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Functional genomics of visual system development and diseases; High throughput technology
Our lab is broadly interested in developing and applying genomic technologies to understand the genetic networking underlying developmental biology and human diseases.
Both experimental and computational approaches are used in combination to identify and model gene functions in both human patients and model organisms, including Drosophila and mice.
Identification of human retinal disease genes
One of the main focuses in our laboratory is to understand the molecular mechanism underlying human retinal disease. Collectively, ocular diseases affect a large population;
approximately 40 million people in the world are blind and another 100 million have substantial visual impairment. Together with our collaborators, we are currently working on identifying disease genes
involved in several human retinal diseases, including Leber congenital amaurosis (LCA), Usher syndrome, retinitis pigmentosa (RP), and AMD. Recently, we have cloned SPATA7 as a novel human
retinal disease gene, mutations in which lead to LCA and RP. In addition, several novel disease loci have been mapped in our patient collection. To identify the mutations in these loci, we are applying
the cutting edge NextGen sequencing technologies to perform both targeted and whole genome sequencing on these patient DNA samples.
Animal models for retinal disease and development
Model organisms including mouse and Drosophila malanogaster are useful tools to understand molecular mechanism of diseases and also identify genetic networks that control retinal
development. Using mouse as the model organism, we have recently generated numerous knock out mice that mimic human retinal diseases. Genetic, genomic, and biochemical approaches to decipher
the molecular function of these genes are currently underway. In Drosophila, a major effort in our laboratory is to understand the molecular mechanism of the early retinal cell fate
determination process. A genome-wide, combinatorial approach, including gene expression profiling with both microarray and mRNA-Seq, comparative genomics at both DNA and mRNA level, and downstream
target identification using ChIP-Seq, has been adopted. Strikingly, our data suggests a highly connected, dynamic genetic network. Further characterization as well as experimental validation and
testing of the network will likely to provide a significant contribution to our understanding of the genetic mechanisms controlling retinal development in general.
Genomic technology development and applications
Introduction of new technologies often leads to breakthrough of scientific discoveries. Recently, the most exciting novel technology in molecular and genomic biology is the Next generation
sequencing. To fully utilize this in our research, a set of protocols and software tools that is specific for the NextGen technology has been developed among our laboratory and our collaborators,
including RNA-Seq, miRNA-Seq, CNV-Seq, ChIP-Seq, chromatin profiling, and mutation detection. Currently, we are applying these tools to various research fields, including development, genetic
disease gene cloning, and cancer biology.
Selected Publications
Rat Genome Sequencing Project Consortium (2004) Genome sequence of the Brown Norway rat yields insights into mammalian evolution. Nature 428:493-521.
Havlak P*, Chen R*, Durbin KJ, Egan A, Ren Y, Song XZ, Weinstock GM, Gibbs RA (2004) The Atlas genome assembly system. Genome Research 14:721-732. (*equal contribution)
Ross MT et al., Chen R et al., Rogers J, Bentley DR (2005) The DNA sequence of the human X chromosome. Nature 434:325-337.
Ostrin EJ, Li Y, Hoffman K, Liu J, Wang K, Zhang L, Mardon G, Chen R (2006) Genome-wide identification of direct targets of the Drosophila retinal determination
protein Eyeless. Genome Research 16:466-476.
Rhesus Macaque Genome Sequencing and Analysis Consortium (2007) Evolutionary and biomedical insights from the rhesus macaque genome. Science 316:222-234.
Srivatsan A, Han Y, Peng J, Tehranchi AK, Gibbs R, Wang JD, Chen R (2008) High-precision, whole-genome sequencing of laboratory strains facilitates genetic studies.
PLoS Genetics 4:e1000139.
Li Y, Wang H, Peng J, Gibbs RA, Lewis RA, Lupski JR, Mardon G, Chen R (2009) Mutation survey of known LCA genes and loci in the Saudi Arabian population.
Investigative Ophthalmology and Visual Science 50:1336-1343.
Wang H, den Hollander AI, Moayedi Y, Abulimiti A, Li Y, Collin RW, Hoyng CB, Lopez I, Bray M, Lewis RA, Lupski JR, Mardon G, Koenekoop RK, Chen R (2009) Mutations in
SPATA7 cause Leber congenital amaurosis and juvenile retinitis pigmentosa. American Journal of Human Genetics 84:380-387.
Daines B, Wang H, Li Y, Han Y, Gibbs R, Chen R (2009) High-throughput multiplex sequencing to discover copy number variants in Drosophila. Genetics 182:935-941.
Contact Information
- Rui Chen, Ph.D.
- Department of Molecular and Human Genetics
- Baylor College of Medicine
- One Baylor Plaza N1519
- Houston, Texas 77030, U.S.A.
- Tel: (713) 798-5194
- Fax: (713) 798-5741
- E-mail: ruichen@bcm.edu
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