Acentric: No centromere.
Acrocentric: See chromosome.
Activating mutation: See mutation.
Activator: A protein that functions to improve gene transcription.
Affordable Care Act: Complex Federal legislation aimed at ensuring that all Americans have practical access to effective health care coverage.
Agenesis: Referring to embryonic formation. Agenesis is the failure of a specific structure to develop. (e.g., agenesis of the corpus callosum means the corpus callosum did not develop at all.)
Hypogenesis: The underdevelopment of a specific structure. (e.g., hypogenesis of the corpus callosum refers to a smaller than normal corpus callosum.)
Allele(s): Alternative forms of a gene, or of a DNA sequence, at a given locus.
Null allele: When applied to a gene that codes for an enzyme, the null allele changes the gene to produce zero enzyme product.
Allelic heterogeneity: See heterogeneity.
Allosteric control: The regulation of an enzyme or other metabolic function via an effector molecule at a site other than the protein’s active site (e.g., an allosteric site).
Allosteric protein: A protein that alters its shape upon binding with another molecule.
Alpha-satellite: Repeating units of DNA which are about 170 bp. They are found mainly in the heterochromatic region around the centromeres.
Alternative splicing: The process of excising introns in different patterns to produce alternate DNA forms for transcription and ultimately resulting in different proteins from the same core sequence.
Anaphase: See cell cycle.
Aneuploid: Not possessing the correct number of chromosomes. There are several descriptors of such abnormalities (also see “Ploidy”). Examples would include:
Disomy: Having two copies of one chromosome.
Monosomy: Having one copy of one chromosome.
Trisomy: Having three copies of one chromosome.
Anneal: The coupling of complementary strands of DNA.
Re-anneal: The coupling of complementary DNA strands after having first been separated.
Anticipation: The apparent worsening of a heritable condition as it is passed down through generations.
Apoenzyme: See enzyme.
Apoptosis: Programmed cell death (sometimes referred to as “cellular suicide”).
Array comparative genomic hybridization (aCGH): See comparative genomic hybridization.
Association: Two or more malformations, which have been found (on a population basis) to occur together more often than would be predicted by chance, but not necessarily due to a specific causal entity.
Autosome (autosomal): Referring to one of the 22 numbered (non-sex) chromosomes.
Auxology (auxologic): The study of human growth.
Auxotrophy: The inability to synthesize all of the biochemical necessary for all of the functions in an organism. (An auxotroph is an organism that exhibits auxotrophy.)
Prototrophs: In contrast to auxotrophy, prototrophy is the ability to synthesize all of the biochemical necessary for cellular function. Prototrophs are organisms that possess these abilities.
Back mutation: See mutation.
Bacterial artificial chromosomes (BACs): Manufactured pieces of DNA derived from bacterial plasmids used as probes in DNA identification.
Bacteriophage: A virus that invades a bacteria and replicates inside it.
Banding: The appearance of bands on cytogenetic studies produced by differential staining. There are multiple types of chromosomal stains that are designed to highlight specific regions. Banding patterns allow for clear distinction of each chromosome pair from the others.
G-banding: The most common type of banding study used in clinical settings. The “G” stands for the stain Giemsa which preferentially stains heterochromatin resulting in darker and lighter visible bands.
High resolution banding: Cytogenetic laboratory method in which the chromosomes are induced to be more elongated, allowing much finer detection of smaller changes in the pattern of banding than usual; also called prometaphase banding.
Benign polymorphism: See polymorphism.
Biopharmaceutical: Medications derived using biotechnology.
Birth defect: A lay term that denotes an abnormality of development present at birth. The most common application of this term is to observable structural changes. (See congenital anomaly.)
Bivalent: A pair of homologous chromosomes that are coupled during meiosis.
Blaschko lines: Developmental linear patches observed in the skin. Blaschko lines do not strictly follow dermatome patterns.
Blastocyst: Early developmental stage in embryonic development characterized by an inner cell mass and a thin cellular layer enclosing a blastocyst cavity.
Blastomere: Cells derived from the cleavage of a fertilized oocyte during early embryonic development.
Blastula: A sphere of cells with a hollow core composed of blastomeres.
C value: The amount of DNA contained within a haploid (n) nucleus. This would be the equivalent of half the amount in a diploid (2n) cell.
cAMP: See cyclic AMP.
Candidate gene: See gene.
Carcinogen: An environmental factor (chemical, ionizing radiation, etc.) that can induce cancer.
Cell cycle: Interphase, prophase, prometaphase, metaphase, anaphase, then telophase.
Cellular differentiation: The process that undifferentiated (stem) cells undergo in becoming progressively more specialized in structure and function.
Centrioles: Subcellular structures that are a grouping of microtubules arranged in a characteristic pattern of 9 microtubule triplets. Centrioles play key roles in cellular division.
Centromere: A highly condensed region of the chromosome where sister chromatids are linked during cell division.
Acentric: A chromosome having no centromere.
Dicentric: A chromosome possessing two centromeres.
Centrosome: A subcellular organelle that serves as the primary microtubule organizing center of eukaryotic cells as well as a regulator of cell cycle.
Chaperones: Proteins that have a primary transport function to assist in the folding/unfolding or assembly/disassembly of proteins.
Chromatid: One of a pair of a duplicated chromosome bound by a single centromere. The two identical strands are called “sister chromatids.”
Chromatin remodeling: Human chromosomes in the neutral state house the DNA in a highly condensed and protected state. Chromatin remodeling is the process of modifying the chromatin architecture to permit access of DNA to the transcription elements.
Chromosomal analysis (karyotype): Cytogenetic analysis to determine the number and structure of chromosomes as seen through microscopic views of prepared cells from an individual’s tissue.
Chromosomal microarray: Using microchips with thousands of wells imbedded with a variety of different types of probes to screen large parts of the genome.
Chromosomes: The structures that house nuclear DNA. Chromosomes are composed of the DNA itself as well as a variety of proteins that allow for compact packaging and protection. In humans the modal (normal) number of chromosomes is 46.
Acrocentric: A chromosome in which the centromere is positioned close to the end of the structure. This results in these chromosomes with short (p) arms.
Telocentric: A chromosome in which the centromere is positioned at the end of the structure. This results in these chromosomes with essentially no (p) arm. Instead, all that is distal to the centromere is satellite DNA.
Chromosome abnormalities (abberations): In karyotype analysis, abnormalities of chromosome structure may be seen. Changes in whole chromosome numbers are referred to as aneuploidy. Partial changes are described as duplications, deletions, inversions, and translocations.
Chromosome painting: Using FISH probes that provide coverage of an entire chromosome to identify structural rearrangements.
Chromosome spindle: A subcellular structure upon which chromosome segregation occurs.
Cis, trans positions: When discussing the relative position of a polymorphism (allele), cis refers to the two polymorphisms being on the same allele of a given pair. Trans means they are on the two different alleles.
Clinical geneticist: A physician with special training in the clinical evaluation of patients suspected to have genetic conditions and birth defects; clinical geneticists historically came from a variety of backgrounds, such as pediatrics, obstetrics/gynecology, internal medicine, neurology, etc. but newly trained individuals may specialize in genetics alone.
Clinical genetics: See genetics.
Clinical genetics laboratory: A laboratory that performs genetic testing for clinical/diagnostic (non-research) indications.
Cloning: Making an exact copy of something. Cloning can be performed at many levels—whole organisms, individual organs, tissues, cells, or even DNA.
Coding (sense) strand: In double-stranded DNA, the coding strand is the strand that contains the actual sequence (codons) used in transcription.
