Chapter 5: Genetic linkage and mapping

what are genes on the same chromosome called

syntenic genes

how are recombinant chromosomes made

when alleles of syntenic genes are reshuffled during crossing over

what are linked genes

syntenic genes that are so close together that their alleles cannot sort independently

• not all syntenic genes are linked

• sorting independently means equal chance of

what are genetic linkage maps

plots the positions of genes and their relative distances from each other on chromosomes

complete genetic linkage

• when genes are located so close together on the same chromosome that they are virtually never separated by crossing over

  • results in alleles for these genes always being inherited together in their original parental configuration

• lack of recombination means offspring only display the original combinations of traits found in the parent generation

• rare in nature but common in male fruit flies where crossing over does not occur

• linked or in linkage diseqm

  • some recombination does occur between incompletely linked genes

recombination frequency in the linkage frequencies

• unlinked genes

  • 50%

• complete linkage

  • 0%

• linked genes

  • less than 50%

how to detect linkage?

• quantify how alleles are associated in gametes or in offspring

• compare to expectations based on independent assortment of alleles at each gene

what is the recombination frequency ( r )

• positively correlated with physical distance between two genes on a chromosome

• the longer distance between genes, the more recombination occurs

• smaller value of r=closer the genes are to one another

  • vise versa

what is the patten between the observed recombination events and expected

• double recombination events are often not detected

  • especially considering the longer the distance between genes, the more recombination events are likely to happen

  • hence the greater difference between observed and expected

what are the factors that influence recombination and the effects

• happens more frequently in some genomic regions

  • called recombination hotspots vs coldspots

• influenced by environmental factors (age, temp, diet)

• natural selection may affect recombination; higher recombination rates may be adaptive

  • recombination can help decouple deleterious mutations from the favoured mutation

recombination differences in sexes

• recombination occurs more in oogenesis

  • leads to a smaller genetic map for males, even in autosomes

  • same chromosome is smaller in males than in females due to recombination being less frequent

• locations differ between the sexes

  • more freq on chromosome tips in males than females

what is an allelic phase

• refers to which alleles are physically attached to each other on the same chromosome

• a heterozygous genotype can be captured by different possible phases

Allelic phase describes the arrangement of alleles on a pair of homologous chromosomes.

In other words:

👉 It tells you which alleles are on the same chromosome.

There are two possible phases for a heterozygote (a gene from each parent) with two genes (A and B).

1. Coupling (cis) phase
Both dominant alleles are on one chromosome, and both recessive alleles are on the other:

• AB / ab

2. Repulsion (trans) phase
Each chromosome has one dominant and one recessive allele:

• Ab / aB

What do allelic phases help with?

• often disease-causing genes are identified by identifying linked polymorphisms

• if a disease causing allele is usually closely linked with other alleles (cis or trans to it), we can use that to identify the disease if recombination removes these genes or separates it

• the closer the markers are to the disease causing allele, the smaller R

  • more stable the phase and better prediction

• if the marker isn’t often with the disease causing allele, we know that they are further apart than expected on the genetic map as alleles really close do not undergo recombination

what is GWAS (genome-wide association study)

the discovery of associations between variations in our genetic code and certain phenotype of interest

• test whether single nucleotide polymorphisms tend to be found in individuals with the disease more frequently than expected

how to perform a GWAS

• for each SNP, the p-value and slope (represents the effect size) are recorded

• done on computer program as this is done for millions of SNPs

• these programs also allow for the addition of covariates (other attributes that may affect the phenotype of interest)

  • age, sex, etc

How can GWAS results differ (in this case its for coronary artery disease and crohn’s disease)

Variation in:

• statistical power

  • larger sample size means higher powered GWAS

• biology

  • one or two genes with large effects vs many genes with small effects

• environmental influence

  • the more enviornmental influence (and the lower the heritability), the weaker the association of genetic variants