M2 L10: chromosome mapping in eukaryotes

Question 1

what is genetic linkage

Answer 1

when genes are on the same chromosome and close enough so that they do not assort independently (inherited as a single unit)

Question 1

what are syntenic genes? Are they always linked?

Answer 1

syntenic genes are genes on the same chrom

they are not always linked, only if close to each other

Question 2

what are recombinant chromosomes

Answer 2

homologs that have exchanged alleles

Question 3

how do recombinant chromosomes allow for gene mapping

Answer 3

recombination is random, constant probability across whole chromosome (frequency of crossover roughly proportional to bp between genes)

genes that are closer together have less recombination between them

genes that are father apart have more recombination between them

Question 4

does linkage obey independent assortment? how many parental and recombinant chromosomes are produced?

Answer 4

does not obey independent assortment

more parental combinations produced than would be expected from independent assortment

Question 5

how to detect genetic linkage

Answer 5

examine chromosomal combinations in F1 hybrids (usually from a testcross)

linkage if parental combinations are more frequent than recombinants (determine deviation from expected frequencies w/ chi square test)

Question 6

complete vs incomplete linkage?

Answer 6

complete: NEVER recomb between genes

incomplete: sometimes recomb between genes (but parental types still more common)

Question 7

how to quantify linkage

Answer 7

r (recombination rate)

r = # recombinants / total offspring

r = 0.5, no linkage

r < 0.5, linkage

Question 8

who first observed linkage in peas? what did they find?

Answer 8

william bateson and reginald punnett

dihybrid cross w/ flower color and pollen shape –> not 9:3:3:1 –> purple / long alleles “coupled”

Question 9

who observed linkage in fruit flies? What did they find?

Answer 9

thomas hunt morgan

white eyed mini wing F crossed w/ WT M (both x-linked genes) –> all F1 males recessive for both traits, all F1 females double hets

F1 x F1 should give 1:1:1:1 –> actually observed more parental phenotypes (white/mini and red/full) than recomb (white/full and red/mini)

Question 10

what’s the crossing over hypothesis

Answer 10

recombinant phenotypes (red/mini and white/full) can only arise if genes are physically exchanged between chrom –> there must be X recomb in female meiosis

Question 11

whats a two point test cross

Answer 11

cross of pure breeding parentals (double dom or double rec for 2 traits - AABB x aabb) –> get F1 offspring

Cross F1s (all hets) to homo rec –> count parental vs recomb phenotypes in F2s –> calc recombination rate to get rel distance between genes (A and B)

Question 12

3 key takeaways from 2pt test crosses

Answer 12

1) genetic linkage is a phys relationship between genes near each other on same chrom

2) when genes are linked, sig more than 50% of gametes have parental allele combos

3) recomb rate between pairs of alleles is proportional to distance between genes

Question 13

who developed the first genetic map? what map units did they use?

Answer 13

alfred sturtevant (under morgan)

map units were 1% recomb rate = 1 map unit (centiMorgan / cM)

Question 14

what is 3 pt mapping

Answer 14

extension of 2pt mapping, can map rel gene order/distance of 3 genes

Question 15

how many gametes can you make in 2pt mapping? 3pt?

Answer 15

2pt: 4 gametes (2 parental, 2 recomb)

3pt: 8 gametes (2 parental, 4 single recomb, 2 double recomb)

Question 16

how to solve 3pt mapping problems?

Answer 16

1) identify parentals (most)

2) identify double crossovers and gene in the middle (smallest #s and allele that’s swapped relative to parentals)

3) identify single crossovers (remaining 4)

4) calculate relative distances
- r1 = (single crossovers + double crossovers) / total

• r2 = (single crossovers + double crossovers) / total

Question 17

what is interference?

Answer 17

problem in 3 pt mapping where double crossovers occur less than the product of the single crossovers (1-c where c = coefficient of coincidence)

c = obs double crossvers / expected double crossovers

expected double crossovers = (single/total)(single/total)(total offspring)

I = “X% fewer double crossovers than expected under independence”

can have neg interference (freq of double recomb higher than expected)

bc crossovers can’t occur in close proximity to e/o

Question 18

how to determine gamete frequencies from a map

Answer 18

% parental = (prob no crossover between A and B)(prob no crossover between B and C)
(1-x)(1-y)

% AB crossover = prob (crossover between A and B)(prob no crossover between B and C)
(x)(1-y)

% BC crossover = vice versa
(1-x)(y)

% double crossover
(x)(y)

DIVIDE BY 2 FOR FREQUENCY OF INDIVIDUAL GAMETES

Question 19

what’s a flaw of genetic maps

Answer 19

underestimate phys distance between genes (r isn’t entirely proportional to distance bc double crossovers w/o an intervening marker are not detected)

underestimate r

Question 20

factors that can affect recombination rates

Answer 20

sex: no recomb in male diptera, heterogametic sex usually has less recomb

age: less recomb in older flies

temp: less recomb outside optimal temp range

diet: less recomb w/ poor diet

location in genome: hot and cold spots

Question 21

what are recomb hotspots? what is one hot and cold spot? what drives them?

Answer 21

places w/ more or less recomb than expected

hotspot between cdc15 and FLO1 –> think genes farther than actual

coldspot between spo7 and cdc15 –> think genes closer than actual

driven in humans/mice by seqrecognized by PRDM9 (protein that initiates crossing over)

PRDM9 binding sites dispersed across genome (preserves general relationship between recomb rate and distance)

[hot/cold spots even e/o out]

Question 22

what are the 2 evo benefits to crossing over

Answer 22

1) put more deleterious alleles on the same chrom –> more concentrated, make a few deleterious chromosomes

2) put more beneficial alleles on the same chrom, don’t have to wait for beneficial mutation to occur randomly

Question 23

what’s linkage disequilibrium

Answer 23

excess of certain allelic combos in a pop

Question 24

2 causes of linkage disequilibtrium

Answer 24

1) migration: two pops both fixed for different genotypes –> one migrates into the other –> can have lots of genotypes from recomb but currently only have 2 genotypes

mating will lower linkage disequilibrium

(ex. ab migrates into AB –> only have ab and AB but could also have aB and Ab)

2) selection: adaptive mutations become more frequent and nearby mutations hitchhike –> excess of chromosomes w/ the same beneficial and neutral muts

recomb will decrease their co-occurrence