Linkage genes and genetic recombination

Linkage genes and genetic recombination

TABUK UNIVERSITYTABUK UNIVERSITY

Faculty of Applied Medical SciencesFaculty of Applied Medical Sciences

Department of Laboratory TechnologiesDepartment of Laboratory Technologies

AY: 1433-1434/2012-2013 Lecture 5

Mendel’s law of independent assortment

• Knowledge of which allele has been inherited at one locus gives no information on the allele has been inherited at the other locus

S/s Y/y

SY Sy sY sy

25% 25% 25% 25%

Mendel’s law of independent assortment: Most pairs of genes assort independently

S Y

s y

S Y

s yGametes

S y

s YNon parental types

Segregation

Parental types

BUT……

• Genes that are located close to each other on the same chromosome are linked and usually travel (segregate) together during meiosis (not independently=dependently).

Genes linkage• Makes an exception to Mendel’s law of

independent assortment.• Linkage ≠ independent assortment

Discovery of Linkage

• In 1900, Mendel’s work was re-discovered. Bateson and Punnett were testing his theories with as many different genes and organisms as possible.

• Individuals with new combinations of genes(non parental) are called recombinants.

• Recombination is a result of Crossing Over

Crossing over occurs during Prophase 1 of meiosis.

Crossing Over: a random event

• When two homologous chromosomes were positioned side by side, they “synapse”, which means to pair closely with each other. DNA strands from the two chromosomes are matched with each other.

• Thus, sections of the two chromosomes might cross, break, and reattach.

Mechanism of crossing-over (in PROPHASE I of meiosis)

Crossing over (exchange) occurs between two non sisters chromatids (each chromatid from one chromosome)

Recombination Process

The Process of Recombination, animated version (Attached youtube video)

What is Linkage?• Linkage occurs when two genes are close to each other on the same chromosome. • Genes far apart on the same chromosome assort independently: they are not linked. • Linkage is based on the frequency of crossing over between the two genes.

Frequency of Crossing Over= Recombination frequency = nombre of recombinant gametes/ total nombre of gametes

The recombinant gametes are those gametes that differ from both of the haploid gametes that made up the original diploid cell (so differ to the parental gametes).

Linkage genes

Otherwise, recombination frequency indicate a genetic distance between two genes on the same chromosomes

Dg-g= RF Shorter the distance between two loci, higher the frequency of

recombinations (chance to occurs) .

• A genetic distance unit, or centiMorgan (cM), is equal to crossing over between 2 genes in 1% of the gametes.

• 1 cM is the distance between genes for which the recombination frequency is 1%.

Detecting Linkage through Testcrosses

• Linked genes are found by looking for deviation from the frequencies expected from independent assortment (different to 25,25,25,25% for each gamete).

• A testcross (one parent is homozygous recessive) works well for analyzing linkage:– If the alleles are not linked (independant), and the second

parent is heterozygous, all four possible combinations of traits will be present in equal numbers in the progeny (25% for each).

– A significant deviation in this ratio (more parental and fewer recombinant types) indicates linkage.

Testcross to show that two genes are linked

Testcross to show that two genes are linked

Demonstration that the recombination frequency between two genes

far apart on the same chromosome cannot exceed 50 %

Demonstration that the recombination frequency between two genes located far apart on the same chromosome

cannot exceed 50 %

offspring of single and double crossovers

LINKED or NON-LINKED?

• A recombination frequency of 50% means that genes are unlinked. There are two ways in which genes may be unlinked:– They may be on separate chromosomes.– They may be far apart on the same

chromosome.

• 0 < recombination frequency ≤50%

Test cross Results• PP LL x pp ll• F1: 100% Pp Ll• F2 results in table• Very significant deviation

from expected Mendelian ratio: chi-square = 97.4, with 3 d.f. Critical chi square value = 7.815.

• The null hypothesis for chi square test with 2 genes is that the genes assort independently. These genes do not assort independently.

phenotype obs exp ratio

exp num

P_ L_ 284 9/16 215

P_ ll 21 3/16 71

pp L_ 21 3/16 71

pp ll 55 1/16 24

Coupling vs. Repulsion• The original test cross we did was PL/pl x p l. Among

the offspring, PL and pl were parental types, and pL and Pl were the recombinant types. There was 24.3% recombination between the genes.

• When the dominant alleles for both genes were on the same parental chromosome (PL), with both recessives on the other parental chromosome (pl), they called “coupling”: the P and L genes are “in coupling phase”.

• When one dominant and one recessive on each parental chromosome (Pl or pL), is called “repulsion”.

Example: Test Cross in Repulsion• Now do the test cross in repulsion: Pl /

pL x p l• Here, the parental types are P l and p L,

and the recombinant types are P L and p l.

• However, the percentage of recombinants is 24.3%.

• 123 P L + 120 p l = 243 recombinant offspring.

243/ 1000 total offspring = 24.3 %• The percentage of recombination

depends on the distance between the genes on the chromosome, and NOT on which alleles are on which chromosome.

phenotype

obs

P L 123

P l 372

p L 385

p l 120

total 1000