Glossary of Key Terms

Acquired susceptibility mutation--A mutation in a genethat occurs after birth from a carcinogenic insult.

Allele--One of several mutational forms of a specific gene.

Autosomal dominant inheritance--Inheritance of a gene,which is located on a chromosome other than the sex (X or Y) chromosome,and which in single state, may give rise to a phenotype that maybe expressed through two or more generations.

Deletion--Loss or removal of a sequence of DNA with theregions on either side being joined together.

Familial adenomatous polyposis (FAP)--An autosomal dominantlyinherited predisposition to multiple adenomatous polyps of thecolon and a risk for colorectal cancer that approaches 100% byage 60. The germ-line mutation for this disease is the APC gene,which stands for adenomatous polyposis coli. Other cancers, includingpapillary thyroid carcinoma, periampullary carcinoma, gastriccancer (particularly in FAP patients in Japan), small bowel cancer,pancreatic cancer, sarcomas and brain tumors, as well as desmoidtumors (which are not cancers) complicate this disease.

Frameshift--Deletions or insertions that alter the three-base-pairframe in DNA that are translated into protein.

Germ-line carriers--A mutation in a gene present in allcells in the body from birth.

Haplotype--The specific combination of alleles in a definedregion of a chromosome.

Heterozygous--A patient with one or more pairs of dissimilaralleles is said to be heterozygous at that particular gene locuson homologous chromosomes.

Hereditary nonpolyposis colorectal cancer (HNPCC)--Autosomaldominantly inherited disease predisposing to colorectal canceron a site-specific basis (Lynch syndrome I) and in associationwith a variety of extracolonic cancers (carcinoma of the endometrium,ovary, stomach, small bowel, and pancreas, and transitional-cellcarcinoma) of the ureter and renal pelvis (Lynch syndrome II).Genes identified in this syndrome include hMSH2, hMLH1, hPMS1,and hPMS2.

Homozygous--A patient with identical alleles at the samelocus of homologous chromosomes is said to be homozygous.

Incomplete penetrance--Absence of expression of the phenotypein an obligate gene carrier.

Inherited susceptibility mutation--A mutation in a genethat is inherited in Mendelian fashion, and thus present in allcells in the body from birth, which causes susceptibility to agiven disease.

Insertion--The gain or addition of a sequence(s) of DNAnot normally present.

Kindred--Individuals who are related by genetics or marriageto all other members of the particular group ("kindred"is often used interchangeably with "family").

Linkage analysis--Genes are said to be "linked"when they reside close together on the same chromosome. Statisticalanalysis of linkage of two genes is then expressed as a Lod score.

Missense mutation--A change in a DNA-base that resultsin a three-base-pair sequence that codes for a different aminoacid than the original code.

Nonsense mutation--Any change in DNA that results in athree-base-pair sequence that does not code for an amino acid,and thus terminates the protein sequence.

Penetrance--The proportion of individuals with the genotype(such as hMSH2 germ-line carriers of HNPCC) who manifest the phenotype.

Promoter mutation--Any mutation in that part of DNA involvedin binding of RNA polymerase to initiate transcription.

Splice mutation--A mutation resulting from imprecise removalof introns and joining of exons in RNA.

Stop codon--A three-base-pair sequence in DNA that doesnot code for an amino acid, and thus results in termination ofthe protein sequence.

Transcription--Synthesis of RNA on a DNA template.

Variable expressivity--Difference in the phenotype, suchas age of onset or specific type of cancer, in an obligate germ-linecarrier.