R W Williams

..This heritability varies greatly. We have tested heritability-weighted averages to define expression of a transcript and found that these allow detection of more QTLs than previously described methods...

..In the current studies, the online GeneNetwork system was employed to further probe P2P-R biological functions. Molecular studies were then performed to confirm the GeneNetwork evaluations...

..We analyzed variation in striatal volume and neuron number in mice and initiated a complex trait analysis to discover polymorphic genes that modulate the structure of the basal ganglia...

..Cytochrome oxidase labeling was used to visualize barrels within the PMBSF...

..Here we use unbiased stereological techniques to map quantitative trait loci (QTLs) that modulate the volume of neocortex...

..We also required verification of mRNA abundance by an independent method, and finally we required either differences in protein levels or confirmed DNA sequence differences...

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..elegans, and Drosophila, mouse RI panels typically consist of fewer than 30 lines. This is a severe constraint on the power and precision of mapping efforts and greatly hampers analysis of epistatic interactions...

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..These models will also be essential to test new treatments in a robust systems context that accounts for genetic variation...

..In contrast to the first two QTLs, B6 alleles at these two loci decrease bulb weight by 0.5-1.0 mg. Collectively, the four loci account for 20% of the phenotypic variance in bulb weight...

..They have proved particularly effective in multidisciplinary genetic studies. Widespread use of RI strains has been hampered by their modest numbers and by the difficulty of combining results derived from different RI sets...

..The QTLs we have discovered are among the first loci shown to modulate the size and architecture of the adult mouse cerebellum...

..Using WebQTL's extensive database of published BXD phenotypes, we also detected a strong and potentially biologically meaningful correlation between hippocampal volume and the acoustic startle response...

..The Hipp gene loci modulate neuron number in the dentate gyrus, collectively shifting the population up or down by as much as 200,000 cells. Candidate genes for the Hipp loci include Rxrg and Fgfr3...

..Rara is of particular interest because this gene is a candidate for Nnc1, a QTL that controls retinal ganglion cell proliferation...

..Our data provide strong evidence that variation in the Per3 transcript is causally associated with and also responsive to stress and alcohol...

..Each receptor is expressed in the retina during development, and their ligands affect the proliferation or survival of retinal cells...

..SNPs that distinguish between the two progenitor strains were used to further winnow the list of candidate modulators. Bayesian network was then used to identify the genetic modulatory relations that best explain the microarray data...

..The genetic basis of variation in eye size in mice was explored, and genes that modulate eye weight, lens weight, and retinal area were mapped...

..In this article, the authors present adult and developmental studies on the retinal phenotype in Bst/+ mice...

..One of the validated genes, the hemolytic complement gene, affected virus titer 7 days after infection. We conclude that H5N1 influenza virus-induced pathology is affected by a complex and multigenic host component...

..The analysis also suggests that dark phase and light phase responses are regulated by different genetic factors...

..Our analysis revealed a highly complex gene expression regulatory interval in Qrr1, composed of multiple loci modulating the expression of functionally cognate sets of genes...

..These studies demonstrate that the albino mutation acts indirectly upon retinal ganglion cells, which in turn respond by making axonal guidance errors at the optic chiasm...

..33; p < 0.01). We conclude that numbers of these two functionally coupled neuron populations are modulated over a wide range by independent genetic and developmental mechanisms...

..Using a systems genetics approach we show that two validated cis-modulated genes, Stk25 and Rasd2, are likely to control expression of downstream targets and affect disease susceptibility...

..Probabilities of linkage were not sufficient for declaration of a quantitative trait locus for REMS but were sufficient to warrant further analysis either with additional RI strains or with F2 panels...

..Probabilities of linkage were not sufficient for declaration of an activity-related quantitative trait locus but were sufficient to warrant further analysis either with additional RI strains or with F2 panels...

..Here we review this approach and give three specific examples of how genes with well-defined functions in retinal development are being mapped and characterized...

..Mice from each of these pedigrees of mutant mice are available for distribution to researchers for independent study...

..Using genome wide PCR analysis, we found that a single major QTLs, Mptp1, located near the distal end of chromosome 1 between D1Mit113 and D1Mit293, accounts for the majority of the strain sensitivity to MPTP...

