Autosomal Dominant Inheritance
Autosomal dominant inheritance is due to a dominant allele carried on one of the autosomes. Autosomal dominant alleles need only be inherited from one parent, either the mother or the father, in order to be expressed in the phenotype. Because of this, any child has a 50 percent chance of inheriting the allele and expressing the trait if one parent has it.
Many normal human traits are due to autosomal dominant alleles, including the presence of dimples, a cleft chin, and a widow's-peak hairline. Note that dominant does not necessarily mean common. Dominant alleles can be rare in a population, and do not spread simply because they are dominant. This phenomenon is explained by the theory known as Hardy-Weinberg equilibrium.
There are hundreds of medical conditions due to autosomal dominant alleles, most of them very rare. They include neurodegenerative disorders such as Huntington's disease, a variety of deafness syndromes, and metabolic disorders such as familial hypercholesterolemia (affecting blood cholesterol levels) and variegate porphyria (affecting the oxygen-carrying porphyrin molecule). Table 1 lists some other examples.
Because inheritance of a harmful dominant allele can be lethal, these alleles tend to be quite rare in the population, and new mutations account for many cases of these conditions. Exceptions include late-onset disorders such as Huntington's disease, in which parents may pass on the gene to off-spring before developing the symptoms of the disease. Other exceptions arise from incomplete penetrance, in which the allele is present, but (for reasons usually unknown) it is not expressed. Genomic imprinting (see below) may explain some cases of incomplete penetrance. Variable expressivity is also possible, in which different individuals express the trait with different levels of severity.
|Condition||Chromosome Location and Inheritance Pattern||Protein Affected||Symptoms and Comments|
|Gaucher Disease||1, recessive||glycohydrolase glucocerebrosidase, a lipid metabolism enzyme||Common among European Jews. Lipid accumulation in liver, spleen, and bone marrow. Treat with enzyme replacement|
|Achondroplasia||4, dominant||fibroblast growth factor receptor 3||Causes dwarfism. Most cases are new mutations, not inherited|
|Huntington's Disease||4, dominant||huntingtin, function unknown||Expansion of a three-nucleotide portion of the gene causes late-onset neurodegeneration and death|
|Juvenile Onset Diabetes||6, 11, 7, others||IDDM1, IDDM2, GCK, other genes||Multiple susceptibility alleles are known for this form of diabetes, a disorder of blood sugar regulation. Treated with dietary control and insulin injection|
|Hemochromatosis||6, recessive||HFE protein, involved in iron absorption from the gut||Defect leads to excess iron accumulation, liver damage. Menstruation reduces iron in women. Bloodletting used as a treatment|
|Cystic Fibrosis||7, recessive||cystic fibrosis transmembrane regulator, in ion channel||Sticky secretions in the lungs impairs breathing, and in the pancreas impairs digestion. Enzyme supplements help digestive problems|
|Friedreich's Ataxia||9, recessive||frataxin, mitochondrial protein of unknown function||Loss of function of this protein in mitochondria causes progressive loss of coordination and heart disease|
|Albinism||11, recessive||tyorsinase||Lack of pigment in skin, hair, eyes; loss of visual acuity|
|Best Disease||11, dominat||VMD2 gene, protein function unknown||Gradual loss of visual acuity|
|Sickle Cell Disease||11, recessive||hemoglobin beta subunit, oxygen transport protein in blood cells||Change in hemoglobin shape alters cell shape, decreases oxygen-carrying ability, leads to joint pain, anemia, and infections. Carriers are resistant to malaria. About 8% of US black population are carriers|
|Phenylketonuria||12, recessive||phenylalanine hydroxylase, an amino acid metabolism enzyme||Inability to breakdown the amino acid phenylalanine causes mental retardation. Dietary avoidance can minimize effects. Postnatal screening is widely done|
|Marfan Syndrome||15, dominant||fibrillin, a structural protein of connective tissue||Scoliosis, nearsightedness, heart defects, and other symptoms|
|Tay-Sachs Disease||15, recessive||beta-hexosaminidase A, a lipid metabolism enzyme||Accumulation of the lipid GM2 ganglioside in neurons leads to death in childhood|
|Breast Cancer||17, 13||BRCA1, BRCA2 genes||Susceptibility alleles for breast cancer are thought to involve reduced ability to repair damaged DNA|
|Myotonic Dystrophy||19, dominant||dystrophia myotonica protein kinase, a regulatory protein in muscle||Muscle weakness, wasting, impaired intelligence, cataracts|
|familial hypercholesterolemia||19, incomplete dominance||low-density lipoprotein (LDL) receptor adenosine deaminase, nucleotide metabolism enzyme||Accumulation of cholesterol-carrying LDL in the bloodstream leads to heart disease and heart attack|
|Severe Combined Immune Deficiency ("Bubble Boy" Disease)||20, recessive||respiratory complex proteins||Immature white blood cells die from accumulation of metabolic products, leading to complete loss of the immune response. Gene therapy has been a limited success|
|Leber's Hereditary Optic Neuropathy||mitochondria, maternal inheritance||transfer RNA||degeneration of the central portion of the optic nerve, loss of central vision|
|Mitochondrial Encephalopathy, Lactic Acidosis, and Stroke (MELAS)||mitochondria, maternal inheritance||lignoceroyl-CoA ligase, in peroxisomes||recurring, stroke-like episodes in which sudden headaches are followed by vomiting and seizures; musle weakness|
|Adrenoleukodystrophy||X||dystrophin, muscle structural protein||Defect causes build-up of long-chain fatty acids. Degeneration of the adrenal gland, loss of myelin insulation in nerves. Featured in the film "Lorenzo's Oil"|
|Duchenne Muscular Dystrophy||X||Factor VIII, part of the blood clotting cascade||Lack of dystrophin leads to muscle breakdown, weakness, and impaired breathing|
|Hemophilia A||X||Uncontrolled bleeding, can be treated with injections or replacement protein|
|Rett Syndrome||X||methyl CpG-binding protein 2, regulates DNA transcription||Most boys die before birth. Girls develop mental retardation, mutism and movment disorder|
- Inheritance Patterns - Autosomal Recessive Inheritance
- Inheritance Patterns - Molecular Meaning Of Dominance And Recessiveness
- Other Free Encyclopedias
Medicine EncyclopediaGenetics in Medicine - Part 2Inheritance Patterns - Phenotype And Genotype, Alleles, Dominance Relations, Molecular Meaning Of Dominance And Recessiveness, Autosomal Dominant Inheritance - Mitochondrial Inheritance