Noncoding (antisense) strand: In double-stranded DNA, the strand that contains the sequence not used in transcription (anticodons).
Co-dominance: See dominance.
Codon: A specific triplet nucleotide sequence.
Anticodon: The triplet nucleotide sequence that is complementary to the codon found on the tRNA.
Sense codon: The 61 triplets that bind a tRNA anticodon and result in the addition of an amino acid during translation.
Stop codon(s): Three RNA triplets (UAG, UGA, and UAA) designate the end of a coding sequence—because there are no correlate tRNAs for these triplets. These may also be called termination codons, or in the case of mutations, nonsense codons.
Coefficient of inbreeding: A calculated value for an individual that quantifies the degree of genetic code that is shared based on common ancestry.
Coefficient of relationship: A calculated value between two individuals to determine the degree (if any) of consanguinity.
Coenzyme: See enzyme.
Cofactor: An inorganic compound that works to augment enzymatic function. In humans many cofactors are “vitamins.”
Comparative genomic hybridization (CGH): Hybridizing control DNA with patient DNA in order to identify copy number variants. When performed on a microarray platform, this is referred to as array CGH (aCGH).
Compound Heterozygosity: See heterozygous.
Concordance (concordant): The occurrence of the same phenotypic feature in different individuals. Most commonly concordance is used to describe the correlation of features in twins. Discordance (discordant) then is the presence of a phenotype in one individual but not the other.
Congenital anomaly: An abnormality present at birth. The most common use of the term is in structural malformations. (See birth defects.)
Consanguinity (consanguineous): Sharing of a common (“blood”) relative by two individuals.
Contiguous gene syndromes: Recognizable patterns of malformations due to loss or gain of a chromosomal segment containing several consecutive (contiguous) genes. These may be difficult or impossible to detect by routine cytogenetic analysis. Identification of the change may require high resolution chromosomal analysis, or a molecular cytogenetic test for confirmation.
Copy number variants (CNVs): Deviations from the normal expected chromosomal make up. Microdeletions or micro-duplications detected by chromosomal microarray are such examples. Identified CNVs are classified as known benign, known pathogenic, or of unknown clinical significance. Copy number variant is now the preferred term over “copy number change.”
Covalent modification: Modification (regulation) of enzyme activity via a donor molecule which provides a functional moiety that alters the properties of that enzyme.
CpG island: Regions of the genome that contain high concentrations of “CpG sites.” A CpG site is characterized by cytosine (C) and Guanine (G) nucleotides which are on the same strand of DNA joined by a phosphodiester (p) bond.
Crossing over: See recombination.
Cyclic AMP (cAMP): 3′5′ cyclic adenosine monophosphate. cAMP is a cell secondary messenger important in intracellular signal transduction.
Cytogenetics: Referring to the analysis of chromosomes within cells, by culturing living cells or preparing actively dividing cells from body tissues and use of various identification methods to detect individual chromosome structure.
Cytokinesis The process of physically dividing a parent cell into daughter cells by splitting the membrane and cytoplasm.
Decoding function: Ribosomal RNA provides a mechanism for decoding mRNA into amino acids. The accuracy of the codon-anticodon pairing is assisted by the decoding function associated with the 16S rRNA in the small subunit.
Deamination: The removal of an amine group.
Deformation: A congenital structural variation or abnormality which is the result of external physical forces.
Degeneracy (of code): This term refers to the fact that the RNA trinucleotides that code for amino acids in translation do not have a one-on-one correlation. Specifically more than one triplet may code for the same amino acid.
Degree(s) of relationship:
First Degree: Parents, siblings, offspring of the proband.
Second Degree: Grandparents/grandchildren, uncles/aunts, nieces/nephews.
Third Degree: Cousins, etc.
Degrees of freedom: In calculating the variance, the degree of freedom is N-1.
Deletion (deficiency): See chromosome abnormalities.
Depurination: A type of DNA mutation in which the purine base (adenine or guanine) is removed from the deoxyribose sugar between them.
Diagnostic yield: Essentially the “batting average” of a clinical genetic diagnostic evaluation. Specifically what percentage of the time does a diagnostic evaluation for a specific condition provide a known cause (etiology) for the condition?
Diandry: The mechanism of the occurrence of a triploid zygote due to a haploid ovum fertilized by a diploid sperm. The result of diandry is a triploid zygote.
Dicentric: See centromere.
Dideoxy sequencing: See sequencing.
Digenic inheritance: An inheritance pattern in which two different loci are involved in the determination of a phenotype. See also inheritance patterns.
Digyny: The mechanism of the occurrence of a triploid zygote due to diploid ovum becoming fertilized by a haploid sperm.
Diploid: See ploidy.
Discordant: See concordance.
Disease: An abnormality of function in a biologic system that results in observable signs and symptoms.
Disorder: A disease not caused by an infectious illness.
Dispersed duplication: See duplication.
Dispermy: The mechanism of the occurrence of a triploid zygote due to an oocyte being (abnormally) fertilized by two spermatozoa.
Disruption: A congenital abnormality which is the result of a destructive event or process, leading to incomplete or abnormal formation.
DNA fingerprint: A person-specific pattern of DNA obtained by a variety of methods of breaking the DNA up into small fragments.
DNA polymerase: Critical enzyme that catalyzes the addition of nucleotide chain.
DNA sequencing: See sequencing.
DNA strand: The individual runs of nucleotides in the DNA molecule. Human, nuclear DNA is double stranded possessing a coding strand and the complementary binding strand.
Coding stand: The template strand for transcription. Sometimes called the “sense” strand. The complementary strand is the anti-sense strand.
Lagging strand: Replication of the second DNA strand is more complicated. Replication of this lagging strand is in a non-continuous fashion because it is going against the unzipping of the replication fork.
Leading strand: During DNA replication, the leading strand is replicated in a relatively straightforward manner. It is the strand that is copied continuously.
Domain: See protein domain.
Dominance/dominant inheritance: Dominant conditions are those expressed in heterozygotes, i.e., individuals with one copy of a mutant allele and one copy of a normal (wild type) allele.
Co-dominance: The simultaneous expression of both alleles in a dominant fashion.
Incomplete or semi dominance: A dominant condition in which a milder phenotype is observed in heterozygotes as compared to homozygotes.
Quasi-dominance: The appearance of dominant transmission of a condition in a pedigree that is actually due to a recessive condition. This occurs when the recessive allele is sufficiently common in the general population.
True/complete dominance: True dominance is characterized by the complete (full) phenotype being seen in both heterozygotes and homozygotes. Specifically homozygotes are not more severely affected.
Dominant negative effect: In terms of pathogenesis, some dominant mutations exert their effect via the gene product adversely affecting the wild-type (normal) gene product within the same cell.
Duplication: A chromosome abnormality in which a segment of the chromosome has been abnormally replicated.
Dispersed duplication: Chromosomal duplication in which the duplicated segments lie away from each other.
Tandem duplication: Chromosomal duplication in which the duplicated segments lie adjacent to each other.
Dyshistogenesis: Abnormal embryonic formation at the tissue level.
Dysmorphology (dysmorphologist): A specialist trained in the recognition of physical variations and malformations and their diagnostic and clinical significance.
Dysmorphic: Literally, abnormally shaped. Dysmorphic refers to a physical feature which is sufficiently different from average as to be notable.
Dysplasia: A congenital abnormality due to abnormal development at the tissue level of organization (dyshistogenesis).
Ectoderm: See trilaminar embryo.
