A5088672980- Genomic variations and chromosomal abnormalities
- Congenital heart defects research
- Genomics and Rare Diseases
- Chromosomal and Genetic Variations
- Prenatal Screening and Diagnostics
- Genetics and Neurodevelopmental Disorders
- Chromatin Remodeling and Cancer
- RNA and protein synthesis mechanisms
- Autism Spectrum Disorder Research
- Genomics and Chromatin Dynamics
- Metabolism and Genetic Disorders
- RNA modifications and cancer
- Genomics and Phylogenetic Studies
- CRISPR and Genetic Engineering
- Protein Degradation and Inhibitors
- Folate and B Vitamins Research
- Congenital Heart Disease Studies
- Congenital Ear and Nasal Anomalies
- Williams Syndrome Research
- Cancer Mechanisms and Therapy
- Cancer-related gene regulation
- Porphyrin Metabolism and Disorders
- Genetic Associations and Epidemiology
- Neurofibromatosis and Schwannoma Cases
- interferon and immune responses
University of Pennsylvania
1999-2023
University of Colorado Denver
2014-2023
University of Colorado Anschutz Medical Campus
2013-2021
Invitae (United States)
2018
Hudson Institute
2017
John Wiley & Sons (United Kingdom)
2017
Pediatrics and Genetics
2010-2015
Children's Hospital of Philadelphia
1999-2010
Philadelphia University
2010
St. Joseph's Hospital
2007
Attention-deficit/hyperactivity disorder (ADHD) is a common and highly heritable disorder, but specific genetic factors underlying risk remain elusive. To assess the role of structural variation in ADHD, we identified 222 inherited copy number variations (CNVs) within 335 ADHD patients their parents that were not detected 2026 unrelated healthy individuals. Although no excess CNVs, either deletions or duplications, found cohort relative to controls, rare CNV-associated gene set was...
The 22q11.2 deletion syndrome, which includes DiGeorge and velocardiofacial syndromes (DGS/VCFS), is the most common microdeletion syndrome. majority of deleted patients share a 3 Mb hemizygous 22q11.2. remaining include those who have smaller deletions that are nested within typically region (TDR) few with rare no overlap TDR. identification chromosome 22-specific duplicated sequences or low copy repeats (LCRs) near end-points TDR has led to hypothesis they mediate entire been sequenced,...
Alveolar capillary dysplasia with misalignment of pulmonary veins (ACD/MPV) is a rare, neonatally lethal developmental disorder the lung defining histologic abnormalities typically associated multiple congenital anomalies (MCA). Using array CGH analysis, we have identified six overlapping microdeletions encompassing FOX transcription factor gene cluster in chromosome 16q24.1q24.2 patients ACD/MPV and MCA. Subsequently, four different heterozygous mutations (frameshift, nonsense, no-stop)...
A wealth of genetic associations for cardiovascular and metabolic phenotypes in humans has been accumulating over the last decade, particular a large number loci derived from recent genome wide association studies (GWAS). True complex disease-associated often exert modest effects, so their delineation currently requires integration diverse phenotypic data to ensure robust meta-analyses. We have designed gene-centric 50 K single nucleotide polymorphism (SNP) array assess potentially relevant...
We present a database of copy number variations (CNVs) detected in 2026 disease-free individuals, using high-density, SNP-based oligonucleotide microarrays. This large cohort, comprised mainly Caucasians (65.2%) and African-Americans (34.2%), was analyzed for CNVs single study uniform array platform computational process. have catalogued characterized 54,462 individual CNVs, 77.8% which were identified multiple unrelated individuals. These nonunique mapped to 3272 distinct regions genomic...
Patients with nonketotic hyperglycinemia and deficient glycine cleavage enzyme activity, but without mutations in AMT, GLDC or GCSH, the genes encoding its constituent proteins, constitute a clinical group which we call 'variant hyperglycinemia'. We hypothesize that some patients aetiology involves genetic result deficiency of cofactor lipoate, sequenced involved lipoate synthesis iron-sulphur cluster biogenesis. Of 11 individuals identified variant hyperglycinemia, were able to determine...
Alu elements are a family of interspersed repeats that have mobilized throughout primate genomes by retroposition from few "master" genes. Among the 500,000 in human genome members human-specific subfamily not fixed species; is, all chromosomes carry an element at particular locus. Four such polymorphic insertions were analyzed rapid, PCR-based assay uses primers flank insertion point to determine genotypes based on presence or absence element. These four shown be absent number nonhuman...
