Download Additional Glossary and Concepts List for Vertebrate Genetics

Additional Glossary and Concepts List for Vertebrate Genetics Lectures
BAC recombineering
The use of homologous recombination technology in E. coli to introduce targeted mutations (or
reporter genes) into BACs. It permits facile manipulation of BAC DNA.
Blastocyst
Early embryo, consisting of inner mass of cells that will develop into the animal, and an outer
ring of cells that becomes the placenta.
Chimera
An animal bearing cells or tissues derived from transplantation from another animal. Typically
the host animal is genotypically distinct from the donor.
Dosage compensation
The mechanism whereby loci on the shared sex chromosome are expressed at equivalent levels
between the sexes. In mice and humans, for example, dosage compensation ensures that the loci
on the two X chromosomes in females are expressed at a level equivalent to the loci on the single
X chromosome found in the male (see X-inactivation below).
Gene targeting
The manipulation of a locus by homologous recombination. Includes knock-ins and knock-outs
(see below).
Genetics, Forward
An approach that starts with an interesting mutant phenotype and then goes about characterizing
the mutation at the molecular level. In other words, you proceed from phenotype to genotype.
Genetics, Reverse
An approach that starts with an interesting segment of DNA (or protein), and then introduces
targeted mutations in the genome to understand the function of the cloned DNA (or protein). In
other words, you proceed from genotype to phenotype.
Imprinting
An epigenetic modification that renders the parental contribution non-equivalent in the progeny.
Usually this means that at particular loci, either the maternal or the paternal allele (but not both)
will be expressed. Individual loci can be imprinted in particular tissues or they can be imprinted
throughout the body. Most commonly described in plants and mammals.
Knock-in
The introduction of a mutation or reporter or other heterologous DNA sequence into a locus by
homologous recombination.
Knock-out
The generation of a deletion in a locus by homologous recombination. Typically results in a lof
allele. But can also be used to refer to the deletion of an exon that encodes a particular protein
domain, resulting in altered activity of the protein encoded by the remaining exons. Note that
lowering the expression of a locus by shRNA is usually referred to as knock-down and not
knock-out.
Mono-allelic expression (allelic exclusion)
Cellular expression of only one of the two alleles encoded in the genome for the particular gene.
The allele that is expressed can be randomly chosen (eg, olfactory receptor encoding alleles,
antigen receptors on B or T cells) or the expression can depend on the parent-of-origin (see
Imprinting above).
Mosaic
The admixture of cells with distinct genotypes within a tissue(s). Can occur normally (see Xinactivation below) or in disease (eg, cancerous cells often bear numerous somatic mutations that
distinguish them from each other and from neighboring non-cancerous cells).
Mouse strain definitions (Definitions adapted from Lee Silver’s Mouse Genetics.)
Co-isogenic
A strain which differs exactly by one allele at a given locus from the isogenic strain (see below)
from which it was derived; note that the co-isogenic strain may be homozygous or heterozygous
for the allele.
Congenic
A mouse strain that is bred to be “isogenic with an inbred strain except for a selected differential
chromosomal segment.” In practical terms, a mouse strain is considered to be congenic if the
founder mouse bearing a particular allele has been back-crossed to the inbred strain of interest
for !10 generations; in each generation, one selects progeny carrying the allele of interest for
back-crossing to the inbred strain.
Inbred
A mouse strain that is “genetically homogeneous and homozygous at all loci.” A strain is
considered to be inbred after !20 generations of sib-sib matings.
Isogenic
A mouse strain in which all mice have an identical genome (in the case of sex chromosomes:
identical X in all females and males; identical Y in all males). A mouse strain is considered to be
isogenic after !60 generations of sib-sib matings.
Position effect
The control of a phenotype(s) imposed by the specific genomic location of the gene regulating
the phenotype.
Pseudogene
A non-functional genetic locus related to a functional gene (sequence homology) in the same or
other species. The pseudogenized locus may have lost expression due to mutations in the
regulatory regions; often the locus no longer codes for a protein due to mutations in the open
reading frame. Note that in the latter case the pseudogene may be transcribed.
Synteny
Conservation between species of gene order across a stretch of the genome. So if genes A, B, C,
D and the intervening intergenic regions on rat chr 17 are found in the same order on mouse chr
12, then one would refer to these stretches on the chr 17 and 12 as being syntenic between rat
and mouse. Can find such syntenic regions between mouse and human as well. Useful for
finding conserved regulatory elements, finding mapping human disease loci on to model
organisms etc.
Transgene
In vertebrate parlance, this is usually taken to mean a gene that has been introduced into the
genome by random integration (cf. gene targeting). Thus, a transgenic construct, unless stated
otherwise, means a DNA plasmid designed to be introduced into the genome by transgenesis
(pronuclear injection, for example). In my lectures, I will use transgene in this context only.
Confusingly, a transgene can also refer to any heterologous gene that has been introduced into
the genome. In this sense, a reporter gene such as LacZ is a transgene, even if it has been
inserted into a locus by homologous recombination.
X-inactivation
Dosage compensation in most mammals wherein one of the two X chromosomes is randomly
silenced. Since males are XY and females XX, X-inactivation permits equivalent expression of
the loci on the X in the two sexes. The silenced X chromosome is mitotically stably inherited.