eyeing up genetic misconceptions final lesson...

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Eyeing Up Genetic Misconceptions Final Lesson Plan

Suzette Bielinski (Mayo Clinic) and Laura Unterholzner (Century High School) Rochester MN

Concepts to be addressed (misconceptions):

1. Patterns of inheritance (probability, modes of inheritance, interpretation of Punnett squares)

2. Monogenic and Polygenic traits (deterministic nature of disease) 3. Inherited and acquired genetic diseases (genetic basis of disease)

State Standards addressed:

1. 9.4.3.1.2 In the context of a monohybrid cross, apply the terms phenotype, genotype, allele, homozygous, heterozygous.

2. 9.4.4.2.1 Describe how some diseases can sometimes be predicted by genetic testing and how this affects parental and community decisions.

Objectives:

1. The students will be able to explain patterns of inheritance. 2. The students will be able to compare and contrast monogenic and polygenic traits. 3. The students will be able to explain, compare, and contrast inherited and acquired

diseases. Timing: This lesson took place after the Mendelian and Molecular Genetics Units in the spring of 2010. Lesson Plan Evaluation: Pre-test (pg. 4)

• Identical pre- and post-tests will be given and questions will target three areas of common misconceptions identified by Shaw et al 2008 – namely ‘Deterministic Nature of Genes’, ‘Patterns of Inheritance’, and Genetic Basis of Disease’.

• Test development – Unterholzner & Bielinski collaboration • Classroom execution - Unterholzner

Engagement/Exploration: Inherited Human Traits Lab (pg. 5) • Lab will explore variations in each student’s physical features. Students will be asked to

observe both Mendelian traits (cheek dimples, cleft chin, earlobe attachment, face freckles, Hitchhikers thumb, and widow’s peak) and polygenic traits (eye color, hair color, tongue rolling, toe length, finger shape, and handedness). A reference “Inherited Human Traits: A Quick Reference” was found on the Genetic Science Learning Center website. It has photos and information about many of the different traits. This was shown from the projector as different traits were introduced. This lab does include PTC testing and it should be noted that PTC has been found to be poisonous in large doses in rats. In this activity/discussion. Students consider the roles of poly and mono genetics and the environment in different human traits.

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• Lab development – Unterholzner & Bielinski collaboration • Classroom execution – Unterholzner • Resources – The Genetic Science Learning Center. Inherited Human Traits : A Quick

Reference http://learn.genetics.utah.edu/content/begin/traits/activities/pdfs/Inherited%20Human%20Traits%20Quick%20Reference_Public.pdf

Explain: Inherited and Acquired Genetic Disease (see attached PowerPoint)

• Using two disease examples, likely cystic fibrosis and lung cancer, inherited versus acquired genetic disease will be compared and contrast. Furthermore, the influence of gene-gene interaction to determine cystic fibrosis severity will be highlighted to show the complexity within ‘monogenic’ disease. Environmental component of disease for lung cancer will be highlighted.

• Lecture development – Unterholzner & Bielinski collaboration • Classroom execution - Bielinski

Elaboration: Eye Color Activity (pg. 6-8)

• Eye color lab- The students will examine the misconception that eye color is dominant/recessive. Students will examine their own eye colors and create a dihybrid cross to predict offspring eye color. They are given a small color chart to compare their own eye color. They will also be reminded that a dihybrid cross is still not completely effective in predicting eye color. In this activity, students again examine the complexities of human traits.

• Lab development – Unterholzner & Bielinski collaboration • Classroom execution – Unterholzner • Resources: http://www.color-chart.org/color-charts/human-eye-color-chart2.jpg and

http://museum.thetech.org/ugenetics/eyeCalc/eyecalculator.html Evaluation: Post-Test (pg. 9)

• Test development – Unterholzner & Bielinski collaboration • Classroom execution - Unterholzner

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Additional Collaborative Activities: PowerPoint Slide Development for use in other genetics units: 1. Chromosomes and genes 2. Types of mutations – updating language and providing interesting examples 3. Function of mutations Reference Genetics Texts: The following genetic reference texts were sent to Laura Unterholzner.

