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GENA Final Intervention Report Toni Pollin Lalita Noronha-Blob June 14, 2008 GENA Learning Plan Development Outline: Toni Pollin Lalita Noronha-Blob GENA Team Update: On December 7, 2007, Toni came to Lalita’s 9th grade honors biology class and spoke with them about careers in genetics and some of her own research regarding the role of genes in common trait variation. In February, Lalita provided background on the six major scientific concepts addressed below (#3), emphasizing the integration of inheritance and molecular biology. In March, Lalita and Toni finalized their plans for two additional visits that Toni will make to Lalita’s class in order to implement two activities, which are described below. These activities will take place in Lalita’s 9th grade honors biology class on April 4th and 8th and will be followed by homework assignments. Toni has made a contact with a contact who knows a young woman with PKU who may be able to talk to the class at the end of the unit.. 1. Name of learning plan: Real Genes, Real People 2. State Standards:

3.3.2: The student will illustrate and explain how expressed traits are passed from parent to offspring. 3.3.3: The student will explain how a genetic trait is determined by the code in a DNA molecule. 1.5.2: The student will explain scientific concepts and processes through drawing, writing, and/or oral communication.

3. Major scientific concepts we intend to address: a. Mendel’s first law (law of segregation) b. Probability c. Central Dogma: DNA RNA Protein d. Protein Phenotype e. Environmental influences on genetic disease f. Pedigree construction/interpretation

4. Objectives in terms of learning outcomes (what will the students be able to do?)

a. Construct a pedigree from a set of phenotype and relationship descriptions

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b. Interpret pedigrees regarding inheritance pattern c. Describe autosomal recessive inheritance d. Be able to discuss the role of the environment in genetic condition e. Be able to describe in utero effects as an environmental influence on genetic

disease f. Be able to describe the impact of a mutation on the function of an enzyme and

how that functional change results in a specific phenotype g. Explore ethical implications of refusal to comply with diet.

5. Misconceptions and how they will be addressed: a. Genetic determinism:

Effects of dietary modification on intellectual development of children with PKU

b. Modifying the diet for individuals with PKU eliminates all problems: Discussion of how the diet works and its limitation Guest speaker with PKU if possible

c. Dietary modification is easy: PKU formula tasting Guest speaker with PKU Expansion to thinking about exercise, diet to protect against common diseases

d. Birth defects are all genetic: Maternal PKU syndrome

e. Probability is cumulative: Creation of pedigrees using coin flipping, demonstrating that overall risk is 25% for two carriers, each incident does not affect the next, actual ratios will vary, especially within small families

6. Materials a. Case studies b. Pencils c. Paper d. Pedigree templates e. Coins f. Guthrie cards g. PKU formula h. Guest speaker with PKU i. Online databases

7. Skills used

a. Drawing b. Writing c. Oral communications d. Making inferences e. Critical thinking f. Interpretation

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g. Prediction/hypothesis making h. Mathematical processes

Students will be adept at analysis of data, logical thinking and making inferences. They will be able to critically think through genetic problems, interpret case histories and predict the outcome from probability studies. They will be able to draw, write a paper on gene and chromosomal mutations and orally communicate their learning. In late April, selected studies from this project will be presented to parents, administration and faculty as part of the “Journey through Exploration” Symposium. 8. Where the concepts fit into a conceptual sequence: Lalita Prior to Intervention students will be familiar with: Classical Mendelian genetics and its relationship to inheritance; variations of Mendel’s laws such as codominance and incomplete dominance, the structure of chromosomes and DNA, the connection between genes, proteins and phenotype/disease, which includes transcription, post transcriptional modification, translation, tertiary protein structure and its function. This will lay the foundation for how mutations result in specific dysfunctional proteins in diseases such as PKU. Examples such as sickle cell anemia, color blindness, Turner’s Syndrome and many other human conditions will be correlated to different types of gene and chromosomal aberrations. The role of the environment and life style choices on gene expression will also be discussed. During the intervention, these concepts will be brought together and enhanced by the in-depth study of one condition—PKU. Family health histories will be symbolically represented as pedigree. Inheritance patterns will be examined to predict future offspring (probability) and the identity of the disease will be deciphered from its presentation. 9. Outline of the learning plan: February 2008: Major scientific concepts (see #3 above) addressed March 2008: Students were asked to research PKU from a genetic and clinical perspective. April 4, 2008 Engage (and assessment of previous assignment): 1. What is PKU? 2. What did you learn about the genetics of PKU? 3. What kinds of mutations cause PKU? 4. How does a mutation cause PKU? 5. What else influences the phenotype (also impact of newborn screening)? 6. What happens if a woman with PKU has children? Exercise:

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Simple case example (student volunteer draws pedigree as we explain it): Carol is born and identified via newborn screening as having elevated phenylalanine levels. She is diagnosed with PKU. Her diet is adjusted and monitored. Her parents are concerned about the possibility of future children having PKU, so her gene is sequenced and two mutations are found. Her parents are confirmed to be carriers of these mutations. Twenty-five years later, Carol marries Benjamin and they give birth to a baby boy with a small head. Newborn screening is negative for PKU. Subsequently the child is found to be slow in learning to be slow in meeting motor milestones. Could there be a relationship with PKU? Explain? Assessment: Homework: Additional cases April 8, 2008 Probability Lab Engage: Suppose two carriers have four children together. How many will have PKU? Suppose two carriers have one child with PKU. What’s the chance their next child will have it. Exercise: Pair up students “Mother” gets a quarter “Father” gets a quarter and a penny Quarter: Heads is normal allele, tails is allele with mutation Penny: Heads = female, Tails = male Each pair also gets

• Family card (family “name” and number of children [2, 4 or 12]) • Father mutation card • Mother mutation card

Procedure (Toni & Lalita model first on the board): 1. Draw the parents indicating their genotypes 2. Father flips penny and draws the appropriate symbol for the sex 3. Mother flips quarter to determine whether child inherits mutation and fills in half of

symbol appropriately 4. Father flips quarter to determine inheritance of his mutation and indicates 5. Repeat for additional children 6. Enter data on the spreadsheet 7. Repeat for additional families until all 20 families are completed Twenty minutes before class is over: Calculate sums and proportions Verbal assessment:

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• What proportion of all of the kids were expected to have PKU? What proportion were observed?

• What proportion were expected to be carriers? What proportion were observed? • Of the people who did not have PKU, what proportion were expected and observed to

be carriers? • Are there differences between the proportions in individual families vs. total? Why? Assessment: Homework: Write a 2-3 page report of your experience with this exercise, addressing the following points: • Describe the methods. • Describe and interpret the results, addressing at least the following questions:

1. What do you notice? 2. What proportion of all of the kids were expected to have PKU? What

proportion were observed? 3. What proportion were expected to be carriers? What proportion were

observed? 4. Of the people who did not have PKU, what proportion were expected and

observed to be carriers? 5. Are there differences between the proportions in individual families vs. total?

Why? 6. Do different family sizes have different proportions of affected children?

Why or why not? 7. Compare the number of boys to the number of girls. 8. Are there differences in the occurrence of the disease in boys and girls? 9. Provide possible explanations for differences between what you observed and

what you expected? 10. What have you learned that you hadn’t thought about before regarding

autosomal recessive inheritance? Part II: Learning Cycle Engagement: Object, event or question used to engage students. Connections facilitated between what students know and can do. Assign PKU as a research topic to all students Find out what students know about issues in PKU including inheritance pattern, allelic heterogeneity, biochemistry, clinical symptoms, maternal PKU Discuss what the expected probabilities are of children with PKU in carrier couples Exploration: Objects and phenomena explored. Hands-on activities, with guidance

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Provide family history and class creates pedigree together Additional cases/pedigrees assigned for homework Probability lab Explanation Students explain their understanding of concepts and processes New concepts and skills are introduced as conceptual clarity and cohesion are sought. Explain why child in sample pedigree has PKU-related phenotype without having PKU Explain how probability manifestation depends on sample size and notion of independent events Elaboration Activities allow students to apply concepts in contexts, and build on or extend understanding and skill New cases to investigate from all these aspects Environmental exposures (smoke, alcohol.) and interaction with genes in polygenic diseases Additional questions regarding sex ratios addressed in report following probability exercise Evaluation Students assess their knowledge, skills and abilities. Activities permit evaluation of student development and lesson effectiveness. PKU essay 2 Homework assignments • Pedigree drawing/analysis • Interpretation of probability lab findings

