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The genomes of any two people are 99.7 percent identical. The 0.3 percent that varies from person to person, along with environmental influences, is responsible for differences between members of the human species. This genetic variation has a major impact on our health. Three broad categories of genetic disorders are chromosomal abnormalities, single gene disorders, and complex genetic disorders.

Chromosomal abnormalities occur when an individual has something other than the normal number of 46 chromosomes in each cell. For example, Turner syndrome occurs in females who have only one copy of the X chromosome instead of two. Individuals with an extra copy of Chromosome 21 have what is called Trisomy 21, or Down syndrome.

Single-gene disorders are the result of an alteration in a gene that causes the product of the gene, a protein, to be abnormal in some way. For example, in sickle cell anemia, a mutation in the hemoglobin beta gene on Chromosome 11 gives the red-blood cell protein hemoglobin an abnormal shape. As a result, some of the red blood cells form a crescent shape or sickle shape, leading to the name of the condition. These sickle cells can block small blood vessels, causing the problems seen in sickle cell anemia.

Single gene disorders can be either recessive or dominant. This distinction is based on the fact that every individual has two copies of each gene, one from each parent. With a dominant genetic disorder such as Huntington disease, one abnormal copy of the gene will cause the disease. In the case of a recessive genetic disorder like sickle cell anemia or cystic fibrosis, both copies of the gene must be abnormal in order for a person to be affect by the disease. An individual who has only one abnormal copy of a recessive disease gene is called a carrier. Carriers are almost always asymptomatic, but if two carriers have a child together, there is a 25 percent chance that the child will inherit two abnormal copies of the gene and therefore have the disease.

Genetic mutations are not always inherited. They also can be acquired during one’s lifetime. Certain environmental factors, such as cigarette smoking or exposure to ultraviolet light, increase the risk of acquiring a mutation in some of the cells of the body. This can lead to cancer in some cases. An acquired mutation will not be passed to future generations unless the mutation occurs in the DNA of a sex cell (eggs or sperm). Since the completion of the Human Genome Project in 2003, which mapped out the sequence of DNA molecules that make up the human genome, scientists have come a long way in identifying the genes involved in many single-gene disorders.

Complex genetic disorders are a new focus of intense research in genetics because many of them are very common in the population. Examples include heart disease, diabetes, asthma, and most cancers. Unlike single-gene disorders, complex genetic disorders involve alterations in many different genes. Another difference is that complex genetic disorders may have a significant environmental component. For example, depending on the gene variants that a person inherited from their parents, her genetic make-up may indicate an increased risk for developing diabetes, but her diet and exercise habits also will play a considerable role in determining whether she develops the disease. To prevent or treat complex genetic disorders one must consider both genes and environment.

Genome-wide association studies (GWAS) have provided a critical tool in understanding complex genetic disorders. Using GWAS, researchers compare the genomes of a group of individuals with a certain disease to a group of individuals without the disease. With a large enough sample of individuals, researchers can often make an association between having certain genetic variants and the likelihood of developing a disease. Type II diabetes, also known as adult-onset diabetes, is a prime example. The lifetime risk of developing diabetes is one in three for the average man and two in five for the average woman. For individuals that possess a certain mutation, or alteration, in the TCF7L2 gene, GWAS studies found that the likelihood is significantly higher. These high-risk individuals can take important steps to prevent developing diabetes.

Illuminating the complex relationship between genes and environment holds great promise for understanding disease and developing more effective interventions.

Last updated 8/2008 by Graham Watson