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21.
The knowledge of human genetic variation that will come from the human genome sequence makes feasible a polygenic approach to disease prevention, in which it will be possible to identify individuals as susceptible by their genotype profile and to prevent disease by targeting interventions to those at risk. There is doubt, however, regarding the magnitude of these genetic effects and thus the potential to apply them to either individuals or populations. We have therefore examined the potential for prediction of risk based on common genetic variation using data from a population-based series of individuals with breast cancer. The data are compatible with a log-normal distribution of genetic risk in the population that is sufficiently wide to provide useful discrimination of high- and low-risk groups. Assuming all of the susceptibility genes could be identified, the half of the population at highest risk would account for 88% of all affected individuals. By contrast, if currently identified risk factors for breast cancer were used to stratify the population, the half of the population at highest risk would account for only 62% of all cases. These results suggest that the construction and use of genetic-risk profiles may provide significant improvements in the efficacy of population-based programs of intervention for cancers and other diseases. 相似文献
22.
Vetter DE Li C Zhao L Contarino A Liberman MC Smith GW Marchuk Y Koob GF Heinemann SF Vale W Lee KF 《Nature genetics》2002,31(4):363-369
Urocortin is a member of the corticotropin-releasing hormone peptide family and is found in many discrete brain regions. The distinct expression pattern of urocortin suggests that it influences such behaviors as feeding, anxiety and auditory processing. To better define the physiological roles of urocortin, we have generated mice carrying a null mutation of the urocortin gene. Urocortin-deficient mice have normal basal feeding behavior and stress responses, but show heightened anxiety-like behaviors in the elevated plus maze and open-field tests. In addition, hearing is impaired in the mutant mice at the level of the inner ear, suggesting that urocortin is involved in the normal development of cochlear sensory-cell function. These results provide the first example of a function for any peptidergic system in hearing. 相似文献
23.
Meijers-Heijboer H van den Ouweland A Klijn J Wasielewski M de Snoo A Oldenburg R Hollestelle A Houben M Crepin E van Veghel-Plandsoen M Elstrodt F van Duijn C Bartels C Meijers C Schutte M McGuffog L Thompson D Easton D Sodha N Seal S Barfoot R Mangion J Chang-Claude J Eccles D Eeles R Evans DG Houlston R Murday V Narod S Peretz T Peto J Phelan C Zhang HX Szabo C Devilee P Goldgar D Futreal PA Nathanson KL Weber B Rahman N Stratton MR;CHEK-Breast Cancer Consortium 《Nature genetics》2002,31(1):55-59
Mutations in BRCA1 and BRCA2 confer a high risk of breast and ovarian cancer, but account for only a small fraction of breast cancer susceptibility. To find additional genes conferring susceptibility to breast cancer, we analyzed CHEK2 (also known as CHK2), which encodes a cell-cycle checkpoint kinase that is implicated in DNA repair processes involving BRCA1 and p53 (refs 3,4,5). We show that CHEK2(*)1100delC, a truncating variant that abrogates the kinase activity, has a frequency of 1.1% in healthy individuals. However, this variant is present in 5.1% of individuals with breast cancer from 718 families that do not carry mutations in BRCA1 or BRCA2 (P = 0.00000003), including 13.5% of individuals from families with male breast cancer (P = 0.00015). We estimate that the CHEK2(*)1100delC variant results in an approximately twofold increase of breast cancer risk in women and a tenfold increase of risk in men. By contrast, the variant confers no increased cancer risk in carriers of BRCA1 or BRCA2 mutations. This suggests that the biological mechanisms underlying the elevated risk of breast cancer in CHEK2 mutation carriers are already subverted in carriers of BRCA1 or BRCA2 mutations, which is consistent with participation of the encoded proteins in the same pathway. 相似文献
24.
The notion that behaviour influences perception seems self-evident, but the mechanism of their interaction is not known. Perception and behaviour are usually considered to be separate processes. In this view, perceptual learning constructs compact representations of sensory events, reflecting their statistical properties, independently of behavioural relevance. Behavioural learning, however, forms associations between perception and action, organized by reinforcement, without regard for the construction of perception. It is generally assumed that the interaction between these two processes is internal to the agent, and can be explained solely in terms of the neuronal substrate. Here we show, instead, that perception and behaviour can interact synergistically via the environment. Using simulated and real mobile robots, we demonstrate that perceptual learning directly supports behavioural learning and so promotes a progressive structuring of behaviour. This structuring leads to a systematic bias in input sampling, which directly affects the organization of the perceptual system. This external, environmentally mediated feedback matches the perceptual system to the emerging behavioural structure, so that the behaviour is stabilized. 相似文献
25.
