What is an autosomal recessive disease?
An autosomal recessive disease is an inherited disease that typically is not seen in every generation, but may affect several members of one generation (siblings or cousins). Autosomal diseases usually affect males and females equally.
Return to top
The meaning of autosomal
Human genes are organized into 23 separate "packages," called chromosomes. All somatic cells within the human body, that is, all cells except for egg cells in females and sperm cells in males, contain two copies of each of the 23 chromosomes. Chromosomes 1 through 22 are called autosomes, and the genes located on them are known as autosomal genes. Both females and males inherit one copy of each autosome from the mother and the other copy from the father. Chromosome 23, called the sex chromosome, occurs in 2 forms, the X chromosome and the Y chromosome. Females have two copies of the X chromosome, one inherited from the mother and the other from the father. Males have one copy of the X chromosome and one copy of the Y chromosome. Males inherit the X chromosome from their mother and the Y chromosome from their father. Genes located on the X and Y chromosomes are called X-linked and Y-linked, respectively.
Return to top
The meaning of autosomal recessive inheritance
Autosomal recessive diseases only develop if a disease-associated genetic variation is present on both copies of a given autosomal chromosome. Disease can develop if both copies harbor the same disease-associated genetic variation and also if each copy harbors a different disease-associated genetic variation. Presence of a disease-associated genetic variation only on the chromosome copy inherited from the mother or only on the chromosome copy inherited from the father is not sufficient to cause disease. Individuals who harbor a disease-associated genetic variation on only one of the two copies of a given autosomal chromosome are called carriers. If both parents are carriers, each child has a 25% chance of being affected.
Return to top
Why should family members of patients with an autosomal recessive disease be tested for that disease?
The siblings of a patient with an autosomal recessive disease have, on average, a 25% chance of being affected with the same disease and a 50% chance of being carriers. Once the familial mutation(s) associated with the disease is/are known, genetic family testing can identify who among the family members harbors the familial mutation(s) on both chromosome copies and is at great risk of the disease, who harbors a familial mutation on one chromosome copy and is a carrier of the disease, and who is neither at high risk of the disease nor a carrier.
Return to top
Why is genetic testing better than other diagnostic methods for family testing?
Genetic testing is often the best tool for identifying carriers of disease-associated genetic variations, since carriers typically do not show any symptoms.
Return to top
The meaning of mosaicism
Mosaicism means that a certain genetic variation does not occur in all cells of the body, but only in some. In other words, an individual can be a "mosaic" of cells that harbor the genetic variation and cells that do not harbor the genetic variation. Genetic testing may or may not be able to detect a genetic variation in a mosaic individual, depending on how many cells and which cells harbor the genetic variation. The risk of inheriting a disease-associated genetic variation from a mosaic individual varies widely and cannot be predicted.
Return to top
The meaning of "de novo" genetic variation
Sometime, a disease-associated genetic variation is newly generated in an individual. In other words, an inherited disease can suddenly appear within a member of a previously unaffected family. The descendants of the affected family member are then at high risk of inheriting the newly generated familial mutation. In addition, the siblings of the affected family member may also be at increased risk of the disease, since the familial mutation may, in fact, have been generated in one of the patient’s parents – ie, one of the parents could be a mosaic for the genetic variation. It is therefore important to consider genetic testing of the index patient’s siblings even if the genetic variation found in the index patient cannot be detected in either parent.
Return to top
Copyright © 2008, Correlagen Diagnostics, Inc. All rights reserved.
