Algorithm for Age Related Macular Degeneration Prediction
Jeffrey A. Canter, Margaret A. Pericak-Vance, Kylee M. Spencer and
Jonathan Haines
Problem
A variety of genetic markers have been associated with AMD. These markers have a varying correlation with disease, i.e. some are strongly associated with AMD while other markers are more weakly associated with AMD. Thus individuals may have one or more of these markers will have a certain risk for developing this disease. In addition there are several environmental factors which have also been linked to AMD. Thus the prediction of an individuals risk factor quickly becomes complex when trying to weigh all of these factors.
Solution
This technology offers a solution to identifying individuals who maybe a risk for developing AMD. By statistically combining and weighing the relevant risk factors that an individual possesses or has been exposed to this test can predict approximately 90% of the population that will likely develop AMD.
Competitive Advantage
Currently an individual can be sampled for particular polymorphisms that have been linked to AMD however there is no way to weigh these for relevance. Moreover there is no way to combined these with environmental factors and accurately predict an individuals risk for developing AMD. This algorithm uses all the currently know markers, both genetic and environmental, as well as a novel mitochondrial gene recently implicated in AMD to accurately predict individual risk factor.
Applications
This technology will allow individuals to predict whether they will develop disease. Using all of the current markers and the new mitochondrial marker, approximately 90% of individuals who may develop the disease can be identified. In addition, identifying individuals who may develop AMD prior to the onset of disease will allow the development of new treatment strategies.
Patent Status
International Paten Application PCT/US2009/034882 was filed on February 23, 2009.
Licensing Opportunity
The University of Miami and Vanderbilt University seek partners for research, development and licensing of this technology.
About the Inventors
Margaret Pericak-Vance, Ph.D. is the Director of the Miami Institute for Humans Genomics. She is a founding fellow of the American College of Medical Genetics and a board-certified PhD medical geneticist. Dr. Pericak-Vance is a global leader in the genetics of common diseases. She excels at the integration of genomic and statistical technologies and their application to diseases of public health importance in general, and to neurologic diseases in particular. Her more than 360 peer-reviewed papers demonstrate outstanding productivity and establish important milestones in diseases that include tuberous sclerosis, the muscular dystrophies, amyotrophic lateral sclerosis (ALS), Parkinson disease (PD), multiple sclerosis (MS), autism, and Alzheimer disease (AD). She pioneered the use of novel disease gene mapping, leading to the identification of apolipoprotein E (APOE) as the major susceptibility gene for AD. Her recent accomplishments include the 2005 discovery of the CFH gene that determines an individuals risk for developing age-related macular degeneration, and the identification of a gene contributing to the expression of age-at-onset in AD and PD in 2003. Her greatest contribution has been her leadership in the application of methodological innovations capitalizing on the Human Genome Project that affect not only the neurological sciences but all of medicine. Dr. Pericak-Vance is internationally recognized by her peers as a leader in human genetics research. In 1997, Newsweek magazine named Dr. Pericak-Vance to the "Century Club: 100 People to Watch as We Move to the Next Millennium. Dr. Pericak-Vance holds numerous research grants through the National Institutes of Health that support her research into the genetics of complex disease
Jonathan Haines, Ph.D. is the Director of the Center for Human Genetics Research at Vanderbilt University, the T.H. Morgan Professor of Human Genetics, Professor of Molecular Physiology & Biophysics, the Chief of the Division of Human Genomics, and an investigator in the John F. Kennedy Center for Research on Human Development. Dr. Haines research focuses on gene discovery and gene localization in complex human diseases. Dr. Haines has made major genetic discoveries in Alzheimer disease, multiple sclerosis, and macular degeneration and numerous Mendelian genetic disorders including Batten disease, tuberous sclerosis, and neuromuscular disorders. Most recently helped direct the effort that elucidated the role IL7R in multiple sclerosis, the first gene identified for MS in over 30 years. In collaboration with Dr. Pericak-Vance, they have redefined the paradigms for gene discovery in complex diseases and translating this information into practical and clinical applications. Dr. Haines has published over 350 peer reviewed papers and is internationally recognized for his work in these and other debilitating human diseases.
Selected References
Corder EH, Saunders AM, Strittmatter WJ, Schmechel DE, Gaskell PC, Small GW, Roses AD, Haines JL, and PERICAK-VANCE MA. Gene dose of Apolipoprotein E Type 4 allele and the risk of Alzheimer disease in late onset families. Science 261:921-923, 1993.
Li YJ, Scott WK, Hedges DJ, Zhang F, Gaskell PC, Nance MA, Watts RL, Hubble JP, Koller WC, Pahwa R, Stern MB, Hiner BC, Jankovic J, Allen FA, Jr., Goetz CG, Mastaglia F, Stajich JM, Gibson RA, Middleton LT, Saunders AM, Scott BL, Small GW, Nicodemus KK, Reed AD, Schmechel DE, Welsh-Bohmer KA, Conneally PM, Roses AD, Gilbert JR Vance JM, Haines JL, PERICAK-VANCE MA. Age-at-onset in two common neurodegenerative diseases is genetically controlled. Am J Hum Genet 70:985-993, 2002
Haines JL, Hauser MA, Schmidt S, Scott WK, Olson LM, Gallins P, Spencer KL, Kwan SY, Noureddine M, Gilbert JR, Schnetz-Boutaud N, Agarwal A, Postel EA, PERICAK-VANCE MA. Complement Factor H variant increases the risk of age-related macular degeneration. Science 5:308:419-21, 2005.
Ma DQ, Whitehead PL, Menold MM, Martin ER, Ashley-Koch AE, Mei H, Ritchie MD, DeLong MR, Abramson RK, Wright HH, Cuccaro ML, Hussman JP, Gilbert JR, PERICAK-VANCE MA. Identification of significant association and gene-gene interaction on GABA receptor subunit genes in autism. Am J Hum Genet 2005 Sep;77(3):377-88.
Zuchner S, Wang G, Tran-Viet KN, Nance MA, Gaskell PC, Vance JM, Ashley-Koch AE, PERICAK-VANCE MA. Mutations in the Novel Mitochondrial Protein REEP1 Cause Hereditary Spastic Paraplegia Type 31. Am J Hum Genet. 2006 Aug;79(2):365-9.
Haines JL, PERICAK-VANCE MA. Rapid dissection of the genetic risk of age-related macular degeneration: achieving the promise of the genomic era. JAMA. 2007 Jan 24;297(4):401-2.
Ma DQ, Cuccaro ML, Jaworski JM, Haynes CS, Stephan DA, Parod J, Abramson RK, Wright HH, Gilbert JR, Haines JL, PERICAK-VANCE MA. Dissecting the locus heterogeneity of autism: significant linkage to chromosome 12q14. Mol Psychiatry. 2007 Apr;12(4):376-84
Gregory SG, Schmidt S, Seth P, Oksenberg JR, Hart J, Prokop A, Caillier SJ, Ban M, Goris A, Barcellos LF, Lincoln R, McCauley JL, Sawcer SJ, Compston DA, Dubois B, Hauser SL, Garcia-Blanco MA, PERICAK-VANCE MA, Haines JL. Interleukin 7 receptor alpha chain (IL7R) shows allelic and functional association with multiple sclerosis. Nat Genet. 2007 Sep;39(9):1083-91.
The International Multiple Sclerosis Genetics Consortium. Risk Alleles for Multiple Sclerosis Identified by a Genomewide Study. N Engl J Med. 2007 Aug 30;357(9):851-62.
