Genomics in general practice


Last revised: 30 Nov 2018

Glossary of terms

A glossary of terms used throughot this guideline - listed in alphabetical order.


Anticipation describes a situation where a genetic condition appears at an earlier age with successive generations. The severity of the condition can also increase. This phenomenon is often seen in conditions caused by trinucleotide repeats, such as Huntington’s disease, myotonic dystrophy and Fragile X syndrome. In these cases, the size of the trinucleotide repeat increases when it is passed from parent to child, which can result in earlier onset and more severe disease.

For more information, refer to the Genetics Home Reference’s explanation ‘What do geneticists mean by anticipation?’ and ‘What are the different ways in which a genetic condition can be inherited?’


When a condition follows an autosomal dominant pattern of inheritance, the family tree will usually reveal multiple affected members on the same side of the family. Dominant conditions or traits are expressed when only a single gene variant is inherited. They are usually inherited on one side of the family and can be seen in multiple generations.

Wide variability in clinical expression is common in many autosomal dominant conditions, even within the same family.

Early onset of conditions, such as cancer, can be indicative of autosomal dominant inheritance within a family.

Not all dominant conditions show 100% penetrance (eg BRCA1 gene mutations).

Autosomal recessive conditions affect either sex, and often occur in the absence of any family history. Recessive conditions or traits appear when an individual inherits two copies of the same gene variant (one from each parent).

Parents of a child with an autosomal recessive condition are usually asymptomatic carriers. The affected child will carry two copies of the particular gene change.

The recurrence risk of autosomal recessive conditions is one in four for each pregnancy.

Wide variability in clinical expression is common in many autosomal recessive conditions, even within the same family.

Consanguinity is noted to occur more often among the parents of individuals with rare autosomal recessive conditions.


A balanced translocation is a rearrangement of the chromosome with no apparent loss or gain of chromosomal material. Individuals with balanced translocations are not usually affected.


Recessive genetic conditions such as cystic fibrosis (CF) occur when a person inherits a particular gene variant from each parent. A carrier is an individual who only has one copy of the gene variant and generally does not have symptoms, but can pass the variant to their children.
Some conditions are linked to the X chromosome ( X-linked recessive inheritance). Typically, these conditions affect more males (who have the sex chromosomes XY) than females (who have the sex chromosomes XX). A woman who is a carrier of an X-linked condition has the variation on one of her X chromosomes, which she can pass on to her children. However, if the biological male partner is a carrier, he will not pass it to his sons, but will pass it to his daughters.


Carrier screening is a test to determine whether an individual carries a genetic variant or chromosomal alteration that does not generally affect that individual’s health, but increases his or her chance of having children with the condition in question. The outcome of such testing can influence future reproductive decisions. Carrier screening is performed on individuals who are not necessarily known to be at increased risk for a particular genetic condition. Screening tests can be conducted on individuals, groups such as those from a common ethnic background and entire populations (eg newborn screening).


Cascade screening involves testing the close biological relatives of an individual who has a genetic condition in order to determine whether these relatives carry the genetic variant or chromosomal alternation (thereby increasing their chances of developing the condition or having a child with the condition).


A compound heterozygote is an individual with two different pathogenic alleles at a particular location in a pair of chromosomes. For example, in hereditary haemochromatosis, compound heterozygotes have both a C282Y and an H63D variant, and are less likely to develop iron overload than C282Y homozygotes. However, the impact will be assessed on a case-by-case situation as it depends on the variant (allele) and its pathogenicity. Additionally, as one allele will have come from the mother and the other from the father, there might be implications in terms of cascade testing within the family.


Consanguinity describes a relationship between two people who are related to each other because of a common ancestor. Consanguineous relationships occur in all population groups, but may occur more frequently in certain cultures. The most common form of consanguineous relationships is between first cousins.
Individuals who are blood relatives share a greater proportion of their genes than unrelated people, thus, these individuals potentially share pathogenic variants for recessive conditions. When individuals are first cousins and there is no family history of a specific condition, or of other consanguineous relationships in previous generations, the risk of them having a child with a genetic condition is approximately 5–6%, compared with 3–4% in the general population. This risk will increase in communities where there is a multi-generational tradition of first-cousin marriages, rendering couples closer in genetic relationship.


A de novo variant is a new genetic variation that arises in the fetal stage of development (ie was not present in either parent).


The exome is the part of the genome that contains protein-coding genes only. The exome represents less than 2% of the genome, but contains about 85% of known disease-causing gene variants.


Gene variants are small deoxyribonucleic acid (DNA) sequence changes (ie additions, duplications, deletions, substitutions). These variants can have a range of effects: some may cause disease (pathogenic variant), while others do not cause disease but may modify an individual’s risk of disease (eg increase risk, provide a protective effect).


The genome is the entire set of genetic material, including all coding and non-coding genes.



Genotyping (also known as genomic profiling or genomic scanning) is a test to determine an individual’s single nucleotide polymorphism (SNP) profile. A SNP profile may be used to predict disease susceptibility, tailor treatment and provide non–health related information (eg paternity, ancestry).


