Table of Contents > Genomics > Single gene disorders Print

Single gene disorders

Image

Also listed as: Monogenic disorder
Related terms
Background
Methods
Research
Implications
Limitations
Safety
Future research
Author information
Bibliography

Related Terms
  • Acid alpha-glucosidase, acid alpha-glucosidase gene, acid maltase deficiency, autoimmune lymphoproliferative syndrome, chromosome, dominant, Fas gene, GAA gene, inherited genetic condition, monogenic, monogenic disorders, PCR, polymerase chain reaction, recessive.

Background
  • A single gene disorder, also referred to as a monogenic disorder, is an inherited genetic disease that may develop due to a mutation, or defect, in just one gene. Genes are sequences of DNA (deoxyribonucleic acid) that provide instructions for making proteins in the body. There are about 6,000 different single gene disorders that affect humans. Single gene disorders are different from polygenic disorders, in which more than one gene contributes to causing a disease in an individual.
  • DNA is located in a compartment of the cell called the nucleus and is packaged in structures called chromosomes. In addition to DNA, chromosomes also contain proteins, such as histones, which help package the DNA in an orderly way. Human cells contain a total of 46 chromosomes, including 22 pairs of autosomes, and a pair of sex chromosomes. Females have two X chromosomes while males have one X and one Y chromosome. Each chromosome contains hundreds of genes, each of which contains the instructions for making proteins in the body. Individuals have two copies of most genes, one inherited from the father and one from the mother.
  • Single gene disorders may be inherited, or passed down from a parent to a child. If a single gene disorder follows a dominant inheritance pattern, only one parent must carry the disease-causing genetic mutation for a child to be at risk of inheriting the trait. However, if a single gene disorder follows a recessive inheritance pattern, both parents must carry a copy of the defective gene for a child to be at risk of inheriting the disease.
  • In X-linked diseases, the causative genetic mutation is located on the X chromosome. When females inherit a single defective X-linked gene, the normal copy of the gene located on the other X chromosome often compensates for the defective gene. Males need to inherit only one copy of a mutant gene to inherit an X-linked single gene disorder, even if the disease has a recessive inheritance pattern. This is because males have only one X chromosome and therefore do not have a "backup" copy of the gene to compensate for the defective gene. This is why some X-linked single gene disorders are more common in males than females.
  • In some cases, single gene disorders are not inherited. Rather, they may be caused by a spontaneous or random genetic mutation that occurs during egg or sperm development or embryonic development.
  • Many human diseases are known to be single gene disorders. Acid maltase deficiency, a disease in which patients experience a progressive loss of muscle function, is a recessive single gene disorder caused by mutations in the acid alpha-glucosidase gene. Normally, this gene provides instructions for making a protein called the acid alpha-glucosidase enzyme. This enzyme breaks down glycogen in muscle cells to supply energy to the cells. Autoimmune lymphoproliferative syndrome is a dominant single gene disorder caused by mutations in the Fas gene, which normally functions to cause specific cells to die (such as lymphocytes). Autoimmune lymphoproliferative syndrome is an autoimmune disorder, meaning the immune system malfunctions and begins to attack normal components of the body.

