Glossary Adenine A base pair or nucleotide of DNA and RNA.

Pairs with thymine in DNA, and pairs with uracil in RNA.

Allele The various sequences of DNA nucleotides for a locus or gene. E.g., the ABO blood system locus has the A, B, and O alleles and the Rhesus (Rh) blood group locus has positive (+) and negative (-) alleles. A gene or locus that has more than one common alelle is called a polymorphism.

Alternative (RNA) Splicing The phenomenon in which the transcribed RNA from different exons of the same gene are differentially spliced together to give different mRNA and hence different polypeptide chains. For example, one splice might contain exons 1, 2, 3, and 4 of a gene, whereas a different splice may have only exons 1 and 3 of the same gene. The APP gene (amyloid precursor protein) undergoes alternative splicing and the differential splices may influence the development of Alzheimer's disease.

Amino Acid(s) The basic building block of proteins and enzymes. There are twenty amino acids, each of which is coded for by a codon (three adjacent nucleotides). Amino acids are usually abbreviated by three letters--e.g., PHE=phenylalanine, GLN=glutamine, TYR=tyrosine.

Amniocentesis Prenatal diagnostic technique in which a needle is inserted into the abdomen of a pregnant woman (usually in the 16th week of pregnancy) and a small amount of amniotic fluid is extracted. Fetal cells in the amniotic fluid are then analyzed for genetic abnormalities.

Anticipation (Sherman's Paradox) Term used to denote a disorder that has an earlier age of onset and greater severity in more recent generations of a pedigree. Examples are Fragile X Syndrome and Huntington's Disease.

Anticodon Series of three adjacent nucleotides on a molecule of transfer RNA (tRNA). The anticodon acts as a "bar code" to denote the specific amino acid carried by the TRNA molecule. In translation, the anticodon pairs with its appropriate codon of messenger RNA (mRNA) and the amino acid carried by the tRNA is added to the growing polypeptide chain. Autosome A pair of chromosomes that are alike in males and females; any chromosome other than the X and Y sex chromosomes.

Base pairs (bp) Also called nucleotides, base pairs comprise the information of DNA and RNA. They are linearly arranged with each nucleotide pairing with a complementary nucleotide. There are four base pairs for DNA. Adenine (A) pairs with thymine (T) and cytosine (C) pairs with guanine (G). For RNA, uracil (U) takes the place of thymine.

Binding Site

Specific area of a molecule (usually a protein, an enzyme or a protein-based complex like a receptor) that another molecule "recognizes" and binds to. Mutations that alter the animo acid sequence in a binding site often render the molecule ineffective.

bp Abbreviation for base pair.

cDNA Abbreviation for complementary DNA.

centiMorgan (cM) Named after Thomas Hunt Morgan who discovered linkage and recombination. A unit used to measure the statistical distance between two loci. One cM is roughly equal to 1,000,000 base pairs. At very short distances, one cM is equivalent to a recombination frequency of 1%.

Chromosome A structure comprised of DNA "packaged" around histone proteins and protein scaffolds. The chromosome is the physical unit of inheritance. Each human chromosome contains hundreds to thousands of genes. Humans have 23 pairs of chromosomes, one of each pair being contributed by the mother and the other by the father. Genes are linearly arranged on the chromosome.

Cloning Cloning has two different meanings. (1) Two or more organisms with identical genotypes, usually with the implication that one organism has been derived from the genetic material of another organism. (2) Gene cloning refers to the isolation (and often sequencing of that gene) and the subsequent production of many copies of the gene to study it.

CNV See copy number variants.

cM Abbreviation for centiMorgan.

Codon A sequence of three nucleotides that code for an amino acid. E.g., in DNA, the sequence adenine-adenine-adenine (AAA) codes for the amino acid phenylalanine, and in mRNA, the complementary sequence uracil-uracil-uracil (UUU) will also code for phenylalanine. Some codons also work as punctuation marks denoting the start and stop of a peptide chain.

Complementary DNA (cDNA) A single strand of DNA that is synthesized in the laboratory to have a complementary sequence to a particular messenger RNA. Mostly used to make probes (qv) for mRNA in some types of arrays (gene "chips:).

