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1.
Arnaiz-Villena A Guillén J Ruiz-del-Valle V Lowy E Zamora J Varela P Stefani D Allende LM 《Cellular and molecular life sciences : CMLS》2001,58(8):1159-1166
Mitochondrial cytochrome b (cyt b) from 24 Carduelini species including crossbills, bullfinches, grosbeaks, rosefinches, and other related, but not conclusively classified species, was sequenced. These sequences were also compared with all the available sequences from the genera Carduelis, Serinus, and Passer. Phylogenetic analyses consistently gave the same groups of finches and the calculated divergence times suggest that speciation of the studied species occurred between 14 and 3 million years ago (Miocene-Pliocene), appearing before the Passer, Carduelis, and Serinus genera. Pleistocene glaciations may have been important in sub-speciation. Crossbills are integrated within the genus Carduelis, and within redpolls; the common crossbill shows subspeciation with Loxia japonica in the Pleistocene epoch. Pinicola enucleator groups together with bullfinches and is probably the ancestor of the group. Hawfinch is only distantly related to the studied groups, and might either represent an isolated genus or be related to the New World genus Hesperiphona. The grosbeak genera Eophona and Mycerobas are clearly sister groups, and species belonging to the former might have given rise to Mycerobas species. The isolated (in classification) Uragus sibiricus and Haematospiza sipahi are included within the genus Carpodacus (rosefinches); Carpodacus nipalensis is outside the genus Carpodacus in the molecular analyses and might be an isolated species or related to the genus Montifringilla. 相似文献
2.
Stephens PJ Tarpey PS Davies H Van Loo P Greenman C Wedge DC Nik-Zainal S Martin S Varela I Bignell GR Yates LR Papaemmanuil E Beare D Butler A Cheverton A Gamble J Hinton J Jia M Jayakumar A Jones D Latimer C Lau KW McLaren S McBride DJ Menzies A Mudie L Raine K Rad R Chapman MS Teague J Easton D Langerød A;Oslo Breast Cancer Consortium 《Nature》2012,486(7403):400-404
All cancers carry somatic mutations in their genomes. A subset, known as driver mutations, confer clonal selective advantage on cancer cells and are causally implicated in oncogenesis, and the remainder are passenger mutations. The driver mutations and mutational processes operative in breast cancer have not yet been comprehensively explored. Here we examine the genomes of 100 tumours for somatic copy number changes and mutations in the coding exons of protein-coding genes. The number of somatic mutations varied markedly between individual tumours. We found strong correlations between mutation number, age at which cancer was diagnosed and cancer histological grade, and observed multiple mutational signatures, including one present in about ten per cent of tumours characterized by numerous mutations of cytosine at TpC dinucleotides. Driver mutations were identified in several new cancer genes including AKT2, ARID1B, CASP8, CDKN1B, MAP3K1, MAP3K13, NCOR1, SMARCD1 and TBX3. Among the 100 tumours, we found driver mutations in at least 40 cancer genes and 73 different combinations of mutated cancer genes. The results highlight the substantial genetic diversity underlying this common disease. 相似文献
3.
Defects in whirlin,a PDZ domain molecule involved in stereocilia elongation,cause deafness in the whirler mouse and families with DFNB31 总被引:22,自引:0,他引:22
Mburu P Mustapha M Varela A Weil D El-Amraoui A Holme RH Rump A Hardisty RE Blanchard S Coimbra RS Perfettini I Parkinson N Mallon AM Glenister P Rogers MJ Paige AJ Moir L Clay J Rosenthal A Liu XZ Blanco G Steel KP Petit C Brown SD 《Nature genetics》2003,34(4):421-428
The whirler mouse mutant (wi) does not respond to sound stimuli, and detailed ultrastructural analysis of sensory hair cells in the organ of Corti of the inner ear indicates that the whirler gene encodes a protein involved in the elongation and maintenance of stereocilia in both inner hair cells (IHCs) and outer hair cells (OHCs). BAC-mediated transgene correction of the mouse phenotype and mutation analysis identified the causative gene as encoding a novel PDZ protein called whirlin. The gene encoding whirlin also underlies the human autosomal recessive deafness locus DFNB31. In the mouse cochlea, whirlin is expressed in the sensory IHC and OHC stereocilia. Our findings suggest that this novel PDZ domain-containing molecule acts as an organizer of submembranous molecular complexes that control the coordinated actin polymerization and membrane growth of stereocilia. 相似文献
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5.
