Modes of Inheritance

1) How Recessive Conditions are Inherited

2) Inheritance of X-Linked Conditions

Additional Informational Links

How Recessive Conditions are Inherited

Tay-Sachs and most of the allied diseases are autosomal recessive disorders; that is, they are transmitted through the genes in the same way as eye color is passed from parent to child. Even though they are inherited conditions, most families are not aware that they carry genes for a disease until the birth of an affected child. Children with Tay-Sachs or an allied disease are most often born to parents with no family history of the disease.

Almost all of our genes come in pairs, one inherited from each of our parents. A carrier of a genetic condition is a person who has one copy of the same gene. A recessive condition like Tay-Sachs results when a child inherits two copies of an altered gene, one from each parent. Both parents must be carriers of the same recessive disease gene in order for any of their children to be affected. Carriers themselves do not have the disease, and carrier status does not affect the mother or father physically, mentally or in any other way; the only consequence of being a carrier of a recessive genetic trait is the possibility of transmitting the particular genetic trait to a child.

High-risk couples, in which the man and the woman are carriers of the same genetic condition, have a 25% chance with each pregnancy of conceiving a child with that condition. There is a 50% chance of producing a child who is a carrier like the parents and a 25% chance that the child will be neither a carrier nor affected with the disease. These numbers are illustrated in the following chart:

Transmission of Autosomal Recessive Traits

If only one parent is a carrier, there is no chance of producing a baby with a recessive disease. There is, however, a 50% chance in each pregnancy that the child will be a carrier, as is illustrated below:

Transmission of Autosomal Recessive Carrier Traits

Inheritance of X-Linked Conditions

A few of the allied diseases - Fabry Disease, Hunter Syndrome, X-Linked Adrenoleukodystrophy, and Pelizaeus Merzbacher Disease - follow an x-linked inheritance pattern. The term X-Linked refers to the location of the genes causing these diseases on the X chromosome.

Human cells, with the exception of sperm and egg cells, each contain 46 chromosomes. The chromosomes exist in pairs, one of each pair inherited from each parent. One pair of chromosomes, the sex chromosomes, determine whether a person is male or female. The sex chromosomes are also called X and Y chromosomes: males have one X chromosome and one Y chromosome, while females have two X chromosomes. In addition to determining gender, the X chromosome contains many genes which are essential for growth and development.

An X-linked condition results when a person has a mutation in one of the genes on the X chromosome. X-linked conditions usually affect males more often and more severely than females, because females with a mutation in a gene on the X-chromosome usually have a non-mutated gene on their other X-chromosome which can compensate for the mutation. Females with a mutation in a gene on one X chromosome and a normal copy of the gene on the other X chromosome are called carriers. They are generally healthy, but they may have sons who are affected with the condition.

A carrier female of an X-linked condition may pass on either of her X chromosomes to her children. On average, half of her sons will be affected, and half of her sons will not be affected. Half of her daughters will be carriers, and half will not be carriers and therefore will have no chance of having a child with the condition. These possible outcomes are illustrated in the figure below:

Transmission of X-Linked Traits

When a male is diagnosed with an X-linked condition, it is possible that the condition resulted from a new mutation in his X-chromosome. It is important for the mother of an affected male to have carrier testing to determine whether or not she is a carrier. If she is found not to be a carrier, the chance of her having another affected son is very low.

Additional Informational Links

The following websites are recommended for their coverage of Mendelian inheritance as it pertains to the Allied Diseases:

• The Rare Genetic Diseases In Children website's Human Genetic Disease: A Layman's Approach relates in detail the biological processes of genetic inheritance, particularly as it pertains to Lysosomal Storage Disorders.

• Boys Town Fact Sheet on Autosomal Recessive Inheritance.

• Boys Town Fact Sheet on X-Linked Recessive Inheritance.

• MendelWeb portrays a broader look at classical genetics for those interested in the the full scope of genetic inheritance.

• The Merck Manual's General Principles of Medical Genetics: Inherited Disorders.

• Mosby Consumer Health's Genetics Primer.

• Primer on Molecular Genetics, by the Department of Energy and Johns Hopkins, may be too technical for some, but worthwhile for others wanting the full picture.