1. Genetics in Medicine, Thompson and Thompson, 7th Edition 2007 2. Human Evolutionary Genetics, Jobling, 2004

Classroom References Dr. Bielinski provided a 6ft poster illustrating the sequence of the ABO gene. This was shipped to Mrs. Unterholzner for use as a classroom display. Capital Upgrades: Dr. Bielinski pursued a small grant opportunity internally within Mayo and successfully acquired grant monies for capital upgrades. A Smart Board, laptop, projector, clickers and installation were ordered and delivered. We are currently awaiting their installation.

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Genetic Misconceptions Pre-Test True/False (circle one)

1. T or F – genes are either dominant or recessive.

2. T or F – many genes affect eye color.

3. T or F - a gene is smaller than a chromosome.

4. T or F- everyone with Down’s syndrome is afflicted to the same degree.

5. T or F- a mutation will most likely benefit a person.

Short Answer:

1. Explain why the mutations that affected the Teenage Mutant Ninja Turtles are unlikely.

2. Why roles do environment and genetics play in a trait such as intelligence?

3. How can scientists use genetics to help medicate people more accurately?

4. How are polygenics different from monogenics?

5. Is it possible for two parents with brown eyes to have a baby with blue eyes?

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Inherited Human Traits The reflection of your image in the mirror reveals much about yourself, but you may not have noticed all the many variations which exist between yourself and others. Variations in obvious features and also at the molecular level are present in human populations and in any given family.

1. Earlobes A. Attached B. Unattached 2. Tongue rolling A. Roller B. Non-roller 3. Cleft Chin A. Cleft B. No cleft 4. Handedness A. Righty B. Lefty 5. Freckles A. Freckles B. No freckles 6. Naturally Curly Hair A. Curly B. Not curly 7. Allergies A. Allergies B. No allergies 8. Hand folding A. Left on top B. Right on top 9. Colorblindness A. Normal B. Colorblind 10. Widow’s Peak A. Yes B. No 11. PTC taster A. Taster B. Non-taster 12. Bent or straight little finger A. Bent B. Straight 13. Eye color A. Blue B. not- blue 14. Mid- digital hair A. Some B. none 15. Arm Folding A. L over R B. R over L 16. Hitch-Hiker’s Thumb A. Yes B. No 17. Toe Length A. Big toe long B. Second toe long

1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17.

1. Put a star next to the traits that are inherited?

2. Which of these traits are not inherited and are purely environmental?

3. Circle the traits that are a mixture of both?

4. Which traits are mutations?

5. How many people have all the same traits as you?

6. How many people in class have all the same traits as someone else?

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The Polygenics of Eye Color Eyes are an organ designed to focus light and images on the retina and transmit this information to the brain. A common misconception of genetics is that eye color is determined by 1 gene. That is not the case. In fact, scientists hypothesize that eye color is determined by many genes. (poly means many) Eye color is a mystery in many ways. Although often 2 blue-eyed parents will have a blue-eyed child, there is a possibility they could have a brown-eyed child. And vice-versa, 2 blue eyed parents could have a brown eyed child. Eye color is complex. In humans we know of at least 3 genes that are involved in eye color. Gene 1: EYCL 1 (gey) / on chromosome 19. The green/blue eye color gene. Gene 2: EYCL 2 (bey1)/ possibly on chromosome 15. The central brown eye color gene. Gene 3: EYCL 3/ OCA 2 / (bey2)/ on chromosome 15. The brown/blue eye color gene Gene 4 ? a second gene for green? Are your eyes gray, hazel, multiple shades? Sorry there is no explanation for you – yet. In rare cases, a person’s eyes may appear to be red in color. This is a result of no or very low amounts of pigmentation that would normally obscure the red color of the blood vessels. A condition known as albinism results in low amounts of pigment.

