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Linkage genes and genetic recombination

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1 Linkage genes and genetic recombination
TABUK UNIVERSITY Faculty of Applied Medical Sciences Department of Laboratory Technologies Linkage genes and genetic recombination AY: / Lecture 5

2 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%

3 Mendel’s law of independent assortment: Most pairs of genes assort independently
Gametes Non parental types Segregation Parental types Here we’re labelling the DNA from the father red and the mother blue.

4 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

5 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

6 Crossing over occurs during Prophase 1 of meiosis.

7 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.

8 Mechanism of crossing-over (in PROPHASE I of meiosis)
Crossing over (exchange) occurs between two non sisters chromatids (each chromatid from one chromosome)

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

10 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).

11 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%.

12 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.

13 Testcross to show that two genes are linked

14 Testcross to show that two genes are linked

15 Demonstration that the recombination frequency between two genes
Demonstration that the recombination frequency between two genes far apart on the same chromosome cannot exceed 50 %

16 Demonstration that the recombination frequency between two genes located far apart on the same chromosome cannot exceed 50 %

17 offspring of single and double crossovers

18 LINKED or NON-LINKED? 0 < recombination frequency ≤50%
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%

19 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 = 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_ pp ll 55 1/16 24

20 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”.

21 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 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

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