Genomic Technologies in Clinical

Diagnostics - Glossary

The glossary below provides a list of key terms used throughout the course so
you may refer back to this list if you are unsure of the terminology being used.

Term Definition

Alignment The process of matching reads back to their

original position in the reference genome.

Allele An allele is one of a number of alternative forms of

the same gene or genetic locus.

Amniocentesis Invasive prenatal test in which a small sample of

amniotic fluid is extracted from around the fetus
for genetic testing. Can be carried out from around
15 weeks gestation.

Annealing Binding of two complementary single strands of

DNA to form double-stranded DNA. Often used to
describe binding of a probe or primer to a
template strand.

Array comparative Method for identifying gains or losses in the

chromosomal material by the comparison of
genomic hybridization
patient DNA with a reference DNA.
(Array CGH)

BRCA1 and BRCA2 The BRCA1 and BRCA2 genes encode proteins that
repair damaged DNA. People who inherit a
genes
mutation in either of these genes have defective
DNA repair, such that their cells are more likely to
accumulate DNA damage, which can lead to
cancer. Female carriers of BRCA1/2 mutations have
an increased risk of breast and ovarian cancers.

Capillary Technique used in DNA sequencing to separate

DNA fragments based on their size and read the
electrophoresis
fluorescent signal from the terminal nucleotide of
each fragment.

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Capture A method for selecting a specific portion of the
genome to undergo sequencing. Also referred to as
‘target enrichment’ or ‘pull down’.

Cell-free fetal DNA Fetal DNA circulating in the mother’s plasma

during pregnancy. Originates from the trophoblast.
(cffDNA)
Can be used for non-invasive prenatal testing.

Chorionic villus Invasive prenatal test in which a sample of the

developing placenta (trophoblast) is taken for
sampling (CVS)
genetic analysis. Usually done between 11-13
weeks gestation. The trophoblast and fetus are
both derived from the fertilised egg and therefore
should share the same genetic make-up.

Clinical exome Differs by laboratory, but usually involves

sequencing of all genes known to be associated
with human disease.

cDNA Complementary DNA (cDNA) is DNA generated by

reverse transcription from an RNA template.

Coverage The number of reads giving information about the

base present at a set position in the reference
sequence.

Driver mutation Mutation which promotes uncontrolled growth in a

cancer cell.

Epigenome Describes modifications to the genome that do not

affect the DNA sequence but determine whether
genes are switched on or off where and when they
are needed.

Exome The part of the genome that codes for proteins.

The exome constitutes 1-2% of the human genome. 

Fusion gene A hybrid gene formed from component parts of

two different genes combining, following a
structural rearrangement of the DNA.

Gene panel A collection of genes to be sequenced together,

which are usually linked by common biological
pathways, or known disease associations.

Genome The entirety of an individual’s genetic material

including coding and non-coding regions.

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Genome-wide Type of study used to identify genetic markers
(SNPs) that are associated with a particular
association study
common complex disease. GWAS studies look at
(GWAS) cases vs controls, and identify variants that
appear enriched in the genomes of the cases.

Germline mosaicism Type of mosaicism where some of the gametes

(sperm or egg) carry a mutation, but some do not.
The mutation may be passed on to offspring.

Histones Proteins around which DNA is wrapped to form the

nucleosome, the basic unit of chromatin.

Human Genome International collaboration to sequence the entire

human genome.
Project

Immunoprecipitation Technique of precipitating a protein antigen out of

solution using an antibody that specifically binds
to it.

Indel An insertion or deletion mutation.

In silico analysis Computational prediction of the effect a variant is

likely to have on protein structure and function.

Library preparation Fragmentation of genomic DNA and addition of

adaptors, in preparation for NGS.

Mapping See Alignment.

Massively parallel Sequencing millions of fragments of DNA at the

same time (see next generation sequencing).
sequencing

Missense mutation See nonsynonymous mutation.

Mosaicism Condition in which cells within the same person

have a different genetic make up.

Next generation High-throughput DNA sequencing where hundreds

of thousands of DNA fragments are sequenced in
sequencing (NGS)
parallel.

Non-invasive prenatal Genetic testing of cell-free fetal DNA circulating in

the mother’s bloodstream. Can be used for fetal
diagnosis (NIPD)
sex determination or prenatal diagnosis of some
monogenic disorders. Does not require
confirmation with an invasive test.

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Non-invasive prenatal Genetic testing of cell-free fetal DNA circulating in
the mother’s bloodstream. Can be used for
testing (NIPT)
aneuploidy screening. Positive results require
confirmation with invasive testing.

