Genetics problem for fun.

I

Idle Mind

What the hell, man?
Valued Senior Member
Here is a problem that geneticists actually encountered some time ago. This is meant merely as a thought exercise, and isn't to be taken too seriously. My professor gave the impression that it is quite a difficult problem unless you consider elements that aren't directly given in the question. There is quite a bit of background info that goes along with it, but you'll want to read carefully. It is taken directly from my genetics text. Here it is:


In Norway in 1934, a mother with two mentally retarded children consulted the physician Asbjorn Folling. In the course of the interview, Folling learned that the urine of the children had a curious odour. He later tested their urine with ferric chloride and found that, whereas normal urine gives a brownish colour, the children's urine stained green. He deduced that the chemical responsible must be phenylpyruvic acid. Because of the chemical similarity to phenylalanine, it seemed likely that this substance had been formed from phenylalanine in the blood, but there was no assay for phenylalanine. However, a certain bacterium could convert phenylalanine into phenylpyruvic acid; so the level of phenylalanine could be measured by using the ferric chloride test. The children were indeed found to have high levels of phenylalanine in their blood, and the phenylalanine was probably the source of the phenylpyruvic acid. This disease, which came to be known as phenylketonuria (PKU), was shown to ne inherited and caused by a recessive allele.

It became clear that phenylalanine was the culprit and that this chemical accumulated in PKU patients and was converted into high levels of phenylpyruvic acid, which then interfered with the normal development of nervous tissue. This finding led to the formulation of a special diet low in phenylalanine, which could be fed to newborn babies diagnosed with PKU and which allowed normal development to continue without retardation. Indeed, it was found that, after the child's nervous system had developed, the patient could be taken off the special diet. However, tragically, many PKU women who had developed normally with the special diet were found to have babies who were born mentally retarded, and the special diet had no effect on these children.


a.) Why do you think the babies of the PKU mothers were born retarded?

b.) Why did the special diet have no effect on them?

c.) Propose a treatment that might allow PKU mothers to have unaffected children.

Remember, this is only for fun, and to stimulate thought. Try to do it without searching the net too much, because what's the fun in that?

Also, if you have any questions with any of the vocabulary or wording, then don't hesitate to ask. I just assumed everyone has an idea of what everything is.

Cheers.
 
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Well clearly the phenylalanine or forming acid crosses the umbilical cord membrane(planceta membrane),and increase in residual volume of the childs serum, more than likly it is the acid that makes the cross where it can soften the planceta membrane and pass to contaminate the childs blood. A build up of the acid in the child will cause adaption to of the child to produce phenylalanine under conversion of chemical process. in addtion to this ablity of the acid to cross the membrane, the child also inherits the alleles that cause the production conversion reaction.
The diet has little effect as its effect is on the mother and its effect of low counts of causing agent or other protiens, do not cross the membrane to feed the child in the womb.
Finding a cure for such a problem by natural means seems very difficult, as it the mother female does not contribute her bodies or somatic cell infromation to her egg cells, which eliminates the ablity to form a new alleles, also meaning that the orginal alleles was created by a male, if the female carries such a alleles it was given to her by her father. In general this means that and natyral means of getting ride of the alleles will remain a factor of the male contributing his Dna, here the possiblity of replacing the alleles by recombination or the formation of a replacing alleles can take effect eliminating the problem alleles in the somatic cell of the child causing for normal life. evenso such a introduction by the male of new genetic information capable of eliminating the problem in the somatic cells of the child, will not eliminate the alleles in the reproductive cells of the child and therfore there is a high chance of the next generation contacrting the problem alleles. if the child is female then the problem alleles will have a 50% chance of occuring, if a male child there is then the possiblity of eliminating the alleles from the next generating with greater than 50%, this relys only on the fact that the somatic cells of the male child will not carry the alleles as it was eliminated from its somatic cells by the fathers dna replacement of the alleles in the childs somatic cells(remaining still in the germ cells). As the reproductive cells still carry the problems, it will pass the alleles, except where the reproductive cell must chose a different combination base as the somatic cells did not provide the base nessacary to form the problem alleles, here a sperm cell will be created without the problem alleles and the problem will not pass. in such there is no way to give a gurantee that the reproductive cell will not consturct the problem alleles. in other words a % of the sperm produced will carry the problem and a % will not carry the problem. how ever this will be the effect of only one reproductive cell, and means that there is a greater than 50% chance that the problem will be eliminated.
Treating the mother with genetic alteration will not eliminated the problem as the problem exist in the reproductive cell and of which she contributes not somatic cell information. treatment of the female eggs would be a isolated treatment of the eggs and not of her body as the eggs are isolated. the female mother has a 50% chance of donating a egg that does not have the alleles problem, and in such case it would be possible to effect some treatment of the mother to prevent the crossing of the acid that causes the problem of chemical adaption by the child. Here the cause of the creation of the acid is unknown, but it sounds like the locus or the acids creation is in the liver, and so it would be nessacary to treat the liver or locus of the acid creating membrane to eliminated the acids production, rather than a diet meathod. it would also seem that the effect causes retardation in the first weeks and contiunes with a profound effect on the adaption mechanism of the embryo, where the planecta membrane is weakly formed, also where it maybe that the membrane actaully adapts to allow the acid passage. changing the adapation of the planceta membrane to the acid would seem to be the only meathod of prevention directly to the mother besides treating the liver. the only other meathod would be to inaddtion provide rna, dna of the specific gene locus of the allese that is correct in form to the diet of the mother or injected into the blood stream, in the first weeks of pregancy in the hopes that the new replecating cells will use this code to alter that problem locus alleles.
DWAYNE D.L.RABON
 
