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11.
Mutations in PTPN11, encoding the protein tyrosine phosphatase SHP-2, cause Noonan syndrome. 总被引:23,自引:0,他引:23
M Tartaglia E L Mehler R Goldberg G Zampino H G Brunner H Kremer I van der Burgt A H Crosby A Ion S Jeffery K Kalidas M A Patton R S Kucherlapati B D Gelb 《Nature genetics》2001,29(4):465-468
Noonan syndrome (MIM 163950) is an autosomal dominant disorder characterized by dysmorphic facial features, proportionate short stature and heart disease (most commonly pulmonic stenosis and hypertrophic cardiomyopathy). Webbed neck, chest deformity, cryptorchidism, mental retardation and bleeding diatheses also are frequently associated with this disease. This syndrome is relatively common, with an estimated incidence of 1 in 1,000-2,500 live births. It has been mapped to a 5-cM region (NS1) [corrected] on chromosome 12q24.1, and genetic heterogeneity has also been documented. Here we show that missense mutations in PTPN11 (MIM 176876)-a gene encoding the nonreceptor protein tyrosine phosphatase SHP-2, which contains two Src homology 2 (SH2) domains-cause Noonan syndrome and account for more than 50% of the cases that we examined. All PTPN11 missense mutations cluster in interacting portions of the amino N-SH2 domain and the phosphotyrosine phosphatase domains, which are involved in switching the protein between its inactive and active conformations. An energetics-based structural analysis of two N-SH2 mutants indicates that in these mutants there may be a significant shift of the equilibrium favoring the active conformation. This implies that they are gain-of-function changes and that the pathogenesis of Noonan syndrome arises from excessive SHP-2 activity. 相似文献
12.
Insertion of DNA sequences into the human chromosomal beta-globin locus by homologous recombination 总被引:18,自引:0,他引:18
A 'rescuable' plasmid containing globin gene sequences allowing recombination with homologous chromosomal sequences has enabled us to produce, score and clone mammalian cells with the plasmid integrated into the human beta-globin locus. The planned modification was achieved in about one per thousand transformed cells whether or not the target gene was expressed. 相似文献
13.
Wang Y Putnam CD Kane MF Zhang W Edelmann L Russell R Carrión DV Chin L Kucherlapati R Kolodner RD Edelmann W 《Nature genetics》2005,37(7):750-755
Most cancers have multiple chromosomal rearrangements; the molecular mechanisms that generate them remain largely unknown. Mice carrying a heterozygous missense change in one of the DNA-binding domains of Rpa1 develop lymphoid tumors, and their homozygous littermates succumb to early embryonic lethality. Array comparative genomic hybridization of the tumors identified large-scale chromosomal changes as well as segmental gains and losses. The Rpa1 mutation resulted in defects in DNA double-strand break repair and precipitated chromosomal breaks as well as aneuploidy in primary heterozygous mutant mouse embryonic fibroblasts. The equivalent mutation in yeast is hypomorphic and semidominant and enhanced the formation of gross chromosomal rearrangements in multiple genetic backgrounds. These results indicate that Rpa1 functions in DNA metabolism are essential for the maintenance of chromosomal stability and tumor suppression. 相似文献
14.
S. Mastanaiah D. Chengal Raju D. Ravi Varma K. S. Swami 《Cellular and molecular life sciences : CMLS》1979,35(1):69-70
Summary The activity levels of aldolase and isocitrate dehydrogenase were assayed in the heart muscle of scorpion,Heterometrus fulvipes. The enzyme activities showed a circadian rhythmicity with a peak value at 20.00 h in the heart muscle. 相似文献
15.
Zusammenfassung Herz und Magenmuskulatur des Frosches verlieren in halb-isotoner Rohrzuckerlösung innert 1 h alles Natrium. Trotzdem bleibt die spontane Kontraktilität erhalten. Natrium ist also für die Erregbarkeit dieser Muskeln nicht Voraussetzung. 相似文献
16.
D. Chengal Raju M. D. Bashamohideen C. Narasimham 《Cellular and molecular life sciences : CMLS》1973,29(8):964-965
Zusammenfassung Experimenteller Nachweis einer reziproken Tagesrhythmik von Blutzucker und Leberglykogen beim Skorpion.Heterometrus fulvipes. 相似文献
17.
I Cho S Yamanishi L Cox BA Methé J Zavadil K Li Z Gao D Mahana K Raju I Teitler H Li AV Alekseyenko MJ Blaser 《Nature》2012,488(7413):621-626
Antibiotics administered in low doses have been widely used as growth promoters in the agricultural industry since the 1950s, yet the mechanisms for this effect are unclear. Because antimicrobial agents of different classes and varying activity are effective across several vertebrate species, we proposed that such subtherapeutic administration alters the population structure of the gut microbiome as well as its metabolic capabilities. We generated a model of adiposity by giving subtherapeutic antibiotic therapy to young mice and evaluated changes in the composition and capabilities of the gut microbiome. Administration of subtherapeutic antibiotic therapy increased adiposity in young mice and increased hormone levels related to metabolism. We observed substantial taxonomic changes in the microbiome, changes in copies of key genes involved in the metabolism of carbohydrates to short-chain fatty acids, increases in colonic short-chain fatty acid levels, and alterations in the regulation of hepatic metabolism of lipids and cholesterol. In this model, we demonstrate the alteration of early-life murine metabolic homeostasis through antibiotic manipulation. 相似文献
18.
Time series of categorical data is not a widely studied research topic. Particularly, there is no available work on the Bayesian analysis of categorical time series processes. With the objective of filling that gap, in the present paper we consider the problem of Bayesian analysis including Bayesian forecasting for time series of categorical data, which is modelled by Pegram's mixing operator, applicable for both ordinal and nominal data structures. In particular, we consider Pegram's operator‐based autoregressive process for the analysis. Real datasets on infant sleep status are analysed for illustrations. We also illustrate that the Bayesian forecasting is more accurate than the corresponding frequentist's approach when we intend to forecast a large time gap ahead. Copyright © 2016 John Wiley & Sons, Ltd. 相似文献
19.
Résumé Le cur de grenouille continue à battre de lui-même et répond à une stimulation électrique durant 5–6 h s'il reçoit une injection contenant une demi solution isotonique de saccharose, de pyrophosphate de sodium et d'adénosinetriphosphate ou de citrate de sodium. Le chloride de sodium annule ces deux réactions. 相似文献
20.
McPherson JD Marra M Hillier L Waterston RH Chinwalla A Wallis J Sekhon M Wylie K Mardis ER Wilson RK Fulton R Kucaba TA Wagner-McPherson C Barbazuk WB Gregory SG Humphray SJ French L Evans RS Bethel G Whittaker A Holden JL McCann OT Dunham A Soderlund C Scott CE Bentley DR Schuler G Chen HC Jang W Green ED Idol JR Maduro VV Montgomery KT Lee E Miller A Emerling S Kucherlapati Gibbs R Scherer S Gorrell JH Sodergren E Clerc-Blankenburg K Tabor P Naylor S Garcia D de Jong PJ Catanese JJ Nowak N 《Nature》2001,409(6822):934-941
The human genome is by far the largest genome to be sequenced, and its size and complexity present many challenges for sequence assembly. The International Human Genome Sequencing Consortium constructed a map of the whole genome to enable the selection of clones for sequencing and for the accurate assembly of the genome sequence. Here we report the construction of the whole-genome bacterial artificial chromosome (BAC) map and its integration with previous landmark maps and information from mapping efforts focused on specific chromosomal regions. We also describe the integration of sequence data with the map. 相似文献