The Role of the Genome Project in
Determining Gene Function: Insights from Model Organisms G.L.G. Miklos and G.M. Rubin Cell (1996) 86:521 - 529
If the model organism genome projects are to be maximally useful in assigning functions to human DNA sequences, they will need to utilize the powerful tools for
determining gene function that are available to them so that not only the sequences of the genes, but also their biological functions, are determined.
Two projects will be done jointly with the Karolinska Institute in Stockholm: Molecular biologist David Baillie of Simon Fraser University in Burnaby, British Columbia, was awarded $ 6.73 million to study protein function in the soil nematode Caenorhabditis elegans, and microbiologist Sherif Abou Elela of the University of Sherbrooke, Quebec, received $ 3.75 million to test modified nucleic acid technologies for
determining gene function.
The article published on the journal Molecular Biology and Evolution provides the framework for posing new hypotheses on the phylogenetic relations among poriferans,
determining gene function in sponges and the early evolution of molecular complexity in metazoans.
Using adipose samples from their previous studies, McNamara, Sumner and the Kemin team extracted the RNA and ran microchip array analyses to
determine gene function.
3:15 PM Yeast / zebrafish: Genetic models to
determine gene function and a potential therapy for an inherited anemia.
Not exact matches
After
determining the proper dosage of tamoxifen — an early trial resulted in a number of mouse deaths due to overactivation of Mecp2 — researchers settled on a four - week regimen of ramping up the
gene's
function.
Epigenetic tags help tell
genes — stretches of DNA that act as biological instruction manuals — when to switch «on» and «off,» ultimately
determining cell type and
function.
To
determine the effect of mutations that reduce TET2
function in abnormal stem cells, the research team genetically engineered mice such that the scientists could switch the TET2
gene on or off.
«We used the Allen Human Brain Atlas data to quantify how consistent the patterns of expression for various
genes are across human brains, and to
determine the importance of the most consistent and reproducible
genes for brain
function.»
«The power of this study is that we looked at
genes discovered to be over-expressed in patients» tumors and
determined their
function in kidney cancer, which has not been done on a large scale before,» he says.
Traditionally,
gene function was
determined one
gene at a time, but today's microarray technology enables scientists to monitor the expression of tens of thousands of
genes on a single glass slide.
The researchers developed a computational framework to
determine the structure of protein interaction networks in each sample and infer which
genes performed different cellular
functions within these networks.
Additional research is also needed to
determine how the C version of the
gene affects the protein's
function.
To try to
determine how those changes influenced the
gene's
function, that group put the human version of the
gene in mice.
«If there are 1,000
genes in the population that can contribute to risk in varying degrees and each has multiple developmental
functions, it is not immediately obvious how to move forward to
determine what is specifically related to autism,» State said.
«If you line up these [variants] and
determine the likely
function of the
genes, do they tell the same story?»
It can take up to a year to
determine the
function of a single
gene, which has slowed efforts to develop new, more targeted drugs and vaccines.
Eliminating
genes in mice is a standard technique for
determining their
function; the resultant animals are called knockout mice.
«In model organisms, like yeast or flies, scientists often generate mutations to
determine which letters in a DNA sequence are needed for a particular
gene to
function,» explains CSHL Professor Adam Siepel.
During their study, Hsu and his colleagues
determined that Insl3 and a second relaxin, Rln3, whose
function is unknown, evolved from an ancestral
gene found in fish.
The expression of specific
genes in a particular root cell
determine its fate — the zone in which it will
function, Subramanian explained, so he is identifying which micro-RNAs direct
gene expression to achieve this differentiation.
To
determine whether shifts in the balance of anterior and posterior field occurred during fin - to - limb evolution, Onimaru, postdoctoral researcher currently at Sharpe's lab (CRG), and his colleagues carefully compared the expression,
function and regulation of
genes involved in anterior - posterior patterning in pectoral fins of catsharks, with those of mice.
A second project, dubbed Eumorphia, will organize more than a dozen labs in nine countries to systematically screen new mouse mutants for interesting characteristics — a key step in
determining the
function of newly identified
genes.
On 18 March, the EC announced the creation of three pan-European projects, including the twin study, a new project to identify the
function of
genes in mutant mice, and an effort to
determine the structures of disease - related proteins.
To
determine whether the FLRG transgene was causing increased muscle growth by blocking myostatin activity, I examined the effect of combining the FLRG transgene with a loss - of -
function mutation in the myostatin
gene.
