Neurological Sciences

, 32:883 | Cite as

Inherited and somatic mitochondrial DNA mutations in Guam amyotrophic lateral sclerosis and parkinsonism-dementia

  • Dana M. Reiff
  • Rita Spathis
  • Chim W. Chan
  • Miguel G. Vilar
  • Krithivasan Sankaranarayanan
  • Daniel Lynch
  • Emily Ehrlich
  • Samantha Kerath
  • Risana Chowdhury
  • Leah Robinowitz
  • J. Koji Lum
  • Ralph M. Garruto
Original Article


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.


Guam ALS PD Inherited mutation Somatic mutation 



The authors would like to thank the patients and their families and those who participated as healthy controls in this study. Their long-term participation and cooperation in these studies, along with the assistance of local physicians, administrators and public health officials, have given the neurosciences a much greater understanding of ALS and PD on Guam. We also thank the National Institute of Neurological Disorders and Stroke of the National Institutes of Health, Bethesda, Maryland and the Binghamton University Serum Archive Facility who provided blood and brain tissues for this study. We thank Dr. Anthony Fiumera for his assistance in the Real Time PCR studies. Finally we would like to thank Rebecca Dimond for administrative support.


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Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Dana M. Reiff
    • 1
    • 2
    • 3
  • Rita Spathis
    • 1
    • 2
    • 3
  • Chim W. Chan
    • 1
    • 2
    • 3
  • Miguel G. Vilar
    • 2
    • 3
    • 4
  • Krithivasan Sankaranarayanan
    • 2
    • 5
  • Daniel Lynch
    • 1
    • 2
    • 3
    • 6
  • Emily Ehrlich
    • 1
    • 3
  • Samantha Kerath
    • 1
    • 3
  • Risana Chowdhury
    • 1
    • 3
  • Leah Robinowitz
    • 1
    • 3
  • J. Koji Lum
    • 2
    • 3
    • 5
  • Ralph M. Garruto
    • 1
    • 3
    • 5
  1. 1.Laboratory of Biomedical Anthropology and NeurosciencesState University of New York at BinghamtonBinghamtonUSA
  2. 2.Laboratory of Evolutionary Anthropology and HealthState University of New York at BinghamtonBinghamtonUSA
  3. 3.Department of AnthropologyState University of New York at BinghamtonBinghamtonUSA
  4. 4.Department of AnthropologyUniversity of PennsylvaniaPhiladelphiaUSA
  5. 5.Department of Biological SciencesState University of New York at BinghamtonBinghamtonUSA
  6. 6.Coriell Institute for Medical ResearchCamdenUSA

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