Chapter 15 Mutation And Molecular Medicine

Front 1

What exactly are genetic mutations?

Back 1

Changes in the nucleotide sequence of DNA that are passed on to the next generation

Front 2

Mutations can be divided into two types. What are they?

Back 2

1. Somatic mutations
2. Germ line mutations

Front 3

What is a somatic mutation?

Back 3

They occur in body (somatic) cells only and they are passed on to daughter cells through mitosis

Front 4

What is germ line mutation?

Back 4

Mutations that occur in specialized cells (germ line) that give rise to gametes. This mutation is passed on at fertilization

Front 5

Mutations have 4 different types of phenotypic effects? What are they?

Back 5

1. Silent mutations
2. Loss of function mutations
3. Gain of funciton mutations
4. Conditional mutations

Front 6

What are silent mutations?

Back 6

Mutations that DO NOT affect protein function. They can be found in either coding or non coding sequences

Front 7

What is a loss of function mutation?

Back 7

Mutations that DO affect proteins. They are almost always recessive

Front 8

What is a gain of function mutation?

Back 8

Mutations that lead to proteins with altered functions. They are usually dominant

Front 9

What is a conditional mutation?

Back 9

Mutations that cause their phenotypes only under CERTAIN restrictive conditions. For example: temperature

Front 10

At the molecular level, we can divide mutations into two categories. What are they?

Back 10

1. Point mutations
2. Chromosomal mutations

Front 11

All mutations are alterations in the ______ sequence of ______.

Back 11

nucleotide, DNA

Front 12

What is a point mutation?

Back 12

Results from a GAIN, LOSS or SUBSTITUTION of a single nucleotide

Front 13

What is a chromosomal mutation?

Back 13

More extensive that point mutation. May change the position or cause a DNA segment to be lost or duplicated

Front 14

Point mutations can result in errors in ______ OR to environmental ______

Back 14

replication, mutagens

Front 15

Point mutations usually result in the mRNA being altered, however silent mutations (by definition) have absolutely NO EFFECT on the resulting proteins. T or F?

Back 15

True

Front 16

There are four types of point mutations. What are they?

Back 16

1. Silent
2. Missense
3. Nonsense
4. Frame-shift

Front 17

What are characteristics of silent mutations?

Back 17

1. Have no effect on amino acids
2. Usually in non-coding regions
3. A substitution MAY be repaired in translation
4. Results in genetic diversity

Front 18

What are characteristics of missense mutations?

Back 18

1. A substitution of one amino acid for another
2. May result in defective or reduced protein efficiency
3. A great example would be sickle-cell disease

Front 19

What are characteristics of nonsense mutations?

Back 19

1. When a base substitution creates a STOP codon on the mRNA
2. A shortened chain is formed - which will most likely not be functional
3. If it occurs near the "natural" end of the mRNA, then it may be harmless

Front 20

What are characteristics of frame-shift mutations?

Back 20

1. An ADDITIONAL base or a DELETION of a base on DNA.
2. This interferes with translation and the 3-codon reading is "shifted"
3. The protiens made in this fashion are non-functional

Front 21

There are 4 types of chromosomal mutations. What are they?

Back 21

1. Deletions
2. Duplications
3. Inversions
4. Translocations

Front 22

What are characteristics of deletions in chromosomes?

Back 22

1. Genetic material is removed
2. Severe consequences
3. No effect if noncoding DNA

Front 23

What are characteristics of duplications in chromosomes?

Back 23

1. Homolgous chromosomes break in different places and re-attach to the wrong partner
2. Can happen at the same time as deletions

Front 24

What are characteristics of inversions in chromosomes?

Back 24

1. When bases break off, but then flip before re-attaching
2. These bases end up in reverse order

Front 25

What are charateristics of translocations in chromosomes?

Back 25

1. Bases break off one chromosome and re-attach to a completely different chromosome (a non-homozygous pair)
2. Often leads to duplications and deletions
3. May result in sterility because meiosis (the making of sex cells) is interrupted

Front 26

There are two CAUSES of mutations. What are they?

Back 26

1. Spontaneous
2. Induced

Front 27

Spontaneous mutations occur with no ______ influence.

Back 27

outside

Front 28

Induced mutations occur due to ______ agent OR ______

Back 28

outside, mutagen

Front 29

Both spontaneous and induced mutations are not always permenant. T or F?

Back 29

False: they are always permenant

Front 30

Mutations have several benefits. What are they?