1. Determine your eye color: Look into a handheld mirror. What color are your eyes? Some people think that their eyes change color. The pigment isn’t changing when this occurs. However they may

appear to change color due to the size of the pupils (black openings in the middle of the iris). When the pupils dilate (get bigger) they push the eye pigment to the sides and the color of the eye becomes darker. These are David Bowie’s eyes. He received an injury when he was young that left him with his left pupil permanently dilated. The size of your pupil is

influenced by light, but also by feelings like love or anger. For our purposes observe your eyes under medium light. What color are your eyes?

2. Now look at the chart provided http://www.color-chart.org/color-charts/human-eye-color-chart2.jpg. What section do you find your eye color in?

3. How many different types of brown are there? How many different colors of blue are there? Do you think there are more?

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4. Observe your eyes in bright light when they are constricted and in low light where they are more dilated. How does the amount of light affect your eye color?

5. How do the changes you observe relate to genetics and to environment?

6. The OCA2 gene controls the amounts of melanin pigment produced. It accounts for about 74% of eye color variation in humans. Melanin is a brown pigment. Do your eyes contain melanin?

7. Create a simple monohybrid cross with someone who is brown-eyed Bb with someone who is blue-eyed bb. (B = brown, b = blue)

8. What percentage of the offspring will have brown eyes?

9. In addition to the OCA2 gene, the gey gene affects blue/green coloration. It is hypothesized that it may weaken or turn off the OCA2 gene. Or it might create a small amount of melanin that will make blue eyes turn green if the OCA2 turn off. Do you have green eyes?

10. Create a simple monohybrid cross for someone with the green gey and blue gey gene (Gb) and someone with two blue gey genes. (G =green, b = blue)

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11. Create a dihybrid cross using both the OCA2 and gey genes for someone who has green eyes and the genotype bbGb and someone who has brown eyes and the genotype BbGb.

12. Remember there are more than 2 genes that affect eye color. So using a dihybrid cross will not be completely accurate. How many squares would your Punnett chart need if you were to use all 4 genes?

13. Use this website: http://museum.thetech.org/ugenetics/eyeCalc/eyecalculator.html to predict the possible eye color of your children.

a. What results do you get if your spouse has a green eyes phenotype?

b. What results do you get if your spouse has a brown eyes phenotype?

c. What results do you get if your spouse has a blue eyes phenotype?

14. Why isn’t this calculator completely accurate?

15. Why should/shouldn’t eye color be used to determine paternity?

Resources: http://www.allaboutvision.com/conditions/eye-color-chart.htm http://www.thetech.org/genetics/news.php?id=39 http://museum.thetech.org/ugenetics/eyeCalc/eyecalculator.html http://discovermagazine.com/2007/mar/eye-color-explained

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Genetic Misconceptions Post-Test True/False (circle one)

1. T or F – genes are either dominant or recessive.

2. T or F – many genes affect eye color.

3. T or F - a gene is smaller than a chromosome.

4. T or F- everyone with Down’s syndrome is afflicted to the same degree.

5. T or F- a mutation will most likely benefit a person.

Short Answer:

6. Explain why the mutations that affected the Teenage Mutant Ninja Turtles are unlikely.

7. Why roles do environment and genetics play in a trait such as intelligence?

8. How can scientists use genetics to help medicate people more accurately?

9. How are polygenics different from monogenics?

10. Is it possible for two parents with brown eyes to have a baby with blue eyes?

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Reflection: In February we planned to alter our lesson plan due to the successful acquisition of grant monies to be used for capital upgrades. The upgrades included the installation of a Smart Board and associated equipment (laptop, projector, etc.) as well as a classroom set of clickers. It was hoped that this new technology would be available to be integrated into our lesson plan. Unfortunately we are still awaiting the installation of the Smart Board and materials. Although we were hoping to use this exciting new equipment to enhance our current lesson, for the time being the lesson was written for use without a Smart Board and associated equipment. This lesson was used as a culminating activity that followed the Mendelian and molecular genetics units. It was used to cement the concepts used in the previous units and identify and correct any misconceptions that may have carried over. The students took their pre-test and participated in the Inherited Human Traits lab. The Inherited Human traits lab in one form or another is commonly used in many biology classes. It gave students an opportunity to study themselves and apply what they are learning to their own lives. It is important to note that some of the traits are only environmental, only genetic, or in many cases a combination of environmental and genetic. We used the website from the Genetic Science Learning Center during the activity to help identify some traits and their method of inheritance. Dr. Bielinski then visited class and presented her PowerPoint for the hour (attached). It included: media misconceptions, the onset of Down’s syndrome, the role of the BRCA1 and BRCA2 genes in the occurrence of breast cancer, and the role of genetics in individualizing drug therapy. During her visit, Dr. Bielinski pointed out the misconception that many biology teachers use brown/blue eye color as an example of a dominant/recessive trait. She explained that eye color is founded on several genes. She also discussed other eye traits including the darkened colored rim around the iris and patterns of color in the eye. As an elaboration activity, Mrs. Unterholzner designed an eye color inheritance lesson. The eye color lesson addresses the wide spectrum of eye color shades, the simplified inheritance of eye color, and why the simplified “equation” for predicting eye color is not correct. The students then completed the post test. As a teacher, one wants to simplify the topic of genetics to help students more quickly and easily understand the topic. It is important to remember, that most genetic conditions and diseases are not simple. They are a result of the complex interactions between genes and environment. It is important to always be cognizant of these interactions during the genetics unit each year. Additionally, it is worth the time to make sure that these misconceptions are addressed and nullified so that our students can successfully grow in their genetics knowledge in future studies and in life. Through our alliance, we were able to combine genetic expertise and instructional methods. Our lesson plan looks genetic misconceptions in the “eye” and makes them defunct.

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Basic GeneticsBasic GeneticsSuzette J. Bielinski, PhDSuzette J. Bielinski, PhD

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Chromosome 2~243,000,000 base pairs

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G-CT-AA-TG-CA-TG-CC-GA-TT-AC-GT-AA-TT-AG-C

Illustration of DNA Depends on Scale

14 base pairs

Gene (Average gene is 15,000 base pairs)

Exon 1

Intron 1

Exon 2

Intron 2

Exon 3

Intron 3

Exon 45’ 3’Exon 5

Intron 4

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24

23

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Chromosome 9145,000,000 base pairs

ABO gene (~20,000 bases)

Exon 1 Exon 2 Exon 3 Exon 4 Exon 5 Exon 6 Exon 7

Exon 6

Common protein types encode for by ABO on red blood cells

AA BB ABAB OO

Relationship of Chromosomes, Genes & Proteins

No protein

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1. Single Nucleotide Polymorphism (SNP-pronounced SNIP)

2. Insertion or deletion

3. Microsatellite

4. Chromosomal mutations

1. Single Nucleotide Polymorphism (SNP-pronounced SNIP)


3. Microsatellite


Major Types of Mutations

Mutations, variation, variants, polymorphisms all used interchangeably

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Single Nucleotide Polymorphism (SNP)

DNA sequence variation when a single nucleotide (A, T, SP, C, G) differs between members of the same species

• Occurs throughout the genome in genes (coding and non-coding) and intergenic regions

• SNPs makeup 90% of human variation (ie, the most common mutation in humans)

• Estimate 10-30 million SNPs in humans

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24

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Chromosome 9

ABO gene


Single Nucleotide Polymorphism (SNP)

Exon 3 ABO geneGenotype

Person 1

Person 2

(rs8176696)

A C G T C A A T G C

T G C A G T T A C G

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1. Single Nucleotide Polymorphism (SNP)


3. Microsatellite





3. Microsatellite



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Insertion or Deletion (Indel)

• Insertion or deletion of one or more bases (indel of 1 base is also considered a type of SNP)

• In introns, unless indel is a multiple of 3, they produce a frame shift mutation(change in amino acid sequence from the point of the indel until the end of the intron)

