The terms anomaly, abnormality, disorder, defect, disease, and syndrome are not used consistently, and do not have precise definitions.
Human beings have cells with 46 chromosomes -- 2 sex chromosomes and 22 pairs of nonsex (autosomal) chromosomes. Males are "46, XY" and females are "46, XX." The chromosomes are made up of strands of genetic information called DNA.
Genes are sections of DNA. The location of the gene is called the locus. Most genes carry information that is necessary to make a protein.
The pairs of autosomal chromosomes (one from the mother and one from the father) carry basically the same information. That is, each has the same genes. However, there may be slight variations of these genes. These slight differences occur in less than 1% of the DNA sequence and produce variants of a particular gene called alleles.
If a gene is abnormal, it may lead to an abnormal protein or an abnormal amount of a normal protein. Since the autosomal chromosomes are paired, there are two copies of each gene, one from each parent. If one of these genes is defective, the other may make enough protein so that no disease is seen. This is called a recessive disease, and the gene is said to be inherited in a recessive pattern.
However, if only one abnormal gene is needed to produce a disease, it's called a dominant hereditary disorder. In the case of a dominant disorder, if one abnormal gene is inherited from mom or dad, the child will likely show the disease.
A person with one abnormal gene is termed heterozygous for that gene. If a child receives an abnormal recessive disease gene from both parents, the child will show the disease and will be homozygous for that gene.
If two parents each have one copy of a recessive disease gene, then each child has a 25% (1 in 4) chance of showing the disease. If one parent has two copies of the disease gene and the other has one copy, then each child has a 50% (1 in 2) chance of being homozygous.
Almost all diseases have a genetic component. However, the importance of that component varies. Disorders in which genes play an important role (genetic diseases) can be classified as:
- Single-gene defects
- Chromosomal disorders
A single gene disorder (also called Mendelian disorder) is caused by a defect in one particular gene. Single gene defects are rare. But since there are about 18,000 known single gene disorders, their combined impact is significant.
Single-gene disorders are characterized by how they are passed down in families. There are six basic patterns of single gene inheritance:
The observed effect of a gene (the appearance of a disorder) is called the phenotype.
People with one copy of a recessive disease gene are called carriers. Carriers usually don't show the disease. However, the gene can often be found by sensitive laboratory tests.
In autosomal dominant inheritance, the abnormality or abnormalities usually appear in every generation. Each affected child of an affected parent has a 50% chance of inheriting the disease.
In autosomal recessive inheritance, the parents of an affected individual may not show 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. However, 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. All of their daughters will be affected, however. Sons or daughters of affected females will have a 50% chance of getting the disease.
EXAMPLES OF SINGLE GENE DISORDERS
Only a few, rare, disorders are X-linked dominant. One of these is hypophosphatemic rickets , also called vitamin D -resistant rickets.
In chromosomal disorders, the defect is due to an excess or lack of the genes contained in a whole chromosome or chromosome segment.
Chromosomal disorders include:
Many of the most common diseases involve interactions of several genes and the environment (for example, illnesses in the mother and medications). These include:
MITOCHONDRIAL DNA-LINKED DISORDERS
Mitochondria are small organisms found in most of the body's cells. They are responsible for energy production inside cells. Mitochondria contain their own private DNA.
In recent years, more than 60 hereditary disorders have been shown to result from changes (mutations) in mitochondrial DNA. Because mitochondria come only from the female egg, most mitochondria-related disorders are passed down only from the mother.
Mitochondrial disorders can appear at any age. They have a wide variety of symptoms and signs. These disorders may cause:
- Developmental delay
- Gastrointestinal problems
- Hearing loss
- Heart rhythm problems
- Metabolic disturbances
- Short stature