Chapter 3.5 - Mutations

mutation

a change in the nucleotide sequence of a gene that is in less than 1% of the population; introduces variation

polymorphism

a change in the nucleotide sequence of a gene that is in more than 1% of the population; introduces variation

molecular or chromosomal

mutation may occur at the _______ or ________ level

loss of function, gain of function, silent mutations

3 effects of mutations

dominant

the gain of function due to mutations is usually _______ inherited

mutant

_____ refers to an unusual phenotype; the result of a mutation

somatic or germline

whether mutations are inherited or not depends on if they are ________ or _______ mutations

somatic mutations

this mutation occurs in any cell of the body except the germline (gametes); affects subsequent somatic cell descendants but is not transmitted to offspring

germline mutations

mutation that occurs in the germline cells; possibility of transmission to offspring (heritable)

sickle cell anemia

this mutation encodes valine in place of glutamic acid

homozygous recessive

sickle cell anemia is … (homozygous/heterozygous)

thalessemia

caused by another beta hemoglobin mutation that causes too few beta hemoglobin molecules; the excess of alpha hemoglobin leads to iron release, which destroys RBCs, damages heart, liver, and endocrine glands

thalassemia minor

this version of Thalassemia is heterozygous and less severe

Thalassemia major

this version of thalassemia is homozygous and more servere

collagen

_______ is used in lots of different tissues and a malfunction in this specific gene because of a glycine mutations in triple helix is manifested in different ways in these different tissues

True

True or False: one gene can cause one disorder, many disorders, or the same gene/different mutation can cause different changes in different tissues

spontaneous mutation

errors in DNA replication, not caused by exposure to a known mutagen

tautomers

DNA bases that have slight chemical instability

mispairing

as replication fork encounters unstable tautomers, _______ can occur

mutational “hot spots”

specific regions that are very prone to mutation; repeats prone to mutation

repeat regions

areas that are most susceptible to mutation; they are the repetition of one, two, or three base pairs

repeat of a nucleotide

A A A A A A A A

direct repeat of a dinucleotide

G C G C G C G C

direct repeat of a trinucleotide

T A C T A C T A C T A C

palindrome

section of DNA that is the same read backwards; this can cause the sequence of DNA that matches itself to pairs with itself during replication causing a mutation

gene duplication

misaligned crossing over; causes addition/deletion during meiosis 1

more

larger genes tend to have _____ mutations

induced mutations

caused by mutagens, many are also carcinogens and cause cancer

alkylating agents

induced mutation that removes a base

acridine dyes

induced mutation that adds or removes a baseq

x-rays

induced mutation that breaks chromosomes or deletes a few nucleotides

UV radiation (UVB)

induced mutation that creates thymine dimers

ionizing radiation

removes electrons and changes charge, can break DNA backbone

point mutations

a change of a single nucleotide

transition

type of point mutation where you replace a purine for a purine or a pyrimidine for a pyrimidine

transversion

type of point mutation where purine replaces pyrimidine or prymididine replaces purine

missense mutation

a point mutation that changes the codon

missense mutation

this type of mutation causes a substitution of an amino acid

missense mutation

hemoglobin mutation where glutamic acid to valine causes sickle cell anemia this is an example of what type of mutation?

nonsense mutation

a point mutation changing a codon for an amino acid into a stop codon; creates truncated proteins that are often nonfunctional

nonsense mutation

clotting factor IX deficiency is a ______________ changing glutamic acid to a “stop,” the short protein cannot function in clotting; this is an example of what type of mutation?

truncated protein

a protein that is shorter than its full-length counterpart due to a premature stop codon in the DNA sequence

splice site mutations

alters a site where introns are normally removed causing the introns to be translated OR exons skipped

splice site mutation

Cystic fibrosis and BRCA1 are examples of what type of mutation?

triplet nucleotides

the genetic code is read in ________ ________

reading frame

addition or subtraction of nucleotides not in multiples of three leads to a change in the _____ _____

frameshift; alters

insertions or deletions cause a ______ and ______ amino acids after mutation

expanding repeats

when there is the insertion of triplet repeats that leads to extra amino acids; a already existing repeat is made longer; some genes are particularly prone to these

anticipation

the expansion of the triplet repeat with an increase in severity of phenotype with subsequent generations

earlier; more servere

the more repeats you have in the nucleotides, the ____ the onset and the ____ _____ the phenotype

third position wobble

refers to the flexibility in base pairing at the third position of an mRNA codon during translation that allows for a silent mutation

second position mutation

the second position if changed, the amino acid it is coded for is chemically similar so it doesn’t alter the AA as much

conditional mutation

mutations that only manifest in specific environment such as infections, drugs, food, etc.

conditional mutation

GP6D is an example of what type of mutation (or mutation lessening effect)

excision repair

damaged DNA is removed by excision of the bases and the bases are replaced by a DNA polymerase

nucleotide excision repair

replaces up to 30 bases; used in repair of UVB and some carcinogens

base excision repair

replaces 1-5 bases; repairs oxidative damage (free radicals)

mismatch repair

enzymes detect nucleotides that do not base pair in newly replicated DNA; the incorrect base is excised and replaced;

proofreading

with mismatch repair, ______ is the detection of mismatches

use information in cells to repair; sister chromatid or homologous chromosome

how to repair double strand breaks

trichothiodystrophy

repair disorder where there is faulty nucleotide excision repair or base excision repair or both; 5 genes

trichothiodystrophy

repair disorder associated with dwarfism, mental retardation, premature aging, scaly skin, etc.

xeroderma pigmentosa

autosomal recessive repair disorder involving the mutation in any of 7 genes; the malfunction of excision repair or deficient “sloppy” DNA polymerase which allows thymine dimers to remain and block replication; must avoid UV light; super rare only 250 cases worldwide