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NCI Dictionary of Genetics Terms

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  • affected  listen  (uh-FEK-ted)
    Individuals in a pedigree who exhibit the specific phenotype under study.

  • allele  listen  (uh-LEEL)
    One of two or more DNA sequences occurring at a particular gene locus. Typically one allele (“normal” DNA sequence) is common, and other alleles (mutations) are rare.

  • allelic heterogeneity  listen  (uh-LEE-lik HEH-teh-roh-jeh-NEE-ih-tee)
    Different mutations in the same gene that cause different phenotypic manifestations or severity of disease.

  • aneuploidy  listen  (AN-yoo-PLOY-dee)
    The occurrence of one or more extra or missing chromosomes leading to an unbalanced chromosome complement, or any chromosome number that is not an exact multiple of the haploid number (which is 46).

  • ART 
    A term used to describe collectively a number of noncoital methods of conception that are used to treat infertility with donor or nondonor eggs and sperm including in vitro fertilization (IVF), gamete intrafallopian transfer (GIFT), and zygote intrafallopian transfer (ZIFT). Also called assisted reproductive technology.

  • Ashkenazi Jews  listen  (ASH-keh-NAH-zee jooz)
    One of two major ancestral groups of Jewish individuals, comprised of those whose ancestors lived in Central and Eastern Europe (e.g., Germany, Poland, Russia). The other group is designated Sephardic Jews and includes those whose ancestors lived in North Africa, the Middle East, and Spain. Most Jews living in the United States are of Ashkenazi descent.

  • assisted reproductive technology  listen  (uh-SIS-ted REE-proh-DUK-tiv tek-NAH-loh-jee)
    A term used to describe collectively a number of noncoital methods of conception that are used to treat infertility with donor or nondonor eggs and sperm including in vitro fertilization (IVF), gamete intrafallopian transfer (GIFT), and zygote intrafallopian transfer (ZIFT). Also called ART.

  • attributable risk  listen  (uh-TRIH-byoo-tuh-bul …)
    Proportion of a disease in exposed individuals that can be attributed to an exposure. In the context of genetic studies, the "exposure" is the frequency of a specific genetic variant.

  • autosomal  listen  (AW-toh-SOH-mul)
    Refers to any of the chromosomes numbered 1-22 or the genes on chromosomes 1-22. This term excludes the sex-determining chromosomes, X and Y.

  • autosomal dominant  listen  (AW-toh-SOH-mul DAH-mih-nunt)
    Autosomal dominant inheritance refers to genetic conditions that occur when a mutation is present in one copy of a given gene (i.e., the person is heterozygous).

  • autosomal recessive  listen  (AW-toh-SOH-mul reh-SEH-siv)
    Autosomal recessive inheritance refers to genetic conditions that occur only when mutations are present in both copies of a given gene (i.e., the person is homozygous for a mutation, or carries two different mutations of the same gene, a state referred to as compound heterozygosity).

  • band  listen  (band)
    When chromosomes at a particular stage in cell division are stained using one of several laboratory techniques, a specific pattern of light and dark stripes (bands) appears when the chromosomes are viewed through a microscope; the banding pattern assists in assigning each chromosome its particular number and evaluating its structure.

  • base pair  listen  (bays payr)
    Two nitrogen-containing bases pair together between double-stranded DNA; only specific combinations of these bases (e.g., adenine with thymine; guanine with cytosine) are possible, a fact which facilitates accurate DNA replication; when quantified (e.g., 8 base pairs, or bp), this term refers to the actual number of base pairs in a sequence of nucleotides.

  • carrier  listen  (KAYR-ee-er)
    In classical genetics, an individual who carries one deleterious allele for an autosomal recessive disorder. In clinical discussions, may refer to an individual who carries a deleterious allele that predisposes to disease.

  • carrier frequency  listen  (KAYR-ee-er FREE-kwen-see)
    The proportion of individuals in a population who have a single copy of a specific recessive gene mutation; also sometimes applied to the prevalence of mutations in dominantly acting genes such as BRCA1 and BRCA2. Also called carrier rate.

  • carrier rate  listen  (KAYR-ee-er rayt)
    The proportion of individuals in a population who have a single copy of a specific recessive gene mutation; also sometimes applied to the prevalence of mutations in dominantly acting genes such as BRCA1 and BRCA2. Also called carrier frequency.

  • chromosome  listen  (KROH-muh-some)
    Discrete physical structures inside a cell nucleus that consist of proteins and DNA organized into genes.

  • clone  listen  (klone)
    An identical copy of a DNA sequence or entire gene; one or more cells derived from and identical to a single ancestor cell OR to isolate a gene or specific sequence of DNA.

  • CNV 
    Refers to the genetic trait involving the number of copies of a particular gene present in the genome of an individual. Genetic variants, including insertions, deletions, and duplications of segments of DNA, are also collectively referred to as CNVs. CNVs account for a significant proportion of the genetic variation between individuals. Also called copy number variant.

  • codon  listen  (KOH-don)
    In DNA or RNA, a sequence of 3 consecutive nucleotides that codes for a specific amino acid or signals the termination of gene translation (stop or termination codon).

  • conformation-sensitive gel electrophoresis  listen  (KON-for-MAY-shun-SEN-sih-tiv jel ee-LEK-troh-fuh-REE-sis)
    A type of mutation testing in which a segment of DNA is screened for mismatched pairing between normal and mutated base pairs. Also called CSGE.

