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11.
Mary J. Emond Tin Louie Julia Emerson Jessica X. Chong Rasika A. Mathias Michael R. Knowles Mark J. Rieder Holly K. Tabor Debbie A. Nickerson Kathleen C. Barnes NHLBI GO Exome Sequencing Project Lung GO Ronald L. Gibson Michael J. Bamshad 《PLoS genetics》2015,11(6)
Discovery of rare or low frequency variants in exome or genome data that are associated with complex traits often will require use of very large sample sizes to achieve adequate statistical power. For a fixed sample size, sequencing of individuals sampled from the tails of a phenotype distribution (i.e., extreme phenotypes design) maximizes power and this approach was recently validated empirically with the discovery of variants in DCTN4 that influence the natural history of P. aeruginosa airway infection in persons with cystic fibrosis (CF; MIM219700). The increasing availability of large exome/genome sequence datasets that serve as proxies for population-based controls affords the opportunity to test an alternative, potentially more powerful and generalizable strategy, in which the frequency of rare variants in a single extreme phenotypic group is compared to a control group (i.e., extreme phenotype vs. control population design). As proof-of-principle, we applied this approach to search for variants associated with risk for age-of-onset of chronic P. aeruginosa airway infection among individuals with CF and identified variants in CAV2 and TMC6 that were significantly associated with group status. These results were validated using a large, prospective, longitudinal CF cohort and confirmed a significant association of a variant in CAV2 with increased age-of-onset of P. aeruginosa airway infection (hazard ratio = 0.48, 95% CI=[0.32, 0.88]) and variants in TMC6 with diminished age-of-onset of P. aeruginosa airway infection (HR = 5.4, 95% CI=[2.2, 13.5]) A strong interaction between CAV2 and TMC6 variants was observed (HR=12.1, 95% CI=[3.8, 39]) for children with the deleterious TMC6 variant and without the CAV2 protective variant. Neither gene showed a significant association using an extreme phenotypes design, and conditions for which the power of an extreme phenotype vs. control population design was greater than that for the extreme phenotypes design were explored. 相似文献
12.
SHIGERU TANSHO-NAGAKAWA YOSHINORI SATO TSUNEYUKI UBAGAI TAKANE KIKUCHI-UEDA GO KAMOSHIDA SATOSHI NISHIDA YASUO ONO 《Polish journal of microbiology》2021,70(4):469
Acinetobacter baumannii is the main causative pathogen of nosocomial infections that causes severe infections in the lungs. In this study, we analyzed the histopathological characteristics of lung infection with two strains of A. baumannii (ATCC 19606 and the clinical isolate TK1090) and Pseudomonas aeruginosa PAO-1 in C3H/HeN mice to evaluate the virulence of A. baumannii. Survival was evaluated over 14 days. At 1, 2, 5, or 14 days postinfection, mice of C3H/HeN were sacrificed, and histopathological analysis of lung specimens was also performed. Histopathological changes and accumulation of neutrophils and macrophages in the lungs after infection with A. baumannii and P. aeruginosa were analyzed. Following intratracheal inoculation, the lethality of ATCC 19606- and TK1090-infected mice was lower than that of PAO-1-infected mice. However, when mice were inoculated with a sub-lethal dose of A. baumannii, the lung bacterial burden remained in the mice until 14 days post-infection. Additionally, histopathological analysis revealed that macrophages infiltrated the lung foci of ATCC 19606-, TK1090-, and PAO-1-infected mice. Although neutrophils infiltrated the lung foci of ATCC 19606- and TK1090-infected mice, they poorly infiltrated the lung foci of PAO-1-infected mice. Accumulation of these cells in the lung foci of ATCC 19606- and TK1090-infected mice, but not PAO-1-infected mice, was observed for 14 days post-infection. These results suggest that A. baumannii is not completely eliminated despite the infiltration of immune cells in the lungs and that inflammation lasts for prolonged periods in the lungs. Further studies are required to understand the mechanism of A. baumannii infection, and novel drugs and vaccines should be developed to prevent A. baumannii infection. 相似文献
13.
