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1.
Hum Genet ; 139(6-7): 769-776, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32405658

RESUMO

Over the last decade next generation sequencing (NGS) has been extensively used to identify new pathogenic mutations and genes causing rare genetic diseases. The efficient analyses of NGS data is not trivial and requires a technically and biologically rigorous pipeline that addresses data quality control, accurate variant filtration to minimize false positives and false negatives, and prioritization of the remaining genes based on disease genomics and physiological knowledge. This review provides a pipeline including all these steps, describes popular software for each step of the analysis, and proposes a general framework for the identification of causal mutations and genes in individual patients of rare genetic diseases.


Assuntos
Biologia Computacional/métodos , Genes/genética , Doenças Genéticas Inatas/etiologia , Genoma Humano , Mutação , Medicina de Precisão , Doenças Raras/etiologia , Doenças Genéticas Inatas/patologia , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Doenças Raras/patologia , Software
2.
Adv Exp Med Biol ; 1236: 1-38, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32304067

RESUMO

The laboratory mouse has become the model organism of choice in numerous areas of biological and biomedical research, including the study of congenital birth defects. The appeal of mice for these experimental studies stems from the similarities between the physiology, anatomy, and reproduction of these small mammals with our own, but it is also based on a number of practical reasons: mice are easy to maintain in a laboratory environment, are incredibly prolific, and have a relatively short reproductive cycle. Another compelling reason for choosing mice as research subjects is the number of tools and resources that have been developed after more than a century of working with these small rodents in laboratory environments. As will become obvious from the reading of the different chapters in this book, research in mice has already helped uncover many of the genes and processes responsible for congenital birth malformations and human diseases. In this chapter, we will provide an overview of the methods, scientific advances, and serendipitous circumstances that have made these discoveries possible, with a special emphasis on how the use of genetics has propelled scientific progress in mouse research and paved the way for future discoveries.


Assuntos
Pesquisa Biomédica , Modelos Animais de Doenças , Genes , Camundongos/genética , Mutação , Animais , Humanos , Reprodução
3.
BMC Bioinformatics ; 21(1): 151, 2020 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-32312224

RESUMO

BACKGROUND: Molecular characters have been added in integrative taxonomic approaches in recent years. Nevertheless, taxon diagnoses are still widely restricted to morphological characters. The inclusion of molecular characters into taxon diagnoses is not only hampered by problems, such as their definition and the designation of their positions in a reference alignment, but also by the technical effort. RESULTS: DeSignate is a tool for character-based taxon diagnoses that includes a novel ranking scheme. It detects and classifies individual and combined signature characters (diagnostic molecular characters) based on so-called character state vectors. An intuitive web application guides the user through the analysis process and provides the results at a glance. Further, formal definitions and a uniform terminology of characters are introduced. CONCLUSIONS: DeSignate facilitates the inclusion of diagnostic molecular characters and their positions to complement taxon diagnoses. Compared to previous solutions, the tool simplifies the workflow and improves reproducibility and traceability of the results. The tool is freely available as a web application at (https://designate.dbresearch.uni-salzburg.at/) and is open source (https://github.com/DatabaseGroup/DeSignate/).


Assuntos
Genes , Filogenia , Alinhamento de Sequência , Software , Sequência de Bases , Reprodutibilidade dos Testes
4.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 37(4): 373-377, 2020 Apr 10.
Artigo em Chinês | MEDLINE | ID: mdl-32219816