Ectopia: Occurring in the wrong place. In general ectopia refers to misplacement at the organ or structural level (i.e., ectopic lens). See also heterotopia.
Ethical Legal and Social Implications (of human genetics) (ELSI): This acronym refers to the complex issues surrounding genetics in clinical medicine. It is also an ongoing specifically funded federal program to address these needs.
Endoderm: See trilaminar embryo.
Endoduplicated (endoduplication): Making a copy of the nuclear genome outside the process of cell division.
Endophenotype: A defined subgroup of a specific phenotype or diagnosis.
Enzyme: A protein that functions as a catalyst in a biochemical reaction.
Apoenzyme: The state of an enzyme that requires a cofactor when the cofactor is not bound.
Coenzyme: Organic molecules that are needed by certain enzymes to carry out their catalytic function. (In contrast to cofactors which are inorganic compounds with the same function.)
Holoenzyme: The active form of an enzyme when all of the components (e.g., cofactors, coenzymes) are appropriately bound.
Enzyme replacement therapy: Using enzyme replacement to treat patients with inborn errors of metabolism. The enzyme may be procured from multiple sources including biologic or engineered systems.
Epigenesis (epigenetic): Modifying gene function without changing sequence. One of the several factors (in addition to alternate splicing, opposite transcripts, posttranslational modification) that allows for the small number of functioning human genes and yet the great diversity/flexibility in human development.
Epistasis: The influence of one gene on the function of others.
Etiology: The specific cause of a disorder.
Euploid: See ploidy.
Exon: The parts of a gene that are codes for the actual protein product.
Expression (expressivity): The observed phenotype of a genetic condition.
Variable expression: Different degrees of clinical expression given the same genotype. In describing the phenotype associated with a specific condition, variability in expression can usually be identified. In some ways variable expression may be seen as defining severity.
Familial: This simply means that a condition “runs in the family.” Familial disorders may be due to genetic factors, environmental factors or both.
Family centered medical home: An important care-delivery concept in which the family (patient) is at the center of all decision making regarding their own care.
Fetal alcohol spectrum disorders: The full range of congenital anomalies due to the teratogenic effects of maternal ethanol consumption.
Field defect: A recognizable pattern of congenital anomalies due to disruption of a common primordial tissue.
Fluorescence in situ hybridization (FISH): A molecular cytogenetic method in which a molecular probe is linked to a fluorescent dye on the slide; views under a fluorescent microscope reveal presence or absence of the desired region of the chromosome through adhesion of the probe or lack thereof.
Multi-color FISH: Using multiple different colored fluorescent labels to “mark” specific target regions of the genome
Single locus FISH: A FISH test utilizing probes for a unique and single locus.
Sub-telomeric FISH: A panel of 40 to 42 probes that hybridize to the sub-telomeric regions of the chromosomes.
Forward mutation: See mutation.
Founder effect: The relatively high frequency of a particular allele in the gene pool that occurs as the result of a new isolated population being founded by a small number of individuals possessing limited genetic variation.
Frameshift mutation: See mutation.
Functional mosaicism: See mosaicism.
G-banding: See banding.
G protein: Short for “guanine nucleotide-binding proteins.” G proteins are a family of proteins involved signaling cascades—typically as secondary messenger. They are common mediators in post receptor-ligand binding.
Gamete: In humans, an oocyte or a spermatozoa (aka germ cells).
Gamete complementation: The phenomenon of two gametes (oocyte and sperm) possessing complementary abnormalities that essentially “fix” the other, e.g., an oocyte with no copies of a specific chromosome and the spermatozoa having 2 copies of the same chromosome.
Gastrulation: Embryologic process.
Gene: A unit of heredity. A gene refers to a specific segment of DNA that can be delineated by a start and stop position. Genes typically code for a specific product (oftentimes a protein molecule).
Candidate gene: In research studies, a candidate gene is a gene identified in a region of interest which is deemed as possibly associated with a condition of interest.
Gene dosage: The number of copies of a given gene in a given cell.
Structural gene: A gene that codes for a functional protein (in contrast to those genes that code for regulatory functions not mediated by proteins).
Gene dosage: See gene.
Gene pool: The total of all genes in a defined population.
Gene therapy: In the broadest sense “gene therapy” refers to treatments that are targeted at the molecular level. A stricter use of the term would be limited to those therapies that utilize molecular/DNA technologies.
Gene × environmental interactions: The current understanding of human genetic disorders involves an interaction of the individual’s genome with the environment that ultimately defines the phenotype.
General population screening: See genetic screening.
Genetic: A medical condition is said to be genetic if the pathophysiology of the disorder is based in a change in the DNA.
Genetic code: The “code” in genomics refers to the particular amino acid coded for by a specific trinucleotide group.
Genetic counseling: A process by which individuals or families receive information about genetic disorders or malformations and risks for these conditions after review of family and medical history; includes analysis of diagnostic information, review of natural history of the relevant conditions, options for dealing with risks and enhancement of family decision making through nonjudgmental support.
Genetic counselor: A professional trained in counseling families about genetic conditions, genetic risks and decision making, and adapting to a genetic condition.
Genetic damage rate: See mutation.
Genetic discrimination: Use of information about genetic traits in order to identify at-risk individuals for a different selection process in employment, housing, insurance, or other usually non-medical settings; typically used to refer to an unfair selection process by which individuals are denied or presented with barriers to their application, such as much higher premiums for insurance.
Genetic heterogeneity: See heterogeneity.
Genetic Information Non Discrimination Act (GINA): Federal legislation enacted in 2008 that protects patients from having their genetic information used to their detriment (in things such as insurance and employment).
Genetic screening: The search for healthy individuals in a specified population who possess a genetic change that may cause or predispose to certain disorders. Genetic screening can be designed for “individual screening,” “selected population screening,” or at whole (general) “population screening.”
Sensitivity: The screening detection rate. That is, what proportion of truly affected individuals is detected by the screening?
Specificity: The accuracy of the screening process. That is, what proportion of individuals identified by screening as a “presumptive positive” actually has the condition?
Genetic support group: A group or organization developed around a specific condition or group of conditions related to genetics or malformations, in order to provide information and support to families.
Genetic test: In the broadest sense, a genetic test is any test performed to make a diagnosis of a genetic condition. Most often it refers to testing that involves analyzing DNA or RNA in some manner.
Genetics: In the realm of medicine, genetics are the principles applied to human disorders.
Clinical genetics: Genetics applied to direct health care practice.
Human genetics: The genetics of humans. Encompasses all aspects (including population genetics and the genetics of non-disease traits).
Medical genetics: Genetics of human health. Can be clinical or research.
Genomics: The discipline of genetics that focuses at the level of the genome.
Genotype: The genetic information of an individual. The genotype can be at various levels of testing (chromosomal, gene, nucleotide sequence).
Genotype × environmental interactions: Most phenotypes are influenced by a combination of genetic and environmental factors.
Gonadal (germ-line) mosaicism: See mosaicism.
Gonadal (germ-line) mutation: See mutation.
Haploid: See ploidy.
Hemizygous: Males have a single X chromosome. Thus for most genes coded on the X-chromosome there is not a complementary allele. Males are thus hemizygous at these loci.
Hereditary: Inherited or heritable through the gametes of biological parents; commonly refers to traits related to a single gene or specific chromosome alteration.
Heterochromatin: Darkly stained regions of the chromosomes.
Heterochromatic regions are characterized by tight packaging and increased concentrations of protective proteins.
