Clue 1: Orient yourself
Where does the broad scan find candidate signals?
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
Where does the broad scan find candidate signals?
Why it matters: Clinical recommendations affect real children and families. Fair comparisons, bias control, ethical limits, and honest uncertainty keep a promising result from becoming a harmful claim. Today you practice the professional reasoning behind that work: Gene discovery combines broad scans, family structure, quality control, and independent replication.
On your WebXam
Reading over-transmission in a case-parent trio (TDT)
For life
One result can have many causes; the outcome alone never tells you which.
Principle: Many roads, one ending
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 citywide signal scan needs family checkpoints and a second city
A citywide scan can find many signals by chance. Family checks and a second city test whether the same signal follows a pattern and appears again.
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 does the family gate check transmission?
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
Why must another city repeat the result?
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.
- 1Where does the broad scan find candidate signals?
- 2How does the family gate check transmission?
- 3Why must another city repeat the result?
Tier 1 check
Finish with the everyday model
Use the everyday picture to answer today's question in plain words: Where does the broad scan find candidate signals?
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: Scan broadly without choosing only favorite genes.
Rule 2: Use family or population structure to test the signal.
Rule 3: Require quality control and independent replication.
Where the analogy stops: DNA variants are not streetlights, and nearby signals can mark a region without naming the causal gene.
Carry the previous idea forward
Cohorts establish time order, while twin comparisons estimate population patterns under assumptions rather than one person's cause.
Today's technical takeaway
Gene discovery combines broad scans, family structure, quality control, and independent replication.
Now map the same rules onto biology
Move from a GWAS signal to a replicated cleft-risk locus
Citywide scan
Genome-wide association study
Family checkpoint
Trio transmission test
Second city
Independent replication sample
Educational illustration, not a clinical photograph or a patient-specific study plan. Use the supplied evidence cards and claim ceiling.
Mateo's case file: evidence supplied in this lesson
EXP06-E1
A GWAS compares millions of common variants across many people.
Why it matters: It can reveal risk-associated regions without selecting one candidate in advance.
EXP06-E2
A case-parent trio can test whether one allele is transmitted to affected children more often than expected.
Why it matters: Family structure can reduce some population-stratification problems.
EXP06-E3
Genotyping quality, ancestry structure, sample size, and independent replication affect credibility.
Why it matters: A single peak is not yet a proven causal gene.
Make the clinical decision
You are the statistical geneticist reviewing a new genome-wide peak.
One sample shows a strong signal near a developmental gene, but no second cohort has tested it.
ACall it a candidate locus and require quality checks plus independent replication.
BName the nearest gene as Mateo's proven cause.
CIgnore the signal because GWAS can never find useful loci.
Choose the next step and distinguish a locus, an associated variant, and a causal mechanism.
Evidence required
EXP06-E1 + EXP06-E2 Claim ceiling
You may nominate a replicated risk locus. You may not name a causal gene or patient diagnosis from proximity 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: Experimental Design lesson 6: Finding a Risk Gene Among Millions of Bases
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
- A starts with the exposure and follows people forward to the outcome; a prospective cohort records exposure before the outcome, so it is largely immune to .
- A compares identical (about 100 percent shared DNA) and fraternal (about 50 percent shared) concordance to estimate heritability, after confirming zygosity.
If not, review
Today's new idea is only
A genome-wide scan finds risk locations without guessing, and a trio test uses parents as built-in controls to flag a real .
Goal: Students will explain how GWAS scans the whole genome and how the (TDT) uses parents as built-in controls to flag a real .
Know by the end
- A SNP is a single-letter spot where people commonly differ; a genome-wide association study (GWAS) tests hundreds of thousands to millions of SNPs at once without guessing a gene first.
- The (TDT) uses case-parent trios; a heterozygous parent should pass a 50 percent of the time by chance, so over- flags an associated .
- Using a child's own parents as controls neutralizes , a trap where ancestry differences create a false-looking association.
- A real study tested IRF6 in 77 European American, 146 Taiwanese, 34 Singaporean, and 40 Korean trios; the Taiwanese over- was striking (p about 9 x 10^-5), and rs642961 is one SNP studied near IRF6.
1
The scan
Model start: A GWAS scans the whole genome at many SNPs and lets the data point to risk locations, without guessing a gene first.
- A GWAS scans the ____ genome at hundreds of thousands of SNPs and asks, at each one, whether a version is more common in people with the .
- Its great strength is that it does not have to ____ (guess) the gene in advance; the data point to the location.
2
The trio test
- A TDT tests a suspected gene using case-parent ____ (trios); a heterozygous parent should pass the about ____ percent of the time by chance.
- If the affected child inherits it much more often, that is over-, which flags the as associated.
3
The built-in safety feature
- In a plain case-control comparison, if cases and controls come from different ancestral backgrounds, an that simply differs by ancestry can look associated; that trap is .
- Because a child's parents share the child's ancestry, using parents as internal controls neutralizes this trap; the cost is that trios are hard to collect.
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: A genome-wide scan finds risk locations without guessing, and a trio test uses parents as built-in controls to flag a real .
Words to unlock first
SNPGWAStransmission disequilibrium testcase-parent trioover-transmission
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 · Experimental Design domain · Gene-association study design (GWAS and the TDT)
WebXam domain
Molecular and Genetic Technology
Evidence to produce
Read a simplified trio tally for one SNP (among 100 heterozygous parents, the risk version was transmitted 68 times and not transmitted 32 times): state how many transmissions chance predicts, whether 68 is above or below it, and one sentence on what this suggests plus one reason you would want more evidence.
Lab / skill
Biomedical Innovations (BI) · Medical Interventions (MI)
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.
- Park JW, et al. 2007. Association between IRF6 and nonsyndromic cleft lip with or without cleft palate in four populations. Genet Med. [PMID:17438386]
- Grosen D, et al. 2011. Risk of Oral Clefts in Twins. Epidemiology. [PMID:21423016]
- Robinson K, et al. 2024. Genome-wide gene-by-sex interactions for cleft palate. Hum Genet. [DOI:10.1007/s00439-024-02704-y]
- Claim: One reliable way to identify a -risk gene is the using case-parent trios.
- Evidence: In the IRF6 trio study, the data showed ____ (striking over- in the Taiwanese trios, p about 9 x 10^-5).
- Reasoning: This points to a real association rather than an ancestry artifact because the child's own parents share the child's ancestry, which neutralizes ____ ().
How this is graded (rubric)
For: Read a simplified trio tally for one SNP (among 100 heterozygous parents, the risk version was transmitted 68 times and not transmitted 32 times): state how many transmissions chance predicts, whether 68 is above or below it, and one sentence on what this suggests plus one reason you would want more evidence.
| 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 "Read a simplified trio tally for one SNP (among 100 heterozygous parents, the risk version was transmitted 68 times and not transmitted 32 times): state how many transmissions chance predicts, whether 68 is above or below it, and one sentence on what this suggests plus one reason you would want more evidence.".
- 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: A scan and a trio test both flagged rs642961 near IRF6. But a flag is not proof. With millions of SNPs and hundreds of trios, some hits happen by pure luck. How do we tell a real association from a lucky roll of the dice?