Genetics & Kidney Disease

Some Basic Information About Genes

Some diseases in the kidneys are caused by problems (mutations) in genes.  People have about 25,000-30,000 genes.  The genes are made of DNA (deoxyribonucleic acid), a chemical that has four major types (or bases) which are abbreviated as A, T, G , and C.  The sequence, or order, of these bases acts as a code to tell the body how to build proteins and  how to maintain itself. 

The genes are located together in a central place in cells called the nucleus, and are grouped together on long strands of DNA and protein  that are called chromosomes.  Most people have 46 chromosomes, with 23 coming from the mother, and another matched set of 23 coming from the father.

Illustration of a DNA Strand

Mutations are errors in the gene code that can affect the way that proteins are made and used in the body.  These mutations can make it almost certain that a particular disease will happen, or they can just make it possible that the disease will happen.  The types of mutations in a gene can also determine how severe the disease will be, and when it will show up in a person.

Most of the 25,000 – 30,000 genes come as pairs, with a person getting one copy from his/her mother and another copy from his/her father.  (The exception to this are the genes that are located on the X and Y chromosomes.  For  these genes, there is usually only one copy.)

Some diseases can be caused by a mutation in just one of the two copies of a gene, with the mutated gene being strong enough to overcome the affects of the other, normal gene.  This is called Autosomal Dominant Inheritance.  An example of this is the disease Autosomal Dominant Polycystic Kidney Disease (ADPKD).  If a person has an autosomal dominant genetic disease, it is likely that one of that person’s parents also had the disease, and also likely that some of that person’s children may inherit the disease.

Some diseases require a person to have mutations in both copies of a gene.  This is called Autosomal Recessive Inheritance.  In this case, having both copies of the gene with a mutation leaves the person without any normal protein from that gene, and leads to the disease.  For  these diseases, having one gene that is normal can cover up the mutation in the other gene and prevent the disease, or at least make it much less severe.  Because of this, it is unlikely that parents or children of the affected person will have the disease.  (If a parent or child has one copy of the gene with the mutation, they almost always will have a normal copy of the gene as well).  An example is Autosomal Recessive Polycystic Kidney Disease.

Problems with genes found on the X chromosome are a little different.  Since women have two X chromosomes and men have only one, any mutation in a gene on the X chromosome will be paired in women, but will be the only copy in men.  This is why mutations in genes on the X chromosome usually affect only men, or at least affect men more severely than women.  These types of diseases are called X-linked.  An example of this kind of disease are many cases of Alport Syndrome.

In some cases, a person may inherit a gene with a mutation that usually leads to a disease, but never get that disease.  This is an idea called penetrance.   In these cases, it is thought that either other, unrelated genes that a person inherits can protect from developing the disease, or else both  the mutation in the gene and some environmental exposure are required to get the disease, and the person without the disease just never had that environmental exposure.

While many diseases are known that are caused by mutations in a single gene, many other diseases seem to be caused by collections of minor mutations in many different genes.  Diseases like this are more difficult to understand, as they often lead to a “risk” of developing the disease, and have many possible combinations of inherited genes, and therefore inherited risk.  Most cases of high blood pressure (hypertension) and autoimmune diseases (like Lupus) likely fall into this category.  How these types of diseases show up may also depend on what kind of environmental exposures a person has.