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What are the different ways in which a genetic condition can be inherited?
Some genetic conditions are caused by mutations in a single gene. These conditions are usually inherited in one of several straightforward patterns, depending on the gene involved:
Many other disorders are caused by a combination of the effects of multiple genes or by interactions between genes and the environment. Such disorders are more difficult to analyze because their genetic causes are often unclear, and they do not follow the patterns of inheritance described above. Examples of conditions caused by multiple genes or gene/environment interactions include heart disease, diabetes, schizophrenia, and certain types of cancer. For more information, please see What are complex or multifactorial disorders? (http://ghr.nlm.nih.gov/handbook/ mutationsanddisorders/complexdisorders).
Disorders caused by changes in the number or structure of chromosomes do not follow the straightforward patterns of inheritance listed above. To read about how chromosomal conditions occur, please see Are chromosomal disorders inherited? (http://ghr.nlm.nih.gov/handbook/inheritance/chromosomalinheritance).
Other genetic factors can also influence how a disorder is inherited: What are genomic imprinting and uniparental disomy? (http://ghr.nlm.nih.gov/handbook/ inheritance/updimprinting)
For more information about inheritance patterns:
The Genetics and Public Policy Center provides an introduction to genetic inheritance patterns (http://www.dnapolicy.org/science.gh.php).
The Centre for Genetics Education provides information about each of the inheritance patterns outlined above:
• Autosomal dominant inheritance (http://www.genetics.edu.au/lnformation/ Genetics-Fact-Sheets/Autosomal-Dominant-lnheritance-FS9)
• Autosomal recessive inheritance (http://www.genetics.edu.au/lnformation/ Genetics-Fact-Sheets/Autosomal-Recessive-lnheritance-FS8)
• X-linked inheritance (http://www.genetics.edu.au/lnformation/Genetics- Fact-Sheets/X-Linked-lnheritance-FS10)
• Mitochondrial inheritance (http://www.genetics.edu.au/lnformation/ Genetics-Fact-Sheets/Mitochondial-lnheritance-Complex-Patterns-of- lnheritance-2-FS12)
Additional information about inheritance patterns is available from The Merck Manual (http://www.merckmanuals.com/professional/special_subjects/general_principles_ of_medical_genetics/single-gene_defects.html).
Illustrations
In this example, a man with an autosomal dominant disorder has two affected children and two unaffected children.
In this example, two unaffected parents each carry one copy of a gene mutation for an autosomal recessive disorder. They have one affected child and three unaffected children, two of which carry one copy of the gene mutation.
In this example, a man with an X-linked dominant condition has two affected daughters and two unaffected sons.
In this example, a woman with an X-linked dominant condition has an affected daughter, an affected son, an unaffected daughter, and an unaffected son.
In this example, a man with an X-linked recessive condition has two unaffected daughters who each carry one copy of the gene mutation, and two unaffected sons who do not have the mutation.
In this example, an unaffected woman carries one copy of a gene mutation for an X-linked recessive disorder. She has an affected son, an unaffected daughter who carries one copy of the mutation, and two unaffected children who do not have the mutation.
The ABO blood group is a major system for classifying blood types in humans. Blood type AB is inherited in a codominant pattern. In this example, a father with blood type A and a mother with blood type B have four children, each with a different blood type: A, AB, B, and O.
In one family, a woman with a disorder caused by a mutation in mitochondrial DNA and her unaffected husband have only affected children. In another family, a man with a condition resulting from a mutation in mitochondrial DNA and his unaffected wife have no affected children.
If a genetic disorder runs in my family, what are the chances that my children will have the condition?
When a genetic disorder is diagnosed in a family, family members often want to know the likelihood that they or their children will develop the condition. This can be difficult to predict in some cases because many factors influence a person's chances of developing a genetic condition. One important factor is how the condition is inherited. For example:
• Autosomal dominant inheritance: A person affected by an autosomal dominant disorder has a 50 percent chance of passing the mutated gene to each child. The chance that a child will not inherit the mutated gene is also 50 percent (illustration on page 82).
