Genetic Variation in Healthy Oldest-Old
| Autor: | Joseph M. Connors, Marco A. Marra, Angela Brooks-Wilson, Markus Pieczyk, Nhu D. Le, Anita Kollar, Jennifer A. Collins, Graydon S. Meneilly, Georgios Agalaridis, Lisa Oliveira, Ruth Thomas, Kenneth M. Madden, Nasim Monfared, So Yamada, Julius Halaschek-Wiener, Christian Sailer, Mahsa Amirabbasi-Beik |
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| Přispěvatelé: | University of Zurich, Halaschek-Wiener, J |
| Jazyk: | angličtina |
| Rok vydání: | 2009 |
| Předmět: |
Aging
Candidate gene dbSNP lcsh:Medicine Single-nucleotide polymorphism 1100 General Agricultural and Biological Sciences Disease 580 Plants (Botany) Biology Bioinformatics Polymorphism Single Nucleotide 03 medical and health sciences 0302 clinical medicine 10126 Department of Plant and Microbial Biology 1300 General Biochemistry Genetics and Molecular Biology Genetics and Genomics/Population Genetics Genetic variation medicine Humans lcsh:Science Genetics and Genomics/Genetics of Disease Aged 030304 developmental biology Genetic association Aged 80 and over Genetics 1000 Multidisciplinary 0303 health sciences Progeria Multidisciplinary lcsh:R Genetic Variation Genetics and Genomics medicine.disease 3. Good health DNA methylation lcsh:Q 030217 neurology & neurosurgery Research Article |
| Zdroj: | PLoS ONE, 4 (8) PLoS ONE, Vol 4, Iss 8, p e6641 (2009) PLoS ONE |
| ISSN: | 1932-6203 |
| Popis: | Individuals who live to 85 and beyond without developing major age-related diseases may achieve this, in part, by lacking disease susceptibility factors, or by possessing resistance factors that enhance their ability to avoid disease and prolong lifespan. Healthy aging is a complex phenotype likely to be affected by both genetic and environmental factors. We sequenced 24 candidate healthy aging genes in DNA samples from 47 healthy individuals aged eighty-five years or older (the ‘oldest-old’), to characterize genetic variation that is present in this exceptional group. These healthy seniors were never diagnosed with cancer, cardiovascular disease, pulmonary disease, diabetes, or Alzheimer disease. We re-sequenced all exons, intron-exon boundaries and selected conserved non-coding sequences of candidate genes involved in aging-related processes, including dietary restriction (PPARG, PPARGC1A, SIRT1, SIRT3, UCP2, UCP3), metabolism (IGF1R, APOB, SCD), autophagy (BECN1, FRAP1), stem cell activation (NOTCH1, DLL1), tumor suppression (TP53, CDKN2A, ING1), DNA methylation (TRDMT1, DNMT3A, DNMT3B) Progeria syndromes (LMNA, ZMPSTE24, KL) and stress response (CRYAB, HSPB2). We detected 935 variants, including 848 single nucleotide polymorphisms (SNPs) and 87 insertion or deletions; 41% (385) were not recorded in dbSNP. This study is the first to present a comprehensive analysis of genetic variation in aging-related candidate genes in healthy oldest-old. These variants and especially our novel polymorphisms are valuable resources to test for genetic association in models of disease susceptibility or resistance. In addition, we propose an innovative tagSNP selection strategy that combines variants identified through gene re-sequencing- and HapMap-derived SNPs. ISSN:1932-6203 |
| Databáze: | OpenAIRE |
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