Somatosensory basis of speech production 总被引:1,自引:0,他引:1
The hypothesis that speech goals are defined acoustically and maintained by auditory feedback is a central idea in speech production research. An alternative proposal is that speech production is organized in terms of control signals that subserve movements and associated vocal-tract configurations. Indeed, the capacity for intelligible speech by deaf speakers suggests that somatosensory inputs related to movement play a role in speech production-but studies that might have documented a somatosensory component have been equivocal. For example, mechanical perturbations that have altered somatosensory feedback have simultaneously altered acoustics. Hence, any adaptation observed under these conditions may have been a consequence of acoustic change. Here we show that somatosensory information on its own is fundamental to the achievement of speech movements. This demonstration involves a dissociation of somatosensory and auditory feedback during speech production. Over time, subjects correct for the effects of a complex mechanical load that alters jaw movements (and hence somatosensory feedback), but which has no measurable or perceptible effect on acoustic output. The findings indicate that the positions of speech articulators and associated somatosensory inputs constitute a goal of speech movements that is wholly separate from the sounds produced. 相似文献
26.
K-means clustering is arguably the most popular technique for partitioning data. Unfortunately, K-means suffers from the well-known
problem of locally optimal solutions. Furthermore, the final partition is dependent upon the initial configuration, making
the choice of starting partitions all the more important. This paper evaluates 12 procedures proposed in the literature and
provides recommendations for best practices. 相似文献
27.
28.
Thirty-six species of aquatic Oligochaeta (Lumbriculidae, Haplotaxidae, Naididae, Tubificidae) are now known form Utah. Aquatic habitats in 27 counties were sampled, with 32 oligochaete species identified. An additional 4 species were added from other published investigations. The majority of species are cosmopolitan and occur in other areas of North America. Nais barbata, N. alpina, and N. pardalis are reported from the western United States for the first time. Ilyodrilus frantzi was found to be a major component of the oliogochaete fauna in the Great Basin lentic environment. The North American distribution of Telmatodrilus vejdovskyi is extended significantly eastward. Tow undetermined species of Tubificidae are discussed. 相似文献
29.
An inventory of the terrestrial vertebrate fauna and the seasonal occurrence of each species was determined for a man - made radioactive leaching pond complex in southeastern Idaho. Three reptile, 11 mammal, and 94 bird species were identified from February 1974 through January 1978. Fewest species were observed during the winter and most during the summer. Eight bird species nested at the pond complex, while 19 species of birds were common or seasonally abundant. It appears that the Test Reactor Area radioactive leaching pond complex is an important water source and provides habitat for some species of wildlife. 相似文献
30.
Henry Rogers Durkee collected 74 egg sets of 27 avian species in 1870 at Gilmer, Uinta County, in southwestern Wyoming. Despite the paucity of documented breeding evidence from this region during the late 19th and early 20th centuries, his material at the Smithsonian Institution was generally overlooked and has never been critically examined. Durkee's egg sets included 5 species (Sandhill Crane, Grus candensis ; Northern Rough-winged Swallow, Stelgidoteryx serripennis ; Grasshopper Sparrow, Ammodramus savannarum ; Fox Sparrow, Passerella iliaca ; Cassin's Finch, Carpodacus cassinii ) whose breeding distribution was then poorly known, 25 to more than 70 years before nests and eggs were otherwise documented in Wyoming. Durkee also collected complete egg sets of Lark Bunting ( Calamospiza melanocorys ) over 70 years before breeding was confirmed at other peripheral locations in Wyoming. In addition, Durkee's incomplete egg sets of Grasshopper Sparrow were the 1st western subspecies ( A. s. perpallidus ); his complete egg set and nest of the Fox Sparrow collected at Gilmer constituted the 2nd locality for the species or species group ( P. i. schistacea ). Although the number of egg sets Durkee collected is modest, he made a meaningful contribution to the early history of avifaunal exploration in Wyoming. 相似文献