Gene mapping and linkage Flashcards
Homologous recombination:
Crossing over during meiosis I (prophase I)
Reciprocal process
Results in recombinant chromosomes
recombinant chromosomes
(non-parental chromosomes)
have different alleles than parental chromosome
Parental chromosomes Nonrecombinant chromosomes
Chromosomes that do not cross-over retain all the same alleles as the parent chromosomes
syntenic genes
Genes that are located on the same chromosome
What does independent assortment predict?
50% parental gametes and 50% non parental gametes
What happens when syntenic genes are located closely together?
Alleles may be unable to independently assort
Results in genetic linkage
Produces a distinctive pattern of gamete genotypes since they recombine less during meiosis
Denoted with a slash
What happens if syntenic genes are very far apart?
hat are very far apart do assort following Mendel’s law of independent assortmen
What is true for linked genes?
- Linked genes are always syntenic and located near one another on the chromosome
Syntenic genes that are very far apart will assort independently due to crossing over of homologous alleles - Genetic linkage leads to the production of different expected gamete frequencies
Greater number of parental gametes (combinations of alleles) than recombinants expected compared to independent assortment
Smaller number than expected for recombinant gametes - Crossing over is less likely to occur between linked genes that are closer
together than those further apart
Frequency of cross-over is roughly proportionate to the distance between a gene
How can you detect genetic linkage?
compare observed frequencies of gamete genotypes/progeny phenotypes with the expected frequencies under the assumptions of independent assortment
If linked:
Parental gametes will be produced more than by chance (»50%)
Progeny will therefore show parental phenotypes more than expected
Recombinant gametes will be produced less than by chance («50%)
If unlinked:
Parental gametes with parental alleles will be produced the same amount as recombinant gametes
Produces 4 genetically different gamete combinations in a ratio of 1:1:1:1
Compare independent assortment and genetic linkage
- 4 genetically different gametes are expected at 25% each when the genes assort independently
- when genes are linked parental gametes are much more frequent than expected
Complete linkage
o recombination at all occurs between linked genes
A dihybrid produces two equally frequent gametes containing only parental allele combinations
Ie no recombinant alleles
Drosophila and Diptera males exhibit complete linkage on homologous chromosomes
Incomplete linkage:
sulting recombination between the homologs produces a mixture of parental and recombinant gametes
more common
A dihybrid produces 4 genetically different gametes
Two are parental
Two are recombinants
The parental gametes have ~same frequency and equal >50% of gametes produced
The recombinant gametes have ~same frequency and equal <50% of gametes produced
recombination frequency
Rate of recombination of syntenic genes
𝑟 = 𝑛𝑢𝑚𝑏𝑒𝑟 𝑜𝑓 𝑟𝑒𝑐𝑜𝑚𝑏𝑖𝑛𝑎𝑛𝑡 𝑜𝑓𝑓𝑠𝑝𝑟𝑖𝑛𝑔/ 𝑡𝑜𝑡𝑎𝑙 𝑛𝑢𝑚𝑏𝑒𝑟 𝑜𝑓 𝑜𝑓𝑓𝑠𝑝𝑟𝑖𝑛𝑔
How can recombination frequency be interpreted?
- Crossing over occurs at a higher rate between genes that are further apart than those closer together
- Linked genes with higher recombination frequencies are more distant from each other than other linked genes with lower recombination frequencies
What did Bateson and Punnet discover?
Looked at flower colour and pollen grain shape
When studied separately, the two traits generated
3:1 phenotypic ratio in the F2 When studied as a dihybrid:
Crossed pure-breeding purple flowers and long pollen (PPLL) x pure–breeding red flowers and round pollen (ppll)
F1: all offspring with purple flowers and long pollen
F2: progeny showed more parental phenotypes
produced compared to recombinants
ie did not produce 9:3:3:1 ratio
Purple-long and red-round phenotypes»_space; purple-round and red-long phenotypes
Termed this “coupling” of the parental traits (i.e. PL and pl remained together)
What did Morgan find?
