Interactive lab · Genetic and developmental disorders

Centerpiece

Five pedigrees (pattern, genotypes, probability), a 46-chromosome Down syndrome and six parent-of-origin puzzles.

In context: 5.1 Mutations and Mendelian inheritance →

Centerpiece · Pedigree Lab

Pedigree Lab

Read the family, not the disease name. For each pedigree: pick the pattern and the clue that proves it, genotype the marked people, then compute a risk. Two more exercises follow the same logic into chromosomes: a 46-chromosome Down syndrome and the parent-of-origin puzzles of chromosome 15.

A daughter with cystic fibrosis

III-1 has cystic fibrosis. Her parents and siblings are healthy, and so is the rest of the family. Her sister III-2 wants to know whether she could be a carrier.

male
female
affected
proband

Cystic fibrosis (CFTR) · dashed rings mark the people you will genotype in step 2.

Step 1

Inheritance pattern and the decisive clue

Pick the pattern.

Which observation decides it?

Step 2

Assign genotypes

Settle the pattern in step 1 first: genotypes depend on it.

Tap a person with a dashed ring, then tap the genotype that is certain for them. Use “+/?” when the data cannot decide.

People

Genotypes

Tap a person (here or on the pedigree), then a genotype, or the other way round.

Step 3

Compute the probability

Finish the genotypes first: the calculation starts from them.

III-2 is healthy. What is the probability that she is a carrier?

Causal chains

CGG expansion, nondisjunction, ΔF508, maternal diabetes and RDS: fill the missing step.

In context: 5.1, 5.2, 5.3, 5.4, 5.6 →

Core activity · The Missing Arrow

The Missing Arrow

Complete the causal chain. Place the missing step by dragging a card onto a gap, or tap a card and then tap the gap. Some gaps need an event; others need the mechanism that links one event to the next.

A boy inherits an FMR1 allele from his mother that expanded from 90 to over 600 CGG repeats. Complete the chain from DNA to phenotype.

One gap needs the mechanism that silences the gene; another needs the event that the brain actually lacks.

Full mutation: > 200 CGG repeats in the 5′ untranslated region of FMR1 (Xq27.3)
FMR1 transcription is shut off
no FMR1 mRNA to translate
Intellectual disability, autistic features, long face, large ears, macroorchidism after puberty

Cards

Tap or drag a card. Placing a used card moves it.

Look-alikes

Prader–Willi vs Angelman, AIS vs 5α-reductase, free vs translocation trisomy, CMV vs toxoplasmosis.

In context: 5.2, 5.3, 5.4, 5.5 →

Core activity · Almost Twins

Almost Twins

Two look-alikes side by side. Decide what they share, then pick the clue that separates them and say why it works.

Look-alike A

Prader–Willi syndrome

Paternal deletion
PWS genes ✗ · UBE3A ✓
Prader–Willi (~70%)
Maternal UPD
PWS genes ✗ · UBE3A ✓
Prader–Willi (~25%)

Blue = paternal 15, pink = maternal 15. Green box = working copy, gray = silenced by imprinting (methylation), dashed red = deleted.

Loss of the paternal 15q11–q13 contribution (schematic).

Defect in 15q11–q13
Paternal copy missing: paternal deletion (~70%) or maternal UPD (~25%)
Neonatal hypotonia and poor feeding → hyperphagia, obesity, hypogonadism, small hands
Mild to moderate intellectual disability; temper outbursts

Step 1 · What they share

What do the two syndromes share?

Select every feature that both show.

Case reasoning

Change maternal age, the parent of a deletion, a hidden Y or the timing of a drug.

In context: 5.2, 5.3, 5.5 →

Core activity · One Fact Changes

One Fact Changes

Answer a case and name the decisive clue. Then exactly one fact changes. Decide whether the answer moves, and why.

1 · The original case

A 42-year-old woman delivers her third child. The baby has a flat facial profile, upslanting eyes, epicanthal folds, Brushfield spots, a protruding tongue and a loud murmur. The karyotype is pending.

What is the most likely mechanism?

Which fact carried the most weight?