RESUMO

OBJECTIVE: To determine the type and carrier rate of deafness-related variants in Dongguan, China. METHODS: A total of 16 182 subjects were screened. Heel blood samples were collected from newborns, while peripheral venous blood samples were collected from the remainders. For each individual, 100 variations of 18 deafness susceptibility genes were detected. RESULTS: In total 1631 deafness-related variants (including 5 homozygous mutations) were detected, which gave a detection rate of 10.08%. The detection rate of SLC26A4 gene variants was the highest (845 cases, 5.22%), which was followed by GJB2 (673 cases, 4.16%), GJB3 (100 cases, 0.62%), TMC1 (12 cases, 0.07%), and MYO15A (1 case, 0.01%). The detection rate for GJB2 c.235delC variant was the highest (524 cases, 3.24%), which was followed by SLC26A4 IVS7-2A>G variant (270 cases, 1.67%). Thirty three individuals (0.20%) carried two variants at the same time, 7 of them (0.04%) carried compound heterozygous variants of the same gene. CONCLUSION: To expand the range of screening can help with determination of the carrier status and provision of early intervention and genetic counseling for the examinees.


Assuntos
Surdez/genética , Genes , Predisposição Genética para Doença , China , Análise Mutacional de DNA , Aconselhamento Genético , Testes Genéticos , Variação Genética , Humanos , Recém-Nascido , Mutação , RNA Ribossômico
5.
Mol Genet Genomics ; 295(3): 591-606, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32006176

RESUMO

Achaete-scute complex (ASC) genes play essential roles in regulating neurogenesis of metazoans. Various metazoan species have greatly different numbers of genes in ASCa, ASCb and ASCc families. To explore evolutionary mechanisms of metazoan ASC genes, Blast (basic local alignment search tool) searches and phylogenetic analyses were conducted to identify ASC genes in metazoan species and to infer phylogenetic relationship between various ASC genes. As a result, 2784 ASC genes were identified in 804 metazoan species. The phylogenetic tree constructed using 1237 unique bHLH motifs shows that metazoan ASCa, ASCb and ASCc families contain six (a1-a6), five (b1-b5) and three (c1-c3) bHLH genes, respectively. Further phylogenetic analyses suggest that ASC genes in metazoans are derived from a primitive c gene, those in insects are derived from c2 gene, and those in chordates are derived from a2 and a3 genes. Data of gene linkage demonstrate that insect a6 is derived from a4 but not from a5, and chordate a2 is ancestral to b5 only, whilst a3 is ancestral to both b3 and b5. It is concluded that current ASC gene families in metazoans were established through a series of sub- and/or neo-functionalization to duplicated ancestral ASC gene(s). These results provide good references for exploring evolutionary mechanisms of other bHLH genes in metazoans. Besides, gene subtyping is considered as an efficient method for evolutionary studies on closely related homologous genes.


Assuntos
Região do Genoma do Complexo Achaete-Scute/genética , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Evolução Molecular , Genes/genética , Filogenia , Animais , Genômica
8.
PLoS One ; 15(1): e0228456, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31999769

RESUMO

The combination of a fluorescent reporter and enzymatic reporter provides a flexible and versatile way for the study of diverse biological processes, such as the detection of transcription and translation. Thus, there is an urgent need to develop this novel bifunctional reporter system. This study reports the design, construction, and validation of a new dicistronic mCherry-lacZα reporter system by artificial lac operon and pbr operon models in lacZM15-producing E. coli. It allows two reporter genes to be co-transcribed into a dicistronic mRNA strand, followed by coupled expression of mCherry and lacZα. In artificial lac operons, expression of the downstream lacZα was demonstrated to be positively related to expression of the upstream ORF. In artificial pbr operons, compared with the insertion of downstream full-length lacZ, the insertion of downstream lacZα exerted a slight effect on the response from the upstream mCherry. Furthermore, the downstream lacZα reporter showed stronger response to Pb(II) than the downstream full-length lacZ. Importantly, the response sensitivity of downstream lacZα was still higher than that of upstream mCherry in a dual RFP-lacZα reporter construct. The highly efficient expression profile of the reporter lacZα peptide makes it a preferred downstream reporter in polycistronic constructs. This novel bifunctional reporter system offers a robust tool for biological studies.


