3.1 essential questions & key terms 1. what is sickle cell disease? 2. why does the sickling of...
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UNIT THREE: SICKLE CELL DISEASE
3.1 Essential Questions & Key Terms
1. What is sickle cell disease?
2. Why does the sickling of red blood cells cause health problems?
3. What is sickle cell anemia?
4. How is anemia diagnosed?
5. How does sickle cell disease affect daily life?
Key Terms
Anemia
Blood Plasma
Erythrocytes (Red Blood Cells)
Hematocrit
Leukocytes (White Blood Cells)
Sickle Cell Disease
Thrombocytes (Platelets)
Sickle Cell Disease• Disease passed down through families • Caused by an abnormal type of hemoglobin called
hemoglobin S• Affects red blood cells
• Red blood cells (normally shaped like a disc) form an abnormal sickle/crescent shape
Hemoglobin• Protein• Primary component of red blood cells• Composed of four sub-units
• Each carries one oxygen molecule
• People with sickle cell have abnormal hemoglobin
Sickle Cell Disease• Sickled Red Blood Cells
1. Deliver less oxygen
2. Get stuck more easily in small blood vessels
3. Fragile- break into pieces that can interrupt healthy blood flow
• Decrease the amount of oxygen flowing to body tissues even more
• …feedback loop?
The Effects of SCD• Millions of people throughout
the world- major public health concern
• 3% of people with SCD die annually- sudden death• More prone to blood clots
• Heart attacks• Strokes• Pulmonary embolisms
• Increased susceptibility to bacterial and viral infections.
Anemia• Blood is deficient in
red blood cells, in hemoglobin, or in total volume
• SCD often causes anemia
• Referred to as Sickle Cell Anemia
Activity 3.1.1: Blood Detectives• Anna Garcia’s autopsy report shows she had SCD• You will learn the components and function of blood in order
to better understand SCD and it’s impact on the body
1. You will examine Anna’s blood with a microscope
2. You will design an experiment to see how cell shape impacts movement
3. You will complete a hematocrit blood test to determine whether Anna’s SCD was causing other related health problems
Career Journal• Phlebotomist• ANY format
• Brochure• Want-Ad• Sketch• Computer Graphic
• Same INFO• Education and/or Training • Responsibilities and Daily Activities• Salary Range• Documentation of Sources• Self-Reflection
Blood Plasma• The pale yellow fluid portion of whole blood
Erythrocytes (Red Blood Cells)• Hemoglobin-containing cells that carry oxygen to tissues
and take carbon dioxide back to your lungs to be exhaled• Responsible for the red color of vertebrate blood
Leukocytes (White Blood Cells)• Colorless blood cells that lack hemoglobin and contain a
nucleus: lymphocytes, monocytes, neutrophils, eosinophils, and basophils
• Destroy bacteria• Produce antibodies against bacteria and viruses• Fight malignant diseases
Thrombocytes (Platelets)• A minute colorless anucleate (no nucleus) disk-like body
of mammalian blood • Main function is to interact with clotting proteins to stop or
prevent bleeding
Hematocrit• The percent of the volume of whole blood that is
composed of red blood cells • Determined by separation of red blood cells from the
plasma usually by centrifugation
Hematocrit Results
Anna’s hematocrit is approximately 30% red blood cell volume. Anything less than 35% for a female is considered a low hematocrit
Component: Function:Plasma
Fluid that is composed of about 92% water, 7% vital proteins such as albumin, gamma globulin, anti-hemophilic factor, and other clotting factors, and 1% mineral salts, sugars, fats, hormones and vitamins. It is also the vehicle by which blood cells are carried around the body.
Red Blood Cells (Erythrocytes)
Cells that carry oxygen from the lungs to your body’s tissue and take carbon dioxide back to your lungs to be exhaled.
White Blood Cells (Leukocytes)
Cells that travel throughout the body and destroy bacteria, some produce antibodies against bacteria and viruses, and others help fight malignant diseases.
Platelets (Thrombocytes) Small, colorless cell fragments in the blood whose main function is to interact with clotting proteins to stop or prevent bleeding.
