10/26 Genetics

Question 1

allow us to determin the disance between two loci

Answer 1

crossovers

Question 2

analysis used to find the locations of disease cuasing genes

Answer 2

linkage analysis

Question 3

the nonrandom association of alleles at linked loci

Answer 3

linkage disequilibrium

Question 4

what does it mean that tow alleles are linked?

Answer 4

they are on the same chromosome and close to each other on that chromosome, and therefore they are usually inherited together.

Question 5

what does it mean to be unlinked but syntenic?

Answer 5

genes are on the same chromosome but they are far away on that chromosome and so they are not always inherited together.

Question 6

what is the purpose of linkage analysis

Answer 6

to figure out which parent the chromosome and the disease causing allele came from.

Question 7

what is saought in linkage analysis?

Answer 7

we seek markers that are closely linked to a disease-causing mutation

Question 8

the DNA sequence found on one member of the chromosome pair

Answer 8

haplotype

Question 9

how can we create unique haplotype from the haplotypes of the parents?

Answer 9

crossover can switch out sections of the haplotype of the parents to give unique combinations and a new haploytype.

Question 10

how can the realative location of an allele with another affect the rate of recombination?

Answer 10

alleles that are close to each other on the chromsome are less likely to experience recombination.

Question 11

job syndrome

Answer 11

severe eczema, recurrent skin and lung infections high serum IgE, absent T cell development, cuased by dominant negative STAT3 mutation.

Question 12

how could you use linkage analysis to determine that a disease causing mutation is on the same chromosome as a given marker?

Answer 12

see the inheritence of the marker following the occurence of the disease.

Question 13

how can we find how close the disease causing mutation is to a marker on the chromose?

Answer 13

look at the recombination rate (rate at which a child has the marker but not the disease) and then the recombination rate is equal to the centiMorgans (% of recombination) and 1cM is about 1 megabase (Mb) of DNA

Question 14

How to determine the recombination rate for an autosomal dominant disease locus?

Answer 14

look at the occurance of the disease in two generations and associate it with a specific marker (1,2,3 etc) and then see in the subsequent generation how often that marker allele occurs without the disease or the disease occurs without the marker. each of these would rep. a recombination and these then rep. the rate of recombination out of the total number of offspring

Question 15

calculated for each possible recombination frequency and tells which recombination frequency is most likely to be the true one.

Answer 15

Log of the odds of linkage vs. no linkage (LOD)

Question 16

what is the equation for LOD

Answer 16

LOD = log [ p(@=x)/P(@=.5)] where @ is the recombination frequency and p is the probability of a given recombination frequency and x is between 0 and .5

Question 17

how to inturpret the LOD

Answer 17

LOD > 3 is significant evidence of linkage (1,000 to 1 odds in favor of linkage or the numerator is 1000 times larger than the denominator in the LOD equaiton) while LOD

Question 18

the probability that a crossover occurs between two loci during meiosis. or a measure of the distance between two loci.

Answer 18

recombination frequency.

Question 19

how to interpret a LOD vs. recombination frequency graph?

Answer 19

the highest LOD corresponds to the most likely rate of recombination for this set of two loci

Question 20

what would a recombination rate of zero be?

Answer 20

then most likely there is no recombination…?

Question 21

how can you compare multiple families with a given disease? to get a significant location of the locci?

Answer 21

can combine LOD scores and recombination rates to get a total and sig. LOD

Question 22

what is linkage disequilibrium

Answer 22

closely linked loci will show non-random association of alleles at linked loci. when you get farther from the mutation then the assortment of alleles is more random, but close by you have the same alleles almost always.

Question 23

what if you have equilibrium of alleles and you want to know the prob. of a specific haplotype?

Answer 23

just do the “and” rule of probability for each of the individual frequencies for the alleles

Question 24

how could we identify linkage disequilibrium?

Answer 24

see a occurence of a haplotype that is not equal to the product of the individual alleles…look for linkage disequilibrium.

Question 25

what does linkage disequilibrium mean for the location of two alleles?

Answer 25

the two alleles are very close together on the chromosome.

Question 26

what is a polygenic mode of inheritance

Answer 26

many genes affecting a trait

Question 27

what is multifactorial inheritance?

Answer 27

there are multiple genetic and environmental factors that affect a trait

Question 28

how many factors affect height?

Answer 28

180 loci that affect height

Question 29

the threshold multifactorial model

Answer 29

many multifactorial traits and environmental factors are build up until you get above a threshold and then you will actually manefest disease.

Question 30

how can the multifactorial threshold model explain the difference in occurence in males and females?

Answer 30

the threshold is different for male and female, for example the threshold for a female may be higher so that there must be more “liability factors” for a female to be affected

Question 31

why would a female be more likely to pass on a pyloric stenosis?

Answer 31

they require more liability factors to get above the multifactorial threshold and so have more to pass off to offspring!

Question 32

why would females be more likely to pass on autism?

Answer 32

4:1 ration of male to female occurrence, so if a female has it they must have more liability factors that they can pass on to offspring.

Question 33

the factors for autism…number of genes.

Answer 33

more than a hundred different loci

Question 34

what is the multi-factorial threshold model

Answer 34

there are a great number of liability factors that can add to give a phenotype but that phenotype will not manifest unless you get above a threshold of a number of liability factors.