"Genom 2005" is a feature rich and user friendly application for analysing array-experiments (e.g. from provider Affymetrix).
What are microarrays?
A short overview on the microchip technology.
GeneChip arrays enable scientists to attain ambitious goals
from identifying genetic variations associated with disease to
discovering new drug targets. Leveraging technologies adapted
from the semiconductor industry, the manufacture of GeneChip
arrays uses photolithography and solid-phase chemistry to
produce arrays containing hundreds of thousands of
oligonucleotide probes packed at extremely high densities. The
probes are designed to maximize sensitivity, specificity, and
reproducibility, allowing consistent discrimination between
specific and background signals, and between closely related
target sequences.
Attesting to their powerful capabilities, GeneChip arrays are
applied in a wide variety of DNA and mRNA analyses. Recent
analytical accomplishments include the elucidation of
interactions between signaling pathways involved in
development, the discovery of a new class of leukemia, and the
development of new assays to track drug metabolism.
Although all of the cells in the human body contain identical genetic material, the same genes are not active in every cell. Studying which genes are active and which are inactive in different cell types helps scientists to understand both how these cells function normally and how they are affected when various genes do not perform properly. In the past, scientists have only been able to conduct these genetic analyses on a few genes at once. With the development of DNA microarray technology, however, scientists can now examine how active thousands of genes are at any given time.
Microarray technology will help researchers to learn more about many different diseases, including heart disease, mental illness and infectious diseases, to name only a few. One intense area of microarray research at the National Institutes of Health (NIH) is the study of cancer. In the past, scientists have classified different types of cancers based on the organs in which the tumors develop. With the help of microarray technology, however, they will be able to further classify these types of cancers based on the patterns of gene activity in the tumor cells. Researchers will then be able to design treatment strategies targeted directly to each specific type of cancer. Additionally, by examining the differences in gene activity between untreated and treated tumor cells - for example those that are radiated or oxygen-starved - scientists will understand exactly how different therapies affect tumors and be able to develop more effective treatments.
DNA microarrays are created by robotic machines that arrange
minuscule amounts of hundreds or thousands of gene sequences on
a single microscope slide. Researchers have a database of over
40,000 gene sequences that they can use for this purpose. When
a gene is activated, cellular machinery begins to copy certain
segments of that gene. The resulting product is known as
messenger RNA (mRNA), which is the body's template for creating
proteins. The mRNA produced by the cell is complementary, and
therefore will bind to the original portion of the DNA strand
from which it was copied.
To determine which genes are turned on and which are turned
off in a given cell, a researcher must first collect the
messenger RNA molecules present in that cell. The researcher
then labels each mRNA molecule by attaching a fluorescent dye.
Next, the researcher places the labeled mRNA onto a DNA
microarry slide. The messenger RNA that was present in the cell
will then hybridize - or bind - to its complementary DNA on the
microarray, leaving its fluorescent tag. A researcher must then
use a special scanner to measure the fluorescent areas on the
microarray.
If a particular gene is very active, it produces many
molecules of messenger RNA, which hybridize to the DNA on the
microarry and generate a very bright fluorescent area. Genes
that are somewhat active produce fewer mRNAs, which results in
dimmer fluorescent spots. If there is no fluorescence, none of
the messenger molecules have hybridized to the DNA, indicating
that the gene is inactive. Researchers frequently use this
technique to examine the activity of various genes at different
times.
Scientists know that a mutation - or alteration - in a particular gene's DNA often results in a certain disease. However, it can be very difficult to develop a test to detect these mutations, because most large genes have many regions where mutations can occur. For example, researchers believe that mutations in the genes BRCA1 and BRCA2 cause as many as 60 percent of all cases of hereditary breast and ovarian cancers. But there is not one specific mutation responsible for all of these cases. Researchers have already discovered over 800 different mutations in BRCA1 alone. The DNA microchip is a revolutionary new tool used to identify mutations in genes like BRCA1 and BRCA2. The chip, which consists of a small glass plate encased in plastic, is manufactured somewhat like a computer microchip. On the surface, each chip contains thousands of short, synthetic, single-stranded DNA sequences, which together, add up to the normal gene in question
Because chip technology is still relatively new, it is currently only a research tool. Scientists hope to be able to use it to conduct large-scale population studies - for example, to determine how often individuals with a particular mutation actually develop breast cancer. As we gain more insight into the mutations that underly various diseases, researchers will likely produce new chips to help assess individual risks for developing different cancers as well as heart disease, diabetes and other diseases.
To determine whether an individual possesses a mutation for BRCA1 or BRCA2, a scientist first obtains a sample of DNA from the patient's blood as well as a control sample - one that does not contain a mutation in either gene. The researcher then denatures the DNA in the samples - a process that separates the two complementary strands of DNA into single-stranded molecules. The next step is to cut the long strands of DNA into smaller, more manageable fragments and then to label each fragment by attaching a fluorescent dye. The individual's DNA is labeled with green dye and the control - or normal - DNA is labeled with red dye. Both sets of labeled DNA are then inserted into the chip and allowed to hybridize - or bind - to the synthetic BRCA1 or BRCA2 DNA on the chip. If the individual does not have a mutation for the gene, both the red and green samples will bind to the sequences on the chip. If the individual does possess a mutation, the individual's DNA will not bind properly in the region where the mutation is located. The scientist can then examine this area more closely to confirm that a mutation is present.
The number of arrays for different species is growing very fast. Lately a lot array for plants have been developed by Affymetrix. The following table shows a list of all species that are currently supported.
Platform:
Windows XP / 2000 / 2003 or later.
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