Genetic screening for mutations- Forward genetics

Question 1

a process that identifies genes that affect biological processes by introducing random mutations into a population and then looking for mutants with specific phenotypes.

Answer 1

Mutant screening

Question 2

The ________ is defined as the gametes and any of their developmental precursors, and is therefore distinct from the ________ (i.e. non-reproductive cells) of the body.

Answer 2

germline, somatic cells

Question 3

Because most induced mutations are recessive, the progeny of mutagenized individuals must be mated in a way that allows the new mutations to become

Answer 3

homozygous (or hemizygous)

Question 4

These alleles are due to changes in the DNA sequence that cause it to no longer produce the same level of active protein as the wild-type allele.

Answer 4

loss-of-function allele

Question 5

alleles tend to be recessive because the wild-type allele is haplosufficient

Answer 5

loss-of-function allele

Question 6

loss-of-function allele that produces no active protein

Answer 6

amorph or null

Question 7

alleles with only a partial loss-of-function

Answer 7

hypomorphic

Question 8

More rarely, a mutant allele may have a gain-of-function, producing either more of the active protein

Answer 8

hypermoprh

Question 9

producing an active protein with a new function

Answer 9

neomorph

Question 10

alleles have an activity that is dominant and opposite to the wild-type function; also known as dominant negative mutations.

Answer 10

antimorph

Question 11

5 types of mutant allele

Answer 11

(1) amorph, (2) hypomorph, (3) hypermorph, (4) neomorph, and (5) antimorph.

Question 12

They make no active product – zero function.

Answer 12

amorph

Question 13

The absence of function in amorph can be due to a lack of ______ or due to the __________

Answer 13

transcription (gene regulation mutation), production of a malfunctioning (protein coding mutation) product

Question 14

They make an incompletely functioning product.

Answer 14

Hypomorph

Question 15

Hypomorph could occur via ____ or via the production of a _______.

Answer 15

reduced transcription, product that lacks complete activity

Question 16

Hypomorph alleles are sometimes referred to as ________, because they provide some function, but not complete function.

Answer 16

Leaky mutations

Question 17

True or false. Both amorphs and hypomorphs tend to be dominant to wild type because the wild type allele is usually able to supply sufficient product to produce a wild type phenotype called ______

Answer 17

False. recessive, haplo-sufficient

Question 18

________ alleles are almost always dominant to the wild type allele.

Answer 18

Gain-of-funtion

Question 19

Hypermorph can occur via ______ or by changing the product to make it more efficient/effective at its function.

Answer 19

increased transcription

Question 20

It can be either new expression (new tissue or time) or a mutation in the product to create a new function (additional substrate or new binding site), not present in the wild type product.

Answer 20

Neomorph

Question 21

These alleles usually have no normal function of their own and they interfere with the function from the wild type allele.

Answer 21

Antimorph

Question 22

also known as dominant negative mutations.

Answer 22

antimorph

Question 23

All mutations can be sorted into one of the five morphs base on how they behave when heterozygous with other alleles – deletion alleles (zero function), wild type alleles (normal function), and duplication alleles (double normal function).

Answer 23

Identifying Muller’s Morphs

Question 24

deletion alleles function

Answer 24

zero function

Question 25

wild type alleles function

Answer 25

normal function

Question 26

duplicated alleles function

Answer 26

double normal function

Question 27

True or false. After mutagen treatment, the vast majority of base pair changes (especially substitutions) have effect on the phenotype.

Answer 27

False, no effect

Question 28

When the mutagen treatement happened, majority of base pair changes have no effect on te phenotype, this is because?

Answer 28

the change occurs in the DNA sequence of a non-coding region of the DNA, such as in inter-genic regions (between genes) or within an intron region.

Question 29

Also, even if the change occurs in a base within a codon, it may not change the amino acid that it encodes (recall that the genetic code is degenerate; for example, GCT, GCC, GCA, and GCG all encode alanine) and is referred to as a _______.

Answer 29

Silent mutation

Question 30

True or false. The base substitution may change an amino acid, but this doesn’t alter the function of the product, so phenotypic change would occur.