Dwayne,

Unfortunately what they do in this situation is extract a multiple ova from the mother and fertilize them with the father’s sperm. Test each ova and only implant the ones they do not have a PKA allele. The embryos that do are stored or thrown away. Gene therapy on embryos is still experimental and at present there is no way of removing a defective gene, just ways of over riding it. This means that a defective allele remains in place and can be spread to offspring.
 
Well, as for the cause of the mental retardation in the babies born to PKU mothers, you are on the right track, Dwayne. Maybe you want to clarify a little.

However, you are overthinking the treatment. It is very simple, and if you are thinking correctly about how a PKU mother can be born normal, and grow up normal, but give birth to mentally retarded children, then it should jump out at you.

I will give the others a little while longer before I offer an explanation.
 
I suppose that is a viable option...but still too complicated.

For the sake of the problem, we will say that the allele in question codes for an enzyme that metabolises the phenylpyruvic acid into something harmless. However, people affected with PKU have a mutant allele that doesn't allow the enzyme to be created in the body. I'm not sure if this is exactly what happens, but for the sake of this, it is a possibility. The allele is recessive.

You have to think about where it says the high levels of phenylalanine are found.

Read the question carefully.
 
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put the mother back on the diet before they become pregnat AND while they are beast feeding?
 
Correct.

Solution:

a.) When the PKU mother was born normal, it means that her mother was heterozygous dominant (it doesn't matter whether the father is heterozygous dominant, or homozygous recessive for this particular problem). As she developed, she shared her mother's blood, which contained the enzyme* that could metabolize the phenylpyruvic acid, and therefore had normal development during gestation. She was put on the special diet as a child, so she could develop normally, and once her nervous system was finished developing she was taken off the low phenylalanine diet. When she was impregnated, she shared her blood with her fetus. However, since she herself didn't have the enzyme in her blood, the neural development was hindered during gestation, regardless of whether or not the child expressed the condition.

* This isn't necessarily how it happens, but offers a fairly simple explanation.

b.) Since the damage had already been done during gestation, the diet was of little consequence. It could help prevent further damage if the child were PKU, but it couldn't repair what had already happened.

c.) The treatment: Asguard answered this correctly. Simply have the PKU mother go back on the special diet during pregnancy so that the fetus could properly develop.

I was hoping to have more people involved, but I think I overestimated the amount of traffic here. It's not quite as high as some of the other message boards I frequent. That's okay though, you guys were thinking. That's what counts, after all.
 
i dont get how that was hard

i mean everyone knows that what the mother eats before birth and during breast feeding, the baby eats

thats why pregant women shouldnt drink or smoke
 
My professor specifically stated that the part that was difficult would be the sharing of the blood between the fetus and mother. I guess since we were supposed to be thinking genetics or something.

I, however, didn't say that it was overly difficult. Especially if you have a good grasp on developmental biology. Kudos anyways.
 
I knew what PKU is :p You know what all the warnings on diet pop cans are? well that’s because aspartame (artificial sweetener) decays into phenylalanine, methanol and formaldehyde in the blood stream. Being that the amino acid phenylalanine can not be broken down by people with PKU disorder they have to put a warning on the cans. As for the other stuff I did a research project that showed that Aspartame was infect a mutagen so despite the controversy over if it produces methanol and formaldehyde in the blood it did produce a mutagenic effect in Drosophila and formaldehyde is a mutagen,,,

I thought you said proper diet had failed? Why would the mother not be on a proper diet anyways before, during and after pregnancy? PKU diet has to sustained because phenylalanine in high amounts is toxic.
 
In this particular case, the problem mentions that phenylpyruvic acid disrupts neural development. So, according to what is given, it wasn't necessary to continue the diet after development had been completed. The diet worked for the PKU mother, but unless she was on the diet while she was pregnant, her child would have her blood, high in phenylalanine flowing through its body. This would inhibit neural develpment during gestation.
 
I know a PKU and he is still on that diet, I though they all were forever?
Click to expand...

they are. but, the question is, if they understand/catch it in time while the kid is still a baby....often times this enzyme deficiency is overlooked. only recently have they really started realizing/understanding the implications and checking more carefully(than in the past) for this "syndrome". if the doctors discover the baby has this lack of enzyme, it is best discovered very, very early, therefore, the child will not grow up retarded, because they can offer a diet that will allow the child to develop normally. in otherwords, the mental retardation CAN be avoided by careful examination by good doctors, if detected in time.
 
Also remember that the problem takes place in 1934. I don't think they had a good understanding of PKU, and thus didn't feel it necessary to continue the diet after the brain had fully developed even if the diet should have been maintained. It explains why she gave birth to sons that were underdeveloped anyways.
 
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