Rough draft.This research track is under review with Dr. Atit's lab. Content and sequence may still change.
Craniofacial Research Track
Session 9The Molecular Cause, NovemberLens: Genetics of Disease
When a cleft runs in a family: Van der Woude
Discovery question
Mateo's aunt has small pits on her lower lip, and a cousin was born with a . Could the same gene be moving through the family, and what pattern would that follow?
Some clefts run in families. , usually caused by an IRF6 , is the most common single-gene cause of clefting. It follows an autosomal dominant pattern, often shows , and reminds us to separate syndromic from non-syndromic clefts.
The plan
Prerequisite check
Before this page, you should know
- Several genes are linked to clefts, including IRF6, , CDH3, MSX1, and .
- These genes act in different steps: some are factors, one is a signal, and one helps cells stick together.
Today's new idea is only
Some clefts run in families. , usually caused by an IRF6 , is the most common single-gene cause of clefting. It follows an autosomal dominant pattern, often shows , and reminds us to separate syndromic from non-syndromic clefts.
Learn first
What to learn
Goal: Explain autosomal dominant inheritance and penetrance, distinguish syndromic from non-syndromic clefts, and identify Van der Woude as the most common single-gene cause.
Know by the end
- In autosomal dominant inheritance, one altered copy of the gene is enough to cause the condition.
- Penetrance is the fraction of people with the disease-linked who actually show the trait, so a family pattern can look uneven.
- Syndromic clefts come with other features as part of a named syndrome; non-syndromic clefts occur on their own.
- , usually from an IRF6 , is the most common single-gene cause of clefting and often shows small lower-.
The plan
Guided notes
1
Reading the pattern
Model start: Autosomal dominant means one altered copy is enough, so an affected parent can pass the condition to a child in each pregnancy.
- Define autosomal dominant in your own words.
- On a simple pedigree, mark who could carry the altered IRF6 copy if it is dominant.
2
Why the family looks uneven
Model start: Penetrance is the share of people with the who show the trait, so a can have only , or no obvious sign at all.
- Define penetrance and explain how it can make a dominant condition skip a person who still carries the gene.
- The aunt has but no . Explain how that fits one IRF6 family.
3
Syndromic or not
Model start: A comes with other features; Van der Woude's clue is the small pits on the lower lip.
- Write the difference between a syndromic and a non-.
- Open the Van der Woude page and list the feature, besides the , that points toward this syndrome.
Explore
Reading the Research
What to read
Read the title and the abstract only, not the whole paper. Peer-reviewed literature on IRF6 in clefting (PubMed)
Why this source matters
This is the published evidence behind today's idea: Some clefts run in families. , usually caused by an IRF6 , is the most common single-gene cause of clefting. It follows an autosomal dominant pattern, often shows , and reminds us to separate syndromic from non-syndromic clefts.
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.
Lab day
Using the database (what to capture)
MedlinePlus
Open the tool Plain-language explanations of a gene or condition, written for patients and families.
When you use this: Use this when a research paper is too dense, or when you need to explain a finding to Mateo's family in everyday words.
What the screen looks like
Step by step
- 1Open medlineplus.gov/genetics and search the gene or condition (IRF6).
- 2Read the summary written in everyday words.
- 3Note the conditions the gene is linked to at the bottom of the page.
Capture these fields
- Topic: IRF6 gene
- Plain-language summary: IRF6 helps the tissues of the face join correctly before birth.
- Linked conditions: Van der Woude syndrome; nonsyndromic cleft
How to read it: Start here when a research paper is too dense. MedlinePlus gives you the gist in everyday words so you can go back to the harder source knowing what it is about.
Lost? About MedlinePlus Genetics NCBI Gene
Open the tool The full reference record for a gene: its official symbol, ID, location, and what it does.
When you use this: Use this first, when you have a gene name and need its official ID and address. It is the home base every other database points back to.
What the screen looks like
Step by step
- 1Go to ncbi.nlm.nih.gov/gene and type the gene symbol IRF6 in the search box, then press Search.
- 2Open the top result whose organism is Homo sapiens (human).
- 3At the top of the record, read three things and write them down: the official symbol, the Gene ID number, and the location ( band).
Capture these fields
- Symbol (official gene name): IRF6
- Gene ID (the stable number): 3664
- Location (chromosome band): 1q32.2
- Summary (one line on its job): A transcription factor needed for the skin-surface cells that let the lip and palate fuse.
How to read it: The symbol and Gene ID let you find the exact same gene in every other database. The location should match the band you mapped (1q32). The summary tells you the gene's job in one sentence.
Lost? NCBI Gene help manual (how to use the Gene database) ClinVar
Open the tool Lists DNA variants that have been reported, the condition each is linked to, and a clinical-significance call.
When you use this: Use this when you have a specific DNA change and need to know whether anyone has reported it before and whether it was called harmful.
What the screen looks like
Step by step
- 1Open ncbi.nlm.nih.gov/clinvar and search IRF6[gene].
- 2Open one variant from the list (for example R84C).
- 3Read its clinical significance and the review status (how many labs agree).
Capture these fields
- Variant name: R84C (or c.250C>T)
- Condition: Popliteal pterygium syndrome
- Clinical significance: Pathogenic
- VUS vs pathogenic call: Pathogenic, not a VUS, because it recurs in many affected families
How to read it: A pathogenic call means strong evidence the variant causes disease; benign means evidence it does not; a means there is not enough evidence yet. A call can change as more families are reported, so always note the date.
Lost? ClinVar overviewExplore
Vetted links for this session
- Van der Woude syndrome (MedlinePlus Genetics, NLM)
- IRF6 gene (plain-language gene card) (MedlinePlus Genetics, NLM)
- IRF6, Gene ID 3664 (the full gene record) (NCBI Gene, NLM)
- Talking Glossary of Genomic and Genetic Terms (NHGRI)
- Peer-reviewed literature on IRF6 in clefting (PubMed) (PubMed, NLM)
- ClinVar variants reported in IRF6 (ClinVar, NLM)
Learn first
Pick your level
Level 1, Guided
Use the sentence starters, a word bank from the vocabulary, a labeled diagram, and the exact source link.
Level 2, Collaborative
Complete a partly blank model or table and explain it.
Level 3, Independent
Make a claim from a new example or an unfamiliar entry in the same database.
The plan
Work as a research team
Team roles
- Manager: keeps the group moving
- Recorder: writes the shared model or table
- Evidence checker: verifies each claim against the source
- Reporter: explains the group's reasoning
Process reflection
- What evidence changed your thinking today?
- What did your group disagree about, and how did you resolve it?
- What question is still unresolved?
Check yourself
Demonstration of learning
By the end of this session, submit ONE of: a labeled diagram with a 2-sentence explanation; a claim, evidence, reasoning paragraph; a completed data table from a real database; or a one-question exit ticket using today's vocabulary.
Meets standard if your explanation correctly connects structure, timing, gene or protein function, or evidence source to Mateo's case: Explain autosomal dominant inheritance and penetrance, distinguish syndromic from non-syndromic clefts, and identify Van der Woude as the most common single-gene cause.
How this is graded (rubric)
For: Explain autosomal dominant inheritance and penetrance, distinguish syndromic from non-syndromic clefts, and identify Van der Woude as the most common single-gene cause.
| 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 "Explain autosomal dominant inheritance and penetrance, distinguish syndromic from non-syndromic clefts, and identify Van der Woude as the most common single-gene cause.".
- 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.