..Finally, we embed these methods in a hypothetical line of cerebellar research to illustrate the vast potential of combining complex trait analysis with a systems neuroscience perspective...

..Our results show that the combination of gene eQTL mapping and phenotypic spectrum analysis may provide a valuable approach to uncovering gene regulatory relations underlying mammalian phenotypes...

..This study is an important first step in identifying genetic factors underlying tongue size, papillae size, and papillae number using QTL analysis...

..Collectively, our data support a model in which genetic variation in glutamatergic neuroplasticity in corticolimbic circuitry underlies phenotypic variation in responsivity to stress...

..nervenet.org/genome_mixer/. GenomeMixer can be compiled on any system with support for the Trolltech Qt toolkit, including Windows...

..The first QTL is located on Chromosome (Chr) 17, near or proximal to H2. The second QTL is located on Chr 6 in a region spanning the Tcrb and Cd8a loci...

..Other candidates include Large, and Thra. Responses to drugs of abuse and locomotor activity were the most notable behavioral correlates of the BLAc traits...

..It is a resource for studying PolymiRTSs and their implications in phenotypic variations. PolymiRTS database can be accessed at http://compbio.utmem.edu/miRSNP/...

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..This strategy integrates gene-phenotype relations from decades of experimental mutagenesis studies and new genomic resources to provide an approach to rapidly expand knowledge on genetic loci modulating phenotypes...

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..Indeed, this process appears to be influenced by a wide variety of genetic and environmental factors. In this study we explored the genetic basis for differences in ganglion cell death in two inbred strains of mice...

..This work provides support for the role of CD81 in the regulation of astrocyte and microglial number, perhaps by regulating cell proliferation by a contact inhibition-dependent mechanism...

..We examined the causes of expression differences, and in their linkage to sequence variants, functional differences, and ocular pathophysiology...

..The critical problem with naïve mapping approaches in AIL populations is that the individual is not an exchangeable unit...

..Many phenotypes are now associated with enough mapping data that meta-analysis could help refine locations of known QTLs and detect many novel QTLs...

..Herein we present its retinal phenotype and genetic basis...

..This study represents the first description of a RNA target for mammalian Puf proteins and the first molecular confirmation of information obtained using the WebQTL database...

..We also have fine-mapped the mutation, ldis1 (lens disrupter 1), and have evaluated positional candidate genes...

..By repeatedly studying the same panel of mice, early data can be re-examined in light of technological advances unforeseen at the time of their initial collection...

..The present study defines genomic loci underlying coordinate changes in gene expression following retinal injury...

..Finally, we note that while trans-acting QTL do not replicate well between data sets in general, at least one cluster of trans-acting QTL on distal Chr 1 is notably preserved between data sets...

..Data indicate that these p47 GTPases have cell-autonomous effects that result in vastly different inflammatory stimulations, leading to either recovery or death...

..We built these tools into an open web resource called WebQTL that can be used to test a broad array of hypotheses...

..By using the Molecular Genetics of Schizophrenia data set, we were able to test and confirm that markers in NRXN1 and GSK3B have epistatic interactions in human populations that can jointly modulate risk of schizophrenia...

..The consistent effect of null alleles at tyrosinase suggests a comparably tight linkage between the biochemical activity of this enzyme and the mechanisms that control decussation phenotype...

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..Despite a host of drastic abnormalities at all level of the visual system, from retina to cortex, this animal was behaviorally indistinguishable from normal dogs and did not have any detectable oculomotor abnormalities...

..J. Hitzemann, and (5) The use of gene arrays in conjunction with transgenic and selected animals to understand anxiety in alcoholism, by. B. Tabakoff...

..This study identifies the key sequence variant that leads to differences in Comt mRNA and protein levels among mice, and that modulates synaptic function and pharmacological and behavioral traits...

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..Our goal is efficient service to INIA and NIAAA investigators. ..

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..All of these data are being integrated into a sophisticated and universally accessible database available on the World Wide Web at nervenet.org. ..

..Understanding how different QTLs affect different parts of the eye will ultimately contribute to a far better understanding of molecular and developmental mechanisms associated with eye growth in humans. ..