When speaking of an inherited disease, health professionals often use the disease’s pattern or mode of inheritance to estimate the risk for that disease to occur in a family.
Therefore, your family’s health history is a major factor in determining the likelihood of you, or of someone in your family, having a wide range of inherited disorders. By using AccessDNA's family history tool, you will be taking an essential step towards learning your risk of having or passing down these diseases. Click below to use the tool or scroll down to read more about patterns of inheritance.
Definition
A pattern (mode) of inheritance is the manner in which a particular genetic trait or genetic condition is passed from one generation to the next. Common modes of inheritance are listed below.
Autosomal Dominant Inheritance
An autosomal dominant condition means that the condition is expressed in people who have one damaged copy of the gene. These conditions are caused by genes that are located on chromosomes other than the sex chromosomes (X and Y). Autosomal dominant conditions typically include the following characteristics:
- Both males and females can be affected equally and the condition can be inherited from either parent.
- There is no such thing as "skipping" people (or generations).
- Multiple generations may be affected in a family.
- Some people are the first one to be affected in their family, as a result of a new ("de novo"), sporadic mutation in the germline cells (egg and sperm cells).
Risks to children:
- When only one parent is affected, every child he/she has a 50% chance to be affected and a 50% chance to be unaffected.
- When both parents are affected, every child they have has a 75% chance to be affected, and a 25% chance to not be affected. Of note, in some conditions having two damaged copies of the gene is too severe and may not be compatible with life.
Autosomal dominant inheritance with incomplete penetrance is the major exception to the rule. Penetrance refers to the percentage of people with the damaged gene that show the physical feature and symptoms of the disorder. Most autosomal dominant conditions have complete penetrance, but some have incomplete (or reduced) penetrance. Incomplete penetrance is most likely a result of the way the gene interacts with other genes as well as the environment. Lastly, it may cause the disorder to look like it is "skipping" people or generations, while in reality it is not. An example of a condition with incomplete penetrance includes some familial types of Parkinson's disease.
Autosomal Recessive Inheritance
An autosomal recessive condition means that the condition is expressed in people who have two damaged copies of the same gene (or one damaged copy from each parent). Some of them occur in higher frequencies in certain ethnic groups. These conditions are caused by genes that are located on chromosomes other than the sex chromosomes, X and Y. Autosomal recessive conditions typically include the following characteristics:
- Both males and females can be affected equally.
- People with one damaged copy of the gene are called carriers (or heterozygous for the gene) and usually do not have any symptoms of the condition.
- Affected people (or people who are homozygous for the gene) are often born to unaffected, carrier parents.
- Multiple generations are typically not affected, while people within the same generation, such as siblings, are affected.
- People who share common relatives (such as some religious communities, isolated populations, or marrying within the same family) are more likely to be affected.
Risks to children:
- When both parents are carriers, every child they have has a 25% chance of being affected, a 50% chance to be a carrier, and a 25% to neither be affected nor a carrier.
- When one parent is a carrier and the other is not a carrier or affected, every child they have has a 50% chance to be a carrier and a 50% chance to neither be a carrier nor affected. No child will be affected.
- When one parent is affected, and the other parent is a carrier, every child they have has a 50% chance to be affected and a 50% chance to be a carrier.
- When one parent is affected and the other is not a carrier or affected, every child they have will be a carrier. No child will be affected.
X-Linked Recessive Inheritance
Females have two X chromosomes, while males have one X and one Y. X-linked recessive conditions are caused by genes that are located on the X chromosome. In a male, the condition is expressed in everyone with one damaged copy of the gene, as males do not have a second gene to compensate. In females, the condition is expressed in everyone with two damaged copies of the gene, while everyone with one damaged copy is a carrier. X-linked recessive conditions typically include the following characteristics:
- As it is rare for females to have two damaged copies, far more males are affected than females.
- Carrier females usually do not have any symptoms of the condition, but there are some conditions in which a carrier female may present with a milder expression (or degree) of symptoms.
- Affected males often born to unaffected, carrier mothers.
- In some cases, a male is affected as result of a new ("de novo"), sporadic mutation.
Risks to children:
- When a female is a carrier and the male is unaffected, every male child they have has a 50% chance of being affected and a 50% chance to not be affected; while every female childe they have has a 50% chance to be a carrier and a 50% to neither be affected nor a carrier.
Risks to children:
- When a male is affected and the female is not a carrier, every male child they have will not be affected, while every female child born will be a carrier. These conditions are never passed down from father to son.
- When a male is affected and the female is a carrier, every male child they have has a 50% chance to be affected and a have a 50% chance to not be affected; while every female they have has a 50% chance to be affected and a 50% chance to be a carrier.
X-Linked Dominant Inheritance
Females have two X chromosomes, while males have one X and one Y. X-linked dominant conditions are caused by genes that are located on the X chromosome. X-linked dominant conditions typically include the following characteristics:
- Both males and females can be affected.
- There is no such thing as "skipping" people (or generations).
- Multiple generations may be affected in a family.
- Male often have more severe (sometimes lethal) symptoms, as they do not have a second X to compensate.
- In some cases, a person is affected as result of a new ("de novo") sporadic mutation.
Risks to children:
- When a female is affected and the man is not affected, every child (both male and female) they have has a 50% chance of being affected and a 50% chance to be unaffected.
Risks to children:
- When a man is affected and the woman is not affected, every male child they have will be unaffected, while every female child they have will be affected. These conditions are never passed down from father to son.
- When a females is affected and the man is affected, every male child they have has a 50% chance to be affected, while every female child they have will be affected.
Y-Linked Inheritance
Females have two X chromosomes, while males have one X and one Y. Y-linked conditions are caused by genes that are located the Y chromosome and can only be passed down from father to son. Y-linked conditions typically include the following characteristics:
- No females are ever affected.
- There is no such thing as "skipping" generations.
- All males with a damaged copy of the gene are affected, as there is no second copy.
Risks to children:
- When a male is affected, every male child he has will be affected. No female child will ever be affected.
Mitochondrial (Maternal) Inheritance
Mitochondrial inheritance means that condition is expressed in people with mutations in mitochondrial DNA (mtDNA). All mitochondria and as such, mtDNA, descend from a small number of mitochondria present in the mother's egg at conception. Male sperm typically do not contribute mitochondria.
- Each human cell contains hundreds to thousands of mitochondria all of which typically have identical copies of mtDNA.
- When every single mitochondrion in a cell has a mtDNA mutation this is called homoplasmy.
- On the other hand, heteroplasmy is when a cell contains a mix of normal mitochondria (no mtDNA mutations) and defective mitochondria (with a mtDNA mutation). Most mitochondrial disorders are heteroplasmic, as homoplasmy would be too severe.
- The proportion of defective mitochondria typically must exceed a "critical threshold level" for there to be an adverse effect.
- As a general rule, the symptoms are worse if the defective mitochondria are present in large amounts and are distributed in high-energy tissues which have a lower "critical threshold level" like muscle, brain or nerve cells.
- Although males and females should be affected equally, in some conditions this is not the case and there is an unexplained sex-bias. An example of a male sex-biased condition is Leber’s Hereditary optic neuropathy (LHON).
Risks to children:
- When a female has a mtDNA mutation, every child she has may or may not be affected depending on the distribution and amount of defective mitochrondria and if there is a sex-bias.
- When a male has a mtDNA mutation, every child he has will not be affected.