , Genoma , Genótipo , Humanos , Células-Tronco Mesenquimais/fisiologia , Fenótipo , Gravidez , Transcriptoma/genética , Trissomia/genética , Gêmeos Monozigóticos/genética
9.
Depress Anxiety ; 37(5): 475-484, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-31944483

RESUMO

BACKGROUND: Adolescence is critical to intercept chronic/persistent pain and decipher its association with anxiety. We ascertained adolescent pain trajectories, their demographic and clinical correlates, the longitudinal association with opiate prescriptions at age 19, and the etiology of the covariation between adolescent pain problems and anxiety symptoms. METHODS: Longitudinal assessment of: 6 common pain problems at age 12, 13, 14, 15, and 17 years; 7 common anxiety symptoms at age 12, 13, and 14 years; opiates' prescriptions at age 19, in the Quebec Newborn Twin Study birth cohort of 667 twin pairs born between 1995-1998. RESULTS: Analyses yielded three trajectories of: "none-to-minimal" (34.3%), "sporadic" (56.7%), and "frequent" (9.0%) pain problems between age 12-17. Anxiety (odds ratios [OR] ORage12 : 2.38; confidence interval [CI]: 1.26-4.47; ORage13 : 3.96; CI: 1.73-9.05; ORage14 : 5.45; CI: 2.67-11.11), the female sex (OR: 3.69; CI: 2.20-6.21), and lower socioeconomic status (OR: 0.87; CI: 0.77-0.98) were associated with the "frequent" compared to the "none-to-minimal" pain trajectory. Only the "frequent" pain trajectory predicted opioid prescriptions at age 19 (OR: 4.14; CI: 1.16-14.55). A twin bivariate latent growth curve model and a cross-lagged model showed that genetic factors and non-shared environmental factors common to both phenotypes influence the longitudinal association between anxiety and adolescent pain problems. CONCLUSIONS: The relatively common, adolescent "frequent pain" trajectory predicts early opioid prescriptions, and anxiety and adolescent pain share multiple etiological components. These data can inform diagnostic reasoning, clinical practice, and help reducing opioid prescriptions and abuse.


Assuntos
Analgésicos Opioides/uso terapêutico , Ansiedade/psicologia , Dor Crônica/tratamento farmacológico , Prescrições de Medicamentos/estatística & dados numéricos , Adolescente , Ansiedade/etiologia , Dor Crônica/psicologia , Estudos de Coortes , Doenças em Gêmeos/genética , Feminino , Humanos , Recém-Nascido , Estudos Longitudinais , Masculino , Fenótipo , Quebeque , Fatores de Risco , Gêmeos , Adulto Jovem
10.
Mol Genet Metab ; 129(3): 236-242, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31917109

RESUMO

Disorders of the white matter are genetically very heterogeneous including several genes involved in mitochondrial bioenergetics. Diagnosis of the underlying cause is aided by pattern recognition on neuroimaging and by next-generation sequencing. Recently, genetic changes in the complex I assembly factor NUBPL have been characterized by a consistent recognizable pattern of leukoencephalopathy affecting deep white matter including the corpus callosum and cerebellum. Here, we report twin boys with biallelic variants in NUBPL, an unreported c.351 G > A; p.(Met117Ile) and a previously reported pathological variant c. 693 + 1 G > A. Brain magnetic resonance imaging showed abnormal T2 hyperintense signal involving the periventricular white matter, external capsule, corpus callosum, and, prominently, the bilateral thalami. The neuroimaging pattern evolved over 18 months with marked diffuse white matter signal abnormality, volume loss, and new areas of signal abnormality in the cerebellar folia and vermis. Magnetic resonance spectroscopy showed elevated lactate. Functional studies in cultured fibroblasts confirmed pathogenicity of the genetic variants. Complex I activity of the respiratory chain was deficient spectrophotometrically and on blue native gel with in-gel activity staining. There was absent assembly and loss of proteins of the matrix arm of complex I when traced with an antibody to NDUFS2, and incomplete assembly of the membrane arm when traced with an NDUFB6 antibody. There was decreased NUBPL protein on Western blot in patient fibroblasts compared to controls. Compromised NUBPL activity impairs assembly of the matrix arm of complex I and produces a severe, rapidly-progressive leukoencephalopathy with thalamic involvement on MRI, further expanding the neuroimaging phenotype.


