Linkage Flashcards
Concept of genetic linkage
Genes on the same chromosome should segregate together. They are physically linked, so they should theoretically be inherited as a single unit.
This isn’t true in practice due to crossing over.
Linked genes
genes on the same chromosome; segregate together
linkage can be complete or incomplete
Cause of incomplete linkage
recombination of the alleles on a chromosome can ‘break’ the linkage between two genes
an unexpected allele is inherited at a loci that crossed over
two genes exist between a single homologous pair, and no crossing over occurs
two parental gametes, representing the two gene copies on homologous chromosomes
genes are inherited together on the chromosome
Complete linkage
genes are too close to be separated by crossing over, so they are always inherited together
crossing over unlikely to be detected
produces only parental gametes in equal proportions
Parental gametes
a gamete that hasn’t undergone recombination; contains parental genotypes
two genes exist between a single homologous pair, and crossing over occurs
four different gametes
- two recombinant chromatids
- two parental chromatids
Frequency of crossing over between two linked genes
proportional to the distance separating the loci along the chromosome
crossing over is equally likely to happen anywhere along the chromosomal length
far apart = more
closer together = less
FREQUENCY genes far apart
Wider length to work with
more crossovers able to happen in this length
higher frequency of crossovers, and thus of recombinant gametes
FREQUENCY genes close together
Very narrow length to work with
fewer crossovers likely to happen in this length
lower frequency of crossovers, and higher proportion of parental gametes
FREQUENCY loci very far apart
the number of recombinant gametes reaches 50%
With 50%, a 1:1:1:1 ratio of the four gametal types occurs (two parental and two recombinant)
transmission of these linked genes is indistinguishable from that of two unlinked genes
Linked gene designations
Each set above the line is one homolog, and below the line is the other homolog.
In the above example, P1 is a cross between two homozygotes for both traits.
Linkage ratio
For two heterozygotes for completely linked genes and the same chromosomal arrangement: 1:2:1
These heterozygotes are the F1 of truebreeding AB/AB and ab/ab, or etc
Interpret linked gene designation
parent 1 has hv+ bw / hv+ bw
parent 2 has hv bw+ / hv bw+
With a large number of mutant genes investigated, what can be done?
genes located on the same chromosome show evidence of linkage
“linkage groups” can be established for each chromosome
Linkage groups
group of linked genes that are located on the same chromosome
number of linkage groups corresponds to haploid # of chromosomes
Concept behind genetic mapping
When investigating two genes on the same chromosome, the percentage of recombinant gametes depends on the distance between the two genes on the chromosome
This can be used to produce maps of loci on a chromosome
Genetic maps show linear order and relative distances between gene loci on a chromosome
Morgan’s discoveries with X-linked genes
Crossing over leads to recombinant gametes, causing unique phenotypes
Linked genes exist in a linear order along the chromosome
Distance between genes relates to recombination frequency
How to “map” genetic sequence using frequencies
recombination frequencies between linked genes are additive
Yellow-white are very close together, as they have a low frequency of recombination.
White-miniature are apparently far apart, due to their high frequency.
Yellow-miniature are farther apart than white-miniature.
Because W-M < Y-M, W-M must be between these two genes.
Map unit
Distance between genes
1 map unit (mu) = 1% recombination between 2 genes
Recombination %
number recombinant offspring / total # of offspring
Practical use of single crossovers
used to determine the distance between two linked genes
How can genes be incompletely linked?
recombination of the alleles on a chromosome can ‘break’ the linkage between two genes
an unexpected allele is inherited at a loci that crossed over
If SCO doesn’t occur between genes A and B
Their linkage is unbroken and parental gametes are formed. The exchange is undetected
If SCO occurs between genes A and B
Their linkage is broken. The exchange separates the alleles, resulting in recombinant gametes. These are detectable.
Only two nonsister chromatids are involved in the crossover; the other chromatids are parental
4 gamete genotypes
% crossover in SCO
% crossover is 2x % of recombinant gametes
How many SCOs occur in meiosis and why?
limited # of crossover events occur
These events occur randomly
In a SCO between 2 homologs
only 2 chromatids are involved in the SCO
the other 2 chromatids are parental
even if SCO occurs 100% of the time, recombination is only observed in 50% of potential gametes
Limit of observed recombination
even if SCO occurs 100% of the time, recombination is only observed in 50% of potential gametes
only half the chromatids actually recombine
only half the gametes will be recombinant
When is crossing over 100%
When two linked genes are very far apart (more than 50 mu), a crossover can be expected to occur between them in 100% of tetrads.
