mutation change in DNA sequence allele a particular form of a gene etiology causation of disease, or the study of causation allele a particular form of a gene oooc ,oc other family members who have the disease. If individuals with the disease have a higher frequency of affected relatives compared with individuals without the disease, there is evidence of familial aggregation. Although familial aggregation for a disorder is consistent with the involvement of genetics, it may also reflect the presence of a common environmental factor to which all family members have been exposed (such as pesticides or contaminated drinking water).
Relative risk ratios are another method commonly used to determine if there exists a genetic basis to a disease. For example, in cystic fibrosis, an autosomal recessive Mendelian disorder, the risk of disease in the siblings prevalence frequency of of an affected individual is 1 in 4. The prevalence of the disease is about 1
a disease °i- ^nditbn in 1,600 in the general population. in a population
In 1990 Neil Risch demonstrated that by comparing the risk of a disease occurring in the relatives of an affected individual with the risk of the disease occurring in the general population, one could measure the significance of the genetic component of the disease. The risk ratio, labeled AR, where R is the type of relative (such as sibling), is the ratio of the risk of disease in the relative of type R to the prevalence of the disease in the general population. Thus in cystic fibrosis, As = 1/4 — 1/1600 = 400. This means that the risk of developing cystic fibrosis is four hundred times greater for siblings of an affected individual than for an individual in the general population. This clearly demonstrates the effect that genetics plays in the development of cystic fibrosis.
As a general rule, the larger the AR, the stronger the genetic component. However, this ratio is extremely sensitive to the frequency of the disease in the general population. The more common the disorder, the lower the Ar, although this does not necessarily preclude a genetic component to the disorder.
Twin and adoption studies provide a unique opportunity to tease apart the role of genetics and the influence of a common familial environment. Because twins were born at the same time, the environments to which they were exposed are very similar. This holds true for the prenatal environment, and often for the childhood environment, but rarely for adult environments.
Monozygotic (MZ), or identical, twins share 100 percent of their genetic makeup, and dizygotic (DZ), or fraternal, twins share on average 50 percent of their genetic makeup. Twin studies compare disease "concordance" in MZ twins with DZ twins. When both twins in a pair have the disease, the twins are said to be concordant. When one twin has the disease and the other does not, the twins are said to be discordant. If the disorder has a genetic component, then MZ twins will be concordant more often than DZ twins. The difference between the MZ and DZ concordance rates can be used to assess the strength of the genetic component.
In summary, geneticists are finding that some disorders have a large genetic effect and others have a small genetic effect. There are several methods geneticists can use to determine the size of the genetic effect of a disease. However, ultimately, researchers trying to fully understand genetic disorders must identify the genes that are involved and determine their function. The revolution in human genetics, primarily due to the successes of
the Human Genome Project, has made and will continue to make an impact on scientists' ability to define the role of genetics in human disease. see also Alzheimer's Disease; Cancer; Cardiovascular Disease; Complex Traits; Cystic Fibrosis; Diabetes; Epidemiologist; Gene Discovery; Hemoglobinopathies; Inheritance Patterns; Muscular Dystrophy; Triplet Repeat Disease; Twins.
DNA (deoxyribonucleic acid) was discovered in the late 1800s, but its role as the material of heredity was not elucidated for fifty years after that. It occupies a central and critical role in the cell as the genetic information in which all the information required to duplicate and maintain the organism. All information necessary to maintain and propagate life is contained within a linear array of four simple bases: adenine, guanine, thymine, and cytosine.
DNA was first described as a monotonously uniform helix, generally called B-DNA. However, we now know that DNA can adopt many different shapes and conformations. Moreover, many of these alternative shapes have biological importance. Thus, the DNA is not simply an informational repository, from which information flows through RNA into proteins. Rather, structural information exists within the specific sequence patterns of the bases. This structural information dictates the interaction of DNA with proteins to carry out processes of DNA replication, transcription into RNA, and repair of errors or damage to the DNA.
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