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GENETICS
Larry M. Frolich, Ph.D.
GENETICS
• Cells divide and pass on
instructions coded in DNA of
chromosomes
• Each chromosome is a huge DNA
molecule with coded information
– DNA replicates to pass on information
– DNA is transcribed to make proteins
that run cell metabolism
• Cancer—example of what happens
when genetic control goes awry
• Normal inheritance and meiosis
Larry M. Frolich, Ph.D.
GENETICS
• Cells divide and pass on
instructions coded in DNA
of chromosomes
•
Each chromosome is a huge DNA molecule with coded
information
– DNA replicates to pass on information
– DNA is transcribed to make proteins that run cell
metabolism
•
•
Cancer—example of what happens when genetic
control goes awry
Normal inheritance and meiosis
Larry M. Frolich, Ph.D.
DNA and chromosomes
• Long DNA molecules (millions
of base pairs long) in nucleus
are called chromosomes
• Each chromosome is organized
and packaged or wrapped up
with proteins giving it a certain
shape
• In humans, 23 pairs of
chromosomes
– 1 of each pair from mother
– 1 of each pair from father
• Total view of all 23 pairs is
called karyotype
Larry M. Frolich, Ph.D.
Mitosis—cell division
• Why do cells divide?
– Growth—so tissues/structures can become
larger
– Replacement—many tissues are constantly
being replaced because they get worn out or
used up. E.g. blood, skin, lining of gut, sperm
– Repair—when tissues get damaged due to
injury
Larry M. Frolich, Ph.D.
Mitosis—what happens (overview)
• DNA/chrosomes replicate
(make exact copies
• Copies line up at center
of cell
• Copies pulled to opposite
ends of cells by
centromeres/spindles
• Cell membrane pinches
off and splits cell into two
Larry M. Frolich, Ph.D.
Mitosis—details/stages
1. Prophase
3. Anaphase
2. Metaphase
4. Telophase
Larry M. Frolich, Ph.D.
1. Mitosis: Prophase
•
Chromosomes condense and
become visible
•
Nuclear envelope fragments
•
Nucleolus disappears
•
Centrosomes move to
opposite poles
•
Spindle fibers appear and
attach to the centromere
Larry M. Frolich, Ph.D.
2. Mitosis: Metaphase
• Chromosomes line
up at the middle of
the cell (equator)
• Fully formed spindle
Larry M. Frolich, Ph.D.
3. Mitosis: Anaphase
• Sister chromatids
separate at the
centromeres and
move towards the
poles
Larry M. Frolich, Ph.D.
4. Mitosis:Telophase and cytokinesis
•
•
•
•
•
•
Chromosomes arrive at
the poles
Chromosomes become
indistinct chromatin
again
Nucleoli reappear
Spindle disappears
Nuclear envelope
reassembles
Two daughter cells are
formed by a ring of actin
filaments (cleavage
furrow)
Larry M. Frolich, Ph.D.
Mitosis—constant, fast,
keeps body functioning
• Remember, mitosis produces two identical
daughter cells
• Mitosis is constantly happening in your body
to allow for growth, replacement and repair
• While you read this slide, millions of new
cells were produced by mitosis in the tissues
of your body!
• Don’t forget cellular scale and intelligence—
it’s a whole planet happening at the submicroscopic level
Larry M. Frolich, Ph.D.
GENETICS
•
Cells divide and pass on instructions coded in DNA of
chromosomes
• Each chromosome is a huge
DNA molecule with coded
information
– DNA replicates to pass on
information
– DNA is transcribed to make
proteins that run cell metabolism
•
•
Cancer—example of what happens when genetic
control goes awry
Normal inheritance and meiosis
Larry M. Frolich, Ph.D.
Chrosomes
• REVIEW: Each
chromosome is a
single DNA molecule
wrapped up within a
special group of
proteins giving it a
particular shape
Larry M. Frolich, Ph.D.
DNA is structured to replicate
• DNA is “double helix”—
two complementary
strands wound in a spiral
• Strands separate and
DNA replicates by filling
in other half of each
separated strand
• Famous Watson-Crick
model (Nobel prize)
Larry M. Frolich, Ph.D.
DNA replicates to pass on information
(to daughter cells in mitosis)
Larry M. Frolich, Ph.D.
DNA is transcribed to make proteins
that run cell metabolism
•
•
•
•
•
DNA is transcribed to mRNA
mRNA is translated to amino acid sequence
Amino acid sequence folds up into protein
Proteins catalyze reactions of cell metabolism
This process is called “gene expression”—the
information in one region of the DNA—a
“gene”—is being expressed so that the cell’s
metabolism can function
Larry M. Frolich, Ph.D.
