2 3.1 Essential Questions & Key Terms AnemiaBlood PlasmaErythrocytes (Red Blood Cells)HematocritLeukocytes (White Blood Cells)Sickle Cell DiseaseThrombocytes (Platelets)What is sickle cell disease?Why does the sickling of red blood cells cause health problems?What is sickle cell anemia?How is anemia diagnosed?How does sickle cell disease affect daily life?
3 Sickle Cell Disease Disease passed down through families Caused by an abnormal type of hemoglobin called hemoglobin SAffects red blood cellsRed blood cells (normally shaped like a disc) form an abnormal sickle/crescent shape
5 Hemoglobin Protein Primary component of red blood cells Composed of four sub-unitsEach carries one oxygen moleculePeople with sickle cell have abnormal hemoglobin
6 Sickle Cell Disease Sickled Red Blood Cells Deliver less oxygen Get stuck more easily in small blood vesselsFragile- break into pieces that can interrupt healthy blood flowDecrease the amount of oxygen flowing to body tissues even more…feedback loop?
7 The Effects of SCDMillions of people throughout the world- major public health concern3% of people with SCD die annually- sudden deathMore prone to blood clotsHeart attacksStrokesPulmonary embolismsIncreased susceptibility to bacterial and viral infections.
8 AnemiaBlood is deficient in red blood cells, in hemoglobin, or in total volumeSCD often causes anemiaReferred to as Sickle Cell Anemia
9 Activity 3.1.1: Blood Detectives Anna Garcia’s autopsy report shows she had SCDYou will learn the components and function of blood in order to better understand SCD and it’s impact on the bodyYou will examine Anna’s blood with a microscopeYou will design an experiment to see how cell shape impacts movementYou will complete a hematocrit blood test to determine whether Anna’s SCD was causing other related health problems
10 Career Journal Phlebotomist ANY format Same INFO Brochure Want-Ad SketchComputer GraphicSame INFOEducation and/or TrainingResponsibilities and Daily ActivitiesSalary RangeDocumentation of SourcesSelf-Reflection
11 Blood PlasmaThe pale yellow fluid portion of whole blood
12 Erythrocytes (Red Blood Cells) Hemoglobin-containing cells that carry oxygen to tissues and take carbon dioxide back to your lungs to be exhaledResponsible for the red color of vertebrate blood
13 Leukocytes (White Blood Cells) Colorless blood cells that lack hemoglobin and contain a nucleus: lymphocytes, monocytes, neutrophils, eosinophils, and basophilsDestroy bacteriaProduce antibodies against bacteria and virusesFight malignant diseases
14 Thrombocytes (Platelets) A minute colorless anucleate (no nucleus) disk-like body of mammalian bloodMain function is to interact with clotting proteins to stop or prevent bleeding
16 HematocritThe percent of the volume of whole blood that is composed of red blood cellsDetermined by separation of red blood cells from the plasma usually by centrifugation
17 Hematocrit ResultsAnna’s hematocrit is approximately 30% red blood cell volume. Anything less than 35% for a female is considered a low hematocrit
18 Activity 3.1.1: Blood Detectives Component:Function:PlasmaFluid 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.
19 3.1.2 Sickle Cell DiariesAlmost every patient with SCD experiences painful episodes called crisesThe crises can be severe enough to require a hospital stayAnna’s doctor asked her to keep a diary documenting all of her crisesIn this activity you are going to investigate what life is like living with SCD…
20 3.1.2 Sickle Cell Diaries All docs are online Graphic Organizer=Table Pick any patient4 year old male being treated with antibiotics and folic acid supplements7 year old female being treated with chronic transfusion therapy15 year old male who will have a bone marrow transplant
21 3.1.2 Sickle Cell Diaries Table DiaryEntryCrisis SymptomsBenefits of TreatmentRisks of TreatmentProfessionals InvolvedLifestyle ConcernsAnna 10Anna 17Anna 22Anna 314 year old male7 year old female15 year old male
22 This Week! Today: Newsletters due Tomorrow Wednesday-Thursday Friday Survival of the Sickest PresentationsNotebook and portfolio checksQuiz up to slide 33Wednesday-ThursdayCommunity Benefit ProjectFridayProject Summary Due!All gifts in for Pitino ShelterWrap Party!
23 3.1 The Disease: Review What is sickle cell disease? Why does the sickling of red blood cells cause health problems?What is sickle cell anemia?How is anemia diagnosed?How does sickle cell disease affect daily life?Key TermsAnemiaBlood PlasmaErythrocytes (Red Blood Cells)HematocritLeukocytes (White Blood Cells)Sickle Cell DiseaseThrombocytes (Platelets)
24 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.