Congenital adrenal hyperplasia (CAH)

Sometimes referred to as adrenogenital syndrome, CAH is a genetically heterogeneous collection of Mendelian recessive disorders where androgenizing substance build up in a developing fetus and masculinize the organism. The degree of masculinization is usually incomplete and dependent upon the actual Mendelian disorder. Individuals who are chromosomally XX are given gender corrective surgery, hormone replacement therapy, and then are raised as girls.

Conserved DNA sequences Sequences of DNA that have changed very little over evolution. They are believed to code for proteins, enzymes, or regulatory regions that are especially important for life. A classic example of conserved sequences are Hox genes (qv) which regulate the axis of embryonic development.

Copy Number Variants (CNV) Long sequences of DNA with structural polymorphisms (insertions, deletions, translocations, duplications, inversions). The minimum length for a CNV is usually taken as 1000 base pairs or 1 kilobase. Some CNVs can be several millions of base pairs.

Crossing over (recombination) The pairing up of homologous chromosomes and the exchange of genetic material. As a result of recombination, a mixture of a parental chromosome and a maternal chromosome is transmitted to the next generation.

Cystic fibrosis A recessive genetic disorder that involves an accumulation of fluid in the lungs,pancreas, and other organs creating difficulty in breathing and providing a ripe medium for infections. The most common Mendelian disorder among individuals of European ancestry.

Cytosine A base pair or nucleotide of DNA and RNA. Pairs with guanine.

DNA (deoxyribonucleic acid) The molecule that contains the genetic code for all earthly life forms except for a few types of virus. The molecule resembles a spiral staircase. The sides of the staircase are composed of sugars and phosphates and the rungs consist of a pair of nucleotides (or base pairs). The particular ordering of the nucleotides is responsible for the genetic instructions behind growth and development and behind the regulations of many physiological functions.

DNA fingerprint A series of DNA polymorphisms types in a single individual and usually encountered in forensic applications and paternity testing.

DNA probe A single-stranded DNA sequence labeled with special chemicals. The sequence of nucleotides for the probe is engineered to complement another single-stranded DNA or RNA (the target sequence). The probe binds with the target and then techniques are used to "light up" the special chemical to see exactly where the target is located.

Dominance

The fact that phenotype for a heterozygote is the same as the phenotype for one of the homozygotes. One of Mendel's original laws which he though applied to all hereditary traits but now know to apply to only some.

Editing The process during which the introns in transcription RNA are cut out and the exons are spliced together to form messenger RNA.

Embryonic stem cells Genetically undifferentiated embryonic cells. Embryonic stem cell taken from a mouse, rat, or other organism engineered by homologous recombination to produce transgenic organisms.

Endoplasmic reticulum A network-like structure scattered throughout the cell. Ribosomes, the locations for protein manufacture, are densely located on the endoplasmic reticulum.

Enzyme A type of protein responsible for a chemical reaction in the body. A substrate binds to the enzyme, the enzyme performs the reaction, and the substrate is converted into a product. Enzymes typically end in the suffix "ase" with the body of the term denoting the effect. E.g., polymerase results in a polymer chain being created (as in splicing two sections of DNA together). EST See Expressed sequence tag.

Exon A nucleotide sequence within a gene that contains part of the blueprint for a polypeptide chain. Often, the exons within a gene are interspersed with noncoding regions (or introns). After transcription of the DNA into RNA, the introns are spliced out and the exons are joined together to form messenger RNA. Exons are also called "coding regions."

Expressed sequence tag (EST) A short part of a complementary DNA (cDNA) sequence derived from a mRNA molecule.

FISH See Fluorescent In Situ Hybridization.

Fluorescent In Situ Hybridization (FISH) A cytogenetic technique that allows fluorescently tagged probes to bind with the DNA of chromosomes. Usually used to detect microdeletions (q.v.).

Fragile sites A particular section of a chromosome where, under the microscope, the chromosome appears to break apart (or nearly break apart) when the chromosomes are chemically treated in an appropriate way. There are several fragile

sites throughout the genome, the most widely reported of which is the site on the X chromosome responsible for Fragile X syndrome.