Assuntos
Doenças em Gêmeos/genética , Complexo I de Transporte de Elétrons/metabolismo , Leucoencefalopatias/genética , Mitocôndrias/metabolismo , Proteínas Mitocondriais/genética , Tálamo/diagnóstico por imagem , Linhagem Celular , Corpo Caloso/diagnóstico por imagem , Corpo Caloso/patologia , Doenças em Gêmeos/diagnóstico por imagem , Doenças em Gêmeos/metabolismo , Doenças em Gêmeos/fisiopatologia , Complexo I de Transporte de Elétrons/deficiência , Complexo I de Transporte de Elétrons/genética , Cápsula Externa/diagnóstico por imagem , Cápsula Externa/patologia , Olho/fisiopatologia , Fibroblastos/metabolismo , Humanos , Lactente , Ácido Láctico/metabolismo , Leucoencefalopatias/diagnóstico por imagem , Leucoencefalopatias/metabolismo , Leucoencefalopatias/fisiopatologia , Imagem por Ressonância Magnética , Espectroscopia de Ressonância Magnética , Masculino , Mitocôndrias/genética , Proteínas Mitocondriais/metabolismo , Mutação , NADH Desidrogenase/metabolismo , Gêmeos Monozigóticos/genética , Substância Branca/diagnóstico por imagem , Substância Branca/patologia , Sequenciamento Completo do Exoma
11.
BMC Pediatr ; 20(1): 34, 2020 01 27.
Artigo em Inglês | MEDLINE | ID: mdl-31987033

RESUMO

BACKGROUND: Acrodermatitis enteropathica (AE) is a rare autosomal recessive hereditary skin disease caused by mutations in the SLC39A4 gene and is characterized by periorificial dermatitis, alopecia and diarrhoea due to insufficient zinc absorption. Only one of the three known sets of twins with AE has genetic information. This case reports the discovery of new mutation sites in rare twin patients and draws some interesting conclusions by analysing the relationship between genetic information and clinical manifestations. CASE PRESENTATION: Here, we report a pair of 16-month-old twin boys with AE exhibiting periorificial and acral erythema, scales and blisters, while subsequent laboratory examination showed normal plasma zinc and alkaline phosphatase levels. Further Sanger sequencing demonstrated that the patients were compound heterozygous for two unreported SLC39A4 mutations: a missense mutation in exon 5 (c.926G > T), which led to a substitution of the 309th amino acid residue cysteine with phenylalanine, a splice site mutation occurring in the consensus donor site of intron 5 (c.976 + 2 T > A). A family study revealed that the boys' parents were heterozygous carriers of these two mutations. CONCLUSION: We identified a new compound heterozygous mutation in Chinese twins with AE, which consisted of two previous unreported variants in exon 5 and intron 5 of SLC39A4. We propose an up-to-date review that different mutations in SLC39A4 may exhibit different AE manifestations. In conjunction with future research, our work may shed light on genotype-phenotype correlations in AE patients and provide knowledge for genetic counselling and treatment for AE patients.


Assuntos
Acrodermatite/genética , Proteínas de Transporte de Cátions/genética , Doenças em Gêmeos/genética , Mutação , Zinco/deficiência , Acrodermatite/tratamento farmacológico , Feminino , Heterozigoto , Humanos , Lactente , Masculino , Linhagem , Zinco/uso terapêutico
12.
PLoS One ; 14(12): e0226164, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31805172

RESUMO

BACKGROUND: MicroRNAs (miRNAs) are small RNAs regulating gene expression post-transcriptionally. Recent studies demonstrated that miRNAs are involved in the development of congenital heart defects (CHD). In this study, we aimed at identifying the specific patterns of miRNAs in blood of monozygotic twin pairs discordant for CHD and to assess whether miRNAs might be involved in the development or reflect the consequences of CHD. METHODS: miRNA microarray analysis and Real-Time Quantitative PCR (RT-qPCR) were employed to determine the miRNA abundance level from 12 monozygotic twins discordant for CHD and their non-CHD co-twins (n = 12). Enrichment analyses of altered miRNAs were performed using bioinformatics tools. RESULTS: Compared with non-CHD co-twins, profiling analysis indicated 34 miRNAs with a significant difference in abundance level (p<0.05, fold change ≥ 1.3), of which 11 miRNAs were up-regulated and 23 miRNAs were down-regulated. Seven miRNAs were validated with RT-qPCR including miR-511-3p, miR-1306-5p, miR-421, miR-4707-3p, miR-4732-3p, miR-5189-3p, and miR-890, and the results were consistent with microarray analysis. Five miRNAs namely miR-511-3p, miR-1306-5p, miR-4732-3p, miR-5189-3p, and miR-890 were found to be significantly up-regulated in twins < 10 years old. Bioinformatics analysis showed that the 7 validated miRNAs were involved in phosphatidylinositol signaling, gap junction signaling, and adrenergic signaling in cardiomyocytes. CONCLUSIONS: Our data show deregulated miRNA abundance levels in the peripheral blood of monozygotic twins discordant for CHD, and identify new candidates for further analysis, which may contribute to understanding the development of CHD in the future. Bioinformatics analysis indicated that the target genes of these miRNAs are likely involved in signaling and communication of cardiomyocytes.


