A mitochondrial mutator plasmid that causes senescence under dietary restricted conditions |
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Authors: | Marc FPM Maas Rolf F Hoekstra Alfons JM Debets |
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Affiliation: | 1. Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Boston, MA, USA 2. The CBR Institute for Biomedical Research, Boston, MA, USA 3. Department of Medicine, Harvard Medical School, Boston, MA, USA 4. Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA 5. Molecular Diagnostics Laboratory, Dana-Farber Cancer Institute, Boston, MA, USA 6. Department of Pathology, Harvard Medical School, Boston, MA, USA 7. Instituto Nacional de Enfermedades Respiratorias, Mexico City, Mexico 8. Department of Medical Genetics, Mayo Clinic, Rochester, MN, USA 9. Department of Pediatrics, Harvard Medical School, Boston, MA, USA
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Abstract: | Background The definition of human MHC class I haplotypes through association of HLA-A, HLA-Cw and HLA-B has been used to analyze ethnicity, population migrations and disease association. Results Here, we present HLA-E allele haplotype association and population linkage disequilibrium (LD) analysis within the ~1.3 Mb bounded by HLA-B/Cw and HLA-A to increase the resolution of identified class I haplotypes. Through local breakdown of LD, we inferred ancestral recombination points both upstream and downstream of HLA-E contributing to alternative block structures within previously identified haplotypes. Through single nucleotide polymorphism (SNP) analysis of the MHC region, we also confirmed the essential genetic fixity, previously inferred by MHC allele analysis, of three conserved extended haplotypes (CEHs), and we demonstrated that commercially-available SNP analysis can be used in the MHC to help define CEHs and CEH fragments. Conclusion We conclude that to generate high-resolution maps for relating MHC haplotypes to disease susceptibility, both SNP and MHC allele analysis must be conducted as complementary techniques. |
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