25 Genetic Basis for Sickle Cell Disease Sickle Cell Link (Video)A bit on evolution….
26 What were Darwin’s Main ideas anyway??? What were Darwin’s Main ideas anyway???Species change over timeLiving 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
27 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.
28 Natural SelectionProduce more offspring than the environment can supportIndividuals of a population vary in their characteristicsMany characteristics can be inheritedBeneficial characteristics are preferentially passed down
29 Darwin found convincing evidence for his ideas in the results of artificial selectionWith humans playing the role of the environmentHundreds to thousands of years of breeding (artificial selection)Ancestral dog (wolf)
34 Throughout Human Evolution The best genes survive from one generation to nextWhy do we still have some deleterious genetic mutations?Various mutations have provided a benefitExtra IronSickle CellWe continue to see these mutations in modern day humanity even when the benefit no longer exists (leftover)
35 3.2 Essential Questions & Key Terms Amino AcidAnticodonCodonHydrophilicHydrophobicMessenger RNA (mRNA)MutationNucleotideProteinProtein SynthesisRibonucleic Acid (RNA)RibosomeTranscriptionTransfer RNA (tRNA)TranslationWhat is the DNA code?What is the connection between genes and proteins?How are proteins produced in a cell?How does the sequence of nucleotides in DNA determine the sequence of amino acids in a protein?What is a mutation?What determines the shape of a protein?Is the shape of a protein affected by its surrounding environment?How does a change in the DNA code affect the shape of a protein?Can changing just one nucleotide in a gene change the shape of a protein?
36 Proteins What we know… DNA codes for proteins Proteins produce all our genetic traitsResponsible for just about everything our bodies doAmazingly…All the proteins we need are manufactured based on the DNA code: A,T, C and GThe arrangement of nucleotides dictates everything we are genetically and runs our whole bodies because they dictate what proteins our bodies produce
38 3.2.1 Protein SynthesisThe information on DNA is copied onto an mRNA strandAs, Cs, Gs and Us (in place of Ts)mRNA leaves the nucleus and moves into the cytoplasmA ribosome attaches to the mRNAtRNA molecules bring amino acids (there are 20) into the ribosomeThe tRNA anti-codons match the mRNA codons (3 nucleotides at a time)The ribosome assembles the amino acids into the specific protein originally coded for by the gene on the DNA
49 Activity 3.2.2: The Genetic Code Decode messagesTranscription and translationEffect of mutations on protein productionGenetic mutation that causes SCDChose 1 to illustrate with any supplies you choseDecode the others in your lab book
50 Activity 3.2.3: Does Changing One Nucleotide Make a Big Difference?
51 Nova DocumentaryThe sickle form of the hemoglobin gene:A is changed to a T6th amino acid in the b-globin protein from GAG to GUG6th amino acid in the protein to become valine instead of glutamic acidThat single amino acid replacementAlters the shape and the chemistry of the hemoglobin moleculeCausing it to polymerizeDistort the red blood cell into the sickle shape
52 Genetic mutation to hemoglobin, causing sickle cell disease
53 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____________
54 Protein shape dictates function! What dictates shape? Amino acids presentCharge- positive vs. negative amino acidsHydrophobic vs. hydrophilicThe order of amino acidsSurrounding EnvironmentOilWater
55 3.2 It’s in the Genes: Review Key TermsAmino AcidAnticodonCodonHydrophilicHydrophobicMessenger RNA (mRNA)MutationNucleotideProteinProtein SynthesisRibonucleic Acid (RNA)RibosomeTranscriptionTransfer RNA (tRNA)TranslationWhat is the DNA code?What is the connection between genes and proteins?How are proteins produced in a cell?How does the sequence of nucleotides in DNA determine the sequence of amino acids in a protein?What is a mutation?What determines the shape of a protein?Is the shape of a protein affected by its surrounding environment?How does a change in the DNA code affect the shape of a protein?Can changing just one nucleotide in a gene change the shape of a protein?
56 3.3 Chromosomes How is DNA passed to new cells during cell division? Key TermsAlleleAutosomeChromosomeDominant traitGeneGenetic MaterialGenotypeHeredityHomologous ChromosomesKaryotypeMeiosisMitosisMutationPedigreePhenotypeRecessive TraitHow is DNA passed to new cells during cell division?What is a chromosome?How are traits passed through the generations?Should a person have rights to their organs and tissues? (Optional)
57 How do you get Sickle Cell Disease? Caused by an abnormal geneInherited DiseaseE.g., Tay Sachs, hemophilia, cystic fibrosis, and Huntington’s diseaseVs. Infectious (like…)How are mutations in DNA passed down from one generation to the next?
