Since the entire sequence of the human genome has become available, our goal is to use this information to assess the whole range of genetic variation in the human population. This will allow us to answer a myriad of questions, including the most immediate: Which genetic variants (or their combinations) predispose humans to different inherited disorders?

Our laboratory focuses on discovering genetic defects underlying Mendelian and complex disorders with special emphasis on eye diseases. The first step in discovering the underlying mechanisms of a disorder is the cloning and characterization of the relevant gene(s) and determining the mutation spectrum, causative for each individual phenotype. This goal is achieved in our lab by the systematic screening of candidate genes on large collections of patient DNA with semi-automated, high-throughput mutation detection and genotyping technologies. These include denaturing high performance liquid chromatography (DHPLC) and gene chip arrays. Among candidate genes under analysis, we are specifically interested in those who belong to the ATP-binding cassette (ABC) transporter superfamily. Members of this family are ubiquitous membrane proteins that carry out vital transport functions in all cells and cellular organelles. We have succeeded in defining several ABC genes as involved in various human inherited diseases (ABCR, ABC7, ABCG5) and in important cellular functions such as multi-drug resistance during cancer chemotherapy (ABCP).

Major research objectives of the laboratory are: (1) Exhaustive characterization of genes from human ABC transporter superfamily in human inherited diseases; (2) Association analysis of genetic variation in candidate genes for Mendelian and complex disorders; (3) Development of microarray-based screening technologies and new approaches for ABC gene therapy.

Selected Publications:

• Allikmets, R., Singh, N., Sun, H., Shroyer, N.F., Hutchinson, A., Chidambaram, A., Gerrard, B., Baird, L., Stauffer, D., Peiffer, A., Rattner, A., Smallwood, P., Li, Y., Anderson, K.L., Lewis, R.A., Nathans, J., Leppert, M., Dean, M., and Lupski, J.R.: A photoreceptor cell-specific ATP-binding transporter gene (ABCR) is mutated in recessive Stargardt macular dystrophy. Nature Genetics 15: 236-246, 1997.
• Allikmets, R., Shroyer, N.F., Singh, N., Seddon, J.M., Lewis, R.A., Bernstein, P., Peiffer A., Zabriskie, N., Li, Y., Hutchinson, A., Dean, M., Lupski, J.R., and Leppert, M.: Mutation of the Stargardt disease gene (ABCR) in age-related macular degeneration. Science 277: 1805-1807, 1997.
• Allikmets, R., Schriml, L., Hutchinson, A., Romano-Spica, V., and Dean, M.: A human placenta-specific ATP-binding cassette gene (ABCP) on chromosome 4q22 that is involved in multidrug resistance. Cancer Res. 58: 5337-5339, 1998.
• Allikmets, R., Raskind, W.H., Hutchinson, A., Schueck, N.D., Dean, M., and Koeller, D.M.: Mutation of a putative mitochondrial iron transporter gene (ABC7) in X-linked sideroblastic anemia and ataxia (XLSA/A). Hum. Mol. Genet. 8: 743-749, 1999.
• Allikmets, R. and the International ABCR Screening Consortium: Further evidence of an association of ABCR alleles with age-related macular degeneration. Am. J. Hum. Genet. 67: 487-491, 2000.
• Allikmets, R. Simple and complex ABCR: genetic predisposition to retinal disease. Am. J. Hum. Genet. 67:793-799, 2000.
• Lee, M.-H., Lu, K., Hazard, S., Yu, H., Shulenin, S., Hidaka, H., Kojima, H., Allikmets, R., Sakuma, N., Pegoraro, R., Srivastava, A.K., Salen, G., Dean, M., and Patel, S.B. Identification of a gene, ABCG5, important in the regulation of dietary cholesterol absorption. Nature Genet. 27: 79-83, 2001.
• Zhang, K., Kniazeva, M., Han, M., Li, W., Yu, Z., Yang, Z., Li, Y., Metzker, M.L., Allikmets, R., Zack, D.J., Kakuk, L.E., Lagali, P.S., Wong, P.S., MacDonald, I.M., Sieving, P.A., Figueroa, D., Austin, C.P., Gould, R.J., Ayyagari, R., and Petrukhin, K. A 5-bp deletion in ELOVL4 is associated with two related forms of autosomal dominant macular dystrophy. Nature Genet. 27: 89-93, 2001.
• Dean, M., Rzhetsky, A., and Allikmets, R. The Human ATP-Binding Cassette (ABC) Transporter Superfamily. Genome Res. 11:1156-1166, 2001.