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Making Cells & Proteins · Chapter 6 of 7
Seventeen, and it ended on paper. After the October-to-February season — strep, teardrops, shingles (Integumentary 5.2 and Immunity 22.5 follow it) — came the guidance counselor’s number and the news that she would have to repeat senior year. “So I’m done. I signed the paper. Mom signed under me and didn’t say anything, and Dad said I could get a GED at the community college, people do it all the time.” Two parents on one page. Nine years earlier a doctor had asked whether anybody else in the family got the fevers, and Mom had said no, just me. This chapter is about how a body gets one copy of everything from each of the two parents on that page — the division that halves a genomeThe complete set of genetic material in an organism. and shuffles it, the Punnett square that predicts what a child can get — and what that square quietly assumes.
The question you will answer
A family history of “just me” sounds like the end of a genetic question. Before you can weigh it you need to know how genes actually travel: meiosis halves the chromosomes and deals them out at random, fertilization puts one set from each parent back together, and a Punnett square predicts the odds — if its assumptions hold. The question for the chapter: when a disease is called recessive, what can one copy do?
Opener · Two Signatures · about 2¼ minutes
The opener is the same narrated animation you will watch in Scene 1.
Watch the opener first. It sets the question; the chapter answers it.
1
Read the chart
Patient chart · Stina
Oct 1992 – early 1993 · age 17 · three diagnoses, a number, and a signed paper
1983 · 8
Module 1’s year: Dr. Gonzalez asks how often the fevers come, how long they last, “and whether anybody else in the family gets them. Mom said no, just me.” She asks for a calendar with the fever days marked.
Oct 1992 – Feb 1993 · 17
Senior year: the October-to-February season — strep, teardrops, shingles (Integumentary 5.2 and Immunity 22.5 tell it).
early 1993 · 17
The guidance counselor shows her the days missed and says she would have to repeat senior year. “So I’m done. I signed the paper. Mom signed under me and didn’t say anything, and Dad said I could get a GED at the community college, people do it all the time.”
Told
“Guttate psoriasis, from the strep.” Shingles “unusual for my age.” “Whether I’d been under a lot of stress.” “Repeat senior year.” Chart: “Three diagnoses, three creams, three different doctors.” Family history, at eight: “just me.”
Chart clues this module: 4 · this module (the Chart Reveal, logged in Chapter 7) — this chapter answers “what one copy can do”; no gene test exists in her childhood (MEFV was found in 1997)
Before you go on · your prediction
Two parents on one withdrawal paper, and an old answer from when she was eight: “no, just me.” Before you learn how genes travel through a family, what does a family history of “just me” most likely tell you?
Open the one you lean toward. Nothing is recorded and nothing is revealed — you come back to it at the end.
Nothing runs in the family — “no, just me”
Watch how a recessive alleleDifferent versions of a gene that determine specific traits. can travel through people who never get sick, and how much a single generation of a family tree can actually show.
A changed copy can pass through people who never look ill
Watch what a Punnett square assumes about carriersMembrane proteins that transport substances across a cell membrane., and whether one changed copy is ever enough.
It’s her circumstances, not her genes — “whether I’d been under a lot of stress”
Watch what penetrance means, and what a family history can and can’t record.
From Stina’s diary
2
The story
Three short movements: the case, the anatomyThe study of the structure of the human body. and physiologyThe study of how the body functions., then the tie back to Stina. Each links to the scene where you’ll see it move.
I · Done
Senior year had come apart one piece at a time — the October-to-February season of strep, teardrops and shingles that Integumentary 5.2 and Immunity 22.5 follow. By the end of it she had missed so much school that the guidance counselor called her in, showed her the number and said she would have to repeat senior year to graduate. “I said I’d rather not.” And then, in three short sentences: “So I’m done. I signed the paper. Mom signed under me and didn’t say anything, and Dad said I could get a GED at the community college, people do it all the time.” Two parents, two reactions, one page: her mother’s signature under hers, and her father’s suggestion of a GED. Nobody in that room was thinking about genes. But every cell in the girl who signed first carried one set of chromosomes from the woman who signed under her and one from the man who offered the GED, and that is this chapter’s subject. Nine years before, a doctor who actually looked had asked whether anybody else in the family got the fevers. Mom had said no, just me. It was an honest answer about what anyone had ever seen. Whether it was also an answer about genes is the question a family tree can ask and a Punnett square can sharpen, and neither can settle it on its own.
