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B.4 Medicine
A Comic Sans Production
By Jacob Dayton and Darren Nguyen
Pathogens
• Pathogens-bacteria or
viruses that infect us and
cause an immune response.
• If disease is genetic, it can
be identified by genetic
variations in the DNA
sequence called markers.
• Pathogens are detected by
the immune system by
antigens and responds with
antibody production.
Pathogens
• Pathogens-bacteria or
viruses that infect us and
cause an immune response.
• If disease is genetic, it can
be identified by genetic
variations in the DNA
sequence called markers.
• Pathogens are detected by
the immune system by
antigens and responds with
antibody production.
Pathogens
• Pathogens-bacteria or viruses that
infect us and cause an immune
response.
• If disease is genetic, it can be identified
by genetic variations in the DNA sequence
called markers.
• Pathogens are detected by the immune
system by antigens and responds with
antibody production.
• The Enzyme-Linked Immunosorbent
Assay (ELISA) can detect pathogens
through the presence of antibodies
• Ex: p24 antigen for the HIV virus
http://www.bio-rad.com/LifeScience/jobs/2004/04-0522/040522_ELISA.html
http://media.hhmi.org/biointeractive/vlabs/immunology/index.html
Enzyme-Linked Immunosorbent Assay
Genetic Markers
• Genetic markers
are particular
alleles which are
associated with a
predisposition to
having a genetic
disease.
Genetic Markers
• Markers may exist within a
coding or non-coding
sequence, contributing to
the disease in a coding
sequence or being
genetically linked to the
gene that influences the
disease.
• Markers are used to
predict genetic disorders
• Markers have more
predictive power when
linked to a disease specific
to one gene
Metabolites
• Metabolites are
molecules that are
produced as a result
of a metabolic
process.
At the right illustrates a
summary of just animal
metabolism of proteins,
lipids, and
carbohydrates.
Metabolites
• Mutations in single genes can lead to disorders in which a single enzyme becomes
non-functional.
• This can lead to the overproduction or shortage of molecules.
• The metabolites that are produced from the dysfunctional metabolic process can be used to
detect genetic disorders that affect metabolism.
Metabolic
Metabolic pathway that
Disease
functioning
LeschNyhan
syndrome
is not
Production of purines (adenine and guanine)
because Mutations in
the HPRT1 gene which provides instructions
for making an enzyme called hypoxanthine
phosphoribosyltransferase 1. This enzyme is
responsible for recycling purines.
Zellweger
syndrome
Assembly of peroxisomes (organelles
essential for the degradation of long chain
fatty acids found in many lipids) Mutations
in at least 12 genes have been found to
cause Zellweger spectrum disorder. These
genes provide instructions for making a
group of proteins known as peroxins,
Metabolite that
is detected
symptoms
Uric acid
crystals in
the urine
abnormal involuntary muscle movements, such as
tensing of various muscles, jerking movements and
generally use a wheelchair. Self-injury (including
biting and head banging) is the most common.
Elevated
very long
chain fatty
acids in the
blood
at the severe end of the spectrum, develop
symptoms as a newborn. They experience weak
muscle tone (hypotonia), feeding problems, hearing
and vision loss, and seizures. These problems are
caused by the breakdown of myelin, which is the
covering that protects nerves. Children with
Zellweger syndrome typically do not survive beyond
Metabolites
Which metabolite
molecule would
you want to
develop a blood
test for to test
for Alkaptonuria?
Common amino acid found in
dietary protein!
Alkaptonuria genetic
mutation metabolic disorder
Metabolites
Which metabolite
molecule would you
want to develop a
blood test for to
test for
Alkaptonuria?
High levels of
homogentisic acid
detected in both the
urine and the blood by
thin layer
chromatography and
paper chromatography
Common amino acid found in
dietary protein!
Alkaptonuria genetic
mutation metabolic disorder
Microarrays
• Microarray- A small
surface that has a large
range of DNA probe
sequences adhering to the
surface.
• Can be used to test for
expression of a very large
number of DNA sequences
simultaneously.
• http://www.bio.davidson.edu/course
s/genomics/chip/chip.html
Microarrays
• Microarray- A small surface that has a large range of DNA probe
sequences adhering to the surface.
• Can be used to test for expression of a very large number of DNA
sequences simultaneously.
