GENETICS

1
GENETICS
2
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
• Cancerexample of what happens when genetic
  control goes awry
• Normal inheritance and meiosis

3
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
• Cancerexample of what happens when genetic
  control goes awry
• Normal inheritance and meiosis

4
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

5
Mitosiscell division

• Why do cells divide?
• Growthso tissues/structures can become larger
• Replacementmany tissues are constantly being
  replaced because they get worn out or used up.
  E.g. blood, skin, lining of gut, sperm
• Repairwhen tissues get damaged due to injury

6
Mitosiswhat 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

7
Mitosisdetails/stages
1. Prophase
3. Anaphase
4. Telophase
2. Metaphase
8
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

9
2. Mitosis Metaphase

• Chromosomes line up at the middle of the cell
  (equator)
• Fully formed spindle

10
3. Mitosis Anaphase

• Sister chromatids separate at the centromeres and
  move towards the poles

11
4. MitosisTelophase 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)

12
Mitosisconstant, 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!
• Dont forget cellular scale and intelligenceits
  a whole planet happening at the sub-microscopic
  level

13
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
• Cancerexample of what happens when genetic
  control goes awry
• Normal inheritance and meiosis

14
Chrosomes

• REVIEW Each chromosome is a single DNA molecule
  wrapped up within a special group of proteins
  giving it a particular shape

15
DNA is structured to replicate

• DNA is double helixtwo 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)

16
DNA replicates to pass on information (to
daughter cells in mitosis)
17
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 expressionthe
  information in one region of the DNAa geneis
  being expressed so that the cells metabolism can
  function

18
2 steps of gene expression

• Transcription DNA is read to make a mRNA in the
  nucleus of our cells
• Translation Reading the mRNA to make a protein
  in the cytoplasm

19
Transcription

• Happens in nucleus
• DNA double helix opens up
• mRNA transcript is made from DNA template

20
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

21
RNA-protein translation code

• Every three RNA bases codes for one amino acid
• This code is very evolutionary conservativeworks
  almost the same in all forms of life

22
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
23
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

24
Regulation of gene expression

• Gene expression is regulatednot all genes are
  constantly active and having their protein
  produced
• The regulation or feedback on gene expression is
  how the cells 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
  wrongcancer!

25
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 weve 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 youll find the DNA technologies
and our ability to manipulate cell metabolism
fascinating!
26
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
• Cancerexample of what happens when genetic
  control goes awry
• Normal inheritance and meiosis

27
Characteristics of cancer cells

• Lack differentiation and do not contribute to
  body functioning
• Have abnormal nuclei that are enlarged and may
  have an abnormal number of chromosomes
• 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
• 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
• Can divide without growth factors
• Become abnormal gradually through a multistage
  process
• Undergo angiogenesis and metastasis

28
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

29
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

30
Comparing these genes in normal and cancer cells
31
Types of cancer
CANCER QUICK COURSEWHAT CAN YOU DO TO
PREVENT/TREAT?

• 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

32
Causes of cancer
CANCER QUICK COURSEWHAT CAN YOU DO TO
PREVENT/TREAT?

• Genetics
• Environmental carcinogens
• Radiation
• Environmental carcinogens (tobacco smoke and
  pollutants)
• Viruses

33
Genetic causes of cancer
CANCER QUICK COURSEWHAT CAN YOU DO TO
PREVENT/TREAT?

• 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

34
Environmental causes of cancer
CANCER QUICK COURSEWHAT CAN YOU DO TO
PREVENT/TREAT?

• 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 Burkitts lymphoma
• Human papillomavirus can cause cervical cancer

35
Seven warning signs of cancer
CANCER QUICK COURSEWHAT CAN YOU DO TO
PREVENT/TREAT?

• 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

36
Some routine screening tests for cancer
CANCER QUICK COURSEWHAT CAN YOU DO TO
PREVENT/TREAT?

• 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

37
Health Focus Self exams
CANCER QUICK COURSEWHAT CAN YOU DO TO
PREVENT/TREAT?
38
Detecting skin cancer
CANCER QUICK COURSEWHAT CAN YOU DO TO
PREVENT/TREAT?

• A asymmetry
• B border is irregular
• C color varies from one area to another
• D diameter is larger than 6mm

39
Other ways to detect cancer
CANCER QUICK COURSEWHAT CAN YOU DO TO
PREVENT/TREAT?

• 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

40
Standard cancer treatments
CANCER QUICK COURSEWHAT CAN YOU DO TO
PREVENT/TREAT?

• 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

41
Newer cancer therapies
CANCER QUICK COURSEWHAT CAN YOU DO TO
PREVENT/TREAT?

• Immunotherapy inject immune cells that are
  genetically engineered to bear the tumors
  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

42
Bioethical focus Control of tobacco
CANCER QUICK COURSEWHAT CAN YOU DO TO
PREVENT/TREAT?

• Food for thought
• Smoking diminishes the health of the smoker and
  damages nearly every major organ
• Within minutes of smoking, a smokers 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?

43
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
• Cancerexample of what happens when genetic
  control goes awry
• Normal inheritance and meiosis

44
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

45
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)

46
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)

47
Fertilization

• After meiosis, male and female gametes (sperm and
  egg) unite to form a new cella zygotethat has
  the full set of 23 pairs of chromosomes.

48
Embryonic developmentmitosis produces
tissues/structures of adult
49
(No Transcript)
50
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
51
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.
52
(No Transcript)
53
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
• Cancerexample of what happens when genetic
  control goes awry
• Normal inheritance and meiosis

54
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
• Cancerexample of what happens when genetic
  control goes awry
• Normal inheritance and meiosis

55
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

56
Mitosiswhat 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

57
Mitosisconstant, 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!
• Dont forget cellular scale and intelligenceits
  a whole planet happening at the sub-microscopic
  level

58
DNA is structured to replicate

• DNA is double helixtwo 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)

59
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 expressionthe
  information in one region of the DNAa geneis
  being expressed so that the cells metabolism can
  function

60
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
61
Regulation of gene expression

• Gene expression is regulatednot all genes are
  constantly active and having their protein
  produced
• The regulation or feedback on gene expression is
  how the cells 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
  wrongcancer!

62
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

63
Fertilization

• After meiosis, male and female gametes (sperm and
  egg) unite to form a new cella zygotethat has
  the full set of 23 pairs of chromosomes.

64
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.