Mode of Inheritance

Mode of Inheritance is the manner in which a genetic trait or disorder is passed from one generation to the next. Autosomal dominant, autosomal recessive, X-linked dominant, X-linked recessive, multifactorial, and mitochondrial inheritance are examples. Each mode of inheritance results in a characteristic pattern of affected and unaffected family members.³

Autosomal Dominant

Autosomal dominant inheritance refers to genetic conditions that occur when a variant is present in one copy of a given gene (i.e., the person is heterozygous).³
Clinical Example: Hereditary Breast/Ovarian Cancer Syndrome associated with pathogenic variants in BRCA1, BRCA2, and PALB2 is a common example of an autosomal dominant genetic disorder.
Autosomal Dominant Inheritance Graphic

Autosomal Recessive

Autosomal recessive inheritance refers to genetic conditions that occur only when variants are present in both copies of a given gene (i.e., the person is homozygous for a variant, or carries two different variants of the same gene, a state referred to as compound heterozygosity).³
Recessive Illustration

First Degree Relative

A first-degree relative is a family member who shares about 50 percent of their genes with a particular individual in a family. First degree relatives include parents, offspring, and siblings.⁴

Mitochondrial

Mitochondria make most of the energy for the cell and have their own genetic material that is different from the genetic material found in the nucleus. Mitochondrial DNA is the small circular chromosome found inside mitochondria. The mitochondria, and thus mitochondrial DNA, are passed from mother to offspring.^2,4
MItochondrial DNA Illustration

Second Degree Relative

The aunts, uncles, grandparents, grandchildren, nieces, nephews, or half-siblings of an individual. Also called SDR.³

Third Degree Relative

Third degree relatives in a genetic family history are identified as those individuals with two other family members between them, for example first cousins. These relatives share on average 12.5% of their DNA.

X-Linked Dominant

X-linked dominant inheritance refers to genetic conditions associated with variants in genes on the X chromosome.³
Example: A single copy of the variant is enough to cause the disease in both males (who have one X chromosome) and females (who have two X chromosomes). In some conditions, the absence of a functional gene results in the death of affected males.³

X-Linked Recessive

X-linked recessive inheritance refers to genetic conditions associated with variants in genes on the X chromosome.³
Example: A male carrying such a variant will be affected, because he carries only one X chromosome. A female carrying a variant in one gene, with a normal gene on the other X chromosome, is generally unaffected.³

Subcategory - Family History

Consanguinity

Genetic relatedness between individuals who are descendants of at least one common ancestor.³

Founder Effect

The founder effect is the reduction in genetic variation that results when a small subset of a large population is used to establish a new colony. The new population may be very different from the original population, both in terms of its genotypes and phenotypes. In some cases, the founder effect plays a role in the emergence of new species.⁴

Pedigree

A graphic illustration of family history.²
Example: The pedigree shows the relationships between family members and indicates which individuals express or silently carry the trait in question.⁴
Pedigree Illustration

Proband

A proband is an individual being studied or reported on. A proband is usually the first affected individual in a family who brings a genetic disorder to the attention of the medical community.⁴