Week 4

Question 1

How can one detect genetic linkage

Answer 1

• Quantify how alleles are associated in gametes or in offspring
• Compare to expectations based on independent assortment of alleles at each gene

Question 2

Recombination Frequency

Answer 2

r = number of recombinants/ total number of progeny
- The recombination frequency is positively correlated with the physical distance between two genes on a chromosome
- The longer the distance between genes, the more recombination
- r less then close, r more further away

Question 3

What is a “centimorgan”?

Answer 3

One centimorgan is the distance between two positions on a chromosome that has a 1% chance of recombination event during meiosis

Question 4

Three-point test cross

Answer 4

• One parent is usually a ‘trihybrid’ and the other is usually homozygous for recessive alleles at all three loci
• The rarest progeny phenotypes result from double crossovers

Question 5

Recombination Interference

Answer 5

In most experiments with trihybrid crosses, the number of observed double crossovers is less than expected
- The synaptonemal complex inhibits complex from forming near by
- less than the product of the two single crossover events
I = 1-c
- higher I indicates more interference

Question 6

Coefficient of Coincidence

Answer 6

c= observed double crossovers/ expected double crossovers

Question 7

Why does mapping genetic differences based on observed recombination result is underestimating actual genetic distances

Answer 7

• Double recombination events often are not detected
• The longer the distance, the greater the difference between observed and expected
• Double recombination events can be missed if they don’t change linkage between pairs of markers

Question 8

Factors affecting recombination frequency

Answer 8

• Can happen more frequently in genomic regions known are recombination hotspots compared to recombination cold spots
• Can be influenced by environmental factors (age, temp, diet)
• Natural selection can affect recombination - higher recombination rates may be adaptive
• Rates may differ between sexes (more recombination in oogenesis)
• Locations differ between sexes

Question 9

Genetic mapping in males vs females

Answer 9

Smaller in males than females, even when physical maps are the same, due to decreased rates of recombination

Question 10

Allelic Phase

Answer 10

Refers to which alleles are physically attached to each other on the same chromosome
- often disease-causing genes are identified by identifying linked polymorphisms

Question 11

Mapping variants associated with a phenotype

Answer 11

If a marker locus is closely linked to a disease-causing gene, specific alleles at the marker locus would be significantly associated with the disease-causing allele at the population level

Question 12

How does one do a Genome-Wide Association (GWAS) study

Answer 12

• Sequence complete genomes of as many people as possible that do and do not have a phenotype of interest
• Test whether single nucleotide polymorphisms tend to be found in individuals with the disease more frequently than expected

Question 13

How do GWAS results differ and why?

Answer 13

• Variation in statistical power: Different sample sizes
• Variation in biology: Many genes with small effect sizes versus on or two genes with large effect size that influence the trait
• Variation in environmental influences: The more environmental influence, the weaker the genetic association of causative genetic variants

Question 14

Logarithm of the odds

Answer 14

LOD score is a calculation that is used to evaluate whether genetic variation at two genes is genetically linked
Lod score = log10 *probability that two loci are linked/probability that two loci are not linked