Genetics is the study of heredity, the process in which a parent passes certain genes onto their children. A person's appearance -- height, hair color, skin color, and eye color -- are determined by genes. Other characteristics, such as mental abilities, natural talents, and your susceptibility to develop certain diseases, are also affected by heredity.

An abnormal trait (anomaly) passed down through families (inherited) may:

• Have no effect on your health or well being -- for example, it may just involve a white patch of hair or an extended ear lobe
• Be of minor consequence -- for example, color blindness
• Have dramatic effect on ypur quality or length of life

For most genetic disorders, genetic counseling is advised. Many people may also want to seek prenatal diagnosis.

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 non-sex (autosomal) chromosomes. Males are "46, XY" and females are "46, XX". The chromosomes are made up of extremely long DNA molecules in combination with proteins.

Genes are defined by intervals along one of the DNA molecules. The location of the gene is called the locus. Most genes carry information which 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, but 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 that are called alleles.

The information contained in the nucleotide sequence of a gene is transcribed to mRNA (messenger RNA) by enzymes in the cell's nucleus and then translated to a protein in the cytoplasm. This protein may be a part of tissue. It may be an enzyme which in involved in a chemical reaction, or it may be a hormone. There are also many other potential functions for proteins.

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 2 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 are each heterozygous for a particular recessive disease gene, then each child has a 25% chance of being homozygous for that gene and therefore, of showing the disease. If one parent is homozygous and the other heterozygous, then each child has a 50% chance of being homozygous.

GENETIC DISORDERS

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 is first seen (or is of immediate interest) is called the proband. The brothers and sisters of the proband are called siblings.

There are five basic patterns of single gene inheritance:

• Autosomal dominant
• Autosomal recessive
• X-linked dominant
• X-linked recessive
• Maternal (mitochondrial) inheritance

The observed effect of a gene (the appearance of a disorder) is called the 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. Carriers usually don't show the disease,but the gene can frequently be identified 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 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.

EXAMPLES OF SINGLE GENE DISORDERS

Autosomal recessive:

• Cystic fibrosis (CF)
• Phenylketonuria (PKU)
• Alpha-1-antitrypsin (AAT) deficiency
• Sickle cell anemia
• ADA deficiency, a rare immunodeficiency disorder, sometimes called the "boy in a bubble" disease

X-linked recessive:

• Duchenne muscular dystrophy
• Hemophilia A

Autosomal dominant:

• Familial hypercholesterolemia
• Huntington's disease

X-linked dominant:

Only a few, very rare, disorders are classified as X-linked dominant. One of these is hypophosphatemic rickets, also called vitamin D -resistant rickets.

CHROMOSOMAL DISORDERS

In chromosomal disorders, the defect is due not to a single gene, but to an excess or deficiency of the genes contained in a whole chromosome or chromosome segment.

Chromosomal disorders include:

• Down syndrome
• Klinefelter syndrome
• Turner syndrome

MULTIFACTORIAL DISORDERS

Many of the most common diseases, including coronary heart disease, hypertension, stroke, and various kinds of cancer, involve interactions of several genes.

MITOCHONDRIAL DNA-LINKED DISORDERS

Mitochondria are small organisms present 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 20 hereditary disorders have been shown to result from mutations in mitochondrial DNA. Because mitochondria come only from the female egg, most mitochondria-related disorders are passed down exclusively from the mother.

Mitochondrial disorders can appear at any age with a wide variety of non-specific symptoms and signs. These disorders may cause metabolic disturbances, developmental delay, blindness, hearing loss, heart rhythm problems, short stature, and gastrointestinal problems.

Goldman L, Ausiello D. Cecil Textbook of Medicine. 23rd ed. Philadelphia, Pa: Saunders Elsevier; 2007.