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Project Summary:
What’s up with nondisjunction?
Tracy Evert, Woodland High School, Woodland California
Sean M. Burgess, Department of Molecular and Cellular Biology, University of
California, Davis
This unit was carried out in a biology course comprising academically gifted freshman
and sophomore students at Woodland High School from. The unit spanned 2 ½ weeks
and involved 6 days of classroom visits by SMB. Overall we feel the unit was very
successful. The students were engaged, inquisitive and learned important research,
presentation and writing skills. Students were challenged to consider both clinical and
human issues associated with certain chromosome abnormalities. On the final day SMB
prepared a handout on careers in biomedical sciences and answered questions.
Overall objectives:
The objective of the unit was to have students gain an understanding of the underlying
genetic basis of disease. Students gained skills in analyzing and interpreting karyotypes
of patients exhibiting chromosomal aneuploidies. Following power point presentations on
cancer and genetic diseases and syndromes (SMB), students worked in groups to
diagnose a disease or syndrome indicated by the karyotype they received. Students then
carried out independent research and drafted a letter to parents of these patients
describing the genetic causes of aneuploidy, symptoms associated with the syndrome,
treatments or cures, heritability, life expectancy and quality of life issues including
schooling and discrimination. In addition the students found foundations and support
groups available on the web for parents to learn more about the disease and find support
groups. On the final day students play-acted acting the role of medical geneticists
meeting with parents of the child patient by presenting the issues discussed in the letter.
Unit outline:
Day 1: Students used a worksheet we prepared to write down their ideas of what causes
cancer, what happens in a cancer cell and how would having an extra chromosome affect
and individual. Call discussion followed.
Day 2: SMB presented a 30-minute presentation on the genetic basis of cancer. Students
took notes using a T-chart listing facts and questions. Misconceptions from day one were
discussed. Students looked slides of human chromosome spreads under the microscope
and drew what they observed.
Day 3: SMB presented a 30-minute presentation on how karyotypes are constructed and a
detailed presentation of Cri-du-chat syndrome that introduced the structure for how the
students would be expected to write their letters.
Day 4: Students in groups of 3 were assigned a karyotype and given a worksheet to
identify chromosome monosomy, trisomy and translocations. Students proceeded to the
library to start research to address the topics of the letter.
Day 5: Student groups reassembled to discuss the outcomes of their research and to give
peer evaluation of the draft letters.
Day 6: The final letter was due. Students met in groups of 5 to present their letters to the
group of whom analyzed a different karyotype.
Outcomes: Class discussion prior to and after the unit showed that the students’
misconceptions of genetic mechanisms underlying cancer and birth defects were largely
addressed. The letters prepared by the students were overall excellent. Several students
showed professionalism, compassion and eloquence in play acting the role of medical
geneticists meeting with parents of the child patient.
Overall evaluation:
We found that the GENA collaboration was an excellent way for SMB and TE to interact
and was a tremendous learning experience for both of us. SMB especially enjoyed
contact with 13-14 year old students and sharing her experiences as a geneticist and as a
university professor. We intend to carry out the unit next year. For the next offering of
this unit SMB will obtain sample slides of human chromosome spreads from her
university colleagues since the commercial preparations were of low quality. Next year
we intend to prepare a manuscript on the effectiveness of the unit in reaching our goals.
For this work we will expand the unit to include more standardized pre and post
assessment to better quantify these effects. Two class periods (~ sixty students total) will
serve as our sample.
GENA Partnership
Teaching Plan Outline
What’s Up with Nondisjunction?
By Sean Burgess, University of Davis, California
Tracy Evert, Woodland High School, Woodland, California
A. Objectives and student misconceptions about this topic:
-Understanding of the underlying genetic basis of disease
-Misconceptions of cures and treatment for genetic diseases/syndromes
-Misconception of causes of cancer
-Ethical issues and prejudice towards people with genetic disorders
B. Standards to be addressed:
State of California Genetics standards
1d, 2a-2g,4c-4d, 5b
C. Major science concepts:
Mitosis/meiosis, central dogma of molecular biology, gene expression, mutation,
chromosome segregation
D. Learning Outcomes:
1. Following this lesson plan students will be able to interpret karyotypes that
are associated with cancer and birth defects. They will be able to determine if
a karyotype shows male or female, Turner’s syndrome, Klinefelter’s,
Down’s, Trisomy 18, cancer or other chromosomal abnormalities.
2. Students will be able to write a letter to the parents of a make-believe child
that includes the karyotype findings and process, causes and inheritance,
symptoms and cures, life expectance and lifestyle (including school and
discrimination concerns, support and contact information.
Skills students will use in this teaching plan:
-Analyze karyotypes and know how they are generated
-Letter writing
-Researching genetic disorders
-Understanding of mitosis and meiosis
E. Curriculum materials that will form the basis of this teaching plan:
Internet, Holt Modern Biology, PowerPoint presentations by geneticist,
research worksheets, laminated cards with different karyotypes, sample
letter to parents of child with birth defect.
Conceptual Sequence for the Unit:
Biology Year
Genetics Unit
Cell Division Unit
Parts:
Mitosis/Meiosis Comparison
Nondisjunction
Fertilization
Our Karyotyping Unit
Key words to know: autosomes, sex chromosomes, chromosome number,
deletion, translocation, anuploidy, trisomy, karyotype, meiosis, mitosis,
chromosomes, chromatids, centromeres, nondisjunction
Prior knowledge: Students will have to have a solid understanding of mitosis
and meiosis, the purpose of each, and the steps of each. They will need to
understand the importance of maintaining a constant chromosome number within a
species and the role of the chromosomes in determining inheritance.
F. We are using the 5 Es learning cycle including engage, explore, explain, evaluate,
and extend.
What is up with nondisjunction?
Day 1
Introduction of Guest Geneticist
Form groups of two students for this day
Engage:
Exercise #1 (Appendix A)
Time: 15 minutes
a. Students will answer the following questions individually on a worksheet (4 minutes).
1. What causes cancer? What happens in a cancer?
2. How would having an extra chromosome affect an individual?
b. Students discuss their answers with their partner and narrow answers to three ideas per
question and record then on the worksheet and come up with further questions (6
minutes).
c. Teacher selects several students to share answers with the entire class (5 minutes)
Explore:
Exercise #2 (Appendix B)
Time: 15 minutes
A. Look at chromosome spread under microscope and write a brief description of what
they see on the worksheet. (10 minutes)
B. Teams of two students will look at printout of chromosome smears and describe any
differences including chromosome number. (5 minutes) The karyotypes used are from:
http://www.biologycorner.com/worksheets/karyotype/chromosomestudy-teacher.html
C. Class discussion (remaining time).
Day 2
Explain:
A. Presentation on Cancer using PowerPoint by guest geneticist.
B. Students will take notes on a T chart with 15 facts in the left column and 10 questions
in the right column.
C. Student will return to Day 1 worksheet and identify and correct misconceptions
regarding cancer.
D. Students share with the class what their misconceptions were regarding cancer.
Day 3
Explain:
A. Presentation on Karyotypes and nondisjunction using PowerPoint (example: Cri-duChat) by guest geneticist.
B. Students will take notes on a T chart with 15 facts in the left column and 10 questions
in the right column.
C. Student will return to Day 1 worksheet and identify and correct misconceptions
regarding having an extra chromosome.
D. Students share with the class what their misconceptions were regarding having an
extra chromosome.
Day 4
Explore:
Karyotype analysis (15 minutes)
A. Teacher will assign groups of 3 students.
B. Groups are given one of 8 possible karyotypes. See Appendix C. Students describe
their assigned karyotype and describe using terms that were presented earlier. A
worksheet with terms will be provided (e.g. trisomy, monosomy, translocation, deletion,
duplication).
Karyotype choices
1. Trisomy 13
2. Trisomy 21
3. Trisomy 18
4. XO
5. XXX
6. XXY
7. XYY
8. Cancer
C. Teacher will check accuracy of assessment.
D. Briefing on research assignment. Pass out research outline. Explain letter writing
assessment. Appendix C (30 minutes)
Day 5
Extend:
Research disease/disorder in computer lab
Day 6
Extend:
½ time spent doing research
½ time spent in a discussion within the three-member team on the same topic
Day 7
Discuss letter more. Answer any questions regarding any of the following parts:
1. How is karyotype performed
2. Findings from analysis
3. Describe genetic cause of aneupoidly
4. Symptoms and treatments
5. (non) Inheritance
6. Life issues to consider
a. Life expectancy
b. Independent living
c. Schooling /discrimination
Write letter as homework
Day 8
Evaluate:
Reintroduce 3 previous misconceptions
Meet in teams of 5 to share portions of letters (each student representing a different
genetic disorder)
Students will use the rubric to evaluate each other during the presentation.
Revise ideas about cancer and aneuploidy
Come up with future questions: What is one thing more you would like to know about
these diseases?
Letter writing will serve as the summative assessment.
The rubrics used are in Appendix C.
Appendix A
------------------------------------------------------------------------------------------------------------
Day 1: What’s up with nondisjunction?
Your name: _____________________
Date: ____________________
Partner’s name: __________________
A. Individual response:
1. What causes cancer? What happens in a cancer cell?
2. How would having an extra chromosome affect an individual?
B. Partner discussion- Record three responses to the above questions.
1. What causes cancer? What happens in a cancer cell?
2. How would having an extra chromosome affect an individual?
C. What more do we want to know about either of these question?
D. (following presentation) How did this presentation change your ideas about
cancer?
E. (following presentation) How did this presentation change your ideas about
having and extra chromosome?
Appendix B
------------------------------------------------------------------------------------------------------------
Day 1: What’s up with nondisjunction?
Your name: _____________________
Date: ____________________
Partner’s name: __________________
A. Look under the microscope of spread metaphase chromosomes from a human cell.
Describe and draw what you see.
B. Look at print-outs of chromosome spreads and note the differences between them,
including chromosome numbers. Remember human females have 22 pairs of
autosomes plus two X chromosomes (46 total); males have 22 pairs of autosomes
plus one X chromosome and one Y chromosome (46 total). You will be using
Normal A and Patient A or Normal A or Patient B.
1. Circle the sex chromosomes in the Normal karyotype (e.g. X and Y)
2. Is the Normal karyotype you have from a male or a female? How can you tell?
3. How are chromosomes within one karyotype different from one another?
4. Compare the two karyotypes, how do they differ? How are they alike?
Normal A
Patient A
Normal B
Normal B
Patient B
Appendix C
-----------------------------------------------------------------------------------------------------------Day 4: What’s up with nondisjunction?
Your name: _____________________
Date: ____________________
Partners’ names: __________________
_______________________
A. You will be given a karyotype from an individual who has a chromosome number that
differs from the normal 46 chromosomes. Examine the print and describe your
interpretation of the abnormality using one or more of the following terms:
Chromosome 1, Chromosome 2, …. Etc.
Y chromosome, X chromosome
Monosomy (monosomic); Trisomy (trisomic)
Translocation, Deletion, Duplication
Put your answer here: _______________________Have the teacher or geneticist make
sure you have identified it correctly.
B. Use the internet to gather information about the human disorder associated with your
assigned karyotype. A starting place is listed below.
National Library of Medicine :http://www.nlm.nih.gov/nlmhome.html.
C. Address each of the following topics in your research to write your final letter:
1. How is a karyotype performed?
2. Findings from your analysis: give the name of the syndrome or disorder associated
with your assigned karyotype.
3. Describe a genetic cause of aneupoidy.
4. What symptoms are associated with this syndrome?
5. Is there a treatment or cure?
6. If a mother gives birth to a child with this disorder what are the chances that her
subsequent children will also have it? 100%? 50%? Less than 5%?
7. What is the life expectancy for this individual?
8. Can this individual expect to live independently?
9. Is there anything parents should know about schooling or discrimination associated
with this syndrome?
10. Are there support groups for parents of children with this disorder/disease? What is
the name of the group? How does a parent contact the group?
**Be sure to keep track of your sources of information (e.g. URL’s, books, articles etc.)
since you will need to cite them at the end of the letter as a reference for the parents.
** Put the letter in a letter format.
** Sign the letter with your name and fictitious title.
** Include a date and fictitious names for the parent.
** The letter must be single spaced and typed.
Due Date for the letter is ______________________________!
Appendix C
------------------------------------------------------------------------------------------------------------
What’s up with nondisjunction?
These are the karyotypes we used for the students to identify and research.
The students in the group presentations used this rubric.
Student Name_____________________________________
Assess each student by checking a yes or a no for each of the following ten
items. If they talk about the item you will check yes. If they do not talk about
the item you will ask the question of the student and if they can answer you
are to check yes. If they do not answer then you are to check no. Please total
the number at the bottom of each column.
Items to discuss
Yes
1. How is a karyotype performed?
2. Findings from your analysis: give the name
of the syndrome or disorder associated with
your assigned karyotype
3. Describe a genetic cause of aneuploidy.
4. What symptoms are associated with this
syndrome?
5. Is there a treatment or cure?
6. If a mother gives birth to a child with this
disorder what are the chances that her
subsequent children will also have it? 100%?
50%? Less than 5%?
7. What is the life expectancy for this
individual?
8. Can this individual expect to live
independently?
9. Is there anything parents should know about
schooling or discrimination associated with this
syndrome?
10. Are there support groups for parents of
children with this disorder/disease? What is the
name of the group? How does a parent contact
the group?
Totals:
Your Name_________________________________________________________
Comments:
No
This is the rubric used by the teacher to evaluate the letters.
Student Name:
Date:
Karyotype Assessment Rubric
criteria
science
information
description
correct, informative,
complete
information
points
earned
0
4
8
12
16
20
readability,
"realness"
of
dialogue between
make-believe
expert and set of
parent
The letter seems
real. It is detailed
and professional. It
reflects sensitivity
towards the issues.
0
2
4
6
8
10
presentation
engaging,
neatness,
letter
format,
date,
signature,
mechanics of letter
0
2
4
6
8
10
grammar,
punctuation,
spelling
the
grammar,
punctuation,
and
spelling
do
not
interfer with the
understanding
of
the letter
0
2
4
6
8
10
total
points
teacher
comments:
Genetic mechanisms of cancer
February 13, 2009
Sean M. Burgess
Associate Professor
Molecular and Cellular Biology
University of California, Davis
What causes cancer?
2007 Estimated US Cancer Deaths*
Lung & bronchus
31%
Men
289,550
Women
270,100
•26% Lung & bronchus
Prostate
9%
Colon & rectum
9%
Pancreas
6%
Leukemia
4%
Liver & intrahepatic
bile duct
4%
Esophagus
4%
Urinary bladder
3%
• 3% Non-Hodgkin
lymphoma
Non-Hodgkin
lymphoma
3%
• 3% Uterine corpus
Kidney
3%
All other sites
•15% Breast
•10% Colon & rectum
• 6% Pancreas
• 6% Ovary
• 4% Leukemia
24%
• 2% Brain/ONS
• 2% Liver & intrahepatic
bile duct
•23%
ONS=Other nervous system.
Source: American Cancer Society, 2007.
All other sites
Cancer originates at a defined location in the body
Cancer name reflect type of cell that is affected
A cancer cell divides out of control
One cell of a tissue becomes a cancer cell and divides
How does cancer spread?
Not all tumors are cancerous
What makes a cell divide out of control?
Mutations change the way cells divide
http://www.cancer.gov/cancertopics/what-is-cancer
Genome catastrophe is a hallmark of cancer
Cancer cell karyotype
Normal karyotype
A near-triploid cell line from lung, metastatic site, lymph node carcinoma.
http://www.path.cam.ac.uk/~pawefish/LungCellLineDescriptions/NCI-H1770.html
Spontaneous cancers are caused by
mutations in growth-control genes
Some mutations inactivate protective genes
Genetic predisposition for breast cancer
Out of every 100 women who
inherit a mutated BRCA1 or
BRCA2 gene, as many as 60
will develop breast cancer by
age 50; by age 70,
approximately 80 will develop
breast cancer.
http://learn.genetics.utah.edu/content/disorders/whataregd/brca/index.html
Hereditary predisposition to cancer
Inherited conditions come from mutations in
tumor suppressor genes
What causes cancer?
Viruses associated with human cancer
Young women should be vaccinated against HPV to prevent cervical cancer
Chemicals that cause cancer
If you smoke you have >90% lifetime risk of
lung cancer
20-year lag time between smoking and lung cancer
Lifetime Probability of Developing Cancer
Men
Women
All sites†
1 in 2
All sites†
1 in 3
Prostate
1 in 6
Breast
1 in 8
Lung and bronchus
1 in 12
Lung & bronchus
1 in 16
Colon and rectum
1 in 17
Colon & rectum
1 in 19
Urinary bladder‡
1 in 28
Uterine corpus
1 in 40
Non-Hodgkin lymphoma
1 in 47
Non-Hodgkin lymphoma
1 in 55
Melanoma
1 in 49
Ovary
1 in 69
Kidney
1 in 61
Melanoma
1 in 73
Leukemia
1 in 67
Pancreas
1 in 79
Oral Cavity
1 in 72
Urinary bladder‡
1 in 87
Stomach
1 in 89
Uterine cervix
1 in 138
Source: DevCan: Probability of Developing or Dying of Cancer Software, Version 6.1.1 Statistical Research and
Applications Branch, NCI, 2006. http://srab.cancer.gov/devcan
What’s up with nondisjunction?
February 17, 2009
Sean M. Burgess
Associate Professor
Molecular and Cellular Biology
University of California, Davis
Mitosis/Meiosis
Dynamic changes in chromosome
structure accompany meiosis
4C
Homolog Pairing
& Recombination
2N
MII
4 X 1N
MI
2 X 2C
Nondisjunction can occur at meiosis I or
meiosis II
1n +1 gamete will form a trisomic
zygote upon fertilization
Normal meiosis
2n --> meiosis --> 1n gametes
1n + 1n --> 2n zygote
Nondisjunction forms 1n+1 gamete
2n --> meiosis with nondisjunction --> 1n +1 gamete
(1n +1) + 1n --> 2n +1 zygote (trisomy)
Effects of nondisjunction on
human health
•Trisomy is the major cause of birth defects and
mental retardation
•Up to 30% of all pregnancies are aborted
spontaneously (miscarriage) due to abnormal
numbers of chromosomes (aneuploidy)
Increased risk of nondisjunction resulting in
trisomy 21 with advanced maternal age
Young women who smoke are at risk of
having children with Down syndrome
Younger mothers (<35 years) who smoke and have meiotic II
error are at an increased risk of having children with Down
syndrome.
The combined use of cigarettes and oral contraceptives
increased the risk even further.
Not all chromosomal-based birth defects
are due to nondisjunction
•Deletion: A small section is missing.
•Translocation: A section of a chromosome is attached to another
chromosome.
•Inversion: A section of chromosome is snipped out and reinserted
upside down.
•Duplication: A section of a chromosome is duplicated, so there is
extra genetic material.
Radiation can induce chromosome
breaks
Repair of breaks can lead to
chromosome rearrangements or
deletions before or during
meiosis
Can occur in both females and
males
Karyotype preparation and analysis
If any birth defects are noticed in a newborn baby, a karyotype
is prepared and analyzed to look for chromosome
abnormalities
1. Cells (from blood, amniotic fluid, etc) are grown in vitro (in a cell
culture dish) to increase their number
2. Cell division is then arrested in metaphase with colchicine (prevents
mitotic spindle fibers from forming)
3. Cells are centrifuged and lysed to release chromosomes
4. Chromosomes are stained, photographed, and grouped by size and
banding patterns
Images of chromosomes in spreads
are organized into a karyotype
A geneticist then looks for extra
chromosomes, deletions or insertions
Cri du chat chromosome 5 deletion
•Most cases (80-85%) are due to sporadic de novo
deletion of 5p (15.3->15.2).
•The deleted chromosome 5 is paternal in origin in
about 80% of cases.
Cri du chat symptoms
Babies with cri-du-chat are usually small at birth, and may have
respiratory problems. Often, the larynx doesn't develop correctly,
which causes the signature cat-like cry.
People who have cri-du-chat have very distinctive features. They may
have a small head (microcephaly), an unusually round face, a small
chin, widely set eyes, folds of skin over their eyes, and a small
bridge of the nose.
Several problems occur inside the body, as well. A small number of
children have heart defects, muscular or skeletal problems, hearing
or sight problems, or poor muscle tone.
Is there a cure?
Although there is no real treatment for cri-du-chat
syndrome, children with the disorder can go through
therapy to improve their language skills, motor skills, and
to help them develop as normally as possible.
Life expectancy?
As they grow, people with cri-du-chat usually have difficulty walking
and talking correctly. They may have behavior problems (such as
hyperactivity or aggression), and severe mental retardation.
Most people with this disorder do not survive to adulthood.
Cri du chat syndrome is very rare
Cri du chat affects about 1 in 20,000 babies
Although very rare, Cri-du-chat is one of the most common syndromes
caused by a chromosomal deletion.
The mutation arises during meiosis. Other cells (somatic) in the mother or
father are not affected.
The probability of having a second child with Cri du chat is still 1 in
20,000.
People with Cri du chat can reproduce and have a 50% chance of having
a child with the sydrome.
Family support groups
Families use community or online
support groups to better understand the
disorder
http://www.fivepminus.org/
Other resources:
•
http://ghr.nlm.nih.gov/condition=criduchatsyndrome
•
•
http://en.wikipedia.org/wiki/Cri_du_chat
http://learn.genetics.utah.edu/content/disorders/whataregd/cdc/index.
html