A5085810963- Genomics and Rare Diseases
- Genetics and Neurodevelopmental Disorders
- Autism Spectrum Disorder Research
- Genomic variations and chromosomal abnormalities
- Metabolism and Genetic Disorders
- Connective tissue disorders research
- Epilepsy research and treatment
- Virology and Viral Diseases
- Hereditary Neurological Disorders
- Mitochondrial Function and Pathology
- Single-cell and spatial transcriptomics
- Amino Acid Enzymes and Metabolism
- Genetic Neurodegenerative Diseases
- Ubiquitin and proteasome pathways
- Signaling Pathways in Disease
- Peptidase Inhibition and Analysis
- Endoplasmic Reticulum Stress and Disease
- CRISPR and Genetic Engineering
- Chronic Lymphocytic Leukemia Research
- Genetic Syndromes and Imprinting
- Chromosomal and Genetic Variations
- Hemophilia Treatment and Research
- RNA and protein synthesis mechanisms
- Cancer-related gene regulation
- Pharmacological Effects and Toxicity Studies
University of California, Los Angeles
2015-2023
Center for Autism and Related Disorders
2018-2023
UCLA Health
2019
The University of Melbourne
2017
Peking University First Hospital
2017
Peking University
2017
The University of Queensland
2017
Austin Health
2017
Sheba Medical Center
2017
Tel Aviv University
2017
PurposeDespite the recognized clinical value of exome-based diagnostics, methods for comprehensive genomic interpretation remain immature. Diagnoses are based on known or presumed pathogenic variants in genes already associated with a similar phenotype. Here, we extend this paradigm by evaluating novel bioinformatics approaches to aid identification new gene–disease associations.MethodsWe analyzed 119 trios identify both diagnostic genotypes and candidate genes. We considered qualifying...
Autism spectrum disorder (ASD) has a complex genetic architecture involving contributions from both de novo and inherited variation. Few studies have been designed to address the role of rare variation or its interaction with common polygenic risk in ASD. Here, we performed whole-genome sequencing largest cohort multiplex families date, consisting 4,551 individuals 1,004 having two more autistic children. Using this study design, identify seven previously unrecognized ASD genes supported by...
We present the analysis of twenty human genomes to evaluate prospects for identifying rare functional variants that contribute a phenotype interest. sequenced at high coverage ten "case" from individuals with severe hemophilia A and "control" genomes. summarize number genetic emerging study this magnitude, provide proof concept identification highly-penetrant by confirming cause is easily recognizable in data set. also show novel single nucleotide (SNVs) discovered per genome seems stabilize...
<h3>Objective:</h3> Following our original description of generalized epilepsy with febrile seizures plus (GEFS+) in 1997, we analyze the phenotypic spectrum 409 affected individuals 60 families (31 new families) and expand GEFS+ spectrum. <h3>Methods:</h3> We performed detailed electroclinical phenotyping on all available family members. Genetic analysis known genes was carried out where possible. compared genetic data to those published literature over last 19 years. <h3>Results:</h3>...
Idiopathic generalized epilepsy (IGE) is a complex disease with high heritability, but little known about its genetic architecture. Rare copy-number variants have been found to explain nearly 3% of individuals IGE; however, it remains unclear whether moderate effect size and frequencies below what are reliably detected genome-wide association studies contribute significantly risk. In this study, we compare the exome sequences 118 IGE 242 controls European ancestry by using next-generation...
Abstract Summary: Here we present Sequence Variant Analyzer (SVA), a software tool that assigns predicted biological function to variants identified in next-generation sequencing studies and provides browser visualize the their genomic contexts. SVA also for flexible interaction with implementing variant association tests allowing users consider both bioinformatic annotation of strength associations studied traits. We illustrate features using two simple examples sequenced genomes harbor...
Two unrelated patients, presenting with significant global developmental delay, severe progressive microcephaly, seizures, spasticity and thin corpus callosum (CC) underwent trio whole‐exome sequencing. No candidate variant was found in any known genes related to the phenotype. However, crossing data of patients illustrated that they both manifested pathogenic variants SLC1A4 gene which codes ASCT1 transporter serine other neutral amino acids. The Ashkenazi patient is homozygous for a...
Hereditary neuralgic amyotrophy (HNA) is an autosomal dominant disorder that manifests as recurrent, episodic, painful brachial neuropathies. A gene for HNA maps to chromosome 17q25.3 where mutations in SEPT9, encoding the septin-9 protein, have been identified.To determine frequency and type of SEPT9 a new cohort 42 unrelated pedigrees.DNA sequencing all exons intron-exon boundaries was carried out affected individual each pedigree from our cohort. Genotyping using microsatellite markers...
<h3>Background</h3> Genomic copy number variants have been shown to be responsible for multiple genetic diseases. Recently, a duplication in septin 9 (<i>SEPT9</i>) was causal hereditary neuralgic amyotrophy (HNA), an episodic peripheral neuropathy with autosomal dominant inheritance. This identified 12 pedigrees that all shared common founder haplotype. <h3>Methods and results</h3> Based on array comparative genomic hybridisation, we six additional heterogeneous tandem <i>SEPT9</i>...
Hereditary neuralgic amyotrophy (HNA) is an autosomal dominant disorder associated with recurrent episodes of focal neuropathy primarily affecting the brachial plexus. Point mutations in SEPT9 gene have been previously identified as molecular basis HNA some pedigrees. However many families, including those from North America demonstrating a genetic founder haplotype, no sequence detected. We report intragenic 38 Kb duplication that linked to 12 American families share common haplotype....
Abstract Genetic studies of autism spectrum disorder (ASD) have revealed a complex, heterogeneous architecture, in which the contribution rare inherited variation remains relatively un-explored. We performed whole-genome sequencing (WGS) 2,308 individuals from families containing multiple affected children, including analysis single nucleotide variants (SNV) and structural (SV). identified 16 new ASD-risk genes, many supported by variation, provide statistical support for 69 genes total,...
Abstract Defining the number, proportion, or lineage of distinct cell types in developing human brain is an important goal modern research. We defined single transcriptomic profiles for 40,000 cells at mid-gestation to identify neocortex. define expression corresponding all known major this developmental period and multiple transcription factors co-factors expressed specific types, providing unprecedented resource understanding neocortical development including first single-cell...
Abstract Autism Spectrum Disorder (ASD) has a complex genetic architecture involving contributions from de novo and inherited variation. Few studies have been designed to address the role of rare variation, or its interaction with polygenic risk in ASD. Here, we performed whole genome sequencing largest cohort multiplex families date, consisting 4,551 individuals 1,004 having 2 more affected children Using this study design, identify seven novel genes supported primarily by finding support...