58 Activity 3.3.1: How is DNA Passed Through the Generations? Chromosomes contain the codes for how to make specific proteinsDetermine the organism’s traitsChromosome CompactionSpecific instructions for a protein are on sections of the chromosome called genes
59 Chromosomes DNA is stored in a compact form called chromosomes 46 chromosomes in somatic (body) cells23 chromosomes in sex cellsEgg cell from the mother fuses with the sperm cell from the father (zygote)= 46 chromosomes, 23 pairsOne from mother and one from father in each pair
61 Chromosomes and Sickle Cell Chromosome 11 carries the instructions (genes) to make the hemoglobin proteinThere are different versions of these genes:Normal – healthyMutated or changed – Sickle cell or other hemoglobin disorder
63 Mitosis (video) The chromosomes coil up A mitotic spindle moves them to the middle of the cellThe sister chromatids then separateMove to opposite poles of the cellTwo nuclei form (1 at each pole)Cytokinesis, in which the cell divides in two
64 Centrosomes (with centriole pairs) INTERPHASEPROPHASEPROMETAPHASELM 250ChromatinCentrosomes (with centriole pairs)NucleolusNuclear envelopePlasma membraneEarly mitotic spindleCentrosomeCentromereChromosome, consisting of two sister chromatidsSpindle microtubulesKinetochoreFragments of nuclear envelope
67 Meiosis (video)Meiosis, like mitosis, is preceded by chromosome duplicationBut in meiosis:The cell divides twice to form four daughter cellsFour DIFFERENT CELLS with HALF the genetic informationHalf the number of chromosomes
68 The first division, meiosis I Starts coping (sisters chromatids) and with synapsis- the pairing of homologous chromosomesIn crossing overHomologous chromosomes exchange corresponding segmentsMeiosis I separates each homologous pairproduce two daughter cells, each with one set of chromosomesMeiosis II is essentially the same as mitosisThe sister chromatids of each chromosome separateThe result is a total of four haploid cells
69 MEIOSIS I: Homologous chromosomes separate INTERPHASE PROPHASE I METAPHASE I ANAPHASE ICentrosomes (with centriole pairs)Sites of crossing overSpindleMicrotubules attached to kinetochoreMetaphase plateSister chromatids remain attachedNuclear envelopeChromatinSister chromatidsTetradCentromere (with kinetochore)Homologous chromosomes separate
70 Prophase l of MeiosisSites of crossing overSpindleHomologous ChromosomesTetrad: via synapsisSister chromatids
72 Meiosis Continued… MEIOSIS II: Sister chromatids separate PROPHASE II METAPHASE II ANAPHASE IITELOPHASE I AND CYTOKINESISTELOPHASE II AND CYTOKINESISCleavage furrowHaploid daughter cells formingSister chromatids separateMEIOSIS II: Sister chromatids separate
73 Two equally probable arrangements of chromosomes at metaphase I GametesMetaphase IITwo equally probable arrangements of chromosomes at metaphase IPossibility 1Possibility 2
74 Mitosis Meiosis Parent cell (before chromosome replication) Meiosis i Chromosomes align at the metaphase plateTetrads align at the metaphase plateSister chromatids separate during anaphaseHomologous chromosomes separate during anaphase I; sister chromatids remain togetherNo further chromosomal replication; sister chromatidsseparate during anaphase IIProphaseMetaphaseAnaphase TelophaseDuplicated chromosome (two sister chromatids)Daughter cells of mitosis2nDaughter cells of meiosis In2n = 4Tetrad formed by synapsis of homologous chromosomesMeiosis iMeiosis iiProphase IMetaphase IAnaphase I Telophase IHaploid n = 2Daughter cells of meiosis II
75 What happens to chromosomes throughout? It’s all in the name… Start as chromatinDuplicateThicken and clump into chromosomesConsist of two sister chromatids- replicatesIn meiosis…Chromosomes (sister chromatid duplicates) find their other half (maternal and paternal)They make homologous pairs, forming an tetradOne chromosome carrying info from the mother, the other carrying info from the father
77 Mutations are the original source of genetic variation Raw material for natural selectionSynapsis and crossing over during prophaseIndependent assortment (orientation) of homologous chromosome pairs along the metaphase plate (during metaphase)Random Fertilization of eggs by sperm
78 3.3 Chromosomes ReviewKey TermsAlleleAutosomeChromosomeDominant traitGeneGenetic MaterialGenotypeHeredityHomologous ChromosomesKaryotypeMeiosisMitosisMutationPedigreePhenotypeRecessive TraitHow is DNA passed to new cells during cell division?What is a chromosome?How are traits passed through the generations?Should a person have rights to their organs and tissues? (Optional)
79 3.4 Inheritance Key Terms Allele Chromosome Dominant Trait Gene GenotypeHeredityPedigreePhenotypePunnett SquareRecessive TraitWhy does sickle cell disease run in families, yet is not present in every generation?How can doctors and genetic counselors calculate the probability of a child inheriting a disease?How does the presence of malaria in a region affect the frequencies of normal versus sickle cell alleles?
