John Hay
John Hay Biomedical
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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 5 of 20Your seat: Molecular geneticist

The Gene at 1q32 Has a Name: IRF6, From DNA to Protein

Discovery question

What is the gene at 1q32, and what does it make?

💡 A gene matters only through the it makes, and IRF6's protein is a master switch for .

The plan

Prerequisite check

Before this page, you should know
  • From the gene hunt, the gene's address is band 1q32.
  • A gene is a stretch of DNA that carries the instructions to build a .
Today's new idea is only
Today's new idea is only this: a gene matters through the it makes, and IRF6's protein is a switch that turns other genes on or off.
Learn first

What you will learn

Goal: Students will trace a gene from DNA to mRNA to ( and ) and identify IRF6 as the gene at 1q32 that makes the IRF6 protein, a and the best-understood window into how clefts happen.

Know by the end
  • The gene at 1q32 is IRF6 (interferon regulatory factor 6), identified by Kondo and colleagues in 2002 as the cause of .
  • A gene becomes a in two steps: copies DNA into mRNA, and builds a protein from the mRNA at the ribosome.
  • The IRF6 is 467 amino acids long and is a , a protein that binds DNA to switch other genes on or off.
  • IRF6 mRNA is high at the medial edge of the fusing , the exact that must seal for the palate to close.
Learn first

Model: The 2002 discovery and the central dogma

Kondo et al. searched the 1q32 region in families with and found mutations in ONE gene, IRF6, in 46 unrelated VWS families, plus distinct mutations in 13 families with the more severe popliteal pterygium syndrome. They also checked where the gene is switched on in the : IRF6 messenger RNA was high along the medial edge of the fusing , the exact that must seal for a palate to close, plus tooth buds, hair follicles, skin, and genitalia. So the gene at 1q32 is IRF6, and it is active in precisely the tissue that fails in a .

Every gene is a DNA recipe the cell reads in two steps. copies the DNA gene into messenger RNA (mRNA), a working copy that leaves the . then has the ribosome read the mRNA and build a chain of amino acids, the . The finished IRF6 protein is 467 amino acids long and is a : its job is to bind DNA and switch OTHER genes on or off. It has a DNA-binding part and a protein-partner part (UniProt O14896). In the 's , IRF6 tells skin-surface cells when to stop dividing and finish maturing so the palate shelves can fuse.

Read this in pieces, one chunk at a time
Learn first

Background and an analogy

Background you need first
  • DNA stays in the ; proteins are built at ribosomes out in the cytoplasm.
  • DNA is read three letters at a time, and each three-letter codon names one amino acid.
  • A is a that turns other genes on or off.
An everyday analogy

A treasured recipe never leaves the cookbook. To cook, you copy that one recipe onto a sticky note, carry it to the stove, and follow the note to make the dish.

How it maps: The cookbook in the drawer is DNA in the . Copying the recipe onto a sticky note is (making mRNA). The cook at the stove following the note is the ribosome doing to build the .

Do the work

Explore (work the model before reading on)

  1. What is the name of the gene Kondo's team found at 1q32, and in how many VWS families did they find mutations in it?
  2. What are the two steps that take a gene to a , and what molecule is made in between?
  3. Why is it meaningful that IRF6 mRNA is high in the exact (the medial edge of the fusing ) that fails in a ?
  4. IRF6 is a . If IRF6 is broken, would the damage stay limited to IRF6, or could it spread to many genes it normally controls? Explain.
  5. If a changed the IRF6 recipe so the could no longer bind DNA, which step still happens, and what job would the finished protein fail to do?
  6. In one sentence, what is the gene at 1q32, and how does it get from DNA to a working ?
The plan

Guided notes

1

Naming the gene

Model start: The gene at 1q32 is IRF6 (interferon regulatory factor 6), identified by Kondo et al. in 2002.
  • The gene at 1q32 is IRF6, identified by Kondo and colleagues in 2002 as the cause of .
  • Mutations were found in 46 unrelated VWS families.
2

DNA to protein

  • copies the DNA gene into a messenger molecule called ____ (messenger RNA), which carries the message out of the .
  • then has the ribosome read the mRNA and build a chain of amino acids, the ; the IRF6 protein is 467 amino acids long.
3

Why IRF6 is powerful

  • IRF6 is a , a that binds DNA and turns ____ genes on or off, so breaking it can throw off many genes.
  • It is switched on at the medial edge of the fusing , which is exactly why losing it causes clefting.
Explore

