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 4 of 20Your seat: Gene mapper
Hunting the Exemplar Cleft Gene: Linkage to 1q32
Discovery question
How do you hunt a gene when you have no address for it?
💡 You can corner an invisible gene by watching what visible signposts it refuses to let go of.
The plan
Prerequisite check
Before this page, you should know
- Clean autosomal dominant inheritance needs one altered copy of a single gene and shows : an affected person in almost every generation.
- Multifactorial (threshold) inheritance has no single controlling gene; many small genetic and environmental factors add up to a total liability, and a appears only when liability crosses a threshold.
If not, review
Today's new idea is only
You can corner an invisible gene by watching what visible signposts it refuses to let go of.
Learn first
What you will learn
Goal: Students will use and co-segregation of DNA markers in informative families to narrow an unknown gene to a chromosomal region (1q32), and understand why scientists use clean Mendelian (Van der Woude) families to find a gene that later informs all clefting.
Know by the end
- A is a known, variable spot in the genome used as a trackable signpost; it is not the disease gene itself.
- is the tendency of two spots close together on a to be inherited together.
- Co-segregation is a marker version and a disease being inherited together in every affected family member, and it is the evidence that the gene sits nearby.
- The Van der Woude gene was first localized to band 1q32 by this kind of co-segregation, before anyone knew it was IRF6.
Learn first
Model: What a DNA marker is, and marker data in a Van der Woude family
A is a spot in the genome that varies between people and is easy to read, like a numbered signpost. It is NOT the disease gene; it is a known address you can track, like a mile-marker on a highway. When two spots are close on a they tend to travel together through generations, which is ; when far apart or on different chromosomes they get shuffled independently.
This next family is NOT Mateo's. It is a large Van der Woude family where clefting and run as a clean dominant trait, the kind scientists use to corner a gene. You three markers, M-A near 8, M-B near chromosome 1 band q32, and M-C near chromosome 4. Across the affected members (an affected grandfather, mother, uncle, and son) every one carries M-B version 7, while no unaffected person (the married-in father, grandmother, daughter) carries version 7. The chromosome 8 and chromosome 4 markers are mixed among the affected people. Family co-segregation of this kind, plus to chromosome 1q32-q41, is how the Van der Woude gene was first localized.
Do the work
Explore (work the model before reading on)
- For marker M-B (chr 1q32), what version do all four affected people carry? Do any unaffected people carry that exact version?
- For markers M-A (chr 8) and M-C (chr 4), do the affected people all share one version, or are they mixed?
- The disease and one marker version are inherited together every time. Which marker co-segregates with the disease?
- Markers M-A and M-C are scattered among affected people. What does that tell you about whether the disease gene is near 8 or chromosome 4?
- If a new cousin in this family inherits M-B version 7, what would you expect about being affected, and why? What is one reason a marker could occasionally be inherited WITHOUT the disease?
- In one sentence, where in the genome does the disease gene live, and how do the markers prove it?
The plan
Guided notes
1
Markers and linkage
Model start: A is a trackable signpost, not the disease gene; markers and diseases that pass down together are linked, meaning they sit close together.
- A is a known, variable spot you can track, but it is not the disease gene itself.
- When a marker and a disease pass down together, they show , meaning they sit ____ together on the same .
2
Reading the co-segregation
- Marker M-B on ____ rides with the trait every time, while the chromosome 8 and chromosome 4 markers are shuffled at random.
- So the gene must sit near M-B, in band 1q32; we have found a (a chromosomal address) without yet knowing the gene's name.
3
The honest caveat
- is statistical, not perfect; can occasionally separate a marker from the gene.
- That is why mappers use many families and many markers, not one.
Explore
Reading the Research
What to read
Read the title and the abstract only, not the whole paper. Kondo S, et al. 2002. IRF6 mutations cause VWS and PPS. Nat Genet. [PMID:12219090]
Why this source matters
This is the published evidence behind today's idea: You can corner an invisible gene by watching what visible signposts it refuses to let go of.
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 · Unit 2 How to Screen Your Genes, 2.1 Genetic Testing and Screening
WebXam domain
Bio-Molecular Technology
Evidence to produce
Write the localization line for the case file stating which marker the disease gene co-segregates with and which chromosome band it therefore maps to, circle the two markers you can rule out, and explain why one recombination event would not overturn the conclusion.
Lab / skill
Medical Interventions (MI) · Principles of Biomedical Science (PBS)
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: Write the localization line for the case file stating which marker the disease gene co-segregates with and which chromosome band it therefore maps to, circle the two markers you can rule out, and explain why one recombination event would not overturn the conclusion.
- Wrote my Claim, Evidence, and Reasoning exit ticket.
Pick your period and code first.
Check yourself
Exit ticket (Claim, Evidence, Reasoning)
- Claim: The exemplar gene is located on ____ at band ____.
- Evidence: In the Van der Woude family, marker ____ (version 7) appears in all ____ affected people and in no unaffected person, while chr 8 and chr 4 markers are mixed.
- Reasoning: Markers that ride with a trait every time are ____ to it, so the gene must sit nearby.
How this is graded (rubric)
For: Write the localization line for the case file stating which marker the disease gene co-segregates with and which chromosome band it therefore maps to, circle the two markers you can rule out, and explain why one recombination event would not overturn the conclusion.
| 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 "Write the localization line for the case file stating which marker the disease gene co-segregates with and which chromosome band it therefore maps to, circle the two markers you can rule out, and explain why one recombination event would not overturn the conclusion.".
- 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
Genetic mapper / statistical geneticist Genomics researcher Bioinformatician
What's next: We have an address, 1q32, but an address is not a name. What is the actual gene sitting there, and what does it make?