the parental phenotypes predominated
and
Parental phenotypes are produced when the gametes in the F1 female predominantly contain X-chromosomes with one of the original parental sets of alleles- sex linked trait so its based on crossing over in females
i.e. w+m+always went together and wm
Sperm are wm/Y
Recombination occurs on homologous X chromosomes- occurs when we don’t get the parental,
i.e. w+m or wm+
Morgans crossing over hypothesis
each homolog initially contains identical sister chromatids
a single cross over produces 2 recombinant chromatids
completion of meiosis produces 2 parental gametes and 2 recombinant gametes
Two-point test-crosses
Dihybrid F1 is crossed to a pure-breeding mate with recessive phenotypes
Morgan used eye colour (red: pr+, purple: pr) and wing size (full wing size: vg+, vestigial wing: vg
P: pr+ vg+/pr+ vg+ x pr vg/pr vg
F1: Red eyed and full wing (pr+ vg+/pr vg)
F2 (test-cross progeny): F1 females x pr vg/pr vg males
Males only contributed recessive alleles Females contributed 1 of 4 gamete
combinations- females controlled phenotype
i
Males have no cross-over on the X- chromosome, so only produces parental gametes- bc they have only one x chromosome wd don’t get crossing over between an x and y, if it has dominant allele it will produce dominant gamete, hemizygous
Females have a single cross-over event, producing 2 parental gametes and 2 recombinant gametes
Morgan expected a 1:1:1:1 phenotypic ratio in the progeny
Morgan actually observed 1:1 ratio in the parentals, and a 1:1 ratio in the recombinants BUT- similar to sex linked traits where if we compared between the sexes we didn’t see the 3:1 ratio but if we compared just females we saw it
Parentals»_space; recombinants
Parentals»_space; 50%
Recombinants «_space;50%
Cytological evidence of recombination
First demonstrated simultaneously by Harriet Creighton/Barbara McClintock in 1931 and Curt Stern (Droosphila)
Harriet Creighton and Barbara McClintock did it in corn (Zea mays)
Chromosome 9 homologs, using kernel colour (c1) and starch type (wx)
Microscopically, one homolog appeared normal and carried c1 and Wx
Other was altered with a knob (C1 end) and a translocated bit of chromosome 8 (wx end)
Observed a physical exchange of genetic information on chromosomes
Genetic Linkage Mapping
Smaller recombination frequencies indicated genes were closer together
Larger recombination frequencies indicated genes were further apart
Why should we be concerned about linked genes?
In humans, hereditary elliptocytosis
Elliptical instead of biconcave red blood cells
Usually autosomal dominant (E_)
Has variable penetrance and expressivity
Confers some resistance to malaria
The gene for HE is 4 map units from the gene that determines your Rh factor (R=+, r=-)
In humans, other examples
Hair colour and eye colour (usually)
Blond hair, blue eyes
Brown hair, brown eyes
Human height and shoe size
White fur in cats and deaf
Red hair and freckles
What is the max frequency you can get?
Max frequency you can get is 50% for complete independent assortment
chiasma interference (I)
Reduction in the observed number of DCOs relative to the number expected if the 2
SCO events happened independently
Indicates the influence of some process(es) that limit the number of crossovers in
short length chromosomes
Compares the frequency of observed DCO events with the number of expected DCOs
Represents the proportion of DCO that are expected but not produced in the
experiment
Negative interference
Sometimes, we can get more DCOs produced than expected
Interference will be 0 if observed DCOs = expected DCOs
What factors affect recombination in genomes ?
Differences in recombination due to sex
Differences in recombination due to age, temperature-dependent variation
Genetic hotspots and coldspots
Discuss why sex cause recombination to vary
In Drosophila, recombination is exclusive to females only and does not occur in males- bc females have 2 x
Heterogametic organisms have lower recombination in general
Male mammals (XY)
Female birds (ZW)
But not limited to just sex chromosomes!
In humans, recombination more frequent in females
Larger recombination map
Hotspots
Recombination occurs more often than average based on the number of nucleotides present
Coefficient of coincidence
Observed DCO / Expected DCO
