Genome Foundations

The genome is the entire set of genetic instructions found in a cell. In humans, the genome consists of 23 pairs of chromosomes, found in the nucleus, as well as a small chromosome found in the cells' mitochondria. Each set of 23 chromosomes contains approximately 3.1 billion bases of DNA sequence.⁴

Allele

An allele is one of two or more versions of a gene. An individual inherits two alleles for each gene, one from each parent. If the two alleles are the same, the individual is homozygous for that gene. If the alleles are different, the individual is heterozygous. Though the term allele was originally used to describe variation among genes, it now also refers to variation among non-coding DNA sequences.⁴

Amino Acid

An amino acid is the fundamental molecule that serves as the building block for proteins. There are 20 different amino acids. A protein consists of one or more chains of amino acids (called polypeptides) whose sequence is encoded in a gene. Some amino acids can be synthesized in the body, but others (essential amino acids) cannot and must be obtained from a person’s diet.⁴

Autosome

An autosome is one of the numbered chromosomes, as opposed to the sex chromosomes. Humans have 22 pairs of autosomes and one pair of sex chromosomes (XX or XY). Autosomes are numbered roughly in relation to their sizes. The largest autosome — chromosome 1 — has approximately 2,800 genes; the smallest autosome — chromosome 22 — has approximately 750 genes.⁴

Base Pair

A base pair is two chemical bases bonded to one another forming a "rung of the DNA ladder." The DNA molecule consists of two strands that wind around each other like a twisted ladder. Each strand has a backbone made of alternating sugar (deoxyribose) and phosphate groups. Attached to each sugar is one of four bases--adenine (A), cytosine (C), guanine (G), or thymine (T). The two strands are held together by hydrogen bonds between the bases, with adenine forming a base pair with thymine, and cytosine forming a base pair with guanine.⁴
Base Pair Illustration

Chromosome

A chromosome is an organized package of DNA found in the nucleus of the cell. Different organisms have different numbers of chromosomes. Humans have 23 pairs of chromosomes--22 pairs of numbered chromosomes, called autosomes, and one pair of sex chromosomes, X and Y. Each parent contributes one chromosome to each pair so that offspring get half of their chromosomes from their mother and half from their father.⁴
Chromosome Illustration

Copy Number Variation

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).⁴

Deoxyribonucleic Acid (DNA)

DNA is the chemical name for the molecule that carries genetic instructions in all living things. The DNA molecule consists of two strands that wind around one another to form a shape known as a double helix. Each strand has a backbone made of alternating sugar (deoxyribose) and phosphate groups. Attached to each sugar is one of four bases--adenine (A), cytosine (C), guanine (G), and thymine (T). The two strands are held together by bonds between the bases; adenine bonds with thymine, and cytosine bonds with guanine. The sequence of the bases along the backbones serves as instructions for assembling protein and RNA molecules.
DNA Graphic

Double Helix

Double helix is the description of the structure of a DNA molecule. A DNA molecule consists of two strands that wind around each other like a twisted ladder. Each strand has a backbone made of alternating groups of sugar (deoxyribose) and phosphate groups. Attached to each sugar is one of four bases: adenine (A), cytosine (C), guanine (G), or thymine (T). The two strands are held together by bonds between the bases, adenine forming a base pair with thymine, and cytosine forming a base pair with guanine.⁴
Double Helix Illustration

Epigenetics

The study of heritable changes that do not affect the DNA sequence but influence gene expression.³

Epigenome

The term epigenome is derived from the Greek word epi which literally means "above" the genome. The epigenome consists of chemical compounds that modify, or mark, the genome in a way that tells it what to do, where to do it, and when to do it. Different cells have different epigenetic marks. These epigenetic marks, which are not part of the DNA itself, can be passed on from cell to cell as cells divide, and from one generation to the next.⁴

Exon

An exon is the portion of a gene that codes for amino acids. In the cells of plants and animals, most gene sequences are broken up by one or more DNA sequences called introns. The parts of the gene sequence that are expressed in the protein are called exons, because they are expressed, while the parts of the gene sequence that are not expressed in the protein are called introns, because they come in between--or interfere with--the exons.⁴
Exon Illustration

Gene

The basic unit of heredity that occupies a specific location on a chromosome. Each consists of nucleotides arranged in a linear manner. Most genes code for a specific protein or segment of protein leading to a particular characteristic or function.³
Gene Illustration