Assuntos
Escherichia coli/genética , Genes Reporter , Chumbo/análise , Técnicas Biossensoriais , Expressão Gênica , Genes , Óperon Lac , Proteínas Luminescentes/genética , RNA Mensageiro/metabolismo
9.
Nucleic Acids Res ; 48(5): 2694-2708, 2020 03 18.
Artigo em Inglês | MEDLINE | ID: mdl-31919519

RESUMO

Diplonemids are highly abundant heterotrophic marine protists. Previous studies showed that their strikingly bloated mitochondrial genome is unique because of systematic gene fragmentation and manifold RNA editing. Here we report a comparative study of mitochondrial genome architecture, gene structure and RNA editing of six recently isolated, phylogenetically diverse diplonemid species. Mitochondrial gene fragmentation and modes of RNA editing, which include cytidine-to-uridine (C-to-U) and adenosine-to-inosine (A-to-I) substitutions and 3' uridine additions (U-appendage), are conserved across diplonemids. Yet as we show here, all these features have been pushed to their extremes in the Hemistasiidae lineage. For example, Namystynia karyoxenos has its genes fragmented into more than twice as many modules than other diplonemids, with modules as short as four nucleotides. Furthermore, we detected in this group multiple A-appendage and guanosine-to-adenosine (G-to-A) substitution editing events not observed before in diplonemids and found very rarely elsewhere. With >1,000 sites, C-to-U and A-to-I editing in Namystynia is nearly 10 times more frequent than in other diplonemids. The editing density of 12% in coding regions makes Namystynia's the most extensively edited transcriptome described so far. Diplonemid mitochondrial genome architecture, gene structure and post-transcriptional processes display such high complexity that they challenge all other currently known systems.


Assuntos
Euglenozoários/genética , Genes , Genoma Mitocondrial , Edição de RNA/genética , Sequência de Bases , Cromossomos/genética , Sequência Conservada , DNA Mitocondrial/genética , Filogenia
10.
Hum Genet ; 139(6-7): 733-743, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31932884

RESUMO

The unique vulnerability to infection of newborns and young infants is generally explained by a constellation of differences between early-life immune responses and immune responses at later ages, often referred to as neonatal immune immaturity. This developmental view, corroborated by robust evidence, offers a plausible, population-level description of the pathogenesis of life-threatening infectious diseases during the early-life period, but provides little explanation on the wide inter-individual differences in susceptibility and resistance to specific infections during the first months of life. In this context, the role of individual human genetic variation is increasingly recognized. A life-threatening infection caused by an opportunistic pathogen in an otherwise healthy infant likely represents the first manifestation of an inborn error of immunity. Single-gene disorders may also underlie common infections in full-term infants with no comorbidities or in preterm infants. In addition, there is increasing evidence of a possible role for common genetic variation in the pathogenesis of infection in preterm infants. Over the past years, a unified theory of infectious diseases emerged, supporting a hypothetical, age-dependent general model of genetic architecture of human infectious diseases. We discuss here how the proposed genetic model can be reconciled with the widely accepted developmental view of early-life infections in humans.


Assuntos
Regulação da Expressão Gênica no Desenvolvimento , Genes/genética , Doenças Genéticas Inatas/complicações , Predisposição Genética para Doença , Variação Genética , Infecções/etiologia , Doenças Genéticas Inatas/genética , Genética Humana , Humanos , Infecções/patologia
11.
BMC Genomics ; 21(1): 63, 2020 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-31959106

