A5016212527- Genomics and Chromatin Dynamics
- Genomics and Rare Diseases
- RNA and protein synthesis mechanisms
- Genetic Associations and Epidemiology
- Epigenetics and DNA Methylation
- RNA Research and Splicing
- Genetics and Neurodevelopmental Disorders
- Genomic variations and chromosomal abnormalities
- Genomics and Phylogenetic Studies
- RNA modifications and cancer
- Chromosomal and Genetic Variations
- CRISPR and Genetic Engineering
- Genetic Neurodegenerative Diseases
- Molecular Biology Techniques and Applications
- Gene expression and cancer classification
- Cancer-related molecular mechanisms research
- Single-cell and spatial transcriptomics
- Mitochondrial Function and Pathology
- Bioinformatics and Genomic Networks
- Cancer Genomics and Diagnostics
- Tryptophan and brain disorders
- DNA Repair Mechanisms
- Immune Cell Function and Interaction
- Bipolar Disorder and Treatment
- T-cell and B-cell Immunology
HudsonAlpha Institute for Biotechnology
2016-2025
Takeda (United States)
2023-2025
Lieber Institute for Brain Development
2024
Public Health England
2020-2022
University of Alabama at Birmingham
1986-2016
Durham University
1986-2014
University of Massachusetts Chan Medical School
2013
Stanford University
2003-2012
ID Genomics (United States)
2010
GlaxoSmithKline (Netherlands)
2009
We present Model-based Analysis of ChIP-Seq data, MACS, which analyzes data generated by short read sequencers such as Solexa's Genome Analyzer. MACS empirically models the shift size tags, and uses it to improve spatial resolution predicted binding sites. also a dynamic Poisson distribution effectively capture local biases in genome, allowing for more robust predictions. compares favorably existing peak-finding algorithms, is freely available.
In vivo protein-DNA interactions connect each transcription factor with its direct targets to form a gene network scaffold. To map these comprehensively across entire mammalian genomes, we developed large-scale chromatin immunoprecipitation assay (ChIPSeq) based on ultrahigh-throughput DNA sequencing. This sequence census method was then used in binding of the neuron-restrictive silencer (NRSF; also known as REST, for repressor element–1 silencing factor) 1946 locations human genome. The...
Human genetic diversity is shaped by both demographic and biological factors has fundamental implications for understanding the basis of diseases. We studied 938 unrelated individuals from 51 populations Genome Diversity Panel at 650,000 common single-nucleotide polymorphism loci. Individual ancestry population substructure were detectable with very high resolution. The relationship between haplotype heterozygosity geography was consistent hypothesis a serial founder effect single origin in...
Chromatin immunoprecipitation (ChIP) followed by high-throughput DNA sequencing (ChIP-seq) has become a valuable and widely used approach for mapping the genomic location of transcription-factor binding histone modifications in living cells. Despite its widespread use, there are considerable differences how these experiments conducted, results scored evaluated quality, data metadata archived public use. These practices affect quality utility any global ChIP experiment. Through our experience...
The basal cell nevus syndrome (BCNS) is characterized by developmental abnormalities and the postnatal occurrence of cancers, especially carcinomas (BCCs), most common human cancer. Heritable mutations in BCNS patients a somatic mutation sporadic BCC were identified homolog Drosophila patched (ptc) gene. ptc gene encodes transmembrane protein that acts opposition to Hedgehog signaling protein, controlling fates, patterning, growth numerous tissues. PTC appears be crucial for proper embryonic...
Genome-wide expression profiling is a powerful tool for implicating novel gene ensembles in cellular mechanisms of health and disease. The most popular platform genome-wide the Affymetrix GeneChip. However, its selection probes relied on earlier genome transcriptome annotation which significantly different from current knowledge. resultant informatics problems have profound impact analysis interpretation data. Here, we address these critical issues offer solution. We identified several...
Marine stickleback fish have colonized and adapted to thousands of streams lakes formed since the last ice age, providing an exceptional opportunity characterize genomic mechanisms underlying repeated ecological adaptation in nature. Here we develop a high-quality reference genome assembly for threespine sticklebacks. By sequencing genomes twenty additional individuals from global set marine freshwater populations, identify genome-wide loci that are consistently associated with...
