Tags: basics; inheritance

Diseases are classified as recessive when both versions of a gene have to be mutated to see disease.   Generally, these mutations cause “loss of function” – the allele isn’t there to produce anything. However, having one working copy of the gene (50% of normal) is often enough of the functional gene product and prevents disease.  But when both alleles are mutated (and less than 50% of the necessary gene product is made), there isn’t enough gene product and disease results.

In recessive disorders, both parents are carriers. They have one “normal” allele and one mutant allele. To be affected of course, their child has to inherit both mutant alleles – one from each parent. The carrier parents don’t show symptoms because, as we now know, their normal allele (their “50%”) makes the necessary amount of gene product. So, recessive diseases pop up when carriers of the same mutation mate. The chance of this happening increases if the carriers are related by descent.

Figuring out Possibilities
To figure out the recurrence risk (the risk of having another affected child), we can do some simple calculations that we can drop into a little table called a Punnet Square.

By convention, dominant alleles are generally written as capital letters and recessive alleles in small letters. Therefore, affected individuals are “aa” and their carrier parents are “Aa”. Now, to figure out the possibility of “aa” occurring again, we just count up the possibilities.

• Mom = A a
• Dad = A a

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

• Mom A + Dad A = AA
• Mom A + Dad a = Aa (carrier)
• Mom a + Dad A = Aa (carrier)
• Mom a + Dad a = aa (affected)

There is one combination that leads to affected child so the probability is ¼ or 25%. There are two possibilities of a carrier, so there is a 50% risk of carrier children (2/4).

Example with Cystic Fibrosis
Cystic Fibrosis is a recessive disorder.  In a hypothetical family with Emily and a brother with Cystic Fibrosis, the parents are unaffected carriers, as illustrated above.  Unhappily, her brother would have inherited both copies of the mutant gene.

Emily does not have the disease, so she is either an unaffected carrier, or she has no mutant genes for CF. To ensure that Emily’s children do not have CF, she will have to make sure that her partner is not an unaffected carrier. If her partner is not a carrier, and Emily is a carrier, her children’s odds for CF look like this:

• Emily A a
• Partner a a

• Emily A + partner a = A a
• Emily a + partner a = a a

Her children will not have CF, but they will have a 50% chance of being a carrier (Aa).

When you look at families with a recessive disorder, the affected person may be the only affected person in the family. If other family members are affected, they are often siblings because the parents are known carriers, and this, as we have seen, leads to higher risk.