ELECTROPHORESIS
OF DNA FRAGMENTS IN AGAROSE GELS
General
Consideration
Any charged ion or group at any pH other than their isoelectric point,
in an electric field, migrate at a rate proportional to:
1. Their charge density.
2. Their weight, the size and shape of the molecule.
3. The environmental conditions (ionic strength, viscosity, temperature
and the kind of support matrix).
Electrophoresis is a technique used to separate and sometimes purify
macromolecules - especially proteins and nucleic acids - that differ
in size, charge or conformation.
When charged molecules are placed in an electric field, they migrate
toward either the positive (anode) or negative (cathode) pole according
to their charge density, their weight, size and shape of the molecule,
and the environmental conditions (ionic strength, viscosity, temperature
and the kind of support matrix).
Some Properties of Nucleic acids:
DNA molecules have much higher molecular weights than proteins.
The phosphate backbone of DNA is highly negatively charged.
The Nucleic acids are polyanionic molecules uniformly charged and therefore the
molecules will be separated according to their molecular weight.
Nucleic acids come in a very wide range of sizes, from several dozen base pairs
to many millions.
Support Matrix:
The most used material as matrix is agarose or polyacrylamide gel.
Agarose, because of its large range of pore size, is mostly used
to separate micro and macromolecules ( such as nucleic acids, large
proteins, protein complexes).
Polyacrylamide is a cross-linked polymer of acrylamide. Generally
it makes smaller pore gels, and therefore is suitable for the separation
of most proteins and smaller nucleic acid fragments, but it is toxic.
The length of the polymer chains is dictated by the concentration of
acrylamide used, which is typically between 3.5 and 20%. Polyacrylamide
gels are significantly more annoying to prepare than agarose gels.
Because oxygen inhibits the polymerization process, they must be poured
between glass plates.
Acrylamide is a potent neurotoxin and should be handled with
care! Wear disposable gloves when handling solutions of acryl amide, and
a mask when weighing out powder. Polyacrylamide is considered to be
non-toxic, but Polyacrylamide gels should also be handled with gloves
due to the possible presence of free acrylamide.
Polyacrylamide gels have a rather small range of separation, but
very high resolving power. In the case of DNA polyacrylamide is used
for separating fragments of less than about 500 bp. However, under
appropriate conditions, fragments of DNA differing is length by a single
base pair are easily resolved. In contrast to agarose, polyacrylamide
gels are used extensively for separating and characterizing mixtures
of proteins.
Agarose:
Agarose is a polysaccharide. It is typically used at concentrations
of 0.5 to 2%. The higher the agarose concentration the "stiffer" the
gel. Agarose gels are extremely easy to prepare: you simply mix agarose
powder with an appropriate buffer solution, melt it by heating, and
pour the gel. It is non-toxic.
Agarose gels have a large range of separation, but relatively
low resolving power. By varying the concentration of agarose, fragments of DNA from
about 100 to 30,000 bp can be separated using standard electrophoretic
techniques.
The gels are run horizontally in an adequate buffer usually at room
temperature.
Agarose Gel electrophoresis is the standard technique to separate,
identifies, and purifies DNA fragments according to their size.
Also, this method is employed to check the progression of a restriction
enzyme digestion, to quickly determine the yield and purity of a DNA
isolation or PCR reaction, and to size fractionated DNA molecules.
The technique is simple, rapid to perform, and capable of resolving
mixtures of DNA fragment that can not be separated adequately by other
sizing procedures.
The percentage of agarose in the gel varies, and affects the migration
of the fragments. A DNA fragment of given size migrates at different
rates through the gels containing different concentrations of agarose.
A 0.7% agarose gel shows good separation of large DNA fragments (5-10kb)
and a 2% gel will show good separation for small fragments (0.2-1kb).
For separation of smaller fragments higher concentration can be used.
Closed circular, nicked circular and linear DNA of the same MW migrates
through the agarose gels at different rates. The relative mobilities
of these three DNA forms are dependent primarily on the agarose concentration
in the gel but are also influenced by the strength of the applied current,
the ionic strength of the buffer, and the density of super helical
twists in the DNA.
The electrophoretic behavior of DNA in agarose gels (by contrast to
polyacrylamide gels) is not significantly affected either by the base
composition of the DNA or the temperature at which the gel is run.
The phosphate molecules that make up the backbone of DNA molecules
have a high negative charge. When DNA is placed on an electrical field
these negatively charged DNA molecules migrate toward the positive
end of the field.
Hellabio Precast Agarose Gels ( HPAG) are ready to use and can be
offered in four size of gels.
According to the User’s demands it is possible to offer precast
agarose gels to fulfil any needs (gel size, number and capacity of
wells, size range of fragments) and to get easily the best results
at a very moderate cost.
The User of the HPAG is insured to get rapid and reproducible results
and to save time and money.
Hellabio offers a complete line of nucleic acid electrophoresis products
such as a broad range of molecular biology grade pre-cast agarose gels,
electrophoresis tank and all necessary accessories, so that the user
works independent and get comfortable the best resolutions result.
Hellabio Electrophoresis Systems [Submarine and Vertical] are offered
for the standard size gel range. In the same time the user has the
ability to choose a variety of gel lengths and comb sizes according
to his protocol
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