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S B Mirza 1314
6th (Afternoon)[Bioinformatics]
10
April 27,
GENE SILENCING TECHNIQUES
2010
Contents
Introduction…………………………………………………………………………………
2
Transcriptional gene
silencing……………………………………………………………..3
Post-transcriptional gene
silencing………………………………………………………..4
Therapeutic applications and
challenges…………………………………………………5
Asthma……………………………………………………………………………………….
6
Knock-Out Mouse[Nude mouse]
………………………………………………………….7
History and
Nomenclature………………………………………………………………...8
Significance………………………………………………………………………………….
8
Immunological Responses of Nude
Mice………………………………………………..8
Uses of Nude Mouse………………………………………………………………………
11
References…………………………………………………………………………………..
12
S B Mirza1314 | GCUF
April 27,
GENE SILENCING TECHNIQUES
2010
Introduction:
“Gene silencing is a general term
describing epigenetic processes of gene
regulation. The term gene silencing is
generally used to describe the "switching
off" of a gene by a mechanism other than
genetic modification. That is, a gene
which would be expressed under normal
circumstances is switched off by
machinery in the cell.”
Cellular components of gene silencing:
Histones
Chromatin and heterochromatin
MicroRNA
siRNA
dsRNA
Dicer
Transposons
S B Mirza1314 | GCUF
April 27,
GENE SILENCING TECHNIQUES
2010
a) Transvection
Genomic Imprinting:
Imprinted genes are either expressed only from the allele inherited from
the mother (eg. H19 or CDKN1C), or in other instances from the allele
inherited from the father (eg. IGF-2). Forms of genomic imprinting have
been demonstrated in insects, mammals and flowering plants.
Paramutation:
2
In epigenetics, paramutation is an interaction between two alleles of a
single locus, resulting in a heritable change of one allele that is induced
by the other allele. Paramutation violates Mendel’s first law, which states
S B Mirza1314 | GCUF
April 27,
GENE SILENCING TECHNIQUES
2010
that in the process of the formation of the gametes (egg or sperm) the
allelic pairs separate, one going to each gamete, and that each allele
remains completely uninfluenced by the other. In paramutation an allele
in one generation heritably affects the other allele in future generations,
even if the allele causing the change is itself not transmitted
Position effect:
Position effect is the effect on the expression of a gene when its location
in a chromosome is changed, often by translocation. This has been well
described in Drosophila with respect to eye color and is known as position
effect variegation (PEV).
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April 27,
GENE SILENCING TECHNIQUES
2010
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April 27,
GENE SILENCING TECHNIQUES
2010
Transvection:
Strategies:
S B Mirza1314 | GCUF
April 27,
GENE SILENCING TECHNIQUES
2010
Asthma
Knock-out Mouse[Nude Mouse]
Asthma:
Asthma is a disease affecting the airways that carry air to and from your
lungs. People who suffer from this chronic
condition (long-lasting or recurrent) are
said to be asthmatic.
Knockout Mouse:
S B Mirza1314 | GCUF
April 27,
GENE SILENCING TECHNIQUES
2010
S B Mirza1314 | GCUF
April 27,
GENE SILENCING TECHNIQUES
2010
S B Mirza1314 | GCUF
April 27,
GENE SILENCING TECHNIQUES
2010
S B Mirza1314 | GCUF
April 27,
GENE SILENCING TECHNIQUES
2010
Significance:
A mutant mouse said to be nude because it is hairless due to the
presence of two copies of the gene ‘nu’. Because they lack a thymus,
Nude mice cannot generate mature T lymphocytes. Therefore they are
unable to mount most types of immune responses, including:
Picture: Placental and foetal weight and litter size were studied on the
18th day of pregnancy in the athymic nude mouse. Placental weight and
litter size were unaffected by the absence of a thymus. Foetal weight was
reduced, probably as a result of the health status of such animals.
Immunological Responses of
Nude Mice:
Mice homozygous for the
mutation nude lack a thymus.
They are deficient in lymphocytes
in thymus dependent areas of peripheral lymphoid organs. They lack cells
bearing ‘θ’ which is a cell surface antigen found on thymocytes and 2
thymus dependent cells. In a preliminary communication it have been
reported that nu/nu mice have impaired heterograft rejection and low
immunoglobulin levels.
S B Mirza1314 | GCUF
April 27,
GENE SILENCING TECHNIQUES
2010
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April 27,
GENE SILENCING TECHNIQUES
2010
D. Chameleon (reptile) at 41
days.
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April 27,
GENE SILENCING TECHNIQUES
2010
References:
1) e Nude Mouse in Experimental and Clinical Research (Vol.1). Fogh, J;
Giovanella, B.C. (eds) Academic Press, 1978, ISBN 0-12-261860-2
2)
The Nude Mouse in Experimental and Clinical Research (Vol.2).
Fogh, J; Giovanella, B.C. (eds) Academic Press, 1982, ISBN 0-12-
261862-9
4) http://jaxmice.jax.org/faq/bulletin/bulletin06.html
5) http://jem.rupress.org
6) http://www.karger.com
7) (OMIM)http://en.wikipedia.org/wiki/Mendelian_Inheritance_in_Man
9) Proc. Natl. Acad. Sci. USA Vol. 81, pp. 886-888, February 1984
Medical Sciences
10) Proc. Natl. Acad. Sci. USA Vol. 81, pp. 886-888, February 1984
Medical Sciences
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