4.2 Haplotypes, population structure, and linkage

exam 2

Haplotypes

• linked combinations of SNPs that tend to be inherited together on a piece of DNA

• As generational time passes, it will get shorter and shorter until equilibrium

Recombination

• does not always happen at the same place

• overtime these —- events happening to chromosomes will cause the ‘blocks’ to shrink over generations

• part of DNA repair pathways in addition to meiosis

equilibrium point

a theoretical state where allele and genotype frequencies in a population remain constant from one generation to the next

average human haplotype block size

5-100kilobases (~60kb average point estimate)

Why do we need many SNPs across the whole genome (autosomes + sex chromosomes)

Population structure is complex, need broad coverage to confidently reconstruct haplotypes

Why are SNPs in a haplotype called "linked"

Because they're often inherited together as a unit

What are the haplotypes in this example alignment?

A) C-T-G, G-C-C, and T-T-A
B) A-T-G, C-A-T, A-C-G
C) C-T-T, A-T-T, C-T-G
D) G-C-C, T-C-C, A-C-C
E) C-T-G, A-T-A, T-T-C

A) C-T-G, G-C-C, and T-T-A

sub-haplotypes

new mutations arise after some time of segregating along a chromosome

haplotype group

a group of individuals of a species that shares a haplotype(s)

Based on what we’ve discussed today, which one of these scenarios represents more recent population admixture (mating) between the blue and red groups?
a) Left (Top)
b) Right (Bottom)

b) Right

Admixture (gene flow)

• is the transfer of DNA between different populations/closely related species via recombination

• recombination has not had a chance to break up the admixed haplotype blocks yet (tracts to be long)

• find smaller haplotype blocks because recombination has broken these regions down

Polymorphisms

• can use the shared variants to figure out the overall relationship between individuals in the populations and the populations themselves

• Recombination is a factor

• The specific combination of shared —- allows us to understand when in time they happened as well

Chromosome Linkage

the tendency for genes located physically close to one another on the same chromosome to be inherited together during cell division

test cross

a breeding method used to determine the unknown genotype (genetic makeup) of an organism that shows a dominant physical trait (phenotype)

iclicker

A)

Crossing Over

• have similar DNA sequences; homologous chromosomes exchange parts of their DNA during Meiosis 1

• also serves as a checkpoint to make sure each chromosome is paired up before the chromosomes divide

• creates recombinant chromosomes

Recombination Frequencies

• between two genes that are correlated with their distance from each other on a chromosome (helps maps chromosomes) aka the measure of how frequently recombination occurs between 2 loci

• far apart = more likely

• close together = less likely and can be 0 in very few cases

Recombination Frequency formula

Recomb.Freq. = recombinants/total offspring

1 Map Unit (M.U.) or centiMorgan = 1% Recombination Frequency

can be affected by chromosome size

Unlinked loci follow Independent Assortment

• Loci that are on separate chromosomes will assort independently

• DNA sequences far apart on the same chromosome assort independently due to recombination

Linked loci travel together during meiosis

DNA sequences close together on the same chromosome

Genetic Linkage

• the tendency for genes located close together on the same chromosome to be inherited together during meiosis

complete linkage; RF = 0 (no recombinant gametes are produced)

partial linkage: 0 < RF < 50% (some recombinant gametes are produced, but fewer than you would expect)

unlinked: RF are = 50%

Linked: RF <50%

Homologous Recombination

• During Prophase I, homologous chromosomes are paired together tightly through a process called synapsis

• Homologous regions of chromatids are cut (“restricted”) and pasted (”ligated”) back together

• results in the exchange of DNA between homologous chromosomes

How many recombination events (crossovers) occurred to produce these gametes?
a. 0
b. 1
c. 2
d. 3
e. 4

b. 1

How many recombination events (crossovers) occurred to produce these gametes?
a. 0
b. 1
c. 2
d. 3
e. 4

c. 2

Single Crossover vs. Double Crossover

Single crossover: 1x
Double crossover: 2x

• Recombination will always extend to the terminal end of the chromosome