See it move: Scene 1 · Two Signatures · Scene 5 · Both From Mom
II · Half a set, shuffled
You have 46 chromosomes, but saying you own 46 chromosomes is like saying you own 46 socks. If you’re my husband, who buys his socks in bulk once a year and they’re all identical, fine. Mine come in pairs, a left and a right: 23 pairs, one member of each from your mother and one from your father — 22 pairs of autosomes plus the sex chromosomes, XX or XY. The partners are homologous chromosomes: same length, same centromereThe region of a chromosome where sister chromatids attach and spindle fibers bind. position, the same genes in the same order — but not necessarily the same versions. Those versions are alleles, and the gene’s position on the chromosome is its locus. Homologs are not spares; they are two sources. Your body cellsThe basic structural and functional units of life. — somatic cellsAny body cell that is not a reproductive cell. — divide by mitosis and keep all 46. A small set of cells in the ovariesThe female gonads that produce eggs and hormones. and testes, the primary oocytesImmature egg cells halted in development until puberty. and spermatocytes, run meiosis instead, and meiosis has two jobs mitosis never has: halve the number and shuffle the deck. Meiosis I pulls the homologous pairs apart, after they have traded segmentsThe subdivisions of lung lobes, supplied by tertiary bronchi. by crossing over in prophaseThe first stage of mitosis where chromatin condenses into visible chromosomes. I; meiosis II pulls the sister chromatids apart, the way mitosis does. First the pairs, then the sisters. One cell becomes four haploid cells with 23 chromosomes each — count the centromeres. Because each pair lines up independently, 23 pairs give 2²³, about 8.4 million combinations per parent: eight million hands dealt from one deck, before crossing over adds more. Fertilization puts 23 and 23 back together into a zygote of 46. A Punnett square is the bookkeeping for one gene’s alleles in that deal: it shows the probability of what a child can get, never what any one child does get.
See it move: Scene 2 · First the Pairs, Then the Sisters · Scene 3 · The Punnett Square
III · Both changes, one side
Here is the answer Modules 1 and 2 promised you: what one copy can do. The zygote that became Stina got both of her changed copies in the set from her mother — one changed MEFV copy, E148Q, on a chromosome 16, and one changed LPIN2 copy on a chromosome 18 — while her father’s set brought unchanged copies of both genes. Two different chromosomes, so in her mother’s ovary each egg had a one-in-four chance of carrying both changes; Stina’s did. Read forward to 2026, the diary’s entry about her mother — the “poison ivy” on the fronts of both shins, seven traits the two women shared — fits a mother who carried both copies; that is a reading, not a result. One changed copy of each gene; heterozygous for both. The textbook square reads that as good news twice over. FMF is classically autosomal recessive, Majeed syndrome is autosomal recessive, and a person with one copy of a recessive variant is supposed to be a healthy carrier. But pyrin is not a channel that one good copy can cover for. It is a sensor, and FMF variants act as gain of function: they lower the thresholdThe minimum voltage needed to trigger an action potential. at which pyrin fires. So a meaningful share of people with FMF carry only one detectable MEFV variant, penetrance is incomplete and variable, and the variants are not equal — M694V usually severe, E148Q mild, disputed, a variant of uncertain significance. That is why “just me” never closed the question: a family can pass a changed copy through people who were never sick enough to be named. Honesty flags: no test was run on anyone in 1993; the diary’s 2026 entries leave Dad’s own test “still pending” and say nothing of results for Mom or her brother; and the idea that one MEFV copy and one LPIN2 copy add up is Amy’s hypothesis — the story’s working model, not a published finding.
See it move: Scene 4 · What the Square Assumes · Scene 5 · Both From Mom · Scene 6 · Rare Is Not Never
3
Watch · explore · think · check
6 scenes. Each one has a short animation or a slide, something to explore, a true/false spot-check of your thinking, and a quick check. Every scene gives you an evidence card for your board.
How to read the scenes
- Animation (dark teal) — a short animated explainer, one idea each
- Slide (dark teal) — a still to study: a micrograph, a diagram or a map
- Explore (purple) — something to push on while you watch
- Game (purple) — a quick challenge
- Think (gold) — reason it out, then spot-check yourself with a few true/false questions; not graded
- Check (gold) — a quick H5P that scores itself
Scene 1 of 6
Two Signatures
Her mother signed under her; her father offered the GED — and every cell in her body carries one set of chromosomes from each of them, though, as Scene 5 shows, both of her changed copies rode in on her mother’s set.
Animation · in production · 2 min 10 s
Two Signatures
A school withdrawal form on a desk, early 1993: a student’s signature, her mother’s under it, and beside the form a speech line for Dad — “a GED at the community college.” The ink line and the speech line unspool into two strands of chromosomes — one set drawn in pink, one in blue, Amy’s own color code for Mom and Dad. They settle into a single round cell: 46 chromosomes, 23 pink and 23 blue. A sock drawer slides open beside it — 46 socks, not 46 identical socks but 23 pairs, a left and a right — and each pink chromosome finds its blue partner by length and by where its waist, the centromere, sits. A label appears on one pair: HOMOLOGS · SAME GENES, SAME ORDER · VERSIONS MAY DIFFER. A word tries to stamp itself across them — BACKUP — and is crossed out. The cell is copied, and copied, into a skinThe body’s largest organ, providing protection and regulation. cell, a gut cell, a neutrophil, a nerve cell: every one of them pink-and-blue (SOMATIC CELLS · MITOSIS · 46). Off to the side, in one small set of cells in the ovary and the testis, a different division waits (SEX CELLS · MEIOSIS · 23). Last frame: a karyotypeA visual representation of an organism’s chromosomes arranged in pairs., all 46 laid out in pairs, with the colors drained to gray — and a question mark over each pair, because from the picture alone nobody can tell which came from Mom and which from Dad.