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GENA Assessment Data April 26, 2008 Team: Toni Pollin Lalita Noronha-Blob Part 1: After a discussion of PKU including clinical features and inheritance, Toni illustrated using a simple case the translation of a PKU case history into a pedigree. Then as a homework assignment students were given a case from which to construct a pedigree and answer questions. Case: April 4, 2008 PKU Unit Instructions: Read the case descriptions and draw or append pedigrees and answer questions provided. Note that newborn screening for phenylketonuria began in the early 1960s. Part1: Mr. and Mrs. Jones have five children, Jack, born in 1953, Jill, born in 1955, Bill, born in 1963, Abigail, born in 1967, and Joe, born in 1968. Jack has severe mental retardation requiring a special education setting and as an adult lives in a group home and works in a supervised employment setting. The rest of the children have intelligence in the non-impaired range and as adults function independently. While in school, Bill and Abigail experienced mild learning disabilities and utilized academic support services. Draw the pedigree for Part 1. How might mutations in the phenylalanine hydroxylase gene explain the mental retardation and learning disabilities in this family? How many of the five children might have PKU? How many would you expect if Mr. and Mrs. Jones are both mutation carriers? Part 2: In 1980, Jill marries Edward and they subsequently have two daughters and one son with intelligence in the normal range. Bill marries Maureen in 1990 and they have two sons with intelligence in the normal range. Abigail marries John in 1998. The first child of this couple, a daughter, has mild mental retardation, an unusually small head, and a hole in her heart. The second and third children of this couple have intelligence in the normal range and no noticeable physical abnormalities. Add these individuals to the pedigree. Based on what you have learned about PKU, what do you think is the cause of the problems in Abigail’s first child? How can you explain the lack of problems in her second and third children?

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Additional Questions: 1. Have you learned anything new about autosomal recessive inheritance? If so, explain. 2. Had you heard of PKU prior to this unit? If so, did you learn anything new about its genetic, clinical or other aspects? Explain. 3. Sometimes we talk about genetic conditions as being either single gene disorders or complex genetic disorders. Is PKU a single gene disorder or

a complex genetic disorder? Explain your reasoning. Student Results: Student Pedigree

Drawing PKU Etiology

Impact of Newborn Screen

# Possibly Affected

Predicted # Affected

Maternal PKU I: Effects

Maternal PKU II: No effects

New about AR Inheritance

New about PKU

Single vs. Complex

JH Yes—and carefully shaded specific sx

Yes—mutations in PAH cause toxic PHE buildup and MR

? 3 Yes—1 or 2

No—thought Abigail’s first child probably has PKU

No—attributed to probability (correct following first response)

only 25% (didn’t say 2 het parents)

learned a lot single gene with multiple possible mutations, ignores other genes in pathway (minor contribution and not covered)

IC Yes—but assumed Abigail’s daughter had PKU,

Yes (but converts vs. catalyzes conversion)

No—but says less affected kids could have been dx early

3 25%, about 1/5

No—sees daughter as likely having PKU

No Yes--+ notes “may come a shock”

learned about its entirety (never heard of it)

Good—talks about one gene but having different possible variants in exons, regulatory and splicing

SH Yes—but shades 4 people including Abigail’s daughter as having PKU

Yes Yes—nb scr 8 years after Jack and 2 yrs before Bill

pedigree shows 3, shows understands 3 is consistent with probability

expect 1, maybe 2, 25% and Punnett square

Yes—gets that it’s more likely than inherited PKU

Yes—says “probability” but then goes on to say that A “saw what her diet should have been and decided to follow the recommended diet which greatly lowers the risk of passing on PKU to your child”

will “remember for a long time” that PKU is AR, glad for opp’y tie all these areas together

sx, testing, tx, other facts

singe gene, only one gene, “does not set off other mutations in other genes of other chromosomes”

CP Yes—shaded Yes Yes all three ¼ Yes— “made sure to often does not heard single gene—missing

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correctly for 3 w/PKU

correctly possibly dx

probability ratio per child

“passed maternal PKU”

stick closer to the treatment during second and third pregnancies, causing her 2nd and 3rd children to be normal”

not follow the ¼ probability

before or depleted PAH

CH Yes—correctly shaded all offspring of affected as carriers and separate shading for maternal PKU

Yes—no mention of buildup of Phe

Yes 3 “have” 25% but “this is just a probability and anything is possible?

