Allele.
An alternate form of a gene at the chromosomal locus on corresponding homologous chromosomes.

Allelic heterogeneity.
The concept that mutations in one gene locus are associated with different clinical presentations of a disease.

Apoptosis.
Programmed cell death, a process by which damaged cells are removed in a predetermined manner.

Autosomal dominant.
An inheritance pattern in which the disease locus is located on an autosomal chromosome and is dominantly expressed.

Autosomal recessive.
An inheritance pattern in which the disease locus is located on an autosomal chromosome and is recessively expressed.

Candidate gene approach.
A strategy of gene cloning in which the biochemical defect associated with a clinical disease is assumed to be present in a candidate gene in the chromosomal region of interest, and mutations are searched in the gene to confirm the assumption.

Chromosome walking.
A strategy of molecular cloning in which a sequential collection of clones carrying overlapping sequences of DNA are isolated. In each step, clones that are located closer to a disease gene are chosen, and these steps are repeated until ultimately the disease gene is identified.

Chromosome jumping.
A method of gene cloning in which larger segments of DNA sequences are cloned. These clones are then “walked” in a manner similar to that used in chromosome walking to eventually identify the disease gene locus.

Consanguinity.
Relationship among persons descended from a common ancestor.

Cosegregation.
Parallel behavior of DNA markers due to their close proximity on a chromosome.

Cytoplasmic inheritance.
An inheritance pattern involving genes located outside the nucleus (e.g., mitochondrial genes).

Deletion.
The loss of a DNA segment.

Denaturing gradient gel electrophoresis.
A method of electrophoresis in which DNA fragments are electrophoretically separated based on their sequences and conformations in a denaturing chemical environment.

Deuteranopic dichromat.
A person whose green cone pigment is absent.

Epigenetic.
A term that refers to factors affecting the phenotype of a disease without changing the genotype.

Exon.
A transcribed region of DNA that is present in messenger RNA.

Expressivity.
The extent to which a genetic disease is expressed.

Familial disease.
A trait which appears more frequently in relatives of a proband than in the general population.

Forward genetics.
The general strategy of genetic analysis in which the biochemical nature of the gene product is known, which prompts the search for the chromosomal location of the gene.

Functional cloning.
A strategy of gene cloning based on the relationship between the pathophysiology of a disease and the biochemical properties of genes examined.

Genetic marker.
A genetic locus with alternative alleles that can be used in a genetic analysis.

Genome.
The complete nuclear DNA sequence of an organism.

Genotype.
Genetic composition of an individual.

Germline mutation.
Mutation that occurs in reproductive cells and can be inherited.

Hereditary trait.
An inheritable genetic trait.

Heterozygote.
A person with two different alleles in a given gene locus.

Homozygote.
A person with two identical alleles in a given gene locus.

Human Genome Project.
A federally funded project to map and sequence the genomes of humans and other organisms.

Hybridization.
A molecular biologic technique in which a DNA probe with a specific sequence of interest is bound to a target DNA (or RNA) fragment immobilized on a solid support.

Insertion.
A chromosomal or DNA abnormality in which an extra piece of chromosome or a DNA fragment is inserted.

Intragenic DNA marker.
A DNA marker located within a given gene.

Intron.
DNA sequences located between exons. Introns are initially transcribed to form a primary RNA transcript and are subsequently removed by splicing.

Kilobase.
One thousand bases of DNA (or RNA).

Kindred.
An extended family.

Linkage analysis.
A method of genetic analysis based on the proximity of location of genes in a chromosome. Genes that are situated close to each other tend to transmit together through meiosis.

Locus.
The chromosomal position of a gene.

Locus heterogeneity.
Same as nonallelic heterogeneity.

LOD score.
The LOD score (LOD defined as “logarithm of the odds favoring linkage”) is used to quantify the distance between the marker and the disease gene. As LOD is calculated as the logarithm to base 10 of the odds in favor of linkage, an LOD score of 3 represents a probability of 1000:1 that the observation of linkage did not occur by chance and is often taken as the minimal LOD value for presumptive evidence of linkage.

Messenger RNA (mRNA).
An RNA molecule transcribed from DNA. mRNA directs ribosomal protein synthesis.

Microsatellite repeat marker.
A type of DNA marker used in gene mapping that consists of a repeat of short DNA sequences.

Missense mutation.
A type of DNA mutation that alters an amino acid.

Mitochondrial inheritance.
An inheritance of a disease caused by genes encoded by the mitochondrial genome.