Non-pathogenic Not disease-causing.

Nonsense mutation See Protein-truncating mutation.

Nonsynonymous A nonsynonymous mutation describes where a

base substitution results in a codon which causes
mutation
the insertion of a different amino acid into a
protein. [Also known as a missense mutation]

Nucleosome The basic unit of chromatin, consisting of genomic

DNA, wrapped around a histone core.

Nucleotide A nucleotide is composed of a DNA base, a

phosphate and a pentose sugar. It forms the basic
unit of DNA.

Oligonucleotide Short DNA/RNA molecule, consisting of just a few

nucleotides, e.g. a probe or primer.

Paired-end sequencing Sequencing of both ends of a fragment during

NGS, enabling mapping of paired reads and
therefore improving accuracy of alignment.

Passenger mutation Mutation that occurs in a cancer cell but does not
itself promote uncontrolled growth or contribute to
the cancer development.

Pathogenic Disease-causing.

Penetrance The penetrance of a disease-causing mutation is

the proportion of individuals with the mutation
who have clinical symptoms of the disease.

Polymerase chain Method used to amplify a specific region of DNA

by several orders of magnitude. Harnesses the
reaction (PCR)
ability of DNA polymerase to synthesise a new
strand of DNA, complementary to a template
strand. Forms the basis of many molecular
techniques used in the clinical laboratory.

Protein-truncating Mutation which results in a truncated and

nonfunctional protein e.g. stop-gain (nonsense),
mutation
frameshift and certain splice site mutations.

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Pseudogene A genomic DNA sequence that is similar to a
normal gene, but non-functional. Pseudogenes are
thought to be defunct copies of functional genes.

Pull down See Capture.

Read A computer-generated sequence of bases

representing the sequenced code from an original
DNA fragment.

Read depth See Coverage.

Reference sequence/ An assembled version of a genome that can be

used to make comparisons to the genomes from
genome
other individuals.

Resequencing Sequencing any genome that has been already

sequenced once before (ie all human genome
sequencing is now actually re-sequencing).

Sanger sequencing Sequencing method developed by Fred Sanger in

1975. The sample DNA is used as a template to
generate a set of fragments that differ in length
from each other by a single base. The fragments
are then separated by size and the bases at the
end are identified, recreating the original sequence
of bases in the template DNA.

Single molecule Sequencing method using a single molecule of

DNA as the template
sequencing

Single nucleotide A single base substitution occurring at high

frequency (more than 1%) in the general
polymorphism (SNP)
population. SNPs are the most common type of
variation in the human genome.

Somatic mosaicism Occurrence of two genetically distinct cell lines

within one individual. Usually due to a postzygotic
mutation.

Stop-gain mutation Point mutation resulting in the creation of a

premature stop codon, and a truncated and
usually nonfunctional protein.

Synonymous variant Base substitution resulting in no change to the

amino acid sequence.

Target enrichment See Capture.

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Transcriptome The full range of RNA molecules transcribed from
the genes of an organism, cell or tissue.

Trio testing Genetic testing of an affected individual plus their

parents.

Variant annotation Identifying the likely effect that a genetic variant

will have on the protein it encodes.

Variant calling Identifying the differences between the sequenced

DNA and the reference genome.

Variant of uncertain An alteration to the DNA sequence where it is

unclear (on the basis of the available evidence)
significance (VUS)
whether it is disease-causing or not.

Virtual gene panel Clinical exome sequencing with the initial data
analysis restricted to a ‘panel’ of genes. Analysis
may subsequently be extended to include other
genes outside the original panel.

Whole exome Sequencing only the portion of the genome that

codes for proteins.
sequencing (WES)

Whole genome Sequencing the entire length of the genome.

sequencing (WGS)

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 Genomic Technologies in Clinical
Diagnostics - Acronyms

The list below provides a list of key abbreviations used throughout the course.

Abbreviations Meaning

Array CGH Array comparative genomic hybridization

cffDNA Cell-free fetal DNA

cDNA Complementary DNA

CTX Cerebrotendinous Xanthomatosis

CNV Copy number variation

CVS Chorionic villus sampling

GWAS Genome-wide associated studies

NGS Next generation sequencing

NIPD Non-invasive prenatal diagnosis

NIPT Non-invasive prenatal testing

PCR Polymerase chain reaction

SMRT Single molecule, real-time sequencing

SNP Single nucleotide polymorphism

VUS Variant of uncertain significance

WES Whole exome sequencing

WGS Whole genome sequencing

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