Phylogeny and rapid Northern and Southern Hemisphere speciation of goldfinches during the Miocene and Pliocene Epochs 总被引:5,自引:0,他引:5
A. Arnaiz-Villena M. Álvarez-Tejado V. Ruíz-del-Valle C. García-de-la-Torre P. Varela M. J. Recio S. Ferre J. Martínez-Laso 《Cellular and molecular life sciences : CMLS》1998,54(9):1031-1041
Mitochondrial cytochrome b (cyt b) from 25 out of 31 extant goldfinches, siskins, greenfinches and redpolls (genus Carduelis) has been sequenced from living samples taken around the world, specimens have also been photographed. Phylogenetic analysis
consistently gave the same groups of birds, and this grouping was generally related to geographical proximity. It has been
supposed that Pleistocene glaciations played a crucial role in the origin of extant diversity and distribution of Northern
Hemisphere vertebrates. Molecular comparison of most extant songbird species belonging to the genus Carduelis does not support this assertion. The fossil record of chicken and pheasant divergence time has been used to calibrate the
molecular clock; cyt b DNA dendrograms suggest that speciation in Carduelinae birds occurred during the Miocene and Pliocene
Epochs (9 – 2 million years ago) in both the Northern and Southern Hemispheres. Only about 4% average amount of nucleotide
substitution per lineage is found between the most distant Carduelis species; this suggests a remarkably rapid radiation when compared with the radiation of other passerine songbird genera.
In addition, a continuum of small songbird speciation may be found during the Miocene Epoch in parallel with speciation of
other orders (i.e. Galliformes, chicken/pheasant). Pleistocene glaciations may have been important in subspeciation (i.e.
Eastern European grey-headed goldfinches/Western European black-headed goldfinches) and also in ice-induced vicariance (isolation)
(i.e. siskin in Western Europe vs. siskin in Far East Asia) around the world. European isolated Serinus citrinella (citril finch) is not a canary, but a true goldfinch. South American siskins have quickly radiated in the last 4 million
years coinciding with the emergence of the Isthmus of Panama; probably, a North American siskin related to C. notata invaded a suitable and varied biotope (the South American island) for Carduelis birds. North American goldfinches may be renamed as siskins, because they have a distant genetic relationship with European
goldfinches. Genus Acanthis could be dropped, and thus redpolls should be separated from twite and linnet, the latter (Europeans) probably being related
to American goldfinches. Also, reproductive barriers are observed between closely related species and not between other more
distant ones. Finally, a tentative classification for genus Carduelis species is suggested.
Received 6 March 1998; received after revision 3 July 1998; accepted 7 July 1998 相似文献
6.
Ramírez CL Cadiñanos J Varela I Freije JM López-Otín C 《Cellular and molecular life sciences : CMLS》2007,64(2):155-170
Disorders in which individuals exhibit certain features of aging early in life are referred to as segmental progeroid syndromes.
With the progress that has been made in understanding the etiologies of these conditions in the past decade, potential therapeutic
options have begun to move from the realm of improbability to initial stages of testing. Among these syndromes, relevant advances
have recently been made in Werner syndrome, one of several progeroid syndromes characterized by defective DNA helicases, and
Hutchinson-Gilford progeria syndrome, which is characterized by aberrant processing of the nuclear envelope protein lamin
A. Although best known for their causative roles in these illnesses, Werner protein and lamin A have also recently emerged
as key players vulnerable to epigenetic changes that contribute to tumorigenesis and aging. These advances further demonstrate
that understanding progeroid syndromes and introducing adequate treatments will not only prove beneficial to patients suffering
from these dramatic diseases, but will also provide new mechanistic insights into cancer and normal aging processes.