Fragile X syndrome An X-linked disorder due to an unstable trinucleotide repeat (CGG), fragile X is characterized by mental retardation, attention and conduct problems, abnormally long face with large ears, and macroorchidism (in postpubertal males). Normal individuals have between 6 and 50 CGG repeats while fragile X individuals have between 230 and 1000 repeats. The most common Mendelian disorder associated with mental retardation, fragile X has a prevalence of 1/1250 (males) and 1/2500 (females).

Gamete A cell containing half of the genetic information that is used for reproduction; a sperm or egg cell.

Gene A sequence of DNA packaged in a chromosome that contains the information to make a polypeptide chain or an RNA molecule. In human genetics, the term may also be used to refer to a contiguous section of DNA with a known location on a chromosome even if the section does not code for a polypeptide chain (seemarker gene).

Gene targeting Creating mutations in a single gene that is then implanted into an embryo for the purpose of creating transgenic animals. See also homologous recombination, embryonic stem cells, and knockout mice.

Genetic heterogeneity The same disorder (or trait) can be due to different loci. E.g., albinism, congenital adrenal hyperplasia (CAH).

Genome The total genetic information for an individual organism or for a species. The human genome consists of about 3 billion nucleotides.

Genome-wide association study (GWA, GWAS) A combination of population association and linkage strategies that scans a very large number of polymorphisms scattered throughout the genomes of individuals to detect areas associated with a phenotype.

Genomic Imprinting (parental imprinting or imprinting) A recently discovered phenomenon in which an allele may be differentially expressed in the phenotype depending on whether it was inherited from the father or the mother. Chromosomal microdeletions and genomic imprinting are responsible for the inheritance of Prader-Willi versus Angelman syndrome.

Genotype Two meanings: (1) The two alleles that a person has at a locus--e.g., the AO genotype at the ABO locus; and (2) a genetic predisposition--e.g., the genotype for schizophrenia.

Germ cell

A cell that gives rise to a sperm or egg cell; sometimes used to refer to the sperm or egg itself.

Golgi apparatus (Golgi body, Golgi complex) An organelle within the cytoplasm of the cell that processes proteins and lipids (fats). A main fuction of the Golgi complex is to act as a "post office" by tagging molecules so that they are sent to the correct place in the cell.

Guanine A base pair or nucleotide of DNA and RNA. Pairs with cytosine.

GWA, GWAS See genome-wide association study.

Haplotype (haploid genotype) A "genotype" consisting of the alleles for two or more linked loci on the SAME chromosome; the alleles on a chromosome. For example, the haplotype Ab/aBdenotes that a person has alleles A and b on one chromosome and alleles a and B on the other chromosome.

HapMap (Haplotype Mapping) Project A collaborative project to detect and map common haplotypesin order to increase the efficieny of linkage and association studies.

Heritability Proportion of observed individual differences in a trait attributable (or predicted by) genetic individual differences. Or, the proportion of phenotypic variance predicted by genotypic variance. Broad sense heritability includes all types of gene action in the genetic variance. Narrow sense heritability includes only the additive effects of genes in the genetic variance.

Heterozygote An organism or genotype that has two different alleles at a locus. E.g., for the ABO blood system, genotypes AB, AO, and BO are heterozygotes.

Homologous recombination A laboratory technique in which a section of DNA on a chromosome is replaced by another similar sequence. The purpose is usually to "knockout" the gene to determine what happens when the gene is disrupted.

Homozygote An organism or genotype that has two copies of the same alleles at a locus. E.g., for the ABO blood system, genotypes AA, BB, and OO are homozygotes.

Huntington's Disease (HD) A presenile dementia caused by an autosomal dominant gene located on the short arm of chromosome 4. The problem with the HD gene is a unstable trinucleotide repeat. The disorder involves gradual loss of motor coordination and dementia (a progressive and irreversible loss of cognitive functioning).

Hybridization Molecular genetic technique for binding a single-stranded DNA or RNA sequence with its complementary nucleotide sequence.

Imprinting See genomic imprinting.

Independent Assortment One of Mendels original laws stating that the hereditary factor for one trait (e.g., pea shape--round vs. wrinkled) is independent of the hereditary factor for another trait (e.g., pea color--yellow vs. green).

