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1.
Proc Natl Acad Sci U S A ; 105(45): 17447-52, 2008 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-18955696

RESUMO

Retrieving a large amount of genetic information from extinct species was demonstrated feasible, but complete mitochondrial genome sequences have only been deciphered for the moa, a bird that became extinct a few hundred years ago, and for Pleistocene species, such as the woolly mammoth and the mastodon, both of which could be studied from animals embedded in permafrost. To enlarge the diversity of mitochondrial genomes available for Pleistocene species, we turned to the cave bear (Ursus spelaeus), whose only remains consist of skeletal elements. We collected bone samples from the Paleolithic painted cave of Chauvet-Pont d'Arc (France), which displays the earliest known human drawings, and contains thousands of bear remains. We selected a cave bear sternebra, radiocarbon dated to 32,000 years before present, from which we generated overlapping DNA fragments assembling into a 16,810-base pair mitochondrial genome. Together with the first mitochondrial genome for the brown bear western lineage, this study provides a statistically secured molecular phylogeny assessing the cave bear as a sister taxon to the brown bear and polar bear clade, with a divergence inferred to 1.6 million years ago. With the first mitochondrial genome for a Pleistocene carnivore to be delivered, our study establishes the Chauvet-Pont d'Arc Cave as a new reservoir for Paleogenetic studies. These molecular data enable establishing the chronology of bear speciation, and provide a helpful resource to rescue for genetic analysis archeological samples initially diagnosed as devoid of amplifiable DNA.


Assuntos
Osso e Ossos/química , DNA Mitocondrial/genética , Extinção Biológica , Filogenia , Ursidae/genética , Animais , Sequência de Bases , Teorema de Bayes , Análise por Conglomerados , França , Funções Verossimilhança , Modelos Genéticos , Dados de Sequência Molecular , Técnicas de Amplificação de Ácido Nucleico/métodos , Análise de Sequência de DNA , Especificidade da Espécie , Ursidae/classificação
2.
Physiol Genomics ; 33(2): 170-9, 2008 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-18252803

RESUMO

Using serial analysis of gene expression, we collected quantitative transcriptome data in 11 regions of the adult wild-type mouse brain: the orbital, prelimbic, cingulate, motor, somatosensory, and entorhinal cortices, the caudate-putamen, the nucleus accumbens, the thalamus, the substantia nigra, and the ventral tegmental area. With >1.2 million cDNA tags sequenced, this database is a powerful resource to explore brain functions and disorders. As an illustration, we performed interregional comparisons and found 315 differential transcripts. Most of them are poorly characterized and 20% lack functional annotation. For 78 differential transcripts, we provide independent expression level measurements in mouse brain regions by real-time quantitative RT-PCR. We also show examples where we used in situ hybridization to achieve infrastructural resolution. For 30 transcripts, we next demonstrated that regional enrichment is conserved in the human brain. We then quantified the expression levels of region-enriched transcripts in the R6/2 mouse model of Huntington disease and the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinson disease and observed significant alterations in the striatum, cerebral cortex, thalamus and substantia nigra of R6/2 mice and in the striatum of MPTP-treated mice. These results show that the gene expression data provided here for the mouse brain can be used to explore pathophysiological models and disclose transcripts differentially expressed in human brain regions.


Assuntos
Encéfalo/metabolismo , Sequência Conservada/genética , Modelos Animais de Doenças , Perfilação da Expressão Gênica , Doenças Neurodegenerativas/genética , 1-Metil-4-Fenil-1,2,3,6-Tetra-Hidropiridina/farmacologia , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/enzimologia , Bases de Dados Genéticas , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Especificidade de Órgãos/efeitos dos fármacos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Tirosina 3-Mono-Oxigenase/genética , Tirosina 3-Mono-Oxigenase/metabolismo
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