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24

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Chromosome 9

ABO gene


Insertion or Deletion (Indel)

Exon 6 ABO geneGenotype

Person 1

Person 2

(rs8176719)

C A C C A C T G G G

G T G G T G A C C C

C A C C A – T G G G

G T G G T – A C C C





G/–

–/–

C A C C A C T G G G

G T G G T G A C C C







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3. Microsatellite





3. Microsatellite



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Microsatellite

• Repeating sequences of 1-6 base pairs of DNA

• Many alleles (repeat lengths) in the population

• Very common and occur every few thousand base pairs

• Used for paternity, population genetic studies, forensics

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Chromosome 10

15.1

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22.1

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Chromosome 10

GenotypePerson 1

Person 2

A A G G

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T T C C

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T T C C

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T T C C

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T T C C

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A A G G

T T C C

A A G G

T T C C

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T T C C

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A A G G

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Microsatellite

(DG105478)

5/9

13/17

1 2 3 4 5

1 2 3 4 5 6 7 8 9

1 2 3 4 5 6 7 8 9 10 11 12 13

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17

(TTCC)5(TTCC)9

(TTCC)13(TTCC)17

Person 1

Person 2

3

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3. Microsatellite





3. Microsatellite



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Chromosomal Mutations

• Change in the number of chromosomes or when structured changes occur in chromosomes(example – translocations, deletions, duplications of whole chunks of chromosomes)

• Tolerance for chromosomal mutations is low given their profound effect on function

• Genes on chromosomes are normal but there are either too few genes (monosomy) or too many (trisomy) = Dose problem

• Only trisomy 13, 18, 21 are compatible with life as these chromosomes have the fewest genes

• Only monosomy of X is compatible with life

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Chromosomal Mutations

Trisomy 21Monosomy

Sex Chromosomes

Down’s Syndrome(1 in 800 live births)

Turners Syndrome(1 in 2500 females)

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What Can Mutations Do?

1. Nothing – most mutations are neutral

2. Lethal – not compatible with life

3. Loss of function – reduce or eliminate the function of the gene product

4. Gain of function – mutation results in protein with a new function

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Title/drp – author: BK – Bielinski, SuzetteSub/drp – Job#: BK – 3027372

Background: CustomBanner/brdr:

Side title: BK• /colhdgs: BK

Highlight: BKSubdue: BK

Subject: Basic Genetics

Footnotes: BK

Plot/brdr: open/BK

COLOR REFERENCE ONLY

PPT shooting instructionsPPT File to Server

(16 images)Text: WT/BK

Artist: kmy Start Date: 1-4-10

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The Complex Reality of Human Genetics

Suzette J. Bielinski, M.Ed., Ph.D.Genetic EpidemiologistAssistant Professor of EpidemiologyMayo Clinic College of MedicineRochester, Minnesota

Examples Used to Teach Human Genetics to Students

Rare Genetic Diseases– Sickle Cell Anemia– Tay-Sachs– Cystic Fibrosis– Hemophilia– Down’s Syndrome

Human traits– Eye Color – Blood Type

These examples promote the misconception that a single gene (or a single mutation) causes a disease

Media tends to reinforce this misconception Complex Reality of Human Genetics

Environmental Effect

Genetic Effect

There are no human diseases completely free of the influence of both genetic and environmental effects

Require a specific type of genetic abnormality

Requires a specific type of environmental exposure

Down’s Syndrome

Syndrome described in 1866 by John Langdon DownIdentified as a trisomy 21 in 1959 by Jerome LejeuneIncidence dependents on age of mother– 1 in 1562 births for maternal ages 20-24– 1 in 214 births for maternal ages 35-39– 1 in 19 birth for maternal age 45+

Combined use of cigarettes and oral contraceptives in younger mothers <35 years of age increases risk

Common Physical Features of Down’s Syndrome

Abnormally small chinUnusually round faceProtruding or oversized tongueAlmond shaped eyesWhite spots on irisShorter limbsShort NeckLonger than normal space between big and 2nd toesSingle crease across the palm of hand

