Inheritance patterns trace the transmission of genetically encoded traits, conditions or diseases to offspring. There are several modes of inheritance:
Note: These explanations use pedigrees to illustrate inheritance patterns. If you are unfamiliar with pedigrees, see Pedigrees for an explanation of the symbols.
Single Gene Inheritance
Genetic conditions caused by a mutation in a single gene follow predictable patterns of inheritance within families. Single gene inheritance is also referred to as Mendelian inheritance as they follow transmission patterns he observed in his research on peas. There are four types of Mendelian inheritance patterns:
Autosomal: the gene responsible for the phenotype is located on one of the 22 pairs of autosomes (non-sex determining chromosomes).
X-linked: the gene that encodes for the trait is located on the X chromosome.
Dominant: conditions that are manifest in heterozygotes (individuals with just one copy of the mutant allele).
Recessive: conditions are only manifest in individuals who have two copies of the mutant allele (are homozygous).
Dominant conditions are expressed in individuals who have just one copy of the mutant allele. The pedigree on the right illustrates the transmission of an autosomal dominant trait. Affected males and females have an equal probability of passing on the trait to offspring. Affected individual’s have one normal copy of the gene and one mutant copy of the gene, thus each offspring has a 50% chance on inheriting the mutant allele. As shown in this pedigree, approximately half of the children of affected parents inherit the condition and half do not.
Autosomal Dominant Conditions: • Huntington Disease • acondroplasia (short-limbed dwarfism) • polycystic kidney disease
Recessive conditions are clinically manifest only when an individual has two copies of the mutant allele. When just one copy of the mutant allele is present, an individual is a carrier of the mutation, but does not develop the condition. Females and males are affected equally by traits transmitted by autosomal recessive inheritance. When two carriers mate, each child has a 25% chance of being homozygous wild-type (unaffected); a 25% chance of being homozygous mutant (affected); or a 50% chance of being heterozygous (unaffected carrier).
Affected individuals are indicated by solid black symbols and unaffected carriers are indicated by the half black symbols.
Autosomal recessive diseases: • Cystic fibrosis • Tay-Sachs • hemochromatosis • phenylketonuria (PKU)
X-linked recessive traits are not clinically manifest when there is a normal copy of the gene. All X-linked recessive traits are fully evident in males because they only have one copy of the X chromosome, thus do not have a normal copy of the gene to compensate for the mutant copy. For that same reason, women are rarely affected by X-linked recessive diseases, however they are affected when they have two copies of the mutant allele. Because the gene is on the X chromosome there is no father to son transmission, but there is father to daughter and mother to daughter and son transmission. If a man is affected with an X-linked recessive condition, all his daughter will inherit one copy of the mutant allele from him.
X-linked Recessive Disorders: • Duchenne muscular dystrophy • hemophilia A • X-linked severe combined immune disorder (SCID) • some forms of congenital deafness
Because the gene is located on the X chromosome, there is no transmission from father to son, but there can be transmission from father to daughter (all daughters of an affected male will be affected since the father has only one X chromosome to transmit). Children of an affected woman have a 50% chance of inheriting the X chromosome with the mutant allele. X-linked dominant disorders are clinically manifest when only one copy of the mutant allele is present.
X-linked Dominant Disorders • some forms of retinitis pigmentosa • Chondrodysplasia Punctata • hypophosphatemic rickets
Most diseases have multifactorial inheritance patterns. As the name implies, multifactorial conditions are not caused by a single gene, but rather are a result of interplay between genetic factors and environmental factors. Diseases with multifactorial inheritance are not genetically determined, but rather a genetic mutation may predispose an individual to a disease. Other genetic and environmental factors contribute to whether or not the disease develops.
Numerous genetic alterations may predispose individuals to the same disease (genetic heterogeneity). For instance coronary heart disease risk factors include high blood pressure, diabetes, and hyperlipidemia. All of those risk factors have their own genetic and environmental components. Thus multifactorial inheritance is far more complex than Mendelian inheritance and is more difficult to trace through pedigrees.
A typical pedigree from a family with a mutation in the BRCA1 gene. Fathers can be carriers and pass the mutation onto offspring. Not all people who inherit the mutation develop the disease, thus patterns of transmission are not always obvious.
Conditions with multifactorial inheritance:
• Alzheimers disease • heart disease • some cancers • neural tube defects • schizophrenia • insulin-dependent diabetes mellitus • intelligence
Mitochondria are organelles found in the cytoplasm of cells. Mitochondria are unique in that they have multiple copies of a circular chromosome. Mitochondria are only inherited from the mother’s egg, thus only females can transmit the trait to offspring, however they pass it on to all of their offspring. The primary function of mitochondria is conversion of molecule into usable energy. Thus many diseases transmitted by mitochondrial inheritance affect organs with high-energy use such as the heart, skeletal muscle, liver, and kidneys.