  • congenital  listen  (kun-JEH-nih-tul)
    A condition or trait present at birth. It may be the result of genetic or non-genetic factors.

  • consanguinity  listen  (KON-sang-GWIH-nih-tee)
    Genetic relatedness between individuals who are descendants of at least one common ancestor.

  • consent process  listen  (kun-SENT PRAH-ses)
    A process of information exchange between a clinician and an individual or their legal proxy designed to facilitate autonomous, informed decision making. The informed consent process for genetic testing should include an explanation of the medical and psychosocial risks, benefits, limitations, and potential implications of genetic analysis, a discussion of privacy, confidentiality, the documentation and handling of genetic test results, as well as options for managing the hereditary disease risk. Also called informed consent.

  • consultand  listen  (kon-SUL-tand)
    An individual who presents for genetic counseling. Also called counselee.

  • copy number variant  listen  (KAH-pee NUM-ber VAYR-ee-unt)
    Refers to the genetic trait involving the number of copies of a particular gene present in the genome of an individual. Genetic variants, including insertions, deletions, and duplications of segments of DNA, are also collectively referred to as copy number variants. Copy number variants account for a significant proportion of the genetic variation between individuals. Also called CNV.

  • cosegregation  listen  (KOH-seh-greh-GAY-shun)
    The transmission, together, of 2 or more genes on the same chromosome, as a result of their being in very close physical proximity to one another (i.e., linked).

  • counselee  listen  (kown-seh-LEE)
    An individual who presents for genetic counseling. Also called consultand.

  • Crohn disease-like reaction  listen  (krone dih-ZEEZ-like ree-AK-shun)
    Discrete aggregates of lymphoid white blood cells, some with germinal centers and surrounding fibrosis, commonly found around some colorectal adenocarcinomas in the absence of a clinical or pathological diagnosis of Crohn disease. Also called Crohn-like reaction.

  • Crohn-like reaction  listen  (krone-like ree-AK-shun)
    Discrete aggregates of lymphoid white blood cells, some with germinal centers and surrounding fibrosis, commonly found around some colorectal adenocarcinomas in the absence of a clinical or pathological diagnosis of Crohn disease. Also called Crohn disease-like reaction.

  • CSGE 
    A type of mutation testing in which a segment of DNA is screened for mismatched pairing between normal and mutated base pairs. Also called conformation-sensitive gel electrophoresis.

  • cytogenetics  listen  (SY-toh-jeh-NEH-tix)
    The study of the structure, function, and abnormalities of human chromosomes.

  • de novo mutation  listen  (deh NOH-voh myoo-TAY-shun)
    An alteration in a gene that is present for the first time in one family member as a result of a mutation in a germ cell (egg or sperm) of one of the parents, or a mutation that arises in the fertilized egg itself during early embryogenesis. Also called new mutation.

  • deleterious mutation  listen  (DEH-leh-TEER-ee-us myoo-TAY-shun)
    A mutation that is documented to be associated with risk of disease.

  • deletion  listen  (deh-LEE-shun)
    Absence of a segment of DNA; may be as small as a single base or as large as a whole chromosome.

  • deoxyribonucleic acid  listen  (dee-OK-see-RY-boh-noo-KLAY-ik A-sid)
    The molecular basis of heredity; encodes the genetic information responsible for the development and function of an organism and allows for transmission of that genetic information from one generation to the next. The DNA molecule is structured as a double-stranded helix held together by weak hydrogen bonds between purine-pyrimidine nucleotide base pairs: adenine (A) paired with thymine (T), and guanine (G) paired with cytosine (C). Also called DNA.

  • dirty necrosis  listen  (DIR-tee neh-KROH-sis)
    Presence of necrotic cellular debris within the lumen of the neoplastic glands in the colorectal mucosa.

  • disease-causing mutation  listen  (dih-ZEEZ-KAW-sing myoo-TAY-shun)
    A gene alteration that causes or predisposes an individual to a specific disease.

  • DNA 
    The molecular basis of heredity; encodes the genetic information responsible for the development and function of an organism and allows for transmission of that genetic information from one generation to the next. The DNA molecule is structured as a double-stranded helix held together by weak hydrogen bonds between purine-pyrimidine nucleotide base pairs: adenine (A) paired with thymine (T), and guanine (G) paired with cytosine (C). Also called deoxyribonucleic acid.

  • domain  listen  (doh-MAYN)
    A specific physical region or amino acid sequence in a protein which is associated with a particular function or corresponding segment of DNA.

  • epigenetic alteration  listen  (EH-pih-jeh-NEH-tik ALL-teh-RAY-shun)
    A heritable change that does not affect the DNA sequence but results in a change in gene expression. Examples include promoter methylation and histone modifications. Also called epimutation.

  • epigenetics  listen  (EH-pih-jeh-NEH-tix)
    The study of heritable changes that do not affect the DNA sequence but influence gene expression.

  • epimutation  listen  (EH-pih-myoo-TAY-shun)
    A heritable change that does not affect the DNA sequence but results in a change in gene expression. Examples include promoter methylation and histone modifications. Also called epigenetic alteration.

