The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform
Eric S. Lander - One of the best experts on this subject based on the ideXlab platform.
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Genetic Dissection of Complex Traits with Chromosome Substitution Strains of Mice
Science, 2004Co-Authors: Jonathan Singer, Annie E. Hill, Lindsay C. Burrage, Keith R. Olszens, Junghan Song, Monica J. Justice, William E. O'brien, David V. Conti, John S. Witte, Eric S. LanderAbstract:Chromosome substitution strains (CSSs) have been proposed as a simple and powerful way to identify quantitative trait loci (QTLs) affecting developmental, physiological, and behavioral processes. Here, we report the construction of a complete CSS panel for a vertebrate species. The CSS panel consists of 22 mouse strains, each of which carries a single chromosome substituted from a donor strain (A/J) onto a common host background (C57BL/6J). A survey of 53 traits revealed evidence for 150 QTLs affecting serum levels of sterols and amino acids, diet-induced obesity, and anxiety. These results demonstrate that CSSs greatly facilitate the detection and identification of genes that control the wide diversity of naturally occurring phenotypic variation in the A/J and C57BL/6J inbred strains.
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Analysing complex genetic traits with chromosome substitution strains
Nature Genetics, 2000Co-Authors: Joseph H. Nadeau, Angabin Matin, Jonathan Singer, Eric S. LanderAbstract:Many valuable animal models of human disease are known and new models are continually being generated in existing inbred strains,. Some disease models are simple mendelian traits, but most have a polygenic basis. The current approach to identifying quantitative trait loci (QTLs) that underlie such traits is to localize them in crosses, construct congenic strains carrying individual QTLs, and finally map and clone the genes. This process is time-consuming and expensive, requiring the genotyping of large crosses and many generations of breeding. Here we describe a different approach in which a panel of chromosome substitution strains (CSSs) is used for QTL mapping. Each of these strains has a single chromosome from the donor strain substituting for the corresponding chromosome in the host strain. We discuss the construction, applications and advantages of CSSs compared with conventional crosses for detecting and analysing QTLs, including those that have weak phenotypic effects.
Leonid Kruglyak - One of the best experts on this subject based on the ideXlab platform.
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finding the sources of missing heritability in a yeast cross
Nature, 2013Co-Authors: Joshua S Bloom, Ian M. Ehrenreich, Leonid Kruglyak, Thuylan Vo LiteAbstract:In a cross between two yeast strains, detected loci are found to explain nearly the entire additive contribution to heritable variation for a number of quantitative traits. Genome-wide studies have yielded important insights into the genetic basis of human disease but the identified loci explain only a minority of the heritable contribution to trait variation. In search of this 'missing heritability', Leonid Kruglyak and colleagues use a large cross between two yeast strains to analyse 46 quantitative traits in great detail. They find that the underlying loci explain nearly the entire additive contribution to heritable variation for these traits. Depending on the trait, the contribution to heritability of gene–gene interactions varies from near zero to 50%. This result implies that when a sufficiently powerful study is carried out, much of the 'missing' heritability is revealed and the remaining missing component arises primarily from many loci with small but not infinitesimal effects. For many traits, including susceptibility to common diseases in humans, causal loci uncovered by genetic-mapping studies explain only a minority of the heritable contribution to trait variation. Multiple explanations for this ‘missing heritability’ have been proposed1. Here we use a large cross between two yeast strains to accurately estimate different sources of heritable variation for 46 quantitative traits, and to detect underlying loci with high statistical power. We find that the detected loci explain nearly the entire additive contribution to heritable variation for the traits studied. We also show that the contribution to heritability of gene–gene interactions varies among traits, from near zero to approximately 50 per cent. Detected two-locus interactions explain only a minority of this contribution. These results substantially advance our understanding of the missing heritability problem and have important implications for future studies of complex and quantitative traits.
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genetic architecture of highly complex chemical resistance traits across four yeast strains
PLOS Genetics, 2012Co-Authors: Ian M. Ehrenreich, Joshua S Loom, Noorossada Torabi, Xin Mei Wang, Yue Jia, Leonid KruglyakAbstract:Many questions about the genetic basis of complex traits remain unanswered. This is in part due to the low statistical power of traditional genetic mapping studies. We used a statistically powerful approach, extreme QTL mapping (X-QTL), to identify the genetic basis of resistance to 13 chemicals in all 6 pairwise crosses of four ecologically and genetically diverse yeast strains, and we detected a total of more than 800 loci. We found that the number of loci detected in each experiment was primarily a function of the trait (explaining 46% of the variance) rather than the cross (11%), suggesting that the level of genetic complexity is a consistent property of a trait across different genetic backgrounds. Further, we observed that most loci had trait-specific effects, although a small number of loci with effects in many conditions were identified. We used the patterns of resistance and susceptibility alleles in the four parent strains to make inferences about the allele frequency spectrum of functional variants. We also observed evidence of more complex allelic series at a number of loci, as well as strain-specific signatures of selection. These results improve our understanding of complex traits in yeast and have implications for study design in other organisms.