Prefer the full lecture? Meiosis (original video on the site)
Explore · in production
Pair the socks
An open sock drawer seen from above, with 46 loose “socks” tumbled in it — each one a duplicated chromosome drawn as an X, in pink or blue, with its length, a simple banding stripe pattern and its centromere (the waist) visible. The student’s task: lay out a karyotype by pairing them on a tray of 23 numbered slots plus a sex-chromosome slot. Before anything is placed, a prediction card asks: how will you know two socks are partners — same color, same length, same waist position, same stripes? The drawer answers by behavior: a pink and a blue of the same length, centromere position and banding snap together into a slot; two of the same color never pair, which teaches the first rule — one partner from each parent. As pairs fill, a readout counts centromeres (“count the centromeres to count the chromosomes”: 46) and pairs (23). The sex-chromosome slot offers XX or XY; the student picks XX for this drawer and a card explains that X and Y are partners for pairing purposes though very different in size. Three cards open once all 23 pairs are made. SAME GENES, SAME ORDER: one highlighted pair shows a gene at the same locus on both, with a small tag on each copy — one tag reads “version A,” the other “version a” — the word allele appears. NOT A BACKUP: a stamp reading BACKUP tries to land on a pair and the student decides whether it fits two cases — a cystic fibrosis channel (loss of function: one working copy makes enough channel, so the healthy copy really does cover) versus a hair-trigger sensor (gain of function: the changed copy fires on its own, and a normal partner can’t stop it); the stamp sticks only on the first. WHICH IS WHOSE?: the colors drain to gray, as in a real karyotype, and the student is asked to point to the chromosome from Mom; the reveal is that nobody can from shape alone — only DNA comparison with the parents can say which homolog came from which side. Last screen: a second drawer opens for a gamete A haploid reproductive cell (sperm or egg). and holds only 23 single socks, one of each number — the setup for Scene 2. Keyboard path: Tab moves through the drawer, Enter picks up a chromosome, arrow keys move between tray slots, Space places it; every pairing is announced in a polite live region (“Pair 7 complete: one maternal, one paternal”). A <details> text version lists the pairing rules, the three cards and the final counts (46 chromosomes, 23 pairs, 23 in a gamete).
Think · not graded
Your two copies of chromosome 16 came from two different people. Explain why it is wrong to call the second copy a “backup,” using two cases: a gene for a membrane channel where one working copy makes enough channel, and a gene for a sensor that fires too easily when one copy is changed. In which case does the normal copy actually protect you?
The true/false spot-check for this prompt is in production.
Check · Single Choice
Which cells are produced by meiosis?
This self-scoring check is in production.
Evidence card 1
Add it to your evidence board
“Mom signed under me and didn’t say anything, and Dad said I could get a GED”: two parents on one page at seventeen.
Scene 2 of 6
First the Pairs, Then the Sisters
Meiosis runs the mitosis playbook twice — and what gets separated each time is the whole trick.
Animation · in production · 2 min 15 s
First the Pairs, Then the Sisters
One primary oocyte drawn with just two chromosome pairs so the eye can follow them: a long pair and a short pair, each with a pink member and a blue member, already duplicated (sister chromatids joined at the centromere). PROPHASE I: the homologs find each other and lie side by side; their arms cross, and at the crossing a pink segment and a blue segment trade places — CROSSING OVER · NEW COMBINATIONS. METAPHASE I: the PAIRS line up on the equator (a side panel shows mitosis lining up single chromosomes instead — “compare the metaphases”). ANAPHASE I: whole homologs part, pink to one pole or blue — two coin flips appear over the two pairs. Two cells, each with one member of every pair. MEIOSIS II: the SISTERS part, as in mitosis. Four haploid cells, each with 2 of the 4 chromosomes in this simplified cell; a counter scales it up to the real thing — 23 per gamete, 2²³ = 8,388,608 possible mixes per parent. A short timeline under the egg side notes that a woman’s primary oocytes begin meiosis I before she is born and pause there for years. A last aside: one pair fails to separate — NONDISJUNCTION — and gametes of 24 and 22 appear; a 24 meeting a 23 makes 47, the counting mistake behind trisomy 21, “a quantity error, not a spelling error.”
