4.1 Unit Overview

Key terminology

Aneuploid

An individual with an error in chromosome number.

Barr body

Early in development, when female mammalian embryos consist of just a few thousand cells, one X chromosome in each cell inactivates by condensing into a structure called a Barr body.

Codon

A codon is a DNA or RNA sequence of three nucleotides (a trinucleotide) that forms a unit of genomic information encoding a particular amino acid or signaling the termination of protein synthesis (stop signals). There are 64 different codons: 61 specify amino acids and 3 are used as stop signals.

Conditional variants

Variants that rely on the concept of phenotype = genotype + environment + interaction. Organisms with this variant express a altered phenotype, but only under specific environmental conditions.

Continuous variation

Many interesting and important traits exhibit continuous variation, meaning they exhibit a continuous range of phenotypes that are usually measured quantitatively, such as intelligence, body mass, blood pressure in animals (including humans), and yield, water use, or vitamin content in crops.

Copy number variant (CNV)

Copy number variation (abbreviated CNV) refers to a circumstance in which the number of copies of a specific segment of DNA varies among different individuals’ genomes. The individual variants may be short or include thousands of bases. These structural differences may have come about through duplications, deletions or other changes and can affect long stretches of DNA. Such regions may or may not contain a gene(s).

De novo variants

Mosaicism (can be somatic or germline) refers to the presence of cells in a person that have a different genome from the body’s other cells. This difference could be due to a specific genomic variant, for example, or the addition or loss of a chromosome. The condition can stem from a genetic error that occurs after fertilization of an egg, during very early embryo development, or it could occur later in development. Mosaicism can affect any type of cell and does not always cause disease.

Deletion

A deletion, as related to genomics, is a type of mutation that involves the loss of one or more nucleotides from a segment of DNA. A deletion can involve the loss of any number of nucleotides, from a single nucleotide to an entire piece of a chromosome.

Deletion-insertion

This variant occurs when a deletion and insertion happen at the same time in the same location in the gene. In a deletion-insertion variant, at least one nucleotide is removed and at least one nucleotide is inserted. However, the change must be complex enough to differ from a simple substitution. The resulting protein may not function properly. A deletion-insertion (delins) variant may also be known as an insertion-deletion (indel) variant.

Discrete variation

Most of the phenotypic traits commonly used in introductory genetics are qualitative. This means the phenotype exists in only two (or possibly a few more) discrete, alternative forms, such as purple or white flowers, or red or white eyes.  These qualitative traits are therefore said to exhibit discrete variation.

Down syndrome

Down syndrome (also called Trisomy 21) is a genetic condition caused by an error in the process that replicates and then divides up the pairs of chromosomes during cell division, resulting in the inheritance of an extra full or partial copy of chromosome 21 from a parent. This extra chromosomal DNA causes the intellectual disabilities and physical features characteristic of Down syndrome, which vary among individuals.

Duplication

Duplication, as related to genomics, refers to a type of mutation in which one or more copies of a DNA segment (which can be as small as a few bases or as large as a major chromosomal region) is produced. Duplications occur in all organisms. For example, they are especially prominent in plants, although they can also cause genetic diseases in humans. Duplications have been an important mechanism in the evolution of the genomes of humans and other organisms.

Essential genes

Variants in essential genes create recessive lethal alleles that arrest or derail the development of an individual at an immature (embryonic, larval, or pupal) stage. This type of variant may, therefore, go unnoticed in a typical variant screen because they are absent from the progeny being screened.

Expressivity

The variability in mutant phenotypes observed in individuals with a particular phenotype.

Euploid

An individual with the appropriate number of chromosomes for their species (22 pairs autosomes and one pair of sex chromosomes in humans).

Frameshift

A frameshift mutation in a gene refers to the insertion or deletion of nucleotide bases in numbers that are not multiples of three. This is important because a cell reads a gene’s code in groups of three bases when making a protein. Each of these “triplet codons” corresponds to one of 20 different amino acids used to build a protein. If a mutation disrupts this normal reading frame, then the entire gene sequence following the mutation will be incorrectly read. This can result in the addition of the wrong amino acids to the protein and/or the creation of a codon that stops the protein from growing longer.

Gain-of-function variants

Some variants can have a positive effects, such as producing new proteins that help an individual better adapt to changes is the environment.

Genetic disorder

Genetic disorders are caused by variants that alter or eliminate a gene’s function leading to morphological or physiological changes.

Genetic redundancy

The lack of phenotypic change from a loss-of-function variant by be attributed to genetic redundancy. That is, the mutant gene’s lost function is compensated by another gene, at another locus, encoding a similarly functioning product. Thus, the loss of one gene is compensated by the presence of another. The concept of genetic redundancy is an important consideration in genetic screens. A gene whose function can be compensated for my another gene, cannot be easily identified in a genetic screen for loss-of-function variants.

Germline variants (inherited)

Are passed from parent to child and are present throughout a person’s life in virtually every cell in the body. These variants are also called germline variants because they are present in the parent’s egg or sperm cells, which are also called germ cells. When an egg and a sperm cell unite, the resulting fertilized egg cell contains DNA from both parents. Any variants that are present in that DNA will be present in the cells of the child that grows from the fertilized egg.

