Almost all diseases have a genetic component, but the importance of that component varies. Disorders where genetics play an important role, so-called genetic diseases, can be classified as single gene defects, chromosomal disorders, or multifactorial.
A single gene disorder (also called Mendelian disorder) is one that is determined by a single genetic locus and the specific allele on one or both members of a chromosome pair. Single gene defects are rare, with a frequency of less than 1 in 200 births. But since there are about 6,000 known single gene disorders, their combined impact is significant.
The incidence of serious single gene disorders is estimated to be about 1 in 200 births.
Single-gene disorders are characterized by the pattern of transmission in families -- this is called a pedigree. The term "kindred" includes the relatives outside of the immediate nuclear family. The affected individual that initially comes to light (or is of immediate interest) is called the proband. The brothers and sisters of the proband are called siblings.
There are only 5 basic patterns of single gene inheritance:
The observed effect of an abnormal gene (the appearance of a disorder) is called the abnormal phenotype. A phenotype expressed in the same way (in both homozygotes and heterozygotes) is dominant. A phenotype expressed only in homozygotes (or, for X-linked traits, expressed in males but not females) is recessive.
Heterozygotes for a recessive gene are called carriers. They usually don't express the phenotype clinically, but it can frequently be identified by sensitive laboratory methods.
In AUTOSOMAL DOMINANT INHERITANCE, the abnormality or abnormalities usually appear in every generation. Every affected child has an affected parent and each child of an affected parent has a 50% chance of inheriting the disease.
Normal members of the family do not transmit the disease. Males and females are equally likely to have the disease and to transmit the disease. Male-to-male transmission can occur (unlike with X-linked inheritance), and males can have unaffected daughters (unlike with X-linked dominant inheritance).
In AUTOSOMAL RECESSIVE INHERITANCE, the parents of an affected individual may not express the disease. On average, the chance of an affected child's brothers or sisters having the disease are 1 in 4. Males and females are equally likely to be affected. For a child to have symptoms of an autosomal recessive disorder, the child must receive the defective gene from BOTH parents.
Because most recessive disorders are rare, a child is at increased risk of a recessive disease if the parents are related. Related individuals are more likely to have inherited the same rare gene from a common ancestor.
In X-LINKED RECESSIVE INHERITANCE, the incidence of the disease is much higher in males than females. Since the abnormal gene is carried on the X chromosome, males do not transmit it to their sons -- they do transmit it to their daughters.
The presence of one normal X chromosome masks the effects of the X chromosome with the abnormal gene. So, almost all of the daughters of an affected man appear normal, but they are all carriers of the abnormal gene. The sons of these daughters then have a 50% chance of receiving the defective gene.
In X-LINKED DOMINANT INHERITANCE, the presence of the defective gene appears in females even if there is also a normal X chromosome present. Since males pass the Y chromosome to their sons, affected males will not have affected sons, but all of their daughters will be affected. Sons or daughters of affected females will have a 50% chance of getting the disease.
