RX314 Module 9

Spontaneous mutations

Errors during DNA replication (proofreading) or spontaneous nucleotide modifications

Induced mutations

Mutations caused by UV radiation, radioactivity, chemical mutagens, or viruses

Trisomy of chromosome 21

Mutation that causes Down syndrome

CFT

Mutation that causes cystic fibrosis

Sirt2

Mutation responsible for fat cell formation

MCR4

Mutation responsible for food intake regulation

Principle of segregation

Assumes that different versions of a gene account for different phenotypes

Principle of independent assortment

Dictates that emergence of one trait will not affect the emergence of another encoded by a different gene

Dominant disorders

Familial adenomatous polyposis, Huntington

Recessive disorders

Phenylketonuria, cystic fibrosis, albinism

A father is affected by Huntington and is heterozygous for this gene. The mother is not affected by this disease. The children will be:

50% affected

3 multiple choice options

A father is affected by cystic fibrosis. The mother is not affected by this disease. The children will be:

Two outcomes above are possible.

3 multiple choice options

Phenotype

Exhibited in physical appearance, sensitivity to specific drugs, genetically-determined disease, mental abilities, etc.

X-linked disorders

Duchenne muscular dystrophy, hemophilia, male baldness

A mother is heterozygous for hemophilia. The father has hemophilia. Their male children will have the chance of having this disease:

50%

3 multiple choice options

Incomplete dominance

Partial expression of recessive gene

Sickle cell anemia (heterozygotes can be critical during general anesthesia)

Incomplete dominance

3 multiple choice options

Heterozygote advantage

Heterozygous individual has a higher fitness than homozygous individuals

Sickle cell anemia (heterozygotes have resistance to malaria)

Heterozygote advantage

3 multiple choice options

Co-dominance

Neither phenotype can be dominant over the other

Blood types (A, B, O)

Co-dominance

3 multiple choice options

Multiple alleles

Phenotype is determined by more than two alleles

Mitochondrial inheritance

Disease can occur in both males and females but is only inherited from mother

Linkage analysis

Combinations of specific SNPs or tandem repeats are associated with disease and have familial inheritance

Euchromatin

Loose, active chromatin

Heterochromatin

Tightly-packed, inactive chromatin

DNA methylation

DNA modification occurring at carbon 5 in the pyrimidine ring protruding into the major groove of DNA, repressing transcription

Histone acetylation

Neutralizes the positive charge on lysine, causing it to interact less efficiently with DNA

Histone is methylated only

Gene silencing

1 multiple choice option

Histone is methylated and acetylated

Gene expression

1 multiple choice option

Histone is phosphorylated and acetylated

Gene expression

1 multiple choice option

Different modifications cannot happen with the same amino acid residue.

False

1 multiple choice option

Reader

Complex complementary to specific histone modifications sequences that binds and attracts other components

Writer

Complex with catalytic activities and additional binding sites that copies histone modifications to neighboring nucleosomes

Epigenetics

ON or OFF state of a gene can be inherited via classical and epigenetic processes and depends on methylation of cytosine

Histone deacetylase inhibitors (HDACs)

Agents that change global gene expression patterns affecting expression of key oncogenes and tumor suppressor genes

DNA methyltransferase (DNMT) inhibitors

Hypomethylating agents that help to restore proper gene activation/repression in cancers with distorted DNA methylation patterns

A patient almost died when administered a normal dose of the anesthetic drug during surgery. Later, it was discovered that the person is the carrier of the recessive mutation in position 6 of the beta-globin gene. This hypersensitivity to the anesthetic drug is an example of...

Incomplete dominance

3 multiple choice options

Only one statement below about epigenetics is incorrect. Which one is it?

DNA methylation is generally associated with higher gene activity.

3 multiple choice options

The mutation will be certainly lethal if it completely eliminates...

a general transcription factor

3 multiple choice options

The mutation will be certainly dominant if...

The second parental wild type allele cannot fully compensate the lost function of the protein expressed from the mutant allele.

3 multiple choice options

If the mother is heterozygous for the hemophilia mutation (does not have the manifestation of hemophilia) and the father does not have hemophilia, then the probability of their male children to be affected by the disease is...

50%

3 multiple choice options