Yes No—no mention of improved dietary control

gives correct ratios but does not say this is with a pair of hets

everything single gene—mutations in both alleles PAH chr 12

EE Yes—not completely chronological—different shadings, nice

not discussed Yes 3 showing signs

No—“would expect though for all of the children to have the disease if the parents are both carriers”

No—“still be able to pass the gene” “daughter would be especially affected if her father” was affected or carrier

No ARD “can sometimes incorporate more than one gene mutation” “Because Jill and Edward are both unaffected by the disease their children will not be affected”

no heard of prior

complex—a variety of variability –mutations in genes and symptoms

PD Yes “diseases were not recorded because no information is absolute”

Yes—but assumes PAH base substitution changes the shape of activation site

Yes 3 Yes-- 1 b/c ¼ chance—“most likely situation is that one out of the 5” will have PKU

Yes—good—“doesn’t actually have PKU”

No—“chance of a child contracting Maternal PKU is very unlikely”—but notes rare possibility of father carrier

Yes--“simply a probability”

“taught me nearly everything I know”

single gene disorder in my opinion “only effects the shape of” PAH

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DM Yes—but assumes Abigail and daughter must have PKU

doesn’t discuss etiology

Yes—nice job

3 show possible signs

¼ for 2 carriers

No No—attributes to AR nature

Did not answer additional question #1

“much deeper understanding of PKU, as well as a better understanding of how important detection, treatment and overall genetic research is in terms of bettering people’s lives from the very beginning”

complex disorder because of response to treatment; great summary of disease and role of genetics and treatment/environment importance of early detection

NK Correct structure but no clinical or genetic features highlighted

Yes—pretty well covered

Yes 3 might possibly

¼ or 25% No No but gets that they’re probably carriers

¼ but can “also occur in a larger amount”

“several different mutations on distinct genes”,”special formulas full of proteins but as low as possible in phenylalanine to ensure they develop healthily and build a strong body”

complex—several mutations, different genes, “more factors that tie into this disorder” incorrect but good concept—“on another location, a mutation may not occur and the enzyme that breaks phenylalanine into tyrosine works properly”

MK Correct, shading, indicates diff dxs, sxs

“phenylalanine irregularity”

Yes 3 could ¼ or 25% should

Yes—but calls it “inherited from the mother” but more likely than PKU

not exactly correct—“each offspring has an equal chance of being healthy, of carrying the gene for PKU, of showing

not heard of previously

single gene—within one gene on one chromosome, specifically chrom 12

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symptoms of other disorders related to PKU, or of inheriting PKU completely”

HK Partly correct, but gave Mrs. Jones PKU and made Abigail and Bill children of Edward and Jill in part 2; assumes Jill and Joe are carriers

Yes Yes, but doesn’t actually mention NBS, indicates possibility of PKU in Mrs. Jones with good explanation

3 of 5 might one or two expected

Yes Yes both parents must be carriers or affected; WRONG—that usually if the gene is carried or portrayed by either parent, it is most likely that all of the children are carriers or they have the disease”

not heard of single gene—only decided by one gene

Part 2: Probability Lab (April 7, 2008) Students were assigned to pairs. Each pair represented a couple in which both were PAH mutation carriers. One student was the mother and one the father. Each pair was given three cards:

1. Family name (A-T) and number of children (2, 4 or 12) 2. Paternal mutation 3. Maternal mutation

Mutations were chosen to approximately reflect mutation prevalence in the Phenyalanine Hydroxylase Locus Knowledgebase (http://www.pahdb.mcgill.ca/). A mutation map was displayed on the overhead projector. Fathers flipped a penny to determine sex (heads=female, tails=male) and a quarter to determine PAH allele (heads=non-PKU, tails=PKU mutation). Students constructed pedigrees for the outcome in each family and then entered the data on a spreadsheet (attached). As students finished a family, additional families were distributed until all 20 families were completed. The completed spreadsheet was distributed to all students, who were then required to complete a report as follows:

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April 8, 2008 PKU Unit Probability Lab Homework: Write a 2-3 page report of your experience with this exercise, addressing the following points: • Describe the methods. • Describe and interpret the results, addressing at least the following questions:

11. What do you notice? 12. What proportion of all of the children were expected to have PKU? What proportion were observed? 13. What proportion were expected to be carriers? What proportion were observed? 14. Of the people who did not have PKU, what proportion were expected and observed to be carriers? 15. Are there differences between the proportions in individual families vs. total? Why? 16. Do different family sizes have different proportions of affected children? Why or why not? 17. Compare the number of boys to the number of girls. 18. Are there differences in the occurrence of the disease in boys and girls? 19. Provide possible explanations for any differences between what you observed and what you expected. 20. How do the particular mutations in your families impact the protein structure? 21. What have you learned that you hadn’t thought about before regarding autosomal recessive inheritance?