RESUMO

BACKGROUND: As a major threat to the oyster industry, Pacific Oyster Mortality Syndrome (POMS) is a polymicrobial disease affecting the main oyster species farmed across the world. POMS affects oyster juveniles and became panzootic this last decade, but POMS resistance in some oyster genotypes has emerged. While we know some genetic loci associated with resistance, the underlying mechanisms remained uncharacterized. So, we developed a comparative transcriptomic approach using basal gene expression profiles between different oyster biparental families with contrasted phenotypes when confronted to POMS (resistant or susceptible). RESULTS: We showed that POMS resistant oysters show differential expression of genes involved in stress responses, protein modifications, maintenance of DNA integrity and repair, and immune and antiviral pathways. We found similarities and clear differences among different molecular pathways in the different resistant families. These results suggest that the resistance process is polygenic and partially varies according to the oyster genotype. CONCLUSIONS: We found differences in basal expression levels of genes related to TLR-NFκB, JAK-STAT and STING-RLR pathways. These differences could explain the best antiviral response, as well as the robustness of resistant oysters when confronted to POMS. As some of these genes represent valuable candidates for selective breeding, we propose future studies should further examine their function.


Assuntos
Crassostrea/genética , Crassostrea/microbiologia , Animais , Crassostrea/imunologia , Crassostrea/metabolismo , Genes , RNA-Seq , Estresse Fisiológico/genética , Transcriptoma
12.
Hum Genet ; 139(1): 95-102, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31317254

RESUMO

A central goal in human genetics is the identification of variants and genes that influence the risk of polygenic diseases. In the past decade, genome-wide association studies (GWAS) have identified tens of thousands of genetic loci associated with various diseases. Since the majority of such loci lie within non-coding regions and have many candidate variants in linkage disequilibrium, it has been challenging to accurately identify specific causal variants and genes. To aid in their discovery a variety of statistical and experimental approaches have been developed. These approaches often borrow information from functional genomics assays such as ATAC-seq, ChIP-seq and RNA-seq to annotate functional variants and identify regulatory relationships between variants and genes. While such approaches are powerful, given the diversity of cell types and environments, it is paramount to select disease-relevant contexts for follow-up analyses. In this review, we discuss the latest developments, challenges, and best practices for determining the causal mechanisms of polygenic disease risk variants with functional genomics data from specialized cell types.


Assuntos
Linhagem da Célula/genética , Genes/genética , Genoma Humano , Estudo de Associação Genômica Ampla , Genômica/métodos , Polimorfismo de Nucleotídeo Único , Locos de Características Quantitativas , Predisposição Genética para Doença , Humanos
13.
Sci Adv ; 5(12): eaaw3851, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31840053

RESUMO

Efforts to decipher chronic lung disease and to reconstitute functional lung tissue through regenerative medicine have been hampered by an incomplete understanding of cell-cell interactions governing tissue homeostasis. Because the structure of mammalian lungs is highly conserved at the histologic level, we hypothesized that there are evolutionarily conserved homeostatic mechanisms that keep the fine architecture of the lung in balance. We have leveraged single-cell RNA sequencing techniques to identify conserved patterns of cell-cell cross-talk in adult mammalian lungs, analyzing mouse, rat, pig, and human pulmonary tissues. Specific stereotyped functional roles for each cell type in the distal lung are observed, with alveolar type I cells having a major role in the regulation of tissue homeostasis. This paper provides a systems-level portrait of signaling between alveolar cell populations. These methods may be applicable to other organs, providing a roadmap for identifying key pathways governing pathophysiology and informing regenerative efforts.


Assuntos
Conectoma , Pulmão/citologia , Mamíferos/metabolismo , Análise de Célula Única , Animais , Linhagem Celular , Espaço Extracelular/metabolismo , Genes , Homeostase , Humanos , Ligantes , Alvéolos Pulmonares/metabolismo , Receptores de Superfície Celular/metabolismo , Semaforinas/metabolismo , Transdução de Sinais , Especificidade da Espécie , Fator A de Crescimento do Endotélio Vascular/metabolismo
14.
BMC Bioinformatics ; 20(1): 625, 2019 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-31795929

