Gapless Explanation: The Blue People of Troublesome Creek

The presence or absence of enzymes has shown to be heritable. We know that the

production of the enzyme lactase is genetic and that its absence causes lactose intolerance. This

was shown in CGS 4 when mice that both had lactose intolerance were crossed and all of their

offspring had lactose intolerance. This tells us that it must have come from parents. In addition,

there were some cases where neither parent had lactose intolerance and none of the offspring

ever had it, which also shows that it is inherited.

It was also observed that parents that do not have lactose intolerance when

cross-produced offspring with lactose intolerance. Since the parents did not have lactose

intolerance but the offspring did, it means that both parents must carry the allele for lactose

intolerance. Since both parents have the allele for lactose intolerance, but do not have lactose

intolerance, it means that lactose intolerance is recessive since recessive traits are not expressed

when combined with dominant traits. The Fugates exhibit the same pattern, which suggests that

the lack of the reductase enzyme in the Fugates is caused by a recessive allele that is responsible

for coding for the production of, or in this case the lack of production of, the reductase enzyme.

In the analysis of DNA, we observed that there are two alleles or two different versions

of the gene that are responsible for reductase production or the lack thereof. One of the alleles,

or version of the gene, has a different nucleotide sequence than the other, but only in one base

pair. This allele is the recessive allele that when paired with another recessive allele to make a

homozygous recessive genotype, will code for ineffective reductase activity. The other allele

which does not have the nucleotide change is the dominant allele that codes for normal reductase

activity.
 When reductase activity is normal, the reductase enzyme donates an electron to the iron

in hemoglobin when the iron is in the +3 state. This reduces the iron to a +2 state. Since the

positive charge of the iron in hemoglobin is now lower, the iron atom is not pulling as hard on its

own electrons. This allows neutral oxygen to pull an electron from the iron in the +2 state,

which causes oxygen to become negative and bind to the positive iron. Since the Fugate’s

reductase activity is greatly reduced, they are less able to reduce iron to the +2 state, which limits

the amount of oxygen their blood can bind, therefore their blood carries less oxygen, which is

what contributes to their blue appearance since deoxygenated blood has a more blue and less red

appearance.

This phenotype is observed more often in the Fugates due to their geographical location.

The only way for a recessive trait to be expressed is if both parents have the recessive allele.

Since this recessive allele is rare, very few people in the general population have the recessive

allele. So if someone with the recessive allele were paired with someone that did not have the

recessive allele but only the dominant allele that codes for normal reductase activity, it would be

impossible for their offspring to express the phenotype that causes them to be blue. However,

some (statistically 1/2) of the offspring may carry the recessive allele. Assuming that they had

four offspring that were statistically accurate, 2 out of 4 offspring would have the recessive

allele. If each offspring were paired with a person that did not carry the recessive allele and each

of them had four offspring that matched the statistics, then there would be 16 total offspring. Two

groups that had parents that were homozygous dominant would have a total of 8 offspring none

of which carried the recessive allele. The remainder of the offspring that came from one parent

having the recessive allele would be 4 with the recessive allele and 4 without. So the grand total

for all offspring would be 12 without the recessive allele and 4 with.
 In the next generation, assuming that each of the 16 offspring had 4 of their own

offspring, the total number of offspring would be 64. The 12 parents without the recessive allele

pair with people without the recessive allele, producing 48 offspring without the recessive allele.

The four offspring with the recessive allele pair with people without the recessive allele and

produce 12 without the recessive allele and 4 with the recessive allele. So you can see that in the

next generation, 60 of the 64 do not have the recessive allele and 4 do, which is a significantly

smaller percentage of the total population than in the generation before.

However, the Fugates lived in a very remote part of Kentucky where they did not interact

with people outside of their extended family. As a result, they paired with people that had

similar genetics, which increased the likelihood that both parents carried the recessive allele,

which increased the likelihood of their offspring having the low reductase phenotype. Even if

their children were not affected by methemoglobinemia, there is a 75% probability that their

children will carry the recessive allele. If in the future those children were to pair with someone

that also carries the recessive allele, then there is a 1 in 4 chance that their offspring will have

methemoglobinemia. And so by pairing with people of similar genetics, the recessive allele

continues to remain in the population instead of being extinguished from the gene pool.