Experimental results shown on last page of this document. Student responses by concept summarized below: Student

Methods

Expected PKU

Observed PKU

Expected Carriers

Observed Carriers

Families vs. Total

Family Size

Boys:Girls

Occurrence boys/girls

Explanations Observed vs. Expected

Mutations and protein structure

Other

HK Yes 25% 26.3% 50% (36)

52.7% (38)

size more data even out

38:34, similar to 50%

same but higher carrier in females (not expected)

understands probability “does not always end up as it is expected”

vague—some sort of single based mutation—change the sequence of

66.6% of non-PKU expected carriers, 71.7% observed

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Student

Methods

Expected PKU

Observed PKU

Expected Carriers

Observed Carriers

Families vs. Total

Family Size

Boys:Girls

Occurrence boys/girls

Explanations Observed vs. Expected

Mutations and protein structure

Other

amino acids, protein fold differently

CP Yes 25% 26% 50% 52% individual families—percentages far off; overall, probabilities came closer to expected—balances out

1:2:1 ratio cannot be expressed in family of 2

52%:48% --very close to 50:50 expected; further off in individual families

females appear more likely to be carriers or affected, merely a coincidence, more families would probably make numbers more even

sample size not addressed

25% vs. 21% noncarriers

CA not described accurately or completely

19/72 (26%) 38 carriers 15 noncarriers (20%)

38 (53%)

total has a lower percentage because there are more

observations not very relevant

34:38 fathers less likely give daughter PKU gene, mother less likely to give to

not addressed

not addressed

lots of irrelevant and not quite correct info about mutations; “slight chance” of baby with

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Student

Methods

Expected PKU

Observed PKU

Expected Carriers

Observed Carriers

Families vs. Total

Family Size

Boys:Girls

Occurrence boys/girls

Explanations Observed vs. Expected

Mutations and protein structure

Other

people involved??

son PKU to parents who are carriers

SH Yes 25% 26% 50% 53% total provides more consistent picture than individual

doesn’t discuss

34:38, fairly even (rationalized)

boys more likely not have PKU, more girl carriers than boy carriers, not expected but interesting

not a lot of explanation for observed vs. expected

not addressed

bar graph used appropriately—great!!

NK Yes 25% (1:3)

26.38% 50% 9 families matched, 52.77% overall

not addressed

larger family—more chances passing on mutat genes

38:34, close result

notes differences in individual families

looking for “sinister” explanation but also says “results would be stronger, more accurate and reliable” in more families; sample size

not addressed

seemed to think matching to expected revealed “some hidden method”

DM Yes 25% 26.4% 75% 52.8% individual

larger famili

not stated similar PKU prev

discusses

20:53:27 vs. 1:2:1; realized

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Student

Methods

Expected PKU

Observed PKU

Expected Carriers

Observed Carriers

Families vs. Total

Family Size

Boys:Girls

Occurrence boys/girls

Explanations Observed vs. Expected

Mutations and protein structure

Other

families less likely reflect ratios

es more likely reflect ratios

males/females, but more female carriers—interesting outcome

prevalence, aa substitution

how complicated, many mutation, “showed how predictable, yet delicate genetics really is)

JH Yes 25% only 3 families had this ratio

75% noncarriers or carriers

holds true

not addressed

not addressed but says chance same in 2 or 12 children

no gender preference

low effort, said gained understanding of PKU and chance contract a disease

MK Yes 25% .263889 (26%)

50% .527778 (approx 53%)

confused

confused

34 girls to 38 boys, then nonsequitor

discusses but doesn’t tie to data

not articulated, accuracy vs. consistency

splicing mutation, incorrectly interpreted research on R243Q in

noncarriers .208333 carriers +noncarriers 74%

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Student

Methods

Expected PKU

Observed PKU

Expected Carriers

Observed Carriers

Families vs. Total

Family Size

Boys:Girls

Occurrence boys/girls

Explanations Observed vs. Expected

Mutations and protein structure

Other

thyroid receptor

EE Yes 25% (1/4)

