A5091907972- Genomic variations and chromosomal abnormalities
- Genomics and Rare Diseases
- Genetics and Neurodevelopmental Disorders
- Congenital heart defects research
- Chromosomal and Genetic Variations
- Prenatal Screening and Diagnostics
- Genomics and Chromatin Dynamics
- RNA Research and Splicing
- Cancer Genomics and Diagnostics
- RNA modifications and cancer
- RNA regulation and disease
- Genetic Syndromes and Imprinting
- Epigenetics and DNA Methylation
- Ubiquitin and proteasome pathways
- RNA and protein synthesis mechanisms
- Genetic factors in colorectal cancer
- Chromatin Remodeling and Cancer
- DNA Repair Mechanisms
- Fetal and Pediatric Neurological Disorders
- Renal and related cancers
- Neurogenetic and Muscular Disorders Research
- Congenital Ear and Nasal Anomalies
- Clinical practice guidelines implementation
- Lysosomal Storage Disorders Research
- Immunodeficiency and Autoimmune Disorders
Baylor College of Medicine
2016-2025
Baylor Genetics
2016-2025
National Research Centre
2024
Texas Children's Hospital
2002-2023
Mayo Clinic in Arizona
2020
Neurological Research Institute
2020
Mayo Clinic in Florida
2020
Taian City Central Hospital
2012-2016
National Center on Birth Defects and Developmental Disabilities
2012
Pediatrics and Genetics
2003
Whole-exome sequencing can provide insight into the relationship between observed clinical phenotypes and underlying genotypes.We conducted a retrospective analysis of data from series 7374 consecutive unrelated patients who had been referred to diagnostic laboratory for whole-exome sequencing; our goal was determine frequency characteristics whom more than one molecular diagnosis reported. The phenotypic similarity molecularly diagnosed pairs diseases calculated with use terms Human...
In humans, SOX9 heterozygous mutations cause the severe skeletal dysmorphology syndrome campomelic dysplasia. Except for clinical descriptions, little is known about pathogenesis of this disease. We have generated Sox9 mutant mice that phenocopy most abnormalities syndrome. The +/− died perinatally with cleft palate, as well hypoplasia and bending many structures derived from cartilage precursors. embryonic day (E)14.5 embryos, radius, ulna, tibia cartilages was already prominent. E12.5...
<h3>Importance</h3> While congenital malformations and genetic diseases are a leading cause of early infant death, to our knowledge, the contribution single-gene disorders in this group is undetermined. <h3>Objective</h3> To determine diagnostic yield use clinical exome sequencing critically ill infants. <h3>Design, Setting, Participants</h3> Clinical was performed for 278 unrelated infants within first 100 days life who were admitted Texas Children’s Hospital Houston, Texas, during 5-year...
Given the rarity of most single-gene Mendelian disorders, concerted efforts data exchange between clinical and scientific communities are critical to optimize molecular diagnosis novel disease gene discovery. We designed implemented protocols for study cases which a plausible was not achieved in genomics diagnostic laboratory (i.e. unsolved exomes). Such were recruited research further analyses, order potentially: (1) accelerate discovery; (2) increase yield whole exome sequencing (WES); (3)...
Endosomal protein recycling is a fundamental cellular process important for homeostasis, signaling, and fate determination that implicated in several diseases. WASH an actin-nucleating essential this process, its activity controlled through K63-linked ubiquitination by the MAGE-L2-TRIM27 ubiquitin ligase. Here, we show USP7 deubiquitinating enzyme integral component of ligase WASH-mediated endosomal actin assembly recycling. Mechanistically, acts as molecular rheostat to precisely fine-tune...
Array comparative genomic hybridization (aCGH) is a powerful tool for the molecular elucidation and diagnosis of disorders resulting from copy-number variation (CNV). However, intragenic deletions or duplications--those including intervals size smaller than gene--have remained beyond detection limit most clinical aCGH analyses. Increasing array probe number improves resolution, although higher cost may implementation, enhanced benign CNV can confound interpretation. We designed an with...
Abstract Objective To evaluate the use of array comparative genomic hybridization (aCGH) for prenatal diagnosis, including assessment variants uncertain significance, and ability to detect abnormalities not detected by karyotype, vice versa. Methods Women undergoing amniocentesis or chorionic villus sampling (CVS) karyotype were offered aCGH analysis using a targeted microarray. Parental samples obtained concurrently exclude maternal cell contamination determine if copy number (CNVs) de novo...
Over half of the mature hepatocytes in mice and humans are aneuploid yet retain full ability to undergo mitosis. This observation has raised question whether this unusual somatic genetic variation evolved as an adaptive mechanism response hepatic injury. According model, hepatotoxic insults select for with specific numerical chromosome abnormalities, rendering them differentially resistant To test hypothesis, we utilized a strain heterozygous mutation homogentisic acid dioxygenase (Hgd) gene...
Exome sequencing is now being incorporated into clinical care for pediatric and adult populations, but its integration prenatal diagnosis has been more limited. One reason this the paucity of information about utility exome in setting.We retrospectively reviewed indications, results, time to results (turnaround time, TAT), impact 146 consecutive "fetal exomes" performed a diagnostic laboratory between March 2012 November 2017. We define fetal as one on sample obtained from fetus or product...
We delineated and analyzed directly oriented paralogous low-copy repeats (DP-LCRs) in the most recent version of human haploid reference genome. The computationally defined DP-LCRs were cross-referenced with our chromosomal microarray analysis (CMA) database 25,144 patients subjected to genome-wide assays. This guided approach empirically derived large data set allowed us investigate genomic rearrangement relative frequencies identify new loci for recurrent nonallelic homologous...
In clinical diagnostics, both array comparative genomic hybridization (array CGH) and single nucleotide polymorphism (SNP) genotyping have proven to be powerful technologies utilized for the evaluation of developmental delay, multiple congenital anomalies, neuropsychiatric disorders. Differences in ability resolve changes between these arrays may constitute an implementation challenge clinicians: which platform (SNP vs might best detect underlying genetic cause disease patient? While only...
Alu repetitive elements are known to be major contributors genome instability by generating Alu-mediated copy-number variants (CNVs). Most of the reported CNVs simple deletions and duplications, mechanism underlying Alu–Alu-mediated rearrangement has been attributed non-allelic homologous recombination (NAHR). Chromosome 17 at p13.3 genomic region lacks extensive low-copy repeat architecture; however, it is highly enriched for elements, with a fraction 30% total sequence annotated in human...