Prefer the full lecture? Meiosis (original video on the site)
Explore · in production
Deal the hands
A green card table. Across the top sit 23 numbered card pairs, face up — for each chromosome number one pink card (from Mom) and one blue card (from Dad); a few carry a small gene label so the student can follow them (pair 16 shows MEFV; pair 18 shows LPIN2; pair 7 shows CFTR). The dealer button says DEAL A GAMETE. Before the first deal a prediction card asks: will a gamete get the whole pink set, the whole blue set, or some of each? Each deal flips 23 coins at once — one per pair — and moves one card of every pair into the gamete hand; the hand always holds exactly 23 cards, one of each number (a check line: “one of every number, never both, never neither”). A tally keeps a running count of how many distinct hands have appeared, with a counter beside it that shows the total possible: 2²³ = 8,388,608. A CROSSING OVER toggle adds a step before the deal: the pink and blue cards of a pair are laid together, a cut line is drawn and the ends swap, so a card can come out half pink, half blue — the counter’s label changes to “8,388,608 × far more,” and a card explains that crossing over happens in prophase I and makes chromosomes that never existed before in either parent. A SIBLINGS button deals two hands from the same deck side by side and highlights how many of the 23 match — usually about half, the family-resemblance-but-not-quite around every dinner table. A FOLLOW ONE GENE switch hides all but one pair (16, MEFV): if Mom carries one changed MEFV copy, each of her eggs has a 1-in-2 chance of carrying it — the card is either the changed one or the other, never both; the same holds for her pair 18 (LPIN2), and a pair with no change on it passes a plain card every time. A last MISTAKE card lets the student make pair 21 fail to separate: one hand ends with 24 cards and one with 22, and joining the 24-card hand to a normal 23 shows 47 — trisomy 21 — labeled “a counting error, not a spelling error.” Keyboard path: Tab to the dealer and toggles, Enter deals, arrow keys move through the hand; every deal is announced (“Gamete dealt: 12 maternal, 11 paternal chromosomes”). A <details> text version gives the rules, the 2²³ arithmetic, the one-gene 1-in-2 odds and the nondisjunction count.
Think · not graded
Two sisters share both parents, yet they can differ in which copy of chromosome 16 each received from their mother. Using independent assortment and crossing over, explain how one sister could carry their mother’s changed MEFV copy and the other not — and why that makes “no, just me” a weak argument that a gene isn’t in the family.
The true/false spot-check for this prompt is in production.
Check · Drag the Words
Put meiosis in order: what each division separates, where the variety comes from, and what comes out. Two distractors are on the bank.
This self-scoring check is in production.
Evidence card 2
Add it to your evidence board
At eight, Dr. Gonzalez asked whether anybody else in the family got the fevers; Mom said “no, just me.”
Scene 3 of 6
The Punnett Square
A Punnett square doesn’t show you what you get. It shows you what you can get.
Slide · in production
The Punnett Square
A Punnett square for cystic fibrosis, the textbook autosomal recessive disease: two carrier parents, Aa × Aa, their possible gametes (A or a) along the top and the side. Four boxes: AA — homozygous dominant, no disease; Aa and aA — heterozygous, a carrier, no disease but can pass it on; aa — homozygous recessive, has the disease. Per child: 25% affected, 50% carriers, 25% neither — every pregnancy rolls the same dice. Vocabulary in one line each: a gene is a stretch of DNA that codes for a product; its locus is the address; alleles are the versions; genotype is the pair you carry (AA, Aa, aa); phenotype is what shows — and more than appearance. Beside it, a pedigree key and a small three-generation pedigree for a recessive disease: two unshaded parents, half-shaded as carriers once you know, one filled child — the shape that reads as “it came out of nowhere.” Caption lines under the slide: (1) The square predicts probability, never outcome: “they don’t show you what you get, they show you what you can get.” (2) Two carriers face a 25% chance per child — not 50% or 75% (site slip 37). (3) In cystic fibrosis the carrier is healthy because one working CFTR copy makes enough channel; that is a loss-of-function rule, and Scene 4 asks whether it holds for every gene.
Explore · in production
Fill the square, draw the tree
A blank 2 × 2 grid on graph paper with empty gamete slots along the top and the left, a tile tray (A and a), and below it an empty pedigree canvas with a symbol palette (square, circle, filled, half-filled, a partner line, a child line, a ? box). Round 1 — a cystic fibrosis cross, Aa × Aa. The student first predicts the share of affected children (0%, 25%, 50%, 75%, 100%), then drags each parent’s possible gametes onto the sides — the step where, as the BIO121 page says, “mistakes happen” — and fills the four boxes. A readout computes AA / Aa / aa and turns them into percents per child: 25% affected, 50% carriers, 25% neither; a card corrects the common slip that two carriers mean a 50% or 75% chance of an affected child. Round 2 — Aa × AA: no affected children, half carriers (“0% is an acceptable answer”). Round 3 — Aa × aa: half affected. Each round ends with a pedigree to draw: the student places two parents and four children and shades them to match one possible outcome, and a dice button rerolls the family to show that four real children can come out 0, 1, 2 or more affected even when the square says 25% — “probability, not outcome.” Round 4 — a dominant contrast (Huntington disease, Hh × hh): half affected, every affected child has an affected parent, so the pedigree never skips; a note corrects the old site line that HH people “do not exist” (rare, but they do). Final card: the pedigree of a recessive disease often looks like “just me” — carriers are unshaded until someone tests them — and it asks the student what a family history of one would look like on this canvas (one filled symbol, everyone else blank). Keyboard path: Tab to each slot, Enter picks a tile, arrow keys move across the grid, Space places it; the pedigree palette is a radio group with arrow-key placement on a snap grid. A <details> text version gives all four crosses and their percents as tables.
