Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 14.560
Filtrar
1.
Nat Commun ; 11(1): 4368, 2020 08 31.
Artigo em Inglês | MEDLINE | ID: mdl-32868758

RESUMO

Increased extracellular sodium activates Th17 cells, which provide protection from bacterial and fungal infections. Whilst high salt diets have been shown to worsen autoimmune disease, the immunological consequences of clinical salt depletion are unknown. Here, we investigate immunity in patients with inherited salt-losing tubulopathies (SLT). Forty-seven genotyped SLT patients (with Bartter, Gitelman or EAST Syndromes) are recruited. Clinical features of dysregulated immunity are recorded with a standardised questionnaire and immunological investigations of IL-17 responsiveness undertaken. The effects of altering extracellular ionic concentrations on immune responses are then assessed. Patients are hypokalaemic and hypomagnesaemic, with reduced interstitial sodium stores determined by 23Na-magnetic resonance imaging. SLT patients report increased mucosal infections and allergic disease compared to age-matched controls. Aligned with their clinical phenotype, SLT patients have an increased ratio of Th2:Th17 cells. SLT Th17 and Tc17 polarisation is reduced in vitro, yet STAT1 and STAT3 phosphorylation and calcium flux following T cell activation are unaffected. In control cells, the addition of extracellular sodium (+40 mM), potassium (+2 mM), or magnesium (+1 mM) reduces Th2:Th17 ratio and augments Th17 polarisation. Our results thus show that the ionic environment typical in SLT impairs IL-17 immunity, but the intracellular pathways that mediate salt-driven Th17 polarisation are intact and in vitro IL-17 responses can be reinvigorated by increasing extracellular sodium concentration. Whether better correction of extracellular ions can rescue the immunophenotype in vivo in SLT patients remains unknown.


Assuntos
Síndromes de Imunodeficiência/etiologia , Interleucina-17/metabolismo , Túbulos Renais Distais/patologia , Adolescente , Adulto , Idoso de 80 Anos ou mais , Animais , Pré-Escolar , Doença Crônica , Estudos de Coortes , Feminino , Doenças Genéticas Inatas , Humanos , Magnésio/metabolismo , Masculino , Pessoa de Meia-Idade , Potássio/metabolismo , Sais/metabolismo , Sais/uso terapêutico , Sódio/metabolismo , Cloreto de Sódio/metabolismo , Cloreto de Sódio na Dieta/uso terapêutico , Células Th17/metabolismo , Células Th2/metabolismo , Adulto Jovem
4.
Am J Hum Genet ; 107(3): 418-431, 2020 09 03.
Artigo em Inglês | MEDLINE | ID: mdl-32758451

RESUMO

While genome-wide association studies have identified susceptibility variants for numerous traits, their combined utility for predicting broad measures of health, such as mortality, remains poorly understood. We used data from the UK Biobank to combine polygenic risk scores (PRS) for 13 diseases and 12 mortality risk factors into sex-specific composite PRS (cPRS). These cPRS were moderately associated with all-cause mortality in independent data within the UK Biobank: the estimated hazard ratios per standard deviation were 1.10 (95% confidence interval: 1.05, 1.16) and 1.15 (1.10, 1.19) for women and men, respectively. Differences in life expectancy between the top and bottom 5% of the cPRS were estimated to be 4.79 (1.76, 7.81) years and 6.75 (4.16, 9.35) years for women and men, respectively. These associations were substantially attenuated after adjusting for non-genetic mortality risk factors measured at study entry (i.e., middle age for most participants). The cPRS may be useful in counseling younger individuals at higher genetic risk of mortality on modification of non-genetic factors.