Insertion

An insertion, as related to genomics, is a type of mutation that involves the addition of one or more nucleotides into a segment of DNA. An insertion can involve the addition of any number of nucleotides, from a single nucleotide to an entire piece of a chromosome.

Karyotype

A karyotype is an individual’s complete set of chromosomes. The term also refers to a laboratory-produced image of a person’s chromosomes isolated from an individual cell and arranged in numerical order. A karyotype may be used to look for abnormalities in chromosome number or structure.

Klinefelter syndrome

The XXY chromosome complement, corresponding to one type of Klinefelter syndrome, corresponds to male individuals with small testes, enlarged breasts, and reduced body hair.

Intergenic regions

Intergenic regions are the stretches of DNA located between genes. In humans, intergenic regions are non-protein-coding and comprise a large majority of the genome. Some intergenic DNA is known to regulate the expression of nearby genes.

Introns

An intron is a region that resides within a gene but does not remain in the final mature mRNA molecule following transcription of that gene and does not code for amino acids that make up the protein encoded by that gene. Most protein-coding genes in the human genome consist of exons and introns.

Inversion

An inversion in a chromosome occurs when a segment breaks off and reattaches within the same chromosome, but in reverse orientation. DNA may or may not be lost in the process.

Lethal variants

Variants that cause the premature death of an organism.

Loss-of-function variant

Variants that cause the loss-of-function of a gene, yet do not cause a change in phenotype, even when the mutant allele is homozygous.

Missense

A missense mutation is a DNA change that results in different amino acids being encoded at a particular position in the resulting protein. Some missense mutations alter the function of the resulting protein

Mitochondrial DNA

Mitochondrial DNA is the circular chromosome found inside the cellular organelles called mitochondria. Located in the cytoplasm, mitochondria are the site of the cell’s energy production and other metabolic functions. Offspring inherit mitochondria — and as a result mitochondrial DNA — from their mother.

Mitochondrial encephalomyopathies

Mitochondrial disorders that cause both muscular and neurological problems.

Mitochondrial myopathies

Mitochondrial disorders that mostly cause muscular problems.

Monogenic disorder

Multifactorial inheritance disorder or polygenic inheritance.

Morphological variants

Variants that cause changes in the visible form of the organism as they give rise to altered forms of a trait.

Mutation

A mutation is a change in the DNA sequence of an organism. Mutations can result from errors in DNA replication during cell division, exposure to mutagens or a viral infection. Germline mutations (that occur in eggs and sperm) can be passed on to offspring, while somatic mutations (that occur in body cells) are not passed on. The preferred term is “variant,” though mutation can be used to refer to a pathogenic variant.

Nonsense

A nonsense mutation occurs in DNA when a sequence change gives rise to a stop codon rather than a codon specifying an amino acid. The presence of the new stop codon results in the production of a shortened protein that is likely non-functional.

Penetrance

The proportion of individuals with a particular genotype that display a corresponding phenotype.

Permissive conditions

Under permissive conditions, conditional variants show a wild type phenotype.

Pleiotropic

Pleiotropy occurs when one gene influences two or more seemingly unrelated phenotypic traits. Such a gene that exhibits multiple phenotypic expression is called a pleiotropic gene.

Polymorphisms

One of two or more variants of a particular DNA sequence.

Polyploid

An individual with more than the correct number of chromosome sets (two for diploid species).

Reciprocal translocation

Result from the exchange of chromosome segments between two nonhomologous chromosomes such that there is no gain or loss of genetic information.

Repeat expansion

Some regions of DNA contain short sequences of nucleotides that are repeated a number of times in a row. For example, a trinucleotide repeat is made up of sequences of three nucleotides, and a tetranucleotide repeat is made up of sequences of four nucleotides. A repeat expansion is a variant that increases the number of times that the short DNA sequence is repeated. This type of variant can cause the resulting protein to function improperly.

Restrictive conditions

Under restrictive conditions, conditional variants express the altered phenotype.

Silent variants

When the variant does not have an obvious effect on the phenotype. This could be because the change occurs in the DNA sequence in a non-coding region such as intergenic regions or introns. Alternatively, a change in a single nucleotide may result in a codon that produces the same amino acid.

Single nucleotide polymorphisms (SNP – pronounced “snip)

A single nucleotide polymorphism (abbreviated SNP, pronounced snip) is a genomic variant at a single base position in the DNA. Scientists study if and how SNPs in a genome influence health, disease, drug response and other traits.

Somatic variants (non-inherited)

Occur at some time during a person’s life and are present only in certain cells, not in every cell in the body. Because non-inherited variants typically occur in somatic cells (cells other than sperm and egg cells), they are often referred to as somatic variants. These variants cannot be passed to the next generation. Non-inherited variants can be caused by environmental factors such as ultraviolet radiation from the sun or can occur if an error is made as DNA copies itself during cell division.

Substitution

Substitution, as related to genomics, is a type of mutation in which one nucleotide is replaced by a different nucleotide. The term can also refer to the replacement of one amino acid in a protein with a different amino acid.

Translocation

A translocation, as related to genetics, occurs when a chromosome breaks and the (typically two) fragmented pieces re-attach to different chromosomes. The detection of chromosomal translocations can be important for the diagnosis of certain genetic diseases and disorders.

Turner syndrome

Characterized by the presence of only one X chromosome in women instead of two.

Variant

A difference in the DNA sequence. See mutation.