A5085826245- Hearing, Cochlea, Tinnitus, Genetics
- Genetic Associations and Epidemiology
- Genomics and Rare Diseases
- Genomic variations and chromosomal abnormalities
- Genetics and Neurodevelopmental Disorders
- Genetic Mapping and Diversity in Plants and Animals
- Connective tissue disorders research
- RNA regulation and disease
- Congenital heart defects research
- Cancer-related molecular mechanisms research
- Ear Surgery and Otitis Media
- RNA and protein synthesis mechanisms
- Vestibular and auditory disorders
- Aortic Disease and Treatment Approaches
- Epigenetics and DNA Methylation
- RNA modifications and cancer
- Mitochondrial Function and Pathology
- Biochemical Analysis and Sensing Techniques
- Genetic and phenotypic traits in livestock
- Skin and Cellular Biology Research
- Chromosomal and Genetic Variations
- Connexins and lens biology
- Cell Adhesion Molecules Research
- RNA Research and Splicing
- Cellular transport and secretion
Columbia University Irving Medical Center
2019-2025
Columbia University
1990-2025
Baylor College of Medicine
2012-2023
University of Amsterdam
2022
Amsterdam University Medical Centers
2022
Rockefeller University
1997-2021
Baylor Genetics
2005-2020
Universidad de Antioquia
2019
University of Washington
2011-2018
Washington Center
2018
As a first step toward understanding how rare variants contribute to risk for complex diseases, we sequenced 15,585 human protein-coding genes an average median depth of 111× in 2440 individuals European (n = 1351) and African 1088) ancestry. We identified over 500,000 single-nucleotide (SNVs), the majority which were (86% with minor allele frequency less than 0.5%), previously unknown (82%), population-specific (82%). On average, 2.3% 13,595 SNVs each person carried predicted affect protein...
The discovery of rare genetic variants is accelerating, and clear guidelines for distinguishing disease-causing sequence from the many potentially functional present in any human genome are urgently needed. Without rigorous standards we risk an acceleration false-positive reports causality, which would impede translation genomic research findings into clinical diagnostic setting hinder biological understanding disease. Here discuss key challenges assessing disease, integrating both...
Opioid drugs play important roles in the clinical management of pain, as well development and treatment drug abuse. The mu opioid receptor is primary site action for most commonly used opioids, including morphine, heroin, fentanyl, methadone. By sequencing DNA from 113 former heroin addicts methadone maintenance 39 individuals with no history or alcohol abuse dependence, we have identified five different single-nucleotide polymorphisms (SNPs) coding region gene. prevalent SNP a nucleotide...
We previously described two members of a family affected by an apparently genetically determined fatal disease characterized clinically progressive insomnia, dysautonomia, and motor signs pathologically severe atrophy the anterior ventral mediodorsal thalamic nuclei. Five other who died this disease, which we termed "fatal familial insomnia," had broader neuropathologic changes suggesting that insomnia could be prion disease.
Thoracic aortic aneurysms leading to acute dissections (TAAD) can be inherited in families an autosomal dominant manner. As part of the spectrum clinical heterogeneity familial TAAD, we recently described with multiple members that had TAAD and intracranial or abdominal manner.To identify causative mutation a large family inheritance by performing exome sequencing 2 distantly related individuals identifying shared rare variants.A novel frame shift mutation, p. N218fs (c.652delA), was...
Mutations in several genes have been identified that are responsible for 25% of families with familial thoracic aortic aneurysms and dissections. However, the causative gene remains unknown 75% families.To identify mutation autosomal dominant inheritance dissections.Exome sequencing was used to a large family A heterozygous rare variant, c.839G>T (p.Ser280Arg), LOX, encoding lysyl oxidase, segregated disease family. Sanger exome investigate mutations LOX an additional 410 probands from...
Non-syndromic low frequency sensorineural hearing loss (LFSNHL) affecting only 2000 Hz and below is an unusual type of that worsens over time without progressing to profound deafness. This LFSNHL may be associated with mild tinnitus but not vertigo. We have previously reported two families autosomal dominant linked adjacent non-overlapping loci on 4p16, DFNA6 DFNA14. However, further study revealed individual in the family who had a recombination event excluded DFNA14 candidate region was...
Inefficient mitochondrial electron transport chain (ETC) function has been implicated in the vicious cycle of reactive oxygen species (ROS) production that may predispose an individual to late onset diseases, such as diabetes, hypertension, and cancer. Mitochondrial DNA (mtDNA) variations affect efficiency ETC ROS production, thus contributing cancer risk. To test this hypothesis, we genotyped 69 mtDNA 156 unrelated European-American females with familial breast 260 age-matched female...
There is solid evidence that rare variants contribute to complex disease etiology. Next-generation sequencing technologies make it possible uncover within candidate genes, exomes, and genomes. Working in a novel framework, the kernel-based adaptive cluster (KBAC) was developed perform powerful gene/locus based variant association testing. The KBAC combines classification testing coherent framework. Covariates can also be incorporated analysis control for potential confounders including age,...
The left ventricular outflow tract (LVOTO) malformations, aortic valve stenosis (AVS), coarctation of the aorta (COA), and hypoplastic heart (HLH) constitute a mechanistically defined subgroup congenital defects that have substantial evidence for genetic component. Evidence from echocardiography studies has shown bicuspid (BAV) is found frequently in relatives children with LVOTO defects. However, formal inheritance analysis not been performed. We ascertained 124 families by an index case...