Assuntos
Doenças Genéticas Inatas/mortalidade , Predisposição Genética para Doença , Herança Multifatorial/genética , Medição de Risco/estatística & dados numéricos , Bancos de Espécimes Biológicos , Feminino , Doenças Genéticas Inatas/genética , Doenças Genéticas Inatas/patologia , Estudo de Associação Genômica Ampla , Humanos , Masculino , Pessoa de Meia-Idade , Fenótipo , Polimorfismo de Nucleotídeo Único/genética , Modelos de Riscos Proporcionais , Fatores de Risco , Reino Unido
5.
PLoS One ; 15(7): e0236962, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32735577

RESUMO

The diffusion of next-generation sequencing technologies has revolutionized research and diagnosis in the field of rare Mendelian disorders, notably via whole-exome sequencing (WES). However, one of the main issues hampering achievement of a diagnosis via WES analyses is the extended list of variants of unknown significance (VUS), mostly composed of missense variants. Hence, improved solutions are needed to address the challenges of identifying potentially deleterious variants and ranking them in a prioritized short list. We present MISTIC (MISsense deleTeriousness predICtor), a new prediction tool based on an original combination of two complementary machine learning algorithms using a soft voting system that integrates 113 missense features, ranging from multi-ethnic minor allele frequencies and evolutionary conservation, to physiochemical and biochemical properties of amino acids. Our approach also uses training sets with a wide spectrum of variant profiles, including both high-confidence positive (deleterious) and negative (benign) variants. Compared to recent state-of-the-art prediction tools in various benchmark tests and independent evaluation scenarios, MISTIC exhibits the best and most consistent performance, notably with the highest AUC value (> 0.95). Importantly, MISTIC maintains its high performance in the specific case of discriminating deleterious variants from benign variants that are rare or population-specific. In a clinical context, MISTIC drastically reduces the list of VUS (<30%) and significantly improves the ranking of "causative" deleterious variants. Pre-computed MISTIC scores for all possible human missense variants are available at http://lbgi.fr/mistic.


Assuntos
Doenças Genéticas Inatas , Mutação de Sentido Incorreto , Software , Sequenciamento Completo do Exoma/métodos , Biologia Computacional , Doenças Genéticas Inatas/diagnóstico , Doenças Genéticas Inatas/genética , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos , Aprendizado de Máquina
6.
Mol Cell ; 79(3): 504-520.e9, 2020 08 06.
Artigo em Inglês | MEDLINE | ID: mdl-32707033

RESUMO

Protein kinases are essential for signal transduction and control of most cellular processes, including metabolism, membrane transport, motility, and cell cycle. Despite the critical role of kinases in cells and their strong association with diseases, good coverage of their interactions is available for only a fraction of the 535 human kinases. Here, we present a comprehensive mass-spectrometry-based analysis of a human kinase interaction network covering more than 300 kinases. The interaction dataset is a high-quality resource with more than 5,000 previously unreported interactions. We extensively characterized the obtained network and were able to identify previously described, as well as predict new, kinase functional associations, including those of the less well-studied kinases PIM3 and protein O-mannose kinase (POMK). Importantly, the presented interaction map is a valuable resource for assisting biomedical studies. We uncover dozens of kinase-disease associations spanning from genetic disorders to complex diseases, including cancer.


Assuntos
Redes Reguladoras de Genes , Doenças Genéticas Inatas/genética , Neoplasias/genética , Proteínas Quinases/genética , Proteínas Serina-Treonina Quinases/genética , Proteínas Proto-Oncogênicas/genética , Biologia Computacional/métodos , Conjuntos de Dados como Assunto , Regulação da Expressão Gênica , Ontologia Genética , Doenças Genéticas Inatas/enzimologia , Doenças Genéticas Inatas/patologia , Humanos , Redes e Vias Metabólicas/genética , Anotação de Sequência Molecular , Distrofias Musculares/enzimologia , Distrofias Musculares/genética , Distrofias Musculares/patologia , Neoplasias/enzimologia , Neoplasias/patologia , Doenças Neurodegenerativas/enzimologia , Doenças Neurodegenerativas/genética , Doenças Neurodegenerativas/patologia , Mapeamento de Interação de Proteínas/métodos , Proteínas Quinases/química , Proteínas Quinases/classificação , Proteínas Quinases/metabolismo , Proteínas Serina-Treonina Quinases/química , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Proto-Oncogênicas/química , Proteínas Proto-Oncogênicas/metabolismo , Transdução de Sinais
7.
Surg Clin North Am ; 100(4): 695-705, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32681870

