Week 5 Flashcards
Linkage, Chi Square Analysis, and Mapping
what does it mean for genes to be genetically linked
they are in close proximity to one another and tend to assort together
what does departure from a 1:1:1:1 ratio of F1 gametes indicate
two genes are on the same chromosome and not completely independent
how can we track genes of chromosomes
looking at the F2 offspring of a testcross
why are drosophila used to study genetics
- ~75% or known human disease genes have a similar gene match in the genome of fruit flies
- ~50% of fly protein sequences have a similar protein match in mammals
what are drosophila used to study
- neurodegenerative diseases: Parkinson’s, Huntington’s, Alzheimer’s
- research on processes of aging, diabetes, drug abuse
what indicates that genes are linked
parental combinations outnumber recombinant types
how do we represent the genotype of the F1 to keep track of parental allelic combinations
vgb/vg+b+ = alleles from father/alleles from mother
how are recombinant phenotypes formed
crossing over between non-sister chromatids
what does recombination frequency depend on
the distance between the gene pair
what does a higher recombination frequency indicate
the genes are further apart
what is an example of linkage in humans
Nail-patella syndrome gene is linked to gene I or ABO blood group
is linkage 100%
it is never 100%
what is the expected ratio of parental to recombination class number in unlinked genes
1:1:1:1
what is the chi square test used for in terms of genetic linkage
used to evaluate if two genes assort independently or are genetically linked
what is the chi square test method (in terms of genetics)
1) use the data obtained from a breeding experiment to determine the total number of offspring, the number of different classes of offspring and the number of offspring observed in each class
2) calculate the number of offspring that would be expected for each class if the null hypothesis were correct (% predicted x total number of offspring)
3) x2 = ∑(number observed - number expected)2/number expected
4) determine the degrees of freedom (df) = number of classes - 1
5) find the chi-square value and number of degrees of freedom on a chi square table, to determine a p value: the probability that a deviation from the predicted numbers at least as large as that observed in the experiment will occur by chance
6) evaluate the significance of the p value. the convention is that a 0.05 p value is the boundary between accepting and rejecting the null hypothesis. very small p values indicate a high degree of significant difference
what does a high p value from a chi square test indicate
the null hypothesis is correct; the deviation from expected is due to chance, the difference is not significant, and the genes are not linked
what is the null hypothesis for the chi square analysis for gene linkage
the genes are not linked (50% should be parent, 50% should be recombinant)
does sample size matter for the chi square test
yes, a large sample size is needed, the larger the better
what is the evidence of recombination
physical markers: cytologically visible abnormalities that make it possible to keep track of specific chromosome parts from one generation to the next
who proved recombination in 1931
Harriet Creighton and Barbara McClintock
what species did Creighton and McClintock use to study recombination
corn
who studies recombination with drosophila
Curt Stern
who first proposed that chiasmata were the points of crossing over that resulted in recombination
Thomas Hunt Morgan
who proposed that recombination frequency (RF), could be used as a gauge of the physical distance between any two genes on the same chromosome
A. H. Sturtevant
what is a map unit (m. u.)
1% RF = 1 centimorgan (cM) [cM is outdated]
what provides the basis of genetic mapping
recombination frequencies
what percentage are experimental recombination frequencies between 2 genes never greater than
50%
what does a recombination frequency of 50% between two genes represent
the genes are either not on the same chromosome or are at a great distance from each other on the same chromosome
how do you determine if genes are on the same chromosome if they are far apart
show linkage with other genes that lie between them
what is a limitation of two-point crosses
1) in crosses involving genes lying close together it may be difficult to determine the correct order
2) the actual distances on the map do not always add up for genes that are far apart
what are the advantages of three-point crosses
- faster and more accurate method for mapping genes
- allows correction for double crossovers
how do you conduct a three-point cross
establish a heterozygote (trihybrid) and do a test cross
how do you identify the classes in a three-point cross
- parental classes are the two with the highest frequency
- next two highest frequencies will be single crossover recombinants between the two most distant adjacent genes
- next two highest will be single crossovers between two closest adjacent genes
- two with the least frequency are double crossovers
how do you find map distances with a three-point cross
- pick 2 genes to start with
- sum all the offspring with recombinant phenotype
- divide by total number of offspring and multiply by 100
- repeat for each gene pair
- construct the map
- perform correction for the 2 genes that are the furthest distance apart
how many times do you need to add double crossovers when finding the distance between the 2 furthest genes
twice
how do you easily tell which gene is in the middle
the gene whose alleles have been “switched” between parental and double crossover classes
when does interference occur
when examining 3 genes that are relatively close together, when it is difficult to get double crossover events
how do you calculate interference
1 - coefficient of coincidence (frequency observed/frequency expected)
what does no interference indicate (interference = 0)
observed frequency of double crossovers is equal to the expected frequency
what does complete interference indicate (interference = 1)
there are no double crossovers observed