Marina Pais Joe Win Kentaro Yoshida Graham J Etherington Liliana M Cano Sylvain Raffaele Mark J Banfield Alex Jones Sophien Kamoun Diane GO Saunders 《Genome biology》2013,14(6):211
Recent pathogenomic research on plant parasitic oomycete effector function and plant host responses has resulted in major conceptual advances in plant pathology, which has been possible thanks to the availability of genome sequences. 相似文献
14.
CMA Iwegbue OV Beecroft JE Ogala FE Egobueze GO Tesi GE Nwajei 《African Journal of Aquatic Science》2018,43(3):241-253
The concentrations of nine metals were measured by atomic absorption spectrophotometry in surface sediments of three coastal creeks, namely, the Ifie, Egbokodo and Ubeji creeks, in the Niger Delta of Nigeria, from August 2012 to January 2013. The aim of the study was to provide information on the spatial and seasonal distribution patterns, degree of contamination, and ecological risks of metals in these sediments. The mean concentrations of the nine metals in these creek sediments ranged from 0.30 to 3.20?mg kg?1 Cd; 10.7 to 24.7?mg kg?1 Pb, 125 to 466?mg kg?1 Cr; 3.1.10 to 14.9?mg kg?1 Cu; 4.7 to 14.3?mg kg?1 Co; 61.1 to 115?mg kg?1 Ni; 106 to 183?mg kg?1 Mn; 52.0 to 170?mg kg?1 Zn and 5 469 to 20 639?mg kg?1 Fe. In general, the metal concentrations were higher in the dry season than the wet season, except for Cr. The concentrations of Cd, Cr, Ni and Zn were above their regulatory control limits in sediment as specified by the Nigerian Regulatory Authority and Cd was identified as the main ecological risk factor. The enrichment factors for the studied metals followed the order: Cd > Cr > Ni > Zn > Pb > Co > Mn > Cu. The average multiple pollution index values indicated that these sediments were severely polluted with significant inputs from Cd, Ni and Cr. 相似文献
15.
Benjamin Stich Bettina IG Haussmann Raj Pasam Sankalp Bhosale C Tom Hash Albrecht E Melchinger Heiko K Parzies 《BMC plant biology》2010,10(1):216
Background
The distribution area of pearl millet in West and Central Africa (WCA) harbours a wide range of climatic and environmental conditions as well as diverse farmer preferences and pearl millet utilization habits which have the potential to lead to local adaptation and thereby to population structure. The objectives of our research were to (i) assess the geographical distribution of genetic diversity in pearl millet inbreds derived from landraces, (ii) assess the population structure of pearl millet from WCA, and (iii) identify those geographical parameters and environmental factors from the location at which landraces were sampled, as well as those phenotypic traits that may have affected or led to this population structure. Our study was based on a set of 145 inbred lines derived from 122 different pearl millet landraces from WCA. 相似文献16.
Elisabeth?A. Rosenthal Jane Ranchalis David?R. Crosslin Amber Burt John?D. Brunzell Arno?G. Motulsky Deborah?A. Nickerson NHLBI GO Exome Sequencing Project Ellen?M. Wijsman Gail?P. Jarvik 《American journal of human genetics》2013,93(6):1035-1045
Hypertriglyceridemia (HTG) is a heritable risk factor for cardiovascular disease. Investigating the genetics of HTG may identify new drug targets. There are ∼35 known single-nucleotide variants (SNVs) that explain only ∼10% of variation in triglyceride (TG) level. Because of the genetic heterogeneity of HTG, a family study design is optimal for identification of rare genetic variants with large effect size because the same mutation can be observed in many relatives and cosegregation with TG can be tested. We considered HTG in a five-generation family of European American descent (n = 121), ascertained for familial combined hyperlipidemia. By using Bayesian Markov chain Monte Carlo joint oligogenic linkage and association analysis, we detected linkage to chromosomes 7 and 17. Whole-exome sequence data revealed shared, highly conserved, private missense SNVs in both SLC25A40 on chr7 and PLD2 on chr17. Jointly, these SNVs explained 49% of the genetic variance in TG; however, only the SLC25A40 SNV was significantly associated with TG (p = 0.0001). This SNV, c.374A>G, causes a highly disruptive p.Tyr125Cys substitution just outside the second helical transmembrane region of the SLC25A40 inner mitochondrial membrane transport protein. Whole-gene testing in subjects from the Exome Sequencing Project confirmed the association between TG and SLC25A40 rare, highly conserved, coding variants (p = 0.03). These results suggest a previously undescribed pathway for HTG and illustrate the power of large pedigrees in the search for rare, causal variants. 相似文献
17.