Heteroplasmy (heteroplasmic): In reference to mitochondrial DNA, heteroplasmy denotes the status of not all mitochondria having the same DNA sequence. The opposite of heteroplasmy is homoplasmy.
Heterotopia (heterotopic): In the wrong place. In contrast to “ectopia,” heterotopia is at the tissue or cellular level. (i.e., neuronal heterotopias). Heterotopias may be developmental or migrational. See also ectopia.
Heterogenous nuclear RNA (hnRNA): See RNA.
Heterodimer: See homodimer.
Heterodisomy: See uniparental disomy.
Heterogeneity: A state in which variable or divergent components exist. In medical genetics heterogeneity typically focus on genomic variability. The opposite of heterogeneity would be homogeneity.
Allelic heterogeneity: Refers to different mutations at the same locus causing the same or similar phenotype.
Genetic heterogeneity: Different mutations causing an identical or similar phenotype.
Locus heterogeneity: Refers to mutations at different loci causing the same or similar phenotypes.
Heterozygote: An individual who is heterozygous for one allele at a particular locus is said to be a heterozygote for that condition.
Advantage: The situation in which a person who is heterozygous for a mutation in a particular gene has a (population) selective advantage for reproduction.
Compound: A person possessing two heterogeneous recessive alleles at a particular locus is said to be a compound heterozygote.
Disadvantage: The situation in which a person who is heterozygous for a mutation in a particular gene has a (population) selective disadvantage for reproduction.
Heterozygous: Possessing a different DNA sequence at the two alleles of a particular gene.
High resolution karyotype: See banding.
High-throughput sequencing: See sequencing.
Holandric: Referring to genes on the Y chromosome.
Holoenzyme: See enzyme.
Homeobox: See homeotic genes.
Homeodomain: See homeotic genes.
Homeotic genes (HOX): Primordial genes that are primary organizers of multicellular organisms. Homeotic genes determine basic organizational templates such as sidedness, anterior versus posterior, and superior versus inferior developmental domains.
Homeobox: A family (grouping) of homeotic genes which work in concert in the development of specific embryonic structures or regions.
Homeodomain: A region of common sequence in a homeotic gene—usually a common string of 60 amino acid residues which are usually similar among HOX genes.
Homeotic mutations: Simply, mutations in homeotic genes.
Hox complex: Highly conserve clusters of homeotic genes.
Homodimer: In protein assembly, a homodimer is the result of coupling of two identical protein strands.
Heterodimer: In protein assembly, a heterodimer is the result of coupling of two different protein strands.
Homodisomy: See uniparental disomy.
Homogeneity: A state in which uniformity exists. In medical genetics homogeneity refers to identical genetic codes.
Homologous chromosomes: In the human genome, chromosome pairs exist in the nucleus. Homologous pairs are those that are of the same type (i.e., the two chromosomes #2).
Homoplasmy (homoplasmic): See heteroplasmy.
Homozygous (homozygote): If both alleles at a locus are identical, the individual is homozygous at that locus (a homozygote for that condition).
Hox complex: See homeotic genes.
Human genetics: See genetics.
Hypogenesis: See agenesis.
Imprinting: In general terms “imprinting” means to make a mark or stamp on something. In genetics, the term applies to pre-programming of the expression of specific genes.
Imprinting domains: Clusters of imprinted genes non-randomly distributed across the genome.
Inactivation: In its simplest form, genetic inactivation involves the “turning off” of a specific gene or set of genes. Inactivation can occur at any level including that of an entire chromosome (see X-inactivation).
Incomplete dominance: See dominant inheritance.
Incomplete penetrance: See penetrance.
Independent assortment: The random segregation of alleles on different pairs of homologous chromosomes due to the separation of these pairs during meiosis.
Individual screening: See genetic screening.
Inducible gene: A gene whose expression can “turn on” by specific external factors.
Informed consent: The process of explaining a test or a procedure to a patient that explains the details of the process including risks, benefits, and what will be done with the information. Informed consent must be understandable to the patient at his or her level of understanding and be finalized with a formal signed form.
Inheritance patterns: Observable patterns of the transmission of heritable traits as evidenced by the family history, pedigree, or gene analysis.
Digenic inheritance: A clinical trait is expressed when mutation on two different genes (loci) are present.
Monoallelic inheritance: A clinical trait is expressed when only one allele of a single gene pair is altered.
Multi-locus inheritance: The expression of a condition due to the progressive accumulation of mutations in multiple genes (loci).
Triallelic inheritance: A clinical trait is expressed only after a particular combination of 3 different alleles possess a mutation.
Initiation factors: Proteins that bind the ribosome during the start of translation (protein synthesis).
Interphase: See cell cycle.
Intron: The noncoding regions of a gene.
Inverse disorders: Genetic disorders that are reciprocal to genetic changes. For example, the deletion of a particular chromosome region may be associated with a recognizable syndrome. Likewise duplication of the same region may produce a different condition. These would be known as reciprocal or inverse disorders.
Inversion: A chromosome rearrangement that results from two breakpoints on a chromosome and the subsequent rotation of the “freed” segment along the axis of the chromosome.
Paracentric inversion: An inversion in which both endpoints are on the same arm of the chromosome.
Pericentric inversion: An inversion in which the endpoints are on opposite arms of the chromosome and the centromere is included.
Karyotype: See chromosomal analysis.
Krebs (citric acid) cycle: The middle component of energy generation which starts with acetyl CoA which proceeds through 8 enzyme catalyzed reactions that ultimately yields 3 NADH, 1 GTP, and 1 FADH molecules for further metabolism.
Kinetochore: A subcellular component of the chromatids which connect to the spindle fibers during cell division to aid in sister chromatids separation.
Liability (liabilities): When discussing gene × environment interactions, deleterious genetic and environmental factors that contribute to the phenotype are known as liabilities toward expression.
Linear sequencing: See sequencing.
Linkage: The tendency of alleles to segregate together based upon their proximity on the chromosome.
Linkage disequilibrium: The co-occurrence of alleles more often than would be predicted by chance.
Linkage group: A set of loci/alleles that segregate together during chromosome replication.
Locus (loci): A genetic locus is a specific position or location on a chromosome. Frequently, locus is used to refer to a specific gene.
Locus heterogeneity: See heterogeneity.
Long-term follow-up: A formal process of following a defined population over time with data collection on objective parameters with the primary focus being clinical outcomes.
Looped domains: The basic structural unit of eukaryotic chromatin. In the condensation of DNA nucleosomes are compacted together to form chromatin fibers. The chromatin fibers are then folded into looped domain. (The looped domains are subsequently organized into chromosomal structures.)
Lyonization: X chromosome inactivation originally described by Dr. Mary Lyon.
Lysosomal storage disorder: An inborn error of metabolism in which a lysosomal function is disrupted. The end result is normal synthesis of a biochemical, but disrupted degradation leading to accumulation (storage).
Malformation: An abnormality of development during embryogenesis. Malformation refers to structures that inherently develop abnormally.
Major malformation or anomaly: A congenital structural abnormality which has significant effect on function or social acceptability; example: cleft lip; in its strictest definition, malformation defines a structural abnormality resulting from an abnormal developmental process, but common usage includes all structural abnormalities as malformations, regardless of cause.
Minor malformation: Congenital structural abnormality which has little functional or societal significance on its own.
Marker chromosome: An extra piece of chromosomal material that can be detected by a karyotype that segregates with the other normal chromosomes during cell division. Marker chromosomes can be composed of almost any part and combination of the other “normal” chromosomes.