RESUMO

Wound healing is affected by several factors. Preexisting diagnoses may significantly alter, delay, or inhibit normal wound healing. This is most commonly seen with chronic disorders, such as diabetes and renal failure, but also occurs secondary to aging and substance abuse. Less commonly, genetic or inflammatory disorders are the cause of delayed wound healing. In some cases, it is not the illness, but the treatment that can inhibit wound healing. This is seen in patients getting chemotherapy, radiation, steroids, methotrexate, and a host of other medications. Understanding these processes may help treat or avoid wound healing problems.


Assuntos
Falência Renal Crônica/fisiopatologia , Cicatrização/fisiologia , Ferimentos e Lesões/fisiopatologia , Fatores Etários , Antineoplásicos/efeitos adversos , Doenças Autoimunes/complicações , Doenças Autoimunes/fisiopatologia , Doença Crônica , Doenças Genéticas Inatas/complicações , Doenças Genéticas Inatas/fisiopatologia , Humanos , Infecções/complicações , Infecções/fisiopatologia , Falência Renal Crônica/complicações , Transtornos Nutricionais/complicações , Transtornos Nutricionais/fisiopatologia , Lesões por Radiação/complicações , Lesões por Radiação/fisiopatologia , Pele/efeitos da radiação , Dermatopatias/complicações , Dermatopatias/fisiopatologia , Fumar/efeitos adversos , Fumar/fisiopatologia , Ferimentos e Lesões/complicações
9.
Nucleic Acids Res ; 48(14): 7623-7639, 2020 08 20.
Artigo em Inglês | MEDLINE | ID: mdl-32644123

RESUMO

RNA therapeutics are a promising strategy to treat genetic diseases caused by the overexpression or aberrant splicing of a specific protein. The field has seen major strides in the clinical efficacy of this class of molecules, largely due to chemical modifications and delivery strategies that improve nuclease resistance and enhance cell penetration. However, a major obstacle in the development of RNA therapeutics continues to be the imprecise, difficult, and often problematic nature of most methods used to measure cell penetration. Here, we review these methods and clearly distinguish between those that measure total cellular uptake of RNA therapeutics, which includes both productive and non-productive uptake, and those that measure cytosolic/nuclear penetration, which represents only productive uptake. We critically analyze the benefits and drawbacks of each method. Finally, we use key examples to illustrate how, despite rigorous experimentation and proper controls, our understanding of the mechanism of gymnotic uptake of RNA therapeutics remains limited by the methods commonly used to analyze RNA delivery.


Assuntos
RNA/metabolismo , RNA/uso terapêutico , Aptâmeros de Nucleotídeos/uso terapêutico , Núcleo Celular/metabolismo , Citosol/metabolismo , Doenças Genéticas Inatas/tratamento farmacológico , Técnicas Genéticas , Humanos , MicroRNAs/uso terapêutico , Microscopia Eletrônica , Oligonucleotídeos Antissenso/uso terapêutico , RNA/química , RNA/farmacocinética , RNA Interferente Pequeno/uso terapêutico , Espectrometria de Fluorescência
10.
Am J Hum Genet ; 107(1): 3-14, 2020 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-32619490

RESUMO

Secondary genomic findings are increasingly being returned to individuals as opportunistic screening results. A secondary finding offers the chance to identify and mitigate disease that may otherwise be unrecognized in an individual. As a form of screening, secondary findings must be considered differently from sequencing results in a diagnostic setting. For these reasons, clinicians should employ an evaluation and long-term management strategy that accounts for both the increased disease risk associated with a secondary finding and the lower positive predictive value of a screening result compared to an indication-based testing result. Here we describe an approach to the clinical evaluation and management of an individual who presents with a secondary finding. This approach enumerates five domains of evaluation-(1) medical history, (2) physical exam, (3) family history, (4) diagnostic phenotypic testing, and (5) variant correlation-through which a clinician can distinguish a molecular finding from a clinicomolecular diagnosis of genomic disease. With this framework, both geneticists and non-geneticist clinicians can optimize their ability to detect and mitigate genomic disease while avoiding the pitfalls of overdiagnosis. Our goal with this approach is to help clinicians translate secondary findings into meaningful recognition, treatment, and prevention of disease.