25% 1/50 (confused population expectations vs. carrier couple expectations)

52% not addressed

larger families higher percentage affected

not addressed

more female carriers, understood gender independent

not addressed

not addressed

IC Yes 25% 21% 50% 53% gets that it’s hard to see the proportions (to be a “reality” in a small sample (family)

gets proportions more likely in larger families

not addressed

more female carriers

“These observations must also take into consideration chance, because these are not actual statistics and probability depicts possible outcomes”

discusses splice mutations

learned about different mutations causing PKU—531 to date, affect different parts of protein

PD Yes—list

25% (18)

19(26.38%)

50% (38), also 35 of 53

50% (38), 38 of 53

notes differences and nicely

larger families—varies

38:34, 36:36 expected, “very

similar number of male and female

realistic sense—expected to be “less

explores ethnic differences,

gave ranges of proportions for individual families

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Student

Methods

Expected PKU

Observed PKU

Expected Carriers

Observed Carriers

Families vs. Total

Family Size

Boys:Girls

Occurrence boys/girls

Explanations Observed vs. Expected

Mutations and protein structure

Other

unaffected (66%)

notes ranges observed in families

proportion (no)—provides more opp’y affected children--yes

close” affected children

probability equivalent data” but departs from perfect ; “probability is simply an estimate and can never determine the outcome of actual experiments”

splicing vs. missense mutations, says splicing makes “the correct amino acids are not paired together”

CH Yes 25% 26% 50% 53% “more families that are calculated, the more close to the exact probability the percentages will

notes for example one child can’t show enough variation to see proportions,

38:34 vs. 50:50

no difference in occurrence in girls vs. boys

way probability works, not a guarantee, just a likelihood that an event will occur, larger investigation, closer to predicted percentage

not addressed

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Student

Methods

Expected PKU

Observed PKU

Expected Carriers

Observed Carriers

Families vs. Total

Family Size

Boys:Girls

Occurrence boys/girls

Explanations Observed vs. Expected

Mutations and protein structure

Other

come.” family of 12 more accurate representation

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GENA Final Assessment June 14, 2008 Team: Toni Pollin Lalita Noronha-Blob Student understanding of concepts taught in the two modules was assessed in written assignments. Toni and Lalita then each read all student papers. They then together analyzed student responses for understanding and articulation of several key concepts. Feedback was then returned to the students. Results of this evaluation are summarized here. For assignment 1, students completed a pedigree based on a simulated family case study and answered questions regarding PKU and related phenotypes. Concepts assessed and results were as follows: 1. Pedigree drawing:

Most students drew the pedigree correctly with respect to the symbols and relationships among individuals. Most students shaded affected individuals correctly; a few assumed that offspring of female with PKU had PKU themselves (rather than the maternal PKU syndrome suggested by history) in their shading. However, this was a new and advanced concept.

2. PKU etiology: This was sporadically discussed. A few students incorrectly assumed a specific mutation (e.g., base substitution, mutation changing the activation site) was necessary. Only a few talked about the biochemical etiology.

3. Impact of newborn screen: Most students demonstrated understanding that the children born after newborn screening began in the early 60s were likely less affected owing to early detection and dietary intervention.

4. Number of individuals possibly affected with PKU: Most students correctly identified that 3/5 children may have PKU.

5. Predicted number of individuals with PKU: Most students indicated 25%, with a couple going further and indicating that this is just a probability, so 3/5 is still consistent. One student expected all children of 2 carriers to have PKU.

6. Maternal PKU I: Cause of Abigail’s first child’s symptoms: About half the students thought the child had PKU and half correctly identified that she most likely had maternal PKU resulting from in utero exposure to hyperphenylalaninemia. A few were off with terminology a little (“PKU inherited from the mother”) and a few were very articulate in saying that the child did not have PKU.

7. Maternal PKU II: Why Abigail’s other children were unaffected A few students understood the role of dietary control. Some attributed it to probability and incorrectly said that maternal PKU effects were unlikely.

8. New understanding of AR inheritance:

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Variety, but most commonly a new appreciation of 25% probability vs. empirical was noted. One person still thought parents had to be affected to have an affected child.

