title: A 122.5-kilobase deletion of the P gene underlies the high prevalence of oculocutaneous albinism type 2 in the Navajo population.
abstract: Oculocutaneous albinism (OCA) is a genetically heterogeneous disorder. There are four known types of OCA: OCA1-OCA4. The clinical manifestations of all types of OCA include skin and hair hypopigmentation and visual impairment. Although there are a few documented observations of high frequency of albinism among Native Americans, including the Hopi, Zuni, Kuna, Jemez, Laguna, San Juan, and Navajo, no causative molecular defect has been previously reported. In the present study, we show that albinism in one Native American population, the Navajo, is caused by a LINE-mediated 122.5-kilobase deletion of the P gene, thus demonstrating that albinism in this population is OCA2. This deletion appears to be Navajo specific, because this allele was not detected in 34 other individuals with albinism who listed other Native American origins, nor has it been reported in any other ethnic group. The molecular characterization of this deletion allele allowed us to design a three-primer polymerase chain reaction system to estimate the carrier frequency in the Navajo population by screening 134 unrelated normally pigmented Navajos. The carrier frequency was found to be approximately 4.5%. The estimated prevalence of OCA2 in Navajos is between approximately 1 per 1,500 and 1 per 2,000. We further estimate that this mutation originated 400-1,000 years ago from a single founder.
authors.affiliation: Department of Pediatrics, College of Medicine, University of Arizona, Tucson, AZ 85724, USA.
authors.forename: Zanhua
authors.initials: Z
authors.lastname: Yi
authors.forename: Nanibaa'
authors.initials: N
authors.lastname: Garrison
authors.forename: Orit
authors.initials: O
authors.lastname: Cohen-Barak
authors.forename: Tatiana M
authors.initials: TM
authors.lastname: Karafet
authors.forename: Richard A
authors.initials: RA
authors.lastname: King
authors.forename: Robert P
authors.initials: RP
authors.lastname: Erickson
authors.forename: Michael F
authors.initials: MF
authors.lastname: Hammer
authors.forename: Murray H
authors.initials: MH
authors.lastname: Brilliant
mesh_terms: D016115:Albinism, Oculocutaneous / Q000453:epidemiology / Q000235:genetics*; D000483:Alleles; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics*; D002872:Chromosome Deletion; D018703:Founder Effect; D006239:Haplotypes / Q000235:genetics; D006579:Heterozygote; D006801:Humans; D007198:Indians, North American / Q000235:genetics*; D015810:Linkage Disequilibrium; D020084:Long Interspersed Nucleotide Elements / Q000235:genetics; D008565:Membrane Proteins / Q000235:genetics*; D026901:Membrane Transport Proteins; D015995:Prevalence; D013997:Time Factors
chemical_list: D002352:Carrier Proteins; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; C489600:OCA2 protein, human