Methods
  • Classification: Single gene disorders may be classified as dominant or recessive based on their pattern of inheritance. Only one parent must carry a disease-causing genetic mutation for a child to inherit the trait for a dominant disorder, but both parents must carry a mutation for a child to be at risk for a recessive disorder in most cases. Therefore, diseases with a dominant inheritance pattern generally affect people more frequently than those with recessive patterns. By examining families with a history of a disease and observing the pattern by which the disease is inherited, researchers or doctors may be able to classify a specific single gene disorder as dominant or recessive.
  • Identification of mutation: Humans contain thousands of genes, and different single gene disorders are caused by mutations in different genes. For some single gene disorders, researchers have already identified the underlying genetic mutation. To find a causative mutation for a particular single gene disorder, researchers may perform a detailed comparison between chromosomes from people with a specific disease and those from healthy individuals. By looking for similar features in a DNA sequence (the order of chemical bases in DNA) that appear among the people with a specific disease but not among the healthy individuals, researchers may be able to determine which chromosomal region is mutated in the affected people and likely responsible for causing the disease. Once a disease-causing mutation is identified, however, researchers may need to perform a variety of additional experiments in the laboratory to determine how that mutation causes a disease. Additional experiments may involve deactivating the gene in cells or in model organisms or identifying other proteins that interact with the protein made by the gene of interest.
  • Patient diagnosis: Once a causative mutation for a single gene disorder is identified, doctors may perform genetic testing to look for that mutation in patients to help diagnose a disease. Commonly, genetic testing may be performed by removing a small amount of a patient's blood and extracting the patient's DNA. To check for mutations in the DNA, a technique called polymerase chain reaction (PCR) may be used. PCR allows a researcher to generate many copies of a specific DNA sequence from a small sample. After DNA is amplified, or copied, using PCR, researchers may sequence the DNA to check for the mutation.
  • If there is a family history of disease, parents may also choose to perform prenatal genetic screening on a developing fetus. Genetic testing may be performed on a developing fetus through amniocentesis, in which the amniotic fluid surrounding the fetus is sampled through a needle inserted into the mother's abdomen. Chorionic villus sampling (CVS) is another type of prenatal diagnosis that can detect genetic problems in a fetus. Samples are taken from the chorionic villus, or placental tissue. Any prenatal test carries a risk of miscarriage because these tests are invasive procedures that may disturb or damage the fetus. Consent is needed to perform prenatal testing.

Research
  • A number of single gene disorders that affect humans have been identified. In some cases, researchers have been able to determine which gene is mutated in a particular disease and they have used this information to better understand how the mutation causes the disease.
  • Acid maltase deficiency: Acid maltase deficiency (AMD) is a single gene disorder that affects muscle function. AMD is caused by mutations in a gene called acid alpha-glucosidase or GAA. Normally, this gene provides instructions for making a protein called the acid alpha-glucosidase enzyme, also called the acid maltase enzyme. In patients with AMD, these mutations cause the acid alpha-glucosidase enzyme to lose most or all of its normal function in muscle cells to break down glycogen, a form of starch used to store short-term energy. Without this breaking down process, glycogen builds up the in the muscles of people with AMD, which causes damage to the muscles and can lead to progressive muscle weakening. This glycogen buildup may also weaken the muscles of the heart and respiratory system. Cardiac or respiratory failure is the most common cause of death in patients with AMD.
  • AMD is a recessive single gene disorder. Individuals who inherit two copies of a mutant GAA gene will develop AMD. Individuals who inherit only one copy of the mutation may not have symptoms of AMD but are known as "carriers" because they can pass on the mutation to their children.
  • If one parent has one copy of the mutated gene, then each child will have a 50% chance of inheriting one mutated gene and also of being a carrier. If both parents are carriers, each child has a 25% chance of inheriting two mutated genes, a 50% chance of inheriting only one mutated gene, and a 25% chance of inheriting neither of the mutated genes. Thus, if both parents are carriers, approximately one out of every four children will develop AMD. If one parent has AMD and the other parent does not carry the trait, then all of the children will be carriers. If one parent has AMD and the other parent is a carrier, then each child has a 50% chance of having AMD and a 50% chance of being a carrier. If both parents have AMD, then all of their children will also have AMD.
  • Autoimmune lymphoproliferative syndrome: Autoimmune lymphoproliferative syndrome (ALPS) is a condition that usually develops in early childhood. Normally, the immune system attacks foreign invaders, such as bacteria. Antibodies are a component of the immune system that normally attack foreign invaders to help destroy them. In autoimmune conditions, the immune system malfunctions and begins to attack its own tissues.
  • Patients with ALPS have a mutation, or error, in a gene called Fas, which normally functions to cause specific cells, such as lymphocytes, to die. If these cells do not undergo death, their accumulation may lead to disease. A defect in the Fas gene could reduce the amount of cell death among lymphocytes after they have finished fighting an infection, leading to higher numbers of lymphocytes that continue to create antibodies. Some of the antibodies that the extra lymphocytes produce attack normal components of the body, such as red blood cells or platelets, causing them to malfunction. Common symptoms that patients may display include weakness, bruises or nosebleeds, or increased risk of bacterial infection.
  • ALPS is a dominant single gene disorder. For a dominant disorder to appear, only one defective copy of the Fas gene has to have been inherited. If one parent has the disorder, there is a 50% chance that his or her child will have the disorder. If both parents have the disorder, there is a 75% chance that their child will have the disorder.