Abstract In the present study, DNA from 28 pediatric low‐grade astrocytomas was analyzed using Illumina HumanHap550K single‐nucleotide polymorphism oligonucleotide arrays. A novel duplication in chromosome band 7q34 identified 17 of 22 juvenile pilocytic and three six fibrillary astrocytomas. The spans 2.6 Mb genomic sequence contains approximately 20 genes, including two candidate tumor HIPK2 BRAF . There were no abnormalities , analysis mutation hot‐spots revealed a V600E only one without...
The HS subfamily of Alu sequences is comprised a group nearly identical members. Individual members share 97.7% nucleotide identity with each other and 98.9% the consensus sequence. are on average 2.8 million years old, were probably derived from single source 'master' gene sometime after human/great ape divergence. recent family member insertions provide better image structure retroposons before they have had opportunity to change significantly. All flanked by perfect direct repeats as...
A high-resolution genomic profiling and comprehensive targeted analysis of INI1/SMARCB1 a large series pediatric rhabdoid tumors was done. The aim to identify regions copy number change loss heterozygosity (LOH) that might pinpoint additional loci involved in the development or progression define spectrum alterations INI1 this malignancy.
Abstract Kabuki syndrome is a rare, multiple malformation disorder characterized by distinctive facial appearance, cardiac anomalies, skeletal abnormalities, and mild to moderate intellectual disability. Simplex cases make up the vast majority of reported with syndrome, but parent‐to‐child transmission in more than half‐dozen instances indicates that it an autosomal dominant disorder. We recently caused mutations MLL2 , gene encodes Trithorax‐group histone methyltransferase, protein...
Autism spectrum disorders (ASDs) comprise a constellation of highly heritable neuropsychiatric disorders. Genome-wide studies autistic individuals have implicated numerous minor risk alleles but few common variants, suggesting complex genetic model with many contributing loci. To assess commonality biological function among rare alleles, we compared functional knowledge genes overlapping inherited structural variants in idiopathic ASD subjects relative to healthy controls. In this study show...
Kabuki syndrome (KS) is a rare multiple congenital anomaly characterized by distinctive facial features, global developmental delay, intellectual disability and cardiovascular musculoskeletal abnormalities. While mutations in KMT2D have been identified majority of KS patients, few patients KDM6A. We analyzed 40 individuals clinically diagnosed with for Mutations were detected 12 KDM6A 4 cases, respectively. Observed included single-nucleotide variations indels leading to frame shifts,...
Genomic disorders contribute significantly to genetic disease and, as detection methods improve, greater numbers are being defined. Paralogous low copy repeats (LCRs) mediate many of the chromosomal rearrangements that underlie these disorders, predisposing chromosomes recombination errors. Deletions proximal 22q11.2 comprise most frequently occurring microdeletion syndrome, DiGeorge/Velocardiofacial syndrome (DGS/VCFS), in which breakpoints have been localized a 3 Mb region containing four...
The presence of chromosome-specific low-copy repeats (LCRs) predisposes chromosome 22 to deletions and duplications. current diagnostic procedure for detecting aberrations at 22q11.2 is chromosomal analysis coupled with fluorescence in situ hybridization (FISH) or PCR-based multiplex ligation dependent probe amplification (MLPA). However, there are copy number variations (CNVs) that only detected by high-resolution platforms such as array comparative genomic (aCGH). We report on development...
Multiple genetic syndromes are caused by recurrent chromosomal microdeletions or microduplications. The increasing use of high-resolution microarrays in clinical analysis has allowed the identification previously undetectable submicroscopic copy number variants (CNVs) associated with disorders. We hypothesized that patients congenital heart disease and additional dysmorphic features other anomalies would be likely to harbor undetected CNVs, which might identify new loci disease-related genes...
<h3>Background</h3> Mitochondrial disease is often suspected in cases of severe epileptic encephalopathy especially when a complex movement disorder, liver involvement and progressive developmental regression are present. Although mutations either mitochondrial DNA or <i>POLG</i> present, other nuclear defects replication protein translation have been associated with encephalopathy. <h3>Methods results</h3> We identified proband an encephalopathy, disorder combined respiratory chain enzyme...