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Lecture 14

HMB265H1 Lecture Notes - Lecture 14: Genetic Linkage, Phenotypic Trait, Frequency Distribution

Human Biology
Course Code
Naomi Levy-Strumpf, Stephen Wright

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Genetic Mapping, Association of Genetic Markers & Complex Traits
GWAS & Correlational Studies
- The false positive rates of such studies is very high
Quantitative Trait Loci → a region of DNA that is associated with a particular phenotypic trait
- A number of genes can have a major effect on phenotype
- We can identify the genes involved using genetic mapping and association of genetic
markers with the trait
- Statistical methods allow us to identify more than one QTL at a time
How do we determine which genes are involved in controlling the quantitative trait?
1. Make an informative cross between individuals that are “inbred” relative to each other
but differ at the trait(s) of interest
2. Determine the frequency distribution in the F2 generation
3. Use molecular markers to “genotype” the individuals, attempting to find markers that co-
segregate with the trait
4. Use a statistical method to determine if these markers are co-segregating (ie.
associating) wait the trait
5. Plot the degree of association (logarithm of odds - LOD score) on a linkage map
a. Odds Ratio (OR) = (probability of linkage) / (probability of no linkage)
b. LOD = Log (OR)
i. OD score must be 3 or larger to conclude that there is an association (ie.
there is a 99.9% chance the association is real)
a. Inbred lines are produced by scientists (ie. these strains do not occur in nature)
b. After we determine which loci are important, we can go out in nature and find
which loci are relevant in nature
EXAMPLE Variation in Tomato Fruit Size
1. Take one of the largest fruits and cross it with one of the smallest fruits
2. F1 generation will all be medium sized (heterozygotes); since there is no genetic
variation, as long as we keep the environment constant, all the fruit will be identical
3. F2 generation will produce a distribution of fruit size
a. Recombination events play a role
b. As long as we keep the environment constant, all the variation in tomato fruit size
is due to genetic differences
4. Using a gel, separate out the alleles from parent I and parent II from each F2 fruit
a. We typically want to observe the loci where parent I and parent II are
homozygous for different alleles
b. We want to see which allele each of the F2 fruit has to determine alleles that are
always present in the large fruit (but not in the small fruit) and vice versa
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