WEEK 3: LINKAGE, RECOMB, AND GENETIC MAPPING Flashcards
if two genes are linked on the same chromosome will they assort independently?
- NO!!
What do genetic maps show?
- The position of genes (loci) in relation to each other along the chromosomes
What are 4 reasons why generating genetic maps are good?
- Can determine whether mutations affect different genes or not (mapping provided the first indication that there were two forms of Haemophilia)
- Can CLONE genes using their map position (e..g CFTR gene)
- Enhances our ability to predict inheritence patterns (counselling)
- Very useful for genome sequencing projects
What is one form of Haemophilia linked to (gene) ?
- The colour blindness gene
What are genes on the same chromosome said to be?
- Linked
What is the F2 ratio for two genes on two different homologous pairs of chromosomes?
- 9:3:3:1
Does exchange occur in linked genes?
- NO - no crossing over
Which structure on the chromosome is the physical evidence of crossing over during meiosis?
- Chiasmata - evidence of crossing over in Meiosis I
Can linked genes be separated by recombination in meiosis?
- YES
If the genes assort independently, what is the predicted phenotypic ratio in the test cross progeny?
- 1:1:1:1 (unlinked)
What is the coupling phase known as?
- When the dominant alleles of the different genes stayed together as did the recessive alleles
What is the repulsion phase known as?
- Where one dominant and one recessive allele stay together e.g. A and b stay together and a and B stay together
Which test can be used to distinguish between independent assortment and linkage?
- Chi squared test
What is the recombination frequency?
- The number of recombinants OVER the total progeny *100
If crossovers never occur between two gene loci what is the recombination frequency (RF)?
- 0
What is the maximum RF?
- 50%
If one crossover always occurred, then what would the RF be and what is this the same for?
- 50%
- The same for independent assortment
Why is the RF never >50?
- because there are always (nearly) two non-crossover gametes from a single meiosis
What can a testcross be used to measure and explain it?
- RF
- Heterozygote for two or more genes and homozygous recessive for all genes –> can determine whether recombination has occurred during gamete formation in heterozygous parent
With test crosses to measure RF, are we looking at the gametes for one or both parents?
- Only 1 parent
In a test cross, what do the phenotypes of the zygotes equal and what does this tell us?
- The genotypes of the heterozygous parent gametes
- Tells us that the phenotypes of the offspring tells us the number of RECOMBINANT and parental gametes.
If two genes are very close together is there a small or large chance of crossover?
- A SMALL chance of crossover
if two genes are FAR APART is there a small or large chance of a crossover occurring?
- A LARGE chance with lots of recombinant offspring
What is the percentage of recbominant offspring correlated with and what is this called?
- The distance between two genes
- Called the MAP distance
What is map distance defined as?
- The distance between two loci that will generate 1% of recombination between them
- Units are Map UNITS (mu)
What do double crossovers make long distances in terms of accuracy?
- They make them inaccurate
- Double crossovers cancel out the recombinants for distant markers
Does recombination frequency= crossover frequency?
- NO
- recombination frequency= recombinant gametes in progeny
- crossover frequency= two sister chromatids
When genes are very far apart on the same chromosome, why does the RF no longer accurately measure the distance between them?
- Because of double recombinants
At what RF % do we need to do a statistical test (Chi2) to determine if the genes are linked or not?
- > 25% need to do a test for linkage
What is the GENERAL genetic hypothesis?
- That the genes are UNLINKED and we do the chi squared test to see if they are linked or not
- Linked= we do not support
- Unlinked= we support
Why is mapping human genes difficult and from this, what is it restricted to analysis of ?
- Because of the small numbers of progeny.
- Can’t perform desired number of crosses
- Restricted to analysis of pedigrees
What is the Coefficient of coincidence (C)?
- the observed number of doubles (crossovers)/ expected number of doubles
What is positive interference?
- Where the observed number of crossovers was less than the expected
- One crossover interferes with another occurring nearby
- Thus reducing the number of double recombinants
What is the equation for the degree of interference?
- 1- coefficient of coincidence (C)
What does a degree of interference (I) of 0.6 mean?
- That 60% of second crossovers were “prevented” from occurring
What are the C and I values for no double crossovers resepctively?
- 0 and 1
What are the C and I values for the same number of double crosovers expected respectively?
- > 1 and <0
What are the C and I values respectively for more double crossovers than expected?
- > 1 and <0
What does an I value of less than 0 mean?
- the occurrence of one crossover occurring is causing ADDITIONAL crossovers to occur
Can crossover occur in MITOSIS??
- YES occasionally
- Produces new combinations of alleles
What happens if MITOTIC crossover occurs early in development?
- It will give rise to a patch of tissue with characteristics different to the rest –> MITOTIC CLONE
What do mitotic clones allow for?
- Developmental genetecists to follow cell line lineages (providing that the gene product stays within the cell–> genes action is autonomous)
What does crossover in MITOSIS play a role in?
- Important in cancer–> tumour suppressor genes
What does mitotic recombination allow us to create?
- Create mosaic animals (basically heterozygous) –> but have mutant tissues
What is intragenic recombination and which organisms does it occur in ?
- Where the unit of recombination is smaller than the gene and recombination is measured between two close genes.
- Occurs in all organisms but hard to measure
