排序方式: 共有33条查询结果,搜索用时 93 毫秒
31.
Puente XS Pinyol M Quesada V Conde L Ordóñez GR Villamor N Escaramis G Jares P Beà S González-Díaz M Bassaganyas L Baumann T Juan M López-Guerra M Colomer D Tubío JM López C Navarro A Tornador C Aymerich M Rozman M Hernández JM Puente DA Freije JM Velasco G Gutiérrez-Fernández A Costa D Carrió A Guijarro S Enjuanes A Hernández L Yagüe J Nicolás P Romeo-Casabona CM Himmelbauer H Castillo E Dohm JC de Sanjosé S Piris MA de Alava E San Miguel J Royo R Gelpí JL Torrents D Orozco M Pisano DG 《Nature》2011,475(7354):101-105
Chronic lymphocytic leukaemia (CLL), the most frequent leukaemia in adults in Western countries, is a heterogeneous disease with variable clinical presentation and evolution. Two major molecular subtypes can be distinguished, characterized respectively by a high or low number of somatic hypermutations in the variable region of immunoglobulin genes. The molecular changes leading to the pathogenesis of the disease are still poorly understood. Here we performed whole-genome sequencing of four cases of CLL and identified 46 somatic mutations that potentially affect gene function. Further analysis of these mutations in 363 patients with CLL identified four genes that are recurrently mutated: notch 1 (NOTCH1), exportin 1 (XPO1), myeloid differentiation primary response gene 88 (MYD88) and kelch-like 6 (KLHL6). Mutations in MYD88 and KLHL6 are predominant in cases of CLL with mutated immunoglobulin genes, whereas NOTCH1 and XPO1 mutations are mainly detected in patients with unmutated immunoglobulins. The patterns of somatic mutation, supported by functional and clinical analyses, strongly indicate that the recurrent NOTCH1, MYD88 and XPO1 mutations are oncogenic changes that contribute to the clinical evolution of the disease. To our knowledge, this is the first comprehensive analysis of CLL combining whole-genome sequencing with clinical characteristics and clinical outcomes. It highlights the usefulness of this approach for the identification of clinically relevant mutations in cancer. 相似文献
32.
The first hominin of Europe 总被引:3,自引:0,他引:3
Carbonell E Bermúdez de Castro JM Parés JM Pérez-González A Cuenca-Bescós G Ollé A Mosquera M Huguet R van der Made J Rosas A Sala R Vallverdú J García N Granger DE Martinón-Torres M Rodríguez XP Stock GM Vergès JM Allué E Burjachs F Cáceres I Canals A Benito A Díez C Lozano M Mateos A Navazo M Rodríguez J Rosell J Arsuaga JL 《Nature》2008,452(7186):465-469
The earliest hominin occupation of Europe is one of the most debated topics in palaeoanthropology. However, the purportedly oldest of the Early Pleistocene sites in Eurasia lack precise age control and contain stone tools rather than human fossil remains. Here we report the discovery of a human mandible associated with an assemblage of Mode 1 lithic tools and faunal remains bearing traces of hominin processing, in stratigraphic level TE9 at the site of the Sima del Elefante, Atapuerca, Spain. Level TE9 has been dated to the Early Pleistocene (approximately 1.2-1.1 Myr), based on a combination of palaeomagnetism, cosmogenic nuclides and biostratigraphy. The Sima del Elefante site thus emerges as the oldest, most accurately dated record of human occupation in Europe, to our knowledge. The study of the human mandible suggests that the first settlement of Western Europe could be related to an early demographic expansion out of Africa. The new evidence, with previous findings in other Atapuerca sites (level TD6 from Gran Dolina), also suggests that a speciation event occurred in this extreme area of the Eurasian continent during the Early Pleistocene, initiating the hominin lineage represented by the TE9 and TD6 hominins. 相似文献
33.
Maria J. Marcaida Inés G. Muñoz Francisco J. Blanco Jesús Prieto Guillermo Montoya 《Cellular and molecular life sciences : CMLS》2010,67(5):727-748
Homing endonucleases (HE) are double-stranded DNAses that target large recognition sites (12–40 bp). HE-encoding sequences
are usually embedded in either introns or inteins. Their recognition sites are extremely rare, with none or only a few of
these sites present in a mammalian-sized genome. However, these enzymes, unlike standard restriction endonucleases, tolerate
some sequence degeneracy within their recognition sequence. Several members of this enzyme family have been used as templates
to engineer tools to cleave DNA sequences that differ from their original wild-type targets. These custom HEs can be used
to stimulate double-strand break homologous recombination in cells, to induce the repair of defective genes with very low
toxicity levels. The use of tailored HEs opens up new possibilities for gene therapy in patients with monogenic diseases that
can be treated ex vivo. This review provides an overview of recent advances in this field. 相似文献