mutation and variation

Question 1

Mutation

Answer 1

= a process that produces a gene or chromosome that differs from
the wild type

Question 2

Mutation =

Answer 2

the gene or chromosome that results from a mutational process

Question 2

mutant

Answer 2

a mutant is the organism or cell whose changed phenotype is attributed to a
mutation

Question 3

General Types of mutation

Answer 3

1. Gene mutation = the allele of a gene changes (this chapter)
2. Chromosome mutation = segments of chromosomes, whole chromosomes, or
   entire sets of chromosomes change

Question 4

What does wild type (wt) mean?

Answer 4

Wild type is an arbitrary standard for what
“normal” is for an organism. Please remember that what is considered wild type today
may have been a mutant in the evolutionary past.

Question 5

Direction of the mutation

Answer 5

Forward mutations are changes away from the wt
2. Reverse mutations (reversions) are changes from the mutant allele back to the
wt allel

Question 6

Mechanisms for gene mutation

Answer 6

1. Errors in DNA replication
2. Errors in DNA repair
3. Environmental mutagen causes DNA damage that is not repaired correctly
4. Transposons and insertion sequences (a mobile DNA elements that can move
   from one location in the chromosome to another; the element may “jump” into a
   gene thereby mutating it)

Question 7

Why study gene mutation?

Answer 7

1. Variants in genes (which are caused by mutations) are needed to study the
   transmission of traits
2. Mutations can tell the researcher about the function of a gene product in a
   biological system
3. Mutations are the basis for cancer and other genetic diseases
4. Gene mutations serve as the source for most alleles in a population and is
   therefore the origin of genetic variation within a population
5. Mutations drive evolution: mutations are the raw material upon which natural
   selection acts

Question 8

Classification of mutations: Point of origin

Answer 8

Somatic mutations
a) mutations that are in the somatic tissues of the body
b) mutations are NOT transmitted to progeny
c) the extent of the phenotypic effect depends upon whether the mutation
is dominant or recessive (dominant mutations generally have a greater
effect)
d) the extent of the phenotypic effect depends upon whether it occurs
early or late in development (early arising mutations have a greater effect)
e) sectoring phenotypes may be seen when the mutation occurs during
embryonic development
f) cancer caused by somatic mutations

Germinal mutations
a) mutations that are in the germ tissues of the body
b) mutations MAY BE transmitted to progeny
c) dominant mutations are seen in first generation after the mutation
occurs
d) if a female gamete containing an X-linked mutation is fertilized, the
males will show the mutant phenotype
e) recessive mutations will only be seen upon the chance mating with an
individual carrying the recessive allele too; thus, the recessive mutation
may remain hidden for many generations

Question 9

Germinal mutations

Answer 9

a) mutations that are in the germ tissues of the body
b) mutations MAY BE transmitted to progeny
c) dominant mutations are seen in first generation after the mutation
occurs
d) if a female gamete containing an X-linked mutation is fertilized, the
males will show the mutant phenotype
e) recessive mutations will only be seen upon the chance mating with an
individual carrying the recessive allele too; thus, the recessive mutation
may remain hidden for many generations

Question 10

Somatic mutations

Answer 10

a) mutations that are in the somatic tissues of the body
b) mutations are NOT transmitted to progeny
c) the extent of the phenotypic effect depends upon whether the mutation
is dominant or recessive (dominant mutations generally have a greater
effect)
d) the extent of the phenotypic effect depends upon whether it occurs
early or late in development (early arising mutations have a greater effect)
e) sectoring phenotypes may be seen when the mutation occurs during
embryonic development
f) cancer caused by somatic mutations