Prefer the full lecture? Punnett Squares (original video on the site)
Think · not graded
Two carriers of a cystic fibrosis allele have four children, and none of them has CF. Does that prove the Punnett square wrong? Use the words probability and outcome. Then explain why the same family’s pedigree might read as “no family history” for generations.
The true/false spot-check for this prompt is in production.
Check · Fill in the Blanks
The textbook rule, worked on cystic fibrosis — the loss-of-function disease where one working copy makes enough. Fill in each blank.
This self-scoring check is in production.
Evidence card 3
Add it to your evidence board
“No, just me”: a family history with one affected person — the shape a recessive pedigree draws when carriers are never tested.
Scene 4 of 6
What the Square Assumes
The Punnett square is honest about its math and quiet about its assumptions — and FMF strains every one of them.
Animation · in production · 2 min 20 s
What the Square Assumes
The cystic fibrosis square from Scene 3 sits center screen, confident. Four assumptions rise out of it one at a time and hang above it like price tags: ONE GENE DECIDES IT · EVERYONE WITH THE GENOTYPE SHOWS IT · ONLY THE HOMOZYGOTE IS ILL · EVERY VARIANT IS THE SAME. The letters swap from CFTR to MEFV, and the tags are tested one by one. ONLY THE HOMOZYGOTE IS ILL: a pyrin molecule drawn as a sensor with a trigger; the normal copy needs a big signal to fire, the changed copy a small one — GAIN OF FUNCTION · A LOWERED THRESHOLD — and one hair-trigger copy fires even with a normal partner beside it; a CF channel next to it shows why loss of function is different (one working copy makes enough channel). The tag tears. EVERYONE SHOWS IT: a row of people with the same genotype, shaded from bright to pale — PENETRANCE IS INCOMPLETE AND VARIABLE. The tag tears. EVERY VARIANT IS THE SAME: four MEFV variants on a strip, no numbers on it — M694V, usually severe and the most common in the classic populations, with a higher amyloidosis risk; M680I; V726A, often milder; E148Q, mild, disputed, of uncertain significance — and a small note: a few MEFV variants act as dominant, one copy causing disease in whole families. The tag tears. ONE GENE DECIDES IT: a second chromosome slides in labeled ANOTHER GENE? and the tag is left half-torn, with a question mark — Scene 5. Last frame: the square again, unchanged, with a new caption under it: STILL TRUE MATH · DIFFERENT QUESTION.
Prefer the full lecture? Complex Inheritance (original video on the site)
Explore · in production
Switch off an assumption
A Punnett square for one gene in the middle of a control panel, with a readout above it — PREDICTED: SHARE OF CHILDREN WITH SYMPTOMS — and four labeled toggle switches below it, all ON at the start: ONLY TWO COPIES CAUSE DISEASE · FULL PENETRANCE · ALL VARIANTS EQUAL · ONE GENE ONLY. The starting cross is a carrier parent × a non-carrier parent (Aa × AA) for MEFV, and with every switch ON the readout says 0% — “a carrier family; nobody will be ill” — which is what the textbook rule predicts. Before each switch is flipped the student predicts whether the readout will go up, go down or stay. ONLY TWO COPIES → OFF: the panel replaces the recessive rule with a gain-of-function sensor and the boxes holding one changed copy light up partly — the readout becomes a range labeled “some,” not a number, with a card explaining why (pyrin’s changed surface lowers its firing threshold, so one copy can be enough; how often is uncertain and cohort-dependent). FULL PENETRANCE → OFF: each lit box becomes a little row of figures shaded from strong to faint — the same genotype, different degrees of illness — and the word penetrance is defined; a second word, expressivity, is introduced for how severe it is when it shows. ALL VARIANTS EQUAL → OFF: a variant picker opens with four cards and qualitative labels only — M694V (often severe, common in the classic populations, linked to amyloidosis risk), M680I (variable), V726A (often milder), E148Q (mild or uncertain; classified differently by different labs; common enough that many healthy people carry it) — and the lit boxes brighten or dim with the choice; a footnote card names the rare dominant-acting MEFV variants reported in some families, including Northern European ones. ONE GENE ONLY → OFF: a second square slides in beside the first for another gene and the panel says only “the textbook has no square for two half-diseases — Scene 5.” Last screen: the student flips all four back ON and back OFF and writes one sentence in a box from given starters: “The square was right about ______ and silent about ______.” (the odds of inheriting a copy; what one copy does). Keyboard path: the switches are native toggle buttons with aria-pressed; the variant picker is a radio group; every readout change is announced in a live region. A <details> text version gives each switch, what it changes and the evidence behind it, with “estimates vary” wherever a share would go.