Received 28 July 2006; received after revision 5 September 2006; accepted 13 October 2006 相似文献
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Shaw-Smith C Pittman AM Willatt L Martin H Rickman L Gribble S Curley R Cumming S Dunn C Kalaitzopoulos D Porter K Prigmore E Krepischi-Santos AC Varela MC Koiffmann CP Lees AJ Rosenberg C Firth HV de Silva R Carter NP 《Nature genetics》2006,38(9):1032-1037
Recently, the application of array-based comparative genomic hybridization (array CGH) has improved rates of detection of chromosomal imbalances in individuals with mental retardation and dysmorphic features. Here, we describe three individuals with learning disability and a heterozygous deletion at chromosome 17q21.3, detected in each case by array CGH. FISH analysis demonstrated that the deletions occurred as de novo events in each individual and were between 500 kb and 650 kb in size. A recently described 900-kb inversion that suppresses recombination between ancestral H1 and H2 haplotypes encompasses the deletion. We show that, in each trio, the parent of origin of the deleted chromosome 17 carries at least one H2 chromosome. This region of 17q21.3 shows complex genomic architecture with well-described low-copy repeats (LCRs). The orientation of LCRs flanking the deleted segment in inversion heterozygotes is likely to facilitate the generation of this microdeletion by means of non-allelic homologous recombination. 相似文献
9.
Exome sequencing identifies frequent mutation of the SWI/SNF complex gene PBRM1 in renal carcinoma 总被引:1,自引:0,他引:1
Varela I Tarpey P Raine K Huang D Ong CK Stephens P Davies H Jones D Lin ML Teague J Bignell G Butler A Cho J Dalgliesh GL Galappaththige D Greenman C Hardy C Jia M Latimer C Lau KW Marshall J McLaren S Menzies A Mudie L Stebbings L Largaespada DA Wessels LF Richard S Kahnoski RJ Anema J Tuveson DA Perez-Mancera PA Mustonen V Fischer A Adams DJ Rust A Chan-on W Subimerb C Dykema K Furge K Campbell PJ Teh BT Stratton MR Futreal PA 《Nature》2011,469(7331):539-542
10.
Yusa K Rashid ST Strick-Marchand H Varela I Liu PQ Paschon DE Miranda E Ordóñez A Hannan NR Rouhani FJ Darche S Alexander G Marciniak SJ Fusaki N Hasegawa M Holmes MC Di Santo JP Lomas DA Bradley A Vallier L 《Nature》2011,478(7369):391-394
Human induced pluripotent stem cells (iPSCs) represent a unique opportunity for regenerative medicine because they offer the prospect of generating unlimited quantities of cells for autologous transplantation, with potential application in treatments for a broad range of disorders. However, the use of human iPSCs in the context of genetically inherited human disease will require the correction of disease-causing mutations in a manner that is fully compatible with clinical applications. The methods currently available, such as homologous recombination, lack the necessary efficiency and also leave residual sequences in the targeted genome. Therefore, the development of new approaches to edit the mammalian genome is a prerequisite to delivering the clinical promise of human iPSCs. Here we show that a combination of zinc finger nucleases (ZFNs) and piggyBac technology in human iPSCs can achieve biallelic correction of a point mutation (Glu342Lys) in the α(1)-antitrypsin (A1AT, also known as SERPINA1) gene that is responsible for α(1)-antitrypsin deficiency. Genetic correction of human iPSCs restored the structure and function of A1AT in subsequently derived liver cells in vitro and in vivo. This approach is significantly more efficient than any other gene-targeting technology that is currently available and crucially prevents contamination of the host genome with residual non-human sequences. Our results provide the first proof of principle, to our knowledge, for the potential of combining human iPSCs with genetic correction to generate clinically relevant cells for autologous cell-based therapies. 相似文献