Back 30

1. Provide genetic diversity
2. Can benefit the organism immediatley (in somatic cells)
3. Can cause advantageous change in offspring

Front 31

How do bacteria fight off viruses?

Back 31

Through restriction enzymes. The virus shoot it's DNA into the bacteria and the restriction enzymes within the bacteria cleave it up into small fragements making it useless.

Front 32

Where do restriction enzymes come from?

Back 32

They are harvested from the cells that actually make them (i.e. the restriction enzyme EcoRI comes from the bacteria E.coli)

Front 33

How does a bacteria keep its native restriction enzyme from cleaving up its OWN dna?

Back 33

Methyl groups at restrictions sites BLOCK the restriction enzyme

Front 34

What process do we use to separate DNA fragments that have been cut by restrictions enzymes?

Back 34

Gel electrophoresis

Front 35

In gel electrophoresis, do shorter or longer DNA fragments travel faster and longer through the gel?

Back 35

Shorter fragements

Front 36

When a mutation is expressed phenotypically (because of proteins that differ from the "norm"), we usually call this a ______.

Back 36

Disease

Front 37

An example of a disease that results from an abnormal enzyme phenylalanine hydroxylase is called what?

Back 37

PKU (Phenylketouria Disease)

Front 38

Explain the disease PKU.

Back 38

1. In normal people, phenylalanine hydroxylase catalyzes dietary phenylalanine into tyrosine
2. PKU patients have an abnormal version of this enzyme and therefore DO NOT catalyze tyrosin. As a result, dietary phenylalanine builds up in their bodies.
3. Causes retardation, light skin, light hair color

Front 39

Explain sickle-cell anemia

Back 39

1. Patiens have an abnormal allele that creates an abnormal hemoglobin which is sickle shaped
2. These cells block blood flow and causes anemia

Front 40

What is reverse genetics?

Back 40

1. Normally, a protein phenotype is discovered first, then the gene which produced the protein
2. In reverse genetics, the abnormal gene is located FIRST, and THEN the protein it created is characterized

Front 41

What is an example disease that was discovered using reverse genetics?

Back 41

Cyctic fibrosis (sickle cell anemia was discovered using the standard way)

Front 42

In reverse genetics, in order to identify the mutant gene, close linkage to a ______ sequence is used

Back 42

marker

Front 43

What is a genetic marker?

Back 43

A reference point for gene isolation

Front 44

In order to design therapy treatments, it is important to identify the ______ involved in a disease.

Back 44

protien

Front 45

What does RFLP stand for?

Back 45

Restriction fragement length polymorphisms

Front 46

What are RFLP's?

Back 46

They are differences in DNA sequences (due to mutations) that PREVENT restrictions enzymes from chopping up the DNA.

For example, a specific restriction enzyme can cut up GAATTC. But the mutated version GAGTTC can NOT be cut up.

Front 47

What is SNP?

Back 47

Single-nucleotide polymorphism

For example, take the following strings:
AAGCCTA and
AAGCTTA

They differ by just one single nucleotide. This is an SNP

Front 48

Now that the human genome has been fully sequenced, what does this provide us with?

Back 48

An easier way to identify markers that are more closely linked to the gene of interest.

Front 49

Once a linked DNA region is identified, many methods are available to identify the actual gene responsible for a genetic ______.

Back 49

disease

Front 50

Being able to isolate genes that are responsible for diseases has led to what?

Back 50

1. Tests for mutations
2. Protein identification
3. Possible treatements

Front 51

What is genetic screening?

Back 51

Use of a test to determine if an induvidual has a genetic disease, or if predisposed to one or is a carrier

Front 52

What are several example of genetic screening?

Back 52

1. Pre-natal screening
2. Screening of newborns
3. Screening asymptomatic people with relatives who have genetic diseases

Front 53

There are two main approaches to treating genetic diseases. What are they?

Back 53

1. Modifying the disease phenotype
2. Replacing the defective gene

Front 54

Modifiying a disease phenotype can be accomplished in 3 ways. What are they?

Back 54

1. Restricting the substrate - reducing it so it does not cause problems
2. Metabolic inhibitors - drugs that target proteins
3. Supply the missing protien - for example, a supplement

Front 55

How do we replace the defective gene through gene therapy?

Back 55

The missing allele can be supplied by inserting a new gene that will eventually be expressed in the host

Front 56

What are some challenges with gene therapy?

Back 56

1. Ensuring precise insertion into the host DNA
2. Ensuring appropriate expression
3. Ensuring the correct cells are targeted

Front 57

Break down of ALL mutation types, effects, categories and causes.

Back 57

See illustration