Massively parallel sequencing: See sequencing
Maternal effects: Maternal effects refer to the fact that the earliest stages of embryonic development are controlled by the maternal genome.
Mean: A statistical calculated value that is the sum of all measurements (ΣX) divided by the number of individuals in the sample (N).
Medical geneticist: A professional with a doctoral degree and special training in the relationships between genes and disease (see Clinical geneticist).
Medical genetics: See genetics.
Medical home neighbor: One role that the medical geneticist may fill in the care of patients with genetic disorders. The medical home neighbor helps the primary medical home provide the level of specialty care without disrupting the medical home relationship with the primary care provider.
Meiosis: The process of halving the chromosome number in the formation of gametes.
Mendel, Gregor: Austrian monk credited with defining the principles of independent of assortment of single alleles. The term “Mendelian inheritance” is a credit to this work.
Mendelian inheritance: Pattern of inheritance of a genetic trait due to a single gene variation which follows the classical patterns of autosomal recessive, autosomal dominant, or X-linked (dominant or recessive) inheritance.
Mesoderm: See trilaminar embryo.
Messenger: In cellular systems, messengers are compounds that facilitate communication at a variety of levels.
Primary messenger: The initial compound involved in a communication. A hormone would be an example of a primary messenger.
Secondary messenger: Cellular messages are often facilitated through a primary contact which initiates a subsequent transmissible response. Compounds involved in subsequent steps are referred to as secondary messengers. Examples would include G proteins, cAMP and CREB.
Messenger RNA: See RNA.
Metabolic dietician: A health care professional with training in nutrition with special training and emphasis in working with person with inborn errors of metabolism.
Metabolomics: The study of genetic processes involving metabolites. In genetic analysis it is the study of linked proteins in chemical systems that interact around a common pathway or process.
Metagenomics: The isolation and sequencing of the DNA of microorganisms taken from the environment, without the need for culturing the organism. It is sometimes also called “community genomics” or “environmental genomics.”
Metaphase: See cell cycle.
Microdeletion syndrome: A recognizable pattern of anomalies due to the deletion of multiple contiguous genes.
Microduplication syndrome: A recognizable pattern of anomalies due to the duplication of multiple contiguous genes.
Microsatellite: Repeated sequences of 2 to 6 bps of DNA. Microsatellites have proven to be important sources of genomic variability that can be used in mapping and linkage.
Microsatellite instability: Although microsatellites are quite variable between individuals, the actual number in a given person is a set number. In individuals who have mutations involving mismatch repair genes, acquired mutations in the microsatellites can alter their length. The laboratory identification of multiple lengths of microsatellites in an individual is termed “microsatellite instability” (msi).
Minisatellites: Repeating units of DNA around 15 to 100 nucleotides. Overall runs are 1 to 5 kb. Also called variable number tandem repeats (VNTRs).
Mismatch repair genes: Genes that function as biologic “spell-checkers” that identify errors in DNA replication and then initiate the process of correcting the error.
Missense mutation: See mutation.
Mitochondrial disorder: A medical condition due to disruption of mitochondrial function. A mitochondrial disorder may be due to mutations in either mitochondrial or nuclear genes.
Mitochondrial inheritance: The pattern of heritability seen with mutations in the mitochondrial DNA. Mitochondrial inheritance has several characteristics distinct from nuclear inheritance.
Mitosis: The process of duplicating chromosomes for somatic cell replication.
Modifier genes: Genes that affect the expression of other “major” genes. These may or may not have a primary function of their own.
Molecular cytogenetics: The interface of cytogenetic techniques with molecular techniques. Examples would include tests such as FISH.
Molecular decay: It is assumed that DNA replication systems will malfunction without external influence. The assumption is that over time, with enough replications, a mistake will eventually occur for no apparent reason—this is referred to as molecular decay.
Molecular (DNA) test: Laboratory analysis of an individual’s genetic material for a designated piece of DNA coding for a region or gene of interest.
Monoallelic expression: A phenotype that can be explained by variances in a single gene (locus). See also inheritance patterns.
Monogenic: Due to a single gene.
Monosomy (monosomic): Possessing only one copy of a particular chromosome pair.
Morphogen: A substance directing the process of morphogenesis.
Morphogenesis: The development of form. The process of structure and organ formation in embryogenesis.
Morpholino oligonucleotides: Analogs to cDNA which are altered to be resistant to nucleases. Such nucleotide segments can bind with mRNA and can alter gene expression.
Morula: Early embryonic structure (preceding the blastula). It is a solid mass of blastomere cells. The name morula comes from its physical resemblance to a mulberry.
Mosaicism: The situation in which not all cells in an organism possess the same genotype. Mosaicism usually occurs as the result of postconceptional (acquired) changes.
Functional mosiacism: Mosaicism that occurs as a result of differential expression of certain genes—not a change in the genetic code. (For example, X-chromosome inactivation results in functional mosaicism for females for X-linked genes).
Gonadal (germ-line) mosaicism: Mosaicism occurring in gonadal tissue. Gonadal mosaicism involving the gametes may be heritable.
Somatic mosaicism: Mosaicism occurring only in somatic cells.
Multi-color FISH: See FISH.
Multi-locus inheritance: A condition in which the observed phenotype can be explained by changes in more than one gene. Expression requires changes in multiple loci. See also inheritance patterns.
Multimeric protein: See protein.
Mutagen: A substance that is known to induce mutations.
Mutation: A change (deviation) of the genetic code from the normal, wild-type sequence.
Activating mutation: A mutation which exerts its deleterious effects by actually increasing the function of that gene.
Mutations can occur in two directions. A “forward mutation” is a change from the wild type to a mutant sequence. A “backward mutation” is a return from a mutant sequence to the wild type.
A “point mutation” is the change in a single nucleotide. It is sometimes referred to as a single-base substitution. There are three major types of point mutations: (1) Nonsense mutations result in a premature stop codon (and thus a truncated protein product); (2) Missense mutations change the nucleotide sequence. A “transition mutation” changes a purine to another purine or a pyrimidine to another pyrimidine. A “transversion mutation” changes from a purine to a pyrimidine or vice versa; and (3) Frame shift mutations result in a shift in the reading frame. This will disrupt all of the downstream nucleotide triplets.
Mutations can occur at any point in the ontogeny of an organism. Postconception mutations may occur in somatic (somatic mutations) or germinal cells (germ-line mutations).
For many possible reasons, not all mutations will produce a problem. Such mutations may be referred to as “silent mutations” or “neutral mutations.” Alternatively those mutations that do result in pathologic events are called “deleterious mutations” or “pathogenic mutations.”
A newly acquired mutation is called a “spontaneous mutation” in contrast to heritable (familial) mutations.
A “mutation suppressor” is a second mutational event which alleviates or corrects the phenotypic effects of the first mutation.
A genetic “lethal mutation” is a mutation that renders the organism incapable of passing along its genetic material.
Mutation rate: The mutation rate is the number of new mutant alleles for a given locus detected in the offspring as compared to their parents.
Genetic damage rate: All the genetic errors that occur during a cycle of replication. (Most of these however will be corrected by DNA repair systems.)
Mutation frequency: The ratio of mutant to normal (wild type) alleles in the population at a given time.
Mutation hot spot: The mutation rate is not even across the genome. Certain loci have a higher than baseline rate. Such loci are termed “hotspots.”
Mutational event rate: The unrepaired genetic errors that persist after repair systems have finished their work.
Natural history: Typical course of a medical condition in the absence of specific intervention.
Noncoding RNA: See RNA.
Nonsense mutation: See mutation.
