Areas of Interest
Molecular Genetics of Glaucoma and Other Inherited
Conditions
Glaucoma is a group of inherited ocular condition that affects
over 70 million people worldwide. The clinical manifestation of
this condition extends from birth to 80 years of age. Over the
last decade, our laboratory has identified 8 of the 11 known
genetic loci for this condition and we have further cloned 3 of
the 4 published Glaucoma genes. In 1997, we identified the
CYP1B1 (Cytochrome P450 1B1) for Primary Congenital Glaucoma ,
and in 2002, we reported the first gene for “Low Intraocular
Pressure” form of Adult-Onset Primary Open Angle Glaucoma (POAG)
that we subsequently named Optineurin (For Optic Neuropathy
Inducing protein; OPTN). In 2005, we identified and reported a
new gene (named WD40 Repeat Protein 36 or WDR36) for “High
Intraocular Pressure” form of POAG. For CYP1B1, and in
collaboration with Dr. Schenkman’s laboratory, both in vivo and
in vitro functional analyses of this protein are currently in
progress. For OPTN, our laboratory has already cloned the
orthologue of this gene in both mouse and Rhesus monkey and
further studied the mRNA distribution and protein profiling of
Optineurin in various human, monkey and mouse ocular and
non-ocular tissues and cell lines. Similar studies for the WDR36
gene and its mRNA and protein products are currently in
progress.
Lab Rotation Projects
Students may participate in many different aspects of this
project including Glaucoma genetic mapping, gene identification,
mutation screening, mRNA characterization, protein-protein
interaction, functional profiling of protein domains,
transgenetic animal studies as well as other biochemical and
functional analysis of various glaucoma-causing genes. Similar
projects on other ocular and non-ocular inherited conditions are
also available.
Selected Publications
Rezaie T., Waitzman D., Seeman J., Kaufman P., Sarfarazi M.
(2005). Molecular Cloning and Expression Profiling of Optineurin
in Rhesus Monkey. Inves. Ophthal. & Vis. Sci. (In Press).
Rezaie T., Sarfarazi M. (2005). Molecular Cloning, Genomic
Structure and Protein Characterization of Mouse Optineurin.
Genomics 85(1): 131-138.
Monemi S., Spaeth G., Child A., DaSilva A., Ilitchev E.,
Liebmann J., Ritch R., Crick R.P., Sarfarazi M. (2005).
Identification of a Novel Adult-Onset Primary Open Angle
Glaucoma (POAG) Gene on 5q22.1. Human Molecular Genetics 14(6):
725-733.
Sarfarazi M., Stoilov I., Schenkman J.B. (2003). Genetics and
Biochemistry of Primary Congenital Glaucoma. Ophthalmology
Clinics of North America. 16(4): 543-554.
Sarfarazi M., Rezaie T. (2003). Optineurin in Primary Open
Angle Glaucoma. Ophthalmology Clinics of North America. 16(4):
529-541.
Rezaie T., Child A., Hitchings R., Brice G., Miller L., Coca-Prados
M., Héon E., Krupin T., Ritch R., Kreutzer D., Pitts Crick R.,
Sarfarazi M. (2002). Adult-Onset Primary Open Angle Glaucoma
Caused by Mutations in Optineurin. Science 295: 1077-1079. |
