Estimation of carrier frequency of a 2.7 kb deletion allele of the P gene associated with OCA2 in African-Americans
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ABSTRACT: In this study, we report on a Cameroonian family from the Ewondo ethnic group, presenting with three oculocutaneous albinism type 2 (OCA2) patients homozygous for the 2.7-kb deletion of the P gene. In one of these patients OCA2 was associated with sickle cell anaemia and in two with the sickle cell trait. We took this opportunity to determine single nucleotide polymorphism (SNP) haplotypes within the P gene in this family in comparison with a group of 53 OCA2 patients homozygous for the same mutation and with a matched unrelated full-coloured control group of 49 subjects, originating from seven different ethnic groups of Southern Cameroon including Ewondo. A combination of five exonic and intronic SNPs in the OCA2 gene was genotyped by sequencing PCR products. We found 3 different haplotypes (TAGCT, TAGTT and TAGCC with frequencies of 0.66, 0.28 and 0.06, respectively) associated with the mutation in the 53 OCA2 patients, while 11 different haplotypes were observed in the control group. These observations suggest that the mutation appeared on the relatively frequent haplotype TAGCT, and that the two other haplotypes are derived from two independent recombination events. These haplotypic data, associated with a value of 1/15,000 for the prevalence of the 2.7-kb mutation, a present effective population size of 10,000,000 for Cameroon and a recombination rate of 0.0031, allowed us to estimate that this mutation originated 4,100-5,645 years ago.Journal of Human Genetics 02/2007; 52(9):771-80. DOI:10.1007/s10038-007-0181-y · 2.53 Impact Factor
Chapter: Oculocutaneous Albinism Type 1[Show abstract] [Hide abstract]
ABSTRACT: Oculocutaneous albinism type 1 (OCA1) is characterized by reduced synthesis of melanin in the skin, hair, and eyes, associated with ocular findings of nystagmus, reduced iris pigment with iris translucency, reduced retinal pigment, foveal hypoplasia with significantly reduced visual acuity usually in the range of 20/100 to 20/400, and misrouting of the optic nerves resulting in alternating strabismus and reduced stereoscopic vision. Individuals with OCA1A have white hair, white skin that does not tan, and fully translucent irises that do not darken with age. At birth, individuals with OCA1B have white or very light yellow hair that darkens with age, white skin that over time develops some generalized pigment and may tan with sun exposure, and blue irises that change to green/hazel or brown/tan with age. Visual acuity may be 20/60 or better in some individuals. The diagnosis of OCA1 is established by clinical findings of hypopigmentation of the skin and hair and characteristic eye findings. Molecular genetic testing of the tyrosinase gene, TYR, is clinically available; it is rarely used in diagnosis and is most commonly used in genetic counseling for carrier detection. OCA1 is inherited in an autosomal recessive manner. At conception, the sibs of an affected individual have a 25% chance of being affected, a 50% chance of being asymptomatic carriers, and a 25% chance of being unaffected and not carriers. Prenatal diagnosis of OCA1 by fetal skin biopsy or molecular genetic testing is possible in pregnancies at 25% risk.GeneReviews™, Edited by Roberta A Pagon, Thomas D Bird, Cynthia R Dolan, Karen Stephens, Margaret P Adam; University of Washington, Seattle.
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ABSTRACT: Oculocutaneous albinism (OCA2) is the most common autosomal recessive disorder in the South African Negroid population, occurring with a prevalence of 1/3900 individuals. The OCA2 locus, P, has been mapped to chromosome 15q11-q13 and a 2.7-kb interstitial deletion has been found to be the common mutation in Africa. This study reports the detection of the deletion allele in OCA2-affected individuals from the southern African, Zambian and Central African Republic (CAR) Negroid populations (0.77, 131/170 OCA2 chromosomes; 0.79, 11/14; 0.33, 4/12, respectively). Normally pigmented individuals from different African countries were also tested. The deletion mutation was found at a frequency of 0.013 (10/780) in the normally pigmented southern African Negroid population and at a lower frequency in individuals from central Africa (0.002; 2/834), including individuals from Zambia, Cameroon, Zaire and the CAR. The study confirms the African origin of this deletion allele. Haplotype analysis suggests that the deletion mutation probably occurred only once and that it arose before the divergence of these African populations, which is estimated to be about 2000-3000 years ago. The unusually high frequency of OCA2 mutations, in particular the 2.7-kb deletion, suggests some selective agent or genetic drift.Human Genetics 05/1997; 99(4):523-7. DOI:10.1007/s004390050400 · 4.52 Impact Factor