Genetics Question: How can two parents with a recessive disease have children that do not have the disease?

Question

Ok- so this is the question that our Genetics prof has posed to us: How is it possible that two parents with a recessive disease that they both have (I.E: they have the recessive disease), have a child that does not have the disease? According to pundit squares and the such like- this should not be possible- but does anyone have any explanations as to how this could occur?

Answer 1

Lets say the variable is t

If both parents have Tt then 1/4 of their offspring have a chance of TT which would be total dominance, not showing the disease

This is assuming that only one recessive t is needed for the disease (if 2 recessive t's are needed then it's not possible).

Answer 2

So the key to this question is understanding what an allele is, and how many alleles can have similar effects, yet be different.

Proteins are composed of several domains. Suppose that the father in this instance is homozygous for a mutation that affects a domain that is involved recieving a signal, but all downstream activity is fine. Functionally, the protein is not able to work, thus he has the disease.

Suppose the mother, on the other hand, is homozygous for a different mutation in the same protein. Her mutation is not in signal reception, but in downstream transduction of this signal. Functionally, she is the same as the father, but for different reasons.

Their offspring however, will have 1/2 of this particular protein that cannot respond, but can transduce, and 1/2 that can transduce, but not respond. Thus, they would not be affected, as they would have some level of activity.

In this type of scenario, a more useful punnet square is one such as with blood type, where you account for different allelic variants. Simply looking at genes as "dominant" or "recessive" is of little use unless you consider the context of what they are dominant or recessive to.

Answer 3

Let me elaborate a little on what Long said by giving you an example. The gene that causes cystic fibrosis (CF) is called CFTR, and CF is inherited recessively. Basically there are several types of mutations of this gene that cause CF, the most significant being a deletion of a phenylalanine residue at codon #508 (the mutation is called deltaF508). This mutation alone is not going to cause CF, because the protein from the other chromosome is enough to prevent CF. If both alleles have a deltaF508 mutation, then you will have full blown CF.

Now, a parent with CF, might have deltaF508 on one chromosome, and have a DIFFERENT CF mutation called R117H on the other chromosome. If both parents have this combination deltaF508 and R117H, guess what, they both have CF, but theres a 1/4 chance their child will inherit the alleles from the parents with R117H and NOT GET deltaF508 at all. Someone who has 2 CFTR alleles, both with R117H will NOT HAVE CF!!! Even though both their parents had CF, the child will not!!!

Not all diseases are inherited like CF, CF is VERY complex in its inheritance. Many mutations in CFTR can cause CF, and thus there are many combinations (and degrees of phenotype) associated with the condition. This is definitely the exception not the rule. In most cases of Mendelian inheritance, 2 affected parents with recessive diseases will pass the condition on to ALL offspring, but this is an exception, and there are others.

Answer 4

It might be possible if the disease can be passed down by one of two alleles. For example, either gene t or gene g can cause the disease. If one parent with the disease is tt GG (or even tt Gg), and the other parent is TT gg, then the possible gametes would be
Parent 1: tG
Parent 2: Tg
Then the offspring would be Tt Gg and would not have the disease. The human genome is very complex, and multiple different mutation in multiple genes can cause specific diseases.

Answer 5

It's possible that the same disease is caused by mutations in two different genes. Both parents have the disease but each of them is homozygous mutant for a different gene. The children will then have a good copy of each gene and be normal.

If the disease is caused by mutations in only gene, then you may have something called intragenic complementation. This occurs when two mutant proteins (mutant in two different locations of the protein) are able to complex together to form a functional protein. An example of this is alpha-complementation of Beta-galactosidase in E.coli.

Answer 6

Cannot be decided due to not having information about their grandparents and their future children gender. Colorblindness is dominant on males so if it can be a son there would be better probabilities but not adequate to reach the 25%. Additionally the style of colorblindness wasn't indicated.... Too much missing information

Answer 7

it's probably a complex gene action and not simple recessiveness. it's probably an epistatic situation where a second gene is also controlling the expression of the condition....,or you can always fall back on the mutation

Answer 8

consider other concepts in genetics such as incomplete dominance or codominance.

Answer 9

Perhaps the disease is lying dormant for now.

Answer 10

uh, the word is "punnet" square, and it is simply because the gene is recessive and the human genome is a really, really complex thing....