MAŁGORZATA OŻGO 《Biological journal of the Linnean Society. Linnean Society of London》2011,102(2):251-262
The present study reports on a natural experiment with twelve replicates in which rapid, predictable and consistent divergence of Cepaea nemoralis populations occurred in response to repeated selection gradient of adjacent open and shaded habitats. Because the frequencies of various genetically‐based phenotypes varied widely among surveyed populations, and there was a large overlap between habitat types, no overall association with habitat was apparent. In paired comparisons, however, significant changes were consistently towards higher frequencies of light morphs in the open than corresponding shaded habitats, and this result is attributable to natural selection. This shows that the knowledge of the genetic composition of reference populations is often essential for discerning selection from random processes. At each site, a different morph combination contributed to the divergence of populations, indicating that there are many genetic solutions to similar ecological problems; this likely enhances the maintenance of high levels of polymorphism. Adaptation of populations occurred in contemporary time and was fast. In one case where it was possible to follow changes, significant shifts in morph frequencies occurred within just two snail generations (selection coefficients of 0.404 and 0.518). High evolvability may be one of the factors contributing to the ecological success of Cepaea nemoralis. © 2011 The Linnean Society of London, Biological Journal of the Linnean Society, 2011, 102 , 251–262. 相似文献
18.
MAŁGORZATA OŻGO ZDZISŁAW BOGUCKI 《Biological journal of the Linnean Society. Linnean Society of London》2011,104(2):462-470
At the eastern margins of the geographical distribution in Europe, populations of Cepaea nemoralis are sparse and limited to urban environments to which they are possibly confined by relatively warmer climates. In 1999 we introduced 1101 C. nemoralis individuals originating from nine urban populations to a rural location in the area. The snails established a viable population, which suggests that confinement to urban settings is dispersal‐ rather than climate‐limited. The snails filled available habitats at a rate of approximately 400–600 m2 year?1. On the whole, morph frequencies remained remarkably stable; changes that occurred are attributable to segregation of alleles or chromosomes. However, snails responded to habitat heterogeneity: consistent and predictable divergence occurred between habitat types, such that light‐shelled snails were repeatedly more frequent in the open than in adjoining shaded habitats. This suggests the operation of climatic and/or visual selection. As the whole area encompassing seven distinct habitat patches was only 0.3 ha, and the maximum duration of population divergence was only 11 years (fewer than four snail generations), these results indicate extremely small temporal and spatial scales of adaptation during initial phases of population establishment and spread. © 2011 The Linnean Society of London, Biological Journal of the Linnean Society, 2011, 104 , 462–470. 相似文献
19.
Adebola AJ Raji James V Anderson Olufisayo A Kolade Chike D Ugwu Alfred GO Dixon Ivan L Ingelbrecht 《BMC plant biology》2009,9(1):118-11
Background
Cassava (Manihot esculenta Crantz), a starchy root crop grown in tropical and subtropical climates, is the sixth most important crop in the world after wheat, rice, maize, potato and barley. The repertoire of simple sequence repeat (SSR) markers for cassava is limited and warrants a need for a larger number of polymorphic SSRs for germplasm characterization and breeding applications. 相似文献20.
Margarethe Biong Inger T Gram Ilene Brill Fredrik Johansen Hiroko K Solvang Grethe IG Alnaes Toril Fagerheim Yngve Bremnes Stephen J Chanock Laurie Burdett Meredith Yeager Giske Ursin Vessela N Kristensen 《BMC medical genomics》2010,3(1):1-13