Development of a multi-species quantitative trait loci database and a system for annotation of genes and QTL: QTL MatchMaker

After the sequencing of the human genome, finding the underlying causes of physiological and disease traits presents one of the biggest challenges to researchers. A lot of effort is focused on the mapping of loci containing alleles affecting the expression of phenotypic traits. Despite the success in defining QTL, finding the genes controlling these traits is still a difficult task.

In order to approach this problem we have developed a database of quantitative trait loci from humans and rodents and analysis software named QTL MatchMaker. QTL MatchMaker is available at http://pmrc.med.mssm.edu:9090/QTL/jsp/qtlhome.jsp. This web-based application compiles data from many sources (Pub Med, RGD, MGD, UCSC Genome Browser, EntrezGene) and allows users to analyze their genes of interest in the context of genetic traits. QTL MatchMaker maps GenBank accession numbers and mRNA RefSeq numbers against a curated quantitative trait loci database and reports whether a gene is located inside a QTL. In addition QTL MatchMaker reports predicted orthologs of the candidate gene and provides information on the QTL and the gene located inside it. As a result users can find out if a gene of interest is located in QTL across all three species.

QTL MatchMaker is used at present for co-localizing transcripts culled from microarray experiments to physiologically related QTL in mouse, rat and human. The Cross Species search page maps genesets from transcriptome analysis of human diseases to related rodent QTL allowing for prioritization of the candidate genes. Another use of this software is mapping of genes identified in mutagenesis screens to QTL. If a mutated gene results in a phenotype similar to the QTL trait and the gene maps inside the QTL, this gene becomes a likely candidate for controlling the quantitative variation in the trait of interest. The QTL MatchMaker appears in the January, 2006 database issue of Nucleic Acids Research.

SYSTEMS BIOLOGY, TOXICOGENOMICS, AND DRUG DISCOVERY USING RATS

July 17-18, 2006
Medical College of Wisconsin, Milwaukee, WI

PhysGen Program for Genomic Applications and PhysioGenix (http://ratresources.com) invite you to participate in this two-day workshop covering the use of rat models in understanding complex diseases, phenotyping strategies to link biology to the genome, available bioinformatics resources, and strategies for effective study design. Lectures and hands-on computer tutorials will introduce the participants to available tools and resources to attach physiological traits to the genome to allow for drug discovery and assessment.

The goal of this conference is to provide scientists with state of the art approaches using rat models to design studies that will enhance the understanding of complex diseases with drug discovery as the ultimate goal. The participants will be introduced to novel approaches aimed at understanding the genetic contribution of complex diseases involving heart, lung, blood and sleep. This conference is appropriate for scientists studying the underlying mechanisms of complex diseases and interested in using novel rat models to identify pathways and genes to enhance drug discovery.

Registration deadline: June 12, 2006


For complete information and registration contact: mrdwinel@mcw.edu


Meeting organizers:
Mindy Dwinell, Ph.D., Medical College of Wisconsin (mrdwinel@mcw.edu)
Annette Dahly-Vernon, Ph.D., PhysioGenix, Inc. (avernon@physiogenix.com)

For further information: http://pga.mcw.edu

New Related Structures Link from Proteins in Entrez

One of the first steps in modeling the 3D structure of a protein is to find solved structures of proteins that have a high degree of sequence similarity to a target sequence. Because only about 1% of the protein sequences in the Entrez protein database are derived from protein structures, it will usually be necessary to find sequence-related structures in order to link a protein to a 3D structure. Entrez now displays new Related Structures links that perform this function with a single click of the mouse. Each protein sequence in Entrez Protein that has a BLAST hit to a structure-derived sequence now has a Related Structure link in the Links menu to the right of the record in the Entrez display; almost 36% of the 7.3 million protein sequences in Entrez have such links. Following this link displays the BLAST alignments of the related structures to the query either graphically or as a table, and these results can be sorted by BLAST score, E-value, aligned length, or sequence identity. Clicking on any of the alignment bars displays a detailed pairwise alignment and allows the alignment to be loaded into Cn3D for viewing. Figure 1 displays the non-identical related structures to NP_690059, the NCBI RefSeq for coagulation factor VII in rat. Sequence-similar structures align to both the catalytic heavy chain and the calcium-binding light chain of the protein. Figure 2 shows alignment of the query to 1KLI_H, the heavy chain of the human homolog displayed in Cn3D.