Gene Expression

Gene expression is the process by which the information encoded in a gene is used to direct the assembly of a protein molecule. The cell reads the sequence of the gene in groups of three bases. Each group of three bases (codon) corresponds to one of 20 different amino acids used to build the protein.⁴
Gene Expression Illustration

Genetics

The study of genes and heredity. Heredity is the passing of genetic information and traits (such as eye color and an increased chance of getting a certain disease) from parents to offspring.²

Genotype

A genotype is an individual's collection of genes. The term also can refer to the two alleles inherited for a particular gene. The genotype is expressed when the information encoded in the genes' DNA is used to make protein and RNA molecules. The expression of the genotype contributes to the individual's observable traits, called the phenotype.⁴
Genotype Illustration

Germ Line

A germ line is the sex cells (eggs and sperm) that are used by sexually reproducing organisms to pass on genes from generation to generation. Egg and sperm cells are called germ cells, in contrast to the other cells of the body that are called somatic cells.⁴
Germ Line Illustration

Genomics

Genomics refers to the study of the entire genome, essentially all the genes that can be found in an organism.⁴

Example: If you wanted to study the genomics of an organism or a person you could sequence all of their genes and all of their DNA and look for changes and make comparisons with other individual's genomes.⁴

Haplotype

A haplotype is a set of DNA variations, or polymorphisms, that tend to be inherited together. A haplotype can refer to a combination of alleles or to a set of single nucleotide polymorphisms (SNPs) found on the same chromosome. Information about haplotypes is being collected by the International HapMap Project and is used to investigate the influence of genes on disease.⁴

Heterozygous

Heterozygous refers to having inherited different forms of a particular gene from each parent. A heterozygous genotype stands in contrast to a homozygous genotype, where an individual inherits identical forms of a particular gene from each parent.⁴
Heterozygous Illustration

Homologous Recombination

Homologous recombination is a type of genetic recombination in which nucleotide sequences are exchanged between two similar or identical molecules of DNA. During the formation of egg and sperm cells (meiosis), paired chromosomes from the male and female parents align so that similar DNA sequences can cross over, or be exchanged, from one chromosome to the other. This exchanging of DNA is an important source of the genomic variation seen among offspring.⁴

Homozygous

Homozygous is a genetic condition where an individual inherits the same alleles for a particular gene from both parents.⁴
Homozygous Illustration

Intron

An intron is a portion of a gene that does not code for amino acids. In the cells of plants and animals, most gene sequences are broken up by one or more introns. The parts of the gene sequence that are expressed in the protein are called exons, because they are expressed, while the parts of the gene sequence that are not expressed in the protein are called introns, because they come in between the exons.⁴
Intron Illustration

Locus

A locus is the specific physical location of a gene or other DNA sequence on a chromosome, like a genetic street address. The plural of locus is "loci".⁴

Loss of Heterozygosity (LOH)

If there is one normal and one abnormal allele at a particular locus, as might be seen in an inherited autosomal dominant cancer susceptibility syndrome, loss of the normal allele produces a locus with no normal function. When the loss of heterozygosity involves the normal allele, it creates a cell that is more likely to show malignant growth if the altered gene is a tumor suppressor gene.³

Methylation

A chemical reaction in which a small molecule called a methyl group is added to other molecules. Methylation of proteins or nucleic acids may affect how they act in the body. There can be hypo- or hyper- methylation. ²

Microbiome

A microbiome is all of the genetic material found within an individual microbe such as a bacterium, fungal cell, or virus. It also may refer to the collection of genetic material found in a community of microbes that live together.⁴
Microbiome Illustration

Microsatellite

Microsatellite sequences are repetitive DNA sequences usually several base pairs in length. They are used as genetic markers to follow the inheritance of genes in families.⁴

Microsatellite Instability (MSI)

A change that occurs in certain cells (such as cancer cells) in which the number of repeated DNA bases in a microsatellite (a short, repeated sequence of DNA) is different from what it was when the microsatellite was inherited. MSI may be caused by mistakes that don’t get corrected when DNA is copied in a cell. It is found most often in colorectal cancer, gastric cancer, and endometrial cancer, but it may also be found in many other types of cancer. Knowing whether a cancer has MSI may help plan the best treatment. Also called microsatellite instability.²

