Genetics Basics - Lesson 3: Modes of Inheritance
3.1 Modes of Inheritance
Inheritance patterns describe how a disease is transmitted in families.
These patterns help to predict the recurrence risk for relatives.
In general, inheritance patterns for single gene disorders are classified based on whether they are autosomal or X-linked and whether they have a dominant or recessive pattern of inheritance. These disorders are called Mendelian disorders, after the geneticist Gregor Mendel.
3.2 Autosomal Dominant Inheritance
With each pregnancy, there is a one in two (50%) chance the offspring will inherit the disease allele.
Unless a new mutation has occurred, all affected individuals will have at least one parent who carries the disease allele.
Autosomal dominant inheritance is often called vertical inheritance because of the transmission from parent to offspring.
Across a population, the proportion of affected males should be equal to the proportion of affected females.
Male-to-male transmission can be observed.
3.3 Autosomal Recessive Inheritance
In autosomal recessive inheritance, two copies of a disease allele are required for an individual to be susceptible to expressing the phenotype.
Typically, the parents of an affected individual are not affected but are gene carriers.
With each pregnancy of carrier parents:
There is a one in four (25%) chance the offspring will inherit two copies of the disease allele and will therefore have the phenotype.
There is a one in two (50%) chance the offspring will inherit one copy of the disease allele and will be a carrier.
There is a one in four (25%) chance the offspring will inherit no copies of the disease allele and will not express the phenotype or be a carrier. This individual would not be at risk for passing the disorder on to his/her offspring.
As with autosomal dominant inheritance, the proportion of affected males should be equal to the proportion of affected females in a given population.
Examples of diseases with autosomal recessive inheritance include sickle cell anemia and cystic fibrosis.
Clinical Information on Diseases
3.3.1 Autosomal Recessive Diseases
Autosomal recessive diseases are observed more frequently in consanguineous relationships (relationships in which the couple is related by blood, such as first cousins) because the individuals are descendants of the same ancestors and are, therefore, more likely to carry the same gene mutations.
Many autosomal recessive disorders are seen more frequently in individuals of certain ethnic backgrounds than others because these individuals are descendants of the same ancestors. However, because these common ancestors are generally more distantly related to these individuals, couples of the same ethnic background would generally have fewer genes in common than consanguineous couples.
3.4 X-Linked Dominant Inheritance
As in autosomal dominant inheritance, only one copy of a disease allele on the X chromosome is required for an individual to be susceptible to an X-linked dominant disease.
Both males and females can be affected, although males may be more severely affected because they only carry one copy of genes found on the X chromosome. Some X-linked dominant disorders are lethal in males.
When a female is affected, each pregnancy will have a one in two (50%) chance for the offspring to inherit the disease allele. When a male is affected, all his daughters will be affected, but none of his sons will be affected.
3.4.1 Oral-Facial-Digital syndrome type I
3.5 X-Linked Recessive Inheritance
As in autosomal recessive inheritance, two copies of a disease allele on the X chromosome are required for an individual with two X chromosomes (a female) to be affected with an X-linked recessive disease.
Since males are hemizygous for X-linked genes (they have only one X chromosome), any male with one copy of an X-linked recessive disease allele is affected.
Females are usually carriers because they only have one copy of the disease allele. Affected males are related through carrier females.
For a carrier female, with each pregnancy there is a one in two (50%) chance her sons will inherit the disease allele and a one in two (50%) chance her daughters will be carriers.
Affected males transmit the disease allele to all of their daughters, who are then carriers, but to none of their sons.
Women are affected when they have two copies of the disease allele. All of their sons will be affected, and all of their daughters will be unaffected carriers.
(A) Hair and (B) teeth of a male with ectodermal dysplasia.
3.5.1 Hypohidrotic or anhidrotic ectodermal dysplasia
3.6 Complex Inheritance
Complex disorders (once known as multifactorial disorders) are caused by the interactions of variations in multiple genes and environmental factors.
The genes involved may make a person susceptible to the disorder, and the environmental factors may trigger this susceptibility.
The liability to exhibit the phenotype of the complex disorder is determined by both genetic and environmental factors. Only individuals with enough genetic liability (multiple genes) who are in the presence of certain environmental factors will exhibit the phenotype. The threshold is the point at which these factors combine sufficiently for the individuals to exhibit the phenotype.
Complex disorders are often common disorders in the population and include heart disease, diabetes, asthma, and many birth defects, such as cleft lip +/- cleft palate.
|(A) Severe and (B) mild forms of cleft lip +/- palate.
(Reprinted from Emery’s Elements of Medical Genetics, 10th ed., Mueller R.F. and Young I.D., ©1998, with permission from Elsevier Science.)
3.6.1 Cleft Lip +/- Cleft Palate
Recurrence Risks to Siblings
|Unilateral isolated cleft lip||4.0%|
|Unilateral cleft lip and palate||4.9%|
|Bilateral isolated cleft lip||6.7%|
|Bilateral cleft lip and palate||8.0%|