Think · not graded
Cystic fibrosis carriers are healthy; some people with one changed MEFV copy have fevers. Both diseases are called “autosomal recessive” in textbooks. Explain the difference in terms of what each protein does — a channel you need enough of versus a sensor that fires too easily — and say which Punnett-square assumption fails for FMF.
The true/false spot-check for this prompt is in production.
Check · Drag the Words
FMF inheritance, textbook rule and exceptions. Drag the right word into each blank; four words are left over.
This self-scoring check is in production.
Evidence card 4
Add it to your evidence board
Nobody else in the family “gets them” — the shape incomplete penetrance can draw.
Scene 5 of 6
Both From Mom
Two changed copies in two different genes, both carried in one egg — the combination no one-gene Punnett square in a textbook was drawn for.
Animation · in production · 2 min 20 s
Both From Mom
Two parent icons, pink and blue. Beside the pink one, Mom’s four relevant chromosomes: two 16s, one with a small mark — MEFV · E148Q · EXON 2 — and two 18s, one with a mark — LPIN2 VARIANT. Beside the blue one, Dad’s four: all plain. Mom’s ovary deals eggs: because 16 and 18 are different chromosomes, each pair sorts on its own coin flip, and four kinds of egg fan out in equal shares — neither change, the MEFV change only, the LPIN2 change only, both. Dad’s sperm come in one kind for these two genes: plain. One egg with both marks meets a plain sperm — a zygote with two pronuclei — and one card stamps it: HETEROZYGOUS FOR BOTH · BOTH CHANGED COPIES FROM MOM. Side panel, LPIN2: lipin-2, the lipid enzyme of Module 2.4; MAJEED SYNDROME · AUTOSOMAL RECESSIVE · TWO COPIES; first described in 1989 in three related children; a few dozen patients ever reported; a small line beneath — and in the first families, some one-copy parents had psoriasis (a hedged note). A grid assembles — Mom’s four kinds of egg across the top, Dad’s one kind of sperm down the side — and shows the four equal outcomes for any child of these two parents: neither change, MEFV only, LPIN2 only, both (1 in 4). Side panel, MEFV: E148Q, a variant of uncertain significance (Chapter 4). Then a hand-drawn sketch, captioned as STINA’S DRAWING · 2026 · A HYPOTHESIS: a spark (a changed pyrin firing too easily → IL-1β) and kindling soaked by lipin-2’s shortfall (louder macrophages → more IL-6), with the label NOT A PUBLISHED FINDING. Last frame: the pedigree of the Lindqvists as the childhood record leaves it — a filled-with-a-question-mark circle for Stina, her mother’s circle marked as the source of both copies but otherwise unshaded (no diagnosis, no result), her father’s square plain, a ? box for a brother who never appears in her childhood diary, and grandparents with blank boxes: “no, just me,” and every box but one still unread.
Prefer the full lecture? Punnett Squares (original video on the site)
Explore · in production
Follow the copies down the tree
A three-row family tree on a soft paper background: grandparents’ boxes and circles at the top (all blank, each with a ? badge), Mom (circle, pink) and Dad (square, blue) in the middle, and below them a zygote slot and three child slots. Each parent is drawn with two homologs of chromosome 16 and two of chromosome 18 beside their symbol — Mom carries one 16 with a small E148Q mark and one 18 with an LPIN2-variant mark; Dad’s four are plain. A banner across the top: “In 1993 nobody had tested anyone.” Step 1, meiosis: the student presses MAKE AN EGG and MAKE A SPERM; each parent’s pairs separate with a coin flip per pair, and the chosen chromosomes ride a dotted gamete path down the tree. The student predicts before each flip. Step 2, fertilization: the egg and sperm meet in the zygote slot, and a readout reads the genotype — none, MEFV change only, LPIN2 change only, or both. Dad’s flips always deliver plain copies, so every outcome is decided by Mom’s egg. A tally of repeated pairings fills a grid — Mom’s four kinds of egg across the top, Dad’s one kind of sperm down the side — and settles near one in four for each outcome; the student is asked to explain why (two independent 1-in-2 chances in one parent: ½ × ½ = ¼ for an egg with both). A switch then lets the student try a different family — one change in each parent — and see that the share with both is also one in four, but that now each parent is a carrier of one gene, not one parent of two. Step 3, the Stina zygote: a button sets the 1975 zygote to “both,” from one of the quarter of Mom’s eggs that carried both changes. Step 4, mitosis fans it out: the zygote divides into a spreading fan of cells that resolves into tissues — skin, gut lining, bone, a neutrophil, a monocyte, a nerve cell — every one carrying the same two marks. A WHICH CELLS READ MEFV toggle lights the neutrophils, monocytes/macrophages, eosinophils and dendritic cellsImmune cells in the epidermis that help fight infections. brightly and leaves skin and nerve dark (presence vs expression, Chapter 5); a WHERE MAJEED STRIKES toggle lights bone, bone marrow (red-cell precursors), skin and macrophages, labeled “Majeed syndrome’s tissues — with two LPIN2 copies”, with a note that LPIN2 is read in many tissues (the liverA large organ that produces bile, detoxifies blood, and stores nutrients. too) and that one copy is a carrier state, not Majeed syndrome. Step 5, the reading: a panel asks the student to sort four statements into ESTABLISHED and HYPOTHESIS — “Majeed syndrome needs two LPIN2 copies” (established), “some people with one MEFV variant have FMF symptoms” (established), “E148Q’s effect on its own is uncertain” (established — that is what VUS means), “one MEFV copy and one LPIN2 copy add up to her illness” (hypothesis — the story’s working model). The pedigree ends with Stina’s circle marked with a question mark, the brother’s square as a ? box that never fills, and the grandparents still blank. Keyboard path: every button is reachable with Tab and fires with Enter; each coin flip and readout is announced; the sort is a pair of radio groups per statement. A <details> text version narrates one full pass through the tree, gives the two-gene grid as a table and lists the four statements with their answers.