Interference RNA (RNAi) A short sequence of RNA that binds with messenger RNA (qv) and either prevents translation or marks the mRNA for degradation. A post-transcriptional control mechanism. Biotech firms are rushing to exploit RNAi in the hopes of blocking the translation of mRNA from genes causing disease.

Intron A section of DNA within a gene that does not code for a polypeptide chain. When a gene is transcribed into RNA the transcript RNA contains both the introns and the sections that contain the code for the peptide (exons). Introns are cut out and exons are spliced together to form messenger RNA.

Karyotype Pictures of stained chromosomes ordered by size.

kb Abbreviation for kilobase.

Kilobase (kb) A contiguous sequence of 1,000 base pairs or nucleotides

Knockout mice Mice genetically engineered by homologous recombination so that a particular gene does not function and hence is "knocked out." Has nothing to do with Mike Tyson.

Locus Usually, another name for a gene; a continuous section of DNA on a chromosome.

Lyonization (Lyon hypothesis, X chromosome inactivation) The inactivation of one of the X chromosomes in the somatic cells of a female. Hence, females are genetic mosaics with respect to their X chromosomes. Named after its discoverer, Mary Lyons.

Lysosome Organelle in the cytoplasm that contains digestive enzymes used to degrade old organelles, virus, and bacteria.

Major gene (major locus) A gene that is part of a polygenic or oligogenic system but has a large influence on the phenotype.

Marker gene (marker locus or markers) A continuous sequence of DNA with a known chromosomal location. Markers are used in linkage analysis to find a gene for a trait or disease.

Meiosis Process of cell division during which a germ cell containing the full chromosome complement of an organism produces the sperm or egg cells with one-half of the chromosome complement of the organism.

Mendelian disorder or trait (monogenic disorder or trait) A disorder or trait due to a single gene.

Messenger RNA (mRNA) RNA that has been transcribed from DNA and then edited to contain the information for making a polypeptide chain.

Microdeletion A delection of a DNA strand that oftens spans several genes but it too small to detect using conventional karyotyping. Currently, FISH (q.v.) is used to detect microdeletions.

Microsattelite See Tendem Repeat Polymorphism. A tandem repeat polymorphism in which the repeated nucleotide sequence consists of a small number of repeated base pairs--e.g., 2, 3, or 4 repeated nucleotides. For example: CGCGCGCG, CAGCAGCAGCAGCAGCAG, CAGTCAGTCAGTCAGT.

Methylation In genetics, the attachment of methyl groups to nucleotides, especially cytosine, resulting in a reduced transcription of genes.

Mitochondria Organelles scattered through the cell that are responsible for oxidative metabolism. Mitochondria contain mitochondrial DNA (mtDNA) that is inherited through only the mother.

Mitosis Process of cell division that ends in two identical cells.

Monogenic disorder or trait (Mendelian disorder or trait) A disorder or trait due to a single gene.

Mosaic The existence of two genetically different cell lines in the same individual.

Multiplex pedigree A pedigree with more than one affected individual. Multiplex pedigrees jave been very useful in detecting single-gene forms of disorders with complex gen etics. See simplex pedigree.

Mutagen An energy source or chemical that can cause a mutation (e.g., UV radiation, X-rays, dioxin).

Mutation A irregular change in the DNA or a "spelling error" in the nucleotide sequence during cell division. Germinal mutations occur in the production of sperm or egg and are transmitted to the next generation. Somatic mutation, far more common than germinal mutations, influence all other cells of the organism. Mutations may affect only a single nucleotide (point mutation) or large sections of DNA up to a whole chromosome (e.g., trisomy 21 that causes Down's syndrome).

Nucleotide see base pair.

Neutral gene (or neutral locus) A section of DNA that does not contribute to reproductive fitness.

Nucleus The part of a cell that containing the chromosomes. With few exceptions (e.g., red blood cells), all cells have a nucleus.

Oligogenic disorder or trait Polygenic transmission but the number of genes influencing the disorder or trait is small.

Oligonucleotide A short nucleotide sequence of single-stranded DNA usually used as a probe to find a matching sequence of DNA or RNA.

Oncogene A gene that can transform cells into cancer cells.