Nuclear matrix: A network of fibers located within the cell nucleus. This network is analogous to the cytoplasmic cytoskeleton.
Nuclear membrane: A membrane (double lipid bilayer) that encases the nuclear contents and defines the boundaries of the nucleus.
Nuclear lamina: A dense layer of intermediate filaments inside the nuclear membrane that provide support and regulatory functions.
Nucleolus (nucleoli): A defined subdomain of the nucleus that assembles ribosomal subunits.
Nucleosome: The basic unit of DNA packaging. It comprises a short length of DNA wrapped around a core of histone proteins.
Noncoding strand: See coding.
Nondisjunction: The failure of separation of homologous chromosome pairs during cell division.
Nucleotide: The basic unit of DNA and RNA. Nucleotides are composed of a nitrogenous base, a 5-carbon sugar (either ribose or 2-deoxyribose), and a phosphate group.
Ochronosis: A dark (blue/black) discoloration of the skin. This finding has been classically associated with the inborn error of metabolism, alkaptonuria.
Okazaki fragments: Short segments of newly synthesized DNA which are complementary to the lagging template strand.
Oligonucleotide: A small segment of connected nucleotides.
Oogenesis: The process of forming oocytes from primordial germ cells.
Operon: A grouping of associated genes that are under the control of a single regulatory signal or promoter.
Paracentric invesion: See inversion.
Parthenogenesis: Asexual reproduction which occurs with the initiation of embryogenesis without fertilization.
Paternity: Pertaining to the male parent of a child.
Mis-assigned paternity: The situation in which the assumed father of a child is not, in fact, the biologic parent.
Pathogenesis: Physiologic process in causing disease.
Pathogenic (deleterious) mutation: See mutation.
Pattern formation: In embryogenesis, pattern formation refers to the complex predetermined organization and outcomes of cell fates spatially and temporally.
Pedigree: A formal diagram of the genetic relationships in a family using standardized symbols and nomenclature, indicating specific medical conditions, the status of each family member in relation to pertinent genetic traits (affected, unaffected, carrier, etc.) and additional relevant information necessary to discern possible patterns of inheritance and genetic risk; typically three or more generations are recorded.
Penetrance: For a given condition, the proportion of patients who show clinical signs of the disorder. Penetrance is disease specific. Some conditions are completely penetrant. Some show incomplete penetrance.
Peptidyl transfer(ase): A nuclear enzyme that catalyzes the cumulative addition of amino acid residues to a lengthening peptide chain in the ribosomes.
Pericentric inversion: See inversion.
Personalized genomics: Specific genetic testing that identifies individual risk profiles for a specific medical condition and or treatment option.
Personalized health care: Customizing diagnostics and treatments to an individual patient’s specific profile.
Personalized medicine: Health care targeted to the inherent biology and physiology of an individual leading to improvements in their medical care.
Pharmacogenetics: A personalized medicine strategy that utilizes genomic data to direct the choice and dosage of medications.
Phenocopy: Similar phenotypes produced by completely different genotypes.
Phenotype: The clinical or behavioral presentation of a genetic variation in an individual.
Expanded phenotype: The full range of phenotypes associated with a given genotype.
Phenotype, abnormal: The clinical presentation of a genetic or malformation disorder in an individual, including associated complications and their severity.
Phenotype, behavioral: The pattern of behavioral abnormalities and traits associated with a specific genetic or malformation disorder.
Plasmid: Circular DNA elements that replicate independent of the chromosomal DNA.
Pleiotropy (pleiotropism): Multiple clinical effects of a single gene.
Ploidy: Referring to chromosome number. One full set of human chromosomes (23) is designated as “n.”
Aneuploid: Having an incorrect number of chromosomes.
Euploid: Having a correct number of chromosomes.
Diploid: Having two full copies of a chromosome set (46, or 2n). This is the normal count for human somatic cells.
Haploid: Having one full set of 23 chromosomes (n). This is the normal count for the germ cells (gametes).
Polyploid: Having a full extra set (or multiples) of 23 beyond the usual 46 chromosomes in the human genome. This could be 69 (3n), 92 (4n), etc.
Triploid: A polyploidy chromosome count of 69 (3n).
Pluripotent: See potency.
Point mutation: See mutation.
Polar body: During meiosis in the formation of the oocyte, all daughter cells are not equally developed. The polar body is a tiny cell containing little or no cytoplasm that is produced and ultimately eliminated.
Poly-A tail: An extended run of up to 200 adenine nucleotides added to the “tail” (3′ end) of the pre-mRNA via the process called polyadenylation catalyzed by the enzyme, polyadenylate polymerase.
Polygenic: Literally “many genes.” Traditionally polygenic inheritance refers to a specific pattern of multifactorial inheritance in which multiple genes contribute in an additive fashion to a quantitative phenotype.
Polymerase chain reaction: A molecular technique of amplifying small amounts (even single copies) of DNA.
Polymorphism: As described in the text, the term polymorphism may be confusing. Population geneticists use the term for mutations that occur in the general population in at least 1% of individuals. Clinical geneticists and clinical genetic laboratory professionals often use the term synonymous with mutation (i.e., any change from the wild-type DNA code).
Benign polymorphism: A polymorphism that does not cause clinical disease
Single nucleotide polymorphism (SNP): A nucleotide change at a single specified locus in the genome different from the accepted “wild-type” code.
Posttranslational modification: Changes made to a transcribed protein that further defines the protein’s structure and function. Such modifications would include glycosylation and acetylation of the protein.
Potency: The capacity of a cell to differentiate along various paths.
Pluripotent cells: have the potential to differentiate in multiple different specialized cells.
Totipotent cells: are completely undifferentiated and have the capacity to proceed down any pathway of cell specialization.
Prereplication complex (pre-RC): A multimeric protein assembled at the initiation step of DNA replication.
Primer: A short segment of nucleotides that function as the initiation point for DNA synthesis.
Proband (propositus, proposita): The first member in a family to be ascertained. If affected, the individual is the index case.
Product rule: In probabilities, the rule is to multiply “and” relationships.
Prometaphase: See cell cycle.
Prometaphase karyotype: See banding.
Promoter: The region of the DNA strand that starts the transcription of a particular gene. Promoters are typically in close proximity to the genes they promote.
Prophase: See cell cycle.
Protein: A biochemical composed of strands of amino acids.
Regulatory protein: Specialized proteins that bind to regulatory sequences of DNA and function to regulate the gene transcription.
Multimeric protein: A protein complex that has a specific function but which is made up of several different protein components.
Protein domain: Proteins often have multiple functions.
Different parts of a given protein can perform site-specific functions.
Protein kinase: A protein that catalyzes phosphorylation of other proteins.
Proteomics: The broad study of proteins including structure, function, regulation, and interactions.
Prototroph: See Autotroph.
Pseudoautosomal regions: Complementary regions of the X and Y chromosomes which allow autosomal like activities for the sex chromosomes—including chromosomal cross-over.
Pseudodominance: See dominant inheritance.
Pseudogene: A DNA segment which shares a large amount of sequence homology to a “true” functioning gene. Pseudogenes may represent degenerate copies of previously functioning genes.
Pyrosequencing: See sequencing.
Qualitative trait: See trait.
Quantitative trait: See trait.
Quasi-dominance: See dominant inheritance.
Reanneal: See anneal.
Recessive (recessiveness): Recessive conditions are clinically manifest only in individuals homozygous for the mutant allele (or compound heterozygotes for two different mutant alleles), i.e., carrying a “double dose” of an abnormal gene.