Think · not graded
Majeed syndrome takes two changed LPIN2 copies; Stina carries one. FMF is classically recessive; Stina carries one MEFV variant, and it is of uncertain significance. By the textbook she is a carrier twice over. Write the textbook reading in one sentence, then the reading Amy’s hypothesis offers in one sentence — and name one thing that would have to be shown before the second could be called a finding.
The true/false spot-check for this prompt is in production.
Check · Single Choice
Stina carries one changed MEFV copy (E148Q) and one changed LPIN2 copy, and both came from her mother. Which description of her genotype is right?
This self-scoring check is in production.
Evidence card 5
Add it to your evidence board
Two parents, a mother who had two brain surgeries in Stina’s childhood, a brother who never appears in her childhood diary — and nothing in the 1993 record says which side anything came from.
Scene 6 of 6
Rare Is Not Never
Uncommon in a group is not the same as impossible in a patient — and someone has to be the first one.
Slide · in production
Rare Is Not Never
A balance scale. On the left pan, a weight labeled PRIOR: FMF is most common in people of Armenian, Turkish, Arab and Jewish (especially North African Jewish) ancestry — a statement about probability, not a rule — and much rarer in Northern Europe, where Stina’s grandparents came from. On the right pan, weights the chart can add: recurring fevers that come and go, serous-membrane pain (the belly, the chest), joint attacks, high markers between attacks (Clue #2), episodes with no germ (Clue #3). The scale tips toward the evidence. Under it, Amy’s lines: “Uncommon in this group is not the same as impossible in this patient.” “Rare is emphatically not never.” “A low prior probability is a reason to keep an open mind, not to close the file.” “Someone has to be the first one.” Caption lines under the slide: (1) Founder effects explain why some populations carry certain MEFV variants often (Module 21’s sidebar) — and dominant-acting MEFV variants have been reported in Northern European families. (2) No MEFV test existed during Stina’s childhood: the gene was found in 1997, when she was 22. The lesson here is about reasoning, not a test that wasn’t ordered.
Explore · in production
Weigh the prior
A large two-pan balance on a lab bench, with a tray of weights beside it. The left pan holds one heavy weight labeled PRIOR, and a selector on its front sets the patient’s ancestry group: an Armenian, Turkish, Arab or Jewish background (the weight is large — FMF is relatively common there) or a Northern European background like the Lindqvists’ (the weight shrinks — FMF is rare there, but the weight never disappears). The right pan starts empty, labeled EVIDENCE. Before adding anything the student predicts which way the scale will settle for a Northern European patient with no evidence on the pan (toward “probably not FMF” — correct, and labeled “a fair starting point”). Then the tray offers weights drawn only from the childhood chart the course has built: fevers that come and go and leave her fine between (Module 1) · belly pain that read as appendicitis, with a normal appendixA small, finger-like pouch attached to the cecum, thought to play a role in immune function. (Module 3’s scene) · a knife in the chest on breathing in, called anxiety (Chapters 3 and 4) · legs that hurt at night and knees that swelled on period days (Modules 1–2) · high inflammatory markers even in good weeks (Clue #2) · no germ found in any workup (Clue #3) · a rash and spots no cream explained. Each weight added tips the scale a little and shows a one-line reason; together they outweigh the small prior. Two trap weights wait on the tray: “She’s anxious” and “It’s too rare to bother with” — dropping either on the evidence pan does nothing, and a card explains why: one is a label the chart applied, not evidence; the other is the prior counted twice. A last card names the reasoning error in Amy’s words — a probability read as a rule, “probabilities wearing the mask of rules” — and adds two honest notes: dominant-acting MEFV variants have been reported in Northern European families, and in Stina’s childhood no gene test existed at all (MEFV was found in 1997). Final task: write the sentence a clinician should have been able to say, from given starters — “For someone of this ancestry FMF is ______, so the chart would need ______; this chart has ______.” (uncommon; a recurring, self-limiting, sterile inflammatory pattern; one). Keyboard path: Tab to the selector and the tray, Enter picks up a weight, Space drops it on the pan; the scale’s tilt is announced in words (“tilting toward evidence”). A <details> text version lists every weight, its reason and the two traps. No numbers are put on the prior (published prevalences vary by study).
