Chapter 5 - Genetic Linkage

Detecting genetic linkage

Examine how alleles are associated in gametes or in offspring & determine whether frequency is consistent with independent assortment

Recombination frequency (r)

# of recombinants/total number of progeny

More recombination

Means longer distance between genes

Recombination frequency

Positively correlated with physical distance between genes

Double recombinant

Rarest result from a trihybrid cross (AbC or aBc)

Coefficient of coincidence

Observed double crossovers/expected double crossovers

Centimorgan (cM)

1 = distance between two positions where chances of recombination are 1%

Recombination hotspots

More frequent recombination

Recombination cold spots

Less frequent recombination

Recombination

Varies between sexes, environmental factors, natural selection

Chromosome tips in males

Experience more recombination

Human males

Genome-wide recombination rate is lower

Smaller genetic map for males

Results from lower genome-wide recombination

Allelic phase

Which alleles are physically attached to each other on the same chromosomes

Disease causing genes

Identified by identifying linked polymorphism
E.g. Disease causing D might be frequently associated with A1 and B1. Because of recombination, A1 & B1 sometimes may not be associated with D, and D may not always be associated with A1 & B1

Single nucleotide polymorphism (SNP)

Single nucleotide changing can cause change in individuals & populations

Mapping variations

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

Genome Wide Association Study (GWAS)

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

Bipolar disorder

Markers show genes appear more commonly in people with the disorder

Statistical power

Affected by sample size

Biology affects results through

Many genes vs one or two influencing traits

Environment influences results by

More environmental influence = less genetic association of causative genetic variants

LOD score (logarithm of the odds)

Log(10) x (probability that two loci are linked/probability that two loci are not linked)