2 steps of gene expression
1. Transcription – DNA
is read to make a
mRNA in the
nucleus of our cells
2. Translation –
Reading the mRNA
to make a protein in
the cytoplasm
Larry M. Frolich, Ph.D.
Transcription
• Happens in nucleus
• DNA double helix
“opens up”
• mRNA transcript is
made from DNA
template
Larry M. Frolich, Ph.D.
Translation
• Happens outside
nucleus
• Ribosomes (special
RNA particles or
organelles) do the
translation
• They glom onto
mRNA and line up
amino acids
according to mRNA
sequence (see next
slide for “code”
Larry M. Frolich, Ph.D.
RNA-protein
translation code
• Every three RNA
bases codes for one
amino acid
• This code is very
evolutionary
conservative—works
almost the same in all
forms of life
Larry M. Frolich, Ph.D.
Overview of transcription and translation
REMEMBER: A particular region of DNA that has the code to make a particular protein is called a “gene.”
Details in web link video animations
Larry M. Frolich, Ph.D.
How does cell decide when to activate
which genes to produce what proteins?
• DNA must be unpackaged
and uncoiled in order to be
transcribed to mRNA
• Lampbrush chromosome
shows loops of DNA that
are being transcribed
• What determines which
regions or genes are going
to be transcribed and
translated?
• This is called regulation of
gene expression
Larry M. Frolich, Ph.D.
Regulation of gene expression
•
•
•
Gene expression is regulated—not all genes are
constantly active and having their protein produced
The regulation or feedback on gene expression is
how the cell’s metabolism is controlled.
This regulation can happen in different ways:
1. Transcriptional control (in nucleus):
•
e.g. chromatin density and transcription factors
2. Posttranscriptional control (nucleus)
•
e.g. mRNA processing
3. Translational control (cytoplasm)
•
e.g. Differential ability of mRNA to bind ribosomes
4. Posttranslational control (cytoplasm)
•
•
e.g. changes to the protein to make it functional
When regulation of gene expression goes wrong—
cancer!
Larry M. Frolich, Ph.D.
DNA technology
• Recombinant DNA
• DNA sequencing and Human Genome
Project
• “Genetic Engineering”
NOTE: This is probably going to be the century for biological technology. What we’ve
done with smart silicon systems will soon seem like nothing compared to what we will
do with smart carbon/life-based systems. The technologies to understand, build,
manipulate and control DNA, protein and cellular systems have been growing for the
last fifty years and will undoubtedly keep doing so. Please view the web links and do
the ethical issue essay for this part of the course. I think you’ll find the DNA
technologies and our ability to manipulate cell metabolism fascinating!
Larry M. Frolich, Ph.D.
GENETICS
•
•
Cells divide and pass on instructions coded in DNA of
chromosomes
Each chromosome is a huge DNA molecule with coded
information
– DNA replicates to pass on information
– DNA is transcribed to make proteins that run cell
metabolism
• Cancer—example of
what happens when
genetic control goes
awry
•
Normal inheritance and meiosis
Larry M. Frolich, Ph.D.
Characteristics of cancer cells
1. Lack differentiation and do not contribute to body functioning
2. Have abnormal nuclei that are enlarged and may have an
abnormal number of chromosomes
3. Unlimited ability to divide
•
one way is through turning on the telomerase gene that allows
telomeres on chromosomes to continually be built thus allowing a cell
to divide over and over again
4. Form tumors
•
Benign tumors are usually encapsulated and do not invade adjacent
tissue while a cancerous tumor usually is not encapsulated and
eventually invades surrounding tissue
5. Can divide without growth factors
6. Become abnormal gradually through a multistage process
7. Undergo angiogenesis and metastasis
Larry M. Frolich, Ph.D.
The 3 phases in the development of
cancer cells
•
Initiation – a single cell
undergoes a mutation
that causes it to divide
repeatedly
•
Promotion – a tumor
develops and cells within
the tumor mutate
•
Progression – a cell
mutates in such a way
that allows it to invade
surrounding tissue
Larry M. Frolich, Ph.D.
The genetic basis for cancer
• Proto-oncogenes – products promote the cell
cycle and prevent cell death (apoptosis)
• Tumor-suppressor genes – products inhibit the
cell cycle and promote apoptosis
• Mutations in the genes above can cause
cancer, in fact proto-oncogenes that have
mutated are cancer-causing genes called
oncogenes
Larry M. Frolich, Ph.D.
