A rare functional variant is a
genetic variant Genetic variant may refer to:
* Single-nucleotide polymorphism (SNP), in a case it is a common genetic variant
* Mutation, in a case where it is a rare genetic variant
* Copy-number variation
* Variant (biology)
See also
* Genetic variation (dis ...
which alters gene function, and which occurs at low
frequency
Frequency is the number of occurrences of a repeating event per unit of time. It is also occasionally referred to as ''temporal frequency'' for clarity, and is distinct from '' angular frequency''. Frequency is measured in hertz (Hz) which is ...
in a population.
Rare variants play a significant role in both complex and
Mendelian
Mendelian inheritance (also known as Mendelism) is a type of biological inheritance following the principles originally proposed by Gregor Mendel in 1865 and 1866, re-discovered in 1900 by Hugo de Vries and Carl Correns, and later populari ...
disease and are responsible for a portion of the missing
heritability of complex diseases. The theoretical case for a significant role of rare variants is that
allele
An allele (, ; ; modern formation from Greek ἄλλος ''állos'', "other") is a variation of the same sequence of nucleotides at the same place on a long DNA molecule, as described in leading textbooks on genetics and evolution.
::"The chro ...
s that strongly predispose an individual to disease will be kept at low frequencies in populations by
purifying selection
In natural selection, negative selection or purifying selection is the selective removal of alleles that are deleterious. This can result in stabilising selection through the purging of deleterious genetic polymorphisms that arise through random ...
. Rare variants are increasingly being studied, as a consequence of
whole exome and
whole genome sequencing
Whole genome sequencing (WGS), also known as full genome sequencing, complete genome sequencing, or entire genome sequencing, is the process of determining the entirety, or nearly the entirety, of the DNA sequence of an organism's genome at a ...
efforts. While these variants are individually infrequent in populations, there are many in human populations, and they can be unique to specific populations. They are more likely to be