Diseases caused by genetic factors are controlled by alleles, which are versions of the same gene that code for different characteristics. Every person will receive one allele from each parent. These may be different or the same and each is typically either dominant or recessive. The influence of a dominant allele will overpower that of a recessive allele. One example of how alleles work to influence disease is the genetic basis of conditions that are known to be autosomal recessive. Sickle cell disease is an autosomal recessive condition. The gene that is responsible for sickle cell, HBB, has many possible alleles. Two types of which are ones that will result in sickle cell and ones that will not result in the condition. If both parents give a dominant allele (one that does not cause sickle cell), then the child will have the dominant trait (no sickle cell). If both parents give a recessive allele (one that does cause sickle cell), then the child will have the recessive trait (sickle cell). If one parent passes on the recessive allele while the other passes on the dominant allele, then the child will still have the dominant trait.
Skipping a Generation
These dominant and recessive alleles mean that a disease can be passed to a child whose parents do not have the condition because both parents have passed on recessive alleles while they themselves also have dominant alleles. This is how many diseases seem to disappear and reappear in different generations of a family without warning.
It is important to note that any person who has received two recessive alleles for this condition would have sickle cell no matter the generation they are in. It is pure chance that both parents in our scenario received both dominant and recessive alleles while they could have just as easily received two recessive alleles from their parents and had the condition (depending of course on whether each of their parents had a recessive allele to give or not). A disease with genetic causes does not take into account that your parents had the condition and then proceed to skip over you. It is simply what alleles you inherit that leave you free (or not) from the condition.
Other Reasons
In some circumstances, inheriting one disease-causing allele may cause an individual of one sex to have the condition and not cause the disease in individuals of another sex. This is true for X-linked recessive conditions. These are conditions caused by mutations of genes on the X chromosome. Because biological males only have one X chromosome, if a gene on that chromosome is mutated they will most likely have the condition associated with it. However, for biological females, they will probably have a non-mutated version of the gene on their second X chromosome. This will prevent them from having the condition but they will still be carriers for the disease. They may pass the mutated gene onto any sons that they have, causing the condition to present itself. This pattern of inheritance will make it appear as if the disease is passing over certain individuals.
There are also situations in which an individual’s genes may indicate that they should have a certain trait or disease but they simply do not. This is called reduced penetrance. And some expressions of mutated genes can differ between people, causing some to not realize that they have the genetic condition. This is referred to as variable expressivity. Reduced penetrance and variable expressivity may cause incorrect assumptions about who is affected by a genetic mutation, therefore, causing some to believe that the associated disease skips people in a family.
