Genetically speaking, what causedBen Stacy to Be Blue?
You be the Physician!
Background Research:
After ruling out heart and lung diseases, the doctor suspected methemoglobinemia, a rare hereditary blood disorder that results from excess levels of methemoglobin in the blood. Methemoglobin which is blue, is a nonfunctional form of the red hemoglobin that carries oxygen. It is the color of oxygen-depleted blood seen in the blue veins just below the skin.
If the blue people did have methemoglobinemia, the next step was to find out the cause. It can be brought on by several things: abnormal hemoglobin formation, an enzyme deficiency, and taking too much of certain drugs, including vitamin K, which is essential for blood clotting and is abundant in pork liver and vegetable oil.
Cawein drew "lots of blood" from the Ritchies and hurried back to his lab. He tested first for abnormal hemoglobin, but the results were negative.
Stumped, the doctor turned to the medical literature for a clue. He found references to methemoglobinemia dating to the turn of the century, but it wasn't until he came across E. M. Scott's 1960 report in the Journal of Clinical Investigation (vol. 39, 1960) that the answer began to emerge.
Scott was a Public Health Service doctor at the Arctic Health Research Center in Anchorage who had discovered hereditary methemoglobinemia among Alaskan Eskimos and Indians. It was caused, Scott speculated, by an absence of the enzyme diaphorase from their red blood cells. In normal people hemoglobin is converted to methemoglobin at a very slow rate. If this conversion continued, all the body's hemoglobin would eventually be rendered useless. Normally diaphorase converts methemoglobin back to hemoglobin. Cawein was eventually able to determine that this same disorder, the lack of the diaphorase enzyme, affected the Blue Fugates.
Genetics—The Blue People of Troublesome Creek
The year is 1975. You are a young physician working in a maternity ward near Hazard,Kentucky. One night, you are called to attend a newborn boy, Ben Stacy, who is in goodhealth in all respects except for his dark blue skin. You have lived around Hazard longenough to remember tales about the ‘blue Fugates’ of Troublesome Creek. You wonderif Ben is related to the Fugates, so you interview his relatives and piece together the
following genealogy. In the early 1800’s, one of Ben’s ancestors, Zacharia ‘Ball CreekZack’ Fugate married Mary Smith. Ball Creek Zack and Mary had 12 children, two ofwhom, John ‘John Blue’, and Lorenzo ‘Blue Anze’, were blue. Ball Creek Zack’s sister,Hannah Fugate, married James Ritchie by whom she had a normal son and daughter.Mary’s sister, Elizabeth Smith, married Martin Fugate, a distant cousin of Ball CreekZack. Elizabeth and Martin had many children (7-11); none were blue. One of theirsons, Levi Fugate married Hannah and James’ daughter Mahala Ritchie. Levi andMahala had 8 children, 7 were normal, but their daughter Luna was blue. Luna marriedJohn Stacy and the couple had 13 normal children. One of Luna and John’s sons (name
unknown) fathered Alva Stacey who is not blue. Alva married Hilda Gosney (also
normal) and they had Ben (born blue).
Hypothesis/Claim:(Write a clear and concise claim statement)
Data
- Watch the tutorial on pedigrees:
- Complete a pedigree diagram.Place the number of each listed person next to the appropriate symbol. Persons 1 and 16 have already been identified on the pedigree as an example.
Fugate family pedigree
1. Zacharia ‘Ball Creek Zack’ Fugate
2. Mary Smith
3. Hannah Fugate
4. James Ritchie
5. Elizabeth Smith
6. Martin Fugate
7. John ‘John Blue’ Fugate
8. Lorenzo ‘Blue Anze’ Fugate
9. Levi Fugate
10. Mahala Ritchie
11. Luna Ritchie
12. John Stacy
13. Luna and John’s son
14. Alva Stacey
15. Hilda Gosney
16. Ben Stacey
- Color in the symbol (circle or square) for affected (blue) people.
Data Analysis
After two days of testing, you determined that Ben Stacey’s blue skin color iscaused by methemoglobinemia. This condition results from the persistence of oxidizediron in hemoglobin. There are several genetic disorders that lead to methemoglobinemia.Before Alva and Hilda took Ben back home to a remote area of Hazard county, you triedto help them understand the genetic basis for their son’s blue skin.
Based on the pedigree, do you tell the Stacey’s that their son’s mutation is
1. dominant or recessive? Why?
2. X-linked or autosomal? Why?
- Which of the listed people on the pedigree must be a carrier (heterozygous)?
A few weeks after Ben Stacey returned home, his parents called to tell you thathe had lost his blue skin tone and appeared normal except that his lips and fingernailsturn blue when he is cold or angry. Family stories report that Ben’s blue ancestors wereblue throughout their lives. Over the course of the next few years, you research manycase histories of blue people and you discover that people heterozygous for mutationsthat cause some forms of methomoglobinemia are blue only during their first few weeksof life. People homozygous for the same mutations are blue throughout their lives.
Conclusion: Genetically, speaking, what caused Ben Stacy to blue?
(Using the CER framework, write a conclusion paragraph.)