Prefer the full lecture? Patterns of Inheritance (original video on the site)
Think · not graded
A disease is much rarer in people with your patient’s ancestry. Explain the difference between using that factA statement based on direct observation that is repeatedly confirmed. to set a starting probability and using it to close the file. Then say what kind of evidence in a chart should be strong enough to move past a low prior — and whether Stina’s childhood chart, as you’ve read it so far, had any.
The true/false spot-check for this prompt is in production.
Check · Multiple Choice
Suppose a clinician reasoned: “Her family is Swedish, so it can’t be FMF.” What is the reasoning error?
This self-scoring check is in production.
Evidence card 6
Add it to your evidence board
From the patient chart: her grandparents emigrated from Sweden — far from the populations where FMF is most often found.
4
Your evidence board
Every scene gave you an evidence card, and the chart adds more. Sort each card into the column it supports: One set from each parent — both changes from one, Neither on its own, or “No, just me”. Some cards can honestly go in more than one place — that’s allowed, and the feedback tells you which cards decide the case.
Evidence board · drag and drop · in production
The sorting board for this chapter’s cards is being built. Until it arrives, sort your evidence cards on paper into the three columns above.
5
Your verdict
Time to decide. Look back at your bet, then build your verdict from statements that hold up — no writing needed.
Look back at your prediction
Two parents, one page, and a family history of “just me” — read through meiosis and the Punnett square, the reading that fits best is…
Find the one you chose at the top. Does the evidence support it, refute it, or revise it?
- Nothing runs in the family — “no, just me”
- A changed copy can pass through people who never look ill
- It’s her circumstances, not her genes — “whether I’d been under a lot of stress”
Build your verdict · no writing
Choose the statement that holds in each set. The ones you keep become your argument.
This activity is in production.
6
The finding
Finding · meiosis and inheritance
Both Changes, One Side
1993, age seventeen: strep, guttate psoriasis and shingles in one season; a withdrawal paper signed by Stina and by her mother, and a father who offered the GED; a family history that, at eight, had been “just me.” Chart entry: every cell carries one set of chromosomes from each parent; meiosis gives each gamete one copy of every gene, at random; and the Punnett square, which predicts the odds, assumes one gene, full penetrance and that only the homozygote is ill — assumptions FMF breaks, because pyrin variants act as gain-of-function, penetrance varies and the variants differ. She carries one MEFV E148Q copy and one LPIN2 copy, both from her mother — two independent coin flips that landed the same way in one egg — and unchanged copies of both from her father: heterozygous for both, a carrier twice over by the textbook. Held open: whether her E148Q copy matters on its own (a variant of uncertain significance), and whether one MEFV copy and one LPIN2 copy add up — Amy’s hypothesis, not a finding; the whole chart is read in Chapter 7.
Next · Chapter 7
One Typo, Every Cell — the Chart Reveal
“Nobody once asked what kind of person gets all three in a row. I’d like to know.” She walks out of that building at seventeen. The narrator lays her whole childhood chart end to end and answers the question for you — decades before anyone answers it for her.
Reliable information on rare diseases
NORD · NIH GARD · Orphanet · MedlinePlus Genetics: FMF · FMF & AID Global Association · Autoinflammatory Alliance · Global Genes · Amyloidosis Foundation
Stina has one rare disease. In the United States, about 1 in 10 people live with one of the more than 7,000 known rare diseases. These organizations are where patients, families and clinicians go for trustworthy information.
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← Familial Mediterranean Fever — case home
All pages for Module 4 — Making Cells & Proteins
4.0 Module Overview
4.1 The Code
4.2 Copying the Code
4.3 Transcription
4.4 Translation — and Then Break It
4.5 The Cell Cycle and Mitosis
4.6 Meiosis and the Family Tree
4.7 One Typo, Every Cell — the Chart Reveal
4.8 Conclusion and Assessment
4.9 Evidence Behind the Case
All Modules
- Anatomical Language, Membranes & Homeostasis
- Just Enough Chemistry
- The Cell & Its Transport
- Making Cells & Proteins
- The Integumentary System
- The Skeletal System
- The Muscular System
- Nervous Tissue & the Senses
- The Spinal Cord
- The Brain & the Blood–Brain Barrier
- The Autonomic Nervous System
- Special Senses (in developmentThe process of growth and differentiation.)
- The Endocrine System
- Blood
- The Heart
- Blood Vessels
- The Digestive System
- The Respiratory System
- The Urinary System
- Fluids, Electrolytes & Acid–Base Balance
- The Reproductive System
- The Immune System
List of terms
- genome
- allele
- carriers
- anatomy
- physiology
- centromere
- cells
- somatic cells
- ovaries
- primary oocytes
- segments
- prophase
- threshold
- skin
- karyotype
- gamete
- dendritic cells
- liver
- appendix
- fact
- development