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991.
A unified mixed-model method for association mapping that accounts for multiple levels of relatedness 总被引:4,自引:0,他引:4
Yu J Pressoir G Briggs WH Vroh Bi I Yamasaki M Doebley JF McMullen MD Gaut BS Nielsen DM Holland JB Kresovich S Buckler ES 《Nature genetics》2006,38(2):203-208
As population structure can result in spurious associations, it has constrained the use of association studies in human and plant genetics. Association mapping, however, holds great promise if true signals of functional association can be separated from the vast number of false signals generated by population structure. We have developed a unified mixed-model approach to account for multiple levels of relatedness simultaneously as detected by random genetic markers. We applied this new approach to two samples: a family-based sample of 14 human families, for quantitative gene expression dissection, and a sample of 277 diverse maize inbred lines with complex familial relationships and population structure, for quantitative trait dissection. Our method demonstrates improved control of both type I and type II error rates over other methods. As this new method crosses the boundary between family-based and structured association samples, it provides a powerful complement to currently available methods for association mapping. 相似文献
992.
Feedback repression is required for mammalian circadian clock function 总被引:13,自引:0,他引:13
Sato TK Yamada RG Ukai H Baggs JE Miraglia LJ Kobayashi TJ Welsh DK Kay SA Ueda HR Hogenesch JB 《Nature genetics》2006,38(3):312-319
993.
994.
Lamellipodia mediate the heterogeneity of central olfactory ensheathing cell interactions 总被引:2,自引:2,他引:0
Louisa C. E. Windus Katie E. Lineburg Susan E. Scott Christina Claxton Alan Mackay-Sim Brian Key James A. St John 《Cellular and molecular life sciences : CMLS》2010,67(10):1735-1750
The growth and guidance of primary olfactory axons are partly attributed to the presence of olfactory ensheathing cells (OECs). However, little is understood about the differences between the subpopulations of OECs and what regulates their interactions. We used OEC-axon assays and determined that axons respond differently to peripheral and central OECs. We then further purified OECs from anatomically distinct regions of the olfactory bulb. Cell behaviour assays revealed that OECs from the olfactory bulb were a functionally heterogeneous population with distinct differences which is consistent with their proposed roles in vivo. We found that the heterogeneity was regulated by motile lamellipodial waves along the shaft of the OECs and that inhibition of lamellipodial wave activity via Mek1 abolished the ability of the cells to distinguish between each other. These results demonstrate that OECs from the olfactory bulb are a heterogeneous population that use lamellipodial waves to regulate cell–cell recognition. 相似文献
995.
Recent studies suggest realized volatility provides forecasts that are as good as option‐implied volatilities, with improvement stemming from the use of high‐frequency data instead of a long‐memory specification. This paper examines whether volatility persistence can be captured by a longer dataset consisting of over 15 years of intra‐day data. Volatility forecasts are evaluated using four exchange rates (AUD/USD, EUR/USD, GBP/USD, USD/JPY) over horizons ranging from 1 day to 3 months, using an expanded set of short‐range and long‐range dependence models. The empirical results provide additional evidence that significant incremental information is found in historical forecasts, beyond the implied volatility information for all forecast horizons. Copyright © 2008 John Wiley & Sons, Ltd. 相似文献
996.
997.
Improper protein folding (misfolding) can lead to the formation of disordered (amorphous) or ordered (amyloid fibril) aggregates.
The major lens protein, α-crystallin, is a member of the small heat-shock protein (sHsp) family of intracellular molecular
chaperone proteins that prevent protein aggregation. Whilst the chaperone activity of sHsps against amorphously aggregating
proteins has been well studied, its action against fibril-forming proteins has received less attention despite the presence
of sHsps in deposits found in fibril-associated diseases (e.g. Alzheimer’s and Parkinson’s). In this review, the literature
on the interaction of αB-crystallin and other sHsps with fibril-forming proteins is summarized. In particular, the ability
of sHsps to prevent fibril formation, their mechanisms of action and the possible in vivo consequences of such associations are discussed. Finally, the fibril-forming propensity of the crystallin proteins and its
implications for cataract formation are described along with the potential use of fibrillar crystallin proteins as bionanomaterials.