Activity 3.1.1: Blood Detectives
3.1.2 Sickle Cell Diaries• Almost every patient with SCD
experiences painful episodes called crises
• The crises can be severe enough to require a hospital stay
• Anna’s doctor asked her to keep a diary documenting all of her crises
• In this activity you are going to investigate what life is like living with SCD…
3.1.2 Sickle Cell Diaries• All docs are online• Graphic Organizer=Table• Pick any patient
• 4 year old male being treated with antibiotics and folic acid supplements
• 7 year old female being treated with chronic transfusion therapy
• 15 year old male who will have a bone marrow transplant
Diary Entry
Crisis Symptoms
Benefits of Treatment
Risks of Treatment
Professionals Involved
Lifestyle Concerns
Anna 10
Anna 17
Anna 22
Anna 31
4 year old male
7 year old female
15 year old male
3.1.2 Sickle Cell Diaries Table
This Week!• Today: Newsletters due• Tomorrow
• Survival of the Sickest Presentations• Notebook and portfolio checks• Quiz up to slide 33
• Wednesday-Thursday• Community Benefit Project
• Friday• Project Summary Due!• All gifts in for Pitino Shelter• Wrap Party!
3.1 The Disease: Review1. What is sickle cell
disease?
2. Why does the sickling of red blood cells cause health problems?
3. What is sickle cell anemia?
4. How is anemia diagnosed?
5. How does sickle cell disease affect daily life?
Key Terms
Anemia
Blood Plasma
Erythrocytes (Red Blood Cells)
Hematocrit
Leukocytes (White Blood Cells)
Sickle Cell Disease
Thrombocytes (Platelets)
Read Survival of the Sickest• This is a book about mysteries and miracles. About medicine and myth. About cold iron, red blood, and neverending ice. It’s a book about survival and creation. It’s a book that wonders why, and a book that asks why not. It’s a book in love with order and a book that craves a little chaos. Most of all, it’s a book about life—yours, ours, and that of every little living thing under the sun. About how we all got here, where we’re all going, and what we can do about it. Welcome to our magical medical mystery tour.
Genetic Basis for Sickle Cell Disease
• Sickle Cell Link (Video)• A bit on evolution….
What were Darwin’s Main ideas anyway???1. Species change over time2. Living species have arisen
from earlier life forms (descending from a common ancestor)
Close ties between organisms and their environments*
Can be traced back to the ancient Greeks
Evolution is the greatest unifying theme in biology, and The Origin of Species fueled an explosion in biological research and knowledge that continues today.
Evolutionary theory continues to expand beyond Darwin’s basic ideas.
Nonetheless, few contributions in all of science have explained so much, withstood as much repeated testing over the years, and stimulated as much other research as those of Darwin.
• Natural Selection
1. Produce more offspring than the environment can support
2. Individuals of a population vary in their characteristics
3. Many characteristics can be inherited
4. Beneficial characteristics are preferentially passed down
• Darwin found convincing evidence for his ideas in the results of artificial selection
• With humans playing the role of the environment
Hundreds to thousands of years of breeding (artificial selection)
Ancestral dog (wolf)
Throughout Human Evolution• The best genes survive from
one generation to next• Why do we still have some
deleterious genetic mutations?
• Various mutations have provided a benefit• Extra Iron• Sickle Cell
• We continue to see these mutations in modern day humanity even when the benefit no longer exists (leftover)
