Genetics Northern California


Clinical Heterogeneity

The production of clinically different phenotypes from mutations in the same gene.

Constant SpringHemoglobin variant that are phenotypically similar too alpha thal trait. Point mutation causes decrease in the amount of alpha chains produced.
De novo mutationA genetic mutation occurring for the first time; not found in a previous generation.
Frameshift mutation

A change in DNA in which a duplication or deletion occurs that is not a multiple of three base pairs.


A chromosomal mutation involving the removal of a chromosome segment, its rotation through l80 degrees, and its reinsertion in the same location. The replacement of a section of a chromosome in the reverse orientation.

Missense mutation

A type of mutation that results in a single amino acid change in the translated gene product.


A deleterious change in the sequence of the DNA molecule in the cell of an organism.

New mutation

Mutation that occurs for the first time in that person and is not seen in any other related family members. Also called "de novo".

Null mutation

A mutation that makes no gene product at all which in turn can cause a disease state.


A gene that normally regulates the cell cycle and protects cells from damage to its genome. If a mutation occurs in this gene, cells can develop cancer. Individuals with Li-Fraumeni cancer syndrome have a defect in their p53 gene.

PremutationsThe first mutation in a multi-step process leading to disease. (e.g. In Fragile X syndrome, individuals with 55-200 CGG repeats in the FMR1 gene are considered to be premutation carriers (normal is <30). They are not affected by the disease, but in passing on that gene to their offspring, the premutation may expand to a full mutation, leading to disease.)

An inactive gene within a gene family derived by mutation of an ancestral active gene.

Southern blot

A technique for transferring DNA segments from an agarose gel to filter paper and which is then probed with radioactivity to see if a particular change or mutation is present in an individual.

Sporadic mutationThe first mutation or occurrence of disease in a family with no apparent genetic transmission pattern.
Tumor suppressor geneGenes that normally restrain cell growth but, when missing or inactivated by mutation allow the cell to grow uncontrolled.
Two hit hypothesis (Knudson's model)

Hypothesis that malignant transformation of cells occurs after at least two cellular mutation events or the "two hit theory".

X-linkedDiseases occurring due to a mutation or defect on the X chromosome.