Each tetrad would yield equal proportions of the four gametes, as in independent assortment.
Multiple crossovers prob, detection, use
As the distance between loci increases, multiple crossover events may happen
To detect multiple crossovers, multiple loci must be monitored
This allows us to determine the sequence of genes
Concept & requirements of double crossover
two separate exchanges of genetic material occur simultaneously
3 loci / gene pairs must be investigated
each gene pair must be heterozygous
Physical changes of double crossovers
DCO cross over between 1st&2nd, and then cross back between 2nd&3rd. This separates the gene in the middle from the other two genes.
Probability of DCO
Frequency much lower than SCOs due to lower probability
the probability of this is equal to the product of the individual probabilities
Product of DCO
Two parental gametes and two double-crossover recombinant gametes are produced.
3 Point Mapping concept
Three loci can be mapped in a trihybrid test cross
3 Point Mapping rules for cross
Genotype of one parent is fully heterozygous, and responsible for producing detectable recombinant gametes
Cross is set up as a test cross
The offspring’s phenotypic class reflects the gamete genotypes from the heterozygous parent
Gametic production of the 3pt heterozygous parent
The heterozygous parent produces 4 types of gametes with regards to crossover status.
NCO (noncrossover / parental)
SCO1 (single crossover between first and second loci)
SCO2 (single crossover between second and third loci)
DCO (two crossovers - one between first and second, one between second and third)
There are two gametic genotypes for each category, for a total of 8 genotypes.
3pt heterozygote how many genotype classes
With 3 genes and 2 alleles, the heterozygote can produce 8 classes of gametic genotypes.
These 8 gametic genotypes determine 8 possible phenotypic classes in testcross offspring.
2 NCO
2 DCO (1st&2nd & 2nd&3rd)
2 SCO1 (1st & 2nd)
2 SCO2 (2nd & 3rd)
[3pt mapping] Determining gene order
Find parental and DCO classes.
Compare alleles in DCO classes with those in NCOs to find middle gene
Write genes in an arbitrary order, with middle gene in middle
How to find middle gene in 3pt mapping
Each class of DCOs should be like one of the NCO for 2 loci, and should differ for one loci.
The different loci is the middle one.
How to find SCO classes in 3pt mapping
Compare alleles in SCO classes with those in NCOs
If SCO class is different from NCO only in 1st gene, it’s a crossover between 1st & 2nd genes (SCO1)
If differs only in 3rd gene, it’s a crossover between 2nd & 3rd genes (SCO2)
Gene proportions in 3pt mapping
NCO: 2 most numerous phenotypes
DCO: 2 least numerous phenotypes
The noncrossover phenotypes exist in the greatest proportion.
The double crossover phenotypes are present in the least numbers. This is because DCOs are extremely low probability.
Remaining phenotypic classes represent SCO categories.
Interference concept
In theory, DCO proportion can be predicted through the probabilities of both SCO classes
However, The observed DCO frequency is less than the predicted frequency due to interference
Interference definition
One crossover interferes with additional crossovers in nearby regions.
Crossovers do not occur independently.
Interference calculation
Determine the coefficient of coincidence (C)
Interference = 1 - C
Coefficient of coincidence
ratio of observed DCOs to expected DCOs
o / e
How to obtain expected DCOs in interference calculation
Multiply product of two SCO probabilities by total # progeny in the cross
Complete interference
no DCOs occur
C=0
I=1
Positive interference
fewer DCOs are observed than expected
I > 0
C < 1
Negative interference
more DCOs observed than expected
I < 0
C > 1
Maize in relation to genetics
Provided evidence for the physical exchange of genetic material
Maize strain has a special chromosome 9
Maize chromosome 9
One of the homologs has 2 markers visible under microscope: knob & long translocated segment
carries 2 genes (kernel color (color C, colorless c), kernel texture (wavy, starchy Wx))
one allele of each was associated with a marker
SCEs
Crossing over also happens in mitosis, but because replicated chromosomes are genetically identical, nothing happens
How to detect SCEs
Detected via staining sister chromatids with BrdU (bromodeoxyuridine)
produces harlequin chromosomes
What increases frequency of SCEs
Agents like viruses, radiation, mutagens induce chromosome damage and increase frequency of SCEs
BrdU
Used to detect SCEs, staining causes segment swaps in mitosis to produce patchy-looking harlequin chromosomes
Harlequin chromosomes
stained sister chromatids involved in SCEs have patchy appearance