3.2 Essential Questions & Key Terms1. What is the DNA code?
2. What is the connection between genes and proteins?
3. How are proteins produced in a cell?
4. How does the sequence of nucleotides in DNA determine the sequence of amino acids in a protein?
5. What is a mutation?
6. What determines the shape of a protein?
7. Is the shape of a protein affected by its surrounding environment?
8. How does a change in the DNA code affect the shape of a protein?
9. Can changing just one nucleotide in a gene change the shape of a protein?
Key TermsAmino AcidAnticodonCodonHydrophilicHydrophobicMessenger RNA (mRNA)MutationNucleotideProteinProtein SynthesisRibonucleic Acid (RNA)RibosomeTranscriptionTransfer RNA (tRNA)Translation
Proteins• What we know…
• DNA codes for proteins• Proteins produce all our genetic traits• Responsible for just about everything our bodies do
• Amazingly…• All the proteins we need are manufactured based on
the DNA code: A,T, C and G• The arrangement of nucleotides dictates everything
we are genetically and runs our whole bodies because they dictate what proteins our bodies produce
3.2.1 Protein Synthesis
1. The information on DNA is copied onto an mRNA strand
2. As, Cs, Gs and Us (in place of Ts)
3. mRNA leaves the nucleus and moves into the cytoplasm
4. A ribosome attaches to the mRNA
5. tRNA molecules bring amino acids (there are 20) into the ribosome
6. The tRNA anti-codons match the mRNA codons (3 nucleotides at a time)
7. The ribosome assembles the amino acids into the specific protein originally coded for by the gene on the DNA
Transcription & Translation
WATCH VIDEO
More on transcription…
From DNA to mRNA to Amino Acid:A=A=C=G=A=T=A=C=C=
UUGCUAUGG
• Polymers of amino acids • Joined by peptide bonds
Structure of Proteins
Activity 3.2.1 Protein Synthesis• You will explore how the body uses DNA to produce proteins
More on translation…
More on transcription…
Activity 3.2.2: The Genetic Code• Decode messages• Transcription and
translation• Effect of mutations on
protein production• Genetic mutation that
causes SCD• Chose 1 to illustrate with
any supplies you chose• Decode the others in
your lab book
Activity 3.2.3: Does Changing One Nucleotide Make a Big Difference?
Nova Documentary
The sickle form of the hemoglobin gene:
1. A is changed to a T
2. 6th amino acid in the b-globin protein from GAG to GUG
3. 6th amino acid in the protein to become valine instead of glutamic acid
That single amino acid replacement
4. Alters the shape and the chemistry of the hemoglobin molecule
5. Causing it to polymerize
6. Distort the red blood cell into the sickle shape
Genetic mutation to hemoglobin, causing sickle cell disease
Activity 3.2.3: Does Changing One Nucleotide Make a Big Difference?
Glutamic Acid:Hydrophilic or hydrophobic? ____Hydrophilic______Positive, negative or neutral? ___Negative_______
Valine:Hydrophilic or hydrophobic? _____Hydrophobic_______Positive, negative or neutral? ____Neutral____________
Protein shape dictates function! What dictates shape?
1. Amino acids present• Charge- positive vs.
negative amino acids • Hydrophobic vs.
hydrophilic
2. The order of amino acids
3. Surrounding Environment• Oil• Water
3.2 It’s in the Genes: Review1. What is the DNA code?
2. What is the connection between genes and proteins?
3. How are proteins produced in a cell?
4. How does the sequence of nucleotides in DNA determine the sequence of amino acids in a protein?
5. What is a mutation?
6. What determines the shape of a protein?
7. Is the shape of a protein affected by its surrounding environment?
8. How does a change in the DNA code affect the shape of a protein?
9. Can changing just one nucleotide in a gene change the shape of a protein?
Key TermsAmino Acid
Anticodon
Codon
Hydrophilic
Hydrophobic
Messenger RNA (mRNA)
Mutation
Nucleotide
Protein
Protein Synthesis
Ribonucleic Acid (RNA)
Ribosome
Transcription
Transfer RNA (tRNA)
Translation
3.3 Chromosomes Key TermsAlleleAutosomeChromosomeDominant traitGeneGenetic MaterialGenotypeHeredityHomologous ChromosomesKaryotypeMeiosisMitosisMutationPedigreePhenotypeRecessive Trait
1. How is DNA passed to new cells during cell division?
2. What is a chromosome?3. How are traits passed
through the generations?4. Should a person have rights
to their organs and tissues? (Optional)
How do you get Sickle Cell Disease?• Caused by an abnormal
gene• Inherited Disease
• E.g., Tay Sachs, hemophilia, cystic fibrosis, and Huntington’s disease
• Vs. Infectious (like…)• How are mutations in DNA
passed down from one generation to the next?
Activity 3.3.1: How is DNA Passed Through the Generations?