RESUMO

BACKGROUND: Transcriptome analysis aims at gaining insight into cellular processes through discovering gene expression patterns across various experimental conditions. Biclustering is a standard approach to discover genes subsets with similar expression across subgroups of samples to be identified. The result is a set of biclusters, each forming a specific submatrix of rows (e.g. genes) and columns (e.g. samples). Relevant biclusters can, however, be missed when, due to the presence of a few outliers, they lack the assumed homogeneity of expression values among a few gene/sample combinations. The Max-Sum SubMatrix problem addresses this issue by looking at highly expressed subsets of genes and of samples, without enforcing such homogeneity. RESULTS: We present here the K-CPGC algorithm to identify K relevant submatrices. Our main contribution is to show that this approach outperforms biclustering algorithms to identify several gene subsets representative of specific subgroups of samples. Experiments are conducted on 35 gene expression datasets from human tissues and yeast samples. We report comparative results with those obtained by several biclustering algorithms, including CCA, xMOTIFs, ISA, QUBIC, Plaid and Spectral. Gene enrichment analysis demonstrates the benefits of the proposed approach to identify more statistically significant gene subsets. The most significant Gene Ontology terms identified with K-CPGC are shown consistent with the controlled conditions of each dataset. This analysis supports the biological relevance of the identified gene subsets. An additional contribution is the statistical validation protocol proposed here to assess the relative performances of biclustering algorithms and of the proposed method. It relies on a Friedman test and the Hochberg's sequential procedure to report critical differences of ranks among all algorithms. CONCLUSIONS: We propose here the K-CPGC method, a computationally efficient algorithm to identify K max-sum submatrices in a large gene expression matrix. Comparisons show that it identifies more significantly enriched subsets of genes and specific subgroups of samples which are easily interpretable by biologists. Experiments also show its ability to identify more reliable GO terms. These results illustrate the benefits of the proposed approach in terms of interpretability and of biological enrichment quality. Open implementation of this algorithm is available as an R package.


Assuntos
Genes , Algoritmos , Análise por Conglomerados , Bases de Dados Genéticas , Ontologia Genética , Humanos , Análise de Sequência com Séries de Oligonucleotídeos/métodos , Saccharomyces cerevisiae/genética
15.
Medicine (Baltimore) ; 98(52): e18493, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31876736

RESUMO

Bronchopulmonary dysplasia (BPD) is a common disease of premature infants with very low birth weight. The mechanism is inconclusive. The aim of this study is to systematically explore BPD-related genes and characterize their functions.Natural language processing analysis was used to identify BPD-related genes. Gene data were extracted from PubMed database. Gene ontology, pathway, and network analysis were carried out, and the result was integrated with corresponding database.In this study, 216 genes were identified as BPD-related genes with P < .05, and 30 pathways were identified as significant. A network of BPD-related genes was also constructed with 17 hub genes identified. In particular, phosphatidyl inositol-3-enzyme-serine/threonine kinase signaling pathway involved the largest number of genes. Insulin was found to be a promising candidate gene related with BPD, suggesting that it may serve as an effective therapeutic target.Our data may help to better understand the molecular mechanisms underlying BPD. However, the mechanisms of BPD are elusive, and further studies are needed.


Assuntos
Displasia Broncopulmonar/genética , Mineração de Dados , Algoritmos , Displasia Broncopulmonar/etiologia , Displasia Broncopulmonar/metabolismo , Biologia Computacional/métodos , Mineração de Dados/métodos , Ontologia Genética , Genes/genética , Genes/fisiologia , Predisposição Genética para Doença/genética , Humanos , Recém-Nascido , Redes e Vias Metabólicas/genética , Processamento de Linguagem Natural , Transdução de Sinais/genética
16.
BMC Bioinformatics ; 20(Suppl 9): 406, 2019 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-31757203