Implications
  • Diagnose disease: When a specific causative genetic mutation for a single gene disorder is known, genetic testing for that mutation can be used to diagnose the disease in patients. Genetic testing is most often used when patients have a family history of a disease or to confirm a diagnosis.
  • Fight disease: The identification of mutations that cause single gene disorders may help researchers fight disease. This is because mutations may cause certain genes to malfunction or be produced at reduced or increased levels. Identifying these abnormalities in gene function or levels may help researchers better understand how a disease is caused. This information may in turn help develop drugs to fight disease.

Limitations
  • Not applicable.

Safety




Future research
  • Even if a disease is known to be a single gene disorder, additional work may be needed to understand the disease. For example, researchers are still searching for the specific gene that is mutated in some single gene disorders. Aicardi syndrome, a neurological condition in which patients experience spasms, seizures, mental insufficiency, and/or lesions on the retina, is thought to be caused by a genetic mutation on the X chromosome, but the specific mutated gene has not yet been identified. Also, for single gene disorders in which the causative genetic mutation is known, researchers may need to perform additional experiments to better understand how that mutation actually causes a disease. When a specific causative genetic mutation has been identified, it may help researchers develop therapies or drugs that target a particular gene or treatments that replace the function of a defective gene.

Author information
  • This information has been edited and peer-reviewed by contributors to the Natural Standard Research Collaboration (www.naturalstandard.com).

Bibliography
  1. Amato AA. Acid maltase deficiency and related myopathies. Neurol Clin. 2000 Feb;18(1):151-65.
  2. Genetics Home Reference. .
  3. Holzelova E, Vonarbourg C, Stolzenberg MC, et al. Autoimmune lymphoproliferative syndrome with somatic Fas mutations. N Engl J Med. 2004 Sep 30;351(14):1409-18.
  4. National Human Genome Research Institute. .
  5. National Library of Medicine. . Accessed July 1, 2008
  6. Natural Standard: The Authority on Integrative Medicine. .
  7. Raben N, Nichols RC, Boerkoel C, et al. Genetic defects in patients with glycogenesis type II (acid maltase deficiency). Muscle Nerve. 1995;3:S70-4.
  8. Rieux-Laucat F, Le Deist F, Fischer A. Autoimmune lymphoproliferative syndromes: genetic defects of apoptosis pathways. Cell Death Differ. 2003 Jan;10(1):124-33.
  9. Worth A, Thrasher AJ, Gaspar HB. Autoimmune lymphoproliferative syndrome: molecular basis of disease and clinical phenotype. Br J Haematol. 2006 Apr;133(2):124-40.

Copyright © 2011 Natural Standard (www.naturalstandard.com)


The information in this monograph is intended for informational purposes only, and is meant to help users better understand health concerns. Information is based on review of scientific research data, historical practice patterns, and clinical experience. This information should not be interpreted as specific medical advice. Users should consult with a qualified healthcare provider for specific questions regarding therapies, diagnosis and/or health conditions, prior to making therapeutic decisions.

Search Site