Week 5

Question 1

Why do I need to know how to classify alleles?

Answer 1

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.

Question 2

bcd1 vs bcd2

Answer 2

these are independent mutant alleles, that arose through independent changes in DNA sequences

Question 3

Functional allele

Answer 3

produces active gene product

Question 4

Allele classification based on transmission

Answer 4

Complete dominance (haplosufficient)
Recessive
Partial/Incomplete dominance (haploinsufficiency)

Question 5

Complete Dominance

Answer 5

haplosufficient

one functional allele is sufficient to make sufficient gene product

look at the heterozygote to asses dominance

Question 6

Haploinsufficient

Answer 6

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.

Question 7

Test haploinsufficiency

Answer 7

add another copy of the functional allele and determine if there is recovery of the wt phenotype

Question 8

Allele classification based on DNA sequence changes in the coding region of a gene

Answer 8

SNP
Silent
Missense
Nonsense

Indel
Frameshift
Insertion/deletion of amino acids

Question 9

Silent allele

Answer 9

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.

Question 10

Nonsense allele

Answer 10

DNA sequence change results in a premature stop codon in the sequence

Question 11

Missense allele

Answer 11

DNA sequence change results in a different amino acid introduced into the polypeptide chain

Question 12

Frameshift allele

Answer 12

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

Question 13

Insertion

Answer 13

Insertion or deletions occurring in multiples of three.

Upon translation of the messenger rna there is an insertion of aa.

Question 14

The problem with calling the functional allele a wild-type allele

Answer 14

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

Question 15

Loss of function allele

Answer 15

generally recessive; exception haploinsufficiency

DNA sequence changes that reduce the function of the protein or RNA encoded by the gene

Question 16

lf subclasses

Answer 16

1-Null alleles: coding and regulatory
2-Weak/hypomorphic alleles: coding and regulatory
3-Conditional alleles: temperature sensitive

Question 17

Null alleles

Answer 17

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

Question 18

Weak alleles/hypomorphic allele

Answer 18

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.

Question 19

weak hypomorphic alleles are subdivided into subtypes

Answer 19

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.

Question 20

Conditional alleles

Answer 20

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

Question 21

Gain-of-function alleles (gf)

Answer 21

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

Question 22

Operator constituitive

Answer 22

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.

Question 23

Loss of negative regulation Ras example.

Answer 23

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.

Question 24

Misexpression of Antennapedia

Answer 24

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.

Question 25

Misexpression of Antennapedia

Answer 25

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.

Question 26

Dominant Negative

Answer 26

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.

Question 27

A dominant negative allele…

Answer 27

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