RESUMO

BACKGROUND: Humans have adapted to widespread changes during the past 2 million years in both environmental and lifestyle factors. This is evident in overall body alterations such as average height and brain size. Although we can appreciate the uniqueness of our species in many aspects, molecular variations that drive such changes are far from being fully known and explained. Comparative genomics is able to determine variations in genomic sequence that may provide functional information to better understand species-specific adaptations. A large number of human-specific genomic variations have been reported but no currently available dataset comprises all of these, a problem which contributes to hinder progress in the field. RESULTS: Here we critically update high confidence human-specific genomic variants that mostly associate with protein-coding regions and find 856 related genes. Events that create such human-specificity are mainly gene duplications, the emergence of novel gene regions and sequence and structural alterations. Functional analysis of these human-specific genes identifies adaptations to brain, immune and metabolic systems to be highly involved. We further show that many of these genes may be functionally associated with neural activity and generating the expanded human cortex in dynamic spatial and temporal contexts. CONCLUSIONS: This comprehensive study contributes to the current knowledge by considerably updating the number of human-specific genes following a critical bibliographic survey. Human-specific genes were functionally assessed for the first time to such extent, thus providing unique information. Our results are consistent with environmental changes, such as immune challenges and alterations in diet, as well as neural sophistication, as significant contributors to recent human evolution.


Assuntos
Evolução Biológica , Encéfalo/imunologia , Encéfalo/metabolismo , Genes , Animais , Bases de Dados Genéticas , Ontologia Genética , Genoma Humano , Genômica , Humanos , Células-Tronco Pluripotentes Induzidas/metabolismo , Neuroglia/metabolismo , Neurônios/metabolismo , Especificidade da Espécie
17.
Nat Commun ; 10(1): 5163, 2019 11 14.
Artigo em Inglês | MEDLINE | ID: mdl-31727886

RESUMO

Fields such as behavioural and evolutionary ecology are built on the assumption that natural selection leads to organisms that behave as if they are trying to maximise their fitness. However, there is considerable evidence for selfish genetic elements that change the behaviour of individuals to increase their own transmission. How can we reconcile this contradiction? Here we show that: (1) when selfish genetic elements have a greater impact at the individual level, they are more likely to be suppressed, and suppression spreads more quickly; (2) selection on selfish genetic elements leads them towards a greater impact at the individual level, making them more likely to be suppressed; (3) the majority interest within the genome generally prevails over 'cabals' of a few genes, irrespective of genome size, mutation rate and the sophistication of trait distorters. Overall, our results suggest that even when there is the potential for considerable genetic conflict, this will often have negligible impact at the individual level.


Assuntos
Adaptação Fisiológica/genética , Genes , Tamanho do Genoma , Modelos Genéticos , Característica Quantitativa Herdável , Sequências Repetitivas de Ácido Nucleico/genética
18.
BMC Genomics ; 20(1): 797, 2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31666004

RESUMO

BACKGROUND: In the pig production industry, artificial insemination (AI) plays an important role in enlarging the beneficial impact of elite boars. Understanding the genetic architecture and detecting genetic markers associated with semen traits can help in improving genetic selection for such traits and accelerate genetic progress. In this study, we utilized a weighted single-step genome-wide association study (wssGWAS) procedure to detect genetic regions and further candidate genes associated with semen traits in a Duroc boar population. Overall, the full pedigree consists of 5284 pigs (12 generations), of which 2693 boars have semen data (143,113 ejaculations) and 1733 pigs were genotyped with 50 K single nucleotide polymorphism (SNP) array. RESULTS: Results show that the most significant genetic regions (0.4 Mb windows) explained approximately 2%~ 6% of the total genetic variances for the studied traits. Totally, the identified significant windows (windows explaining more than 1% of total genetic variances) explained 28.29, 35.31, 41.98, and 20.60% of genetic variances (not phenotypic variance) for number of sperm cells, sperm motility, sperm progressive motility, and total morphological abnormalities, respectively. Several genes that have been previously reported to be associated with mammal spermiogenesis, testes functioning, and male fertility were detected and treated as candidate genes for the traits of interest: Number of sperm cells, TDRD5, QSOX1, BLK, TIMP3, THRA, CSF3, and ZPBP1; Sperm motility, PPP2R2B, NEK2, NDRG, ADAM7, SKP2, and RNASET2; Sperm progressive motility, SH2B1, BLK, LAMB1, VPS4A, SPAG9, LCN2, and DNM1; Total morphological abnormalities, GHR, SELENOP, SLC16A5, SLC9A3R1, and DNAI2. CONCLUSIONS: In conclusion, candidate genes associated with Duroc boars' semen traits, including the number of sperm cells, sperm motility, sperm progressive motility, and total morphological abnormalities, were identified using wssGWAS. KEGG and GO enrichment analysis indicate that the identified candidate genes were enriched in biological processes and functional terms may be involved into spermiogenesis, testes functioning, and male fertility.


