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Comprehensive analysis of the molecular bases of OCA in Indians
Genome Biology volume 11, Article number: P32 (2010)
OCA is a group of autosomal recessive disorders characterized by hypopigmentation and abnormalities related to ocular development. Mutations in genes regulating melanin-biosynthesis cause four classical types of OCA (OCA 1-4). The clinical spectrum of OCA often depends on the pigmentation threshold of a patient, highlighting the importance of ethnic- specific SNPs. We aimed to understand the molecular bases of OCA in India, where it is one of the four major causes of childhood blindness.
Materials and methods
Blood samples were collected from OCA patients and family members, mostly from eastern and southern India. Seven pigmentation related genes were screened for variations. Relevant non-synonymous changes in tyrosinase (TYR) were functionally validated. Eighteen SNPs from three OCA genes were genotyped in 552 normal individuals covering various ethnic groups of India.
Our data suggest that defects in TYR cause albinism in 58% (36/62) of the cases  (and unpublished data; see Figure 1). Functional assays with missense mutations proved that none of mutants are enzymatically active and are retained in the endoplasmic reticulum . Screening of the remaining cases (43%) revealed OCA2 to be the second common locus followed by SLC45A2  (Figure 1). Evaluation of SNPs in TYR, OCA2 and SLC45A2 in normal population suggested definitive bias for some of the SNPs towards specific populations.
Our investigation suggests that ~58% of OCA in India belong to OCA1 category. ER retention is the major cause of lack of TYR activity in OCA1 patients. Information on allelic distribution of SNPs is important for cosegregation analysis of candidate genes in affected families.
Chaki M, Sengupta M, Mondal M, Bhattacharyya A, Mallick S, Bhadra R, Consortium Indian Genome Variation, Ray K: Molecular and functional studies on Tyrosinase among Indian Oculocutaneous Albinism type 1 (OCA1) patients. J Invest Dermatol. 2010.
Sengupta M, Mondal M, Jaiswal P, Sinha S, Chaki M, Samanta S, Ray K: Comprehensive Analysis of the Molecular Basis of OCA in Indian Patients Lacking Mutation in Tyrosinase Gene. Br J Dermatol. 2010, -Epub ahead of print.
SNP analysis in Indian population groups was done as part of a larger study to capture genomic variation among Indians by the Indian Genome Variation Consortium.
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Ray, K., Sengupta, M., Chaki, M. et al. Comprehensive analysis of the molecular bases of OCA in Indians. Genome Biol 11 (Suppl 1), P32 (2010). https://doi.org/10.1186/gb-2010-11-s1-p32
- Missense Mutation
- Functional Assay
- Classical Type
- Clinical Spectrum