Tags: basics; inheritance

Diseases are classified as dominant when only one allele has to be mutated to see disease – in this case, the mutant allele is dominant over the normal one.

Often, dominant mutations are ‘gain of function’ – that is, the gene product is produced at the wrong place or time. Because 50% gene product (one allele) is enough to perform functions, cells can learn a ‘new trick’ from the mutant allele’s product(s) and often mess up normal processes.

Having extra fingers or toes is an example of this. Polydactyly can appear in families as a dominant inherited trait but in most cases, it’s just an anomaly and isn’t linked to genetic disease.

Families with dominant inheritance for a disease show the disease in every generation and there are often several affected family members in each one. Unless the disease involves a sex-limited structure like the uterus or penis, males and females are affected equally. Every affected child has had an affected parent.

Calculating Possibilities
When you do calculations with dominant disorders, the mutant allele is written in CAPITAL LETTERS to distinguish it from ‘normal’ (opposite to the recessive calculations). To keep things really straight, use the letter d when dealing with dominant disorders.

If dad is affected, what is the chance that his child will be affected?

Note: We assume that affected individuals with a dominant condition are heterozygous = one mutant and one normal allele. There is a small theoretical possibility that someone could be homozygous for 2 dominant mutations but it would be incredibly rare. (Geneticists like to stick with the obvious).

Mom = dd
Dad = Dd

Each parent has an equal chance of passing on each allele, so the possibilities are:

1. Mom d + Dad D = Dd (affected)
2. Mom d + Dad d = dd
3. Mom d + Dad D = Dd (affected)
4. Mom d + Dad d = dd

Any child who receives ‘D’ from dad will be affected = 50% (2/4 possibilities).

Dominant Negative
There is another class of dominant disorders that doesn’t lead to a gain of function in the gene product. On the contrary, these kinds of mutations not only disable the gene product from the mutated allele, but they ALSO take the ‘normal’ product down too. Therefore, instead of missing 50% of the gene product as a result of one mutated allele, there is almost no normal product left and disease results.

Osteogenesis Imperfecta is one such disease. In the severe form, the mutated fibre interferes with normal bone growth so disease results, even though one allele is expressed properly. It is kind of like the annoying kid in the back of the class – not only is he not paying attention, he often distracts all the kids around him.