Rough draft.This research track is under review with Dr. Atit's lab. Content and sequence may still change.
The Baby Mateo Case
Developmental domainPrinciples of Biomedical Science (PBS)Lesson 17 of 20Your seat: Epigeneticist
Same DNA, Different Outcome
Discovery question
How can identical DNA give two different outcomes, a fused or a ?
💡 Epigenetic marks and tiny RNAs change gene activity without changing the , so a on top of a can tip one into clefting while another stays fused.
The plan
Prerequisite check
Before this page, you should know
- A teratogen is an environmental agent that can disturb normal development, but only if it acts during the structure's critical window.
- Low maternal is studied as a modifiable ; the protective size for clefts is debated and weaker than for neural-tube defects.
If not, review
Today's new idea is only
Epigenetic marks and tiny RNAs change gene activity without changing the , so a on top of a can tip one into clefting while another stays fused.
Learn first
What you will learn
Goal: Describe how and microRNAs change gene activity without changing the , and use the idea to explain why two embryos with the same can differ.
Know by the end
- is the study of changes in gene activity that do not change the itself.
- adds a methyl group that usually silences a gene; a study found 578 methylation positions associated with nonsyndromic CL/P, enriched in regulatory craniofacial regions.
- MicroRNAs (such as miR-140) repress target genes after they are read to fine-tune networks.
- The model explains penetrance: a is the first hit, and an epigenetic or environmental change can be a second hit that tips a into clefting.
Learn first
Model: A methylation signature in real cleft patients
Researchers compared DNA from people with lip and to controls in two countries (Brazil, UK) (PMID:28550290).
They found 578 methylation variable positions linked to nonsyndromic CL/P, concentrated in active, regulatory regions and enriched in craniofacial pathways including WNT/ and the -mesenchymal transition pathway. Most strikingly, in families carrying a known risk , the relatives who actually clefted had higher promoter methylation of CDH1 (E-cadherin) than relatives with the same mutation who did NOT cleft.
A partner finding: microRNAs such as miR-140 must be at just the right level, and miR-140 is down-regulated by smoking in cells, so a variant plus passive smoking raised risk more than either factor alone (PMID:28420997).
Do the work
Explore (work the model before reading on)
- Did the patients have a different from controls, or a different chemical mark on the DNA?
- Among family members with the SAME risk , what was different between those who clefted and those who did not?
- CDH1 (E-cadherin) is a stickiness/ . If its promoter is methylated and the gene goes quiet, how might that connect to the adhesion-and- step you studied earlier?
- The miR-140 variant alone or the smoking alone raised risk a little, but together raised it more. What does that tell you about how genes and environment combine?
- Mateo has the same kind of these studies examined. If a small inherited needs a to show up, would you expect a clean 50/50 family pattern, or something messier? Why?
The plan
Guided notes
1
Two epigenetic tools
Model start: is the study of changes in gene activity that do NOT change the itself.
- adds a methyl group (CH3) to DNA, usually turning a gene ____ (down/off); from Lesson 16 supplies those methyl groups, so nutrition feeds the epigenome.
- MicroRNAs (miRNAs) are small RNAs that ____ (repress) target genes after they are read; even a small change in miR-140 can shift development.
2
The second hit and penetrance
- An inherited is the first hit; an epigenetic change like CDH1 promoter ____ (methylation) can be a that tips a into clefting.
- This explains ____ (penetrance), the fraction of people with a risk who actually show the trait.
- Isolated clefting looks like a ____ (multifactorial) trait: several small pushes adding up, not one all-or-nothing gene.
Explore
Reading the Research
What to read
Read the title and the abstract only, not the whole paper. Alvizi et al. 2017, Differential methylation in nonsyndromic cleft lip and palate and penetrance (Sci Rep)
Why this source matters
This is the published evidence behind today's idea: Epigenetic marks and tiny RNAs change gene activity without changing the , so a on top of a can tip one into clefting while another stays fused.
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 · Developmental domain · PLTW PBS 072110
WebXam domain
Bio-Molecular Technology
Evidence to produce
Build a two-embryos diagram. Both carry the same small risk allele. Embryo 1 stays under the threshold and the palate fuses. Embryo 2 picks up a second hit (for example, low folate plus a methylation change quieting an adhesion gene) and crosses into clefting. Label the first hit, the second hit, and the outcome for each, then write one sentence on why this additive picture fits an isolated cleft better than a single-gene syndrome.
Lab / skill
Principles of Biomedical Science (PBS)
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: Build a two-embryos diagram. Both carry the same small risk allele. Embryo 1 stays under the threshold and the palate fuses. Embryo 2 picks up a second hit (for example, low folate plus a methylation change quieting an adhesion gene) and crosses into clefting. Label the first hit, the second hit, and the outcome for each, then write one sentence on why this additive picture fits an isolated cleft better than a single-gene syndrome.
- Wrote my Claim, Evidence, and Reasoning exit ticket.
Pick your period and code first.
Check yourself
Exit ticket (Claim, Evidence, Reasoning)
- Claim: Two embryos with identical DNA (can / cannot) end up with different outcomes.
- Evidence: One finding from the methylation or miRNA studies.
- Reasoning: How the idea and penetrance explain why a does not always cause a .
How this is graded (rubric)
For: Build a two-embryos diagram. Both carry the same small risk allele. Embryo 1 stays under the threshold and the palate fuses. Embryo 2 picks up a second hit (for example, low folate plus a methylation change quieting an adhesion gene) and crosses into clefting. Label the first hit, the second hit, and the outcome for each, then write one sentence on why this additive picture fits an isolated cleft better than a single-gene syndrome.
| 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 "Build a two-embryos diagram. Both carry the same small risk allele. Embryo 1 stays under the threshold and the palate fuses. Embryo 2 picks up a second hit (for example, low folate plus a methylation change quieting an adhesion gene) and crosses into clefting. Label the first hit, the second hit, and the outcome for each, then write one sentence on why this additive picture fits an isolated cleft better than a single-gene syndrome.".
- 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
Epigeneticist Genetic counselor Molecular biologist
What's next: Epigenetic marks and tiny RNAs let identical DNA give different outcomes, and isolated clefting behaves like an additive, multifactorial trait. But we just reasoned from human DNA, mouse palates, and zebrafish at once. How do scientists actually watch development happen?