Comparing these genes in normal and
cancer cells
Larry M. Frolich, Ph.D.
CANCER QUICK COURSE—WHAT CAN YOU DO TO PREVENT/TREAT?
Types of cancer
• Oncology – study of cancer
• Carcinomas: cancers of the epithelial tissue
• Adenocarcinomas: cancers of glandular
epithelial cells
• Sarcomas: cancers of muscle and connective
tissues
• Leukemias: cancers of the blood
• Lymphoma: cancers of lymphatic tissues
Larry M. Frolich, Ph.D.
CANCER QUICK COURSE—WHAT CAN YOU DO TO PREVENT/TREAT?
Causes of cancer
• Genetics
• Environmental carcinogens
– Radiation
– Environmental carcinogens (tobacco smoke
and pollutants)
– Viruses
Larry M. Frolich, Ph.D.
CANCER QUICK COURSE—WHAT CAN YOU DO TO PREVENT/TREAT?
Genetic causes of cancer
• Examples of genes associated with cancer:
– BRCA1 and BRCA2 – tumor-suppressor genes that
are associated with breast cancer
– RB – a tumor-suppressor gene that is associated
with an eye tumor
– RET – proto-oncogene that is associated with thyroid
cancer
• Mutations of these genes predispose individuals
to certain cancers but it takes at least one more
acquired mutation during their lifetime to
develop cancer
Larry M. Frolich, Ph.D.
CANCER QUICK COURSE—WHAT CAN YOU DO TO PREVENT/TREAT?
Environmental causes of cancer
•
Radiation:
– Environmental factors such as UV light (in sunlight or tanning
lights) and x-rays can cause mutation in DNA
•
Organic chemicals:
– Tobacco smoke: increases cancer of lungs, mouth, larynx and
others
– Pollutants: substances such as metals, dust, chemicals and
pesticides increase the risk of cancer
•
Viruses:
– Hepatitis B & C: virus that can cause liver cancer
– Epstein-Barr virus: can cause Burkitt’s lymphoma
– Human papillomavirus: can cause cervical cancer
Larry M. Frolich, Ph.D.
CANCER QUICK COURSE—WHAT CAN YOU DO TO PREVENT/TREAT?
Seven warning signs of cancer
•
•
•
•
•
•
•
Change in bowel or bladder habits
A sore that does not heal
Unusual bleeding or discharge
Thickening or lump in breast or elsewhere
Indigestion or difficulty in swallowing
Obvious change in wart or mole
Nagging cough or hoarseness
Larry M. Frolich, Ph.D.
CANCER QUICK COURSE—WHAT CAN YOU DO TO PREVENT/TREAT?
Some routine screening tests for
cancer
•
Self-examination – monthly
exams of breasts and
testicles starting at age 20
•
Colonoscopy – every 5 years
starting at age 50
•
Mammogram – yearly after
age 40
•
Pap smear – should begin
these 3 years after vaginal
intercourse or no later than
age 21
Larry M. Frolich, Ph.D.
CANCER QUICK COURSE—WHAT CAN YOU DO TO PREVENT/TREAT?
Health Focus: Self exams
Larry M. Frolich, Ph.D.
CANCER QUICK COURSE—WHAT CAN YOU DO TO PREVENT/TREAT?
Detecting skin cancer
• A – asymmetry
• B – border is
irregular
• C – color varies from
one area to another
• D – diameter is
larger than 6mm
Larry M. Frolich, Ph.D.
CANCER QUICK COURSE—WHAT CAN YOU DO TO PREVENT/TREAT?
Other ways to detect cancer
• Tumor marker tests – blood tests for tumor
antigens/antibodies
– CEA (carcinoembryonic antigen) antigen can be detected in
someone with colon cancer
– PSA (prostate-specific antigen) test for prostate cancer
• Genetic tests – tests for mutations in proto-oncogenes
and tumor-suppressor genes
– RET gene (thyroid cancer)
– P16 gene (associated with melanoma)
– BRCA1 (breast cancer)
• A diagnosis of cancer can be confirmed by performing a
biopsy
Larry M. Frolich, Ph.D.
CANCER QUICK COURSE—WHAT CAN YOU DO TO PREVENT/TREAT?
Standard cancer treatments
• Surgery – removal of small cancers
• Radiation therapy – localized therapy that causes
chromosomal breakage and disrupts the cell cycle
• Chemotherapy – drugs that treat the whole body that
kills cells by damaging their DNA or interfering with DNA
synthesis
• Bone marrow transplants – transplant bone marrow from
one individual to another
Larry M. Frolich, Ph.D.
