Clue 1: Orient yourself
What happens when one station is empty?
Use the labels and the picture's left-to-right, near-to-far, or before-and-after order. Name only what you can point to.
The question
What happens when one station is empty?
Why it matters: Genetic results can change family counseling and research decisions. They must be interpreted without turning risk into destiny or an uncertain variant into a diagnosis. Today you practice the professional reasoning behind that work: Variant location can change mechanism: reduced dosage and altered DNA binding can produce different IRF6-related outcomes.
On your WebXam
Linking mutation mechanism (haploinsufficiency vs dominant-negative) to disease severity
For life
To find the cause, change one thing and watch what changes.
Principle: Same look, different cause
Five principles we return to
Having it is not using it
Same instructions, different switches
Same look, different cause
Change one thing and watch
Boss or doorman?
Decides the result or only allows it
Held down, not gone
Remove the brake and it returns
Many roads, one ending
One result can begin many ways
Try the everyday version first
A two-person control room can fail in two ways
A control room may require one operator to send a message and another to respond. A failure can begin with either side or with the connection between them.
Do not jump to the biology yet. Treat the picture as a small system. Track its parts, follow one change at a time, and keep more than one explanation open until the picture supplies a way to separate them.
Clue 2: Trace one change
How is a wrong command different from no command?
Follow one object, stage, or path. Point to the first place where the situation changes instead of jumping to the ending.
Clue 3: Keep the cause open
Which failure could disrupt the working operator too?
List more than one explanation that still fits. Name the extra observation that would help you separate those possibilities.
Now inspect the illustration
Work from the visible evidence. A useful answer names the part of the picture that supports it and leaves unknown causes open.
- 1What happens when one station is empty?
- 2How is a wrong command different from no command?
- 3Which failure could disrupt the working operator too?
Tier 1 check
Finish with the everyday model
Use the everyday picture to answer today's question in plain words: What happens when one station is empty?
You can complete today's required check without opening the technical details below.
Ready for the real names? Optional tier 2
Technical rules and limits
Rule 1: One missing functional copy can reduce dosage.
Rule 2: A changed protein can interfere with normal complexes.
Rule 3: Domain location helps predict the mechanism.
Where the analogy stops: The effect of one instruction change can differ from another and is more complex than two operators.
Carry the previous idea forward
DNA variants change proteins in different ways, so variant type is evidence about mechanism, not a verdict by itself.
Today's technical takeaway
Variant location can change mechanism: reduced dosage and altered DNA binding can produce different IRF6-related outcomes.
Now map the same rules onto biology
Compare IRF6 haploinsufficiency and domain-specific disruption
Empty station
Haploinsufficiency or loss of function
Wrong commands
Altered DNA-binding protein
Control panel location
Protein domain
Educational illustration, not a clinical photograph or diagnostic result. Use the labeled evidence cards and claim ceiling.
Mateo's case file: evidence supplied in this lesson
GEN08-E1
Many Van der Woude variants reduce the amount of functional IRF6.
Why it matters: Haploinsufficiency is a supported disease mechanism.
GEN08-E2
Some severe PPS-associated variants cluster at Arg84 in the DNA-binding domain.
Why it matters: Location can alter protein behavior and phenotype.
GEN08-E3
Different substitutions at Arg84 do not always produce the same phenotype.
Why it matters: Position alone does not erase the exact amino-acid effect.
Make the clinical decision
You are comparing two IRF6 variant reports.
One creates an early stop. The other changes Arg84 in the DNA-binding domain.
ADiscuss dosage loss versus domain-specific altered function.
BCall both mechanisms identical without evidence.
CPredict Mateo's phenotype from the gene name alone.
Choose the comparison and cite dosage plus domain evidence.
Evidence required
GEN08-E1 + GEN08-E2 Claim ceiling
You may compare supported mechanisms. You may not guarantee syndrome severity from variant position alone.Go deeper Optional tier 3
Everything required for today is above. Open these only if you want the explainer, source trail, or download files.
The everyday model and Tier 1 check are the complete required path for this lesson.
Use these checks to keep your place. They are not turned in through the portal.
Check off as you finish
- Worked through the everyday picture and answered its three questions.
- Completed the Tier 1 check in plain words.
Turn in: Genetics lesson 8: One Gene, Two Diseases
Go to Schoology to turn this in.
Submit one PDF. Put your first and last name in the document header. Name the file: FirstName LastName - Assignment Title - YYYY-MM-DD.pdf.
Open Schoology PDF upload helpIf you cannot get in, see Mr. Mendoza. Do not skip the work.
Optional legacy technical materials Open only if you want the original notes, vocabulary, artifact, and CER work
Before this page, you should know
- DNA is read three letters at a time as codons; the run of codons is the .
- A change swaps one amino acid; the stays full length but may be altered.
If not, review
Today's new idea is only
The mechanism of a typo, not just the gene, predicts severity: a full-length that interferes () is worse than a missing one ().
Goal: Students will connect mechanism to phenotype, contrasting (truncating, milder Van der Woude) with action (DNA-binding-domain , more severe popliteal pterygium).
