Resources for Genetic Diseases

Acquired Mutation: A genetic alteration that occurs after conception, typically in somatic (body) cells rather than germ cells (eggs or sperm). These mutations are not inherited but can contribute to conditions like cancer.

Adenine (A): One of the four nucleotide bases in DNA, pairing with thymine (T) in the DNA double helix. It is a purine base.

Allele: One of two or more versions of a genetic sequence at a particular location (locus) on a chromosome. Different alleles can result in different observable traits.

Amino Acids: Organic molecules that serve as the building blocks of proteins. There are 20 standard amino acids encoded by the genetic code.

Antisense: is the non-coding DNA strand of a gene. In a cell, antisense DNA serves as the template for producing messenger RNA (mRNA), which directs the synthesis of a protein.

Autism: is a condition related to brain development that can cause significant social, communication and behavioral challenges. Symptoms usually appear before the age of three. The exact cause of autism is not entirely known, although genetics clearly plays an important role. Autism is one of a group of related developmental conditions sometimes called the autism spectrum that affect people differently and to varying degrees.

Autosome: Any chromosome that is not a sex chromosome. Humans have 22 pairs of autosomes.

Base Pair: Two complementary nucleotide bases (adenine-thymine or guanine-cytosine in DNA; adenine-uracil or guanine-cytosine in RNA) held together by hydrogen bonds.

Bioinformatics: The scientific field that uses computational tools and techniques to analyze and interpret biological data, particularly large-scale genetic and genomic datasets.

Birth Defect: (also called a congenital defect) is a physical or physiological abnormality present in a baby at birth. Birth defects can be caused by genetic factors, prenatal events during pregnancy or a combination of both. Some birth defects are easy to see (such as an extra or missing finger), while others (such as an enzyme deficiency) are identified through special tests.

BRCA1 and BRCA2: are the first two genes found to be associated with inherited forms of breast cancer and ovarian cancer. People with mutations in either BRCA1 or BRCA2 have a much higher risk for developing breast, ovarian or other types of cancer than those without mutations in the genes. Both BRCA1 and BRCA2 normally act as tumor suppressors, meaning they help to regulate cell division. Most people have two active copies of these genes. When one of the two copies becomes inactive due to an inherited mutation, a person’s cells are left with only one copy. If this remaining copy also becomes inactivated, then uncontrolled cell growth results, which leads to breast, ovarian or other types of cancer.

Cancer: is a disease in which some of the body’s cells grow uncontrollably. There are many different types of cancer, and each begins when a single cell acquires a genomic change (or mutation) that allows the cell to divide and multiply unchecked. Additional mutations can cause the cancer to spread to other sites. Such mutations can be caused by errors during DNA replication or result from DNA damage due to environmental exposures (such as tobacco smoke or the sun’s ultraviolet rays). In certain cases, mutations in cancer genes are inherited, which increases a person’s risk of developing cancer.

Cancer-Susceptibility Gene: is a gene that, when changed (or mutated), gives an individual an increased risk for developing cancer. Individuals who have inherited mutations in certain cancer-susceptibility genes have a lifetime risk of cancer that is significantly higher than the general population (e.g., BRCA1/BRCA2 ). Individuals in the high-risk category may benefit from more frequent cancer screens. There are also many gene variants associated with a small increase in risk. In some cases, environmental factors may also play a role.

Candidate Gene: A gene suspected to be involved in a particular trait or disease based on its biological function, chromosomal location, or expression pattern.

Carcinogen: Any substance or agent that can cause cancer by damaging DNA or disrupting cellular processes that control growth.
Carrier: An individual who has one copy of a recessive allele for a genetic disorder but does not show symptoms of the condition.
Carrier screening: involves testing to see if a person “carries” a genetic variation (allele) associated with a specific disease or trait. A carrier has inherited a normal and a variant allele for a disease- or trait-associated gene, one from each parent. Most typically, carrier screening is performed to look for recessively inherited diseases when the suspected carrier has no symptoms of the disease, but that person’s offspring could have the disease if the other parent is a carrier of a harmful variant in the same gene.

