Rough draft.This research track is under review with Dr. Atit's lab. Content and sequence may still change.
The Baby Mateo Case
Genetics domainMedical Interventions (MI), with PBS overlapLesson 13 of 20Your seat: Systems geneticist
Does IRF6 Work Alone?
Discovery question
Is IRF6 a lone actor, or one link in a chain of genes, and how would we tell from the patterns in patients?
💡 IRF6 does not work alone: it is one node in the p63 to IRF6 to GRHL3 network, which is why two patients can have the same from breaks in different genes of the same circuit.
The plan
Prerequisite check
Before this page, you should know
- predicts a 's folded 3D shape from its amino-acid sequence; the IRF6 model is AF-O14896-F1.
- A swaps one amino acid for a different one; every amino acid has a with its own size and charge.
If not, review
Today's new idea is only
IRF6 does not work alone: it is one node in the p63 to IRF6 to GRHL3 network, which is why two patients can have the same from breaks in different genes of the same circuit.
Learn first
What you will learn
Goal: Read a from patient and experimental clues, and place IRF6 in the p63 to IRF6 to GRHL3 axis with KLF4 and KLF17 .
Know by the end
- A is a set of genes that switch one another on and off to run a process.
- A is a that turns other genes on or off; IRF6, GRHL3, and p63 are all factors.
- p63 (TP63) is and keeps IRF6 switched on in the ; IRF6 hands the signal to KLF4 (mouse) and KLF17 (zebrafish).
- GRHL3 is a partner of IRF6 in the same pathway, because either one failing causes the same Van der Woude phenotype.
Learn first
Model: Five real clues and a network with one hidden node
Read five real findings before looking at the diagram. Clue A: most ( plus ) is caused by loss-of-function variants in IRF6. Clue B: a smaller set of Van der Woude families have no IRF6 but instead carry mutations in GRHL3, which causes the same and cleft problem. Clue C: in zebrafish and mouse, turning IRF6 off lowers the expression of GRHL3 and of KLF17 (fish) or KLF4 (mouse), and forcing IRF6 back on brings those genes back up. Clue D: the p63 (TP63) sits above IRF6 and is needed to keep IRF6 switched on in the . Clue E: a newly reported cause of Van der Woude is loss of PRKCI, which acts of IRF6.
The circuit to reconstruct is: signals (including PRKCI) feed a hidden node that keeps IRF6 on; IRF6 partners with GRHL3, and either one failing causes the disease; IRF6 then drives KLF4 and KLF17 . The hidden node is the gene in Clue D.
Do the work
Explore (work the model before reading on)
- From Clue D, which gene keeps IRF6 switched on? That is the hidden node. Name it.
- From Clue C, name two genes whose expression drops when IRF6 is turned off.
- Clue B says some patients have the same disease but a in GRHL3, not IRF6. What does that tell you about how IRF6 and GRHL3 are related in the circuit?
- Using Clues C and D, put these in order from switches-on-first to acts-last: IRF6, KLF4, p63. Which is and which is ?
- A patient has classic Van der Woude features but a completely normal IRF6 sequence. Based on this network, name two other genes you would sequence next, and say why.
The plan
Guided notes
1
Upstream, downstream, partners
Model start: A is a gene whose switches other genes on. A gene that acts earlier and controls another is ; a gene that acts later and receives the signal is .
- p63 (TP63) is near the top and keeps ____ switched on in the .
- IRF6 hands the signal to ____ (mouse) and KLF17 (zebrafish).
- Because either IRF6 or GRHL3 failing causes Van der Woude, they are ____ in the same pathway, not a single point of control.
2
Why one disease can have several genes
- Two patients can have the same from breaks in ____ genes of the same circuit.
- means more than one gene can cover a similar job, so losing one is partly ____.
Explore
Reading the Research
What to read
Read the title and the abstract only, not the whole paper. Leslie et al. 2012, IRF6 variants in VWS and PPS (Genet Med)
Why this source matters
This is the published evidence behind today's idea: IRF6 does not work alone: it is one node in the p63 to IRF6 to GRHL3 network, which is why two patients can have the same from breaks in different genes of the same circuit.
Words to unlock first
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
You do not need the methods or statistics yet. If a sentence is about lab technique or math you have not learned, mark it and skip it.
Your output
Write one claim-evidence sentence: what this source claims, and the one piece of evidence that backs it up.
Where this fits
Tested on (Ohio WebXam)
Genetics of Disease · 072130
PLTW lesson
MI · Genetics domain · Gene regulation and transcription factors
WebXam domain
Bio-Molecular Technology
Evidence to produce
Mateo's first IRF6 test came back normal, but his clinical features still strongly suggest a periderm-network problem. As the systems geneticist, write the lab's next-step order: list two or three other genes from this network to sequence, and for each give a one-line reason based on whether it sits upstream of, alongside, or downstream of IRF6.
Lab / skill
Medical Interventions (MI) · AP Biology
Explore
Vetted readings for this lesson
The plan
Track your progress today
Check these off as you work through the lesson, then submit. This tells Mr. Mendoza how you're doing so he can help the class. It does not replace turning in your producible.
Use the code Mr. Mendoza gave you, not your name. Saved on this device.
Check off as you finish
- Read the Model and answered the Explore questions.
- Filled in the guided notes in my own words.
- Defined the new vocabulary with an example.
- Built the producible: Mateo's first IRF6 test came back normal, but his clinical features still strongly suggest a periderm-network problem. As the systems geneticist, write the lab's next-step order: list two or three other genes from this network to sequence, and for each give a one-line reason based on whether it sits upstream of, alongside, or downstream of IRF6.
- Wrote my Claim, Evidence, and Reasoning exit ticket.
Pick your period and code first.
Check yourself
Exit ticket (Claim, Evidence, Reasoning)
- Claim: IRF6 is one node in a network, not a lone cause of clefting (agree or disagree).
- Evidence: Some Van der Woude patients have a in ____ instead of IRF6, and ____ is needed to keep IRF6 switched on.
- Reasoning: and relationships let different genes cause the same outcome, so a break ____ in the same circuit can look like a broken IRF6.
How this is graded (rubric)
For: Mateo's first IRF6 test came back normal, but his clinical features still strongly suggest a periderm-network problem. As the systems geneticist, write the lab's next-step order: list two or three other genes from this network to sequence, and for each give a one-line reason based on whether it sits upstream of, alongside, or downstream of IRF6.
| 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 the right way (Schoology for routine work) 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 "Mateo's first IRF6 test came back normal, but his clinical features still strongly suggest a periderm-network problem. As the systems geneticist, write the lab's next-step order: list two or three other genes from this network to sequence, and for each give a one-line reason based on whether it sits upstream of, alongside, or downstream of IRF6.".
- 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 turned in on Schoology and confirmed.
Explore
Where this leads: careers
Systems Geneticist Molecular Biologist
What's next: We placed IRF6 in a network with p63 above it and GRHL3 and the KLFs alongside and below. But a network of genes is just instructions. What does this network actually make the cells of the do so the lip and can physically close? We chase that next.