BIO 203 Q2

Haploinsufficient

A wild-type allele that is unable to support wild-type function in a heterozygous genotype. Classified as a recessive wild-type allele. 

• Wild type allele is recessive to the mutant allele

• Heterozygote has the mutant phenotype

Haplosufficient

one copy of an allele is sufficient to produce the wild-type phenotype in the heterozygous genotype

• Type of dominant wild-type allele

• Both homozygous dominant and heterozygous can produce the wild-type phenotype

Null allele

A mutant that produces no functional product. Most commonly a recessive allele. Also known as amorphic mutation 

• Loss of function

Hypomorphic

A mutant whose phenotype is similar to, but less than, the wild-type phenotype 

• Leaky mutant allele

• Usually recessive

• Loss of function

Hypermorphic

A mutant whose phenotype is similar to, but greater than, the wild-type phenotype 

• Excessive gene product -> excessive gene action

• Gain of function

Neomorphic

A mutant expressing a new or novel function not seen in the wild type 

• In both homozygous and heterzygous but may be more extreme in homozygotes

• Gain of function

Dominant negative

A dominant mutation that behaves as a loss-of-function, often due to blocking the formation or normal function of a multimeric protein complex 

• Multimeric protein: protein composed of two or more polypeptides 

• Spolider effect on the protein as a whole

• Loss of function

Incomplete Dominance

The observation that the phenotype occurring in heterozygous organisms is intermediate between the phenotypes of homozygous organisms, but more similar to one homozygous phenotype than to the other. Also known as partial dominance 

Codominance

The equal and detectable expression of both alleles in a heterozygous organism 

Loss of function mutation

A mutant that prevents the production of the wild-type protein or renders it inactive. Most commonly a recessive mutation 

Gain of function mutation

A mutation causing a gene to be overexpressed, to be expressed at the wrong time, or to encode a constitutively acting protein; usually inherited as a dominant mutation 

Lethal alleles

An allele that results in the premature death of the organisms that carry it. Lethality most often affects homozygous organisms. 

• In low frequencies in populations

• Raly and Agouti example in yellow mice 

Temperature sensitive allele

A mutation evident only at or above a certain temperature due to an abnormality of the protein product that affects its stability. 

• Protein misfolds and losses function at higher temperature

• Functional at permissive temperature, not function at non-permissive temperature, and intermediate activity at various temperatures

Prototroph

wild type, makes all its required nutrients

Auxotroph

mutant that lacks the ability to make one or more nutrients 

• Can’t grow on minimal media

Epistasis

When one phenotype masks the expression of another phenotype 

• Genes interact which results in altered phenotypic ratios

Types of epistasis

• No genetic interaction- 9:3:3:1

• Complementary- 9:7

• Duplicate- 15:1

• Dominant- 9:6:1

• Recessive epistasis- 9:3:4

• Dominant epistasis- 12:3:1

• Dominant suppression- 13:3

Complementary gene interaction

wild type action from both genes is required for the dominant phenotype

• 9:7

Duplicate gene action

any wild type action creates the dominant phenotype

• 15:1

Dominant gene interaction

different phenotype for homozygous dominant, homozygous recessive, and heterozygotes

• 9:6:1

Dominant epistasis

A characteristic ratio of phenotypes produced by the interaction of two genes that control a trait in which a dominant allele of one gene masks or reduces the expression of alleles of a second gene 

• 12:3:1

Recessive epistasis

A characteristic ratio of phenotypes produced by the interaction of two genes that control a trait in which alleles of one gene mask or reduce the expression of alleles of a second gene 

• 9:3:4

Dominant suppression

the dominant allele of the first gene suppresses the expression of the second gene

• 13:3

Pathway

An ordered progression of gene activities that leads to a biological output 

Complementation group

A group of mutations that affect the same gene 

• Complementation means two mutants are deficient in different functions

• Failure to complement means two mutants are deficient in the same function - form a complementation group

Replica plate

A process in yeast or bacteria where some of the cells on one plate are transferred to another plate

Genetic dissection

separately test the ability of a mutant to execute each step of a biosynthetic pathway and use this data to assemble the steps of a pathway by determining the point at which the pathway is blocked in each mutant

One gene-one enzyme hypothesis

each gene produces an enzyme and each enzyme has a specific role in a biosynthetic pathway

• Updated to include genes that produce transport/structural/regulatory proteins, RNAs, and proteins that join together

Screen

A process where mutants are identified out of large numbers of wild-type individuals after mutagenesis  

Selection

A process where mutants are identified without any accompanying wild-type individuals after mutagenesis 

Mutagenesis

When a mutagen is applied to organisms and mutations occur throughout the genomes of gametes and somatic cells 

Mutagen

Any substance or DNA element that causes a mutation to the genome  

Balancer chromosome

A chromosome with multiple inversions, an allele that confers a dominant phenotype, and a different allele that confers recessive lethality 

• Inverted segments prevent crossing over

• Lethality prevents being homozygous for the balancer

• Dominant mutation producing a visible phenotype so it can be tracked

Cloning by Complementation

Transformation of the mutant organism with plasmids expressing genes. Organisms whose phenotype is restored to wildtype (complemented) contain a plasmid with a wildtype version of the gene. The plasmid can be isolated and sequenced to identify the gene. 

Whole-genome sequencing

Often, short-read sequencing of entire genomes from mutants and the wild-type strain to identify mutations 

Transgenic

Organism that contains genetic material that was inserted by a scientists (generated in the lab outside the animal or in vitro); many times refers to expression of genes from a different organism. 

CRISPR

(Clustered Regularly Interspaced Short Palindromic Repeats) Transcribed repetitive sequence that is processed into unique crRNAs acting in a bacterial or archaeal immune system. 

• Can be NHEJ or HR (CRISPR-Cas9)

CRISPR-Cas9

Complex of the Cas9 protein with tracrRNA and crRNA that acts to target invading nucleic acids in Staphylococcus. This system has been modified for use in gene editing. 

• Uses homologous recombination to add desired nucleotides

crRNA

Unique small RNAs derived from CRISPR loci that combine through complementary base pairing with tracrRNAs in the CRISPR-Cas complex. 

RNAi

RNA interference, knockdown of gene expression using endogenous RNAse machinery

Forward genetics

generate random mutations and identify gene sequence

• What no longer happens in the cell with the KO is the function of the gene

Reverse genetics

directed KO/KD based on what we know about other organisms

• What no longer happens in the cell with the KO is the function of the gene

• RNAi, CRISPR, HR

Synonymous mutation

no amino acid change, silent

Nonsynonymous

amino acid change, missense

Read-through mutation

conversion of a stop codon to an amino acid

Nonsense mutation

conversion to a stop codon