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Rosenberg MJ Agarwala R Bouffard G Davis J Fiermonte G Hilliard MS Koch T Kalikin LM Makalowska I Morton DH Petty EM Weber JL Palmieri F Kelley RI Schäffer AA Biesecker LG 《Nature genetics》2002,32(1):175-179
The disorder Amish microcephaly (MCPHA) is characterized by severe congenital microcephaly, elevated levels of alpha-ketoglutarate in the urine and premature death. The disorder is inherited in an autosomal recessive pattern and has been observed only in Old Order Amish families whose ancestors lived in Lancaster County, Pennsylvania. Here we show, by using a genealogy database and automated pedigree software, that 23 nuclear families affected with MCPHA are connected to a single ancestral couple. Through a whole-genome scan, fine mapping and haplotype analysis, we localized the gene affected in MCPHA to a region of 3 cM, or 2 Mb, on chromosome 17q25. We constructed a map of contiguous genomic clones spanning this region. One of the genes in this region, SLC25A19, which encodes a nuclear mitochondrial deoxynucleotide carrier (DNC), contains a substitution that segregates with the disease in affected individuals and alters an amino acid that is highly conserved in similar proteins. Functional analysis shows that the mutant DNC protein lacks the normal transport activity, implying that failed deoxynucleotide transport across the inner mitochondrial membrane causes MCPHA. Our data indicate that mitochondrial deoxynucleotide transport may be essential for prenatal brain growth. 相似文献
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Jerold L. Petty 《西北部美国博物学家》2011,37(1)
Beetles of Trypophloeus populi attacked green bark of unhealthy aspen ( Populus tremuloides ) and hastened the death of the tree. Beetles of Procryphalus mucronatus favored dead bark and were of little significance in the death of the aspen. These two beetle species were distinguished from each other by their primary galleries, eggs, larvae, larval mines, and mating behavior. In T. populi, there were three larval instars and one to one and one - half generations per year; only larvae overwintered, and the eggs of the first generation were present by mid - July. In P. mucronatus, there were two larval instars and one and one - half to two generations per year; both larvae and adults overwintered, and the first eggs of the new season were present by late May. 相似文献
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介绍了轿车车门断面设计的基本方法,探讨了控制断面的作用和设置原则.结合车门间隙、车门密封、车门运动校核及车门结构件连接等具体设计过程,分析了车门断面设计中需要考虑的控制要素,阐述了轿车车门断面设计的基本思路和程序. 相似文献
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Cornelius F Boerkoel Hiroshi Takashima Joy John Jiong Yan Pawel Stankiewicz Lisa Rosenbarker Jean-Luc André Radovan Bogdanovic Antoine Burguet Sandra Cockfield Isabel Cordeiro Stefan Fründ Friederike Illies Mark Joseph Ilkka Kaitila Giuliana Lama Chantal Loirat D Ross McLeod David V Milford Elizabeth M Petty Francisco Rodrigo Jorge M Saraiva Beate Schmidt Graham C Smith Jürgen Spranger Anja Stein Hannelore Thiele Jane Tizard Rosanna Weksberg James R Lupski David W Stockton 《Nature genetics》2002,30(2):215-220
Schimke immuno-osseous dysplasia (SIOD, MIM 242900) is an autosomal-recessive pleiotropic disorder with the diagnostic features of spondyloepiphyseal dysplasia, renal dysfunction and T-cell immunodeficiency. Using genome-wide linkage mapping and a positional candidate approach, we determined that mutations in SMARCAL1 (SWI/SNF2-related, matrix-associated, actin-dependent regulator of chromatin, subfamily a-like 1), are responsible for SIOD. Through analysis of data from persons with SIOD in 26 unrelated families, we observed that affected individuals from 13 of 23 families with severe disease had two alleles with nonsense, frameshift or splicing mutations, whereas affected individuals from 3 of 3 families with milder disease had a missense mutation on each allele. These observations indicate that some missense mutations allow retention of partial SMARCAL1 function and thus cause milder disease. 相似文献
