Appendix E
Glossary of Terms

Allele

An alternate form of a gene or locus. A locus can have many different alleles which may differ from each other by as little as a single base or by the complete absence of a sequence.
See Allele in the MGI Glossary.

Allele-Specific Oligonucleotide (ASO)

An oligonucleotide designed to hybridize only to one of two or more alternative alleles at a locus. An ASO is usually designed around a variant nucleotide located at or near its center (see Chapter 8).

Anchor locus

A well-mapped locus that is chosen as a marker to "anchor" a particular genomic region to a framework map that is being constructed in a linkage study with a new cross (see Chapter 9).

Anonymous locus

An isolated DNA region with no known function but with at least two allelic states that can be followed through some form of DNA analysis in mapping studies.
See Anonymous DNA Segment in the MGI Glossary.

ASO

See Allele-Specific Oligonucleotide.

B1 repeat

The most prominent SINE class of highly dispersed repetitive elements in the genome with a copy number of ~150,000 (see Chapter 5).

B2 repeat

The second most prominent SINE class of highly dispersed repetitive elements in the genome with a copy number of ~90,000 (see Chapter 5).

B6

An abbreviation for the name of the most commonly used strain of mice — C57BL/6.

Bayesian analysis

A statistical approach that takes prior information into account in the determination of probabilites. The Bayesian approach yields an equation that must be used to convert P values obtained from Chi-squared analysis of recombination data into actual probabilities of linkage between two loci ( Chapter 9).

Backcross

A cross between one animal type that is heterozygous for alleles obtained from two parental strains and a second animal type from one of those parental strains. The term is often used by itself to describe the two generation breeding protocol of an outcross followed by a backcross used frequently in linkage analysis (see Chapter 3 and Chapter 9).
See Backcross in the MGI Glossary.

CA-repeat

The most prominent class of microsatellites found in mammalian genomes (see Chapter 8).

castaneus

The shortened form of M. m. castaneus, a subspecies within the M. musculus group that can be combined with a traditional inbred strain for linkage analysis (see Chapter 2 and Chapter 9).

centimorgan (cM)

The metric used to describe linkage distances. A centimorgan is the distance between two genes that will recombine with a frequency of exactly one percent. This term is named afer Thomas Hunt Morgan, who first conceptualized linkage while working with Drosophila.
See Centimorgan in the MGI Glossary.

Chi-squared

A statistical test used most often by geneticists to ascertain whether experimental data provide significant evidence for linkage between two loci (see Chapter 9).

Chimera

An individual mouse, or other mammal, that is derived from the fusion of two or more preimplantation embryos or an embryo and ES cells (see Chapter 6).
See Chimera in the MGI Glossary.

Chromosome bands

Alternative light and dark-staining regions within chromosomes that are visualized by light microscopy (see Chapter 5).

cM

See centimorgan.

Codominance

Defined for pairs of alleles. The situation in which an animal heterozygous for two alleles (A1 and A2 at the A locus) expresses both of the phenotypes observed in the two corresponding homozygotes. Thus, the heterozygote (A1/A2) and both homozygotes (A1/A1 and A2/A2) are all distinguishable from each other and A1 and A2 would be considered to be "codominant". This term has also been coopted to describe DNA markers defined by alternative visible allelic forms such as different sized restriction fragments or PCR products.
See Codominant in the MGI Glossary.

Coisogenic

A variant strain of mice that differs from an established inbred strain by mutation at only a single locus (see Chapter 3).

Commensal

Pertaining to populations of house mice that depend on human-built habitats and/or food production for survival (see Chapter 2).

Concordance

For two or more loci or traits typed in offspring from a backcross or RI strain, the presence of alleles (or expression of a trait) derived from the same parental chromosome (see Chapter 9).

Congenic

A variant strain of mice that is formed by backcrossing to an inbred parental strain for ten or more generations while maintaining heterozygosity at a selected locus (see Chapter 3).
See Congenic in the MGI Glossary.

Conplastic

A variation on the congenic approach in which the mitochondrial genome from one strain is transferred onto a different genetic background (see Chapter 3).
See Conplastic in the MGI Glossary.

Consomic

A variation on the congenic approach in which an entire chromosome from one strain, usually the Y, is transferred onto a different genetic background (see Chapter 3).
See Consomic in the MGI Glossary.

Contig

A set of contiguous overlapping genomic clones that together span a larger region of the genome than that covered by any one clone (see Chapter 7 and Chapter 10).
See Contig in the MGI Glossary.

CpG island

A genomic region of one or a few kilobases in length that contains a high density of CpG dinucleotides. CpG islands are associated with the 5'-ends of genes (see Chapter 10; previously called an HTF island).

Cross

Refers to one or more mating units set up with males and females that each have a designated genotype chosen to carry out a particular genetic analysis (see Chapter 3).
See Cross in the MGI Glossary.

Crossover product

A chromosome homolog that was formed through the recombination of alleles at different loci present on opposite homologs in one of the parents of the animal in which it is observed (see Chapter 7).

Deme

A breeding group unit. In natural populations of mice, a deme usually consists of one breeding male with a harem of up to 8 females (see Chapter 2).

Differential segment

In the genome of a congenic mouse, the region of chromosome surrounding the selected locus that is derived together with it from the donor genome (see Chapter 3).

Discordance

The opposite of concordance. Inheritance of only one of two alleles or traits associated with a particular parental chromosome.

Disjunction

The normal process by which the two homologs of each chromosome in a meiotic cell separate and move to different gametes (see Chapter 5).

Distal

A relative term meaning closer to the telomere; the opposite of proximal.

DNA marker

A cloned chromosomal locus with allelic variation that can be followed directly by a DNA-based assay such as Southern blotting or PCR (see Chapter 8).
See Anonymous DNA Segment in the MGI Glossary.

domesticus

Short form of M. m. domesticus, a subspecies within the M. musculus group that resides in Western Europe, Africa, and throughout the New World. It is the primary component of the traditional inbred strains (see Chapter 2).

Dominant

A relative term describing the relationship of one allele to a second at the same locus when an animal heterozygous for these alleles expresses the same phenotype as an animal homozygous for the first allele. The second allele of the pair is considered recessive.
See Dominant in the MGI Glossary.

ES cells

Embryonic stem cells. Cultured cells derived from the pluripotent inner cell mass of blastocyst stage embryos. Used for gene targeting by homologous recombination (see Chapter 6).
See ES Cells in the MGI Glossary.

Expressivity

Pertaining to observed quantitative differences in the expression of a phenotype among individuals that have the same mutant genotype. When quantitative differences are observed, a phenotype is said to show "variable expressivity" which can be caused by environmental factors, modifier genes or chance.
See Expressivity in the MGI Glossary.

F₁

The first filial generation; the offspring of an outcross between two inbred strains (see Chapter 3).

Feral

Pertaining to wild populations of animals derived from commensal ancestors; house mice that live apart from, and independent of, humans (see Chapter 2).

Filial generation

Pertaining to a particular generation in a sequence of brother-sister matings that can be carried out to form an inbred strain. The first filial generation, symbolized as F₁, refers to the offspring of a cross between mice having non-identical genomes. When F₁ siblings are crossed to each other, their offspring are considered to be members of the second filial generation or F₂, with subsequent generations of brother-sister matings numbered with integer increments (see Chapter 3).

FISH

Fluorescent in situ Hybridization. An enhanced from of in situ hybridization with high resolution and sensitivity (see Chapter 10).
See FISH in the MGI Glossary.

Genetic drift

Refers to the constant tendency of genes to evolve even in the absence of selective forces. Genetic drift is fueled by spontaneous neutral mutations that disappear or become fixed in a population at random. Inbred lines separated from a common ancestral pair can drift rapidly apart from each other.

Genome

The total genetic information present within a single cell nucleus of an animal. The haploid genome content of the mouse is 3 x10⁹ bp.
See Genome in the MGI Glossary.

Genotype

For any one animal, the set of alleles present at one or more loci under investigation. At any one autosomal locus, a genotype will be either homozygous (with two identical alleles) or heterozygous (with two different alleles).
See Genotype in the MGI Glossary.

Giemsa

A stain and associated protocol used to accentuate visually the difference between bands and interbands on metaphase chromosomes (see Chapter 5).

Haplotype

Pertaining to a particular set of alleles at linked loci (or nucleotide changes within a gene) that are found together on a single homolog. In linkage studies with backcross offspring and RI strains, the haplotypes associated with each sample provide a means for determining the order of loci (see Chapter 9).
See Haplotype in the MGI Glossary.

Heterozygote

An animal with two distinguishable alleles at a particular locus under analysis. In this case, the locus is considered to be heterozygous.
See Heterozygote in the MGI Glossary.

Histocompatible

Pertaining to a genetic state in which cells from two animals can be cross-transplanted without immunological rejection. The opposite of histoincompatible. Histocompatibility is controlled predominantly by genes in the Major Histocompatiblity Complex or MHC (see Chapter 3).

Homolog

This term is used by geneticists in two different senses: (1) One member of a chromosome pair in diploid organisms, and (2) A gene from one species, for example the mouse, that has a common origin and functions the same as a gene from another species, for example humans, Drosophila, or yeast.
See Homolog in the MGI Glossary.

Homozygote

An animal with two identical alleles at a particular locus under analysis. In this case, the locus is considered to be homozygous.
See Homozygote in the MGI Glossary.

Hotspot, recombinational

A localized region of chromosome, usually less than a few kilobases in length, that participates in crossover events at a very high rate relative to neighboring regions of chromosome (see Chapter 7).

House mouse

An animal that is a member of the species M. musculus.

HTF island

See CpG island.

Hybrid sterility

Pertaining to the sterility of animals produced from matings between members of two different species, such as M. musculus and M. spretus. In this case, and in general, only the male hybrids are sterile while the females are fertile (see Chapter 2).

Hybrid zone

A narrow geographical line that separates the natural ranges of two distinct animal populations. The best-characterized house mouse hybrid zone occurs in Central Europe and separates M. m. domesticus to the west and M. m. musculus to the east (see Chapter 2).

Imprinting, Genomic

The situation in which the expression of a gene varies depending on its parental origin (see Chapter 5). Only a small subset of genes in the mammalian genome are imprinted.
See Imprinting in the MGI Glossary.

In situ hybridization

A technique for mapping cloned DNA sequences by hybridization directly to metaphase chromosomes and analysis by microscopy (see Chapter 10).
See In situ Hybridization in the MGI Glossary.

Inbred

Animals that result from the process of at least twenty sequential generations of brother-sister matings. This process is called inbreeding (see Chapter 3).
See Inbred Strain in the MGI Glossary.

Incross

A cross between two animals that have the same homozygous genotype at designated loci; for example, between members of the same inbred strain (see Chapter 3).
See Incross in the MGI Glossary.

Intercross

A cross between two animals that have the same heterozygous genotype at designated loci; for example, between sibling F1 hybrids that were derived from an outcross between two inbred strains (see Chapter 3).
See Intercross in the MGI Glossary.

Interference

The suppression of crossing over that occurs in the extended chromosomal vicinity of an initial crossover event. Interference is responsible for a severe reduction in the expected frequency of double crossover events in ten to twenty centimorgan lengths of the genome (see Chapter 7).

Interspecific cross

A cross between mice from two different species, most often M. musculus (represented by a traditional laboratory strain) and M. spretus for the purpose of linkage analysis. The interspecific cross is carried out to take advantage of the high level of polymorphism between the two parents (see Chapter 9).

Intersubspecific cross

A cross between two subspecies (see Chapter 9). In the case of mouse genetics, this refers most often to a cross between a traditional inbred strain that is predominantly M. m. domesticus and one of the other subspecies in the M. musculus complex, usually M. m. musculus or M. m. castaneus or a combination of both (within the faux species M. m. molossinus).

IRS PCR

Interspersed Repetitive Sequence PCR. A method for amplifying species-specific sequences from a complex hybrid genome (see Chapter 8).

Karyotype

The number of chromosomes present in a given genome and the form that they assume (including banding patterns) when they condense (see Chapter 5). A karyotype is defined entirely by microscopic observation.
See Karyotype in the MGI Glossary.

Library, genomic

A sufficient number of genomic clones such that any sequence of interest is very likely to be present in at least one member of the set. If the library is random, the actual set of original clones must contain a cumulative length of DNA that is equal to multiple "genomic equivalents."
See Library in the MGI Glossary.

Linkage

Pertaining to the situation where two loci are close enough to each on the same chromosome such that recombination between them is reduced to a level significantly less than 50%.
See Linkage in the MGI Glossary.

Linkage group

A set of loci in which all members are linked either directly or indirectly to all other member of the set. Essentially equivalent to the genetic information associated with any single chromosome.

Locus

Any genomic site, whether functional or not, that can be mapped through formal genetic analysis.
See Locus in the MGI Glossary.

Meiosis

The process by which diploid germ cell precursors segregate their chromosomes into haploid nuclei within eggs and sperm.
See Meiosis in the MGI Glossary.

Meiotic product

An individual haploid genome within an egg or sperm cell. Meiotic products are usually observed and analyzed within the context of diploid offspring.

Microdissection

A method for dissecting and cloning from defined subchromosomal regions by microscopic examination and manipulation (see Chapter 8).

Microsatellite

A very short unit sequence of DNA (2 to 4 bp) that is repeated multiple times in tandem. Microsatellites (also called Simple Sequence Repeats or SSRs) are highly polymorphic and make ideal markers for linkage analysis (see Chapter 8). A polymorphism at a microsatellite locus is also referred to as a Simple Sequence Length Polymorphism (SSLP).

Minisatellite

A highly polymorphic type of locus containing tandemly repeated sequences having a unit length of 10 to 40 bp. Minisatellite polymorphisms can be assayed by RFLP analysis or by PCR (see Chapter 8). Also referred to as Variable Number of Tandem Repeat (VNTR) loci.

Multifactorial

A trait controlled by at least two factors, which may be genetic or environmental (see Chapter 9); polygenic traits represent a subset of multifactorial traits.

Mus

The name of the genus that contains all house mice (M. musculus) and other closely related species.

musculus

Abbreviated form of M. musculus, the species that is synonymous with the house mouse (see Chapter 2).

Mutant allele

This term is defined differently by formal geneticists and population biologists. The formal genetic definition is an allele that exerts a deleterious effect on phenotype. The population definition is an allele that is present at a frequency of less than 1% in a natural population; according to this definition, a mutant allele in one population may be considered non-mutant ( wild-type) in another population.

Mutation

An allele present in a progeny that is not present in the genome of either its parents.
See Mutation in the MGI Glossary.

N2, N3, N4 etc.

Used to describe the generation of backcrossing and the offspring that derive from it. The N2 generation describes offspring from the initial cross between an F₁ hybrid and one of the parental strains. Each following backcross generation is numbered in sequence (see Chapter 3).

Outcross

A cross between genetically unrelated animals.
See Outcross in the MGI Glossary.

Parental

An inbred strain of animals that is used in the initial cross of a multi-generational breeding protocol; the meiotic products and offspring that retain the same set of designated alleles as one of the parental strains.

Penetrance

Pertaining to the failure of some animals with a mutant genotype to express the associated mutant phenotype. In any case where less than 100% of genotypically mutant animals are phenotypically mutant, the phenotype is said to be "incompletely penetrant". Incomplete penetrance is usually a matter of chance or modifiers in the genetic background.
See Penetrance in the MGI Glossary.

PFGE

Pulsed Field Gel Electrophoresis. A technique for separating very large DNA molecules from each other (see Chapter 10).

Phenotype

The physical manifestation of a genotype within an animal. A mutant phenotype is caused by a mutant genotype and is manifested as an alteration within an animal that distinguishes it from the wild-type.
See Phenotype in the MGI Glossary.

Phylogenetic tree

A diagram showing the postulated evolutionary relationships that exist among related species in terms of their divergence from a series of common ancestors at specific points in time.

Polygenic

Pertaining to a phenotype that results from interactions among the products of two or more genes with alternative alleles (see Chapter 9).
See Polygenic in the MGI Glossary.

Polymorphic

A term formulated by population geneticists to describe loci at which there are two or more alleles that are each present at a frequency of at least one percent in a population of animals. The term has been co-opted for use in transmission genetics to describe any locus at which at least two alleles are available for use in breeding studies, irrespective of their actual frequencies in natural populations.
See Polymorphism in the MGI Glossary.

Proximal

A relative term meaning closer to the centromere; the opposite of distal.

Quantitative trait

A phenotype that can vary in a quantitative manner when measured among different individuals (see Chapter 9). The variation in expression can be due to combinations of genetic and environmental factors, as well as chance. Quantitative traits are often controlled by the cumulative action of alleles at multiple loci.
See QTL in the MGI Glossary.

Recessive

A relative term describing the relationship of one allele to a second at the same locus when an animal heterozygous for these alleles expresses the same phenotype as an animal homozygous for the second allele. The second allele of the pair is considered dominant.
See Recessive in the MGI Glossary.

Recombinant

The result of a crossover in a doubly heterozygous parent such that alleles at two loci that were present on opposite homologs are brought together on the same homolog. The term is used to describe the chromosome as well as the animal in which it is present.

Recombinant congenic strain

A variation on recombinant inbred strains in which the initial outcross is followed by several generations of backcrossing prior to inbreeding (see Chapter 3).
See Congenic in the MGI Glossary.

Recombinant inbred (RI) strain

A special type of inbred strain formed from an initial outcross between two well-characterized inbred strains followed by at least twenty generations of inbreeding (see Chapter 9).
See Recombinant Inbred in the MGI Glossary.

Restriction Fragment Length Polymorphism (RFLP)

A DNA variation that affects the distance between restriction sites (most often by a nucleotide change that creates or eliminates a site) within or flanking a DNA fragment recognized by a cloned probe (see Chapter 8). RFLPs are detected upon Southern blot hybridization. The term RFLP is commonly used even in situations where the DNA variation may not represent a true polymorphism in the population-based definition of this term.
See RFLP in the MGI Glossary.

Restriction Fragment Length Variant (RFLV)

A more accurate term to use in place of Restriction Fragment Length Polymorphism in those cases where the frequency of the variant in natural populations is not known.

Retroposon

An inserted genomic element that originated from the reverse transcribed mRNA produced from another region of the genome (see Chapter 5).
See Retrotransposon in the MGI Glossary.

RFLP

See Restriction Fragment Length Polymorphism.

RFLV

See Restriction Fragment Length Variant.

RI strain

See Recombinant Inbred strain.

Robertsonian translocation

A fusion between the centromeres of two acrocentric chromosomes to produce a single metacentric chromosome (see Chapter 5).

Satellite DNA

This term was used originally to describe a discrete fraction of DNA visible in a CsCl₂ density gradient as a "satellite" to the main DNA band. The term now refers to all simple sequence DNA having a centromeric location, whether distinguishable on density gradients or not (see Chapter 5).

SDP

See Strain Distribution Pattern.

Simple Sequence Repeat (SSR)

See microsatellite.

SINE

Short INterspersed Element. Families of selfish DNA elements that are a few hundred basepairs in size and dispersed throughout the genome (see Chapter 5).

spretus

Abbreviated form of M. spretus, a species commonly used in interspecific matings for the generation of linkage maps (see Chapter 2 and Chapter 9).

SSCP

Single Strand Conformation Polymorphism. A gel-based means for detecting single nucleotide changes within allelic PCR products that have been denatured and gel-fractionated as single strands.

SSLP

Simple Sequence Length Polymorphism; see microsatellite.

SSR

Simple Sequence Repeat; see microsatellite.

Strain

Refers to a group of mice that are bred within a closed colony in order to maintain certain defining characteristics. Strains can be inbred or non-inbred (see Chapter 3).
See Inbred Strain in the MGI Glossary.

Strain Distribution Pattern (SDP)

The distribution of two segregating alleles at a single locus across a group of animal samples used for analysis in a linkage study (see Chapter 9). Used in the context of backcross data and data obtained from RI strains.

Sympatric

Closely related species that have overlapping ranges in nature but do not interbreed. In different parts of its range, M. musculus is sympatric with M. macedonicus, M. spicilegus, and M. spretus (see Chapter 2).

Syngenic

Literally "of the same genotype". Used most frequently by immunologists to describe interactions between cells from the same inbred strain.

Syntenic

Two loci known to be in the same linkage group. Conserved synteny refers to the situation where two linked loci in one species (such as the mouse) have homologs that are also linked in another species (such as humans).
See Synteny in the MGI Glossary.

Targeting, Gene

A technology that allows an investigator to direct mutations to a specific locus in the mouse genome (see Chapter 6). Also called targeted mutagenesis.
See Targeted Mutation in the MGI Glossary.

Transgene

A fragment of foreign DNA that has been incorporated into the genome through the manipulation of preimplantation embryos (see Chapter 6).
See Transgene in the MGI Glossary.

Transgenic

Pertaining to an animal or locus that contains a transgene (see Chapter 6).

Translocation

Pertaining to a novel chromosome formed by breakage and reunion of DNA molecules into a non- wild-type configuration (see Chapter 5).
See Translocation in the MGI Glossary.

Unequal crossover

A crossover event that occurs between non-allelic sites. Can lead to the duplication of sequences on one homolog and the deletion of sequences on the other (see Chapter 5).

Variant

Literally, an alternative form. Used in conjunction with locus, phenotype, or mouse strain. A "DNA variant" is equivalent to an alternative DNA allele. A variant mouse usually refers to one that carries a mutant allele or expresses a mutant phenotype.

VNTR

"Variable Number of Tandem Repeats" locus; see Minisatellite.

Walking

The sequential cloning of adjacent regions along a chromosome by using the ends of previously-obtained clones to re-screen genomic libraries. Walking allows one to extend the length of contigs (see Chapter 10).

Wild-type

Animal or allele that functions normally and represents a common type found in natural populations at a frequency of at least one percent.
See Wild Type in the MGI Glossary.

YAC

Yeast Artificial Chromosome. A vector for cloning very large genomic inserts of 300 kb to one megabase in length (see Chapter 10).
See YAC in the MGI Glossary.