Multifactorial inheritance.
Inheritance patterns involving multiple genetic and environmental factors.

Mutant.
Either a gene mutation or an organism with a gene mutation.

Nonallelic heterogeneity (locus heterogeneity).
Mutations in several different genes that are associated with various clinical phenotypes of a disease.

Nonsense mutation.
A type of DNA mutation that results in the creation of a premature termination codon.

Northern blot.
A technique of RNA analysis in which RNA fragments are separated with gel electrophoresis, transferred to a solid support, and hybridized with a DNA probe with a specific sequence.

Nucleotide.
A molecule consisting of a nitrogenous base, a pentose, and a phosphate group. It is the building block for DNA.

Oncogene.
A group of genes that, when active, are involved in disregulated cellular proliferation.

Pedigree.
A diagram indicating family relationship and the status of a disease with respect to each family member.

Penetrance.
The percentage of persons carrying a particular mutant allele who are affected.

Phenotype.
The clinical expression of a genotype.

Polygenic.
Term for diseases that are caused by multiple genes.

Polymerase chain reaction.
A method of DNA amplification in which a target DNA is amplified using DNA polymerase and programmed thermal cycles.

Positional cloning.
The main strategy of gene cloning in reverse genetics. Genes are cloned based on linkage analysis and examination of overlapping DNA clones. No prior knowledge of the gene defect or its chromosomal location is needed.

Proband (propositus).
Also termed index case. A family member who comes to medical attention first in a pedigree.

Promoter.
A DNA sequence upstream from the encoding region of a gene. A promoter sequence is involved in the regulation of expression of the corresponding downstream gene.

Probe.
A DNA molecule with a specific sequence used to hybridize and recognize DNA or RNA fragments separated by electrophoresis.

Protanopic dichromat.
A person whose red cone pigment is missing.

Recombinant clone.
A hybrid DNA molecule consisting of a vector and gene insert to be amplified.

Restriction endonuclease.
A type of bacterial enzyme that recognizes and digests DNA fragments with specific sequences.

Restriction fragment length polymorphism.
A type of DNA polymorphism that can be recognized by restriction endonucleases.

Reverse genetics.
The general gene-cloning strategy in which chromosomal locations of genes are sought without knowledge of the biochemical nature of the gene product.

RNA splicing mutation.
DNA mutations occurring near the RNA splice junction sequence.

Single-strand conformational polymorphism.
A method of analysis for detecting the presence of DNA mutations which takes advantage of the fact that a mutant DNA fragment has an altered gel electrophoretic mobility.

Splicing.
The process of removing introns in the primary transcript of a gene.

Somatic mutation.
A type of DNA mutation that occurs in somatic (nongermline) cells and therefore is not inheritable.

Southern blot.
A method of DNA analysis in which DNA fragments are electrophoretically separated, transferred to a solid support such as nitrocellulose, hybridized with a radioactive DNA probe of specific sequence, and finally analyzed using autoradiography.

Transcription.
The process of creating an RNA from a DNA template. It is the first step in gene expression.

Transgenic mice.
A laboratory mouse created with a specific genotype, such as a mutant cancercausing gene.

Transition mutation.
A mutation consisting of a substitution of one purine for another purine molecule (e.g., A for G, or vice versa).

Translation.
The process of making a protein molecule based on an mRNA sequence. Translation occurs on ribosomes in cytoplasm.

Transversion.
A mutation in which a purine is replaced by a pyrimidine, or vice versa (e.g., A replaced by C, or vice versa).

Trichromat.
A person with normal color vision.

Tritanope.
A person whose blue cone pigment is absent.

Tumor-suppressor gene.
A type of gene (e.g., the retinoblastoma gene) that regulates cellular growth and division. Its failure to function results in tumorigenesis.

Variable number of tandem repeats.
A type of DNA marker consisting of a variable number of repeats of short stretches of DNA sequences.

Vector.
A large, circular DNA molecule in which a gene to be amplified can be incorporated to create a recombinant DNA molecule. This recombinant molecule can then be transformed into host cells (e.g., bacteria) and replicated along with the host.

Western blot.
A blotting technique used to analyze protein. The technique is similar to the Southern blot. Protein extracts are separated electrophoretically, transferred to a solid support, and detected with specific antibodies.

Wild type.
A term referring to a normal genotype.

X-linked disease.
A disease with genes located on the X chromosome. A majority of X-linked diseases are X-linked recessive.

Yeast artificial chromosome.
Genetically engineered yeast chromosome used to clone large DNA segments.