Abstract

The aims of this project are to investigate the clinical, ophthalmologic, hematologic, epidemiologic, biochemical, and molecular features of genetic defects of human pigment formation, particularly oculocutaneous albinism. These studies will provide information which we hope will lead to methods of accurate diagnosis, therapy, and family counseling, so that these genetic diseases can be prevented, treated, or ameliorated. Clinical and epidemiologic studies of albinism and the Hermansky-Pudlak syndrome will be carried out in Puerto Rico. The natural history of the disease will be elucidated, including the pigmentary and ocular changes, and the morbidity and mortality which results from the storage of ceroid-like material in the kidneys, lungs, heart, and gastrointestinal tract. The defects in the regulatory mechanisms and membranes in platelets and blood cells in Hermansky-Pudlak syndrome, Chediak-Higashi syndrome, and other inherited pigment disorders will be investigated. The relationship between the storage pool deficiency and the hypopigmentation will be analyzed. Biochemical and molecular studies will provide methods for accurate diagnosis and insight into mechanisms of albinism. Dopachrome oxidoreductase will be purified and characterized, and the role of this enzyme in the regulation of pigment will be analyzed. The tyrosinase gene will be isolated and normal and mutant genes will be characterized. Visual function studies in albinism will be carried out and methods of visual and educational intervention analyzed. The role of thioredoxin reductase in oxygen radical defense in vitiligo will be determined.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Program Projects (P01)
Project #
2P01GM022167-12
Application #
3096019
Study Section
(SSS)
Project Start
1986-12-01
Project End
1991-11-30
Budget Start
1986-12-01
Budget End
1987-11-30
Support Year
12
Fiscal Year
1987
Total Cost
Indirect Cost

  Institution

Name
University of Minnesota Twin Cities
Department
Type
Schools of Medicine
DUNS #
168559177
City
Minneapolis
State
MN
Country
United States
Zip Code
55455

  Publications

Oetting, W S; King, R A (1999) Molecular basis of albinism: mutations and polymorphisms of pigmentation genes associated with albinism. Hum Mutat 13:99-115
Orlow, S J; Brilliant, M H (1999) The pink-eyed dilution locus controls the biogenesis of melanosomes and levels of melanosomal proteins in the eye. Exp Eye Res 68:147-54
Oetting, W S; Armstrong, C M; Ronan, S M et al. (1998) Multiplexed short tandem repeat polymorphisms of the Weber 8A set of markers using tailed primers and infrared fluorescence detection. Electrophoresis 19:3079-83
Sweet, H O; Brilliant, M H; Cook, S A et al. (1998) A new allelic series for the underwhite gene on mouse chromosome 15. J Hered 89:546-51
Wildenberg, S C; Fryer, J P; Gardner, J M et al. (1998) Identification of a novel transcript produced by the gene responsible for the Hermansky-Pudlak syndrome in Puerto Rico. J Invest Dermatol 110:777-81
Oetting, W S; Gardner, J M; Fryer, J P et al. (1998) Mutations of the human P gene associated with Type II oculocutaneous albinism (OCA2). Mutations in brief no. 205. Online. Hum Mutat 12:434
Oetting, W S; Fryer, J P; King, R A (1998) Mutations of the human tyrosinase gene associated with tyrosinase related oculocutaneous albinism (OCA1). Mutations in brief no. 204. Online. Hum Mutat 12:433-4
Lehman, A L; Nakatsu, Y; Ching, A et al. (1998) A very large protein with diverse functional motifs is deficient in rjs (runty, jerky, sterile) mice. Proc Natl Acad Sci U S A 95:9436-41
Gardner, J M; Wildenberg, S C; Keiper, N M et al. (1997) The mouse pale ear (ep) mutation is the homologue of human Hermansky-Pudlak syndrome. Proc Natl Acad Sci U S A 94:9238-43
Puri, N; Durbam-Pierre, D; Aquaron, R et al. (1997) Type 2 oculocutaneous albinism (OCA2) in Zimbabwe and Cameroon: distribution of the 2.7-kb deletion allele of the P gene. Hum Genet 100:651-6

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