caa a22 4500 44535769X CHVBK 20180317142905.0 cr unu---uuuuu 170323e20111001xx s 000 0 eng 10.1007/s10072-011-0735-9 doi (NATIONALLICENCE)springer-10.1007/s10072-011-0735-9 Inherited and somatic mitochondrial DNA mutations in Guam amyotrophic lateral sclerosis and parkinsonism-dementia [Elektronische Daten] [Dana Reiff, Rita Spathis, Chim Chan, Miguel Vilar, Krithivasan Sankaranarayanan, Daniel Lynch, Emily Ehrlich, Samantha Kerath, Risana Chowdhury, Leah Robinowitz, J. Koji Lum, Ralph Garruto] There is increasing evidence for mitochondrial dysfunction in neurodegenerative disorders, although the exact role of mitochondrial DNA (mtDNA) mutations in this process is unresolved. We investigated inherited and somatic mtDNA substitutions and deletions in Guam amyotrophic lateral sclerosis (ALS) and parkinsonism-dementia (PD). Hypervariable segment 1 sequences of Chamorro mtDNA revealed that the odds ratio of a PD or ALS diagnosis was increased for individuals in the E1 haplogroup while individuals in the E2 haplogroup had decreased odds of an ALS or PD diagnosis. Once the disorders were examined separately, it became evident that PD was responsible for these results. When the entire mitochondrial genome was sequenced for a subset of individuals, the nonsynonymous mutation at nucleotide position 9080, shared by all E2 individuals, resulted in a significantly low odds ratio for a diagnosis of ALS or PD. Private polymorphisms found in transfer and ribosomal RNA regions were found only in ALS and PD patients in the E1 haplogroup. Somatic mtDNA deletions in the entire mtDNA genome were not associated with either ALS or PD. We conclude that mtDNA haplogroup effects may result in mitochondrial dysfunction in Guam PD and reflect Guam population history. Thus it is reasonable to consider Guam ALS and PD as complex disorders with both environmental prerequisites and small genetic effects. Springer-Verlag, 2011 Guam nationallicence ALS nationallicence PD nationallicence Inherited mutation nationallicence Somatic mutation nationallicence Reiff Dana Laboratory of Biomedical Anthropology and Neurosciences, State University of New York at Binghamton, PO Box 6000, 13902-6000, Binghamton, NY, USA aut Spathis Rita Laboratory of Biomedical Anthropology and Neurosciences, State University of New York at Binghamton, PO Box 6000, 13902-6000, Binghamton, NY, USA aut Chan Chim Laboratory of Biomedical Anthropology and Neurosciences, State University of New York at Binghamton, PO Box 6000, 13902-6000, Binghamton, NY, USA aut Vilar Miguel Laboratory of Evolutionary Anthropology and Health, State University of New York at Binghamton, PO Box 6000, 13902-6000, Binghamton, NY, USA aut Sankaranarayanan Krithivasan Laboratory of Evolutionary Anthropology and Health, State University of New York at Binghamton, PO Box 6000, 13902-6000, Binghamton, NY, USA aut Lynch Daniel Laboratory of Biomedical Anthropology and Neurosciences, State University of New York at Binghamton, PO Box 6000, 13902-6000, Binghamton, NY, USA aut Ehrlich Emily Laboratory of Biomedical Anthropology and Neurosciences, State University of New York at Binghamton, PO Box 6000, 13902-6000, Binghamton, NY, USA aut Kerath Samantha Laboratory of Biomedical Anthropology and Neurosciences, State University of New York at Binghamton, PO Box 6000, 13902-6000, Binghamton, NY, USA aut Chowdhury Risana Laboratory of Biomedical Anthropology and Neurosciences, State University of New York at Binghamton, PO Box 6000, 13902-6000, Binghamton, NY, USA aut Robinowitz Leah Laboratory of Biomedical Anthropology and Neurosciences, State University of New York at Binghamton, PO Box 6000, 13902-6000, Binghamton, NY, USA aut Koji Lum J. Laboratory of Evolutionary Anthropology and Health, State University of New York at Binghamton, PO Box 6000, 13902-6000, Binghamton, NY, USA aut Garruto Ralph Laboratory of Biomedical Anthropology and Neurosciences, State University of New York at Binghamton, PO Box 6000, 13902-6000, Binghamton, NY, USA aut Neurological Sciences Springer Milan 32/5(2011-10-01), 883-892 1590-1874 32:5<883 2011 32 10072 https://doi.org/10.1007/s10072-011-0735-9 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s10072-011-0735-9 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Reiff Dana Laboratory of Biomedical Anthropology and Neurosciences, State University of New York at Binghamton, PO Box 6000, 13902-6000, Binghamton, NY, USA aut NATIONALLICENCE 700 1- Spathis Rita Laboratory of Biomedical Anthropology and Neurosciences, State University of New York at Binghamton, PO Box 6000, 13902-6000, Binghamton, NY, USA aut NATIONALLICENCE 700 1- Chan Chim Laboratory of Biomedical Anthropology and Neurosciences, State University of New York at Binghamton, PO Box 6000, 13902-6000, Binghamton, NY, USA aut NATIONALLICENCE 700 1- Vilar Miguel Laboratory of Evolutionary Anthropology and Health, State University of New York at Binghamton, PO Box 6000, 13902-6000, Binghamton, NY, USA aut NATIONALLICENCE 700 1- Sankaranarayanan Krithivasan Laboratory of Evolutionary Anthropology and Health, State University of New York at Binghamton, PO Box 6000, 13902-6000, Binghamton, NY, USA aut NATIONALLICENCE 700 1- Lynch Daniel Laboratory of Biomedical Anthropology and Neurosciences, State University of New York at Binghamton, PO Box 6000, 13902-6000, Binghamton, NY, USA aut NATIONALLICENCE 700 1- Ehrlich Emily Laboratory of Biomedical Anthropology and Neurosciences, State University of New York at Binghamton, PO Box 6000, 13902-6000, Binghamton, NY, USA aut NATIONALLICENCE 700 1- Kerath Samantha Laboratory of Biomedical Anthropology and Neurosciences, State University of New York at Binghamton, PO Box 6000, 13902-6000, Binghamton, NY, USA aut NATIONALLICENCE 700 1- Chowdhury Risana Laboratory of Biomedical Anthropology and Neurosciences, State University of New York at Binghamton, PO Box 6000, 13902-6000, Binghamton, NY, USA aut NATIONALLICENCE 700 1- Robinowitz Leah Laboratory of Biomedical Anthropology and Neurosciences, State University of New York at Binghamton, PO Box 6000, 13902-6000, Binghamton, NY, USA aut NATIONALLICENCE 700 1- Koji Lum J. Laboratory of Evolutionary Anthropology and Health, State University of New York at Binghamton, PO Box 6000, 13902-6000, Binghamton, NY, USA aut NATIONALLICENCE 700 1- Garruto Ralph Laboratory of Biomedical Anthropology and Neurosciences, State University of New York at Binghamton, PO Box 6000, 13902-6000, Binghamton, NY, USA aut NATIONALLICENCE 773 0- Neurological Sciences Springer Milan 32/5(2011-10-01), 883-892 1590-1874 32:5<883 2011 32 10072 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer