Week 5 Flashcards
Why do I need to know how to classify alleles?
There are 1,000 upon 1,000 of DNA sequence changes that can affect an organism’s phenotype. Need for systems of organization.
There 5,000 to 30,000 genes in organisms which require a system of organization with respect to the effect of DNA sequence changes.
Familiarity with allele classification simplifies discussion of genetic analysis.
bcd1 vs bcd2
these are independent mutant alleles, that arose through independent changes in DNA sequences
Functional allele
produces active gene product
Allele classification based on transmission
Complete dominance (haplosufficient) Recessive Partial/Incomplete dominance (haploinsufficiency)
Complete Dominance
haplosufficient
one functional allele is sufficient to make sufficient gene product
look at the heterozygote to asses dominance
Haploinsufficient
incomplete dominance
the functional allele is required for the formation of some active product but its not sufficient to get the complete phenotype
quality of the functional allele
the nonfunctional allele uncovers the property of the functional allele.
Test haploinsufficiency
add another copy of the functional allele and determine if there is recovery of the wt phenotype
Allele classification based on DNA sequence changes in the coding region of a gene
SNP
Silent
Missense
Nonsense
Indel
Frameshift
Insertion/deletion of amino acids
Silent allele
because of the redundancy of the genetic code a change in a single nucleotide could result in the same amino acid being introduced
DNA sequence changes that do not change the sequence of the polypeptide produced they are not expected to change the function of the protein.
Nonsense allele
DNA sequence change results in a premature stop codon in the sequence
Missense allele
DNA sequence change results in a different amino acid introduced into the polypeptide chain
Frameshift allele
Mocing the reading frame over by one (if one nucleotide is inserted)
completely changes the amino acid sequence, unless the insertion is in three that results in the addition of an amino acid
Insertion
Insertion or deletions occurring in multiples of three.
Upon translation of the messenger rna there is an insertion of aa.
The problem with calling the functional allele a wild-type allele
wt is often a standard assigned by researchers even when they know there is variation in the population, some alleles are not meant to be functional
Loss of function allele
generally recessive; exception haploinsufficiency
DNA sequence changes that reduce the function of the protein or RNA encoded by the gene
lf subclasses
1-Null alleles: coding and regulatory
2-Weak/hypomorphic alleles: coding and regulatory
3-Conditional alleles: temperature sensitive
Null alleles
Amorphic alleles
completely inactive gene product
Null alleles are DNA sequence changes that result in a completely inactive gene product.
By definition a complete deletion of a gene such that there is not a single nucleuotide left in the genome
There can be null alleles that are a result of DNA sequence changes in the regulatory sequences such that the gene is never transcribed.
If it is never transcribed there is no gene product being produced
Weak alleles/hypomorphic allele
weak hypomorphic alleles are subdivided into subtypes, DNA sequence change results in a partially inactive product
so in a hypomorphic allele the gene product might have some activity, that small presence activity the phenotype produced is less severe and much weaker
multifunctional protein with only 1 of 2 functions affected by the change.
weak hypomorphic alleles are subdivided into subtypes
multifunctional protein with only 1 of 2 functions affected by the change.
DNA sequence change results in a partially inactive product.
So in a hypomotphic allele the gene product might have some activity, that small presence activity the phenotype produced is less severe, much weaker.
Regulatory mutant resulting in partial expression; This gene is not expressed in all cells that it is normally expressed in.
Conditional alleles
temperature sensitive alleles
active gene product at low temperatures
inactive gene product at high temperature
in this case what can occur is a DNA seuqence change results in a protein product that is still active when the organism is grown at a lwo temperature because the protein can fold in its low temperature
Gain-of-function alleles (gf)
Generally associated with mis-regulation of a gene product’s activity and are generally dominant.
The phenotypes of a gain-of-function allele and a loss-of-function allele in a gene are the opposite of one another.
Hypermorph, neomorph
Operator constituitive
DNA sequence changes in the operator that results in the lac repressor not being able to recognize the operator.
LacZ is contuinally active
oc is dominant to the functional allele
Operator constituitive mutations are a result of the loss of the ability of the Lac repressor to surpress expression of beta galactosidase when cells are grown in glucose containing media.
Loss of negative regulation Ras example.
RAS is a GTP binding protein. RAS proteins Exist in two states GTP and GDP binding, these two states are in a dynamic equilibrium with on another.
These two states have two activation states.
Environmental signals regulate the amount of RAS present by shifting the equilibrium.
If a DNA sequence change results in a Ras protein with an AA change that results in an inability to hydrolyse GTP. Ras is stuck in an on state.
The cells will grow themselves to death.
Misexpression of Antennapedia
Spontanoeus mutational changes in which the antennapedia gene is fused to a new promoter that results in the expression of the gene in the antenna primordia.
Or put it behind another promoter which would force expression of antennapedia in the antenna primordia.
The antenna is transformed into a pair of second legs.
Misexpression of Antennapedia
Spontanoeus mutational changes in which the antennapedia gene is fused to a new promoter that results in the expression of the gene in the antenna primordia.
Or put it behind another promoter which would force expression of antennapedia in the antenna primordia.
The antenna is transformed into a pair of second legs.
Dominant Negative
antimorph
the gene product works in a complex, either with itself or another protein, and the activity of all proteins in the complex is essential for the total activity of the complex
hetero/homodimers
Mutation must not affect the ability
of the complex to form.
A dominant negative allele…
reduces activity to a greater extent than a null allele when heterozygous
That’s why they are dominant.
Greater reduction in activity because these proteins assort into complexes independently of one another.
1/4 wt activity
Multiple copies of the dn allele or overexpression
will strongly inhibit wild type activity.
Wt polypeptide cannot find another wt polypeptide to form a complex with
