M2 L10: chromosome mapping in eukaryotes Flashcards
what is genetic linkage
when genes are on the same chromosome and close enough so that they do not assort independently (inherited as a single unit)
what are syntenic genes? Are they always linked?
syntenic genes are genes on the same chrom
they are not always linked, only if close to each other
what are recombinant chromosomes
homologs that have exchanged alleles
how do recombinant chromosomes allow for gene mapping
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
does linkage obey independent assortment? how many parental and recombinant chromosomes are produced?
does not obey independent assortment
more parental combinations produced than would be expected from independent assortment
how to detect genetic linkage
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)
complete vs incomplete linkage?
complete: NEVER recomb between genes
incomplete: sometimes recomb between genes (but parental types still more common)
how to quantify linkage
r (recombination rate)
r = # recombinants / total offspring
r = 0.5, no linkage
r < 0.5, linkage
who first observed linkage in peas? what did they find?
william bateson and reginald punnett
dihybrid cross w/ flower color and pollen shape –> not 9:3:3:1 –> purple / long alleles “coupled”
who observed linkage in fruit flies? What did they find?
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)
what’s the crossing over hypothesis
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
whats a two point test cross
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)
3 key takeaways from 2pt test crosses
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
who developed the first genetic map? what map units did they use?
alfred sturtevant (under morgan)
map units were 1% recomb rate = 1 map unit (centiMorgan / cM)
what is 3 pt mapping
extension of 2pt mapping, can map rel gene order/distance of 3 genes
how many gametes can you make in 2pt mapping? 3pt?
2pt: 4 gametes (2 parental, 2 recomb)
3pt: 8 gametes (2 parental, 4 single recomb, 2 double recomb)
how to solve 3pt mapping problems?
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
what is interference?
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
how to determine gamete frequencies from a map
% 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
what’s a flaw of genetic maps
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
factors that can affect recombination rates
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
what are recomb hotspots? what is one hot and cold spot? what drives them?
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]
what are the 2 evo benefits to crossing over
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
what’s linkage disequilibrium
excess of certain allelic combos in a pop
2 causes of linkage disequilibtrium
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