  • ER-negative PR-negative HER2/neu-negative breast cancer  listen  (... NEH-guh-tiv ... NEH-guh-tiv ... NEH-guh-tiv brest KAN-ser)
    ER-negative PR-negative HER2/neu-negative breast cancer is defined by a lack of expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2/neu). Also called triple-negative breast cancer.

  • exon  listen  (EK-son)
    The sequence of DNA present in mature messenger RNA, some of which encodes the amino acids of a protein. Most genes have multiple exons with introns between them.

  • false-positive result  listen  (… PAH-zih-tiv reh-ZULT)
    A test result that indicates an individual is affected and/or has a certain gene mutation when he or she is actually unaffected and/or does not have the mutation; i.e., a positive test result in a truly unaffected or mutation-negative individual.

  • familial  listen  (fuh-MIH-lee-ul)
    A phenotype or trait that occurs with greater frequency in a given family than in the general population; familial traits may have a genetic and/or nongenetic etiology.

  • family history  listen  (FA-mih-lee HIH-stuh-ree)
    The genetic relationships within a family combined with the medical history of individual family members. When represented in diagram form using standardized symbols and terminology, it is usually referred to as a pedigree or family tree. Also called family medical history.

  • family medical history  listen  (FA-mih-lee MEH-dih-kul HIH-stuh-ree)
    The genetic relationships within a family combined with the medical history of individual family members. When represented in diagram form using standardized symbols and terminology, it is usually referred to as a pedigree or family tree. Also called family history.

  • FDR 
    The parents, siblings, or children of an individual. Also called first-degree relative.

  • first-degree relative  listen  (first-deh-GREE REH-luh-tiv)
    The parents, siblings, or children of an individual. Also called FDR.

  • FISH  listen
    A technique used to identify the presence of specific chromosomes or chromosomal regions through hybridization (attachment) of fluorescently-labeled DNA probes to denatured chromosomal DNA. Examination through a microscope under fluorescent lighting detects the presence of the colored hybridized signal (and hence presence of the chromosome material) or absence of the hybridized signal (and hence absence of the chromosome material). Also called fluorescence in situ hybridization.

  • fluorescence in situ hybridization  listen  (floor-EH-sents in SY-too HY-brih-dih-ZAY-shun)
    A technique used to identify the presence of specific chromosomes or chromosomal regions through hybridization (attachment) of fluorescently-labeled DNA probes to denatured chromosomal DNA. Examination through a microscope under fluorescent lighting detects the presence of the colored hybridized signal (and hence presence of the chromosome material) or absence of the hybridized signal (and hence absence of the chromosome material). Also called FISH.

  • founder mutation  listen  (FOWN-der myoo-TAY-shun)
    A gene mutation observed with high frequency in a group that is or was geographically or culturally isolated, in which one or more of the ancestors was a carrier of the mutant gene. This phenomenon is often called a founder effect.

  • frameshift mutation  listen  (FRAYM-shift myoo-TAY-shun)
    An insertion or deletion involving a number of base pairs that is not a multiple of three, which consequently disrupts the triplet reading frame of a DNA sequence. Such mutations usually lead to the creation of a premature termination (stop) codon, and result in a truncated (shorter-than-normal) protein product.

  • gene  listen  (jeen)
    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.

  • genetic anticipation  listen  (jeh-NEH-tik an-TIH-sih-PAY-shun)
    A phenomenon in which the signs and symptoms of some genetic conditions tend to become more severe and/or appear at an earlier age as the disorder is passed from one generation to the next. Huntington disease is an example of a genetic disorder in which the biological mechanism for this phenomenon has been well documented. In other cases, it may be due to factors such as increased surveillance or other nongenetic causes.

  • genetic counseling  listen  (jeh-NEH-tik KOWN-suh-ling)
    A communication process that seeks to assist affected or at-risk individuals and families in understanding the natural history, disease risks, and mode of transmission of a genetic disorder; to facilitate informed consent for genetic testing when appropriate; to discuss options for risk management and family planning; and to provide for or refer individuals for psychosocial support as needed. The National Society of Genetic Counselors Task Force has also defined the term genetic counseling.

  • genetic heterogeneity  listen  (jeh-NEH-tik HEH-teh-roh-jeh-NEE-ih-tee)
    The production of the same or similar phenotypes (observed biochemical, physiological, and morphological characteristics of a person determined by his/her genotype) by different genetic mechanisms. There are two types: (1) allelic heterogeneity – when different alleles at a locus can produce variable expression of a condition; and (2) locus heterogeneity – the term used to describe disease in which mutations at different loci can produce the same disease phenotype.

  • genetic marker  listen  (jeh-NEH-tik MAR-ker)
    An identifiable segment of DNA (e.g., Single Nucleotide Polymorphism [SNP], Restriction Fragment Length Polymorphism [RFLP], Variable Number of Tandem Repeats [VNTR], microsatellite) with enough variation between individuals that its inheritance and co-inheritance with alleles of a given gene can be traced; used in linkage analysis.

  • genetic predisposition  listen  (jeh-NEH-tik PREE-dih-spuh-ZIH-shun)
    Increased likelihood or chance of developing a particular disease due to the presence of one or more gene mutations and/or a family history that indicates an increased risk of the disease. Also called genetic susceptibility.

  • genetic screening  listen  (jeh-NEH-tik SKREE-ning)
    Genetic testing designed to identify individuals in a given population who are at higher risk of having or developing a particular disorder, or carrying a gene for a particular disorder.