9. New understanding of PKU: Everything (purposely not covered in class prior to this activity)

10. Single gene vs. complex nature of PKU: A variety of answers given, almost all well-justified and quite thoughtful about the ways that PKU can be considered either.

For assignment 2, students reported and analyzed their findings in the probability lab. Concepts assessed and results were as follows:

1. Methods:

Most students correctly and comprehensively described the experimental procedure. 2. Expected proportion of offspring with PKU:

All who answered correctly answered 25%. 3. Observed proportion of offspring with PKU:

Most correctly answered 26%. 4. Expected proportion of carriers:

Most correctly answered 50%. One student gave 1/50 (expected proportion of carriers in the population instead of among offspring of carrier couples).

5. Observed proportion of carriers: Most correctly answered 52-53% (depending whether rounded or truncated from 52.78%).

6. Differences in proportions in individual families vs. total: Several thoughtful answers reflecting evolving understanding of the way that proportions can play out better in larger sample sizes. Some confusion in thinking that differences had to do with larger sample sizes having greater risk of affected children.

7. Family size vs. proportion of affected children: Thoughtful answers similar to #6.

8. Boy:girl ratio: A few didn’t address the issue, but most who did correctly noted that the ratio was close to the expected 50:50.

9. Affection status in boys vs. girls: Some departure noted in number of carriers—a couple people correctly attributed this to nature of probability and sample size.

10. Explanations for differences in observed from expected results: Some did not address, but several showed evolving understanding of the way probability works and its strengths and limitations in predicting empirical data and role of sample size.

11. Impact of mutation on protein structure: Generally not addressed or superficially addressed.

12. New insights about AR inheritance: One student used a bar graph appropriately to show observed vs. expected proportions. One student was skeptical about how well the observed results matched

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the expected (thought maybe something was “fixed”?—suggests incomplete appreciation of probability). One student found that the similarity of observed to expected ratios “showed how predictable, yet delicate genetics really is.” One student appreciated that multiple mutations in one gene can cause the same disorder.

Family Pat Mat # F # M # F # M # M # F # M # F # % % %Name Mutation Mutation Noncarriers Noncarriers Pat carriers Pat carriers Mat Carriers Mat Carriers PKU PKU Total Offspring NoncarriersCarriers PKUA R158Q Y414C 0 1 0 0 0 1 0 0 2 0.5 0.5 0B P281L V388M 0 0 1 1 0 1 0 1 4 0 0.75 0.25C I65T P281L 3 0 0 5 0 3 1 0 12 0.25 0.666667 0.083333D R252W R408W 0 0 1 1 0 0 0 0 2 0 1 0E R243Q IVS10-11G>A 0 2 2 0 0 0 0 0 4 0.5 0.5 0F R408W IVS10-11G>A 0 2 1 1 1 2 4 1 12 0.166667 0.416667 0.416667G F299C F55Lfs 0 1 0 0 0 0 1 0 2 0.5 0 0.5H A300S R261Q 0 0 1 1 0 0 0 2 4 0 0.5 0.5I IVS7+1G>A Y356X 0 0 1 0 0 1 0 0 2 0 1 0J R261Q R158Q 0 0 1 0 1 1 0 1 4 0 0.75 0.25K R243X F39L 1 0 0 0 0 0 1 0 2 0.5 0 0.5L R408W I65T 0 1 1 0 0 0 1 1 4 0.25 0.25 0.5M E280K E390G 0 1 0 1 0 0 0 0 2 0.5 0.5 0N IVS10-11G>A L48S 1 0 1 0 0 1 1 0 4 0.25 0.5 0.25O D415N Y277D 0 0 0 0 0 2 0 0 2 0 1 0P V245A R408Q 0 1 0 1 0 0 0 0 2 0.5 0.5 0Q R261X S349P 0 1 0 0 0 0 0 1 2 0.5 0 0.5R R111X L348V 0 0 0 0 0 1 0 1 2 0 0.5 0.5S G272X IVS10-11G>A 0 0 0 0 1 0 0 1 2 0 0.5 0.5T IVS12+1G>A A403V 0 0 0 1 0 0 0 1 2 0 0.5 0.5Total 5 10 10 12 3 13 9 10 72 0.208333 0.527778 0.263889