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Down’s SyndromeBert Holbrook-80

Other features of Down’s Syndrome

Tend to have lower IQ Most who survive into their 50’s suffer from Alzheimer's diseaseHigher risk of the following– Abnormal heart development – Ear infections and thus hearing loss– Sleep Apnea– Thyroid dysfunctions

Lower Risk of the Following– Most Cancers– Heart Disease (clogging of the arteries)– Diabetic Retinopathy – damage to the eye blood vessels

Genetic Mechanisms of Down’s Syndrome1. Trisomy 21 – gamete (egg or sperm)2. Mosaicism Trisomy 21 – development3. Familial Down’s Syndrome 4. Duplication of part of Chromosome 21

DOSE Problem

Trisomy 21

Caused by a non-disjunction in a gamete (egg or sperm)

95% of cases

88% egg

9% sperm

Moderate to severe symptoms are observed

Mosaic Trisomy

Nondisjunction occurs during embryonic development = normal cells and trisomy 21 cells.

Accounts for 1-2% of cases

Familial Down’s Syndrome

Phenotypically Normal Female

25% of Eggs

Chromosome 14 with 21 attached AND chromosome 21

Accounts for 2-3% of cases

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Duplication of part of Chromosome 21

Rare

Prognosis is Highly Variable

Fertility is reduced in females and rare in males50% of the offspring will be normalLifespan– 9 years in 1929– 25 years in 1980– 49 years in 2002

Genetic Mechanisms are constant – environment has changed

What Explains the Wide Variation in Symptoms and Prognosis?

What is Known …Genetic mechanism explains very little of the differenceLife span has been dramatically influenced by environment

What we hypothesize …Interaction with other genesInteraction with environmental factors Treatment – behavioral, educational, medical

Bottom Line = We do not know!

Medical Applications of Human Genetics

Relatively few medical applications of geneticsUsed in small targeted populationsMost applications of genetics is used to diagnose rare genetic diseasesDiagnosis is not treatment

Breast Cancer

Breast cancer affects 1 in 8 American women during their lifetimeBreast Cancer Genes – BRCA1– BRCA2

Carriers of mutations in these genes have up to an 85% chance of getting cancer

100 Breast Cancer Cases

Only 10 out of 100 cancer cases are caused by mutations in the BRCA1 and BRCA2 genes

Preventive measures –increase frequency of screening, drug therapy (tamoxifen), mastectomy, ovary removal

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Treatment of Leukemia

Acute Lymphoblastic Leukemia (ALL)– Fast growing cancer of the white blood cells– Peak incidence is age 4-5– 4,000 new cases each year– ~80% of childhood leukemias– After chemotherapy survival ~80%

TPMT is a drug metabolizing enzyme for ALL drugs21 TPMT variants are known to decrease enzyme level

Individualized Medicine –Treatment of Leukemia

Activity Alleles

High TPMTH

Low TPMTL

Weinshilboum and Sladek, 1980

For patients that lack the TPMT enzyme the standard doses of thiopurine drug therapy causes severe life-threatening myelosuppression

(decreased bone marrow activity)

Overdose on standard doses

TPMT Genotyping is clinically important for individualizing thiopurine drug therapy

Genetic Epidemiology

Objectives1.Detect the inheritance pattern of disease2.Gene discovery - identify genes associated

with disease (etiology, prediction, prevention, diagnosis, treatment, prognosis)

3.Identify gene-gene and gene-environment interactions associated with disease

Note: Genetic Epidemiology is not specific to one disease or content area

Cardiovascular Disease (CVD)

Leading cause of death in US

Chronic inflammatory disease with complex etiology

Atherosclerosis account for 75% of all CVD deaths and includes coronary artery disease (CHD), stroke, and diseases of the arteries

Lifetime risk of CHD after age 40 is 49% for men and 32% for women

Fatty streaks – the initial stages of atherosclerosis

Atherosclerotic artery

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