Cell-free DNA [ctDNA]: testing is a laboratory method that involves analyzing free (i.e., non-cellular) DNA contained within a biological sample, most often to look for genomic variants associated with a hereditary or genetic disorder. For example, prenatal cell-free DNA testing is a non-invasive method used during pregnancy that examines the fetal DNA that is naturally present in the maternal bloodstream. Cell-free DNA testing is also used for the detection and characterization of some cancers and to monitor cancer therapy.

Chromosome: A thread-like structure made of DNA and proteins that carries genetic information. Humans typically have 46 chromosomes (23 pairs) in each somatic cell.

Cloning: The process of creating genetically identical copies of a biological entity, which can range from a gene to an entire organism.
Codominance: A pattern of inheritance where two different alleles for a gene are both fully expressed in the heterozygote, resulting in a phenotype that shows both traits.

Codon: A sequence of three consecutive nucleotides in DNA or RNA that specifies a particular amino acid or signals the start or stop of protein synthesis.

Complex Disease: A disease influenced by multiple genetic and environmental factors, such as diabetes, heart disease, and most cancers.

Congenital: A condition present at birth, which may be caused by genetic factors, environmental factors, or a combination of both.

CRISPR: (short for “clustered regularly interspaced short palindromic repeats”) is a technology that research scientists use to selectively modify the DNA of living organisms. CRISPR: was adapted for use in the laboratory from naturally occurring genome editing systems found in bacteria.

Cystic fibrosis (abbreviated CF): is a genetic disorder that causes mucus to build up in certain organs of the body, particularly the lungs and pancreas, resulting in breathing problems, respiratory infections and faulty digestion. Caused by a mutation in a single gene (called CFTR), the disorder is inherited as an autosomal recessive trait, meaning that an affected individual inherits two mutated copies of the gene, one from each parent.

Data science: involves the study of large, complex data sets that arise from various types of research projects. With respect to genomic studies, such work requires expertise in quantitative scientific disciplines such as bioinformatics, computational biology and biostatistics.

Deletion: A type of mutation involving the loss of one or more nucleotides from a DNA sequence.

Deoxyribonucleic Acid (DNA): The molecule that carries genetic instructions for the development, functioning, growth, and reproduction of all known organisms.

Diploid: A cell or organism that has two complete sets of chromosomes, one from each parent.

DNA fingerprinting: is a laboratory technique used to determine the probable identity of a person based on the nucleotide sequences of certain regions of human DNA that are unique to individuals. DNA fingerprinting is used in a variety of situations, such as criminal investigations, other forensic purposes and paternity testing. In these situations, one aims to “match” two DNA fingerprints with one another, such as a DNA sample from a known person and one from an unknown person.

DNA Replication: The process by which a cell makes an identical copy of its DNA before cell division.

DNA sequencing: refers to the general laboratory technique for determining the exact sequence of nucleotides, or bases, in a DNA molecule. The sequence of the bases (often referred to by the first letters of their chemical names: A, T, C, and G) encodes the biological information that cells use to develop and operate. Establishing the sequence of DNA is key to understanding the function of genes and other parts of the genome. There are now several different methods available for DNA sequencing, each with its own characteristics, and the development of additional methods represents an active area of genomics research.

Dominant: A pattern of inheritance where only one copy of a gene variant (allele) is needed to express a particular trait.

Double helix:, as related to genomics, is a term used to describe the physical structure of DNA. A DNA molecule is made up of two linked strands that wind around each other to resemble a twisted ladder in a helix-like shape.

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.

Electrophoresis: A laboratory technique used to separate DNA, RNA, or protein molecules based on their size and electrical charge.

Environmental Factors: External conditions and influences (such as diet, toxins, and lifestyle) that can affect gene expression and contribute to health outcomes.
Enzyme: A protein that acts as a biological catalyst, speeding up chemical reactions in cells.

Epigenetics (also sometimes called epigenomics): is a field of study focused on changes in DNA that do not involve alterations to the underlying sequence. The DNA letters and the proteins that interact with DNA can have chemical modifications that change the degrees to which genes are turned on and off. Certain epigenetic modifications may be passed on from parent cell to daughter cell during cell division or from one generation to the next. The collection of all epigenetic changes in a genome is called an epigenome.