Parental imprinting See genomic imprinting.

Penetrance The probability that an organism will exhibit a disorder (or trait) in the phenotype given that the organism has a genotype that allows the disorder (or trait) to be exhibited. If the probability is 1.0, the locus is termed fully penetrant. If the probability is less than 1.0, the locus is described as having incomplete or partial penetrance. Retinoblastoma, a dominant disorder leading to cancer of retinal tissue, is 90% penetrant; hence, 90% of those who carry the gene will exhibit the trait. Modern methods of genotyping have demonstrated that many Mendelian disorders previously thought to be fully penetrant actually have very high penetrance but are not completely penetrant (e.g., cystic fibrosis).

Peptide chain (polypeptide chain) A sequence of two or more amino acids linked together. A gene contains the code for the sequence of amino acids in the polypeptide chain.

Phenocopy An environmental insult that can produce a phenotype (usually a disorder) in anyone regardless of their genetic predisposition.

Phenotype A observable or potentially observable trait.

Pleiotropy The fact that a single gene influences more than a single phenotype. For example, the gene responsible for Huntington's Disease impacts on motoric functioning and cognition.

Polygenic More than a single locus influences the phenotype. Sometimes used to denote the possibility that a large number of loci influence the phenotype.

Polymerase chain reaction (PCR) A technique for making many copies of a DNA sequence from only a small amount of DNA.

Polymorphism A gene that has more than one common allele.

Positional cloning Locating the precise position of a gene for a trait by comparing the DNA of individuals who have the trait with the DNA sequence of their family members who do not have the trait.

Probe A single stranded section of DNA (or RNA) that is labelled (radioactively or fluorescently). The probe will bind to its complementary DNA (or RNA) sequence and the label "lights it up."

Promoter region (promotor gene) A section of DNA usually upstream from a structural gene (i.e., one that codes for a polypeptide chain). The promoter region (gene) is where transcription enzymes and proteins bind and initiate transcription of the structural gene.

Protein One or more polypeptide chains taking on a three dimensional configuration. Proteins serve as structural components of a cell (structural proteins), assist in chemical reactions (enzymes), and serve as signaling molecules.

Pseudogene A gene with a nucleotide sequence very similar to a structural gene, but because of mutations can no longer be transcribed or translated.

Recombination A fancy term for crossing over.

Restriction enzyme (technically, restriction endonuclease) An enzyme that recognizes a certain section of DNA and cuts the DNA at that spot.

Restriction fragment length polymorphism (RFLP) Different alleles for a locus are determined by cutting the DNA with a restriction enzyme and analyzing the lengths of the resulting sections. A RFLP is usually used as a genetic marker.

Ribonucleic acid (RNA) A single-stranded sequence of nucleotides comprised of adenine, uracil, cytosine, and guanine. There are several species of RNA, the most important of which for protein synthesis are messenger RNA (mRNA), ribosomal RNA (rRNA), and transfer RNA (tRNA).

Ribosome A protein-RNA complex that is the site of translation. Messenger RNA (mRNA) attached to the ribosome, a codon enters a "reading frame" and the appropriate transfer RNA (tRNA) binds to the codon. The amino acid carried by the tRNA is added to the growing polypeptide chain.

RNAi Abbreviation for RNA interference. A complex of proteins that includes a short strand of RNA unique to a gene binds to the mRNA for that gene and cleaves the mRNA. This prevents translation and hence down regulates the gene (i.e., reduces gene expression).

Segmental Duplication Sections of DNA with strong homology (hiughkly similar sequence of nucleotides).

Segregation

One of Mendel's original laws stating that of the two parental alleles at a gene, only one taken at random is transmitted to an offspring.

Sequence Tagged Site (STS) A short (100 to 500 base pair) sequence of DNA that is unique within the human gemone (i.e., there is only one copy of this sequence in the genome). Sequence tagged sites are used in mapping and sequencing a genome.

Sequencing Determining the order and positioning of the 4 nucleotides (A, T, C, and G) in a section of DNA. "Sequencing the genome" of an organism (or species) refers to sequencing all the DNA of tht organism.