  • genetic susceptibility  listen  (jeh-NEH-tik suh-SEP-tih-BIH-lih-tee)
    Increased likelihood or chance of developing a particular disease due to the presence of one or more gene mutations and/or a family history that indicates an increased risk of the disease. Also called genetic predisposition.

  • genodermatosis  listen  (JEE-noh-DER-muh-TOH-sis)
    An inherited syndrome that includes a dermatological (skin) phenotype.

  • genome-wide association study  listen  (JEE-nome ... uh-SOH-see-AY-shun STUH-dee)
    Genome-wide association studies (GWAS) are a way for scientists to identify genes involved in human disease. This method searches the genome for small variations, called single nucleotide polymorphisms or SNPs (pronounced “snips”), that occur more frequently in people with a particular disease than in people without the disease. Also called GWAS, WGA study, and whole genome association study.

  • genomic imprinting  listen  (jeh-NOH-mik im-PRIN-ting)
    The process by which one chromosome of a pair is chemically modified, depending on whether the chromosome comes from the father or the mother. These modifications lead to differential expression of a gene or genes on a maternally derived chromosome versus a paternally derived chromosome.

  • genotype  listen  (JEE-noh-tipe)
    At its broadest level, genotype includes the entire genetic constitution of an individual. It is often applied more narrowly to the set of alleles present at one or more specific loci.

  • germline  listen  (JERM-line)
    The cells from which eggs or sperm (i.e., gametes) are derived.

  • GWAS  listen
    GWAS (genome-wide association studies) are a way for scientists to identify genes involved in human disease. This method searches the genome for small variations, called single nucleotide polymorphisms or SNPs (pronounced “snips”), that occur more frequently in people with a particular disease than in people without the disease. Also called genome-wide association study, WGA study, and whole genome association study.

  • haplotype  listen  (HA-ploh-tipe)
    A set of closely linked genetic markers present on one chromosome which tend to be inherited together.

  • heteroduplex analysis  listen  (HEH-teh-roh-DOO-plex uh-NA-lih-sis)
    A method of detecting sequence differences between normal DNA and the DNA to be tested. It is commonly used as a screening method to detect potential mutations in a gene.

  • heterozygous genotype  listen  (HEH-teh-roh-ZY-gus JEE-noh-tipe)
    Occurs when the two alleles at a particular gene locus are different. A heterozygous genotype may include one normal allele and one mutation, or two different mutations. The latter is called a compound heterozygote.

  • homozygous genotype  listen  (HOH-moh-ZY-gus JEE-noh-tipe)
    Occurs when both alleles at a particular gene locus are the same. A person may be homozygous for the normal allele or for a mutation.

  • inconclusive  listen  (IN-kun-KLOO-siv)
    A negative test result in an individual where a clearly deleterious mutation has not been found in any family members. The genetic risk status of such an individual must be interpreted in the context of his or her personal and family history. Also called indeterminate and uninformative.

  • indeterminate  listen  (IN-deh-TER-mih-nut)
    A negative test result in an individual where a clearly deleterious mutation has not been found in any family members. The genetic risk status of such an individual must be interpreted in the context of his or her personal and family history. Also called inconclusive and uninformative.

  • index case  listen  (IN-dex kays)
    A clinically affected individual through whom attention is first drawn to a genetic disorder in a family.

  • informative  listen  (in-FOR-muh-tiv)
    In genetic testing, a test result that reveals definitively the presence or absence of the germline genetic alteration associated with the hereditary disorder being assessed. In linkage analysis, the ability to distinguish between maternally inherited and paternally inherited DNA markers (polymorphisms) within or near a given gene of interest.

  • informed consent  listen  (in-FORMD kun-SENT)
    A process of information exchange between a clinician and an individual or their legal proxy designed to facilitate autonomous, informed decision making. The informed consent process for genetic testing should include an explanation of the medical and psychosocial risks, benefits, limitations, and potential implications of genetic analysis, a discussion of privacy, confidentiality, the documentation and handling of genetic test results, as well as options for managing the hereditary disease risk. Also called consent process.

  • inherited cancer syndrome  listen  (in-HAYR-ih-ted KAN-ser SIN-drome)
    Describes the clinical manifestations associated with a mutation conferring cancer susceptibility.

  • intron  listen  (IN-tron)
    The sequence of DNA in between exons that is initially copied into RNA but is cut out of the final RNA transcript and therefore does not change the amino acid code. Some intronic sequences are known to affect gene expression.

  • inversion  listen  (in-VER-zhun)
    A chromosomal defect in which a segment of the chromosome breaks off and reattaches in the reverse direction.

  • kindred  listen  (KIN-dred)
    An extended family.

  • late or variable onset  listen  (layt … VAYR-ee-uh-bul …)
    The state in which a genetic trait is expressed later in life or is expressed at no fixed time in a life history.

  • LD 
    Where alleles (DNA markers) occur together more often than can be accounted for by chance because of their physical proximity on a chromosome. Also called linkage disequilibrium.

  • linkage  listen  (LING-kij)
    The tendency for genes or segments of DNA closely positioned along a chromosome to segregate together at meiosis, and therefore be inherited together.