Daniel R Noguera - One of the best experts on this subject based on the ideXlab platform.
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genome enabled insights into the ecophysiology of the comammox bacterium candidatus nitrospira nitrosa
mSystems, 2017Co-Authors: Pamela Y Camejo, Jorge Santo W Domingo, Katherine D Mcmahon, Daniel R NogueraAbstract:ABSTRACT The recently discovered comammox bacteria have the potential to completely oxidize ammonia to nitrate. These microorganisms are part of the Nitrospira genus and are present in a variety of environments, including biological nutrient removal (BNR) systems. However, the physiological traits within and between comammox and nitrite-oxidizing bacterium (NOB)-like Nitrospira species have not been analyzed in these ecosystems. In this study, we identified Nitrospira strains dominating the nitrifying community of a sequencing batch reactor (SBR) performing BNR under microaerobic conditions. We recovered metagenome-derived draft genomes from two Nitrospira strains: (i) Nitrospira sp. strain UW-LDO-01, a comammox-like organism classified as “ Candidatus Nitrospira nitrosa,” and (ii) Nitrospira sp. strain UW-LDO-02, a nitrite-oxidizing strain belonging to the Nitrospira defluvii species. A comparative genomic analysis of these strains with other Nitrospira -like genomes identified genomic differences in “ Ca . Nitrospira nitrosa” mainly attributed to each strain’s niche adaptation. Traits associated with energy metabolism also differentiate comammox from NOB-like genomes. We also identified several transcriptionally regulated adaptive traits, including stress tolerance, biofilm formation, and microaerobic metabolism, which might explain survival of Nitrospira under multiple environmental conditions. Overall, our analysis expanded our understanding of the genetic functional features of “ Ca . Nitrospira nitrosa” and identified genomic traits that further illuminate the phylogenetic diversity and metabolic plasticity of the Nitrospira genus. IMPORTANCE Nitrospira -like bacteria are among the most diverse and widespread nitrifiers in natural ecosystems and the dominant nitrite oxidizers in wastewater treatment plants (WWTPs). The recent discovery of comammox-like Nitrospira strains, capable of complete oxidation of ammonia to nitrate, raises new questions about specific traits responsible for the functional versatility and adaptation of this genus to a variety of environments. The availability of new Nitrospira genome sequences from both nitrite-oxidizing and comammox bacteria offers a way to analyze traits in different Nitrospira functional groups. Our comparative genomics analysis provided new insights into the adaptation of Nitrospira strains to specific lifestyles and environmental niches. Author Video : An author video summary of this article is available.
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genome enabled insights into the ecophysiology of the comammox bacterium candidatus nitrospira nitrosa
bioRxiv, 2017Co-Authors: Pamela Y Camejo, Jorge Santo W Domingo, Katherine D Mcmahon, Daniel R NogueraAbstract:The recently discovered comammox bacteria have the potential to completely oxidize ammonia to nitrate. These microorganisms are part of the Nitrospira genus and are present in a variety of environments, including Biological Nutrient Removal (BNR) systems. However, the physiological traits within and between comammox- and nitrite oxidizing bacteria (NOB)-like Nitrospira species have not been analyzed in these ecosystems. In this study, we identified Nitrospira strains dominating the nitrifying community of a sequencing batch reactor (SBR) performing BNR under micro-aerobic conditions. We recovered metagenomes-derived draft genomes from two Nitrospira strains: (1) Nitrospira sp. UW-LDO-01, a comammox-like organism classified as Candidatus Nitrospira nitrosa, and (2) Nitrospira sp. UW-LDO-02, a nitrite oxidizing strain belonging to the Nitrospira defluvii species. A comparative genomic analysis of these strains with other Nitrospira -like genomes identified genomic differences in Ca. Nitrospira nitrosa mainly attributed to each strains9 niche adaptation. Traits associated with energy metabolism also differentiate comammox from NOB-like genomes. We also identified several transcriptionally regulated adaptive traits, including stress tolerance, biofilm formation and micro-aerobic metabolism, which might explain survival of Nitrospira under multiple environmental conditions. Overall, our analysis expanded our understanding of the genetic functional features of Ca. Nitrospira nitrosa, and identified genomic traits that further illuminate the phylogenetic diversity and metabolic plasticity of the Nitrospira genus.
Wahyu W Pandoe - One of the best experts on this subject based on the ideXlab platform.