Sickle cell anemia A recessive disorder due to a point mutation (the change of a single nucleotide) in the locus coding for the b polypeptide chain of the hemoglobin molecule. Under certain conditions, particularly oxygen deprivation, the abnormal hemoglobin molecule will change the shape of a red blood platelet into something resembling a crescent moon or sickle. These sickled cells clog up the fine capillaries, depriving the target organs of oxygen. The sickle cell allele is found in high frequency in malarial regions in Africa, the eastern Mediterranean, some Arab countries, and the Indian subcontinent. The reason for its high frequency is that heterozygotes are more resistant to malaria than normal homozygotes.

Single Nucleotide Polymorphism (SNP) A sequence of DNA that differs among organisms in one and only one nucleotide.

Somatic cell Any cell of the organism that is not a gamete (germ cell).

Structural gene A gene containing the code for making a polypeptide chain, a protein, or an enzyme.

Tandem repeat polymorphisms A sequence of DNA that is repeated, one repeat after the other (i.e., in tandem), in a specific place in the genome. The polymorphism consists of the number of times in which the sequence is repeated. For example, the nucleotide sequence CGG may be repeated over and over at a particular place on a chromosome. Some alleles may have 4 repeats (CGGCGGCGGCGG) while other alleles may have 6 repeats (CGGCGGCGGCGGCGGCGG) at that section of the chromosome. When the nucleotide sequence is short (2 to 5 nucleotides), the polymorphism is referred to as a microsattelite or a STR (short tandem repeat) (qv). When the sequence is long, the polymorphism is termed a VNTR (qv).

Tay Sachs Disease A disorder of lipid (fat) storage caused by an autosomal recessive allele. Infants with Tay Sachs fail to develop normally and usually die within a few months or years after birth. The Tay Sachs allele is found with high frequency among Askenazie Jews (Jews of eastern European ancestry) and Arcadians (Louisiana residents of French Canadian ancestry). Among Askenazie, a concerted effort to identify heterozygotes (carriers) and, if necessary, subject pregnancies to prenatal testing has dramatically reduced the frequency of the disorder.

Thymine A nucleotide of DNA only. Pairs with adenine. In RNA, thymine is replaced by uracil.

Transcription The process whereby a strand of RNA is synthesized from the DNA resulting in a "mirror image" of the DNA in the RNA.

Transfer RNA (tRNA) A molecule of that contains, among other things, a recognition site of 3 nucleotides (called an anticodon) and an amino acid. In protein synthesis, the anticodon pairs with the codon from messenger RNA and the amino acid is transferred into the growing polypeptide chain.

Transgenic organism An organism with a gene from another species placed into its genome. Genes for many human diseases have been placed into mice, rats, or other mammals to create an animal model to study the gene.

Translation The process in which the sequence of information on the messenger RNA is read and a chain of amino acids is synthesized from that information.

Trisomy Having three chromosomes instead of two homologous chromosomes. Trisomy 21 is the most frequent cause of Down's Syndrome.

Tumor-suppression gene A gene whose normal function is to prevent the transformation of a cell into a cancer cell. If a tumor-suppression gene mutates, cancer may result.

Uracil A nucleotide of RNA only. In DNA, thymine takes the place of uracil. Pairs with adenine.

Variable expressivity (variable expression) A single locus can result is a different degrees of expression of a phenotypic trait. E.g., untreated phenylketonuria results in intelligence starting from severe mental retardation but going into the normal range.

Variable number of tandem repeats (VNTR) A polymorphic section of DNA where the polymorphism consists of the number of times that a nucleotide sequence is repeated. E.g., one allele may have the sequence CAGATGTCAT repeated 6 times while another allele may have the same sequence repeated 10 times. When the number of nucleotides is small (2 to 5 nucleotides), the polymorphism is often called a "microsattelite" or "short tandem repeat" (qv). A VNTR is usually defined as a tanden repeat of more than 5 nucleotides.

William's Syndrome Characterized by developmental delays, mild ot moderate mental retardation, and attention problems. Williams cases are overly sociable, enjoy talking, and overly trusting of strangers. Caused by a microdeletion in 7q11.23.

X Chromosone Inactivation See Lyonization.

X-linked A gene located on the X chromosome.

Zygote A fertilized egg.