Molecular Determinants of Pigmentation (MDoP)

“Molecular Determinants of Pigmentation (mDoP)” study aims to identify and characterize new genes and proteins essential for pigmentation development, melanosomes transportation, function and maintenance in humans. Pigmentation disorders (often referred as albinism) represents one of the major causes of childhood vision impairment in United States. Pigmentation disorders can manifest in syndromic, e.g., Hermansky-Pudlak syndrome (HPS), Griscelli syndrome (GS) and nonsyndromic, e.g., Oculocutaneous albinism (OCA), forms under a variety of inheritance models. At present, mutations in at least eighteen loci have been causally linked with albinism in humans.

However, the known genes do not account for all cases of these disorders, which strongly suggests that other genes have yet to be found, leaving a gap in the scientific community’s complete understanding of the makeup and mechanisms of pigmentation and pigmentary disorders. The long-term goal of this research is to fully understand the mechanisms of inherited pigmentation disorders and to develop therapeutic agents for the treatment and prevention of albinism. Our hypothesis is that if a mutated gene causes loss of pigmentation, then the function of that gene will be necessary for normal melanocytes, melanin synthesis and/or transportation. The rationale for the proposed mDoP study is that identifying all causative genes for albinism and understanding their normal function will be pivotal for the development of therapeutic agents to treat these impairments.

Thus, mDoP study is relevant to that part of NIH’s mission that pertains to developing fundamental knowledge that will potentially help to reduce the burdens of human disability. Guided by strong preliminary data, we will test our hypothesis through identification and evaluation of novel albinism genes. The proposed mDoP studies will employ contemporary human and zebrafish genetic, molecular, biochemical, psychophysical and cell biology techniques. The proposed work is innovative, as it stems from preliminary data of several new albinism loci/genes, which represent a significant increase from the known genes, as well as it uses combination of contemporary technologies to identify and functionally characterize novel albinism genes.

The mDoP study is significant because the completion of the proposed research will provide molecular insights to fully understanding and being able to provide targets for effectively treat pigmentation and related vision disorders in humans. Results of mDoP study hold great clinical relevance, with the potential to improve the molecular epidemiology of pigmentation-vision disorders, aid in genetic diagnosis, counseling and precision medicine.

Grant Number: 5R01AR077563-05
NIH Institute/Center: NIH
Principal Investigator: Zubair Ahmed