CANCER QUICK COURSE—WHAT CAN YOU DO TO PREVENT/TREAT?
Newer cancer therapies
• Immunotherapy – inject immune cells that are genetically
engineered to bear the tumor’s antigens
• Passive immunotherapy – antibodies that are linked to
radioactive isotopes or chemotherapeutic drugs are
injected into the body
• p53 gene therapy – a retrovirus in clinical trial that is
injected into the body where it will infect and kill only
tumor cells (cells that lack p53 = tumor cells)
• Angiogenesis inhibition - Angiostatin and endostatin are
drugs in clinical trials that appear to inhibit angiogenesis
Larry M. Frolich, Ph.D.
CANCER QUICK COURSE—WHAT CAN YOU DO TO PREVENT/TREAT?
Bioethical focus: Control of tobacco
• Food for thought:
• Smoking diminishes the health of the smoker and damages
nearly every major organ
• Within minutes of smoking, a smoker’s body begins to heal
• Smoking low-tar or low-nicotine is no different than smoking any
other cigarette
• The tobacco industry targets young people (9 out of 10 smokers
start before age 18)
• It is the single most preventable cause of death and disease in
the US
• Give your thoughts:
• Who should pay for the medical bills associated with smoking?
• Should the government prevent the sale of tobacco or leave it up
to the individual?
Larry M. Frolich, Ph.D.
GENETICS
•
•
Cells divide and pass on instructions coded in DNA of
chromosomes
Each chromosome is a huge DNA molecule with coded
information
– DNA replicates to pass on information
– DNA is transcribed to make proteins that run cell
metabolism
•
Cancer—example of what happens when genetic
control goes awry
• Normal inheritance and
meiosis
Larry M. Frolich, Ph.D.
How are genetic traits combined and
passed on from parent to offspring
• Meiosis produces gametes or sex cells
(eggs and sperm) with just one member of
each chromosome pair
• Fertilization results in union of female
gamete (egg) with male gamete (sperm)
• Subsequent embryonic, fetal and
embryonic development by mitosis and
differentiation of cell types produces new
individual
Larry M. Frolich, Ph.D.
18.3 Meiosis
Overview of meiosis
•
•
•
Two nuclear divisions
occur to make 4 haploid
cells (cells with just one
member of each
chromosome pair)
Meiosis results in
gametes (egg and
sperm)
Has 8 phases (4 in each
meiosis I & II)
Larry M. Frolich, Ph.D.
Alleles
• A particular gene, or protein-coding region of
DNA along a chromosome might have a few
different variations, called alleles
• The combination of alleles, at a particular
gene, or chromosome region, that you get
from your mother and father determine your
hereditary traits
• Please see the Dragon Genetics lab to
understand this (in online lab links for this
section)
Larry M. Frolich, Ph.D.
Fertilization
• After meiosis, male and female gametes (sperm and
egg) unite to form a new cell—a zygote—that has the
full set of 23 pairs of chromosomes.
Larry M. Frolich, Ph.D.
Embryonic development—mitosis produces tissues/structures of adult
Larry M. Frolich, Ph.D.
Larry M. Frolich, Ph.D.
Some adult
features are coded
for genetically in
alleles or gene
varieties of sperm
and egg
Be sure to see
sickle cell
anemia
example in
Web Links for
this section of
the course
Larry M. Frolich, Ph.D.
Inheritance and Natural Selection
• Some combinations of alleles, produced during meiosis
and fertilization might be more advantageous
• This is what leads to natural selection. Individuals with
more advantageous traits will survive to reproduce and
pass on those traits.
• Darwin realized that slow changes in inherited traits, due
to natural selection produced the great evolutinoary
history of life.
• Before his synthesis of all the evidence, no one could
make sense of living systems. Now, “Nothing in Biology
Makes Sense Except in the Light of Evolution”
•
--Theodosius Dobzhansky
Please do the Coyote Lab to see how meiosis, fertilization,
inheritance and natural selection all work together to produce the
gradual change in biological organisms that we call evolution.
You can download this lab from the Online Lab links for this
section of the course.
Larry M. Frolich, Ph.D.
Larry M. Frolich, Ph.D.
GENETICS
• Cells divide and pass on
instructions coded in DNA of
chromosomes
• Each chromosome is a huge DNA
molecule with coded information
– DNA replicates to pass on information
– DNA is transcribed to make proteins
that run cell metabolism
• Cancer—example of what happens
when genetic control goes awry
• Normal inheritance and meiosis
Larry M. Frolich, Ph.D.
