9/8 Immune disease

Question 1

what are the molecular consequences of mutations (3 types)

Answer 1

1. gain of funciton (novel protein product , or over expression or inappropriate isxpression) 2. loss of function (recessive disorders, haploinsufficiency or half othe normal amount of gene product causes disease) 3. dominant negative mutations (product of the altered allele interfered with the normal allele)

Question 2

what is a gain of function mutaiton

Answer 2

new abnormal protien

Question 3

what is a loss of funciton mutation

Answer 3

loss of any protien from that allele

Question 4

what is dominant negative mutations?

Answer 4

the produced allele blocks the normal function of the normal allele

Question 5

what causes mutation?

Answer 5

1. Ionizing Radiation 2. Mutagenic chemicals (base analogues, intercalating agents)

Question 6

How does radiation cause mutaion

Answer 6

ionizing makes double stranded DNA breaks and base substitiustions; Non-ioniznig formation of pyrimidine dimers

Question 7

mutagenic chemicals how work?

Answer 7

alkylating agents (potent mutagens) or sacchrine (weak mutagen)

Question 8

how do we avoid many of our mutations?

Answer 8

DNA repair catches about 99.9% of the mutations. this involves several dozen different enzymes.

Question 9

Xeroderma pigmentosum

Answer 9

dry skin and extra pigmentation; this is a problem with DNA repair, and can’t repair the damage from the sun. 1000 times more likely to get cancer

Question 10

what does UV do to the DNA? and how is it repaired?

Answer 10

Thymine dimer is created and causes kink in the DNA; this is repaired by DNA excission repair. This involves seven different genes and mutation in any of them will give xeroderma pigmentosum.

Question 11

what is the normal mutation rate?

Answer 11

from 10 to the neg four to ten to the neg six

Question 12

what will affect the mutaiton rate?

Answer 12

the position of the gene or the age of the organism.

Question 13

what is a mutation hot spot?

Answer 13

a location that is more likely to mutate for example a cytosine to thyosine mutation.

Question 14

How would an older father affect mutations?

Answer 14

single gene mutations increase with paternal age, with each additional year of age there are about 2 more mutations.

Question 15

why don’t we see increased mutation in female eggs with age?

Answer 15

the female makes all of the oocytes as an embryo. for males we make the sperm after puberty every two weeks or so. at least 3/4 of mutations are transmitted by males. (800 rounds of reproduction vs. 23ish)

Question 16

what type of mutationis most likely to result in the complete loss of a protein product?

Answer 16

nonsense mutation

Question 17

what is gene frequency

Answer 17

the rate at wich a specific genotype appears in the population.

Question 18

how do we calc. the total genotype frequencies?

Answer 18

the number with the genotype/the total number in the population.

Question 19

how do we find the gene frequency of a specific allele

Answer 19

multiply the homozygotes by 2 add the number of heterozygotes and then divide by the population doubled!

Question 20

what is purpose of the hardy weinberg equilibrium

Answer 20

est. the genotype frequencies from gene frequencies and vice-versa

Question 21

what if we have a f(A) =p=.9 and f(a)=q=0.1 what is the probability of getting a heterzygote or either homozygote?

Answer 21

multiply the frequencies together, so the homozygotes are p squared and q squared, and the heterozygotes are the product of each probability. therefore: .81, .09, .09, and .01 for the respective probabilities. the total heterozygote of course would be 2pq.

Question 22

how can we predict the prevelence of a carrier based on the prevalence of occurance?

Answer 22

take the squareroot of the rate of the disease (this will be f(a)) then find the f(A) by doing 1-f(a). then do the 2pq equation and find the carrier frequency!

Question 23

how can you identify autosomal dominant disease?

Answer 23

everyone that has the allele will be phenotyplicaly express the disease. We don’t skip generations. It is common in both male and female (therefore not sex linked). male to male transmission (would rule out the x-linked inheritence) recurrence risk for typical mating is 50%

Question 24

how could we identify x-linked inheritence

Answer 24

won’t see it passed from male to male!

Question 25

what if there is no family history of a autosomal dominant disease?

Answer 25

There may be a new mutation in the sperm or egg (or the milk man effect).

Question 26

what if we see a mutation that is autosomal dominant and occurs repeatedly without a family history?

Answer 26

germline mosaicism. This is when they have the gene for the condition but not in most of their line.

Question 27

what is germline mosaicism?

Answer 27

cells to the ova and spermatozoa are a mixture of two or more genetically different cell lines.

Question 28

what are the characteristics of Achondroplasia

Answer 28

disproporionate reduced stature. chadracteristic facial features. lordosis. macrocephaly. caused by gain of function mutation in fibroblast growth factor receptor 3 gene. (FGFR3)

Question 29

what are some treatments of achondroplasia?

Answer 29

gene therapy through the addition of a ‘decoy receptor’, and surgery.

Question 30

what happens to a Loss-of-Function at the FGFR3 gene?

Answer 30

very, very tall individuals! so opposite of achondroplasia