4 minute read

Inheritance Patterns

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.

Table 1.

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

Additional topics

Medicine EncyclopediaGenetics in Medicine - Part 2Inheritance Patterns - Phenotype And Genotype, Alleles, Dominance Relations, Molecular Meaning Of Dominance And Recessiveness, Autosomal Dominant Inheritance - Mitochondrial Inheritance