Full article access with figures

Source: NCBI News

Rat whiskers lead to brain map

Neuroscientists at the McGovern Institute for Brain Research at MIT have discovered an exquisite micro-map of the brain. It's the size of the period at the end of this sentence, and it's in a most unexpected place -- connected to the whiskers on a rat's face.
Based on discoveries in primates and cats, scientists previously thought that highly refined maps representing the complexities of the external world were the exclusive domain of the visual cortex in mammals. This new map is a miniature schematic, representing the direction a whisker is moved when it brushes against an object.
" This study is a great counter example to the prevailing view that only the visual cortex has beautiful, overlapping, multiplexed maps," said Christopher Moore, a principal investigator at the McGovern Institute and an assistant professor in the Department of Brain and Cognitive Sciences, where he holds the Mitsui Career Development Chair. A paper on the work appeared online in Nature Neuroscience on March 20.
Scientists are interested in studying how fine-scale visual maps develop in the brain and process information as part of their effort to understand how mental illnesses, strokes or epilepsy affect the cortex. But the standard workhorse for studying how brains develop, the rodent, evolved to spend its time underground in dark tunnels, and it lacks such visual maps. Rats instead use their whiskers to navigate.
" Our finding suggests that high-resolution sensory maps that can quickly and accurately handle many different kinds of sensory features are an essential hallmark of high sensory acuity, in whatever mode of perception is most important to the animal," Moore said. "It makes sense that mammals develop intricate sensory maps in the sensory system that is crucial for them -- like vision is for us or the whisker system is for rodents."

Read Full Article

This article from MIT Tech Talk, March 22, 2006
URL:http://web.mit.edu/newsoffice/2006/whiskers.html

Picower researcher explains how rats think

After running a maze, rats mentally replay their actions -- but backward, like a film played in reverse, a researcher at the Picower Institute for Learning and Memory at MIT reports Feb. 12 in the advance online edition of Nature.
In 2001, Matthew A. Wilson, a professor in the Department of Brain and Cognitive Sciences, reported that animals have complex dreams and are able to retain and recall long sequences of events while asleep. Like people, rats go through multiple stages of sleep, from slow-wave sleep to REM sleep.
Slow-wave sleep, also referred to as non-REM sleep, makes up a large fraction of the normal sleep cycle and occurs earlier than REM sleep. REM sleep, which takes its name from the rapid eye movements that occur during this type of sleep, is associated with dreaming.
Wilson found that during slow-wave sleep, animals replayed spatial experiences in the same order they were experienced.
His latest results show that, following a spatial experience such as running laps on a track, the awake animal replays the memory so precisely that its recorded brain activity corresponds exactly to the places it has just been. However, to the researchers' surprise, the episode is replayed in time-reverse order, with the most recent locations first, proceeding sequentially back to the beginning of the task.
This backward instant replay may play a significant role in reinforcing learning, Wilson said. "Understanding this replay is likely to be critical in understanding how animals -- and humans -- learn from experience. This phenomenon may constitute a general mechanism of learning and memory."

Read Full Article

This article from MIT Tech Talk, February 15, 2006
URL:http://web.mit.edu/newsoffice/2006/instant-replay.html

RGD in the Community

Upcoming RGD Activities:

Victoria Petri, PhD, and Jennifer Smith, MS, Scientific Curators at RGD, will attend the GO Annotation Camp, July 10-14, 2006 at Stanford University.

Howard Jacob, PhD, RGD PI and Anne Kwitek, PhD, RGD co-PI, will both be distinguished speakers at the upcoming Systems Biology, Toxicogenomics and Drug Discovery Conference.

The Rat Genome Database will participant at the upcoming ISMB Meeting, Aug. 6-10, 2006 in Fortaleza, Brazil.

Recent RGD Activities:

Victoria Petri, PhD, Scientific Curator at RGD, attended the Biology of Genomes conference and presented a poster entitled: “Pathway Ontology (PW) - a new controlled vocabulary developed at The Rat Genome Database.”

RGD and PhysGen recently hosted a booth entitled “Rat Physiological Genomic Tools” at the Experimental Biology Meeting 2006 in San Francisco, CA.

Facts and Functions of RGD

The RGD User Request System

Users are encouraged to contact RGD with any comments or questions regarding the website’s contents, functions or appearances via the RGD User Request form.

The User Request form is accessible on the RGD homepage, by clicking “Contact Us” under the “Help” header. Most subsequent RGD page headers also contain a “Contact ” link that directs you to the RGD User Request form.

To ensure prompt and thorough answers please be detailed and specific with comments and requests.

If you are reporting an error encountered while using RGD, please include the following information in your user request:

· What tool or data type were you accessing?
· What version of the tool were you accessing (If applicable)?
· What were the specific parameters entered into the tool?
· What did or did not occur when you entered your parameters?
· What operating System are you using?
· What browser are you using?

Providing the above information should allow RGD to replicate the error and quickly resolve the issue.

We thank you in advance for utilizing the RGD User Request System. Your participation and input will allow RGD to become an even greater resource for information.

If you would like to see a particular tool or data type featured in a future installment of “Facts and Functions of RGD”, please send your idea to newsletter@rgd.mcw.edu

RGD Resources:

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