Mosaicism

Mosaicism 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.⁴

Nucleotide

A nucleotide is the basic building block of nucleic acids. RNA and DNA are polymers made of long chains of nucleotides. A nucleotide consists of a sugar molecule (either ribose in RNA or deoxyribose in DNA) attached to a phosphate group and a nitrogen-containing base. The bases used in DNA are adenine (A), cytosine (C), guanine (G), and thymine (T). In RNA, the base uracil (U) takes the place of thymine.⁴
Nucleotide Illustration

Pedigree

A pedigree, as related to genetics, is a chart that diagrams the inheritance of a trait or health condition through generations of a family. The pedigree particularly shows the relationships among family members and, when the information is available, indicates which individuals have a trait(s) of interest.⁴

Promoter

A promoter is a sequence of DNA needed to turn a gene on or off. The process of transcription is initiated at the promoter. Usually found near the beginning of a gene, the promoter has a binding site for the enzyme used to make a messenger RNA (mRNA) molecule.⁴
Promoter Illustration

Protein

Proteins are large, complex molecules that play many important roles in the body. They are critical to most of the work done by cells and are required for the structure, function and regulation of the body’s tissues and organs. A protein is made up of one or more long, folded chains of amino acids (each called a polypeptide), whose sequences are determined by the DNA sequence of the protein-encoding gene.⁴

Pseudogene

A pseudogene is a DNA sequence that resembles a gene but has been mutated into an inactive form over the course of evolution. A pseudogene shares an evolutionary history with a functional gene and can provide insight into their shared ancestry.⁴

Ribonucleic Acid (RNA)

Ribonucleic acid (RNA) is a molecule similar to DNA. Unlike DNA, RNA is single-stranded. An RNA strand has a backbone made of alternating sugar (ribose) and phosphate groups. Attached to each sugar is one of four bases--adenine (A), uracil (U), cytosine (C), or guanine (G). Different types of RNA exist in the cell: messenger RNA (mRNA), ribosomal RNA (rRNA), and transfer RNA (tRNA). More recently, some small RNAs have been found to be involved in regulating gene expression.⁴
RNA Illustration

Telomere

A telomere is the end of a chromosome. Telomeres are made of repetitive sequences of non-coding DNA that protect the chromosome from damage. Each time a cell divides, the telomeres become shorter. Eventually, the telomeres become so short that the cell can no longer divide.⁴
Telomere Illustration

Tumor Suppressor Gene

A tumor suppressor gene directs the production of a protein that is part of the system that regulates cell division. The tumor suppressor protein plays a role in keeping cell division in check. When mutated, a tumor suppressor gene is unable to do its job, and as a result uncontrolled cell growth may occur. This may contribute to the development of a cancer.³
Tumor Suppressor Gene Illustration

Variable Expressivity

Refers to the difference in the way that signs and symptoms of a genetic condition can show up in individual patients who have that condition. For example, some patients with neurofibromatosis type 1 may have only mild symptoms, such as brown spots and freckling on the skin, and others may have more severe symptoms, such as brain tumors and tumors on the nerves.²

Wild-type gene

A term used to describe a gene when it is found in its natural, unchanged form.²

Subcategory: Clinical Genomics

Cascade Genetic Testing

The process of extending genetic testing to individuals at risk for inheriting a pathogenic variant previously identified in a biologic relative. This process is repeated as more pathogenic variant carriers are identified within the family. This process is sometimes referred to as cascade screening, although cascade genetic testing is the preferred term.³

Penetrance

Penetrance refers to the likelihood that a clinical condition will occur when a particular genotype is present. For adult-onset diseases, penetrance is usually described by the individual carrier's age, sex, and organ site.²

Example: The penetrance for breast cancer in female carriers of BRCA1 pathogenic variants is often quoted by age 50 years and by age 70 years.²

Pathognomonic

Findings that are distinctive or characteristic of a particular disease or condition and make the diagnosis.²

Precision Oncology

A form of medicine that uses information about a person’s own genes or proteins to prevent, diagnose, or treat disease. In cancer, precision medicine oncology uses specific information about a person’s tumor to help make a diagnosis, plan treatment, find out how well treatment is working, or make a prognosis. Also called personalized medicine, precision medicine, or precision health.²

Example: Examples of precision oncology include using targeted therapies to treat specific types of cancer cells, such as HER2-positive breast cancer cells, or using tumor marker testing to help diagnose cancer.²