Modern developmental biology relies heavily on genetics and so it is essential that we understand some fundamentals. Hopefully everyone has had the prerequisite course in genetics and so this should serve as a brief refresher.

Genes & Development

DNA (gene) -> RNA -> Proteins:
  1. enzymes (biosynthesis and metabolism)
  2. structural proteins (cytoskeleton, ECM)
  3. regulatory proteins (transcription factors, signaling components)
A cell’s properties are the sum of the proteins, an organism is the sum of it’s cells, and development involves defining and changing cell properties.
Therefore genes are important for development and one of the major goals in developmental biology is to identify and understand the functions of genes that regulate development.
One of the most powerful techniques to identify important genes is via mutations that disrupt interesting developmental processes.

Genes & Mutations

Genes identified by classic genetic means are named after their mutant phenotype. Because of this, gene names often sound opposite their function. For example, wild type flies have red eyes. A loss-of-function mutation was identified that causes white eyes. Thus the gene was named white. The white gene is required for flies to have red eyes. Likewise, white mRNA and protein are required red eyes. white mutants make no white mRNA or protein. Only wild type flies with red eyes express normal white gene products. Confusing, isn't it?

We can use mutations, not only to identify interesting genes, but also to tell us the function of those genes. By analyzing the phenotypic defects in mutant individuals, we can deduce the gene's function. However, mutations come in several flavors and how we interpret a gene's function depends on the nature of the mutation. The two major classes of mutations are loss-of-function and gain-of-function.

Loss-of-function:
These are the most common. As the name implies, the RNA or protein product of a gene is missing, non-functional or reduced in abundance or functionality. These are typically recessive mutations because a wild type copy of the gene can usually cover for the non-functional one.

Gain-of-function:
These mutations usually dominant. They can result from overexpression of a gene, or ectopic expression (expression in the wrong place). Another type of gain-of-function mutation is the dominant negative; the product of the mutant gene can compete or inhibit the function of a wild-type product. You can imagine things like mutant subunits of multimeric proteins resulting in a defective complex even though it also contained wild type subunits.

A classic illustration involves mutations in the Antennapedia (Antp) gene of Drosophila. The gene was identified by (and named for) the mutant phenotype of forming legs on the head in place of antennae. Is this gene required for antenna formation? No. It turns out that this is a dominant, gain-of-function mutation which causes ectopic expression of the Antp gene in the head. Normally it is most highly expressed in the second thoracic segment, where legs form, and not expressed in the head at all. Recessive loss-of-function alleles of Antp give the opposite phenotype, antennae form in place of legs on the second thoracic segment. Two possible interpretations of Antp function that are consistent with both the gain- and loss-of-function phenotypes are that it represses antennae, thereby allowing legs to form, OR that it promotes legs and in the absence of this promoting activity, appendages revert to a default state of antennae.
 

Working list of Genetic Definitions

gene—the DNA that codes for a protein or RNA product and all it’s cis-regulatory   region
alleles—variants a gene containing nucleotide sequence differences
 -often cause functional alterations
locus—position on a chromosome (may be occupied by a gene)

genome—sum total of an organisms’ genetic material

genotype—genetic composition of an individual
 -can be referred to with respect to a single locus (gene) or the entire genome
phenotype—observable characteristics of an organism
 -interaction of genotype and environment
heterozygote—individual containing 2 different alleles of a gene

homozygote—individual containing 2 copies of the same allele

dominant allele—manifests phenotypic effect when in the heterozygous state    (designated with a capitalized symbol)
recessive allele—only manifests phenotypic effect as a homozygote  (designated with lower case symbol)
 -dominance relationships not always hard and fast
   can be allele specific relationships
   depends on level of phenotypic assay
mutation—heritable change in the nucleotide sequence of a gene
 -Must be heritable!!
 -Can be silent.
epigenetic—mitotically or meiotically heritable change in a gene’s expression which does not result from a change in the nucleotide sequence
wildtype—the state that is normal or considered normal
 -can refer to alleles, proteins, phenotype etc.
mutant—containing a mutation or conditioned by a mutation
 -can refer to alleles, proteins, phenotypes
 -opposite of wildtype
mutagenesis—experiment designed to induce new mutations

mutagen—an agent that induces mutations (eg. EMS, UV, X-rays, transposons)

screen—experiment designed to identify individuals with particular phenotypes    from a population