Question 11

Classification of mutations:
Phenotypic effects

Answer 11

1. Morphological mutations are mutations that affect the outwardly visible
   properties of an organism (i.e. curly ears in cats)
2. Lethal mutations are mutations that affect the viability of the organism (i.e.
   Manx cat).
3. Conditional mutations are mutations in which the mutant allele causes the
   mutant phenotype only in certain environments (called the restrictive condition).
   In the permissive condition, the phenotype is no longer mutant. (i.e. Siamese cat
   – mutant allele causes albino phenotype at the restrictive temperature of most of
   the cat body but not at the permissive temperature in the extremities where the
   body temperatures is lower).
4. Biochemical mutations are mutations that may not be visible or affect a
   specific morphological characteristic but may have a general affect on the ability
   to grow or proliferate.
   a) Most microorganisms are prototrophs which means that they can grow
   on a simple growth medium including an energy source and inorganic
   salts. Biochemical mutations include those that affect proteins or enzymes
   required to grow on various nutrients or to synthesize various components.
   Thus, these mutations cause the microorganisms to become auxotrophs
   (they must be supplied with additional nutrients if they are to grow). For
   example, the bacterium Escherichia coli does NOT require the amino acid
   tryptophan for growth because they can synthesize tryptophan. However,
   there are E. coli mutants that have mutations in the trp genes. These
   mutants are auxotrophic for tryptophan, and tryptophan must be added to
   the nutrient medium for growth.
   b) Humans can also have biochemical mutations (also called inborn
   errors in metabolism). Such examples include hemophilia,
   phenylketonuria, and galactosemia

Question 12

1. Morphological mutations

Answer 12

are mutations that affect the outwardly visible
properties of an organism (i.e. curly ears in cats)

Question 13

Lethal mutations

Answer 13

are mutations that affect the viability of the organism (i.e.
Manx cat)

Question 14

Conditional mutations

Answer 14

Conditional mutations are mutations in which the mutant allele causes the
mutant phenotype only in certain environments (called the restrictive condition).
In the permissive condition, the phenotype is no longer mutant. (i.e. Siamese cat
– mutant allele causes albino phenotype at the restrictive temperature of most of
the cat body but not at the permissive temperature in the extremities where the
body temperatures is lower).

Question 15

Biochemical mutations

Answer 15

Biochemical mutations are mutations that may not be visible or affect a
specific morphological characteristic but may have a general affect on the ability
to grow or proliferate.
a) Most microorganisms are prototrophs which means that they can grow
on a simple growth medium including an energy source and inorganic
salts. Biochemical mutations include those that affect proteins or enzymes
required to grow on various nutrients or to synthesize various components.
Thus, these mutations cause the microorganisms to become auxotrophs
(they must be supplied with additional nutrients if they are to grow). For
example, the bacterium Escherichia coli does NOT require the amino acid
tryptophan for growth because they can synthesize tryptophan. However,
there are E. coli mutants that have mutations in the trp genes. These
mutants are auxotrophic for tryptophan, and tryptophan must be added to
the nutrient medium for growth.
b) Humans can also have biochemical mutations (also called inborn
errors in metabolism). Such examples include hemophilia,
phenylketonuria, and galactosemia

Question 16

Loss of function mutations

Answer 16

are those that destroy the function of the gene
product. Many times in diploid organisms, these are recessive mutations because
the other wild type allele still encodes a functional gene product. However, it is
possible to have a dominant loss of function mutation in which the mutant gene
product interferes with the activity of the gene product from the wild type allele

Question 17

Null mutation =

Answer 17

loss of function mutation where gene product is
completely inactive

Question 18

Leaky mutation =

Answer 18

loss of function mutation where gene product is not
completely inactive (partially active still)

Question 19

Gain of function mutations

Answer 19

are those that produce a new function for the gene
product. Gain of function mutations are dominant.