• Autosomal recessive inheritance: Two unaffected people who each carry one copy of the mutated gene for an autosomal recessive disorder (carriers) have a 25 percent chance with each pregnancy of having a child affected by the disorder. The chance with each pregnancy of having an unaffected child who is a carrier of the disorder is 50 percent, and the chance that a child will not have the disorder and will not be a carrier is 25 percent (illustration on page 83).
• X-linked dominant inheritance: The chance of passing on an X-linked dominant condition differs between men and women because men have one X chromosome and one Y chromosome, while women have two X chromosomes. A man passes on his Y chromosome to all of his sons and his X chromosome to all of his daughters. Therefore, the sons of a man with an X-linked dominant disorder will not be affected, but all of his daughters will inherit the condition (illustration on page 84). A woman passes on one or the other of her X chromosomes to each child. Therefore, a woman with an X-linked dominant disorder has a 50 percent chance of having an affected daughter or son with each pregnancy (illustration on page 85).
• X-linked recessive inheritance: Because of the difference in sex chromosomes, the probability of passing on an X-linked recessive disorder also differs between men and women. The sons of a man with an X-linked recessive disorder will not be affected, and his daughters will carry one copy of the mutated gene (illustration on page 86). With each pregnancy, a woman who carries an X-linked recessive disorder has a 50 percent chance of having sons who are affected and a 50 percent chance of having daughters who carry one copy of the mutated gene (illustration on page 87).
• Codominant inheritance: In codominant inheritance, each parent contributes a different version of a particular gene, and both versions influence the resulting genetic trait. The chance of developing a genetic condition with codominant inheritance, and the characteristic features of that condition, depend on which versions of the gene are passed from parents to their child (illustration on page 88).
• Mitochondrial inheritance: Mitochondria, which are the energy-producing centers inside cells, each contain a small amount of DNA. Disorders with mitochondrial inheritance result from mutations in mitochondrial DNA. Although these disorders can affect both males and females, only females can pass mutations in mitochondrial DNA to their children. A woman with a disorder caused by changes in mitochondrial DNA will pass the mutation to all of her daughters and sons, but the children of a man with such a disorder will not inherit the mutation (illustration on page 89).
It is important to note that the chance of passing on a genetic condition applies equally to each pregnancy. For example, if a couple has a child with an autosomal recessive disorder, the chance of having another child with the disorder is still 25 percent (or 1 in 4). Having one child with a disorder does not "protect" future children from inheriting the condition. Conversely, having a child without the condition does not mean that future children will definitely be affected.
Although the chances of inheriting a genetic condition appear straightforward, factors such as a person's family history and the results of genetic testing can sometimes modify those chances. In addition, some people with a disease-causing mutation never develop any health problems or may experience only mild symptoms of the disorder. If a disease that runs in a family does not have a clear-cut inheritance pattern, predicting the likelihood that a person will develop the condition can be particularly difficult.
Estimating the chance of developing or passing on a genetic disorder can be complex. Genetics professionals can help people understand these chances and help them make informed decisions about their health.
For more information about passing on a genetic disorder in a family:
The National Library of Medicine MedlinePlus web site offers information about the chance of developing a genetic disorder on the basis of its inheritance pattern. Scroll down to the section "Statistical Chances of Inheriting a Trait" for each of the following inheritance patterns:
• Autosomal dominant (http://www.nlm.nih.gov/medlineplus/ency/article/ 002049.htm)
• Autosomal recessive (http://www.nlm.nih.gov/medlineplus/ency/article/ 002052.htm)
• X-linked dominant (http://www.nlm.nih.gov/medlineplus/ency/article/ 002050.htm)
• X-linked recessive (http://www.nlm.nih.gov/medlineplus/ency/article/ 002051.htm)
The Centre for Genetics Education (Australia) provides an explanation of mitochondrial inheritance (http://www.genetics.edu.au/lnformation/Genetics-Fact- Sheets/Mitochondial-lnheritance-Complex-Patterns-of-lnheritance-2-FS12).
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