• The results of a microarray are shown on a grid of colored spots
•
•
•
•
Green – Gene is expressed in normal cells, not expressed in cancer cells
Red – Gene is not expressed in normal cells, but expressed in cancer cells
Yellow – Gene is expressed in normal cells and expressed in cancer cells
Black – Gene is not expressed in normal cells nor expressed in cancer cells
• Virtual lab, http://learn.genetics.utah.edu/content/labs/microarray/
Protein Tracking Experiments
• Tracking experiments allow researchers to follow distribution and
localization patterns of a desired product
• Also allow researchers to determine how a specific protein interacts with the target
tissue
• Ex. Tracking tumor cells using transferrin linked to luminescent probes
• Ex. Green Fluorescent Protein (GFP) in transformed organisms
START  translation  STOP
Protein + GFP
Histone
Mouse expressing GFP
Biopharming
Over simplified!
mRNA cDNA
2 separate GM bacteria
A-Insulin polypeptide
made in in one tank,
B-Insulin in another tank.
↓
Biochemistry to modify
And bond  polypeptide
chain  functional insulin
A chain
Disulfide
B chain
bridges
Biopharming
• Biopharming uses genetically
modified animals and plants to
produce proteins for therapeutic
use.
• 3 main protein categories used in
therapy:
• Human proteins
• Ex: Insulin …what advantage would
there be to transforming yeast
instead of bacteria?
• Antibodies
https://www.youtube.com/watch?v=ntwW3EERHEM
• Viral/Bacterial proteins
• Ex: Antigens (In vaccines)
BiopharmingViral/ Bacterial proteins Ex: Antigens (In vaccines)
Vaccination
↓
Memory White Blood Cells
↓
What should happen if you
Are exposed to Hep B virus
After your immunized?
Gene Therapy by
Viral Vectors
In Theory, an Elegant Solution
• In Gene therapy, working
copies of defective gene are
inserted into a person’s
genome.
• Ex: Sever Combined
Immunodeficiency (SCID)
• Cystic Fibrosis and
• Viruses that contain doublestranded DNA, like
adenovirus, cannot cause the
problems found with
retroviruses because the viral
DNA isn’t inserted into the
genome.
In practice: it is more complicated
Gene Therapy by
Viral Vectors
In Theory, an Elegant Solution
• In Gene therapy, working copies
of defective gene are inserted
into a person’s genome.
• Ex: Sever Combined
Immunodeficiency (SCID)
• Cystic Fibrosis and
• Viruses that contain doublestranded DNA, like adenovirus,
cannot cause the problems
found with retroviruses because
the viral DNA isn’t inserted into
the genome.
In practice: it is more complicated
Gene Therapy
• One hundred and thirty six patients
aged 12 and over received monthly
doses of either the therapy or the
placebo for one year.
• July, 2015
• The trial is the first to show that
repeated doses of gene therapy can
have a meaningful effect on the
disease, and change the lung
function of patients. However, the
team say more research is needed to
improve the effectiveness before the
therapy will be suitable for clinical
use.
Patients receive the therapy
by inhaling fat globules (non-viral)
containing DNA from a nebulizer
http://www3.imperial.ac.uk/newsandeventspggrp/imperialcoll
ege/newssummary/news_2-7-2015-14-9-39
Gene Therapy by Viral Vectors
• Two varieties of treatments are:
• Somatic therapy, the use of altered somatic cells
• Germ Line Therapy, injection of therapeutic genes into egg cells so
that missing gene would be expressed in all cells of the organism.
• Why might their be strong bioethical debates around Germ Line
Gene Therapy?
Gene Therapy by Viral Vectors
Why might their be strong bioethical debates around Germ Line Gene Therapy?
However, NIH will not fund any use of gene-editing technologies in human embryos. The
concept of altering the human germline in embryos for clinical purposes has been debated
over many years from many different perspectives, and has been viewed almost universally as
a line that should not be crossed.
• Advances in technology have given us an elegant new way of carrying out genome editing, but the strong
arguments against engaging in this activity remain.
• These include the serious and unquantifiable safety issues, ethical issues presented by altering the
germline in a way that affects the next generation without their consent, and a current lack of compelling
medical applications justifying the use of CRISPR/Cas9 [a direct way to edit DNA of single cells] in embryos.
http://www.nih.gov/about-nih/who-we-are/nih-director/statements/statement-nih-funding-research-using-gene-editing-technologies-human-embryos
• March 2015 Chinese Scientists modified genetics of nonviable human zygote using CRISPR
and let it develop through early embryonic stages, their paper led to Bioethical Debates 
temporary international moratorium until bioethical summit.
http://www.nature.com/news/chinese-scientists-genetically-modify-human-embryos-1.17378
• Dec 2015: Summit rules out international ban on gene editing embryos destined to become
people. Experts, however, say altering DNA of human embryos for clinical purposes is
unacceptable given unknown risks today.
http://www.theguardian.com/science/2015/dec/03/gene-editing-summit-rules-out-ban-on-embryos-destined-to-become-people-dna-human