Problems in Meiosis Lead to Disease
Grade level(s):High School (9-12), Grade 11, Grade 12
Nondisjunction is the failure of chromosomes to seperate during meiosis. This failure can occur at Anaphase I or Anaphase II and results in trisomy or monosomy gametes. Common diseases taught in conjunction with nondisjunction are Down's Syndrome and Turner's Syndrome.
meiosis, prophase, metaphase, anaphase, telophase, spindle fibers, sister chromatids, homologous pairs, centromere, centrioles, nondisjunction, trisomy, monosomy
What you need:
- printouts of the fetal karyotypes (half of the class should receive Greene family, other half Wolf family) (see link)
- printouts of the maternal and paternal karyotypes (corresponding Greene and Wolf parents)
- printouts of the meiosis diagram (blown up, one for the maternal, one for the paternal) (see attachment)
- ~1" pipecleaners (enough for each group to map out meiosis I and II for mom and dad); we used pink and blue pipecleaners to represent the maternal and paternal chromosomes; you may want an additional color to distinguish sex chromosomes from autosomes
Students work in pairs to assemble a fetal karyotype and map out meiosis.
Pairs are then matched (one Greene - extra chromosome - and one Wolf - missing chromosome) to discuss the reasoning behind what happened in meiosis to lead to their fetal karyotype.
Students work through the meiosis problem with their original partner the next day.
In a classroom with two pair per table.
Long tables are needed in order to lay out the meiosis diagrams fully.
~ 40 Minutes to cut and assemble the fetal karyotypes
~ 10 Minutes to discuss and compare
~ 70 Minutes to work through the meiosis simulation
This lesson is a variation on the traditional pipe-cleaner simulation of mitosis/meiosis. Initially, students review the normal process of meiosis. The students are then presented with monosomy and trisomy gametes and asked to work backwards through the stages of meiosis in order to determine where the error may have occurred. Students are then introduced to the concept of nondisjunction.
Students should be familiar with:
- the stages of meiosis
- the concept of genetic disease
- Students will match homologous chromosomes in a karyotype spread.
- Students will simulate meiosis so that they understand how nondisjunction can occur and cause disease.
Humans have 22 pairs of chromosomes (autosomes) and a pair of sex chromosomes (23 chromosome pairs in total). While females have a pair of the sex chromosome X (XX), males have two different sex chromosomes X and Y (XY). The Y chromosome contains the male sex-determining gene SRY and is therefore passed on through the paternal line (males receive the Y chromosome from their father, while females receive one X from each parent).
A karyotype is a photograph of a complete set of chromosome from an individual. Cells are collected, preferably during metaphase, spread on a slide and stained for observation under a light microscope. Once an image is obtained, each chromosome is paired to its homolog (homologous pairs) based on size, banding pattern and the location of the centromere. The arranged karyotype has 22 autosomes, followed by the sex chromosomes at the end. This allows cytogeneticists to inspect any abnormalities in the appearance and count of the chromosomes. It is medically useful to determine the sex of an unborn fetus or to detect chromosomal abnormalities.
In animals, specialized cells (with two sets of chromosomes or diploid 2n) undergo meiosis to produce gametes with one set of chromosomes (haploid n). The process is analogous to mitosis in that it is a form of cell division with similar stages. Homologous recombination occurs when a homologous pair exchanges DNA sequences at the beginning of meiosis. It is an important type of genetic recombination to produce genetic diversity and also as a mechanism of DNA repair. Meiotic cells divide once at two separate stages called Meiosis I and II. Homologous pairs separate (disjunction) during meiosis I while sister chromatids separate during meiosis II. When either separation is abnormal, nondisjunction occurs which can result in the production of daughter cells with one too many (trisomy) or one too few (monosomy) of a particular chromosome. Examples of genetic disorders due to nondisjunction in humans include: Down’s Syndrome (trisomy of chromosome 21) and Turner’s Syndrome (monosomy of XX chromosome).
Down’s Syndrome information can be found here: http://ghr.nlm.nih.gov/condition/down-syndrome
Turner’s Syndrome: http://ghr.nlm.nih.gov/condition/turner-syndrome
This investigation is loosely based on the karyotype lesson plan found at the GENA organization website (see link below). In the first lesson, the student will analyze two sets of human fetal karyotypes to determine whether monosomy or trisomy is present. In doing so, they will learn what chromosomes look like, how to match the homologous chromosome pairs and how to interpret a karyotype. On the second day, the students will work backwards through a visual model of meiosis progression to reflect on the possible causes of trisomy or monosomy.
Fetal karyotypes can be cut up beforehand in order to reduce the amount of time assembling the karyotype.
Lesson Implementation / Outline
Day 1 - Introduction
What are some ways that you can think of to test whether the abnormality of your assigned fetus or infant is genetic or environmental?
(Expected answer(s): blood test, check for family history)
Assemble Fetal Karyotype (40 Mins)
Students are given printouts of fetal mitotic spreads and/or a ziplock with cut out fetal karyotypes. They are instructed to cut out the chromosomes and pair them to create the fetal karyotype. The chromosomes are usually arranged by size, with the sex chromosome pairs at the end.
Discuss/Compare Karyotypes (10 Mins)
Students analyze their karyotypes - count the number of chromosomes (is something missing? are there extras?). How did you match the homologous pairs? What is the sex of the fetus?
Cool Down (10 Mins)
1. What would you expect to see in a normal karyotype?
2. How did your karyotype differ from what you expected?
(Expected answer: 22 pairs of autosomes and 1 pair of sex chromosomes, an extra chromosome 21 or a missing sex chromosome)
3. What could be the genetic consequences of trisomy?
(An additional chromosome may result in the overexpression of genes in that chromosome. For example, dementia sometimes occurs in Down’s Syndrome due to overproduction of the amyloid beta peptide protein in the brain. In other cases, there is no visible difference i.e: triple X syndrome.)
Day 2 - Introduction
1. What other data would you want as a genetic counselor in order to determine if the fetus/baby in question has a random or inherited abnormality? How would this information be helpful for the parents and/or child?
(Expected answer: parental karyotypes can determine if the loss/gain of a chromosome was due to a random event or if it was inherited.)
Give out Parental Karyotypes (5 Mins)
Give out the parental karyotypes and take a few minutes to observe them. Prompt: determine through pair share what this information shows you.
Answer: this will tell students that the missing or extra chromosome was inherited (Greene fetus inherited an extra, Wolf is missing one)
Demonstrating Meiosis of Chromosome in Question Starting with Normal Parent Chromosomes (10 Mins)
Prompt: Start with your chromosome of interest (the chromosome that is abnormal in the fetus/baby) from the parents. Take that chromosome from the mom and show it go through meiosis on the maternal meiosis paper using the pipecleaners provided. Take the chromosome from dad and take it through meiosis on the paternal meiosis paper. After instructor approval, use markers to draw in your chromosomes.
Students should place chromosomes in each cell from a single cell through 4 gametes, for both mom and dad. The center has a spot for zygotes formed between the maternal and paternal gametes.
Determining Issue with Zygote (5 Mins)
Prompt: You already took your chromosomes of interest through maternal and paternal meiosis. Now alter your gametes in a way that could lead to the missing or additional chromosome that you see in the fetus/baby karyotype.
Students should move one of their chromosomes into a different cell (making 2 cells with a maternal and paternal chromosome, 1 with an extra maternal or paternal chromosome and 1 with a missing maternal or paternal chromosome).
Creation of Model (20 Minutes with a check-in at 10 Mins)
Prompt: Considering the gametes that you have just formed, trace the movement of your chromosomes backwards to determine how these abnormal gametes could be formed.
Check-in Prompt: What are some possible theories on how an incorrect number of chromosomes could have happened?
Something happened in Anaphase and the chromosomes didn't separate properly.
Setting Model in Markers (5 Mins)
Prompt: With the approval of the instructors, set your models on your paper using color-coded markers.
Pair Share Model (12 Mins= 3 min share, 3 min feedback x 2)
Prompt: You are now going to do a pair share with a group with a different abnormality. The timer will be set for three minutes for one group to explain their model. Then the timer will be set for three minutes for the other group to give the first group feedback and suggest other models for how the abnormality could have occurred. We will then switch roles.
Cool Down (10 Mins)
What were the similarities and differences between your model and another pair’s model? If each of the gametes you made in your model was joined with a normal gamete and produced a zygote how many chromosomes would each zygote have?
(Expected answer: The error occurred at the same step in meiosis I or II. This is likely II since they work backwards from the zygote. The error could have happened in mom or dad. 2 of the zygotes would be normal, 1 would be missing a chromosome, and 1 would have an extra chromosome.)
Extensions and Reflections
“Adventures in Karyotyping” The Geneticist-Educator Network of Alliances Project.