EVALUATION CRITERIA HIGH SCHOOL GENETICS CURRICULUM MATERIALS

TITLE: or name of resource: Real Genes, Real People SERIES TITLE: if applicable AUTHOR(S): if applicable: Toni Pollin and Lalita Noronha-Blob CITY/STATE: where published: Baltimore, MD PUBLISHER/SOURCE: COPYRIGHT DATE: ISBN NO: ADVERTISED GRADE LEVEL(S): grades(s) 9th Grade Honors Biology SUPPLIES: availability of materials and kits for core curriculum materials: coins, family/mutation cards (included), data entry sheet (Excel), computer, LCD projector, written assignments COST: suggested list price RESOURCE TYPE: student activity book, teacher's guide, books on teaching science, etc. URL if available: SUBJECT: Patterns of Inheritance REVIEWER’S NAME: DATE OF REVIEW: 06/14/08 GRADE LEVEL(S) RECOMMENDED BY REVIEWER IF DIFFERENT FROM THE ADVERTISED LEVEL(S) STATED ABOVE: (Please circle the specific grade level(s) for which you believe these materials are most appropriate or just delete the grade levels that are not applicable.)

7 8 9 10 11 12

GENETICS CONTENT COVERAGE

The 2007 GENA partnerships will be focusing on Patterns of Inheritance. After reviewing your resource, please indicate which topics under this broad theme the resource covers by placing an “X” next to the topic. If we have missed a topic(s) you feel relevant, you may add it under “other.”

_X_Meiosis __Recombination _X_Mendelian genetics/probability __Linkage _X_Alleles _X_Sex determination _X_Human genetic disorders __Complementation __Epistasis _X_Polygenic inheritance _X_Role of the environment __Imprinting _X_Pedigree Analysis _X_Non-Mendelian inheritance __Other- Please Specify _______________________X_Social Issues in Genetics __Other- Please Specify ______________________ After reviewing the resource, please reflect upon how well this tool addresses the following areas of pedagogy and content. Please place your score, 1 through 10 in the box to the right with 10 being the highest rating and 1 being the lowest. If you would like to add comments on why you scored something in a particular way or would like to comment on specific strengths and weaknesses, feel free to do so in the comments section.

Criteria Rating How well does the material address the important goals a high school teacher would have for the teaching of major principles in Patterns of Inheritance? Comments: It complements and extends the teaching of basic principles of inheritance using PKU as a concrete example.

9

How well does the material focus on inquiry and activity as the basis of learning experiences? Comments: The students appeared to find it engaging and exciting—to enjoy “creating families” and thinking about what different size families with different numbers of children with/without disease would be like. Once we set the probability activity in motion, students worked completely independently.

9

How developmentally appropriate are the modes of instruction, writing style and 10

materials and equipment utilized? Comments: How accurate is the science content presented? Comments: As accurate as possible, but it can be difficult to completely portray, for example, the allelic heterogeneity and prevalence of various alleles in the time frame and scope of the activity.

8

How well do the suggested investigations (if applicable) lead to an understanding of basic concepts and principles of science? Comments:

9

How well does this resource reflect the unbiased nature of science (i.e. is the resource free of dogmatism)? Comments: Seems to be. The probability activity in particular was based on true probability without preplanned results.

10

How engaging would high school students find this activity? Comments: These students were quite engaged.

10

How well does the material define scientific terminology and concepts? Comments: All relevant vocabulary was included and applied in written assignments.

9

Does the content provide sufficient information for the teacher to effectively conduct the activity in the context of a complete learning cycle? Comments:

8

Does the content provide sufficient information for the teacher to conduct an effective assessment of student understanding? Comments:

8

Are the materials required easily obtained and affordable for the average high school classroom? Comments: Absolutely. A computer makes it easier to tabulate the results but is certainly not required.

10

RECOMMENDATION BASED ON ALL CRITERIA

Instructions: Complete the section below. If you "recommend with reservations" or "do not recommend" a material for inclusion, briefly state your primary reason in the space provided. Based upon all aspects of my review of this material, X ______ I highly recommend this material. ________ I recommend this material. ________ I recommend this material with reservations.

Primary reasons for reservations: ________ I do not recommend this material.

Primary reasons for rejection:

This document was created using the official National Science Resource Center Evaluation Criteria for Curriculum Materials

designed for Middle Schools and adapted for our use.