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Genetics of retinal development
Our lab is broadly interested in studying and modeling the genetic networks underlying human ocular diseases and controlling vision
development. Taking a systems biology approach, both experimental and computational approaches are used in parallel to identify and model gene functions
during retinal development in both human and model organisms.
Currently, our lab is focusing on identify novel genes involved in Leber congenital amaurosis (LCA), the most common hereditary cause of visual
impairment in infants and children. LCA is a set of inherited, early onset retinopathies that affect about 1 in 15,000 in the general U.S. population
and account for more than five percent of all retinal dystrophies. Unfortunately, to date, no medical or surgical intervention has been shown to alter
the natural course of LCA, nor has any pharmacologic therapy shown an effect on modulating or moderating its progression. Currently, mutations in at
least thirteen genes have been associated with recessive LCA, which account for about 63 percent of all cases. To clone additional LCA disease genes,
in collaboration with Dr. James Lupski and Dr. Richard Lewis, we have collected DNA samples from 38 consanguineous Saudi Arabian and 80 North American
families with recessive LCA. Currently, direct sequencing as well as whole genome linkage scan using the 300K SNP array platform is in progress for
these families. So far, two novel disease loci have been identified and mutation identification using a candidate gene approach of these two loci is
ongoing.
Model organisms including mouse and Drosophila melanogaster are useful tools to understand molecular mechanism of diseases and also
identify genetic networks that control retinal development. In Drosophila, a major effort in our laboratory is to understand the molecular
mechanism of the early retinal cell fate determination process. Retinal cell fate determination is the early phase during fly eye development and only
a handful genes (RD genes) are known to control this process. To better understand the underlying genetic network, microarray experiments were conducted
to identify novel genes that function among or immediately downstream of the RD gene group. A combinatorial approach of comparative genomics, computational
biology and genetic epistasis analysis is used to further identify potential direct downstream targets of the RD genes. In collaboration with
Dr. Graeme Mardon, systematic modeling as well as direct experimental studies of the function of these genes is currently underway.
Finally, developing novel applications that take advantage of the new sequencing technologies, such as Solexa and 454, is another focus of our
lab. The unparalleled high throughput provided by these next generation sequencing tools provide unique opportunities for better understanding many
fundamental questions in molecular biology and genetics. Currently, we are focusing on applying these technologies to understanding the molecular
mechanism of gene regulation networks during retinal development.
Selected Publications
Chen R, Amoui M, Zhang Z, Mardon G (1997) Dachshund and Eyes Absent proteins form a complex and function
synergistically to induce ectopic eye development in Drosophila. Cell 91: 893-903.
Chen R, Halder G, Zhang Z, Mardon G (1999) Signaling by the TGF-β homolog decapentaplegic functions reiteratively
within the network of genes controlling retinal cell fate determination in Drosophila. Development 126:935-943.
Chen R, Bouck JB, Weinstock GM, Gibbs RA (2001) Comparing vertebrate whole-genome shotgun reads to the human genome.
Genome Research 11:1807-1816.
Chen R, Sodergren E, Weinstock GM, Gibbs RA (2004) Dynamic building of a BAC clone tiling path for the rat genome
sequencing project. Genome Research 14:679-684.
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. *co-author
Rat Genome Sequencing Project Consortium (2004) Genome sequence of the Brown Norway rat yields insights into mammalian evolution.
Nature 428:493-521.
Chen R, Mardon G (2005) Keeping an eye on the fly genome. Developmental Biology 282:285-293.
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.
Li Y, Wang H, Peng J, Gibbs RA, Lewis RA, Lupski JR, Mardon G, Chen R (2008) Mutation survey of known LCA Genes and loci in the
Saudi Arabian population. Investigative Ophthalmology and Visual Science, Oct 20 online, PMID: 18936139.
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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