With the relevance of genomics in clinical practice increasing, here are simple explanations of some key genetic terms:

Penetrance:
The proportion of individuals with a gene variant who actually go on to develop features of the condition.

Expressivity:
This term describes the range and severity of signs and symptoms that can occur in different people with the same genetic condition.

 Anticipation:
The earlier onset of symptoms of a condition, sometimes combined with increased severity, in successive generations.

De novo Variant:
A new gene change that arises in a person, it is not inherited from their parents.

Mosaicism:
When an individual carries 2 or more genetically different sets of cells in his or her body due to a change that happens after fertilisation. There are 2 key types to know:

• Somatic mosaicism: The variant line of cells is present in some of the body’s’ cells e.g. skin/blood. Individuals with this type can often vary in the symptoms they exhibit.
• Germline mosaicism: The variant line of cells is only presenting the reproductive cells i.e. sperm/eggs. The parent is not symptomatic but can pass the variant to the offspring who may be affected.

Homozygous:
Homozygous = An individual carries two altered copies with the same pathogenic gene change (e.g. sickle cell disease).

Heterozygous:
Heterozygous = An individual carries one altered copy and one normal copy of a gene (e.g. Huntington’s disease or carrier status).

Compound Heterozygous:
When an individual carries two different variants within the same gene on different alleles.
Example: Some cystic fibrosis cases.

Carrier:
When an individual carries a single altered gene copy, usually they’re not symptomatic but can pass it on.

Genetic Variant:

A change in the DNA which is not seen in the reference sample.

Variant Types:

• Pathogenic = The DNA change causes disease
• Likely Pathogenic = High probability that a variant causes disease
• Variant of Unknown Significance = Unsure of its’ clinical significance – will likely need further   interpretation from a clinical geneticist
• Benign = DNA change is highly unlikely to be associated with disease, it is part of normal genetic variation.

Inheritance Patterns:

• Autosomal dominant = A single faulty gene copy is enough to cause disease. Affected individuals have a 50% (or 1 in 2) chance of passing it on. Males and females equally affected. Example: Marfan’s syndrome
• Autosomal recessive = Disease occurs only when both copies of a gene are faulty. Parents are usually carriers and unaffected. Example: Cystic Fibrosis
• X-linked dominant = Describes a genetic condition where a variant in only one copy of the gene is needed to cause the condition. Males and females can both be affected. In some conditions, the severity in males may result in death in utero.  Example: Rett syndrome
• X-linked recessive = A pathogenic variant in a gene on the X chromosome which leads to disease, males are affected, and females are usually unaffected as they have a second functioning X chromosome. Female carriers may sometimes show signs of the condition but will usually be less severe than in males. Example: Duchenne muscular dystrophy
• Mitochondrial = Caused by mutations in mitochondrial genome, passed only from the mother. High-energy organs like brain and muscles are most affected. Example: Leber’s Hereditary Optic Neuropathy
  
  

Genotype:
Genotype = The DNA sequence of an individual.

Phenotype:

Phenotype = The clinical symptoms and signs exhibited from a gene variant.

Written by Isra Khalil (FY2)

Edited by Dr Charlotte Sherlaw-Sturrock (Clinical Genetics ST5)