African, Native American, and European mitochondrial DNAs in Cubans from Pinar del Rio Province and implications for the recent epidemic neuropathy in Cuba. Cuba Neuropathy Field Investigation Team.

Genetic predisposition, particularly specific mitochondrial DNA (mtDNA) backgrounds, has been proposed as a contributing factor in the expression of an epidemic of bilateral optic neuropathy that has affected residents of Cuba since 1991. To substantiate or refute the possibility that specific subsets of mtDNAs could participate in disease expression, we took advantage of the heterogeneous ethnic origin of the Cuban population and the recent identification of a number of mtDNA polymorphisms that appear to be specific for Africans, Native Americans, and Europeans. The screening of both carefully selected people with epidemic neuropathy and control subjects from the Pinar del Rio Province for these polymorphisms revealed that African, Native American, and European mtDNA haplotypes were equally represented among case and control subjects, and suggested that approximately 50% of Cuban mtDNAs originated from Europeans, 46% from Africans, and 4% from Native Americans. These findings demonstrate that mutations arising in specific mtDNAs are unlikely to play a role in the epidemic neuropathy and indicate that analysis of mtDNA haplotypes can be a valuable tool for assessing the relative maternal contribution of Africans, Native Americans, and Europeans in a mixed population.

Epidemic neuropathy in Cuba not associated with mitochondrial DNA mutations found in Leber's hereditary optic neuropathy patients. Cuba Neuropathy Field Investigation Team.

An epidemic neuropathy in Cuba has caused bilateral optic neuropathies in more than 26,000 people during the past three years. Various pathogenetic factors have been proposed, including toxins, nutritional deficiencies, and an underlying genetic predisposition involving mitochondrial DNA. As part of a case-control collaborative investigation, 135 Cuban blood samples were analyzed for the most common mitochondrial DNA mutations associated with Leber's hereditary optic neuropathy. None of the participants tested were found to have the mitochondrial DNA mutations at nucleotide positions 11778, 3460, 14484, 7444, or 9804. Of 57 definite case subjects and 69 normal control subjects, three case and three control subjects had the mutation at nucleotide position 9438, three different case and three different control subjects had the mutation at position 13708, and one case and one control subject had the mutation at position 15257 in association with the mutation at position 13708. The most common mitochondrial DNA mutations associated with Leber's hereditary optic neuropathy do not appear to be contributing factors in the epidemic neuropathy in Cuba. We also identified a large Cuban family with maternally related members who experienced visual loss consistent with the diagnosis of Leber's hereditary optic neuropathy. Maternal family members harbored the highly pathogenetic mutation at nucleotide position 11778.

mtDNA and Y-chromosome polymorphisms in four Native American populations from southern Mexico.

mtDNA sequence variation was examined in 60 Native Americans (Mixtecs from the Alta, Mixtecs from the Baja, Valley Zapotecs, and Highland Mixe) from southern Mexico by PCR amplification and high-resolution restriction endonuclease analysis. Four groups of mtDNA haplotypes (haplogroups A, B, C, and D) characterize Amerind populations, but only three (haplogroups A, B, and C) were observed in these Mexican populations. The comparison of their mtDNA variation with that observed in other populations from Mexico and Central America permits a clear distinction among the different Middle American tribes and raises questions about some of their linguistic affiliations. The males of these population samples were also analyzed for Y-chromosome RFLPs with the probes 49a, 49f, and 12f2. This analysis suggests that certain Y-chromosome haplotypes were brought from Asia during the colonization of the Americas, and a differential gene flow was introduced into Native American populations from European males and females.