Given that Dt2 is not the
gene most closely related to AP1 and that semideterminacy is rarely seen in wild soybeans, Dt2 appears to be a recent gain - of -
function mutation, which has modified the genetic pathways
determining the stem growth habit in soybean.
«It is of eminent importance, for this is the biologically relevant structure of DNA that
determines both
gene function and activity.»
After decades of extrapolating about
gene function in trees based on
gene function in a tiny, less complex plant, a team of scientists has sequenced whole genomes —
determined the DNA sequence of all the
genes — from 544 unrelated trees of the same species.
Just like we test hypotheses about the
functions of
genes in genetic networks by knocking them out and replacing them, we need methods to selectively remove or inhibit specific microbes or metabolisms in microbial networks to
determine their roles,» Brodie added.
«To move beyond cataloging microbes, we will need new tools to rapidly
determine microbial
gene function and monitor the chemicals microbes use to communicate and interact with their environment, and new ways to visualize and model those interactions,» said Eoin Brodie, a staff scientist at Lawrence Berkeley National Laboratory's Earth Sciences Division and an author of the proposal.
Without these tools, scientists are less able to link specific
genes to cell behavior or
determine how microbes interact within their environment and with one another — critical information for understanding how ocean ecosystems
function.
«The mutational analysis of NOTCH clearly indicated the power of genetic changes
determining the
function of these
genes,» said Kenneth W. Kinzler, professor of oncology and a molecular geneticist at Johns Hopkins, co-director of the Ludwig Center at Johns Hopkins, and an author of one of the Science papers.
Dr. Coyle's Laboratory for Psychiatric and Molecular Neuroscience takes advantage of insights into recently identified
genes that confer risk for schizophrenia and related disorders and translates them into genetic mouse models to
determine how these mutations affect brain changes as well as
function, neurochemistry, and behavior.
Howard Hughes Medical Institute researchers have harnessed a mobile
gene from the cabbage looper moth and modified it for routine use to
determine the
function of
genes in mice and other vertebrates...
Armed with this knowledge, the researchers believe they can
determine the cell types, cellular
functions and
genes that are affected by smoking, and how that varies between healthy and COPD - afflicted lungs.
Endowed with the power to control the activity of other
genes, GTF2I might regulate signal pathways
determining the structure and
function of the brain or the production of neurohormones such as vasopressin and oxytoxin.
The IMPC builds on the efforts of IKMC to produce knockout mice and carry out high - throughput phenotyping of each line in order to
determine the
function of every
gene in the mouse genome.
The researchers not only had to figure out how SLC16A11 performed in normal circumstances, but also then
determine how mutations in the
gene disrupted that
function.
Kim and his colleagues were able to deduce the
function of several M. jannaschii proteins based on their structures, a strategy that may prove useful in
determining the
functions of
genes and proteins in other sequenced organisms.
By labeling HAR1 molecules in human and macaque embryos, we discovered that the RNAs
functioned in neurons during patterning and layout of the cortex, 6 a brain structure that expanded greatly in size during human evolution.7 Exactly which
genes HAR1 is regulating remains to be
determined.
Key to the project are lab and bioinformatics exercises that will give students the unique opportunity to work with Cold Spring Harbor Laboratory researcher David Jackson in
determining the cellular analysis of Arabidopsis
genes of unknown
function.
Her current research is focused on discovering how normal and disease melanocyte cell states establish distinct regulatory DNA landscapes, and also
determining how the combination of both genetic variation within these regulatory regions and environmental cell signals alter
gene expression and normal cell
function.
When all the
genes are sequenced, researchers will be able to seek and knock out all copies of a
gene and
determine its
function, according to Yanofsky.
The goal of the ENU Mutagenesis project is to
determine the
function of
genes on mouse Chromosome 11 by saturating the chromosome with recessive mutations.
By
determining the
function of
genes on a mouse chromosome, extrapolation leads to predicting
function on a human chromosome.
In this method, all the
genes are ranked according to the differential expression between two classes, and the Kolmogorov - Smirnoff test is used to
determine the statistical correlation of the ranked
gene list to the
gene set of a given biological process, pathway or molecular
function.
Site - directed mutagenesis in a biologically active nucleic acid for the purpose of reverse genetics of phage Qß; method extended to DNA to
determine structure -
function relationships in the promoter and splice sites of the ß - globin
gene.
We selected 68
genes with putative immune - related
functions, macroarrayed them and
determined their expression profiles following bacterial or trypanosome challenge.
Every cell in the body has the same DNA and
genes, so a cell's properties and
functions are
determined by which
genes are turned on.