From the Guidelines
The primary modes of inheritance include autosomal dominant, autosomal recessive, X-linked dominant and recessive, Y-linked, and mitochondrial inheritance, with the specific mode depending on the disorder in question, such as myotonic dystrophy type 1 being autosomal dominant with nearly complete penetrance but variable expressivity 1. Modes of inheritance are crucial in understanding how genetic traits or disorders are passed from parents to offspring.
- Autosomal dominant inheritance, where a single copy of a mutated gene from one parent causes the trait to appear, is seen in conditions like myotonic dystrophy type 1, as noted in a 2024 technical standard by the American College of Medical Genetics and Genomics (ACMG) 1.
- Autosomal recessive inheritance requires two copies of the mutated gene (one from each parent) for the trait to manifest and is common in many organic acidemias and other inborn errors of metabolism, as discussed in a 2018 update by the ACMG 1.
- X-linked dominant and recessive inheritance patterns involve genes located on the X chromosome, with examples including Fabry disease and Danon disease, which are X-linked and may exhibit symptoms in females regardless of their X-inactivation status, as outlined in a 2022 technical standard by the ACMG 1. Understanding these patterns is vital for genetic counseling, diagnosing genetic conditions, and predicting the likelihood of inheriting specific traits or disorders. Key concepts also include:
- Codominance, where both alleles are fully expressed
- Incomplete dominance, resulting in a blended phenotype
- Polygenic inheritance, involving multiple genes contributing to a trait
- Multifactorial inheritance, combining genetic and environmental factors Pedigree analysis is a valuable tool in clinical settings for determining inheritance patterns through family trees.
From the Research
Modes of Inheritance
The modes of inheritance refer to the ways in which genetic traits are passed down from parents to offspring.
- Autosomal dominant inheritance is one mode, where a single copy of the dominant allele is enough to cause the condition.
- This mode is exemplified by Huntington's disease, which is caused by an elongated CAG repeat on the short arm of chromosome 4p16.3 in the Huntingtine gene 2, 3, 4.
- In autosomal dominant inheritance, each child of an affected parent has a 50% chance of inheriting the mutated gene, regardless of sex.
- The severity and age of onset of the condition can vary, even among family members with the same mutation, as seen in Huntington's disease where the longer the CAG repeat, the earlier the onset of disease 2.