  • linkage analysis  listen  (LING-kij uh-NA-lih-sis)
    A gene-hunting technique that traces patterns of disease in high-risk families. It attempts to locate a disease-causing gene by identifying genetic markers of known chromosomal location that are co-inherited with the trait of interest.

  • linkage disequilibrium  listen  (LING-kij dis-EE-kwih-LIH-bree-um)
    Where alleles (DNA markers) occur together more often than can be accounted for by chance because of their physical proximity on a chromosome. Also called LD.

  • locus  listen  (LOH-kus)
    The physical site or location of a specific gene on a chromosome.

  • locus heterogeneity  listen  (LOH-kus HEH-teh-roh-jeh-NEE-ih-tee)
    The situation in which mutations in genes at different chromosomal loci result in the same phenotype.

  • LOD score  listen  (… skor)
    A statistical estimate of whether two genetic loci are physically near enough to each other (or "linked") on a particular chromosome that they are likely to be inherited together. A LOD score of three or more is generally considered statistically significant evidence of linkage. Also called logarithm of the odd score.

  • logarithm of the odd score  listen  (LAW-guh-RIH-thum … skor)
    A statistical estimate of whether two genetic loci are physically near enough to each other (or "linked") on a particular chromosome that they are likely to be inherited together. A LOD score of three or more is generally considered statistically significant evidence of linkage. Also called LOD score.

  • 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 disorder, 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. Also called loss of heterozygosity.

  • loss of heterozygosity  listen  (… HEH-teh-roh-zy-GAH-sih-tee)
    If there is one normal and one abnormal allele at a particular locus, as might be seen in an inherited autosomal dominant cancer susceptibility disorder, 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. Also called LOH.

  • microsatellite  listen  (MY-kroh-SA-teh-lite)
    Repetitive segments of DNA scattered throughout the genome in noncoding regions between genes or within genes (introns). They are often used as markers for linkage analysis because of their naturally occurring high variability in repeat number between individuals. These regions are inherently genetically unstable and susceptible to mutations.

  • microsatellite instability  listen  (MY-kroh-SA-teh-lite in-stuh-BIH-lih-tee)
    A characteristic of cells that contain an abnormality in DNA mismatch repair (see microsatellite). For example, the presence of MSI in colorectal tumor tissue may be used as a marker for germline mutations in one of the DNA mismatch repair genes associated with HNPCC. MSI can also occur sporadically, and in these cases is related to gene hypermethylation. This is an issue in the differential diagnosis of HNPCC. Also called MSI.

  • missense mutation  listen  (MIS-sens myoo-TAY-shun)
    A single base pair substitution that alters the genetic code in a way that produces an amino acid that is different from the usual amino acid at that position. Some missense mutations will alter the function of the protein.

  • MLPA 
    A laboratory method commonly used for the detection of unusual copy number changes (insertions or deletions) of genomic sequences. Also called multiplex ligation-dependent probe amplification.

  • mode of inheritance  listen  (… in-HAYR-ih-tunts)
    The manner in which a genetic trait or disorder is passed from one generation to the next. Autosomal dominant, autosomal recessive, X-linked dominant, X-linked recessive, multifactorial, and mitochondrial inheritance are examples. Each mode of inheritance results in a characteristic pattern of affected and unaffected family members.

  • mosaicism  listen  (moh-ZAY-ih-SIH-zum)
    The occurrence of 2 or more cell lines with different genetic or chromosomal make-up, within a single individual or tissue.

  • MSI 
    A characteristic of cells that contain an abnormality in DNA mismatch repair (see microsatellite). For example, the presence of MSI in colorectal tumor tissue may be used as a marker for germline mutations in one of the DNA mismatch repair genes associated with HNPCC. MSI can also occur sporadically, and in these cases is related to gene hypermethylation. This is an issue in the differential diagnosis of HNPCC. Also called microsatellite instability.

  • multiplex genomic test  listen  (MUL-tee-plex jeh-NOH-mik test)
    A method for detecting multiple genetic alterations (i.e., gene mutations or single nucleotide polymorphisms in a single gene or across the genome) simultaneously.

  • multiplex ligation-dependent probe amplification  listen  (MUL-tee-plex ly-GAY-shun-deh-PEN-dent probe AM-plih-fih-KAY-shun)
    A laboratory method commonly used for the detection of unusual copy number changes (insertions or deletions) of genomic sequences. Also called MLPA.

  • mutation  listen  (myoo-TAY-shun)
    A change in the usual DNA sequence at a particular gene locus. Mutations (including polymorphisms) can be harmful, beneficial, or neutral in their effect on cell function.

  • mutation analysis  listen  (myoo-TAY-shun uh-NA-lih-sis)
    Germline genetic testing method targeted to detect a specific mutation (such as a deleterious MSH2 mutation previously identified in a family), panel of mutations (such as the 3 BRCA mutations comprising the founder mutation panel for individuals of Ashkenazi Jewish ancestry) or type of mutation (such as a large deletions or insertions in the BRCA1 gene). This type of testing is distinct from complete gene sequencing or mutation scanning. The latter are designed to detect most mutations in the region being tested. Current usage also applies this term to any genetic test.

  • negative predictive value  listen  (NEH-guh-tiv preh-DIK-tiv VAL-yoo)
    The likelihood that an individual with a negative test result is truly unaffected and/or does not have the particular gene mutation in question. Also called NPV.