GENETICS (review)
• Cells divide and pass on
instructions coded in DNA of
chromosomes
• Each chromosome is a huge DNA
molecule with coded information
– DNA replicates to pass on information
– DNA is transcribed to make proteins
that run cell metabolism
• Cancer—example of what happens
when genetic control goes awry
• Normal inheritance and meiosis
Larry M. Frolich, Ph.D.
DNA and chromosomes
• Long DNA molecules (millions
of base pairs long) in nucleus
are called chromosomes
• Each chromosome is organized
and packaged or wrapped up
with proteins giving it a certain
shape
• In humans, 23 pairs of
chromosomes
– 1 of each pair from mother
– 1 of each pair from father
• Total view of all 23 pairs is
called karyotype
Larry M. Frolich, Ph.D.
Mitosis—what happens (overview)
• DNA/chrosomes replicate
(make exact copies
• Copies line up at center
of cell
• Copies pulled to opposite
ends of cells by
centromeres/spindles
• Cell membrane pinches
off and splits cell into two
Larry M. Frolich, Ph.D.
Mitosis—constant, fast,
keeps body functioning
• Remember, mitosis produces two identical
daughter cells
• Mitosis is constantly happening in your body
to allow for growth, replacement and repair
• While you read this slide, millions of new
cells were produced by mitosis in the tissues
of your body!
• Don’t forget cellular scale and intelligence—
it’s a whole planet happening at the submicroscopic level
Larry M. Frolich, Ph.D.
DNA is structured to replicate
• DNA is “double helix”—
two complementary
strands wound in a spiral
• Strands separate and
DNA replicates by filling
in other half of each
separated strand
• Famous Watson-Crick
model (Nobel prize)
Larry M. Frolich, Ph.D.
DNA is transcribed to make proteins
that run cell metabolism
•
•
•
•
•
DNA is transcribed to mRNA
mRNA is translated to amino acid sequence
Amino acid sequence folds up into protein
Proteins catalyze reactions of cell metabolism
This process is called “gene expression”—the
information in one region of the DNA—a
“gene”—is being expressed so that the cell’s
metabolism can function
Larry M. Frolich, Ph.D.
Overview of transcription and translation
REMEMBER: A particular region of DNA that has the code to make a particular protein is called a “gene.”
Details in web link video animations
Larry M. Frolich, Ph.D.
Regulation of gene expression
•
•
•
Gene expression is regulated—not all genes are
constantly active and having their protein produced
The regulation or feedback on gene expression is
how the cell’s metabolism is controlled.
This regulation can happen in different ways:
1. Transcriptional control (in nucleus):
•
e.g. chromatin density and transcription factors
2. Posttranscriptional control (nucleus)
•
e.g. mRNA processing
3. Translational control (cytoplasm)
•
e.g. Differential ability of mRNA to bind ribosomes
4. Posttranslational control (cytoplasm)
•
•
e.g. changes to the protein to make it functional
When regulation of gene expression goes wrong—
cancer!
Larry M. Frolich, Ph.D.
How are genetic traits combined and
passed on from parent to offspring
• Meiosis produces gametes or sex cells
(eggs and sperm) with just one member of
each chromosome pair
• Fertilization results in union of female
gamete (egg) with male gamete (sperm)
• Subsequent embryonic, fetal and
embryonic development by mitosis and
differentiation of cell types produces new
individual
Larry M. Frolich, Ph.D.
Fertilization
• After meiosis, male and female gametes (sperm and
egg) unite to form a new cell—a zygote—that has the
full set of 23 pairs of chromosomes.
Larry M. Frolich, Ph.D.
Inheritance and Natural Selection
• Some combinations of alleles, produced during meiosis
and fertilization might be more advantageous
• This is what leads to natural selection. Individuals with
more advantageous traits will survive to reproduce and
pass on those traits.
• Darwin realized that slow changes in inherited traits, due
to natural selection produced the great evolutinoary
history of life.
• Before his synthesis of all the evidence, no one could
make sense of living systems. Now, “Nothing in Biology
Makes Sense Except in the Light of Evolution”
•
--Theodosius Dobzhansky
Please do the Coyote Lab to see how meiosis, fertilization,
inheritance and natural selection all work together to produce the
gradual change in biological organisms that we call evolution.
You can download this lab from the Online Lab links for this
section of the course.
Larry M. Frolich, Ph.D.