Assuntos
Sêmen , Sus scrofa/genética , Animais , Genes , Variação Genética , Estudo de Associação Genômica Ampla , Locos de Características Quantitativas
19.
Essays Biochem ; 63(4): 433-456, 2019 10 16.
Artigo em Inglês | MEDLINE | ID: mdl-31652314

RESUMO

Nucleic acids, deoxyribonucleic acid (DNA) and ribonucleic acid (RNA), carry genetic information which is read in cells to make the RNA and proteins by which living things function. The well-known structure of the DNA double helix allows this information to be copied and passed on to the next generation. In this article we summarise the structure and function of nucleic acids. The article includes a historical perspective and summarises some of the early work which led to our understanding of this important molecule and how it functions; many of these pioneering scientists were awarded Nobel Prizes for their work. We explain the structure of the DNA molecule, how it is packaged into chromosomes and how it is replicated prior to cell division. We look at how the concept of the gene has developed since the term was first coined and how DNA is copied into RNA (transcription) and translated into protein (translation).


Assuntos
Replicação do DNA , DNA , Genes/genética , Biossíntese de Proteínas/genética , RNA/genética , Bactérias/genética , DNA/genética , DNA/história , Eucariotos/genética , História do Século XX , Conformação de Ácido Nucleico , Ribossomos/metabolismo
20.
Medicine (Baltimore) ; 98(38): e17224, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31567981

RESUMO

BACKGROUND: Multiple sclerosis (MS) is a common autoimmune disease of the central nervous system (CNS), and is associated with genetic factors. FOXP3 gene polymorphism has been reported as the risk factor for MS, however, previous studies have showed conflicting results. The purpose of this study is to investigate the association between FOXP3 gene polymorphism and the susceptibility to MS. METHODS: Pubmed, Embase, library of Cochrane, and Web of Science were used to search the eligible articles from January 1980 up to October 2018. The odds ratio (ORs) and its 95% confidence intervals (CI) were used to evaluate the strength of association. Allele model, homozygote model, heterozygote model, dominant model, and recessive model were used to evaluate the association between FOXP3 gene polymorphism and MS. RESULTS: A total of 5 studies contained 1276 MS patients and 1447 controls (for rs3761548) and 600 MS patients and 640 controls (for rs2232365) were enrolled in this meta-analysis. The association showed significant differences in allele and dominant model for rs3761548 polymorphism. In addition, a clear tendency to significance was detected in homozygote and recessive model for rs3761548 (P = .052). Subgroup analysis indicated a significant risk of MS in all genotype models but heterozygotes in Asians. CONCLUSION: FOXP3 gene polymorphism rs3761548 was associated with a higher MS risk, especially in Asians. This conclusion needs to be validated in more large samples and multiracial studies. LEVEL OF EVIDENCE: Level III diagnostic study.


Assuntos
Fatores de Transcrição Forkhead/genética , Predisposição Genética para Doença/genética , Esclerose Múltipla/genética , Polimorfismo de Nucleotídeo Único/genética , Genes/genética , Humanos , Esclerose Múltipla/etiologia
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