Question 20

Mutation frequency =

Answer 20

of times mutation appears in the population / # of
individuals in the population where a population can be bacterial cells, people,
gametes

Question 21

Mutation rate

Answer 21

= # of mutations / unit time where unit time can be per cell
division, cell generation

Question 22

Frequencies of mutations

Answer 22

Mutations are relatively rare.
4. Different genes have different mutation frequencies (Table 7-1)
5. Different organisms have different overall mutation frequencies (Table 7-2

Question 23

Detection of mutations in humans

Answer 23

1. Detection of germinal dominant mutations by human pedigree analysis (shows
   up in the pedigree as the sudden appearance of a novel phenotype)
2. Detection of germinal recessive mutations are more difficult because they
   remain masked by the dominant allele until the union of two heterozygotes
3. Detection of germinal X-linked mutations arising in female gametes appear in
   some of the males in the generation after the mutation occurred.

Question 24

Detection of mutations using the specific-locus test

Answer 24

a system for detecting recessive mutations in diploids. Heterozygote individual for gene(s)A that give phenotype A is crossed with a homozygous recessive individual for gene(s)a that gives phenotype a. The frequency of the mutant phenotype (a) is quantitated.

Question 25

Detection of X-linked mutations in Drosophila using the ClB chromosome

Answer 25

The ClB chromosome is the X chromosome bearing the C allele which prevents crossover, the l allele which is a recessive lethal, and the Bar allele which is a dominant eye mutation

Question 26

Microorganisms

Answer 26

Microorganisms allow for the use of selective systems for mutation detection vs. the screening systems used for higher organisms. A selective system is one in which the experimenter can DEMAND that the only individuals that grow or survive are the ones that have the mutation of interest. On the other hand, a screening system is one in which the experimenter must examine each individual to see if it has the mutation of interest.

Question 27

Mutations and cancer

Answer 27

A. Cancer is a group of diseases characterized by rapid, uncontrolled proliferation of cells within a tissue resulting in the formation of a tumor. Cancer has many causes and phenotypes but the fundamental mechanism underlying all cancers is genetic. B. There are two types of genes that are involved in cancer formation. 1. Tumor suppressor genes are genes that encode a product that normally stops cell division. Mutations in these genes result in uncontrolled activation of cell division and therefore tumor formation. Mutations are generally recessive and thus you need mutations in both alleles to have cancer. A mutation in one allele predisposes the carrier to cancer. a) Rb gene - retinoblastoma (retinal cancer) b) BRCA1 - hereditary breast cancer gene c) p53 gene mutations are found in a variety of cancers including breast, lung, bladder, and colon cancers. Over 1/2 of all cancers are associated with p53. 2. Proto-oncogenes are genes that encode a product that normally controls cell division (kind of like an on/off switch). Mutations in these genes make the gene product permanently in the on position which results in uncontrolled activation of cell division and therefore tumor formation. a) N-ras – neuroblastoma (tumor formed of embryonic ganglion cells), leukemia b) N-myc – neuroblastoma c) man – mammary carcinoma

Question 28

Tumor suppressor genes

Answer 28

1. are genes that encode a product that normally stops cell division. Mutations in these genes result in uncontrolled activation of cell division and therefore tumor formation. Mutations are generally recessive and thus you need mutations in both alleles to have cancer. A mutation in one allele predisposes the carrier to cancer. a) Rb gene - retinoblastoma (retinal cancer) b) BRCA1 - hereditary breast cancer gene c) p53 gene mutations are found in a variety of cancers including breast, lung, bladder, and colon cancers. Over 1/2 of all cancers are associated with p53.

Question 29

Proto-oncogenes are genes that encode a product that normally controls cell division (kind of like an on/off switch). Mutations in these genes make the gene product permanently in the on position which results in uncontrolled activation of cell division and therefore tumor formation. a) N-ras – neuroblastoma (tumor formed of embryonic ganglion cells), leukemia b) N-myc – neuroblastoma c) man – mammary carcinom

Answer 29

Proto-oncogenes are genes that encode a product that normally controls cell division (kind of like an on/off switch). Mutations in these genes make the gene product permanently in the on position which results in uncontrolled activation of cell division and therefore tumor formation. a) N-ras – neuroblastoma (tumor formed of embryonic ganglion cells), leukemia b) N-myc – neuroblastoma c) man – mammary carcinom