### Re: What is the probability of grandchildren getting disease the parents don't?

Date: Thu May 16 16:57:43 2002
Posted By: Doug Reed, Faculty, Toxinology & Aerobiology, USAMRIID
Area of science: Genetics
ID: 1021574710.Ge
Message:
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The short answer is that it is almost impossible to calculate the chances.

The grand and simple explanation is that there are multiple genes involved
and multiple possible ways in which expression of different genes can
result in diabetes.

Simple Mendelian genetics of inheritance can help explain, however, why
both of your maternal grandparents have diabetes, their children do not
but you are still at risk.

Let's postulate that there two genes, for either there is an allele that
can cause diabetes. Call the genes A and B and the alleles (g) (good) or
(d)(diabetes) A person has two alleles for each gene so for each they can
be (gg), (dd), or (gd) - but only (dd) results in diabetes. So
one maternal grandparent would be A(dd)B(gg) and the other A(gg) B(dd).
Mendelian genetics would say that their offspring would all be A(gd) B
(gd). Since the (g) allele cancels out the (d) allele, none of your
maternal grandparent's children would have diabetes. However, that (d)
allele is still there!

Now, take a look at your father's side of the family. Yes, none of them
have diabetes. BUT, are they homozygous or heterozygous for A or B?
Remember, that (d) allele can be there but you won't see diabetes unless
both alleles are (d). So if, by chance, your grandparents were
heterozygous for either A or B than your father could be A(gd)B(gg), A(gg)B
(gd) or A(gd)B(gd). Combined with your mother being A(gd)B(gd), there are
a number of ways in which you could end up have two (d) alleles for either
A or B, in which case you could end up with diabetes even though none of

BUT, the reality is that diabetes is controlled by more than 2 genes - in
fact, from what I can determine by searching on PubMed we don't know how
many genes are involved. It could be hundreds. So we can't calculate come
up with a mathematical number to tell you what the chances are you could
be diabetic. We can only tell you that yes, there is some risk. I wish I
could be more definitive and give you a better answer, but I can't.

```

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