KARYOTYPES AND INHERITANCE OF CHROMOSOMES

Sharon Zupo
1992 Woodrow Wilson Biology Institute

Rationale:

Too often when teaching heredity, teachers do not emphasize that whole chromosomes (linkage groups) are inherited from parents. Students often think they inherit separate genes. Mendel's Law of Independent Assortment is only applicable if genes are on separate chromosomes. If genes are linked on the same chromosome, the probability of inheriting both those genes increases. Students are also taught that they have half of each parent's chromosomes, twenty-five percent of each grandparent's chromosomes, etc. This exercise will visually present the mode of inheritance of chromosomes through three generations, demonstrating the percent of chromosome inheritance from a grandparent as being a matter of chance.

Intended Audience:

Objectives:

To visually demonstrate the concept that chromosomes (linkage groups) are inherited, and not individual genes.

To familiarize students with the procedure of locating gene loci.

To understand the concept of homologous chromosomes and crossing-over.

To increase understanding of the use of karyotypes and their analysis.

To demonstrate the following genetic concepts: dominance, recessive-ness, homozygous, heterozygous, genotype, phenotype, complete and domi-nance, polygenic inheritance, sex-linkage, probability, gene loci, karyo-typing, and Mendel's laws of Segregation and Independent Assortment.

To understand the relationship between genes on a chromosome and the resulting phenotypes.

Time Allotment: 2 to 3 class periods. Some activities may be completed at home.

Materials:

scissors Scotch tape/paste/glue colored pencils pens - 2 colors per student 1 coin per student

blank paper for Karyotype sheet - 1 per 2 students Chromosome sheet - 2 per student Human Genome sheet -1 per student Case study sheet - 1 per group

Chromosome Sheet

Teacher Information:

This hands-on activity is highly adaptable. It can be used as an introduction to many genetic concepts, or as a reinforcement to concepts already introduced in class. I recommend terms and concepts such as dominant, recessive, homozygous, heterozygous, genotype, phenotype, complete and incomplete dominance, sex linkage, linkage groups, crossing-over, polygenic inheritance, homologous chromosomes, Punnett squares, karyotypes, and Mendel's Laws of Segregation and Independent Assortment should first be introduced to insure the smooth continuance of this model. This activity is an excellent application and it reinforces all the terminology and concepts listed.

I have included the reference numbers from McKusick's Mendelian Inheritance in Man. These will be helpful if further studies include research of the etiology of each condition.

Answers to the application questions are included on the student worksheet.

INHERITANCE OF CHROMOSOMES

Student Worksheet

1. You should have two copies of the chromosome sheet to represent your genetic makeup. One sheet represents the chromosomes of your mother's egg and the other sheet represents the chromosomes from your father's sperm. You should use one pencil color for your mother and another color for your father. (Remember males have an X chromosome from their mother and a Y chromosome from their father. Females have two X chromosomes, one from each parent.) Place the correctly colored dot under each of the metaphase replicated chromosome pairs.

2. Flip a coin (heads = the dominant trait, tails = the recessive trait) to determine the gene carried on each of your parent's chromosomes. Use the Human Genotype sheet to determine the traits obtained. After each flip of the coin, write the allele(s) at the top of each of your parents' chromosomes. After you have completed both parents, your traits will be represented from a combination of both sheets.

3. Determine the locus of each gene listed on the Human Genome sheet. Indicate its position by coloring in the locus using the correct color previously assigned each parent. Some genes are hypothetical to illustrate a concept, so you may place them anywhere on the chromosome.

4. Find a partner to marry. Be sure this person has used two different colors for the parents. You will have one child with this person, sharing your chromosomes to create the next generation. Each of you will have to toss a coin to determine which of your parental chro-mosomes will be passed down in your gamete (e.g., heads will be the chromosome you obtained from mother and tails will be your father's chromosome). You may only pass on one chromosome Ñ your mother's or your father's. Toss your coin 23 times, making a mark by the one which was determined by the toss. Cut out these chromosomes, keeping the colored dot at the bottom and the genotype at the top. Paste or tape the chromosome pairs together on the karyotype sheet, starting with the first chromosome pair and ending with two X's or the X and Y.

5. Determine the entire genotype of your child using the Human Genome sheet. List these in order starting with the first chromosome set.

6. Determine the entire phenotype of your child, describing all traits starting from the first set of chromosomes.

7. Count the number of chromosomes in your child which were inherited from his maternal grandmother, his maternal grandfather, his paternal grandmother, and his paternal grandfather. Determine the total percentage of chromosomes inherited from each grandparent.

Application Questions:

1. What is the significance of using a coin in this exercise? (It represents a 50% chance.)

2. Give one example to illustrate the difference between genotype and phenotype. What other factor(s) will affect phenotypic expression? (Answers will vary.)

3. Give an example to illustrate the difference in phenotype between complete and incomplete dominance. (Answers will vary.)

4. What is the difference in inheritance when two genes are on different chromosomes vs when they are on the same chromosome? (They will be inherited together if they are on the same chromosome, unless crossing over occurs.)

5. Explain how it might be possible that a person could be genetically unrelated to one of his/her biological grandparents. What assumption is being made here? (Through random chance, none of the grandparent's chromosomes ended in one of the gametes producing the person. The assumption here is that no crossing-over occurs on any of the chro-mosomes.)

6. What is the difference between crossing-over in sister chromatids and crossing-over in homologous chromosomes? (There would be no difference in sister chromatids as they are identical. There would be no new genetic recombination.)

7. If two genes linked on the same chromosome have a 50% cross-over rate, what could you summarize about their inheritance? What would you infer about their positions on the chromosome? (It would be the same as their being on separate chromosomes. They probably have loci which are far apart.)

8. What are your assumptions of the probability of inheritance between the two genes for colorblindness and hemophilia vs the genes for Marfans and Familial Hypercholesterolemia? (The genes for colorblindness and hemophilia would be inherited together more frequently due to being linked on the same chromosome.)

9. Which example illustrates polygenic inheritance? (Answers will vary.)

10. Develop a model using chromosomes 13,14,16, and 18 which could illustrate how a male could grow to a height of five feet ten inches. (Example could be: AaBbCcDd = 5'4", each active gene adds 3", therefore AABbCcDD.)

Karyotypes and Inheritance of Chromosomes

Human Genome

CHROMOSOME	GENE	LOCATION	COMMENT
1 (11700)	Rh blood type Rh+, Rh-	1p36 Rh- (AR)	85% Rh+ phenotype
2 (120180)	Ehler-Danlos E=affected e=not affected	2q31 (AD)	Fragile, hyperflex skin 1/150,000
3 ** (with 6)	Acne (2 Locus model) N=active allele for acne n=inactive	anywhere (MF)	NNNN = severe NNNn = moderate NNnn = mild Nnnn = very mild nnnn = none
4 (143100)	Huntington's disease H=Huntington's h= inactive	4p16 (AD)	mid-life neurologic decline 1/20,000
6 **(with 3)	Acne N'=active n'=inactive
6 (222100)	Diabetes mellitus, insulin dependent D=normal d=afflicted	6p21 (AR)
7 (219700)	Cystic Fibrosis C=normal c=cystic fibrosis	7q31 (AR)	1/20 Caucasian carriers
9	ABO blood group IA, IB, i	9q34 (AD), (CoD)
9 (230400)	Galactosemia G=normal g=galactosemia	9p13 (AR)	missing enzyme
10 **	Short/long index finger S=short S'=long male - dominant S'S'=long SS'=short SS=short female-recessive S'S=long SS'=long SS=short	anywhere (sex-influenced)	short long
11 (141900)	Sickle Cell hemoglobin HbA=normal HbS=sickle	11p15 (AR)	HbAHbS=sickle cell trait HbSHbS=sickle cell anemia
12 (261600)	Phenylketonuria P = normal p = PKU	12p24 (AR)	Newborn screening

Karyotypes and Inheritance of Chromosomes

Human Genome

CHROMOSOME	GENE	LOCATION	COMMENT
13 ** (see 14, 16, 18)	Tallness A = active a = inactive
14 **	Tallness B = active b = inactive
15 (272800)	Tay Sachs T = normal t = Tay Sachs	15q23 (AR)	death usually within 2 years
16 **	Tallness C = active c = inactive
17 (162200)	Marfans M = Marfans m = normal	17q21 (AD)	20,000 affected in USA 15% new mutation
17 (162200)	Neurofibromatosis N = normal n = Neurofibromatosis	17q11 (AR)	Elephant Man
18 **	Tallness D = active d = inactive
18 (137589)	Tourette Syndrome T = Normal t = Tourette	18q22 (AR)
19 (143890)	Familial Hypercholesterolemia F = affected f = normal	19p16 (AD)	300-500 Cholesterol levels
X (303700)	Xcb, XN = Colorblindness / Normal	Xq28 (XLR)	8% Caucasian males
X (306700)	Xh, XN = Hemophilia / Normal	Xq28 (XLR)
X (310200)	Xdmd, XN = Duchene Muscular Dystrophy / Normal	Xp21 (XLR)
Y	Testis determining factor (Tdf)		maleness

** Hypothetical

KARYOTYPES AND INHERITANCE OF CHROMOSOMES

CASE STUDY

Dr. John Q. Frothingham III was a very respected, wealthy man from a socially prominent family. He was the head of a major genetics research laboratory in the East. He felt an intense duty to continue his family name and genetic background. At the age of 55, he died in a plane crash. He had stipulated that his estate would go to any males who would carry on his family name and gene pool. His daughter Alice is married with a son and a daughter. His son Gerald is 34 and still single. Dr. Frothingham's second wife Christine is 12 weeks pregnant and her amniocentesis procedure confirmed that her child is male.

Should Alice's son receive the entire estate? Should Reginald receive his share of the estate? Should Alice or her daughter receive any of the estate?

Does Dr. Frothingham have a son with his second wife? Does the fetus have a right to a part of the estate?

If you were a close personal friend of Dr. Frothingham, a colleague at work, and named executor of his will, what would you suggest to follow Dr. Frothingham's intentions as he had meant for them to be carried out?

Karyotyping and Inheritance of Chromosomes

Background:

The haploid human genome contains 23 chromosomes, containing a total of about 50,000 to 100,000 genes. Each chromosome has a few hundred to several thousand genes, depending upon its length and the size of the genes. Chromosomes are arranged on a karyotype form by size, position of centro-mere, and banding patterns.

The largest chromosomes are placed first and sequentially become smaller, except for the X and Y chromosomes. Chromosomes which are metacentric have the centromere (which binds the two replicated chromosomes together) in the middle, submetacentric chromosomes have the centromere off-center, and acrocentric chromosomes have the centromere close to one end. The shorter arms of the chromosomes are called the p- petite arms and are positioned on the top in a karyotype. The longer arms are the q arms. The locus (location on a chromosome) for each gene is represented by the chro-mosome number, which arm it occurs on, the section number, and the gene position. In the illustration, the cystic fibrosis gene is indicated as 7q31. This reading indicates its position is on the seventh chromosome, the q or longer arm, section 3, gene position 1.

Acknowledgements:

Special thanks for original ideas to:

Gordon Mendenhall Lawrence Central High School Indianapolis, Indiana

References:

McKusick, V.A. Mendelian Inheritance in Man . (9th ed.). Baltimore: The Johns Hopkins University Press, 1990.

O'Brien, S.J. (Ed.). Genetic Maps Locus Maps of Complex Genomes (5th ed.). Book 5 Human Maps. Cold Spring Harbor, NY: Cold Spring Harbor Press, 1990.

Offner, S. "A Plain English Map of the Human Chromosomes." The American Biology Teacher Feb (1992) 87-91.

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