Penetrance

Penetrance in genetics is the proportion of individuals carrying a particular variant (or allele) of a gene (genotype) that also expresses an associated trait (phenotype).

[1] Neurofibromatosis type 1 (NF1), is an autosomal dominant condition which shows complete penetrance, consequently everyone who inherits the disease-causing variant of this gene will develop some degree of symptoms for NF1.

[4] The penetrance is said to be reduced if less than 100% of individuals carrying a particular genotype express associated traits, and is likely to be caused by a combination of genetic, environmental and lifestyle factors.

[1] A specific hexanucleotide repeat expansion within the C9orf72 gene said to be a major cause for developing amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) is an example of a genotype with age dependent penetrance.

Familial male-limited precocious puberty (FMPP) caused by a mutation in the LHCGR gene, is an example of a genotype only penetrant in males.

The research concluded that the family had no known DNA-repair syndrome or any other hereditary diseases in the last four generations, and no genetic differences between the studied pair of monozygotic twins were detected in the BRCA1 regulatory region.

However, it may be difficult to transfer these estimates over to the general population because family members may share other genetic and/or environmental factors that could influence manifestation of said disease, leading to ascertainment bias and an overestimation of the penetrance.

Large-scale population-based studies, which use both genetic sequencing and phenotype data from large groups of people, is a different method for determining penetrance.

Phenocopies is when environmental and/or behavioral modifiers causes an illness which mimics the phenotype of a genetic inherited disease.

Because of phenocopies, determining the degree of penetrance for a genetic disease requires full knowledge of the individuals attending the studies, and the factors that may or may not have caused their illness.