80 How do we know all this stuff? Experimental genetics began in an abbey gardenFather of modern geneticsGregor Mendel’s quantitative experimentsParents pass on to their offspring discrete heritable factors, which maintain individuality7 years after Darwin’s Origins in 1859Pea plants
81 The Humble PeaEasy to grow, came in many varieties, easy to ensure self or cross fertilizationCrossed plants that differed in certain characteristicsTraced traits from generation to generationP(parental generation)F1 generationF2 generation
82 Different alleles of 7 genes Flower colorFlower positionSeed colorSeed shapePod colorPod shapeStem lengthPurpleWhiteAxialTerminalRoundWrinkledInflatedConstrictedTallDwarfGreenYellow
83 P generation (true-breeding parents) F1 generation F2 generation Purple flowersWhite flowersAll plants have purple flowersFertilization among F1 plants(F1 F1)of plants have purple flowers34of plants have white flowers1
84 Mendel found for each characteristic… An organism inherits two alleles, one from each parentIf the two alleles of an inherited pair differThen one determines the organism’s appearance and is called the dominant alleleThe other allele as no noticeable effect on the organism’s appearance and is called the recessive allele
86 Homologous chromosomes bear the two alleles for each characteristic Alternative forms of a gene reside at the same locus on homologous chromosomesHomozygous recessiveHomozygous dominantHeterozygousGenotype:PPaaBbHeterozygousPabBGene lociRecessive alleleDominant alleleHomozygous for the dominant alleleHomozygous for the recessive allele
87 Back to…How do you get SCD? It is an inherited blood disorderBoth parents have to have it to pass on the abnormal geneIf you inherit the problem gene from one parent and a normal gene from the other‘Sickle cell trait' or be a CarrierDoesn't usually cause any symptomsCan be passed on to the next generation.
88 Chromosomes and Sickle Cell Chromosome 11 carries the instructions (genes) to make the hemoglobin protein.There are different versions of these genes:Normal--healthyMutated or changed--Sickle cell or other hemoglobin disorder.
89 3.4.1: Family InheritancePedigrees show the occurrence of a particular trait from one generation to the nextP, F1 and F2 generationsMales are represented by squaresFemales are represented by circlesRelationships are represented with linesMake it easier to visualize relationships within familiesUsed to determine the mode of inheritance (dominant versus recessive) of genetic diseasesPedigrees illustrate what is or has beenVs. Punnett Squares & probability (next)
91 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.
92 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?
93 Mendel’s Laws Law of Dominance Law of Segregation 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 traitsLaw of SegregationDuring 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 AssortmentThe 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)
95 A dihybrid cross! Something a bit more challenging Uses Mendel's 3rd Law as well
96 3.4.2 What’s the Probability? How can doctors and genetic counselors calculate the probability of a child inheriting a disease?
97 3.4.2 What’s the Probability? Punnett Squares Create your own handout for this activityWrite four word problems that require Punnett squaresBe creative!Set up one question with chromosomesUse a pedigree for at least oneAlways ask for the genotypic and phenotypic ratioAlways ask a “what’s the percent chance that..” questionBe sure to have an answer keyWork in 1s or 2s, but you’ll need to type and print one handout eachTRADE- Due Monday!Let’s complete some examples
98 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
99 Example with pedigreeAnna’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.
100 Example word problemJuan’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.
101 The Immortal Story of Henrietta Lacks The first cell line, cultured more than 60 years agoThe HeLa Cell-Line has been reproducing independently, fueling biological researchBioethics- The study of controversial ethics brought about by advances in biological or medical research
102 The Great Debate Two sides of the argument Prep time Henerietta’s Dr. Gey’sPrep timeDesign opening and closing statementMake THREE KEY argumentsPlan a defense against your opponent
103 Structure of the Great Debate H: Opening statement (1 minutes)H: Key Point 3 (one minute)G: Opening statement (1 minutes)H: Key Point 1(one minute)G: rebuttalG: Key Point 3 (one minute)H: rebuttalG: Key Point 1(one minute)H: Closing (one minute)G: Closing (one minute)H: Key Point 2 (one minute)G: Key Point 2 (one minute)
104 3.4 Inheritance Review Key Terms Allele Chromosome Dominant Trait Gene Why does sickle cell disease run in families, yet is not present in every generation?How can doctors and genetic counselors calculate the probability of a child inheriting a disease?How does the presence of malaria in a region affect the frequencies of normal versus sickle cell alleles?Key TermsAlleleChromosomeDominant TraitGeneGenotypeHeredityPedigreePhenotypePunnett SquareRecessive Trait