Reciprocal translocation: See translocation.
Recombination: Also called “crossing over.” During meiosis homologous chromosome pairs exchange material by physically bridging from one to another. It is likely that at least one cross-over event is necessary for normal meiosis to proceed.
Recurrence risk: See risk.
Regulation: The concept of altering gene expression without changing the code. Regulation of a gene can include turning that gene “off” or “on” or partially turning it “up” or “down.”
Regulators of organelle gene expression (ROGEs): Organelles such as mitochondria possess DNA separate from the nuclear genome. These extranuclear genetic elements are coordinated and regulated by nuclear elements known as ROGEs.
Regulatory protein: See protein.
Release factor: A protein that functions to terminate translation by locating the termination (stop) codon of a gene.
Replication fork: During the process of DNA replication, the replication fork is the active site of unwinding the parent sequence and synthesizing the daughter code.
Replicative segregation: The separation of subpopulations of mitochondria within a cell by the physical process of cell division.
Replisome: The structure that carries out the activities of the replication fork. The replisome is multimeric unit composed of two DNA polymerase enzymes, primase and DNA.
Repressor (repressible): A regulatory protein that binds to the operator site and blocks transcription of the gene.
Response elements: Short DNA segments that are part of the promoter region of a gene that bind transcription factors to regulate transcription.
Restriction enzyme (point): Also called restriction endonucleases. Enzymes that cleave (cut) DNA by recognizing very specific sequences that is characteristic of that enzyme. The site at which the DNA is cut is the restriction site (point).
Reverse transcriptase: An enzyme which catalyzes the synthesis of DNA from an RNA template (the reverse of normal transcription).
Ribosomal binding site: The nucleotide sequence which signals the beginning of a gene. See Shine-Dalgarno sequence.
Ribosomal RNA: See RNA.
Risk: In clinical genetics, the “risk” identified for a patient is probability of a clinical event occurring.
Empiric risk: The risk of a condition in a defined situation ascertained from simple observational data.
Recurrence risk: The likelihood that a clinical disorder will occur in additional siblings of the same biological parents.
Relative risk: The risk of developing a disease relative to an exposure or other predisposing factor.
RNA: Ribonucleic acid. A biochemical involved in a variety of genetic processes. It is composed of long chains of nucleotides, each of which is assembled from a nitrogenous base attached to a backbone of a ribose sugar, and a phosphate molecule. Messenger RNA (mRNA), ribosomal RNA (rRNA), and transfer RNA (tRNA) are involved in the traditional understanding of transcription and translation.
Noncoding RNA: Many of the other species of RNA do not code for a product. Rather they have a primary regulatory function. Examples would include microRNAs (miRNA) which act through RNA interference (RNAi) as do small interfering RNAs (siRNA). Pri-miRNAs are the primary transcripts for miRNA which are then processed into pre-miRNAs. Nuclear RNAs include small nuclear RNAs (snRNA) whose primary function is in the processing of pre-mRNA also called heterogenous nuclear RNA (hnRNA) in the nucleus.
RNA polymerases (I-V): A family of enzymes involved in the synthesis of various forms of RNA.
Robertsonian translocation: See translocation.
Sanger sequencing: See sequencing.
Satellite DNA: Large arrays of tandemly repeating, noncoding DNA. The name “satellite” comes from a second (“satellite” band) that is adjacent to regular DNA on a density gradient.
Second(ary) messenger: See messenger.
Segmentation genes: Genes that code for embryonic organization into various “segments” (or fields) of the body.
Segregation: Separation of paired homologous chromosomes. Segregation may occur in several different ways if a translocation exists.
Adjacent segregation: The segregation of each of the structurally normal chromosomes with one of the translocated ones is said to be adjacent.
Alternate: The segregation is said to be alternate if the two normal chromosomes segregate together, as do the reciprocal parts of the translocated ones.
Selected population screening: See genetic screening.
Selection: A process that favors the survival of one kind of organism over others by a reproductive advantage.
Directional selection: When natural selection favors a single phenotype.
Diversifying selection: When natural selection favors more than one phenotype. Extreme phenotypes are favored over intermediate ones.
Stabilizing selection: Selection in which genetic diversity decreases as the population stabilizes on a particular trait value. Instead of favoring individuals with extreme phenotypes, it favors the intermediate ones.
Sense codon: See codon.
Sequence: A pattern of related malformations and/or deformations and/or disruptions such that one initial physical abnormality leads to the occurrence of additional abnormalities in a sequential manner.
Sequencing: When applied to genomics, “sequencing” means the determination of the actual order and type of nucleotides in a defined portion of the genome.
DNA sequencing: Determining the nucleotide sequence for DNA molecules.
High-throughput sequencing: A method of DNA sequencing that uses multiple modifications of regular sequencing including robotics and advanced information technology to greatly increase the possible rate of sequencing.
Linear sequencing: Sequencing a segment of genetic material in a linear fashion (i.e., from start codon to terminating sequence in order).
Massively parallel sequencing: One of the newest methods of sequencing that employs techniques of sequencing thousands of small copies (subsets) of the region to be sequenced in tandem.
Pyrosequencing: A newer method of DNA sequencing that utilizes pyrophosphate release on nucleotide incorporation.
Sanger (dideoxy) sequencing: A method of DNA sequencing developed by Frederick Sanger in 1977. The technique utilizes the selective incorporation of chain-terminating dideoxynucleotides.
Whole exome sequencing: Sequencing the entire coding region of an individual’s genome.
Whole genome sequencing: Sequencing an individual’s entire genetic code—both coding and noncoding parts.
Semi-dominance: See dominant inheritance.
Sensitivity: See genetic screening.
Sex (linkage, limited, influenced):
Sex-limited phenotype: The expression of a trait in only one of the sexes, due, for instance, to anatomical differences. Example: uterine or testicular defects.
Sex-influenced phenotype: A phenotype which occurs in both males and females, but with different frequencies. Example: male pattern baldness.
Sex-linked inheritance: Sex-linked genes are those located on either the X or the Y chromosome. Because few genes are known to be located on the human Y chromosome, we will focus on X-linked disorders.
Shine-Dalgarno sequence: A nucleotide sequence (AGGAGGU) that is found in 8 bps upstream of the AUG start codon of mRNA. It functions as a ribosomal binding site.
Signal transduction: The process of converting an extracellular signal into an intracellular response.
Signaling pathway: A series of biochemical reactions in an organism in which chemical signals are sequentially passed from one molecule to the next in succession.
Single nucleotide polymorphism (SNP): See polymorphism.
Tag SNP: A representative SNP in a genomic region (locus) with known high linkage disequilibrium.
Single-locus FISH: See FISH.
Sister chromatids: See chromatid.
Situs abnormalities: “Situs” refers to the place where something originates or should be (i.e., the normal place). In embryogenesis, situs refers to the location where an organ or body part should be found. There are medical descriptors of several different abnormalities of situs (e.g., laterality defects).
Dextrocardia: A situs abnormality of the heart only.
Situs abdominalis: Only the abdominal organs being on the wrong side.
Situs inversus: The description of an organ being in the opposite (mirror image) position of normal.
Situs inversus totalis: All organs being on the opposite side of normal.
Situs solitus: The normal positioning of the abdominal and thoracic organs.
Small nuclear ribonucleoproteins (snRNP): RNA-protein complexes involved in transcription. These complexes are essential to the excision of introns from mRNA.
Somatic mosaicism: See mosaicism.
Somatic mutation: See mutation.
