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HEART UK FH GIT TOOLKIT
Glossary
Allele
Alternative forms of a gene at the same locus
(position on a chromosome).
Autosomal Dominant
A genetic condition with autosomal dominant inheritance
occurs when only one copy of a gene, located on an
autosome, is altered. The other copy is normal. When an
individual with a dominantly inherited condition has a child,
the child has an equal chance of inheriting the condition
or not inheriting it (i.e. a 50% chance or one chance in two)
depending on which gene they inherit.
Autosome
Any of the 22 nuclear chromosomes other than the sex
chromosomes.
Cascade testing
Offering a genetic test to relatives of a person identified
as having a gene mutation that causes a particular disease.
Chromosomes
Chromosomes are tightly packaged bundles of DNA,
the chemical that encodes genetic information. Nearly
all human cells have a set of 46 chromosomes, identified
as 23 pairs; 22 pairs are autosomes with the 23rd pair the
sex chromosomes. Human gametes (sperm and egg cells)
have 23 chromosomes; one copy of each autosome and
one sex chromosome. Each individual therefore inherits one
copy of each pair of chromosomes from their mother and
the other copy from their father.
Consanguineous
Where two people share at least one common ancestor
(“blood relatives”).
Degree of relationship
The degree of relationship helps define the proportion
of genes shared by two blood relatives. First degree
relatives (parents, siblings, children) share ½ (or 50%)
of their genes, Second degree relatives (uncles, aunts,
nephews, nieces, grandparents, grandchildren and halfsiblings) share ¼ (or 25%) of their genes, and third degree
relatives (first cousins, great-uncles, great-aunts, grandnephews, grand-nieces, great-grandparents and greatgrandchildren) share ⅛ (or 12.5%) of their genes.
DNA
DNA (Deoxyribonucleic acid) is the chemical that encodes
genetic information. The code itself is based on four
different chemicals, or bases, known as A (adenine),
C (cytosine), G (guanine) and T (thymine).
DNA testing
This describes molecular genetic testing – testing that
involves the analysis of DNA. Techniques can involve
reading (sequencing) the code of the whole gene or
testing for a known mutation.
Family mutation
This refers to the specific mutation that causes the genetic
disease or condition in a family. Identification of a family
mutation is often required before cascade testing can be
offered if the genetic disease or condition can be caused
by different mutations.
What’s a
family worth?
2
Glossary
For example, familial hypercholesterolaemia can be
caused by a mutation in one of three genes (LDLR, APOB,
PCSK9), and there have been approximately 200 different
mutations in LDLR reported in the UK (there is one
common mutation in APOB and one common mutation
in PCSK9).
First-degree relative
A person’s biological parent, sister, brother or child.
Gene
The basic biological unit of inheritance. A gene consists
of a segment of DNA which produces a polypeptide
chain – usually a specific protein or component of a
protein. It includes coding segments (exons), intervening
sequences (introns) together with regulatory elements.
Human have between 20,000 – 25,000 genes. The genes
are arranged in linear order on the chromosomes. Usually
an individual has two copies of each gene, one inherited
from each parent.
Homozygous FH
Refers to a person with familial hypercholesterolaemia
who has inherited a gene alteration from both parents.
This may be the same mutation (i.e. identical alleles),
different mutations or mutations in different genes.
The term homozygous FH will be used to cover all these
possibilities in this toolkit.
Index individual
The original patient who is the starting point for follow-up
of other members of a family when investigating possible
genetic factors that are responsible for the presenting
condition.
Mutation (gene alteration)
A mutation refers to any change from the normal to an
altered form of a particular gene. This may be disease
causing, where the mutation causes the gene or gene
product to function differently or cease to function,
or a benign, normal variant.
Genetic condition
A condition or illness caused by changes in a gene or
genes, affecting the way the body looks, develops or works.
Pedigree
A diagram of the genetic relationships and medical history
of a family, which uses standard symbols and terminology.
Genetic counselling
Information and support given to individuals affected
by, or at a high probability of a genetic condition.
An explanation of probabilities and options may include
the findings of specific genetic tests. In the UK nondirective genetic counselling is the accepted practice,
i.e. individuals are not told what decisions to make.
Phenotype
The physical and/or biochemical characteristics caused
by a particular gene alteration.
Genetic testing
A test that gives information about genetic status – for
instance whether someone has a condition or is a carrier.
Usually taken to mean DNA testing, but other investigations
(eg biochemical measurements or ultrasound) can also give
genetic information.
Proband (index case)
The first affected individual studied in an investigation of
several related patients with an inherited or familial disorder.
Genotype
The genetic constitution of an individual.
Sex chromosomes
The sex chromosomes determine the sex of an individual.
These are XX in women and XY in men. The non-sex
chromosomes (numbered 1 to 22) are known as the
autosomes.
Heterozygous
Refers to a person who has inherited two different alleles,
one from each parent, at a particular chromosome location.
Heterozygous FH
Refers to a person with familial hypercholesterolaemia who
has inherited a gene alteration from only one parent.
Homozygous
Refers to a person who has inherited two identical alleles,
one from each parent, at a particular chromosome location.
Prevalence
The total number of cases of a condition or disease
in a population at a given point in time.
Second-degree relative
A person’s biological grandparent, grandchild, aunt, uncle,
niece, nephew, half sister or half brother.
Third-degree relative
A person’s biological great-grandparent, great-grandchild,
great-aunt, great-uncle, first cousin, grand-niece or grandnephew.