Hello crzyltlman-ga
A succinct answer to your question is provided by a factsheet from the
European Federation of Biotechnology (EFB) “What’s what in
biotechnology” http://www.kluyver.stm.tudelft.nl/efb/tgppb/pdf/eng6.pdf
“Although they run concurrently, gene mapping and genome sequencing
can be regarded as the two stages of the human (or other) genome
projects. Mapping determines the position of genes relative to each
other on chromosomes. Sequencing is the determination of the order of
individual bases or base-pairs within genes and other pieces of DNA.”
Gene mapping will tell you that a certain gene is found on a certain
chromosome. It does not necessarily require either the sequence or the
function of the gene to be known.
Genome sequencing will tell you the order in which the nucleotides are
present on the DNA. However, it will not in itself tell you which
parts of the sequence are genes. From the EFB factsheet: “… humans
have around 80,000 [genes]. In humans, genes only account for about 4%
of the genome. The rest is sequences of DNA, which perform functions
other than coding for protein, although in most cases, researchers do
not yet understand what.”
In more detail:
Gene mapping can be done either by genetic mapping or by physical
mapping.
Genetic mapping has been done since the beginning of the 20th century.
It does not require knowledge of the sequence of the gene that is
being mapped, nor even knowledge of its true function. All that is
needed is knowledge of the way that gene is expressed phenotypically,
ie through its protein product. It is done, for example, by means of
family studies, looking at the frequency with which two specific genes
are inherited together. This technique is called linkage analysis and
uses statistical techniques.
Genetic mapping looks at how frequently two different genes stay
together from parent to offspring. It gives an idea of the relative
positions of two genes. If they are regularly passed on together,
then that is an indication that they are fairly close together
(linked) on the same chromosome and therefore less likely to be
separated by the process of meiosis. One slight complication is that
the closeness of genes is not a measure of the physical distance
between them on the chromosome, but a measure of the probability that
a cross-over will occur during meiosis on the part of the chromosome
that separates these genes.
Meiosis is a specific form of cell division which is used to produce
germ cells (eg eggs and sperm) which contain only half the genetic
material of an ordinary cell. The cross-overs that occur during
meiosis mix the genetic material of the grandparents, so that the egg
or sperm cell is genetically different to the original parent cell.
You might find it helpful to look at the diagrams at:
http://www.accessexcellence.org/AB/GG/meiosis.html (Access Excellence,
About Biotech)
Physical mapping actually assigns genes to a specific physical
position on the chromosomes. A number of methods can be used for this
purpose. One of the techniques used is known as FISH (fluorescence in
situ hybridization). “A process which vividly paints chromosomes or
portions of chromosomes with fluorescent molecules. This technique is
useful for identifying chromosomal abnormalities and gene mapping.”
http://www.genome.gov/glossary.cfm?key=fluorescence%20in%20situ%20hybridization%20%28fish%29
(Glossary of the National Human Genome Research Institute). Here is
an illustration: http://www.genome.gov/Pages/Hyperion//DIR/VIP/Glossary/Illustration/fish.shtml
DNA sequencing was used to obtain the sequence of the human genome.
The first method used was developed by Frederick Sanger in 1974.
Sanger’s method used an X-ray technique to analyze the sequence of
nucleotides in short strands of DNA. It is a very slow method, so that
many years were needed to sequence just a few million nucleotides.
However, it is very accurate and so still in use by many researchers
today. You can read about this and newer methods at
http://www.uweb.ucsb.edu/~trevorc/histseq.html (History of DNA
sequencing)
Other sources used and further reading:
http://www.republika.pl/jmejnart/wyklady/map_us/#Genetic%20mapping
(lecture notes on gene mapping)
http://www.accessexcellence.com/AB/GG/nhgri_PDFs/fish_TXT.pdf A
detailed description of FISH (fluorescence in situ hybridization) from
the National Human Genome Research Institute
http://www.genome.org/cgi/content/full/10/10/1435 (Linkage
Disequilibrium and the Search for Complex Disease Genes by L.B. Jorde
– a long and highly technical paper on one type of linkage analysis,
published in Genome Research Vol. 10, Issue 10, 1435-1444, October
2000)
http://bioinfo.mbb.yale.edu/course/projects/final-4/ A History of
Genome Sequencing
http://www.intouchlive.com/home/frames.htm?http://www.intouchlive.com/cancergenetics/dnatek.htm&3
Basic techniques of DNA analysis
http://www.blonnet.com/ew/2002/06/12/stories/2002061200050200.htm
(Gene mapping isn’t so easy. An article describing how computers are
used in this field)
I hope this helps, but please request clarification if I have omitted
something. |
Clarification of Answer by
tehuti-ga
on
03 Jan 2003 18:53 PST
Oops, I forgot to comment on the last part of your question about what
other steps will be required after the mapping.
The most important thing will be to analyse the functions of the genes
in health and in disease at a cellular and subcellular level, since
this will open the way to new therapies. To do this, it is necessary
to look at the protein products formed from the gene templates. This
has given rise to the new study of proteomics.
"The term ’proteome’ was coined by Wilkins and Williams as meaning the
entire protein complement of a given genome. Proteomics is ... now
also understood more broadly as simply meaning large scale analysis of
proteins within a single experiment... Proteomics has now branched
into two specific disciplines:
Classical proteomics, in which the proteomes of two (or more)
differentially treated cell (or tissue) lines are initially separated
and visualized by 2D gel electrophoresis... proteins that differ in
abundance between the gels are identified by mass spectrometry.
Functional proteomics, where usually a subset of proteins has been
isolated... Each protein in the subset has a common feature...
[which] can give evidence of the function of each characterized
protein. Since functional proteomics deals with simplified systems
that are easy to study, many more ’real-life’ problems have been
solved with this approach than with classical proteomics"
from the Protana web site
http://www.protana.com/coretechnology/whatisproteomics/default.asp
which has further information about proteomics.
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