Introduction to Genetics of Alport Syndrome

Genetic diseases are usually caused by the absence of a normal protein function. Most other kinds of diseases that we are familiar with such as colds, flu, chicken pox and AIDS are caused by infections with a "germ" such as a virus or a kind of bacteria. When a person is told that they "carry the gene" for a disease, it is easy to think that "the gene" is something extra that is not present in other people like a germ. But nearly all genetic diseases are caused by a change or "flaw" in the DNA that results in the loss of a normal protein.

For nearly every gene that humans have, there are actually two copies, one inherited from the mother and one from the father. This is true for both males and females for about 95% of our genes. The only exception to this is with the chromosomes that determine sex, the X and the Y chromosomes. The X chromosome carries about 5% of all human genes. The Y chromosome carries very few genes, and these are mainly involved in causing males to develop male characteristics. Since females have two X chromosomes, one from their father and one from their mother, all females do have two copies of every gene. Males have one X and one Y. Since the Y chromosome does not have most of the genes that are present on the X chromosome, males have only one copy of most of those genes.

The fact that humans have two copies of nearly every gene, except those on the X, and that different genes encode proteins with different kinds of functions is why there are different kinds of genetic inheritance patterns.

A genetic disease is said to be "dominant" if inheriting one defective gene copy is enough to cause the disease. The idea of "dominance" comes from the fact that the disease is expressed even though there is also a normal copy of the same gene present. When a person with a dominant genetic disease has children, on average, half of the children will inherit the defective gene and develop the disease.

A recessive" genetic disease is one where there is no or little effect of carrying just one defective copy of the gene, but if a person inherits two defective copies, then the absence of any normal copy of that gene results in disease. In order for a person to inherit a recessive disease, both parents must be carriers and both parents must contribute a defective gene to the child. On average this will only happen in 25% of the children of such parents.

For genes on the X chromosome, the situation is complicated by the fact that males only have one X. So a "recessive change, one that does not usually cause severe disease in a female, will be expressed in a male because he does not have any normal copy of the same gene.

The great majority (about 85%) of Alport Syndrome is caused by defects in a particular X-linked gene. About 15% of Alport syndrome is recessive and about 1% is dominant.

The University of Utah study is interested in studying the various causes of Alport Syndrome in families. Part of this work involves laboratory genetics, but a large part is also communicating with families, tracing family pedigrees and learning the medical histories of family members who may have the disease.