Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 4 de 4
Filtrar
Mais filtros











Base de dados
Intervalo de ano de publicação
1.
Clin Genet ; 96(1): 43-52, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30891744

RESUMO

Alternating hemiplegia of childhood (AHC) is a rare and severe neurodevelopmental disorder characterized by recurrent hemiplegic episodes. Most AHC cases are sporadic and caused by de novo ATP1A3 pathogenic variants. In this study, the aim was to identify the origin of ATP1A3 pathogenic variants in a Chinese cohort. In 105 probands including 101 sporadic and 4 familial cases, 98 patients with ATP1A3 pathogenic variants were identified, and 96.8% were confirmed as de novo. Micro-droplet digital polymerase chain reaction was applied for detecting ATP1A3 mosaicism in 80 available families. In blood samples, four asymptomatic parents, including two paternal and two maternal, and one proband with a milder phenotype were identified as mosaicism. Six (7.5%) parental mosaicisms were identified in multiple tissues, including four previously identified in blood and two additional cases identified from paternal sperms. Mosaicism was identified in multiple tissues with varied mutant allele fractions (MAFs, 0.03%-33.03%). The results suggested that MAF of mosaicism may be related to phenotype severity. This is the first systematic report of ATP1A3 mosaicism in AHC and showed mosaicism as an unrecognized source of previously considered "de novo" AHC. Identifying ATP1A3 mosaicism provides more evidence for estimating recurrence risk and has implications in genetic counseling of AHC.


Assuntos
Estudos de Associação Genética , Predisposição Genética para Doença , Hemiplegia/diagnóstico , Hemiplegia/genética , Mosaicismo , Mutação , ATPase Trocadora de Sódio-Potássio/genética , Alelos , Pré-Escolar , Feminino , Genótipo , Humanos , Lactente , Masculino , Linhagem , Fenótipo , Diagnóstico Pré-Natal , Análise de Sequência de DNA
2.
Scientometrics ; 116(2): 655-674, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30147199

RESUMO

"Hot papers" (HPs) are papers which received a boost of citations shortly after publication. Papers with "delayed recognition" (DRs) received scarcely impact over a long time period, before a considerable citation boost started. DRs have attracted a lot of attention in scientometrics and beyond. Based on a comprehensive dataset with more than 5,000,000 papers published between 1980 and 1990, we identified HPs and DRs. In contrast to many other studies on DRs, which are based on raw citation counts, we calculated dynamically field-normalized impact scores for the search of HPs and DRs. This study is intended to investigate the differences between HPs (n = 323) and DRs (n = 315). The investigation of the journals which have published HPs and DRs revealed that some journals (e.g. Physical Review Letters and PNAS) were able to publish significantly more HPs than other journals. This pattern did not appear in DRs. Many HPs and DRs have been published by authors from the USA; however, in contrast to other countries, authors from the USA have published statistically significantly more HPs than DRs. Whereas "Biochemistry & Molecular Biology," "Immunology," and "Cell Biology" have published significantly more HPs than DRs, the opposite result arrived for "Surgery" and "Orthopedics." The results of the analysis of certain properties of HPs and DRs (e.g. number of pages) suggest that the emergence of DRs is an unpredictable process.

3.
Genome Res ; 25(1): 66-75, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25373143

RESUMO

RNA editing increases transcriptome diversity through post-transcriptional modifications of RNA. Adenosine deaminases that act on RNA (ADARs) catalyze the adenosine-to-inosine (A-to-I) conversion, the most common type of RNA editing in higher eukaryotes. Caenorhabditis elegans has two ADARs, ADR-1 and ADR-2, but their functions remain unclear. Here, we profiled the RNA editomes of C. elegans at different developmental stages of wild-type and ADAR mutants. We developed a new computational pipeline with a "bisulfite-seq-mapping-like" step and achieved a threefold increase in identification sensitivity. A total of 99.5% of the 47,660 A-to-I editing sites were found in clusters. Of the 3080 editing clusters, 65.7% overlapped with DNA transposons in noncoding regions and 73.7% could form hairpin structures. The numbers of editing sites and clusters were highest at the L1 and embryonic stages. The editing frequency of a cluster positively correlated with the number of editing sites within it. Intriguingly, for 80% of the clusters with 10 or more editing sites, almost all expressed transcripts were edited. Deletion of adr-1 reduced the editing frequency but not the number of editing clusters, whereas deletion of adr-2 nearly abolished RNA editing, indicating a modulating role of ADR-1 and an essential role of ADR-2 in A-to-I editing. Quantitative proteomics analysis showed that adr-2 mutant worms altered the abundance of proteins involved in aging and lifespan regulation. Consistent with this finding, we observed that worms lacking RNA editing were short-lived. Taken together, our results reveal a sophisticated landscape of RNA editing and distinct modes of action of different ADARs.


Assuntos
Adenosina Desaminase/genética , Caenorhabditis elegans/genética , Edição de RNA , RNA de Helmintos/genética , Adenosina/genética , Animais , Sequência de Bases , Proteínas de Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/metabolismo , Mapeamento Cromossômico , Biologia Computacional , Elementos de DNA Transponíveis/genética , Estudos de Avaliação como Assunto , Deleção de Genes , Estudos de Associação Genética , Dados de Sequência Molecular , Família Multigênica , Conformação de Ácido Nucleico , Polinucleotídeo Adenililtransferase/genética , Polinucleotídeo Adenililtransferase/metabolismo , Proteômica , Análise de Sequência de RNA , Transcriptoma
4.
Cell Res ; 24(11): 1311-27, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25312340

RESUMO

Postzygotic single-nucleotide mutations (pSNMs) have been studied in cancer and a few other overgrowth human disorders at whole-genome scale and found to play critical roles. However, in clinically unremarkable individuals, pSNMs have never been identified at whole-genome scale largely due to technical difficulties and lack of matched control tissue samples, and thus the genome-wide characteristics of pSNMs remain unknown. We developed a new Bayesian-based mosaic genotyper and a series of effective error filters, using which we were able to identify 17 SNM sites from ~80× whole-genome sequencing of peripheral blood DNAs from three clinically unremarkable adults. The pSNMs were thoroughly validated using pyrosequencing, Sanger sequencing of individual cloned fragments, and multiplex ligation-dependent probe amplification. The mutant allele fraction ranged from 5%-31%. We found that C→T and C→A were the predominant types of postzygotic mutations, similar to the somatic mutation profile in tumor tissues. Simulation data showed that the overall mutation rate was an order of magnitude lower than that in cancer. We detected varied allele fractions of the pSNMs among multiple samples obtained from the same individuals, including blood, saliva, hair follicle, buccal mucosa, urine, and semen samples, indicating that pSNMs could affect multiple sources of somatic cells as well as germ cells. Two of the adults have children who were diagnosed with Dravet syndrome. We identified two non-synonymous pSNMs in SCN1A, a causal gene for Dravet syndrome, from these two unrelated adults and found that the mutant alleles were transmitted to their children, highlighting the clinical importance of detecting pSNMs in genetic counseling.


Assuntos
Genoma Humano , Polimorfismo de Nucleotídeo Único , Zigoto/metabolismo , Acetil-CoA Carboxilase/genética , Adulto , Alelos , Teorema de Bayes , Pré-Escolar , Epilepsias Mioclônicas/genética , Epilepsias Mioclônicas/patologia , Feminino , Aconselhamento Genético , Genótipo , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Mosaicismo , Linhagem , Análise de Sequência de DNA
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA