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A principal task in dissecting the genetics of complex traits is to identify causal genes for disease phenotypes. We previously developed a method to infer causal relationships among genes through the integration of DNA variation, gene transcription and phenotypic information. Here we have validated our method through the characterization of transgenic and(More)
IMPORTANCE Clinical exome sequencing (CES) is rapidly becoming a common molecular diagnostic test for individuals with rare genetic disorders. OBJECTIVE To report on initial clinical indications for CES referrals and molecular diagnostic rates for different indications and for different test types. DESIGN, SETTING, AND PARTICIPANTS Clinical exome(More)
Arx is a homeobox-containing gene with a high degree of sequence similarity between mouse and zebrafish. Arx is expressed in the forebrain and floor plate of the developing central nervous systems of these vertebrates and in the presumptive cortex of fetal mice. Our goal was to identify genes in Xp22.1-p21.3 involved in human neuronal development. Our in(More)
Mitochondrial aldehyde dehydrogenase 2 (ALDH2) is expressed in a tissue-specific fashion with high levels in liver, heart, kidney, and muscle, and low levels in most other tissues. The ALDH2 promoter was found to bind nuclear proteins at a pair of adjacent sites approximately 300 bp upstream from the translation start site, each of which was contacted at(More)
The mRNA for the novel aldehyde dehydrogenase 5 (ALDH5) gene was detected in HuH7 hepatoma cells. The cells also expressed cytosolic aldehyde dehydrogenase (ALDH1) mRNA, but no mitochondrial aldehyde dehydrogenase (ALDH2) mRNA. Extracts of the hepatoma cells contained an enzymatic activity with an isoelectric point similar to that of ALDH1. This enzyme(More)
IL1RAPL1 (interleukin-1 receptor accessory protein-like, gene 1) has recently been shown to be mutated in patients with X-linked mental retardation. Clinical experience has suggested that patients with the contiguous gene syndrome, complex glycerol kinase deficiency (cGKD), will have mental retardation (MR) if they have deletions extending from the GK gene(More)
Mitochondrial aldehyde dehydrogenase (ALDH2) activity is produced at low levels in many tissues, with highest production in liver. Transfection assays using the first 600 bp of upstream DNA provided evidence for both positive and negative regulatory elements in the proximal promoter. A region from -79 to -116 bp was protected in DNase I footprinting assays(More)
The liver plays a central role in maintaining whole body metabolic and energy homeostasis by consuming and producing glucose and fatty acids. Glucose and fatty acids compete for hepatic substrate oxidation with regulation ensuring glucose is oxidized preferentially. Increasing fatty acid oxidation is expected to decrease lipid storage in the liver and avoid(More)