Answer 30

False, no phenotypic

Question 31

Give the 4 reasons why some mutations may not have detectable phenotypes

Answer 31

• Silent changes
• Environment and genetic redundancy
• Essential genes and lethal alleles
• Naming genes

Question 32

True of false. There are also situations where a mutation can cause a complete gain-of-function of a gene, yet not produce a change in the phenotype, even when the mutant allele is homozygous. The phenotypic change can be due to environmental effects: the loss of that gene product may not be apparent in that environment, but might in another.

Answer 32

False. loss-of-function of a gene, lack of a phenotypic change

Question 33

The encoding of similarly functioning genes at more than one locus in the genome.

Answer 33

genetic redundancy

Question 34

True or false. genes with redundant functions can be easily identified by mutant screening.

Answer 34

False,cannot be

Question 35

Mutations in essential genes create ___________ that arrest the development of an individual at an __________. This type of mutation may therefore go unnoticed in a typical mutant screen because they are absent from the progeny being screened

Answer 35

recessive lethal alleles, embryonic stage

Question 36

true or false. The progeny of a dihybrid cross involving an embryonic lethal recessive allele may therefore all be of a single phenotypic class, giving a phenotypic ratio of 1:0 (which is the same as 3:0). In this case the mutation may not be detected.

Answer 36

false, monohybrid

Question 37

True or false. Many genes have been first identified in mutant screens, and so they tend to be named after their mutant phenotypes, not the normal function or phenotype.

Answer 37

True

Question 38

For mutations to be used in complementation tests they are?

Answer 38

(1) usually true-breeding (homozygous at the mutant locus), and (2) must be recessive mutations.

Question 39

True or false. Dominant mutation can be used in complementation tests.

Answer 39

False, cannot

Question 40

True or false. Some mutant strains may have more than one gene locus mutated and thus would fail to complement mutants from more than one other locus (or group)

Answer 40

True

Question 41

______ is one of many diseases that geneticists have shown to be caused by mutation of a single, well-characterized gene. _______ is the most common (1/2,500) life-limiting autosomal recessive disease among people of European heritage, with ~ 1 in 25 people being carriers.

Answer 41

Cystric fibrosis (CF)

Question 42

Fail to complement means

Answer 42

allelic mutation

Question 43

can complement means

Answer 43

non-allelic mutation

Question 44

Cystric fibrosis is due to a mutation in the________, which was identified by Lap-chee Tsui’s group at the University of Toronto.

Answer 44

CFTR (Cystic Fibrosis Transmembrane Conductance Regulator) gene

Question 45

Epithelial tissues in some organs rely on the CFTR protein to transport ions (especially Cl-) across their cell membranes. The passage of ions through a six-sided channel is gated by another part of the CFTR protein, which binds to _____.

Answer 45

ATP

Question 46

In the lungs, insufficient CFTR means…..

Answer 46

this causes mucus to accumulate and can lead to infection

Question 47

Defects in CFTR affects what of the following parts of the body?

Answer 47

pancreas, liver, intestines, and sweat glands, all of which need this ion transport.

Question 48

True or false. CFTR is also expressed at high levels in the salivary gland and bladder, but defects in CFTR function do not cause problems in these organs, probably because other ion transporters are able to compensate.

Answer 48

true

Question 49

CFTR allele among CF patients is called

Answer 49

ΔF508 (delta-F508; or PHE508DEL)

Question 50

a deletion of three nucleotides that eliminates a phenylalanine from position 508 of the 1480 aa wild-type protein.

Answer 50

ΔF508 (delta-F508; or PHE508DEL)

Question 51

Mutation _____ causes CFTR to be folded improperly in the endoplasmic reticulum (ER), which prevents CFTR from reaching the cell membrane.

Answer 51

ΔF508 (delta-F508; or PHE508DEL)

Question 52

_______ is effective on only some CFTR mutations, most notably G551D

Answer 52

Kalydeco

Question 53

where glycine is substituted by aspartic acid at position 551 of the protein; GLY551ASP

Answer 53

G551D

Question 54

The _______ mutation affects the ability of ATP to bind to CFTR and open the channel it for transport.

Answer 54

G551D

Question 55

______ compensates for mutation by binding to CFTR and holding it in an open conformation.

Answer 55

Kalydeco