  • new mutation  listen  (noo myoo-TAY-shun)
    An alteration in a gene that is present for the first time in one family member as a result of a mutation in a germ cell (egg or sperm) of one of the parents, or a mutation that arises in the fertilized egg itself during early embryogenesis. Also called de novo mutation.

  • noncarrier  listen  (non-KAYR-ee-er)
    An individual who does not carry a mutation previously identified in his or her family.

  • nonpenetrance  listen  (non-PEH-neh-trunts)
    The state in which a genetic trait, although present in the appropriate genotype, fails to manifest itself in the phenotype (e.g., a woman with a BRCA1 mutation who lives to be elderly and never develops breast or ovarian cancer).

  • nonsense mutation  listen  (NON-sens myoo-TAY-shun)
    A mutation that alters the genetic code in a way that causes the premature termination of a protein. The altered protein may be partially or completely inactivated, resulting in a change or loss of protein function.

  • novel mutation  listen  (NAH-vel myoo-TAY-shun)
    A newly discovered, distinct gene alteration; NOT the same as new or de novo mutation.

  • NPV 
    The likelihood that an individual with a negative test result is truly unaffected and/or does not have the particular gene mutation in question. Also called negative predictive value.

  • nucleotide  listen  (NOO-klee-oh-tide)
    A molecule consisting of a nitrogen-containing base (adenine, guanine, thymine, or cytosine in DNA; adenine, guanine, uracil, or cytosine in RNA), a phosphate group, and a sugar (deoxyribose in DNA; ribose in RNA). DNA and RNA are polymers comprised of many nucleotides, strung together like beads in a necklace.

  • null allele  listen  (nul uh-LEEL)
    A mutation that results in either no gene product or the absence of function at the phenotypic level.

  • nutrigenomics  listen  (NOO-trih-jeh-NOH-mix)
    The study of the interaction of dietary and genetic factors and its effect on metabolism, health status, and risk of disease.

  • pathognomonic  listen  (PA-thog-noh-MAH-nik)
    Findings that are distinctive or characteristic of a particular disease or condition and make the diagnosis.

  • PCR 
    A procedure that produces millions of copies of a short segment of DNA through repeated cycles of: (1) denaturation, (2) annealing, and (3) elongation. PCR is a very common procedure in molecular genetic testing and may be used to generate a sufficient quantity of DNA to perform a test (e.g., allele-specific amplification, trinucleotide repeat quantification). Also called polymerase chain reaction.

  • pedigree  listen  (PEH-dih-gree)
    A graphic illustration of family history.

  • penetrance  listen  (PEH-neh-trunts)
    A characteristic of a genotype; it refers to the likelihood that a clinical condition will occur when a particular genotype is present.

  • phenocopy  listen  (FEE-noh-KAH-pee)
    A phenotypic trait or disease that resembles the trait expressed by a particular genotype, but in an individual who is not a carrier of that genotype. For example, breast cancer in a hereditary breast/ovarian cancer syndrome family member who does not carry the family’s BRCA1 or BRCA2 mutation would be considered a phenocopy. Such an individual does not have the family’s cancer-related mutation and therefore, they do not have the associated cancer risk from that specific mutation.

  • phenotype  listen  (FEE-noh-tipe)
    The observable characteristics in an individual resulting from the expression of genes; the clinical presentation of an individual with a particular genotype.

  • point mutation  listen  (poynt myoo-TAY-shun)
    An alteration in a DNA sequence caused by the substitution of a single nucleotide for another nucleotide.

  • polymerase chain reaction  listen  (puh-LIH-meh-rays chayn ree-AK-shun)
    A procedure that produces millions of copies of a short segment of DNA through repeated cycles of: (1) denaturation, (2) annealing, and (3) elongation. Polymerase chain reaction is a very common procedure in molecular genetic testing and may be used to generate a sufficient quantity of DNA to perform a test (e.g., allele-specific amplification, trinucleotide repeat quantification). Also called PCR.

  • polymorphism  listen  (PAH-lee-MOR-fih-zum)
    A common mutation. “Common” is typically defined as an allele frequency of at least 1%. All genes occur in pairs, except when x and y chromosomes are paired in males; thus a polymorphism with an allele frequency of 1% would be found in about 2% of the population, with most carriers having one copy of the polymorphism and one copy of the normal allele.

  • population risk  listen  (PAH-pyoo-LAY-shun …)
    The proportion of individuals in the general population who are affected with a particular disorder or who carry a certain gene; often discussed in the genetic counseling process as a comparison to the patient’s personal risk given his or her family history or other circumstances.

  • positive predictive value  listen  (PAH-zih-tiv preh-DIK-tiv VAL-yoo)
    The likelihood that an individual with a positive test result truly has the particular gene and/or disease in question. Also called PPV.

  • PPV 
    The likelihood that an individual with a positive test result truly has the particular gene and/or disease in question. Also called positive predictive value.

  • predisposing mutation  listen  (PREE-dih-SPOH-zing myoo-TAY-shun)
    A germline mutation that increases an individual’s susceptibility or predisposition to a certain disease or disorder. When such a mutation is inherited, development of symptoms is more likely, but not certain. Also called susceptibility gene.

  • presymptomatic testing  listen  (PREE-simp-toh-MA-tik TES-ting)
    Genetic analysis of an asymptomatic or unaffected individual who is at risk of a specific genetic disorder.