Assuntos
Doenças Genéticas Inatas/genética , Doenças Genéticas Inatas/diagnóstico , Doenças Genéticas Inatas/prevenção & controle , Genômica/métodos , Humanos , Anamnese
11.
Am J Hum Genet ; 107(2): 352-363, 2020 08 06.
Artigo em Inglês | MEDLINE | ID: mdl-32693025

RESUMO

MORC2 encodes an ATPase that plays a role in chromatin remodeling, DNA repair, and transcriptional regulation. Heterozygous variants in MORC2 have been reported in individuals with autosomal-dominant Charcot-Marie-Tooth disease type 2Z and spinal muscular atrophy, and the onset of symptoms ranges from infancy to the second decade of life. Here, we present a cohort of 20 individuals referred for exome sequencing who harbor pathogenic variants in the ATPase module of MORC2. Individuals presented with a similar phenotype consisting of developmental delay, intellectual disability, growth retardation, microcephaly, and variable craniofacial dysmorphism. Weakness, hyporeflexia, and electrophysiologic abnormalities suggestive of neuropathy were frequently observed but were not the predominant feature. Five of 18 individuals for whom brain imaging was available had lesions reminiscent of those observed in Leigh syndrome, and five of six individuals who had dilated eye exams had retinal pigmentary abnormalities. Functional assays revealed that these MORC2 variants result in hyperactivation of epigenetic silencing by the HUSH complex, supporting their pathogenicity. The described set of morphological, growth, developmental, and neurological findings and medical concerns expands the spectrum of genetic disorders resulting from pathogenic variants in MORC2.


Assuntos
Adenosina Trifosfatases/genética , Anormalidades Craniofaciais/genética , Transtornos do Crescimento/genética , Mutação/genética , Transtornos do Neurodesenvolvimento/genética , Fatores de Transcrição/genética , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Doenças Genéticas Inatas/genética , Heterozigoto , Humanos , Lactente , Deficiência Intelectual/genética , Masculino , Microcefalia/genética , Pessoa de Meia-Idade , Fenótipo , Adulto Jovem
12.
Nat Biotechnol ; 38(7): 845-855, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32601435

RESUMO

Genome editing has the potential to treat an extensive range of incurable monogenic and complex diseases. In particular, advances in sequence-specific nuclease technologies have dramatically accelerated the development of therapeutic genome editing strategies that are based on either the knockout of disease-causing genes or the repair of endogenous mutated genes. These technologies are progressing into human clinical trials. However, challenges remain before the therapeutic potential of genome editing can be fully realized. Delivery technologies that have serendipitously been developed over the past couple decades in the protein and nucleic acid delivery fields have been crucial to genome editing success to date, including adeno-associated viral and lentiviral vectors for gene therapy and lipid nanoparticle and other non-viral vectors for nucleic acid and protein delivery. However, the efficiency and tissue targeting capabilities of these vehicles must be further improved. In addition, the genome editing enzymes themselves need to be optimized, and challenges regarding their editing efficiency, specificity and immunogenicity must be addressed. Emerging protein engineering and synthetic chemistry approaches can offer solutions and enable the development of safe and efficacious clinical genome editing.


