Mitochondrial Genetics and Disease (Genetics & Inherited Conditions)
The unique arrangement of subunits making up individual genes is highly mutable, and thousands of different arrangements, or genotypes, are cataloged in humans. A tiny number of genes in animal cells are strictly inherited from the maternal parent and are found in the mitochondria, located in the cell’s cytoplasm, outside the nucleus, where most genetic information resides in nuclear DNA. Some variants in mitochondrial DNA (mtDNA) sequences can cause severe defects in sight, hearing, skeletal muscles, and the central nervous system. Symptoms of these diseases often include great fatigue. The diseases themselves are difficult to diagnose accurately, and they are currently impossible to treat effectively. New genetic screening methods based on polymerase chain reaction (PCR) technologies using muscle biopsies are essential for correct identification of these diseases.
A person normally inherits a single mtDNA type, but families are occasionally found in which multiple mtDNA sequences are present. This condition, called heteroplasmy, is often associated with mitochondrial disease. Heteroplasmy occurs in the major noncoding region of mtDNA without much impact, but if it exists in the genes that control the production of cellular energy, severe consequences result. Weak muscles and multiple organs are involved in most mitochondrial diseases, and there can be variable expression of a particular syndrome within...
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Particular Mitochondrial Diseases (Genetics & Inherited Conditions)
Mitochondrial diseases show a simple pattern of maternal inheritance. The first mitochondrial disease identified was Leber’s hereditary optic neuropathy (LHON), a condition associated with the sudden loss of vision when the optic nerve is damaged, usually occurring in a person’s early twenties. The damage is not reversible. Biologists now know that LHON is caused by at least four specific mutations that alter the mitochondrial proteins ND1, ND4, and CytB. A second mitochondrial syndrome is myoclonic epilepsy associated with ragged red fiber disease (MERRF), which affects the brain and muscles throughout the body. This disease, along with another syndrome called mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS), is associated with particular mutations in mitochondrial transfer RNA (tRNA) genes that help produce proteins coded for by mtDNA. Finally, deletions and duplications of mtDNA are associated with Kearns-Sayre syndrome (affecting the heart, other muscles, and the cerebellum), chronic progressive external ophthalmoplegia (CPEO; paralysis of the eye muscles), rare cases of diabetes, heart deficiencies, and certain types of deafness. Some of these conditions have been given specific names, but others have not.
Muscles are often affected by mitochondrial diseases because muscle cells are rich in mitochondria. New treatments for these diseases are based on stimulating...
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Further Reading (Genetics & Inherited Conditions)
Berdanier, Carolyn D., ed. Mitochondria in Health and Disease. Boca Raton, Fla.: Taylor and Francis/CRC Press, 2005. Explains how the human mitochondrial genome functions and the relationship of mitochondria to cardiomyopathies, diabetes, and other diseases in humans and animals.
Gvozdjáková, Anna, ed. Mitochondrial Medicine: Mitochondrial Metabolism, Diseases, Diagnosis, and Therapy. London: Springer, 2008. Describes the physiology of mitochondria, defines mitochondrial medicine, and discusses specific types of mitochondrial medicine, including mitochondrial cardiology, diabetology, and nephrology.
Jorde, Lynn B., et al. Medical Genetics. 3d ed., updated ed. St. Louis: Mosby, 2006. Presents a simple discussion of these diseases in the context of other genetic syndromes that are sex-linked or sex-limited in their inheritance patterns. Illustrations, bibliography, index.
Lestienne, Patrick, ed. Mitochondrial Diseases: Models and Methods. New York: Springer, 1999. Focuses on mitochondrial tRNA structure and its mutations. Includes illustrations, some in color.
Losos, Jonathan B., Kenneth A. Mason, and Susan R. Singer. Biology. 8th ed. Boston: McGraw-Hill Higher Education, 2008. Describes mitochondria and how they interact with a cell’s nucleus. Illustrations, maps, index.
Schapira, Anthony H. V., ed. Mitochondrial Function and Dysfunction....
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Web Sites of Interest (Genetics & Inherited Conditions)
Cleveland Clinic, Mitochondrial Disease. http://my.clevelandclinic.org/disorders/Mitochondrial_Disease/hic_Mitochondrial_Disease.aspx. Offers basic information to define this disease, its symptoms, diagnosis, and treatment.
Genetics Home Reference, Mitochondrial Diseases. http://ghr.nlm.nih.gov/conditionGroup = mitochondrialdiseases. A list of links to pages with information on specific mitochondrial diseases, including mitochondrial neurogastrointestinal encephalopathy disease, mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes.
United Mitochondrial Diseases Foundation. http://www.umdf.org. The foundation promotes research and offers support to affected individuals and families. Its Web site explains the genetics of mitochondrial disorders and provides interactive medical advice.
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