Genetic disorders determined by a single gene (Mendelian disorders) are easiest to analyze and the most well understood. If expression of a trait requires only one copy of a gene (one allele), that trait is considered dominant. If expression of a trait requires 2 copies of a gene (2 alleles), that trait is considered recessive. An exception is X-linked disorders. Because males usually have no paired allele to offset the effects of most alleles on the X chromosome, the X chromosome allele is expressed in males even if the trait is recessive.
Table 1
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Examples of Genetic Disorders With Mendelian Inheritance |
Gene
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Dominant
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Recessive
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Non–X-linked
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Marfan syndrome
Huntington's disease
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Cystic fibrosis
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X-linked
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Familial rickets
Hereditary nephritis
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Red–green color blindness
Hemophilia
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Many specific disorders have been described (see Table 1: General Principles of Medical Genetics: Examples of Genetic Disorders With Mendelian Inheritance).
Autosomal Dominant
Only one abnormal allele of a gene is needed to express an autosomal dominant trait; ie, heterozygotes and homozygotes for the abnormal gene are affected. A typical pedigree of an autosomal dominant trait is shown in Fig. 2: General Principles of Medical Genetics: Autosomal dominant inheritance..
In general, the following rules apply:
Autosomal Recessive
Two copies of an abnormal allele are needed to express an autosomal recessive trait. An example of a pedigree is shown in Fig. 3: General Principles of Medical Genetics: Autosomal recessive inheritance..
In general, the following rules of inheritance apply:
Relatives are more likely to carry the same mutant allele, so mating between close relatives (consanguinity) increases the likelihood of having affected children. In parent-child or brother-sister unions (incest), the risk of having abnormal children is increased because so much of their genetic material is the same. In certain populations, the percentage of heterozygotes (carriers) is high because of a founder effect (ie, the group started with few members, one of whom was a carrier) or because carriers have a selective advantage (eg, heterozygosity for sickle cell anemia protects against malaria).
If the trait results in a defect of a specific protein (eg, an enzyme), heterozygotes usually have a reduced amount of that protein. If the mutation is known, molecular genetic techniques can identify heterozygous phenotypically normal people (eg, those with cystic fibrosis most of the time).
X-Linked Dominant
X-linked dominant traits are carried on the X chromosome. Most are rare. Usually, males are more severely affected; some X-linked dominant disorders are often lethal in males. Females who carry only one abnormal allele are affected, but less severely. A typical pedigree is shown in Fig. 4: General Principles of Medical Genetics: X-linked dominant inheritance..
In general, the following rules of inheritance apply:
X-linked dominant inheritance may be difficult to differentiate from autosomal dominant inheritance by studying only inheritance patterns. Large pedigrees are required, with particular attention to children of affected males because male-to-male transmission rules out X-linkage (males pass only their Y chromosomes to their sons).
X-Linked Recessive
X-linked recessive traits are carried on the X chromosome. Thus, nearly all affected people are male because most females have one normal copy of the involved gene (ie, they are heterozygous). A typical pedigree is shown in Fig. 5: General Principles of Medical Genetics: X-linked recessive inheritance..
In general, the following rules of inheritance apply:
Occasionally, females who are heterozygous for X-linked mutations show some expression, but they are rarely affected as severely as affected males.
Last full review/revision May 2007 by Judith G. Hall, MD
Content last modified February 2012
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