  • proband  listen  (PROH-band)
    The individual through whom a family with a genetic disorder is ascertained. In males this is called a propositus, and in females it is called a proposita.

  • proposita  listen  (proh-PAH-zih-tuh)
    The female individual through whom a family with a genetic disorder is ascertained. In males this is called a propositus.

  • propositus  listen  (proh-PAH-zih-tus)
    The male individual through whom a family with a genetic disorder is ascertained. In females this is called a proposita.

  • recurrence risk  listen  (ree-KER-ents risk)
    In genetics, the likelihood that a hereditary trait or disorder present in one family member will occur again in other family members. This is distinguished from recurrence risk for cancer, which is the chance that a cancer that has been treated will recur.

  • risk assessment  listen  (… uh-SES-ment)
    The quantitative or qualitative assessment of an individual’s risk of carrying a certain gene mutation, or developing a particular disorder, or of having a child with a certain disorder; sometimes done by using mathematical or statistical models incorporating such factors as personal health history, family medical history and ethnic background.

  • screening  listen  (SKREE-ning)
    Clinical evaluation of an asymptomatic individual in the general population aimed at identifying abnormalities which might signal the presence of a specific medical condition. The intent is to find diseases at the earliest possible stage in their development in order to improve the chances for cure or reduce morbidity.

  • SDR 
    The aunts, uncles, grandparents, grandchildren, nieces, nephews, or half-siblings of an individual. Also called second-degree relative.

  • second-degree relative  listen  (SEH-kund-deh-GREE REH-luh-tiv)
    The aunts, uncles, grandparents, grandchildren, nieces, nephews, or half-siblings of an individual. Also called SDR.

  • segregation analysis  listen  (SEH-greh-GAY-shun uh-NA-lih-sis)
    The process of fitting formal genetic models to data on expressed disease characteristics (phenotype) in biological family members in order to determine the most likely mode of inheritance for the trait or disease under study.

  • sensitivity  listen  (SEN-sih-TIH-vih-tee)
    The frequency with which a test yields a true positive result among individuals who actually have the disease or the gene mutation in question. A test with high sensitivity has a low false-negative rate and thus does a good job of correctly identifying affected individuals.

  • single nucleotide polymorphism  listen  (SING-gul NOO-klee-oh-tide PAH-lee-MOR-fih-zum)
    DNA sequence variations that occur when a single nucleotide (adenine, thymine, cytosine, or guanine) in the genome sequence is altered; usually present in at least 1% of the population. Also called SNP.

  • single-stranded conformation polymorphism analysis  listen  (SIN-gul-STRAN-ded KON-for-MAY-shun PAH-lee-MOR-fih-zum uh-NA-lih-sis)
    A laboratory test used to separate single-stranded nucleic acids based on subtle differences in their DNA sequence, often a single base pair, which results in a different secondary structure and a measurable difference in mobiity through a gel. Also called SSCP analysis.

  • single-stranded conformational polymorphism  listen  (SIN-gul-STRAN-ded KON-for-MAY-shuh-nul PAH-lee-MOR-fih-zum)
    A type of mutation scanning; the identification of abnormally-migrating single-stranded DNA segments on gel electrophoresis. Also called SSCP.

  • SNP  listen  (snip)
    DNA sequence variations that occur when a single nucleotide (adenine, thymine, cytosine, or guanine) in the genome sequence is altered; usually present in at least 1% of the population. Also called single nucleotide polymorphism.

  • Southern blot  listen  (SUH-thern blot)
    Electrophoresis-based technique used in genetic testing to detect large deletions in DNA that can be missed by PCR-based genetic testing methods.

  • specificity  listen  (SPEH-sih-FIH-sih-tee)
    The frequency with which a test yields a true negative result among individuals who do not have the disease or the gene mutation in question. A test with high specificity has a low false-positive rate and thus does a good job of correctly classifying unaffected individuals.

  • splicing  listen  (SPLY-sing)
    The process by which introns, the noncoding regions of genes, are excised out of the primary messenger RNA transcript, and the exons (i.e., coding regions) are joined together to generate mature messenger RNA. The latter serves as the template for synthesis of a specific protein.

  • sporadic cancer  listen  (spuh-RA-dik KAN-ser)
    This term has two meanings. It is sometimes used to differentiate cancers occurring in people who do not have a germline mutation that confers increased susceptibility to cancer from cancers occurring in people who are known to carry a mutation. Cancer developing in people who do not carry a high-risk mutation is referred to as sporadic cancer. The distinction is not absolute, because genetic background may influence the likelihood of cancer even in the absence of a specific predisposing mutation. Alternatively, sporadic is also sometimes used to describe cancer occurring in individuals without a family history of cancer.

  • SSCP 
    A type of mutation scanning; the identification of abnormally-migrating single-stranded DNA segments on gel electrophoresis. Also called single-stranded conformational polymorphism.

  • SSCP analysis  listen  (… uh-NA-lih-sis)
    A laboratory test used to separate single-stranded nucleic acids based on subtle differences in their DNA sequence, often a single base pair, which results in a different secondary structure and a measurable difference in mobiity through a gel. Also called single-stranded conformation polymorphism analysis.

  • surveillance  listen  (ser-VAY-lents)
    Periodic clinical evaluation of an individual who is at increased risk of developing a condition (compared with the general population) aimed at detecting new or recurrent disease. In public health, surveillance may also refer to the systematic collection of information regarding the incidence, prevalence, and mortality related to various medical conditions or health-related events.

