Sickle Cell Activity: Understanding alleles that are incompletely dominant, looking at the pedigree level and using meiosis.
GenScope File: SickleCell.gs
Both Jack and Jill are carriers of the trait: B+ sc. Under Crossover Options, only alignment is checked. In the Big Meiosis window, alignment is on automatic and crossover is turned off.
Open up the Sickle Cell file. Notice
that both Jack and Jill have the sickle cell trait -in other words, they
have one sickle cell allele and one allele for normal hemoglobin beta.
1. You are going to use the cross tool to give Jack & Jill a family. The file is set so that they will have exactly four kids, but since they get their chromosomes randomly from their parents they won't all be the same. Count how many of the kids have normal hemoglobin beta, how many have sickle cell trait, and how many have sickle cell disease. Then enter your data below.
Sickle Cell trait: ________________
Sickle Cell disease: ______________
The file opens up with pedigree window showing. Jack and Jill are seen to have Sickle Cell trait. (The circle and square which represent the two are both half black and half plain.) When crossed, using the X tool, four offspring are produced. The student counts up the numbers of each type of offspring and records the data on the worksheet.
When the pedigree window appears, the student will see that the 2 individuals in the window have the trait because of the half black/half plain nature of the representation. After crossing the pair, depending on the offspring produced, they will see that there are three different representations possible for Sickle Cell - normal, carriers (having the trait) and diseased. At this point, the student should see the similarity of Sickle Cell inheritance to the inheritance of legs in dragons. If they are really lucky, the offspring will appear in the appropriate ratio and their counts will be 1 normal, 2 sickle cell trait and 1 sickle cell disease.
The student has to keep in mind, with this exercise, that the Sickle Cell alleles are incompletely dominant to each other. Consequently, both of the alleles must be "Normal HB" for the baby to be normal.
3. You've probably noticed that all of Jack and Jill's kids who have normal hemoglobin are blue! This is caused by a disease called "methemoglobin." Methemoglobin is recessive, just as sickle cell is-you get it if you have two recessive (m) alleles. Can you figure out why all the kids who are normal for sickle cell have methemoglobin?
The student will use the chromosome tool to look at chromosome 11. S/he should observe that the Methemoglobin gene is on chromosome11 along with the Sickle Cell gene. However, when the normal "B+" allele appears the methemoglobin allele on the same chromosome is "m". Since the allele which causes the blue color is recessive, then each time an organism appears normal for sickle cell s/he carries two recessive genes for methemoglobin (mm) and appears blue.
Some mental gymnastics is required to
figure this puzzle out. The student has to remember that sickle cell is
an example of incomplete dominance, so the normal individual will have
two alleles for normal HB. S/he must also remember, or figure out, that
methemoglobin is recessive so that two "m's" are needed to cause the condition.
If s/he doesn't remember that sickle cell is an example of incomplete dominance,
then s/he is liable to choose gametes with sc and normal B+ alleles, thinking
that the normal B+ allele will be dominant to the sc. Imagine his surprise
when the new person comes up with sickle cell trait!
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