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temperature and salinity variability in the exit passages of the indonesian throughflow
Deep-sea Research Part Ii-topical Studies in Oceanography, 2003Co-Authors: Janet Sprintall, Susan L Hautala, James T Potemra, Nancy A Bray, Wahyu W PandoeAbstract:Abstract The Indonesian Throughflow was monitored from December 1995 until May 1999 in the five major exit passages of the Lesser Sunda Islands, as it flows from the Indonesian interior seas into the southeast Indian Ocean. The monitoring array included pairs of shallow pressure gauges at each side of the Straits, equipped with temperature and salinity sensors. As in the inferred geostrophic velocity from the cross-strait pressure gauge data, the temperature and salinity data show strong variability over all time scales related to the local regional and remote forcing mechanisms of heat, freshwater and wind. The annual cycle dominates the temperature time series, with warmest temperatures occurring during the austral summer northwest monsoon, except in Lombok Strait where the semi-annual signal is dominant, and related to the Indian Ocean westerly wind-forced Kelvin waves during the monsoon transitions that supply Indian Ocean warmer surface water to the strait. In the salinity data, the annual signal again dominates the time series in all Straits, with a distinct freshening occurring in March–May. This is partly related to the rainfall and resultant voluminous river runoff impacting the region, one month after the wetter northwest monsoon ends in March. The fresh, warm water from the monsoon-transition Indian Ocean Kelvin wave also contributes to the freshening observed in May. There is little cross-strait gradient in near-surface temperature and salinity through the outflow Straits, except in Lombok Strait, where Lombok is warmer (except during the northwest monsoon) and fresher than the Bali site (especially during March through May). A fortnightly signal in temperature is found in Ombai and Sumba Straits, and is probably related to the proximity of these Straits to the interior Banda Sea where the fortnightly tidal signal is strong. The fortnightly signal is also evident at the Bali site, although not at the Lombok site. Numerous ADCP surveys taken during the survey period suggest a western intensification of the flow through Lombok Strait, such that the Bali site also may be more influenced by the internal Indonesian seas. Finally, there is regional variability in temperature and salinity on interannual time scales. From mid-1997 through early 1998, the region is cooler and saltier than normal. These property changes are related to both the strong 1997–1998 El Nino event in the Pacific, and the strong 1997 Dipole Mode in the Indian Ocean, which together can result in lower regional precipitation; lower transport of the fresh, warm Throughflow water; and changes in the upwelling regime along the Lesser Sunda Island chain. From mid-1998 on, warmer conditions returned to the region probably related to the La Nina event.
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velocity structure and transport of the indonesian throughflow in the major Straits restricting flow into the indian ocean
Journal of Geophysical Research, 2001Co-Authors: Susan L Hautala, Janet Sprintall, James T Potemra, Jackson Chong, Wahyu W Pandoe, Nan Bray, Gani A IlahudeAbstract:An array of shallow pressure gauge pairs is used to determine shallow geostrophic flow relative to an unknown mean velocity in the five principal Straits that separate the eastern Indian Ocean from the interior Indonesian seas (Lombok Strait, Sumba Strait, Ombai Strait, Savu/Dao Straits, and Timor Passage). Repeat transects across the Straits over several tidal cycles with a 150-kHz acoustic Doppler current profiler were made during three separate years, and provide a first look at the lateral and vertical structure of the upper throughflow in these Straits as well as a means of "leveling" the pressure gauge data to determine the mean shallow velocity and provide transport estimates. We estimate a total 2-year average transport for 1996 -1997 through Lombok, Ombai, and Timor Straits as 8.4 3.4 Sv toward the Indian Ocean. The flow structure in the upper 200 m is seen to be similar in Lombok, Sumba, and Ombai Straits, with a division into two layers, governed by different dynamics, where the upper layer episodically flows away from the Indian Ocean. Laterally, flow tends to be strongest in the deepest parts of the channel, with the exception of Lombok Strait which shows a consistent intensification of flow toward the western side. Eastward flowing northern boundary currents in Sumba and Ombai Straits suggest that the South Java Current may penetrate to the Banda Sea, farther eastward than previously documented. Although additional observations are required for a conclusive comparison, the estimated transport time series suggest differences in timing of outflow into the Indian Ocean relative to inflow from the Pacific of a size that could significantly impact the Banda Sea thermocline structure.
Fergal Ogara - One of the best experts on this subject based on the ideXlab platform.
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traits of fluorescent pseudomonas spp involved in suppression of plant root pathogens
Microbiological Research, 1992Co-Authors: Daniel J Osullivan, Fergal OgaraAbstract:Certain members of the fluorescent pseudomonad group have been shown to be potential agents for the biocontrol of plant root diseases. The major problems with the commercialization of these beneficial strains are that few wild-type strains contain all the desired characteristics for this process and the performance of strains in different soil and climatic conditions is not reproducible. Consequently, prior to selection and/or improvement of suitable strains for biocontrol purposes, it is necessary to understand the important traits required for this purpose. The production of fluorescent siderophores (iron-binding compounds) and antibiotic compounds has been recognized as important for the inhibition of plant root pathogens. Efficient root colonization is also a prerequisite for successful biocontrol strains. This review discusses some of the characteristics of fluorescent pseudomonads that have been suggested to be important for biocontrol. The genetic organization and regulation of these processes is also examined. This information is necessary for attempts aimed at the improvement of strains based on deregulating pathways or introducing traits from one strain to another. The release of genetically engineered organisms into the environment is governed by regulations, and this aspect is summarized. The commercialization of fluorescent pseudomonads for the biological control of plant root diseases remains an exciting possibility. The understanding of the relevant characteristics will facilitate this process by enabling the direct selection and/or construction of strains which will perform under a variety of environmental conditions.
