Teacher Guide_Those Old Kentucky Blues (methemoglobinemia)_

“Those Old Kentucky Blues: An Interrupted Case Study”
Celeste A. Leander, Departments of Botany and Zoology, University of British Columbia
Robert J. Huskey, Department of Biology, University of Virginia
The purpose of this case, based on an extended family from the Appalchian Mountains which had a high
occurrence of the rare disorder methemoglobinemia, is to provide students with an example of a Mendelian
inheritance pattern that can be viewed as either dominant/recessive or as incompletely dominant, depending
on perspective.
The case has been used in first year biology in both traditional and honors sections. Typically, first-year
science majors have misconceptions about inheritance. The case presents students with a seemingly clearcut example of a dominant/recessive inheritance pattern. However, when examined from the phenotype
of enzyme function, it becomes obvious that this is not clear cut and in fact looks to be an example of
incomplete dominance. Both are correct. It simply depends on the perspective from which the phenotype
is being analyzed. In the first case, the phenotype is skin color. In the second case, the phenotype is enzyme
activity level.
After completing this case, students will understand:
• Hypothesis generation.
• Pedigree construction and analysis.
• Evaluation of inheritance patterns.
• Reconciliation of changing inheritance patterns, depending on perspective.
This case is designed for small groups of four to six students. Each group is responsible for generating
answers to all of the questions. I pass out the first part of the case and allow the students five minutes to read
it and answer the first set of questions. I then open up the floor for five minutes for group discussion. I keep
tally on the board. Student hypotheses based on Ruth’s observations typically fall under two broad headings:
environmental causes (including contaminated food or water) or genetic causes. It is helpful to mention
that methemoglobinemia can be congenital or acquired by exposure to various chemicals (such as some
antibiotics and anesthetics), so both categories of hypotheses are reasonable. Armed with this information, I
then ask the students to report on a way to test these hypotheses. Some will want to do invasive blood tests,
test the water in the area, etc. I then reveal what Ruth did by introducing Part II of the case.
I mention to the students that Ruth knew that if blueness is a heritable trait, it would pass through a lineage
in a predictable pattern. I pass out the second part of the case and allow the students  minutes to read it
and generate a pedigree. Each group draws their pedigree on the board. Once the pedigree is drawn, students
are asked to add genotypes for all individuals. Any conflicts should be pointed out and discussed among the
groups. I walk around and pose questions to the students at this stage. If students are on the right track, I
C T N for “Those Old Kentucky Blues” by Leander & Huskey
Page 
may ask, “How come Elizabeth is heterozygous?” Sometimes groups will fixate on an inheritance pattern that
doesn’t work. An example is sex-linked inheritance. In this case, I may ask, “How come Luna is blue?” Many
students will assign John’s genotype as homozygous dominant (“BB”) because none of his  children were
blue. Other students will argue that we can’t know that for sure. This is a good chance to point out that each
child is an independent statistical event, so we cannot in fact know that John is homozygous dominant. This
discussion and group work typically lasts  to minutes.
Once everyone is satisfied with the pedigree, students are sent back to their seats comfortable with the
decision of a dominant/recessive inheritance pattern for “blueness.” I then pass out the NADH diaphorase
activity graph. After a few minutes, I ask the students to articulate what this graph says. They will typically
agree that the parents (heterozygotes) are somewhere in between the two homozygous phenotypes. This
is an example of incomplete dominance. The difference is that we are no longer analyzing “blueness” as a
phenotype; our perspective has changed. We are now analyzing enzyme activity as our phenotype. I give
them  minutes to answer the questions from Part II in their groups. Students are usually uncomfortable
with the idea that an inheritance pattern is not set in stone but can change depending on the phenotype
analyzed. I leave the last five minutes of class open for questions and clarification.
To wrap up the discussion, I mention that a specific, yet unrelated, mutation in a hemoglobin protein can
also cause congenital blue coloration of the skin. This mutant form of hemoglobin does not allow NADH
diaphorase to interact properly with the iron atom. In this case, the mutation is inherited as a dominant
phenotype with regards to skin color. A heterozygous person appears blue because hemoglobin is a structural
protein; when half of the hemoglobin is non-functional, it becomes evident phenotypically. Enzymes,
however, are effective in very small concentrations. Thus, the mutation in NADH diaphorase, as presented
in this case, is recessive when evaluating a heterozygote because having just half of a regular dose of the
enzyme is enough to get the job done.
Detailed case analysis is provided in a separate file that is password-protected. To access this information,
go to the detailed case analysis. You will be prompted for a username and password. If you have not yet
registered with us, you can see whether you are eligible for an account by reviewing our password policy and
then apply online or write to [email protected]
Contested Geneology
It should be noted that the family history part of the Science  article (Trost, ) on the blue people of
Troublesome Creek does not match well with the evidence compiled by professional genealogists. There was
a Martin Fugate who married Elizabeth Smith (October , ), but there is no evidence that any of their
children were “blue.” At least one record indicates that they had  children, not seven. One of their children
is listed in one source as Zachariah Fugate, but he married Margaret Triplett, not a “Smith” sister of Elizabeth.
One of the children of Martin and Elizabeth was the Levi Fugate (born about  and died about )
who married a “Ritchie,” namely Mahala “Cricket” Ritchie (born June , , and died July , ).
This couple had seven children including Luna Fugate (born June  and died in ).
There was another Martin Fugate whose wife was named Mary, but her maiden name is not known. This
Martin Fugate, a son of Benjamin Fugate and Hannah Devers, was born about  in Russell County,
Virginia, and died about  in Breathitt County, Kentucky. Martin and Mary Fugate had seven children
including Zachariah “Ball Creek Zach” Fugate and Martin “Big Man” Fugate.
C T N for “Those Old Kentucky Blues” by Leander & Huskey
Page 
Zachariah “Ball Creek Zach” Fugate married Mary “Polly” Smith who was a sister to the Elizabeth Smith
who married the first Martin Fugate mentioned. “Ball Creek Zach” and “Polly” had  children including
two who were known to be “blue”—John “John Blue” Fugate and Lorenzo Dow “Blue Anze” Fugate.
It would seem that in the reconstruction of the family line through family stories, hazy memories, and
guesses there was some confusion about which Zachariah belonged to which Martin. We may never be
able to construct a totally accurate pedigree of this interesting family, but it is important to clear up what
confusion we can.
Fugate, Mary. The Fugate Family Newsletter Nov. . Vol. XVII, pg. . (ISSN: -)
Trost, Cathy. The Blue People of Troublesome Creek. Science . November .
http://www.brown.edu/Students/MAT//zowers/downloads/Standard_Artifact.pdf and
Last accessed: January , .
Umbreit, Jay. Methemoglobin—It’s Not Just Blue: A Concise Review. American Journal of Hematology
():–. .
Acknowledgements: This case study was published with support from the National Science Foundation under  Award
. Any opinions, findings and conclusions or recommendations expressed in this material are those of the author(s) and
do not necessarily reflect the views of the National Science Foundation.
Copyright ©  by the National Center for Case Study Teaching in Science. Originally published March ,  at
http://www.sciencecases.org/blue_people/blue_people_notes.asp. Please see our usage guidelines, which outline our policy
concerning permissible reproduction of this work.
C T N for “Those Old Kentucky Blues” by Leander & Huskey
Page 