1,721,100 research outputs found
American Indian prehistory as written in the mitochondrial DNA: a review
No full textNative Americans have been divided into three linguistic groups: the reasonably well-defined Eskaleut and Nadene of northern North America and the highly heterogeneous Amerind of North, Central, and South America. The heterogeneity of the Amerinds has been proposed to be the result of either multiple independent migrations or a single ancient migration with extensive in situ radiation. To investigate the origin and interrelationship of the American Indians, we examined the mitochondrial DNA (mtDNA) variation in 87 Amerinds (Pima, Maya, and Ticuna of North, Central, and South America, respectively), 80 Nadene (Dogrib and Tlingit of northwest North America and Navajo of the southwest North America), and 153 Asians from 7 diverse populations. American Indian mtDNAs were found to be directly descended from five founding Asian mtDNAs and to cluster into four lineages, each characterized by a different rare Asian mtDNA marker. Lineage A is defined by a HaeIII site gain at np 663, lineage B by a 9-bp deletion between the COII and tRNA(Lys) genes, lineage C by a HincII site loss at np 13259, and lineage D by an AluI site loss at np 5176. The North, Central, and South America Amerinds were found to harbor all four lineages, demonstrating that the Amerinds originated from a common ancestral genetic stock. The genetic variation of three of the four Amerind lineages (A, C, and D) was similar with a mean value of 0.084%, whereas the sequence variation in the fourth lineage (B) was much lower, raising the possibility of an independent arrival. By contrast, the Nadene mtDNAs were predominantly from lineage A, with 27% of them having a Nadene-specific RsaI site loss at np 16329. The accumulated Nadene variation was only 0.021%. These results demonstrate that the Amerind mtDNAs arose from one or maybe two Asian migrations that were distinct from the migration of the Nadene and that the Amerind populations are about four times older than the Nadene
Mitochondrial DNA variation in human populations and implications for detection of mitochondrial DNA mutations of pathological significance
No full textHaplotype and phylogenetic analyses of "normal" mitochondrial DNAs (mtDNAs) have allowed a clarification of several controversial issues concerning the origin of humans, the time and colonization pattern of the various regions of the world, and the genetic relationships of modern human populations. More recently, the same type of analyses has also been applied to mtDNA disease studies. A review of these studies indicates that exhaustive screenings of "normal" mtDNA variation in all human populations associated with haplotype and phylogenetic analyses are essential if we are to understand the etiology of mitochondrial pathologies
Phylogenetic analysis of Leber's hereditary optic neuropathy mitochondrial DNA’s indicates multiple independent occurrences of the common mutations
No full textThe mitochondrial DNAs (mtDNA) from 17 Caucasian 11778-positive and 30 Caucasian 11778-negative Leber's hereditary optic neuropathy (LHON) patients were PCR-amplified and subjected to high resolution restriction endonuclease analysis. Concurrently, all patient mtDNAs were screened for the common primary LHON mtDNA mutations at nucleotide pairs (nps) 3460, 11778, and 14484, the ambiguous intermediate-risk LHON mtDNA mutations at nps 5244 and 15257, and the secondary LHON mtDNA mutations at nps 3394, 4216, 4917, 7444, 13708, and 15812. Phylogenetic analysis was performed using mtDNA haplotype data from the 47 LHON patients and 175 non-LHON Caucasian controls. The superimposition of the LHON mutation screening results upon the Caucasian mtDNA phylogeny revealed (1) 35 different LHON haplotypes, (2) that all three common primary mutations have occurred multiple times in Caucasians, (3) that while recurrent mutation is common for the primary mutations, secondary mutations tend to be lineage-specific, (4) that the np 15257 mutation was confined to a single mtDNA lineage but may be etiologically important in some LHON cases since it was found in a LHON pedigree which lacked a common primary mutation; complete sequence analysis of the proband mtDNA revealed only a single other candidate missense mutation (at np 10663 of the ND4L gene) of uncertain pathological significance; and (5) that the np 14484 mutation may be less pathogenic than either the np 3460 or np 11778 mutations, as this mutation most commonly occurred on a single mtDNA lineage and almost always in association with secondary LHON mutations. A phylogenetic approach to this genetically heterogeneous disease has thus provided key genetic data bearing on the relative pathogenicity of the LHON-associated mtDNA mutations
Mitochondrial oxidative phosphorylation defects in Parkinson Disease
No full textParkinson's disease has been associated with defects in oxidative phosphorylation (Oxphos). We analyzed mitochondria isolated from muscle biopsies of 6 patients with Parkinson's disease for deficiencies in Oxphos enzymes and for mutations in the mitochondrial DNA. Oxphos enzyme assays were compared to the 5 to 95% confidence intervals from 16 control subjects. Four patients had complex I defects, whereas 1 patient had a complex IV defect. A genetic basis for Parkinson's disease was suggested by the presence of affected relatives of 2 patients with Parkinson's disease. Known pathological mitochondrial DNA mutations (insertion-deletions or point mutations) were not found. We conclude that Parkinson's disease is a systemic disorder of Oxphos, probably of a complex genetic etiology. Premature cell death in the nigrostriatal dopamine pathway could be due to energetic impairment and accentuated free radical generation caused by an Oxphos defect
Neoplastic transformation is associated with coordinate induction of nuclear and cytoplasmic oxidative phosphorylation genes
No full textNeoplastic transformation was found to have a marked effect on the expression of nuclear DNA (nDNA)- and mitochondrial DNA (mtDNA)-encoded oxidative phosphorylation (OXPHOS) genes. Examining three pairs of human diploid fibroblasts and their SV 40-transformed counterparts revealed that mRNAs for the nuclear-encoded ATP synthase beta and the adenine nucleotide translocator (ANT) isoform 1 and 2 genes were markedly induced, whereas the mRNA for the ANT isoform 3 gene remained unchanged. The mRNA levels for the mtDNA-encoded 12 S rRNA, ND2, ATPase6+8, COIII, ND5+6, and Cytb genes were also increased, whereas the mtDNA number declined. Similar analysis of a cervical carcinoma (HeLa), fibrosarcoma (HT1080), and an Epstein-Barr virus (EBV)-transformed lymphoblastoid line (EBV-L) revealed that all three ANT isoforms were also expressed in these cells. Hence, changes in the expression of OXPHOS genes may be a common feature of transformed cells
Potential of mitochondrial DNA for providing insights into the origin of the Etruscans
No full textThis report of a small pilot survey of mitochondrial DNA (mtDNA) variation in ten individuals whose maternal lineages were from Tuscany emphasizes the problems and potential contributions of mtDNA studies regarding the origin of the Etruscans. An average of 20% of the mtDNA was studied for variations in patterns and nine different patterns were observed. These patterns are common in Europe and encompass most of European mtDNA variation. Consequently, contemporary Tuscan populations do not appear to harbor peculiar mtDNAs which could be attributed to the original Etruscan population. It is suggested that a study of mtDNA variation in skeletons excavated from authentic Etruscan grave sites might reveal mtDNA patterns whose distribution and frequency could be compared to those observed in Tuscans and other modern populations, and in human remains from other burial sites. This comparison could provide clues as to where the Etruscans may have originated
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