Assuntos
Sistemas CRISPR-Cas/genética , Edição de Genes/tendências , Doenças Genéticas Inatas/terapia , Terapia Genética , Doenças Genéticas Inatas/genética , Vetores Genéticos/genética , Vetores Genéticos/uso terapêutico , Humanos , Nanopartículas/uso terapêutico , Engenharia de Proteínas
13.
Medicine (Baltimore) ; 99(27): e20989, 2020 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-32629715

RESUMO

BACKGROUND: Many genetic diseases are known to have distinctive facial phenotypes, which are highly informative to provide an opportunity for automated detection. However, the diagnostic performance of artificial intelligence to identify genetic diseases with facial phenotypes requires further investigation. The objectives of this systematic review and meta-analysis are to evaluate the diagnostic accuracy of artificial intelligence to identify the genetic diseases with face phenotypes and then find the best algorithm. METHODS: The systematic review will be conducted in accordance with the "Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols" guidelines. The following electronic databases will be searched: PubMed, Web of Science, IEEE, Ovid, Cochrane Library, EMBASE and China National Knowledge Infrastructure. Two reviewers will screen and select the titles and abstracts of the studies retrieved independently during the database searches and perform full-text reviews and extract available data. The main outcome measures include diagnostic accuracy, as defined by accuracy, recall, specificity, and precision. The descriptive forest plot and summary receiver operating characteristic curves will be used to represent the performance of diagnostic tests. Subgroup analysis will be performed for different algorithms aided diagnosis tests. The quality of study characteristics and methodology will be assessed using the Quality Assessment of Diagnostic Accuracy Studies 2 tool. Data will be synthesized by RevMan 5.3 and Meta-disc 1.4 software. RESULTS: The findings of this systematic review and meta-analysis will be disseminated in a relevant peer-reviewed journal and academic presentations. CONCLUSION: To our knowledge, there have not been any systematic review or meta-analysis relating to diagnosis performance of artificial intelligence in identifying the genetic diseases with face phenotypes. The findings would provide evidence to formulate a comprehensive understanding of applications using artificial intelligence in identifying the genetic diseases with face phenotypes and add considerable value in the future of precision medicine. OSF REGISTRATION: DOI 10.17605/OSF.IO/P9KUH.


Assuntos
Face/anormalidades , Doenças Genéticas Inatas/diagnóstico , Aprendizado Profundo , Humanos , Desenvolvimento Maxilofacial/genética , Metanálise como Assunto , Fenótipo , Revisões Sistemáticas como Assunto
15.
JAMA ; 323(24): 2503-2511, 2020 06 23.
Artigo em Inglês | MEDLINE | ID: mdl-32573669

RESUMO

Importance: Widespread adoption of rapid genomic testing in pediatric critical care requires robust clinical and laboratory pathways that provide equitable and consistent service across health care systems. Objective: To prospectively evaluate the performance of a multicenter network for ultra-rapid genomic diagnosis in a public health care system. Design, Setting, and Participants: Descriptive feasibility study of critically ill pediatric patients with suspected monogenic conditions treated at 12 Australian hospitals between March 2018 and February 2019, with data collected to May 2019. A formal implementation strategy emphasizing communication and feedback, standardized processes, coordination, distributed leadership, and collective learning was used to facilitate adoption. Exposures: Ultra-rapid exome sequencing. Main Outcomes and Measures: The primary outcome was time from sample receipt to ultra-rapid exome sequencing report. The secondary outcomes were the molecular diagnostic yield, the change in clinical management after the ultra-rapid exome sequencing report, the time from hospital admission to the laboratory report, and the proportion of laboratory reports returned prior to death or hospital discharge. Results: The study population included 108 patients with a median age of 28 days (range, 0 days to 17 years); 34% were female; and 57% were from neonatal intensive care units, 33% were from pediatric intensive care units, and 9% were from other hospital wards. The mean time from sample receipt to ultra-rapid exome sequencing report was 3.3 days (95% CI, 3.2-3.5 days) and the median time was 3 days (range, 2-7 days). The mean time from hospital admission to ultra-rapid exome sequencing report was 17.5 days (95% CI, 14.6-21.1 days) and 93 reports (86%) were issued prior to death or hospital discharge. A molecular diagnosis was established in 55 patients (51%). Eleven diagnoses (20%) resulted from using the following approaches to augment standard exome sequencing analysis: mitochondrial genome sequencing analysis, exome sequencing-based copy number analysis, use of international databases to identify novel gene-disease associations, and additional phenotyping and RNA analysis. In 42 of 55 patients (76%) with a molecular diagnosis and 6 of 53 patients (11%) without a molecular diagnosis, the ultra-rapid exome sequencing result was considered as having influenced clinical management. Targeted treatments were initiated in 12 patients (11%), treatment was redirected toward palliative care in 14 patients (13%), and surveillance for specific complications was initiated in 19 patients (18%). Conclusions and Relevance: This study suggests feasibility of ultra-rapid genomic testing in critically ill pediatric patients with suspected monogenic conditions in the Australian public health care system. However, further research is needed to understand the clinical value of such testing, and the generalizability of the findings to other health care settings.