Assuntos
Doenças em Gêmeos/genética , Perfilação da Expressão Gênica/métodos , Cardiopatias Congênitas/genética , MicroRNAs/genética , Gêmeos Monozigóticos/genética , Adolescente , Estudos de Casos e Controles , Criança , Feminino , Regulação da Expressão Gênica , Humanos , Análise de Sequência com Séries de Oligonucleotídeos , Análise de Sequência de RNA , Adulto Jovem
13.
Twin Res Hum Genet ; 22(6): 609-610, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31840625

RESUMO

Despite the well-known relevance of twin studies in the medical and social sciences and the growing number of twin registries throughout the world, Latin America has not fully incorporated into the twin research community. We describe the first steps taken toward developing a twin registry in Mexico: its aim, organization, recruiting potential and main short-term objectives.


Assuntos
Doenças em Gêmeos/epidemiologia , Doenças em Gêmeos/genética , Sistema de Registros/estatística & dados numéricos , Gêmeos Dizigóticos/genética , Gêmeos Monozigóticos/genética , Adolescente , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Lactente , Recém-Nascido , Masculino , México/epidemiologia , Pais , Seleção de Pacientes , Inquéritos e Questionários
14.
Twin Res Hum Genet ; 22(6): 606-608, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31875802

RESUMO

The South Korean Twin Registry (SKTR) is an ongoing nationwide volunteer registry of South Korean twins and their families. Since its inception, from preschooler to young adult, twins have been registered with the SKTR and have demonstrated that relative influences of genetic and environmental factors explaining individual differences in various psychological, mental health and physical traits in South Koreans are similar to those found in many Western twin studies. Currently, studies at the SKTR focus on identification of the process of gene-by-environment interactions as well as developmental differences in genetic and environmental influences on psychological and mental health traits in South Koreans. This report provides a brief overview, recruitment strategies, current samples, zygosity assessment, measures and future directions of the SKTR.


Assuntos
Doenças em Gêmeos/epidemiologia , Doenças em Gêmeos/genética , Interação Gene-Ambiente , Sistema de Registros/estatística & dados numéricos , Gêmeos Dizigóticos/genética , Gêmeos Monozigóticos/genética , Adolescente , Adulto , Criança , Doenças em Gêmeos/psicologia , Feminino , Seguimentos , Humanos , Masculino , Modelos Genéticos , República da Coreia/epidemiologia , Gêmeos Dizigóticos/psicologia , Gêmeos Monozigóticos/psicologia , Adulto Jovem
15.
Twin Res Hum Genet ; 22(6): 660-666, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31875804

RESUMO

The first twin study in Serbia began in 2011 as a part of the research project, 'Psychological Foundations of Mental Health: Hereditary and Environmental Factors'. At the same time, the research team from the Faculty of Philosophy and Faculty of Medicine in Novi Sad established the first Serbian twin registry. The registry is intended primarily for the purpose of the research in behavioral genetics, as well as potential future studies in human genetics. It includes information on 1658 volunteers, including twin-pairs, their parent and siblings. The behavioral genetic study of adult twins has been focused on the hereditary and environmental sources of variance of different psychological characteristics, such as personality traits, cognitive abilities, executive functions and aggression, as well as some anthropometric measures and aspects of mental and physical health. Certain molecular genetic analyses have also been performed. The research team is currently starting the longitudinal twin study of children, which will be focused on different indicators of emotional, cognitive and physical development.