Heterozygosity refers to the presence of two different alleles (form of a gene variant) at a given location on a pair of chromosomes (eg carrierfor a pathogenic gene variant).


Homozygosity refers to the presence of two identical alleles (form of a gene variant) at a given location on a pair of chromosomes.

Refer to ‘Penetrant and penetrance’.

Multifactorial inheritance, also called complex inheritance, can be attributed to a combination of genetic (ie single gene, multiple genes), environmental and lifestyle factors.

The number of necessary factors, and the impact those factors have on the presence or severity of a condition, will vary for different conditions and individuals.

Often, when there are multiple susceptibility genes involved, there is an additive effect on the outcome.

Early onset of conditions, such as cancer, cardiovascular disease or type 2 diabetes, may be indicative of multifactorial inheritance within a family.

This type of inheritance does not follow a characteristic pedigree pattern, but may look like autosomal dominant inheritance with incomplete penetrance.


A pathogenic variant is a genetic variant that increases an individual’s susceptibility or predisposition to certain diseases. Pathogenic variants are also known as mutations. Some are responsible for normal human variation, and these are known as polymorphisms (eg height).

There are variations that affect the way we metabolise drugs. For some variants, their effects are unknown or uncertain, while others have no effect.


Penetrance refers to the proportion of people with a particular genetic variant who will go on to develop the condition. It describes the extent to which disease or characteristics controlled by the gene, or variation within the gene, will be expressed. For example, people carrying an autosomal dominant variant may not always develop the condition – this is called ‘incomplete penetrance’. If a condition is 100% penetrant, an individual will definitely develop the condition. If penetrance is 80%, most but not all individuals will develop the condition. Other genes and lifestyle factors, such as diet, exercise and smoker status, may affect the onset of some conditions.

For more information, refer to Genetics Home Reference’s ‘What are reduced penetrance and variable expressivity?


Predictive testing aims to determine whether a person who has no signs or symptoms of a specific condition at the time of testing has specific genetic variations that increase the likelihood they will later develop the condition. Predictive testing is often performed in relation to genetic conditions that are not evident at birth, but have their onset during adulthood, such as some cancers. Predictive genetic testing in conditions such as familial cancer can only be conducted when the family-specific genetic variant is known. Hence, genetic testing must first be done on a family member affected with the specific condition, as they are the most likely to carry the genetic variant.


Pre-implantation genetic diagnosis (PGD) is cytogenetic testing, with or without molecular testing, performed on embryos used in assisted reproductive technology procedures. Prenatal testing of successful pregnancies may be recommended for confirmation of the test result.


Pre-symptomatic testing aims to determine whether a person will develop a particular genetic condition (eg Huntington’s disease) at some point in the future when symptoms of the condition have not yet manifested.


Sensitivity is the true positive rate for a test. For example, if the person has the condition, how often will the test give a positive result?


A nucleotide is a single base pair unit of deoxyribonucleic acid (DNA). A single nucleotide polymorphism (SNP or ‘snip’) is a polymorphism in a single nucleotide occurring at a particular site in the genome. For example, one individual may have a ‘G’ at a particular location and another individual a ‘T’. If two or more alternative DNA variants occur at a particular location at a population frequency of >1%, it is defined as a SNP. SNPs are the most common type of genetic variation in the human genome and account for approximately 0.02% of the genome.


Specificity is the true negative rate for a test. For example, if the person does not have the condition, how often will the test give a negative result?


Variable expressivity refers to the range of signs and symptoms that an individual with a particular genetic condition will display.
Variable expressivity is a factor that influences the effect of particular genetic variants. While some genetic variants are consistent in terms of the effect they have on a disease or characteristic, other have a more variable effect. For example, Lynch syndrome (hereditary non-polyposis colorectal cancer [HNPCC]) shows variable expressivity. An individual’s presentation of this disease is modified by their genetic, lifestyle and environment factors.
Variable expressivity is not the same as reduced penetrance.
For more information, refer to the Genetics Home Reference’s ‘What are reduced penetrance and variable expressivity?’ 


Inactivation of most genes on the X chromosome in female somatic cells ensures that males and females have the same number of X chromosome genes instructing the body to perform particular functions.
This is usually a random process; thus, females will have a mixture of cells with respect to the inactivated X chromosomes being of maternal or paternal origin.
The usual random process of X-inactivation means that female carriers of the mutation will not usually show any signs of the condition as there are enough cells with the correct copy of the gene to instruct the body to perform particular functions.
Rarely, some female carriersmay be mildly symptomatic because of unequal or skewed inactivation of the X chromosomes.


Since a male inherits only one X chromosome (from his mother), in a family affected by a condition that follows a pattern of X-linked recessive inheritance, there will be more affected males than affected females. Males are usually more severely affected than females because of X-inactivation.
Since a male only passes his Y chromosome to his sons, there is no male-to-male transmission of X-linked conditions.
With each pregnancy, females who are carriers for a gene variant involved have a one-in-two chance of passing on the variant. Sons who inherit the variant will be affected and daughters who inherit the variation will be carriers like their mothers.
Daughters of affected males can only inherit the variation from their father and are known as ‘obligate carriers’.