Know by the end
- IRF6 has a (residues 7 to 115) and a ; changes are enriched in the DNA-binding domain but not the protein-binding domain.
- Truncating typos (/) spread across the gene cause through (half-dose).
- DNA-binding-domain changes cause more severe popliteal pterygium syndrome by acting , where the faulty interferes with the good copy.
- About 67% of PPS families carry the R84C or R84H hotspot in the , and the rule is strong but not absolute.
1
Haploinsufficiency
Model start: means one working copy is not enough; truncating typos cause milder this way.
- One copy makes no usable , so you run on ____ dose, and one working copy is not enough for normal development.
- This is the mechanism behind milder , caused mostly by ____ typos (, ) spread across the gene.
2
Dominant-negative
- One copy makes a full-length but broken that also ____ with the good copy, dropping function below half.
- This is the mechanism behind more severe popliteal pterygium syndrome, caused by ____ typos concentrated in the ____ domain, especially the R84 hotspot.
3
Why location matters
- IRF6 proteins pair up to grab DNA; a in the DNA-____ domain lets the broken still pair but ruins the grip, so the pair fails.
- This is strong but not absolute, so geneticists pair it with family history.
Everything you need for today is on this page. These links are optional.
What to read
Read the short plain-language explanation written for this lesson. Plain-language explainer for this lesson
Why this source matters
This explanation gives you the background for today's idea without making you decode a research paper: The mechanism of a typo, not just the gene, predicts severity: a full-length that interferes () is worse than a missing one ().
Reading moves
- Skim the title and abstract first to get the gist.
- Circle the one sentence that states the main claim.
- Box the evidence the authors give for that claim.
- Mark one sentence that confuses you, and move on.
Stop point
Stop after the final 'Use it now' section. The research citations are available separately for advanced readers.
Your output
Write one claim-evidence sentence: state the main idea, then name the example or evidence that supports it.
Where this fits
Tested on (Ohio WebXam)
Genetics of Disease · 072130
PLTW lesson
MI · Genetics domain · Unit 2 How to Screen Your Genes, 2.1 Genetic Testing and Screening
WebXam domain
Molecular and Genetic Technology
Evidence to produce
For two of Mateo's relatives' IRF6 results (R250X and R84C), name the likely mechanism (haploinsufficiency or dominant-negative) and the likely disease (milder VWS or more severe PPS), with one-sentence reasoning each.
Lab / skill
Medical Interventions (MI) · Principles of Biomedical Science (PBS)
Everything required for today's decision is already in the case file and plain-language explainer. The links below are original papers and database records for teachers and advanced readers, not assigned student reading.
- Kondo S, et al. 2002. IRF6 mutations cause VWS and PPS. Nat Genet. [PMID:12219090]
- Leslie EJ, et al. 2012. IRF6 variants across 549 families. Genet Med. [PMID:23154523]
- UniProtKB O14896 (IRF6): DNA-binding domain residues 7 to 115
- OMIM VWS1 #119300; PPS #119500 (professional database; use MedlinePlus Genetics if blocked)
- Claim: A DNA-binding-domain in IRF6 tends to cause ____ disease than a truncating change.
- Evidence: The data show changes are enriched in the and ~67% of the severe PPS families carry the ____ hotspot.
- Reasoning: Therefore mechanism predicts severity, because a ____ while only ____.
How this is graded (rubric)
For: For two of Mateo's relatives' IRF6 results (R250X and R84C), name the likely mechanism (haploinsufficiency or dominant-negative) and the likely disease (milder VWS or more severe PPS), with one-sentence reasoning each.
| Criterion | Proficient | Developing | Beginning |
|---|---|---|---|
| Complete | Every required part of the artifact is present and filled in. | Most parts are present, but one is missing or left blank. | Several parts are missing. |
| Accurate | The science and data are correct and match the evidence. | Mostly correct, with a small factual slip. | Key science or data is wrong. |
| Scientific reasoning (CER) | States a claim, backs it with specific evidence, and explains the reasoning. | Has a claim and evidence, but the reasoning is thin or missing. | Gives an answer with no evidence or reasoning. |
| Professional communication | Clear, organized, and labeled the way a clinician or scientist would write it. | Readable but disorganized or missing labels. | Hard to follow. |
| Submitted | Turned in through the route named under Submit here and confirmed. | Turned in, but in the wrong place or unconfirmed. | Not turned in. |
How the model answer scores against this rubric
- CompleteProficient: Nothing is left blank: the model fills every part of "For two of Mateo's relatives' IRF6 results (R250X and R84C), name the likely mechanism (haploinsufficiency or dominant-negative) and the likely disease (milder VWS or more severe PPS), with one-sentence reasoning each.".
- AccurateProficient: Every number and claim matches the case evidence.
- Scientific reasoning (CER)Proficient: It names a claim, cites the specific evidence, and explains the reasoning, not just the answer.
- Professional communicationProficient: It is organized and labeled like a real chart note.
- SubmittedProficient: It would be attached to your class form or handed in, and confirmed.
What's next: The harmful IRF6 changes we studied are rare and cause syndromes. Most clefts are isolated and common. Where is the common, hidden variant, and why have we not seen it in the code?