We have determined the structure, nucleotide sequence, and polymorphisms of the human P gene. Mutations of the P gene result in type II oculocutaneous albinism (OCA2) in humans and pink-eyed dilution (p) in mice. We find that the human P gene is quite large, consisting of 25 exons spanning 250 to 600 kb in chromosome segment 15q11-q13. The P polypeptide appears to define a novel family of small molecule transporters and may be involved in transport of tyrosine, the precursor to melanin synthesis, within the melanocyte. These results provide the basis for analyses of patients with OCA2 and may point toward eventual pharmacologic treatment of this and related disorders of pigmentation.
Bibliographical noteFunding Information:
We thank D. Ledbetter for YACs 93C9 and 149A9, Dr. O. Smithies for the human genomic recombinant hCharon 28 library, and Dr. D. Bennett for melan-a cells. This work was supported by Postdoctoral Grant 997 (to S.-T.L.) and Clinical Research Grant 6-408 (to R.A.S.) from the March of Dimes Birth Defects Foundation and National Institutes of Health Grants AR39892 (to R.A.S.) and AR39750 (SDRC-P and FS7, to R.D.N.). R.D.N. is a Pew Scholar in the Biomedical Sciences. This is Paper 3414 from the Laboratory of Genetics, University of Wisconsin.
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