Assuntos
Estado Terminal , Doenças Genéticas Inatas/genética , Testes Genéticos/métodos , Sequenciamento Completo do Exoma/métodos , Austrália , Criança , Pré-Escolar , Estudos de Viabilidade , Feminino , Doenças Genéticas Inatas/diagnóstico , Humanos , Lactente , Recém-Nascido , Masculino , Programas Nacionais de Saúde , Estudos Prospectivos , Fatores de Tempo
16.
Nucleic Acids Res ; 48(13): 7265-7278, 2020 07 27.
Artigo em Inglês | MEDLINE | ID: mdl-32544229

RESUMO

DNA2 is an essential nuclease-helicase implicated in DNA repair, lagging-strand DNA synthesis, and the recovery of stalled DNA replication forks (RFs). In Saccharomyces cerevisiae, dna2Δ inviability is reversed by deletion of the conserved helicase PIF1 and/or DNA damage checkpoint-mediator RAD9. It has been suggested that Pif1 drives the formation of long 5'-flaps during Okazaki fragment maturation, and that the essential function of Dna2 is to remove these intermediates. In the absence of Dna2, 5'-flaps are thought to accumulate on the lagging strand, resulting in DNA damage-checkpoint arrest and cell death. In line with Dna2's role in RF recovery, we find that the loss of Dna2 results in severe chromosome under-replication downstream of endogenous and exogenous RF-stalling. Importantly, unfaithful chromosome replication in Dna2-mutant cells is exacerbated by Pif1, which triggers the DNA damage checkpoint along a pathway involving Pif1's ability to promote homologous recombination-coupled replication. We propose that Dna2 fulfils its essential function by promoting RF recovery, facilitating replication completion while suppressing excessive RF restart by recombination-dependent replication (RDR) and checkpoint activation. The critical nature of Dna2's role in controlling the fate of stalled RFs provides a framework to rationalize the involvement of DNA2 in Seckel syndrome and cancer.


Assuntos
DNA Helicases/metabolismo , Replicação do DNA , Doenças Genéticas Inatas/genética , Proteínas de Saccharomyces cerevisiae/metabolismo , Pontos de Checagem do Ciclo Celular , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , DNA , Dano ao DNA , DNA Helicases/genética , Humanos , Mutação , Saccharomyces cerevisiae , Proteínas de Saccharomyces cerevisiae/genética
18.
Cell ; 181(6): 1194-1199, 2020 06 11.
Artigo em Inglês | MEDLINE | ID: covidwho-245693

RESUMO

SARS-CoV-2 infection displays immense inter-individual clinical variability, ranging from silent infection to lethal disease. The role of human genetics in determining clinical response to the virus remains unclear. Studies of outliers-individuals remaining uninfected despite viral exposure and healthy young patients with life-threatening disease-present a unique opportunity to reveal human genetic determinants of infection and disease.


Assuntos
Infecções por Coronavirus/genética , Infecções por Coronavirus/imunologia , Predisposição Genética para Doença , Pneumonia Viral/genética , Pneumonia Viral/imunologia , Fatores Etários , Betacoronavirus/fisiologia , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/fisiopatologia , Resistência à Doença , Estudos de Associação Genética , Doenças Genéticas Inatas/imunologia , Variação Genética , Genoma Humano , Interações Hospedeiro-Patógeno , Humanos , Infecções/genética , Infecções/imunologia , Infecções/fisiopatologia , Pandemias , Pneumonia Viral/epidemiologia , Pneumonia Viral/fisiopatologia
19.
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
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA