The Making of the Fittest: LESSON

Natural Selection in Humans STUDENT HANDOUT

MENDELIAN GENETICS, PROBABILITY STATISTICS

INTRODUCTION
Hemoglobin is a protein found in red blood cells (RBCs) that transports oxygen throughout the body. The hemoglobin
protein consists of four polypeptide chains: two alpha chains and two beta chains. Sickle cell disease (also called sickle
cell anemia) is caused by a genetic mutation in the DNA sequence that codes for the beta chain of the hemoglobin
protein. The mutation causes an amino acid substitution, replacing glutamic acid with valine. Due to this change in
amino acid sequence, the hemoglobin tends to precipitate (or clump together) within the RBC after releasing its oxygen.
This clumping causes the RBC to assume an abnormal “sickled” shape.
Individuals who are homozygous for the normal hemoglobin allele (HBA) receive a normal hemoglobin allele from each
parent and are designated AA. People who are homozygous for normal hemoglobin do not have any sickled RBCs.
Individuals who receive one normal hemoglobin allele from one parent and one mutant hemoglobin, or sickle cell allele
(HBS), from the other parent are heterozygous and are said to have sickle cell trait. Their genotype is AS. Heterozygous
individuals produce both normal and mutant hemoglobin proteins. These individuals do not have sickle cell disease, and
most of their RBCs are normal. However, due to having one copy of the sickle cell allele, these individuals do manifest
some sickling of their RBCs in low-oxygen environments. People with sickle cell disease are homozygous for the sickle cell
allele (SS genotype); they have received one copy of the mutant hemoglobin allele from each parent. The resulting
abnormal, sickle-shaped RBCs in these people block blood flow in blood vessels, causing pain, serious infections, and
organ damage.

MATERIALS
critical values table (see page 12)

PROCEDURE
1. Watch the short film The Making of the Fittest: Natural Selection in Humans. While watching, pay close attention to the
genetics of sickle cell trait and the connection to malaria infection.
2. Answer the following questions regarding genetics, probability, pedigrees, and the chi-square statistical analysis test.

Mendelian Genetics, Probability, Pedigrees, and Chi-Square Statistics Published July 2012
Revised October 2013
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 The Making of the Fittest: LESSON
Natural Selection in Humans STUDENT HANDOUT

QUESTIONS
MENDELIAN GENETICS AND PROBABILITY
1. If two people with sickle cell trait have children, what is the chance that a child will have normal RBCs in both high-
and low-oxygen environments? What is the chance that a child will have sickle cell disease? Write the possible
genotypes in the Punnett square.

Normal RBCs in high- and

low-oxygen environments ____________

Sickle cell disease ____________

a. What is the chance that a child will carry the HbS gene but not have sickle cell disease? ___________________
b. What are the chances that these parents will have three children who are homozygous for normal RBCs? (Show
your work.) ___________________________
c. What are the chances that these parents will have three children who have both normal and mutant
hemoglobin beta chains? (Show your work.) ___________________________
d. What are the chances that all three of their children will show the disease phenotype? (Show your work.)
___________________________
e. What are the chances that these parents will have two children with sickle cell trait and one with sickle cell
disease? (Show your work.) ___________________________
f. In the cross above, if you know that the child does not have sickle cell disease, what is the chance that the child has
sickle cell trait? ___________________

2. An individual who has sickle cell trait has children with an individual who does not have the HbS allele.
a. What are the genotypes of the parents? ____________________
b. In the Punnett square, show all the possible genotypes of their children. State the genotype and phenotype
ratios of the offspring.

c. What are the chances that any one of this couple’s children will have sickle cell disease? __________________
d. If this couple lives in the lowlands of East Africa, what are the chances that one of their children would be
resistant to malaria if exposed to the malaria parasite? _________________

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 The Making of the Fittest: LESSON
Natural Selection in Humans STUDENT HANDOUT

3. A woman with sickle cell disease has children with a man who has sickle cell trait. Answer the following questions.
a. What are the genotypes of the parents? ____________________
b. What is the genetic makeup of the gametes the mother can produce? ___________
c. What is the genetic makeup of the gametes the father can produce? ___________
d. In the Punnett square, show all the possible genotypes of their children. Then summarize the genotype and
phenotype ratios of the possible offspring.

e. What are the chances that any one of this couple’s children will have sickle cell disease?
_______________________________________
f. If this couple moves to the lowlands of East Africa and has children, which of their children would be more likely
to survive? Explain your answer.

4. In humans, blood type is a result of multiple alleles: IA, IB, and iO. A few simple rules of blood type genetics are that
• IA is dominant over iO,
• IB is dominant over iO, and
• IAIB are codominant.
Two parents who are heterozygous for type A blood and have sickle cell trait have children. Answer the following
questions.

a. What is the genotype of the parents? ____________________

b. What are the genetic makeups of all the possible gametes they can produce? ____________________
c. Complete the dihybrid Punnett square to determine the frequency of the different phenotypes in the offspring.
(Note: Consider blood type and normal versus mutant hemoglobin in the various phenotypes.)

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 The Making of the Fittest: LESSON
Natural Selection in Humans STUDENT HANDOUT

5. Now try a different way of solving a dihybrid cross. Because of Mendel’s (second) law of independent assortment,
you can work with the blood type gene and the hemoglobin gene separately. Set up two monohybrid crosses with
the following parents: the mother is heterozygous for type B blood and has sickle cell trait, while the father has type
AB blood and also has sickle cell trait.

a. What are the chances that a child of this couple will have type B blood and sickle cell trait? (Show your work.)
_________________________________________
b. What are the chances that a child will have type AB blood and will not have sickle cell disease? (Show your work.)
_________________________________________
c. What are the chances that a child will have type B blood and sickle cell disease? (Show your work.)
_________________________________________
d. What are the chances that a child will have type B blood and at least some normal hemoglobin? (Show
your work.)

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