Next Generation Sequencing Approaches to Childhood Neurological Diseases
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PROVIDER: PRJNA314925 | ENA |
REPOSITORIES: ENA
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Project description:Next Generation Sequencing Approaches to Childhood Neurological Diseases
| PRJNA314926 | ENA
Project description:Next Generation Mendelian Genetics: Hereditary Neurological Disorders
| PRJNA236332 | ENA
Project description:TEFM variants impair mitochondrial transcription elongation causing childhood-onset neurological disease
| PRJNA768394 | ENA
Project description:Pluripotent stem cell derived models of neurological diseases reveal early transcriptional heterogeneity
| PRJNA576257 | ENA
Project description:The development of next-generation sequencing technologies has allowed for the identification of several new genes and genetic factors in human genetics. Common results from the application of these technologies have revealed unexpected presentations for mutations in known disease genes. In this review, we summarize the major contributions of exome sequencing to the study of neurodegenerative disorders and other neurological conditions and discuss the interface between Mendelian and complex neurological diseases with a particular focus on pleiotropic events.
| S-EPMC4170717 | biostudies-literature
Project description:Of 7028 disorders with suspected Mendelian inheritance, 1139 are recessive and have an established molecular basis. Although individually uncommon, Mendelian diseases collectively account for ~20% of infant mortality and ~10% of pediatric hospitalizations. Preconception screening, together with genetic counseling of carriers, has resulted in remarkable declines in the incidence of several severe recessive diseases including Tay-Sachs disease and cystic fibrosis. However, extension of preconception screening to most severe disease genes has hitherto been impractical. Here, we report a preconception carrier screen for 448 severe recessive childhood diseases. Rather than costly, complete sequencing of the human genome, 7717 regions from 437 target genes were enriched by hybrid capture or microdroplet polymerase chain reaction, sequenced by next-generation sequencing (NGS) to a depth of up to 2.7 gigabases, and assessed with stringent bioinformatic filters. At a resultant 160x average target coverage, 93% of nucleotides had at least 20x coverage, and mutation detection/genotyping had ~95% sensitivity and ~100% specificity for substitution, insertion/deletion, splicing, and gross deletion mutations and single-nucleotide polymorphisms. In 104 unrelated DNA samples, the average genomic carrier burden for severe pediatric recessive mutations was 2.8 and ranged from 0 to 7. The distribution of mutations among sequenced samples appeared random. Twenty-seven percent of mutations cited in the literature were found to be common polymorphisms or misannotated, underscoring the need for better mutation databases as part of a comprehensive carrier testing strategy. Given the magnitude of carrier burden and the lower cost of testing compared to treating these conditions, carrier screening by NGS made available to the general population may be an economical way to reduce the incidence of and ameliorate suffering associated with severe recessive childhood disorders.
| S-EPMC3740116 | biostudies-literature
Project description:This study compared whole transcriptome signatures of 6 immune cell subsets and whole blood from patients with an array of immune-associated diseases. Fresh blood samples were collected from healthy subjects and subjects diagnosed type 1 diabetes, amyotrophic lateral sclerosis, and sepsis, as well as multiple sclerosis patients before and 24 hours after the first treatment with IFN-beta. At the time of blood draw, an aliquot of whole blood was collected into a Tempus tube (Invitrogen), while the remainder of the primary fresh blood sample was processed to highly pure populations of neutrophils, monocytes, B cells, CD4 T cells, CD8 T cells, and natural killer cells. RNA was extracted from each of these cell subsets, as well as the whole blood samples, and processed into RNA sequencing (RNAseq) libraries (Illumina TruSeq). Sequencing libraries were analyzed on an Illumina HiScan, with a target read depth of ~20M reads. Reads were demultiplexed, mapped to human gene models (ENSEMBL), and tabulated using HTSeq. Read count data were normalized by the TMM procedure (edgeR package). We performed whole genome RNAseq profiling of immune cell subsets and whole blood from subjects with an array of immune-associated diseases.
2015-01-06 | E-GEOD-60424 | biostudies-arrayexpress
Project description:Microglia play important roles in developmental and homeostatic brain function, and influence the establishment and progression of many neurological disorders. Here, we demonstrate that renewable human iPSCs can be efficiently differentiated to microglial-like cells (iMGL) to study neurological diseases, such as Alzheimer's disease (AD). We find that iMGLs develop in vitro similarly to microglia in vivo and whole transcriptome analysis demonstrates that they are highly similar to adult and fetal human microglia. Functional assessment of iMGLs reveal that they secrete cytokines in response to inflammatory stimuli, migrate and undergo calcium transients, and robustly phagocytose CNS substrates. We also show novel use of iMGLs to examine the effects of fibrillar Aβ and brain-derived tau oligomers on AD-related gene expression and to interrogate mechanisms involved in synaptic pruning. Taken together, these findings demonstrate that iMGLs can be used in high-throughput studies of microglial function, providing important new insight into human neurological disease.
2017-04-19 | GSE89189 | GEO
Project description:Although not an affected cell type, skin fibroblasts from individuals with childhood cerebral adrenoleukodystrophy (CCALD), an early onset X-linked neurological disorder, show defects in very long chain fatty acid (VLCFA) metabolism that provide the basis for clinical diagnostic tests. We report the gene expression profiles of fibroblasts from childhood cerebral adrenoleukodystrophy patients and healthy controls
2012-03-01 | GSE34308 | GEO
Project description:Next-generation sequencing techniques have made vast quantities of data on human genomes and transcriptomes available to researchers. Huge progress has been made towards understanding the basis of many Mendelian neurological conditions, but progress has been considerably slower in complex neurological diseases (multiple sclerosis, migraine, Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and so on). The authors review current next-generation sequencing methodologies and present selected studies illustrating how these have been used to cast light on the genetic etiology of complex neurological diseases with specific focus on multiple sclerosis. The authors highlight particular pitfalls in next-generation sequencing experiments and speculate on both clinical and research applications of these sequencing platforms for complex neurological disorders in the future.
| S-EPMC3836167 | biostudies-literature