• Chromosomes contain the codes for how to make specific proteins
• Determine the organism’s traits
• Chromosome Compaction• Specific instructions for a
protein are on sections of the chromosome called genes
Chromosomes• DNA is stored in a
compact form called chromosomes
• 46 chromosomes in somatic (body) cells
• 23 chromosomes in sex cells
• Egg cell from the mother fuses with the sperm cell from the father (zygote)
• = 46 chromosomes, 23 pairs
• One from mother and one from father in each pair
Early Zygote
Nuclei from egg and sperm fusing
Chromosomes and Sickle Cell• Chromosome 11
carries the instructions (genes) to make the hemoglobin protein
• There are different versions of these genes:• Normal – healthy• Mutated or changed –
Sickle cell or other hemoglobin disorder
Mitosis (video)
1. The chromosomes coil up
2. A mitotic spindle moves them to the middle of the cell
3. The sister chromatids then separate
4. Move to opposite poles of the cell
5. Two nuclei form (1 at each pole)
6. Cytokinesis, in which the cell divides in two
INTERPHASE PROPHASE PROMETAPHASE
LM 2
50
ChromatinCentrosomes(with centriole pairs)
Nucleolus
Nuclearenvelope Plasma
membrane
Early mitoticspindle Centrosome
CentromereChromosome, consistingof two sister chromatids
Spindlemicrotubules
KinetochoreFragmentsof nuclearenvelope
METAPHASE ANAPHASE TELOPHASE&CYTOKINESIS
Spindle
Metaphaseplate
Daughterchromosomes
Nuclearenvelopeforming
Cleavagefurrow
Nucleolusforming
Under the scope…
Meiosis (video)◦ Meiosis, like mitosis, is preceded by chromosome
duplication◦ But in MEIOSIS:◦ The cell divides twice to form four daughter cells◦ Four DIFFERENT CELLS with HALF the genetic
information◦ Half the number of chromosomes
◦ The first division, meiosis I Starts coping (sisters chromatids) and with synapsis-
the pairing of homologous chromosomes◦ In crossing over
Homologous chromosomes exchange corresponding segments
◦ Meiosis I separates each homologous pair produce two daughter cells, each with one set of
chromosomes◦ Meiosis II is essentially the same as mitosis
The sister chromatids of each chromosome separate The result is a total of four haploid cells
MEIOSIS I: Homologous chromosomes separate
INTERPHASE PROPHASE I METAPHASE I ANAPHASE I
Centrosomes (with centriole pairs)
Sites of crossing over
Spindle
Microtubulesattached to kinetochore
Metaphaseplate
Sister chromatids remain attached
Nuclearenvelope Chromatin
Sisterchromatids Tetrad
Centromere(with kinetochore)
Homologouschromosomes separate
Meiosis
Sites of crossing overSpindle
Sister chromatidsHomologous Chromosomes Tetrad: via synapsis
Prophase l of Meiosis
ChiasmaTetrad
Centromere
PROPHASE II METAPHASE II ANAPHASE II
TELOPHASE IAND CYTOKINESIS
TELOPHASE IIAND CYTOKINESIS
Cleavagefurrow
Haploid daughter cellsforming
Sister chromatidsseparate
MEIOSIS II: Sister chromatids separate
Meiosis Continued…
Gametes
Metaphase II
Two equally probablearrangements of chromosomes at
metaphase I
Possibility 1 Possibility 2
Mitosis MeiosisParent cell
(before chromosome replication)
Chromosome replication
Chromosome replication
Chromosomes align at themetaphase plate
Tetradsalign at themetaphase plate
Sister chromatidsseparate during anaphase
Homologous chromosomesseparate duringanaphase I;sister chromatidsremain together
No furtherchromosomalreplication; sisterchromatidsseparateduringanaphase II
Prophase
Metaphase
AnaphaseTelophase
Duplicated chromosome(two sister chromatids)
Daughter cellsof mitosis
2n 2n
Daughtercells of
meiosis I
n n nn
2n = 4
Tetrad formedby synapsis ofhomologouschromosomes
Meiosis i
Meiosis ii
Prophase I
Metaphase I
Anaphase ITelophase I
Haploidn = 2
Daughter cells of meiosis II
What happens to chromosomes throughout?It’s all in the name…
• Start as chromatin• Duplicate• Thicken and clump into chromosomes• Consist of two sister chromatids- replicates• In meiosis…
• Chromosomes (sister chromatid duplicates) find their other half (maternal and paternal)
• They make homologous pairs, forming an tetrad• One chromosome carrying info from the mother,
the other carrying info from the father
Mutations are the original source of genetic variation
Raw material for natural selection
1. Synapsis and crossing over during prophase
2. Independent assortment (orientation) of homologous chromosome pairs along the metaphase plate (during metaphase)
3. Random Fertilization of eggs by sperm
3.3 Chromosomes ReviewKey TermsAlleleAutosomeChromosomeDominant traitGeneGenetic MaterialGenotypeHeredityHomologous ChromosomesKaryotypeMeiosisMitosisMutationPedigreePhenotypeRecessive Trait
