This is a brief summary of the terms used in our clinics. If you would like further clarification The Centre for Genetics Education has some very good fact sheets illustrating each of these terms.
Gene, Chromosomes and Cells
Cells: The smallest independent parts of organisms
Nucleus: the part of the cell that contains our genetic information
Mitochondria : also called the ‘cell’s factory’…contains its own genetic information which produces some of the proteins required for it to function efficiently
Gene: Genes, which are made up of DNA, act as instructions to make molecules called proteins. These proteins are required to ensure the normal functioning and development of the body.
Genome: The total genetic information contained in the nucleus and/or mitochondria of our cells. The nucleargenome is inherited from the biological parents. The mitochondrial genome is only inherited from the mother. The genome contains coding and non coding regions
DNA: The human body is made of trillions of cells, each containing a molecule of DNA. Often called the “building blocks of life”, DNA molecules contain all the genetic instructions used for the growth, development and functioning of living organisms.
Chromosome: Our DNA ( and therefore genetic information) is organised into 23 pairs of chromosomes. Chromosomes are rod-like structures that contain all our genes. We normally have 46 chromosomes arranged in 23 pairs in each cell. Chromosomes come in pairs, one chromosome in each pair from each parent. The first 22 pairs are numbered 1 – 22 according to size ( called Autosomes). The 23rd pair is our sex chromosomes and these are given labels X and Y. Females have two X chromosomes. Males have one X and one Y chromosome. They come in pairs as we inherit a copy from each parent.
Allele: As each piece of genetic information ( or gene) is inherited in pairs, we describe the pair as two alleles. An allele is one member of the pair.
Genotype: the set of genes in our DNA, which is responsible for a particular trait.
Phenotype: physical expression, or characteristics, of that trait
Trait: a feature of a person- physical or otherwise.
Mutation: Deleterious change in a gene that may lead to disease
Polymorphism: multiple forms of a single gene that exists in an individual or among a group of individuals
Protein: responsible for basic cellular functions. Proteins are comprised of amino acids,
Amino acid: the building blocks of proteins.
The level of genetic detail required to make a diagnosis will determine the genetic test we recommend. Most genetic tests require a blood sample. Unlike standard blood tests, results may take some months to return.
Karyotype: cytogenetic chromosome analysis with direct visualisation of the chromosomes to determine chromosome number and structure/content
Array Comparative genomic hybridisation (CGH): Molecular chromosome analysis that provides a detailed assessment of chromosome content
Single Gene Test : Targeted testing for a specific condition. A single gene test is recommended when specific features point to one condition cause by one single gene, such as cystic fibrosis or sickle-cell anaemia
Gene Panel: A panelis a single test that simultaneously analyses a number of genes associated with a similar phenotype ( eg, epilepsy, migraine, connective tissue disorders)
Whole Exome Sequencing (WES) : The exome is part of the genome that contains the protein coding portions, known as exons. Exome sequencing allows analysis of all coding genes, and variances can be identified against approximately 4,600 medically defined conditions.
Whole Genome Sequencing (WGS): Gives a comprehensive view of the entire genome (sequences both coding and non coding parts of the genome). This analysis is often more expensive when compared to the WES, however, provides more comprehensive information
Other terms used:
Mosaicism: the presence of two populations of cells with different genotypes in one individual,
Aneuploidy: disorder of chromosome number
Translocation: disorder of chromosome arrangement
Copy Number Variation: loss or gain of genetic material
Deletion: Loss of chromosomal/genetic material
Duplication: Gain of chromosomal/genetic material
Pre-implantation genetic diagnosis (PGD): "IVF for genetic disorders", enables genetic testing of an
embryo created using IVF technology
Gamete: a cell that fuses with another gamete during fertilisation ie sperm and eggs are gametes
Patterns of genetic inheritance
It is important to remember that Chromosomes are rod-like structures that contain all our genes. We normally have 46 chromosomes arranged in 23 pairs in each cell. Chromosomes come in pairs, one chromosome in each pair from each parent. The first 22 pairs are numbered 1 – 22 according to size (called Autosomes). The 23rd pair is our sex chromosomes and these are given labels X and Y. Females have two X chromosomes. Males have one X and one Y chromosome. They come in pairs as we inherit a copy from each parent.
Autosomal dominant: There only needs to be a mistake in one of the two gene copies in order to develop the disease.
Autosomal recessive: There needs to be a mistake in both gene copies in order to develop the disease. If there is a mistake in only one of the gene copies, then you are a ‘carrier’ of the condition and not affected.
Sex-linked :Genetic conditions associated with genes that are situated on a sex chromosome (X or Y chromosome)
X-linked recessive inheritance: a single faulty gene on the X-chromosome in a male is sufficient to cause disease. Females are usually "protected" by the presence of the normal allele (gene) on the second X chromosome (acting as a "back-up copy"). though may still present with symtpoms.
X-linked dominant inheritance males and females are affected. These conditions are usually lethal in affected males.
Epigenetics: heritable changes in phenotype or gene expressed caused by mechanisms other than due to changes in the underlying DNA sequence eg "imprinting", methylation disorders
Factors influencing genetic inheritance
Fully-penetrant: inheriting a faulty gene leads to development of the disorder in all individuals
Incomplete penetrance: Not all individuals who inherit a faulty gene develop the disorder
Variable expression: the disease manifestations may vary from person-to-person ie age of onset, disease severity, progression, organ systems affected
Sex-limited expression: disorders where males and females are affected differently with different chance of developing a disease and different expression of a disorder
Mutation: Changes to the nucleotide sequence of the genetic material
Missense mutation: alters the amino acid in the mature protein
Nonsense mutations: change in the code creating a "stop signal" that typically truncates the protein
Germline mutation: gene change transmissable to offspring.
Somatic mutation: change in cells outside of the gonadal cells, not usually transmitted to offspring.
De novo mutation: a new mutation in a child or somatic cell, that is not inherited from a parent.
Gonadal mosaicism: Presence of two populations of cells with different genotyes in the gonads of an individual. Can cause recurrence of a genetic disorder where testing may indicate a low chance of recurrence. A mode of inheritance that is difficult to exclude in clinical practice.
A heterozygous mutation: is a mutation of only one allele.
A homozygous mutation: is an identical mutation of both the paternal and maternal alleles.
A compound heterozygous mutation: is two different mutations in the paternal and maternal alleles.