Reading the Research

What to read
Read only the abstract of Kondo et al. (2002), plus the one sentence that says where IRF6 is switched on in the . Kondo S, et al. 2002. IRF6 mutations cause VWS and PPS. Nat Genet. [PMID:12219090]
Why this source matters
This is the paper that put a NAME on Mateo's exemplar gene, IRF6, and showed it is active in the exact that fails in a cleft.
Words to unlock first
transcriptionmRNA (messenger RNA)translationtranscription factorIRF6
Reading moves
  1. Skim the title and abstract first to get the gist.
  2. Circle the one sentence that states the main claim.
  3. Box the evidence the authors give for that claim.
  4. Mark one sentence that confuses you, and move on.
Stop point
You do not need the tables, the exact family counts, or the sequencing methods yet. Mark any sentence about lab technique and skip it.
Your output
Write one claim-evidence sentence: IRF6 is the gene, and the evidence is that mutations in it were found across many Van der Woude families.
Lab day

Using the database (what to capture)

Part of today's expected outcome is to actually open the tool below and write down the value it gives you. That captured value is the evidence you will use in your Claim, Evidence, Reasoning. Follow the steps, use the labeled screenshot so you do not get lost, and record each field.

UniProt
Open the tool

The reference record for a : its length, its domains, and what each part does.

When you use this: Use this when you need to know which PART of the a variant hits, so you can predict whether it breaks a working region.
What the screen looks like
uniprot.org/uniprotkb/O14896 IRF6 human 1 Protein entry: IRF6 2 Length + domains 467 aa · DNA-binding + SMIR domains 3 1 Open the IRF6 entry (O14896). 2 Go to the Family & Domains section. 3 Read the length and which domains exist.
A labeled map of the screen. The circled numbers match the steps.
Step by step
  1. 1Open uniprot.org and search IRF6 human, then open entry O14896.
  2. 2Scroll to the Family and Domains section.
  3. 3Read the length and which domains exist (for example the ).
Capture these fields
  • Accession (the protein's ID): O14896
  • Length (amino acids): 467 aa
  • Domains / regions: A DNA-binding domain and a protein-partner (SMIR) domain
How to read it: The domains tell you which part of the does which job. A variant that lands inside the is more likely to break IRF6's -factor function than one in a spacer region.
Lost? UniProt help: reading protein domains
Where this fits
Tested on (Ohio WebXam)
Genetics of Disease · 072130
PLTW lesson
MI · Genetics domain · Unit 4 When Organs Fail, 4.1 Manufacturing Human Proteins (central dogma)
WebXam domain
Bio-Molecular Technology
Evidence to produce
Fill in the case file's molecular summary naming the 1q32 gene, the DNA-to-mRNA and mRNA-to-protein steps, and the kind of protein IRF6 is, then predict what could go wrong in palate fusion if the IRF6 protein cannot bind DNA.
Lab / skill
Medical Interventions (MI) · Principles of Biomedical Science (PBS)
Words

Vocabulary (the same words your classes use)

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.
  • Opened UniProt and recorded the value it gave me.
  • Built the producible: Fill in the case file's molecular summary naming the 1q32 gene, the DNA-to-mRNA and mRNA-to-protein steps, and the kind of protein IRF6 is, then predict what could go wrong in palate fusion if the IRF6 protein cannot bind DNA.
  • Wrote my Claim, Evidence, and Reasoning exit ticket.
Pick your period and code first.
See the grading rubric
See an example of today's finished work, and a WebXam practice questionA worked model of the producible plus one exam-style item with the answer and full rationale.
Check yourself

Exit ticket (Claim, Evidence, Reasoning)

  • Claim: The exemplar gene we study is ____, located at 1q32.
  • Evidence: In 2002, mutations in this gene were found in ____ Van der Woude families, and its mRNA is high in the ____ ____ of the fusing .
  • Reasoning: A gene acts through its ; IRF6's protein is a ____ ____, so losing it disrupts the genes that close the .
How this is graded (rubric)
For: Fill in the case file's molecular summary naming the 1q32 gene, the DNA-to-mRNA and mRNA-to-protein steps, and the kind of protein IRF6 is, then predict what could go wrong in palate fusion if the IRF6 protein cannot bind DNA.
CriterionProficientDevelopingBeginning
CompleteEvery 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.
AccurateThe 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 communicationClear, organized, and labeled the way a clinician or scientist would write it.Readable but disorganized or missing labels.Hard to follow.
SubmittedTurned 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 "Fill in the case file's molecular summary naming the 1q32 gene, the DNA-to-mRNA and mRNA-to-protein steps, and the kind of protein IRF6 is, then predict what could go wrong in palate fusion if the IRF6 protein cannot bind DNA.".
  • 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

Molecular geneticist Genomics researcher Biotechnologist

What's next: Now that we have the exemplar gene IRF6, where do we look up whether a given variant in it is already known, and whether it is harmful?

Hunting the Exemplar Cleft Gene: Linkage to 1q32Looking Up a Variant
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