Assuntos
Doenças em Gêmeos/epidemiologia , Genética Comportamental , Personalidade/genética , Sistema de Registros/estatística & dados numéricos , Gêmeos Dizigóticos/genética , Gêmeos Monozigóticos/genética , Adolescente , Adulto , Criança , Pré-Escolar , Doenças em Gêmeos/genética , Doenças em Gêmeos/psicologia , Feminino , Seguimentos , Humanos , Lactente , Recém-Nascido , Estudos Longitudinais , Masculino , Saúde Mental , Pessoa de Meia-Idade , Sérvia/epidemiologia , Irmãos , Adulto Jovem
16.
Molecules ; 25(1)2019 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-31861585

RESUMO

We evaluated the in silico expression and circulating levels of interleukin (IL)37 in patients with different forms of multiple sclerosis (MS) and also upon treatment with different disease-modifying drugs. The combined interpretation of the resulting data strengthens and extends the current emerging concept that endogenous IL37 plays an important role in determining onset and progression of MS. The in silico analysis revealed that production of IL37 from cluster of differentiation (CD)4+ T cells from MS patients was reduced in vitro as compared to healthy controls. The analysis of the datasets also demonstrated that "higher" levels of IL37 production from PBMC entailed significant protection from MS relapses. In addition, the in vivo part of the study showed that IL37 was selectively augmented in the sera of MS patients during a relapse and that treatment with the high potency disease-modifying drug fingolimod significantly increased the frequency of patients with circulating blood levels of IL37 (6/9, 66%) as compared to patients receiving no treatment (n = 48) or platform therapy (n = 59) who had levels of IL37 below the limit of the sensitivity of the assay. This finding therefore anticipates that fingolimod may at least partially exert its beneficial effects in MS by upregulating the production of IL37.


Assuntos
Cloridrato de Fingolimode/uso terapêutico , Interleucina-1/sangue , Interleucina-1/genética , Esclerose Múltipla/tratamento farmacológico , Adulto , Linfócitos T CD4-Positivos/imunologia , Estudos de Casos e Controles , Simulação por Computador , Progressão da Doença , Doenças em Gêmeos/tratamento farmacológico , Doenças em Gêmeos/genética , Doenças em Gêmeos/imunologia , Feminino , Cloridrato de Fingolimode/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/genética , Esclerose Múltipla/imunologia , Recidiva , Gêmeos Monozigóticos/genética , Regulação para Cima
17.
Transl Psychiatry ; 9(1): 215, 2019 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-31477685

RESUMO

DNA methylation plays an important role in major depressive disorder (MDD), but the specific genes and genomic regions associated with MDD remain largely unknown. Here we conducted genome-wide profiling of DNA methylation (Infinium MethylationEPIC BeadChip) and gene expression (RNA-seq) in peripheral blood monocytes from 79 monozygotic twin pairs (mean age 38.2 ± 15.6 years) discordant on lifetime history of MDD to identify differentially methylated regions (DMRs) and differentially expressed genes (DEGs) associated with MDD, followed by replication in brain tissue samples. Integrative DNA methylome and transcriptome analysis and network analysis was performed to identify potential functional epigenetic determinants for MDD. We identified 39 DMRs and 30 DEGs associated with lifetime history of MDD. Some genes were replicated in postmortem brain tissue. Integrative DNA methylome and transcriptome analysis revealed both negative and positive correlations between DNA methylation and gene expression, but the correlation pattern varies greatly by genomic locations. Network analysis revealed distinct gene modules enriched in signaling pathways related to stress responses, neuron apoptosis, insulin receptor signaling, mTOR signaling, and nerve growth factor receptor signaling, suggesting potential functional relevance to MDD. These results demonstrated that altered DNA methylation and gene expression in peripheral blood monocytes are associated with MDD. Our results highlight the utility of using peripheral blood epigenetic markers and demonstrate that a monozygotic discordant co-twin control design can aid in the discovery of novel genes associated with MDD. If validated, the newly identified genes may serve as novel biomarkers or druggable targets for MDD and related disorders.