  • susceptibility gene  listen  (suh-SEP-tih-BIH-lih-tee jeen)
    A germline mutation that increases an individual’s susceptibility or predisposition to a certain disease or disorder. When such a mutation is inherited, development of symptoms is more likely, but not certain. Also called predisposing mutation.

  • tagging SNP  listen  (TA-ging snip)
    A single nucleotide polymorphism, or SNP, that is used to “tag” a particular haplotype in a region of the genome. As a subset of all of the SNPs in the genome, tagging SNPs can be extremely useful for testing the association of a marker locus with a qualitative or quantitative trait locus in that it may not be necessary to genotype all of the SNPs. Also called tagSNP.

  • tagSNP  listen  (tag-snip)
    A single nucleotide polymorphism, or SNP, that is used to “tag” a particular haplotype in a region of the genome. As a subset of all of the SNPs in the genome, tagSNPs can be extremely useful for testing the association of a marker locus with a qualitative or quantitative trait locus in that it may not be necessary to genotype all of the SNPs. Also called tagging SNP.

  • transcription  listen  (tran-SKRIP-shun)
    The process of synthesizing messenger RNA (mRNA) from DNA.

  • translation  listen  (trans-LAY-shun)
    The process of synthesizing an amino acid sequence (protein product) from the messenger RNA code.

  • translocation  listen  (TRANZ-loh-KAY-shun)
    A type of chromosomal abnormality in which a chromosome breaks and a portion of it reattaches to a different chromosomal location.

  • trinucleotide repeat  listen  (try-NOO-klee-oh-tide reh-PEET)
    Sequences of 3 nucleotides repeated in tandem on the same contiguous section of chromosome. A certain amount of normal (polymorphic) variation in repeat number with no clinical significance commonly occurs between individuals; however, repeat numbers over a certain threshold can, in some cases, lead to adverse effects on the function of the gene, resulting in genetic disease.

  • triple-negative breast cancer  listen  (TRIH-pul-NEH-guh-tiv brest KAN-ser)
    Triple-negative breast cancer is defined by a lack of expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2/neu). Also called ER-negative PR-negative HER2/neu-negative breast cancer.

  • trisomy  listen  (TRY-soh-mee)
    The presence of an extra chromosome, resulting in a total of three copies of that chromosome instead of the normal 2 copies (e.g., trisomy 21, or Down syndrome).

  • unaffected  listen  (UN-uh-FEK-ted)
    An individual who does not manifest symptoms of a condition or disease occurring in his or her family.

  • unclassified variant  listen  (un-KLA-sih-fide VAYR-ee-unt)
    A variation in a genetic sequence whose association with disease risk is unknown. Also called variant of uncertain significance, variant of unknown significance, and VUS.

  • uninformative  listen  (UN-in-FOR-muh-tiv)
    A negative test result in an individual where a clearly deleterious mutation has not been found in any family members. The genetic risk status of such an individual must be interpreted in the context of his or her personal and family history. Also called inconclusive and indeterminate.

  • variable expression  listen  (VAYR-ee-uh-bul ek-SPREH-shun)
    Variation in the manner in which a trait is manifested. When there is variable expressivity, the trait may vary in clinical expression from mild to severe. For example, the condition neurofibromatosis type 1 may be mild, presenting with café-au-lait spots only, or may be severe, presenting with neurofibromas and brain tumors.

  • variant of uncertain significance  listen  (VAYR-ee-unt … un-SER-tin sig-NIH-fih-kunts)
    A variation in a genetic sequence whose association with disease risk is unknown. Also called unclassified variant, variant of unknown significance, and VUS.

  • variant of unknown significance  listen  (VAYR-ee-unt … UN-none sig-NIH-fih-kunts)
    A variation in a genetic sequence whose association with disease risk is unknown. Also called unclassified variant, variant of uncertain significance, and VUS.

  • VUS 
    A variation in a genetic sequence whose association with disease risk is unknown. Also called unclassified variant, variant of uncertain significance, and variant of unknown significance.

  • WGA study  listen  (... STUH-dee)
    WGA (whole genome association) studies are a way for scientists to identify genes involved in human disease. This method searches the genome for small variations, called single nucleotide polymorphisms or SNPs (pronounced “snips”), that occur more frequently in people with a particular disease than in people without the disease. Also called genome-wide association study, GWAS, and whole genome association study.

  • whole genome association study  listen  (hole JEE-nome uh-SOH-see-AY-shun STUH-dee)
    Whole genome association (WGA) studies are a way for scientists to identify genes involved in human disease. This method searches the genome for small variations, called single nucleotide polymorphisms or SNPs (pronounced “snips”), that occur more frequently in people with a particular disease than in people without the disease. Also called genome-wide association study, GWAS, and WGA study.

  • X-linked recessive  listen  (…. linkt reh-SEH-siv)
    X-linked recessive inheritance refers to genetic conditions associated with mutations in genes on the X chromosome. A male carrying such a mutation will be affected, because he carries only one X chromosome. A female carrying a mutation in one gene, with a normal gene on the other X chromosome, will be unaffected.

  • Z-score  listen  (… skor)
    A score that indicates how many standard deviations a value is above or below the mean.