Sorting signals: Specific amino acids in a protein sequences serve to guide the transport of that protein to specific subcellular compartments.
Southern blot: More formally referred to as a DNA blot test. Named after the British biologist Dr. Edwin Southern. The term “blot” refers to the method of transferring the DNA molecules. This process allows the separation of DNA molecules of differing sizes.
Specificity: See genetic screening.
Spermatogenesis: The embryologic process of starting with undifferentiated germ cells and proceeding to the end point of mature spermatozoa.
Spindle: See chromosome spindle.
Spontaneous mutation: See mutation.
Standard deviation: A statistical term that represents the square root of the variance.
Stop codon(s): See codon.
Structural gene: See gene.
Sub-telomeric FISH: See FISH.
Susceptibility: Genetic susceptibility refers to a genetic change (polymorphism) that renders the individual more susceptible to adverse effects from a specific environmental interaction.
Synapsis: The coupling (pairing) of two homologous chromosomes that happens during meiosis.
Synaptonemal complex: A complex multimeric (three proteins) structure that bridges across the paired chromosomes during prophase I of meiosis.
Syndrome: A recognizable recurrent pattern of malformations and/or deformations and/or disruptions with one or more specific, defined causes.
Tag SNP: See single nucleotide polymorphism.
Tandem duplications: See duplication.
Tandem repeats: Nucleotide sequences that are contiguously repeated at a given locus.
Tautomeric shift: A shift in a proton (hydrogen ion) to form a different isomer. In DNA, a tauomeric shift of a nucleotide may result in a mutation.
Telocentric: See chromosome.
Telomere: The end part of a chromosome composed of repetitive nucleotide sequences.
Telophase: See cell cycle.
Teratogen: An agent capable of inducing one or more malformations in a developing embryo. A teratogen can be environmental exposures or maternal medical conditions.
Threshold: A biologic limit which if crossed, exceeds the capability of an organism to buffer against pathologic changes.
Totipotent: See potency.
Trait: An observable feature or characteristic.
Qualitative: An observable trait.
Quantitative: A measureable trait.
Transcription: The copying of DNA to a complementary segment of mRNA.
Transcription factor: A protein that regulates the rate of DNA transcription, typically by altering RNA polymerase activity.
Transcriptomics: The transcriptome is the total set of transcripts in a given organism. This reflects all of the genes that are being actively expressed at any given time. Transcriptomics is the discipline of studying the transcriptome.
Transfer RNA: See RNA.
Transition: See mutation.
Translocation: A chromosome abnormality in which a portion of one chromosome has moved (translocated) to another location from its normal site.
Balanced: A translocation in which there is no net loss or gain of chromosomal material from the normal amount and makeup.
Reciprocal: A complementary exchange of chromosomal material between two nonhomologous chromosomes.
Robertsonian: A special type of translocation that involves two acrocentric chromosomes. In this type of translocation the satellite material is lost on both chromosomes and the two “q arms” are joined together.
Unbalanced: A translocation in which there is net loss (deletion) or gain (duplication) of chromosomal material.
Transposable elements (transposons): One of several classes of mobile segments of DNA.
Class I transposable elements: These are called retrotransposons. Replication occurs in 2 steps:(1) DNA to RNA via transcription; and (2) From RNA back to DNA by reverse transcription. This method of duplication in retrotransposons is quite similar to retroviruses.
There are three main categories of retrotransposons:
• Long terminal repeats (LTRs). These encode reverse transcriptase, similar to retroviruses
• Long interspersed elements (LINEs). These also encode reverse transcriptase but lack LTRs. They are transcribed by RNA polymerase II.
• Short interspersed elements (SINEs). Similar to LINEs but of course shorter (<500 bp) these do not code for reverse transcriptase. They are transcribed by RNA polymerase III.
Class II transposable elements: These are called DNA transposons. In contrast to retrotransposons, these do not involve an RNA intermediate.
Transversions: See mutation.
Trialleleic inheritance: Certain genetic conditions are caused by mutations at more than one locus (multi-locus). Triallelic inheritance refers to a condition that requires mutations in three different alleles to produce the phenotype. See also inheritance patterns.
Trilaminar embryo: In the first 2 to 3 weeks of gestation, the early embryo becomes a layered structure. The three layers (endoderm, ectoderm, and mesoderm) are the embryonic primordia for future tissue groups.
Ectoderm: The embryonic layer that gives rise to the hair, skin, teeth, nails, and parts of the nervous system.
Endoderm: The embryonic layer that gives rise to the epithelium of the abdominal and lower respiratory tracts, and associated organs such as the liver and pancreas.
Mesoderm: The embryonic layer that gives rise to constitutional components of the body including bone, muscle, connective tissue, dermis layer of the skin, circulatory system, and the reproductive system.
Trinucleotide repeats: Repeating units of 3 nucleotides distributed in a nonrandom fashion across the genome. (See also satellite DNA.)
Trinucleotide repeat disorders: Medical conditions produced by abnormal numbers (typically expansion) of trinucleotide repeats. Through pre-event mutations, transcription of regions of trinucleotide repeats can undergo sequential expansion (increase in the number of repeats beyond the normal baseline counts). Expansion of these regions can disrupt gene function and regulation through a variety of mechanisms. If the expansion exceeds tolerable threshold, human disease can occur. Typically, trinucleotide repeat disorders are neuromuscular conditions.
Triploid: See ploidy.
Trisomy (trisomic): Having a full extra copy (n = 3) of a particular chromosome (e.g., trisomy 21).
True dominance: See dominant inheritance.
Uniparental disomy (UPD): Inheriting two copies of the same chromosome number from one parent (in contrast to the normal situation of receiving one homolog from each parent).
Heterodisomy: Inheriting two of the same chromosome pair from one parent.
Isodisomy: Inheriting both copies of a homolog pair from one parent.
United States Medical Licensing Examination (USMLE): A three-part examination taken by medical students as part of the process of medical licensure.
Upstream factors: Specific proteins that bind DNA and recognize short consensus elements located upstream from the initiation of transcription.
Variability: In clinical genetics, refers to the range (severity) of a phenotype.
Inter-familial variability: Clinical variation of a specific condition as observed between families.
Intra-familial variability: Clinical variation of a specific condition as observed within a family.
Variable expression: See expression.
Variable number tandem repeats (VNTRs): See minisatellite.
Variance: A calculated statistical value which is the average squared deviation of each data point from the mean.
Whole exome sequencing: See sequencing.
Whole genome sequencing: See sequencing.
Wild type: The phenotype or genotype established as the baseline (normal) for a population.
Wobble position: The third nucleotide of a trinucleotide sequence in DNA. Because the human DNA code is degenerate (i.e., more than one trinucleotide combination can code for the same amino acid), the final nucleotide is said to be in the wobble position.
X-chromosome inactivation: Also known as Lyonization. In females—who have 2 X chromosomes–1 X chromosome is inactivated in every cell. This serves as a “balancing” mechanism because males are hemizygous—possessing only one X chromosome.
X-inactivation center (XIC): The locus on the X chromosome that controls the process of X-inactivation.
Skewed X inactivation: Because X-inactivation is presumably a random process, it is predicted that on average, there will be a 50:50 split between the two X chromosomes as far as which is inactivated. There are several pathogenic mechanisms whereby one X may be preferentially inactivated over the other—leading to a skewed ratio between the two X’s.
X-linked inheritance: Transmission of a condition via a gene that is on the X chromosome.
Y-linked inheritance: Sometimes called holandric inheritance. Transmission of a condition via a gene that is on the Y chromosome.