1. How is DNA passed to new cells during cell division?
2. What is a chromosome?3. How are traits passed
through the generations?4. Should a person have rights
to their organs and tissues? (Optional)
3.4 Inheritance
1. Why does sickle cell disease run in families, yet is not present in every generation?
2. How can doctors and genetic counselors calculate the probability of a child inheriting a disease?
3. How does the presence of malaria in a region affect the frequencies of normal versus sickle cell alleles?
Key TermsAlleleChromosomeDominant TraitGeneGenotypeHeredityPedigreePhenotypePunnett SquareRecessive Trait
How do we know all this stuff?• Experimental genetics began in
an abbey garden• Father of modern genetics
• Gregor Mendel’s quantitative experiments
• Parents pass on to their offspring discrete heritable factors, which maintain individuality
• 7 years after Darwin’s Origins in 1859
• Pea plants
• Easy to grow, came in many varieties, easy to ensure self or cross fertilization
• Crossed plants that differed in certain characteristics
• Traced traits from generation to generation• P(parental
generation)• F1 generation • F2 generation
The Humble Pea
Flower color
Flower position
Seed color
Seed shape
Pod color
Pod shape
Stem length
Purple White
Axial Terminal
Round Wrinkled
Inflated Constricted
Tall Dwarf
GreenYellow
Green Yellow
Different alleles of 7 genes
P generation(true-breeding parents)
F1 generation
F2 generation
Purple flowers White flowers
All plants havepurple flowers
Fertilization among F1 plants(F1 F1)
of plantshave purple flowers
34
of plantshave white flowers
14
Mendel found for each characteristic…• An organism inherits two alleles, one from each
parent• If the two alleles of an inherited pair differ
• Then one determines the organism’s appearance and is called the dominant allele
• The other allele as no noticeable effect on the organism’s appearance and is called the recessive allele
P plants
Gametes
Genetic makeup (alleles)
Gametes
F1 plants(hybrids)
F2 plants
PP pp
All P All p
All Pp
Sperm
12 P
P
P
p
p
PP Pp
Pp pp
EggsGenotypic ratio1 PP : 2 Pp: 1 pp
Phenotypic ratio3 purple : 1 white
12 p
• Homologous chromosomes bear the two alleles for each characteristic• Alternative forms of a gene reside at the same locus on homologous
chromosomes
1. Homozygous recessive
2. Homozygous dominant
3. Heterozygous
Genotype: PP aa BbHeterozygous
P a b
P a B
Gene loci
Recessiveallele
Dominantallele
Homozygousfor thedominant allele
Homozygousfor therecessive allele
Back to…How do you get SCD?• It is an inherited blood disorder
• Both parents have to have it to pass on the abnormal gene
• If you inherit the problem gene from one parent and a normal gene from the other• ‘Sickle cell trait' or be a Carrier• Doesn't usually cause any symptoms• Can be passed on to the next generation.
Chromosomes and Sickle Cell
• Chromosome 11 carries the instructions (genes) to make the hemoglobin protein.
• There are different versions of these genes:• Normal--healthy• Mutated or changed--Sickle cell or other hemoglobin disorder.
3.4.1: Family Inheritance• Pedigrees show the occurrence of a particular trait from
one generation to the next• P, F1 and F2 generations
• Males are represented by squares • Females are represented by circles• Relationships are represented with lines
• Make it easier to visualize relationships within families • Used to determine the mode of inheritance (dominant
versus recessive) of genetic diseases• Pedigrees illustrate what is or has been• Vs. Punnett Squares & probability (next)
With two carriers= 25% Chance SCD• For every pregnancy when both parents have sickle trait,
there is a 1in 4 chance that their offspring will have sickle cell anemia.