Eugenics: A discredited field that sought to improve the human population through selective breeding, often based on discriminatory and unethical practices.

Evolution: The process by which populations of organisms change over generations through genetic variation and natural selection.

Exome: The sequence of all the exons in a genome, reflecting the protein-coding portion of a genome. In humans, the exome is about 1.5% of the genome.

Exon: A region of a gene that codes for protein and is included in the mature messenger RNA after splicing.

Family History Information: about health conditions and diseases that have occurred in a person’s biological family, used to assess genetic risk.

First-degree: relative is a family member who shares about half of their genetic information with specific other individuals in their family. First-degree relatives include an individual’s parents, siblings and offspring.

Fluorescence in situ hybridization (abbreviated FISH): is a laboratory technique used to detect and locate a specific DNA sequence on a chromosome. In this technique, the full set of chromosomes from an individual is affixed to a glass slide and then exposed to a “probe”—a small piece of purified DNA tagged with a fluorescent dye. The fluorescently labeled probe finds and then binds to its matching sequence within the set of chromosomes. With the use of a special microscope, the chromosome and sub-chromosomal location where the fluorescent probe bound can be seen.

Frameshift Mutation: A genetic mutation caused by insertions or deletions of nucleotides that shifts the reading frame of the gene, typically resulting in a nonfunctional protein.

Gene: The basic unit of heredity, consisting of a specific sequence of DNA that codes for a functional product (usually a protein).

Gene Amplification: An increase in the number of copies of a particular gene, which can lead to overexpression of the gene product.

Gene Expression: The process by which information from a gene is used to synthesize a functional gene product (protein or RNA).

Gene Mapping: Determining the relative positions of genes on a chromosome and the distance between them.

Gene Pool: The complete set of genetic information (alleles) present in a population of organisms.

Gene Therapy: An experimental technique that uses genes to treat or prevent disease by introducing, removing, or altering genetic material within cells.

Genetic Code: The set of rules by which information encoded in DNA or RNA is translated into proteins.

Genetic Counseling: A communication process that helps individuals and families understand and adapt to the medical, psychological, and familial implications of genetic contributions to disease.

Genetic Discrimination: The unfair treatment of individuals based on their genetic information.

Genetic Drift: Random changes in allele frequencies in a population over time, particularly in small populations.

Genetic Engineering: The direct manipulation of an organism’s genes using biotechnology.

Genetic Map: A representation of the relative positions of genes on a chromosome based on recombination frequencies.

Genetic Marker: A specific DNA sequence with a known location on a chromosome that can be used to identify individuals or track inheritance patterns.

Genetic Mosaic: An individual with cells that have different genetic compositions, often due to mutations occurring after conception.

Genetic Screening: Testing populations or individuals to identify those at increased risk for specific genetic disorders.

Genetic Testing: The analysis of DNA, RNA, chromosomes, proteins, or metabolites to detect heritable disease-related genotypes, mutations, phenotypes, or karyotypes.

Genetics: The study of genes, genetic variation, and heredity in living organisms.

Genome: The complete set of genetic instructions (DNA) for an organism.

Genome-Wide Association Study (GWAS): An approach that involves rapidly scanning markers across the complete sets of DNA of many people to find genetic variations associated with a particular disease.

Genomic Imprinting: An epigenetic phenomenon where genes are expressed in a parent-of-origin-specific manner.

Genomic Medicine: is a medical discipline that involves using a person’s genomic information as part of their clinical care. Other similar terms include individualized medicine, personalized medicine and precision medicine. For some conditions, genomic information can be used to help diagnose disease, predict outcomes and guide treatment.

Genomics: The study of the structure, function, evolution, mapping, and editing of genomes.

Genotype: The genetic makeup of an organism, as distinguished from its physical characteristics (phenotype).

Germ Line: The cells that give rise to gametes (eggs and sperm) and are therefore responsible for passing genetic information to offspring.

Guanine (G): One of the four nucleotide bases in DNA, pairing with cytosine (C) in the DNA double helix. It is a purine base.

Heterozygous: Having two different alleles for a particular gene at a specific locus on homologous chromosomes.

Homologous Chromosomes: A pair of chromosomes containing the same gene sequences, one inherited from each parent.