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Huyen Y Zgheib O Ditullio RA Gorgoulis VG Zacharatos P Petty TJ Sheston EA Mellert HS Stavridi ES Halazonetis TD 《Nature》2004,432(7015):406-411
The mechanisms by which eukaryotic cells sense DNA double-strand breaks (DSBs) in order to initiate checkpoint responses are poorly understood. 53BP1 is a conserved checkpoint protein with properties of a DNA DSB sensor. Here, we solved the structure of the domain of 53BP1 that recruits it to sites of DSBs. This domain consists of two tandem tudor folds with a deep pocket at their interface formed by residues conserved in the budding yeast Rad9 and fission yeast Rhp9/Crb2 orthologues. In vitro, the 53BP1 tandem tudor domain bound histone H3 methylated on Lys 79 using residues that form the walls of the pocket; these residues were also required for recruitment of 53BP1 to DSBs. Suppression of DOT1L, the enzyme that methylates Lys 79 of histone H3, also inhibited recruitment of 53BP1 to DSBs. Because methylation of histone H3 Lys 79 was unaltered in response to DNA damage, we propose that 53BP1 senses DSBs indirectly through changes in higher-order chromatin structure that expose the 53BP1 binding site. 相似文献
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Stephens P Edkins S Davies H Greenman C Cox C Hunter C Bignell G Teague J Smith R Stevens C O'Meara S Parker A Tarpey P Avis T Barthorpe A Brackenbury L Buck G Butler A Clements J Cole J Dicks E Edwards K Forbes S Gorton M Gray K Halliday K Harrison R Hills K Hinton J Jones D Kosmidou V Laman R Lugg R Menzies A Perry J Petty R Raine K Shepherd R Small A Solomon H Stephens Y Tofts C Varian J Webb A West S Widaa S Yates A Brasseur F Cooper CS Flanagan AM Green A Knowles M Leung SY Looijenga LH 《Nature genetics》2005,37(6):590-592
We examined the coding sequence of 518 protein kinases, approximately 1.3 Mb of DNA per sample, in 25 breast cancers. In many tumors, we detected no somatic mutations. But a few had numerous somatic mutations with distinctive patterns indicative of either a mutator phenotype or a past exposure. 相似文献
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Stephens P Hunter C Bignell G Edkins S Davies H Teague J Stevens C O'Meara S Smith R Parker A Barthorpe A Blow M Brackenbury L Butler A Clarke O Cole J Dicks E Dike A Drozd A Edwards K Forbes S Foster R Gray K Greenman C Halliday K Hills K Kosmidou V Lugg R Menzies A Perry J Petty R Raine K Ratford L Shepherd R Small A Stephens Y Tofts C Varian J West S Widaa S Yates A Brasseur F Cooper CS Flanagan AM Knowles M Leung SY Louis DN Looijenga LH Malkowicz B Pierotti MA Teh B Chenevix-Trench G 《Nature》2004,431(7008):525-526
The protein-kinase family is the most frequently mutated gene family found in human cancer and faulty kinase enzymes are being investigated as promising targets for the design of antitumour therapies. We have sequenced the gene encoding the transmembrane protein tyrosine kinase ERBB2 (also known as HER2 or Neu) from 120 primary lung tumours and identified 4% that have mutations within the kinase domain; in the adenocarcinoma subtype of lung cancer, 10% of cases had mutations. ERBB2 inhibitors, which have so far proved to be ineffective in treating lung cancer, should now be clinically re-evaluated in the specific subset of patients with lung cancer whose tumours carry ERBB2 mutations. 相似文献
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R. L. Petty M. Boppré D. Schneider J. Meinwald 《Cellular and molecular life sciences : CMLS》1977,33(10):1324-1326
Summary By gas-chromatography and mass-spectroscopy 7 volatile substances have been found on the abdominal hairpencils ofAmauris ochlea males. 6 substances have been identified. The spatial distribution of compounds is correlated to the 5 types of hairs comprising the scent organ.Acknowledgments. We thank our colleagues M. Kaib and P. Lounibos for their continous effort to supply us with danaids from Kenya. Support by a research grant from the National Institute of Health (AI 12020) is acknowledged with pleasure. 相似文献
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