Genetic Contributions to Health
From WikiGenetics
All diseases have a genetic component. However, the extent to which genes contribute to disease varies and much remains to be learned. Advances in understanding the genetic mechanisms behind these diseases enable the development of early diagnostic tests, new treatments, or interventions to prevent disease onset or minimize disease severity.
All diseases have a genetic component. Mutations may be inherited or developed in response to environmental stresses such as viruses or toxins. The ultimate goal is to use this information to treat, cure, or if possible, prevent the development of disease.
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[edit] History and Physical Test
The diagnosis of a genetic disease requires a comprehensive clinical examination composed of three major elements:
- a physical examination
- a detailed medical family history
- clinical and laboratory testing if available.
While primary care providers may not always be able to make a definitive diagnosis of a genetic disease, their role is critical in collecting a detailed family history, considering the possibility of a genetic disease in the differential diagnosis, ordering testing as indicated and when available, appropriately referring patients to genetic specialists.
[edit] Red Flags for Genetic Disease
There are several factors that raise the possibility of a genetic disease in a differential diagnosis. One major factor is the occurrence of a condition among family members that is disclosed when the family history is obtained (see Family History). The occurrence of the same condition in more than one family member (particularly first-degree relatives), multiple miscarriages, stillbirths, and childhood deaths are all suggestive of a genetic disease. Additionally, family history of common adult conditions (heart disease, cancer, dementia) that occur in two or more relatives at relatively young ages may also suggest a genetic predisposition.
Other clinical symptoms that are suggestive of a genetic disease include developmental delay/mental retardation and congenital abnormalities. Dysmorphologies, often involving the heart and face, as well as growth problems are suggestive of a genetic disorder caused by an inherited mutation, a spontaneous mutation, a teratogen exposure, or unknown factors. While these clinical features may be caused by a number of factors, genetic conditions should also be considered as part of the differential diagnosis, particularly if the patient expresses several clinical features together that might be indicative of a syndrome (for example, mental retardation, distinct facies, and heart defect). Some physical features may appear unique or slightly different than the average such as wide-set or droopy eyes, flat face, short fingers, and tall stature. While these rare and seemingly mild features may not immediately be suggestive of a genetic disease to a primary care provider, an evaluation by a genetics specialist may be helpful in ruling in/out a genetic disease.
While many genetic conditions appear during childhood, a genetic condition should not entirely be ruled out in adolescents or adults. Often a genetic disease can remain undetected for several years until an event such as puberty or pregnancy triggers the onset of symptoms or the accumulation of toxic metabolites manifests in disease. In these cases, a detailed family history and physical examination should be performed and a referral made to a genetics specialist if indicated.
[edit] Major Types of Genetic Disease
Many, if not most, diseases have their roots in genes. Genes—through the proteins they encode —determine how efficiently foods and chemicals are metabolized, how effectively toxins are detoxified, and how vigorously infections are targeted. Genetic diseases can be categorized into three major groups: single gene, chromosomal abnormalities, and multifactorial (or complex conditions).
Thousands of diseases are known to be caused by changes in the DNA sequence of single genes. A gene can be changed (mutated) in many ways resulting in an altered protein product that is unable to perform its function. The most common gene mutation involves a change or “misspelling” in a single base in the DNA. Other mutations include the loss (deletion) or gain (duplication or insertion) of a single or multiple bases. The altered protein product may still retain some function but at a reduced capacity. In other cases, the protein may be totally disabled by the mutation or gain an entirely new but damaging function. The outcome of a particular mutation depends not only on how it alters a protein’s function but also on how vital that particular protein is to survival.
In addition, genetic diseases can be caused by larger changes in chromosomes. Chromosomal abnormalities may be either numerical or structural. The most common type of chromosomal abnormality is known as aneuploidy, an abnormal number of chromosomes due to an extra or missing chromosome. A normal karyotype (complete chromosome set) contains 46 chromosomes including an XX (female) or XY (male) sex chromosome pair. Structural chromosomal abnormalities include deletions, duplications, insertions, inversions, or translocations of a chromosome segment.
Multifactorial diseases are caused by a combination of genetic, behavioral and environmental factors. The underlying etiology of multifactorial diseases is complex and heterogeneous. Examples of these conditions include spina bifada, diabetes, and heart disease. While multifactorial diseases can recur in families, some mutations can be acquired throughout an individual’s lifetime such as in cancer. All genes work in the context of environment and behavior. Alterations in behavior or the environment, such as diet, exercise, exposure to toxic agents, or medications can all have influences on genetic traits.
[edit] References
Gelehrter TD, Collins FS, Ginsburg D. Principles of Medical Genetics. 2nd Edition. Baltimore: Williams & Wilkins, 1998.
Genetic Alliance. 2007. Understanding Genetics: A Guide for Patients and Health Care Professionals. http://www.geneticalliance.org/ws_display.asp?filter=understanding.genetics.download
Mahowald MB, McKusick VA, Scheuerle AS, Aspinwall TJ (eds). Genetics in the Clinic: Clinical, Ethical, and Social Implications for Primary Care. St. Louis: Mosby, Inc. 2001. Scriver CR, Beaudet AL, Sly WS, Valle D (eds.). The Molecular and Metabolic Basis of Inherited Disease. New York: McGraw-Hill, 2001.
Thompson MW, McInnes RR, Willard HF. Thompson & Thompson: Genetics in Medicine, 5th Edition. Philadelphia: W.B. Saunders Company, 1991.
[edit] See Also
- Birth Defects/Congenital Abnormalities
- Genetic Test
- Single Gene Disorders
- Teratogens/Prenatal Substance Abuse
- X-Linked Genetic Diseases
- Genetic Counseling
- Identifying Human Disease Genes
[edit] External Links
American College of Medical Genetics http://www.acmg.net
Department of Energy, Human Genome Project Education Resources. http://www.ornl.gov/sci/techresources/Human_Genome/education/education.shtml
GeneTests(online directory of genetic testing laboratories and genetic testing reviews) http://www.genetests.org
National Library of Medicine, Genetics Home Reference–Your Guide to Understanding Genetic Conditions. http://ghr.nlm.nih.gov/
Online Mendelian Inheritance in Man. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=OMIM