Received 13 June 2008; received after revision 29 July 2008; accepted 05 August 2008 相似文献
998.
I summarize certain aspects of Paul Feyerabend's account of the development of Western rationalism, show the ways in which that account is supposed to run up against an alternative, that of Karl Popper, and then try to give a preliminary comparison of the two. My interest is primarily in whether what Feyerabend called his ‘story’ constitutes a possible history of our epistemic concepts and their trajectory. I express some grave reservations about that story, and about Feyerabend's framework, finding Popper's views less problematic here. However, I also suggest that one important aspect of Feyerabend's material, his treatment of religious belief, can be given an interpretation which makes it tenable, and perhaps preferable to a Popperian approach. 相似文献
999.
Taal HR St Pourcain B Thiering E Das S Mook-Kanamori DO Warrington NM Kaakinen M Kreiner-Møller E Bradfield JP Freathy RM Geller F Guxens M Cousminer DL Kerkhof M Timpson NJ Ikram MA Beilin LJ Bønnelykke K Buxton JL Charoen P Chawes BL Eriksson J Evans DM Hofman A Kemp JP Kim CE Klopp N Lahti J Lye SJ McMahon G Mentch FD Müller-Nurasyid M O'Reilly PF Prokopenko I Rivadeneira F Steegers EA Sunyer J Tiesler C Yaghootkar H;Cohorts for Heart Aging Research in Genetic Epidemiology Consortium 《Nature genetics》2012,44(5):532-538
To identify genetic variants associated with head circumference in infancy, we performed a meta-analysis of seven genome-wide association studies (GWAS) (N = 10,768 individuals of European ancestry enrolled in pregnancy and/or birth cohorts) and followed up three lead signals in six replication studies (combined N = 19,089). rs7980687 on chromosome 12q24 (P = 8.1 × 10(-9)) and rs1042725 on chromosome 12q15 (P = 2.8 × 10(-10)) were robustly associated with head circumference in infancy. Although these loci have previously been associated with adult height, their effects on infant head circumference were largely independent of height (P = 3.8 × 10(-7) for rs7980687 and P = 1.3 × 10(-7) for rs1042725 after adjustment for infant height). A third signal, rs11655470 on chromosome 17q21, showed suggestive evidence of association with head circumference (P = 3.9 × 10(-6)). SNPs correlated to the 17q21 signal have shown genome-wide association with adult intracranial volume, Parkinson's disease and other neurodegenerative diseases, indicating that a common genetic variant in this region might link early brain growth with neurological disease in later life. 相似文献
1000.
Zang ZJ Cutcutache I Poon SL Zhang SL McPherson JR Tao J Rajasegaran V Heng HL Deng N Gan A Lim KH Ong CK Huang D Chin SY Tan IB Ng CC Yu W Wu Y Lee M Wu J Poh D Wan WK Rha SY So J Salto-Tellez M Yeoh KG Wong WK Zhu YJ Futreal PA Pang B Ruan Y Hillmer AM Bertrand D Nagarajan N Rozen S Teh BT Tan P 《Nature genetics》2012,44(5):570-574
Gastric cancer is a major cause of global cancer mortality. We surveyed the spectrum of somatic alterations in gastric cancer by sequencing the exomes of 15 gastric adenocarcinomas and their matched normal DNAs. Frequently mutated genes in the adenocarcinomas included TP53 (11/15 tumors), PIK3CA (3/15) and ARID1A (3/15). Cell adhesion was the most enriched biological pathway among the frequently mutated genes. A prevalence screening confirmed mutations in FAT4, a cadherin family gene, in 5% of gastric cancers (6/110) and FAT4 genomic deletions in 4% (3/83) of gastric tumors. Frequent mutations in chromatin remodeling genes (ARID1A, MLL3 and MLL) also occurred in 47% of the gastric cancers. We detected ARID1A mutations in 8% of tumors (9/110), which were associated with concurrent PIK3CA mutations and microsatellite instability. In functional assays, we observed both FAT4 and ARID1A to exert tumor-suppressor activity. Somatic inactivation of FAT4 and ARID1A may thus be key tumorigenic events in a subset of gastric cancers. 相似文献