3.4.1: Family Inheritance & Pedigrees
• How does analyzing pedigrees help doctors, epidemiologists, researchers, and other scientists understand how diseases are inherited?
• How are pedigrees used to track diseases?• Why does sickle cell disease run in families, yet is not present in every generation?
Mendel’s LawsLaw of Dominance• In a cross of parents that are pure for contrasting traits, only one form of the
trait will appear in the next generation. Offspring that are hybrid for a trait will have only the dominant trait in the phenotype.
• Dominant vs. recessive traits
Law of Segregation• During the formation of gametes (eggs or sperm), the two alleles responsible
for a trait separate from each other. Alleles for a trait are then "recombined" at fertilization, producing the genotype for the traits of the offspring.
• Which of the two alleles ends up in which gamete (monohybrid cross in Punnett square)
Law of Independent Assortment• The different traits do not influence the inheritance of each other. They are
inherited INDEPENDENTLY.• When looking at multiple traits, alleles segregate separately (dihybrid cross in
Punnett square)
Punnett SquaresReginald Punnett
A DIHYBRID CROSS!
• Something a bit more challenging
• Uses Mendel's 3rd Law as well
3.4.2 What’s the Probability?
• How can doctors and genetic counselors calculate the probability of a child inheriting a disease?
3.4.2 What’s the Probability?Punnett Squares
• Create your own handout for this activity• Write four word problems that require Punnett squares
• Be creative!• Set up one question with chromosomes• Use a pedigree for at least one• Always ask for the genotypic and phenotypic ratio• Always ask a “what’s the percent chance that..” question• Be sure to have an answer key
• Work in 1s or 2s, but you’ll need to type and print one handout each
• TRADE- Due Monday!• Let’s complete some examples
Example with chromosomes• Complete a Punnett square
for these parents. Determine the genotypic and phenotypic ratios. Determine the percent chance a child has of having sickle cell anemia from this reproductive pairing
Example with pedigree• Anna’s mother passed away
three years ago, so she was unavailable for genetic testing. Based upon Anna’s family pedigree that you created in the previous activity, determine her mother’s possible genotypes and phenotypes related to sickle cell anemia. Explain your reasoning and describe the information you used to make your prediction.
Example word problem• Juan’s family has a history of sickle cell disease. His father
died of sickle cell disease complications when Juan was six years old. He remembers his father being in great pain. Juan marries Gina. Gina’s maternal grandmother and paternal grandfather had sickle cell disease, but neither of her parents has the disease. Juan does not want to have children because he is convinced they will have sickle cell disease. Gina is not so sure. They have come to you for advice about having whether or not to have children. Based on your calculations of the probability of their child getting sickle cell disease, what is your advice? Show your calculations and explain your reasoning for your response. It may be helpful for you to draw pedigrees and possible Punnett squares for both Juan’s and Gina’s families.
• The first cell line, cultured more than 60 years ago
• The HeLa Cell-Line has been reproducing independently, fueling biological research
• Bioethics- The study of controversial ethics brought about by advances in biological or medical research
The Immortal Story of Henrietta Lacks
The Great Debate
• Two sides of the argument• Henerietta’s• Dr. Gey’s
• Prep time• Design opening and closing
statement• Make THREE KEY
arguments• Plan a defense against
your opponent
• H: Opening statement (1 minutes)• G: Opening statement (1
minutes)• H: Key Point 1(one minute)
• G: rebuttal• H: rebuttal
• G: Key Point 1(one minute)• H: rebuttal• G: rebuttal
• H: Key Point 2 (one minute)• G: rebuttal• H: rebuttal
• G: Key Point 2 (one minute)• H: rebuttal• G: rebuttal
• H: Key Point 3 (one minute)• G: rebuttal• H: rebuttal
• G: Key Point 3 (one minute)• H: rebuttal• G: rebuttal
• H: Closing (one minute)• G: Closing (one minute)
Structure of the Great Debate
3.4 Inheritance Review
1. Why does sickle cell disease run in families, yet is not present in every generation?
2. How can doctors and genetic counselors calculate the probability of a child inheriting a disease?
3. How does the presence of malaria in a region affect the frequencies of normal versus sickle cell alleles?
Key TermsAlleleChromosomeDominant TraitGeneGenotypeHeredityPedigreePhenotypePunnett SquareRecessive Trait