The National Institutes of Health Mammalian Gene Collection (MGC) Program is a multiinstitutional effort to identify and sequence cDNA clone containing complete ORF for each human mouse gene. ESTs were generated from libraries enriched full-length cDNAs analyzed candidate full-ORF clones, which then sequenced high accuracy. MGC has currently verified the full nonredundant set >9,000 >6,000 genes. Candidate clones an additional 7,800 3,500 genes also have been identified. All sequences...
Transcription factors bind in a combinatorial fashion to specify the on-and-off states of genes; ensemble these binding events forms regulatory network, constituting wiring diagram for cell. To examine principles human transcriptional we determined genomic information 119 transcription-related over 450 distinct experiments. We found combinatorial, co-association transcription be highly context specific: combinations at specific locations. In particular, there are significant differences...
Major phenotypic changes evolve in parallel nature by molecular mechanisms that are largely unknown. Here, we use positional cloning methods to identify the major chromosome locus controlling armor plate patterning wild threespine sticklebacks. Mapping, sequencing, and transgenic studies show Ectodysplasin (EDA) signaling pathway plays a key role evolutionary change natural populations evolution of stickleback low-plated phenotypes at most freshwater locations around world has occurred...
Denaturing gradient gel electrophoresis (DGGE) can be used to distinguish two DNA molecules that differ by as little a single-base substitution. This method detects approximately 50% of all possible changes in fragments ranging from 50 1000 base pairs. To increase the number distinguished DGGE, we polymerase chain reaction attach 40-base-pair G + C-rich sequence, designated GC-clamp, one end amplified encompass regions mouse and human beta-globin genes. We show this GC-clamp allows detection...
Adaptive Girdle Loss in Sticklebacks How do molecular changes give rise to phenotypic adaptation exemplified by the repeated reduction pelvic girdle observed separate populations of sticklebacks? Now Chan et al. (p. 302 , published online 10 December) have identified specific DNA that control this major skeletal adaptation. The key locus controlling phenotypes mapped a noncoding regulatory region upstream Pituitary homeobox transcription factor 1 gene, which drives tissue-specific enhancer....
The neurotransmitter serotonin (5HT) activates a variety of second messenger signaling systems and through them indirectly regulates the function ion channels. Serotonin also channels directly, suggesting that it may mediate rapid, excitatory responses. A complementary DNA clone containing coding sequence one these rapidly responding channels, 5HT3 subtype receptor, has been isolated by screening neuroblastoma expression library for functional serotonin-gated currents in Xenopus oocytes....
Amyotrophic lateral sclerosis (ALS) is a devastating neurological disease with no effective treatment. We report the results of moderate-scale sequencing study aimed at increasing number genes known to contribute predisposition for ALS. performed whole-exome 2869 ALS patients and 6405 controls. Several were found be associated, TBK1 (the gene encoding TANK-binding kinase 1) was identified as an gene. bind phosphorylate proteins involved in innate immunity autophagy, including optineurin...
Mammalian telomeres are thought to be composed of a tandem array TTAGGG repeats. To further define the type and arrangement sequences at ends human chromosomes, we developed direct cloning strategy for telomere-associated DNA. The method involves telomere enrichment procedure based on relative lack restriction endonuclease cutting sites near chromosomes. Nineteen (TTAGGG)n-bearing plasmids were isolated, two which contain additional proximal telomeric These telomere-flanking detect BAL...
Chromatin immunoprecipitation coupled with high-throughput sequencing (ChIP-seq) has become the dominant technique for mapping transcription factor (TF) binding regions genome-wide. We performed an integrative analysis centered around 457 ChIP-seq data sets on 119 human TFs generated by ENCODE Consortium. identified highly enriched sequence motifs in most sets, revealing new and validating known ones. The motif sites (TF sites) are conserved evolutionarily show distinct footprints upon DNase...
Genome-wide scans for recent positive selection in humans have yielded insight into the mechanisms underlying extensive phenotypic diversity our species, but focused on a limited number of populations. Here, we present an analysis global sample 53 populations, using genotype data from Human Genome Diversity-CEPH Panel. We refine geographic distributions known selective sweeps, and find overlap between these populations same continental region outside groupings. several examples previously...
The human genome is thought to harbor 50,000 100,000 genes, of which about half have been sampled date in the form expressed sequence tags. An international consortium was organized develop and map gene-based tagged site markers on a set two radiation hybrid panels yeast artificial chromosome library. More than 16,000 genes mapped relative framework that contains 1000 polymorphic genetic markers. gene unifies existing physical maps with nucleotide protein databases fashion should speed...