The Human Genome Project was a large international, collaborative effort that mapped and sequenced the human genome for the first time. Conducted from 1990 to 2003, the project was historic in its scope and scale as well as its groundbreaking approach for the free release of genomic data well ahead of publication, leading to a new ethos for data sharing in biomedical research.

Human Genome Reference Sequence is an accepted representation of the human genome sequence that is used by researchers as a standard for comparison to DNA sequences generated in their studies. The scientists responsible for assembling and updating such reference sequences aim to provide the highest-quality, best possible consensus representations of the sequence and structural diversity found in the human genome among populations. The genome reference sequence provides a general framework and is not the DNA sequence of a single person.

Huntington’s Disease is a rare inherited disorder associated with the progressive loss of brain and muscle function. Symptoms usually develop during middle age and may include uncontrolled movements, loss of intellectual abilities and various emotional and psychiatric symptoms. Huntington’s disease is inherited as an autosomal dominant trait, meaning that a single mutated copy of the responsible gene (called HTT) is sufficient to cause the disease.

Insertion: A type of mutation involving the addition of one or more nucleotides into a DNA sequence.

Intron: A non-coding region of a gene that is removed during RNA splicing and does not appear in the mature messenger RNA.

Inversion: A chromosomal rearrangement in which a segment of a chromosome is reversed end to end.

Knockout: A genetic technique in which one or more of an organism’s genes are made inoperative.

Library: A collection of DNA fragments that have been cloned into vectors so they can be maintained in a host organism.

Li-Fraumeni syndrome (LFS): is an inherited predisposition to a wide range of certain cancers caused by pathogenic TP53 germline variants.

Marker (largely synonymous with the word “landmark” and often referred to as a genomic marker or a genetic marker) is a DNA sequence, typically with a known location in a genome. Markers can reflect random sequences, genomic variants or genes. Markers are used as signposts (or landmarks) in the construction of DNA and genome maps. Markers can also be used to track inheritance of traits or disease risk in families.

Mendelian Inheritance Patterns of inheritance characteristics of organisms that reproduce sexually, as described by Gregor Mendel.

Messenger RNA (mRNA): A type of RNA that carries the genetic information from DNA to the ribosome, where it serves as a template for protein synthesis.

Methylation is a chemical modification of DNA and other molecules that may be retained as cells divide to make more cells. When found in DNA, methylation can alter gene expression. In this process, chemical tags called methyl groups attach to a particular location within DNA where they turn a gene on or off, thereby regulating the production of proteins that the gene encodes.

Microbiome is the community of microorganisms (such as fungi, bacteria and viruses) that exists in a particular environment. In humans, the term is often used to describe the microorganisms that live in or on a particular part of the body, such as the skin or gastrointestinal tract. These groups of microorganisms are dynamic and change in response to a host of environmental factors, such as exercise, diet, medication and other exposures.

Mitosis: The process of cell division that results in two genetically identical daughter cells from a single parent cell.

Monogenic Disorder: A disorder caused by variation in a single gene.

Mosaicism: The presence of two or more populations of cells with different genotypes in one individual.

A mutagen is a chemical or physical agent capable of inducing changes in DNA called mutations. Examples of mutagens include tobacco products, radioactive substances, x-rays, ultraviolet radiation and a wide variety of chemicals. Exposure to a mutagen can produce DNA mutations that cause or contribute to certain diseases.

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.

Newborn Screening is a set of laboratory tests performed on newborn babies to detect a set of known genetic diseases. Typically, this testing is performed on a blood sample obtained from a heel prick when the baby is two or three days old. In the United States, newborn screening is mandatory for a defined set of genetic diseases, although the exact set differs from state to state. Newborn screening tests focus on conditions for which early diagnosis is important to treating or preventing disease

Next-Generation DNA sequencing establishes the order of the bases that make up DNA. Next-generation DNA sequencing (abbreviated NGS) refers to the use of technologies for sequencing DNA that became available shortly after the completion of the Human Genome Project (which relied on the first-generation method of Sanger sequencing). Faster and cheaper than their predecessors, NGS technologies can sequence an entire human genome in a single day and for less than 1,000.

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.

Oncology: The medical specialty that deals with cancer.