Assuntos
Metilação de DNA , Transtorno Depressivo Maior/metabolismo , Doenças em Gêmeos/metabolismo , Epigenoma , Leucócitos Mononucleares/metabolismo , Transcriptoma , Adulto , Transtorno Depressivo Maior/genética , Doenças em Gêmeos/genética , Feminino , Perfilação da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Gêmeos Monozigóticos/genética , Adulto Jovem
18.
Nat Commun ; 10(1): 3933, 2019 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-31477693

RESUMO

It has remained unclear why schizophrenia typically manifests after adolescence and which neurobiological mechanisms are underlying the cascade leading to the actual onset of the illness. Here we show that the use of induced pluripotent stem cell-derived neurons of monozygotic twins from pairs discordant for schizophrenia enhances disease-specific signal by minimizing genetic heterogeneity. In proteomic and pathway analyses, clinical illness is associated especially with altered glycosaminoglycan, GABAergic synapse, sialylation, and purine metabolism pathways. Although only 12% of all 19,462 genes are expressed differentially between healthy males and females, up to 61% of the illness-related genes are sex specific. These results on sex-specific genes are replicated in another dataset. This implies that the pathophysiology differs between males and females, and may explain why symptoms appear after adolescence when the expression of many sex-specific genes change, and suggests the need for sex-specific treatments.


Assuntos
Perfilação da Expressão Gênica/métodos , Proteoma/genética , Proteômica/métodos , Esquizofrenia/genética , Adolescente , Antipsicóticos/uso terapêutico , Clozapina/uso terapêutico , Doenças em Gêmeos/genética , Doenças em Gêmeos/metabolismo , Feminino , Humanos , Masculino , Neurônios/citologia , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Células-Tronco Pluripotentes/citologia , Células-Tronco Pluripotentes/metabolismo , Proteoma/metabolismo , Esquizofrenia/tratamento farmacológico , Esquizofrenia/metabolismo , Fatores Sexuais , Gêmeos Monozigóticos/genética
19.
J Abnorm Psychol ; 128(7): 658-670, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31535887

RESUMO

Familial resemblance in eating pathology is typically attributed to parents providing an environment that leads to the development of eating pathology. However, offspring raised by biological parents receive both their environment and genes from their parents, raising the possibility that genetic influences, environmental influences, and/or gene-environment interplay may account for familial resemblance. Past studies have not explored the possibility of parents' genes influencing the environment they provide (i.e., passive gene-environment correlations or "passive rGE"). If present, passive rGE is most likely to "hide" in estimates of shared environmental influence in classical twin models. The current study used a nuclear twin family design to explore the possibility of passive rGE during pre- and early puberty when past studies have demonstrated the importance of shared environmental influence. Additionally, the present study explored whether sibling-specific (i.e., influences specific to the twin generation) or family-specific (i.e., "cultural" influences within the home) environmental influences account for shared environmental influences found in past studies. Participants included preearly pubertal same-sex female twins and their biological parents (N = 547 families) from the Minnesota Twin Family Study and the Michigan State University Twin Registry. Disordered eating was assessed with self-report measures in the twins and parents. Pubertal status was determined using an established cut-off on a self-report measure. Passive rGE was not indicated in this study of pre- and early pubertal twins. Instead, sibling-specific shared environmental and nonshared environmental influences were most influential. Future research should work to identify the sibling-specific environmental influences that contribute to sibling similarity in disordered eating. (PsycINFO Database Record (c) 2019 APA, all rights reserved).


Assuntos
Transtornos da Alimentação e da Ingestão de Alimentos/genética , Interação Gene-Ambiente , Pais , Puberdade/psicologia , Gêmeos/genética , Criança , Doenças em Gêmeos/genética , Doenças em Gêmeos/psicologia , Transtornos da Alimentação e da Ingestão de Alimentos/psicologia , Feminino , Humanos , Masculino , Sistema de Registros , Autorrelato , Gêmeos/psicologia
20.
Twin Res Hum Genet ; 22(4): 201-209, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31498057

RESUMO

Twin registries have developed as a valuable resource for the study of many aspects of disease and society over the years in many different countries. A number of these registries include large numbers of twins with data collected at varying information levels for twin cohorts over the past several decades. More recent expansion of twin datasets has allowed for the collection of genetic data, together with many other levels of 'omic' information along with multiple demographic, physiological, health outcomes and other measures typically used in epidemiologic research. Other twin data sources outside these registries reflect research interests in particular aspects of disease or specific phenotypic assessment. Twin registries have the potential to play a key role in many aspects of the artificial intelligence/machine learning-driven projects of the future and will continue to keep adapting to the changing research landscape.


Assuntos
Doenças em Gêmeos/genética , Sistema de Registros , Gêmeos/genética , Doenças em Gêmeos/epidemiologia , Feminino , Humanos , Masculino
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