Recombination, linkage and genetic mapping, Lecture notes of Human Genetics

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Recombination, linkage and

genetic mapping

M.Sc. Microbiology, 2nd^ Semester

MCB 202 : Genetics and Gene regulation

Gr. A: Fundamental Genetics

by

Dr. Suman Kumar Halder

Independent assortment and

Recombination

The principle of segregation states that

each individual diploid organism

possesses two alleles at a locus that

separate in meiosis, with one allele going

into each gamete.

The principle of independent assortment

provides additional information about the

process of segregation: it tells us that, in

the process of separation, the two alleles

at a locus act independently of alleles at

other loci.

The independent separation of alleles

results in recombination , the sorting of

alleles into new combinations.

Recombination means that, when one of the F 1 progeny reproduces, the combination of alleles in its gametes may differ from the combinations in the gametes from its parents.

Molecular recombination

• Genetic recombination (or genetic reshuffling) is the

exchange of genetic material between different organisms which leads to production of offspring with combinations of traits that differ from those found in either parent.

• Takes place in both prokaryotes and eukaryotes.
• Best studied in bacteria, archaea, yeast and phage.
• Mediated by breakage and joining of DNA strand.
• Reason: DNA repair, regulation of gene expression,

maintenance of genetic diversity, genetic rearrangement, etc.

Molecular recombination: Types

• At least four types of naturally occurring

recombination have been identified in living

organisms:

• General or homologous recombination
• Illegitimate or non-homologous recombination
• Site-specific recombination
• Replicative recombination

General recombination can appear to result in either an equal or an

unequal exchange of genetic information, which respectively called

reciprocal and non-reciprocal recombination.

• Two homologous chromosomes are distinguished by having wild type alleles on

one chromosome (A+ B+ C+) and mutant alleles on the other (A- B- C-).

• Homologous recombination between genes A and B exchanges the segment of

one chromosome containing the wild type alleles of genes B and C (B+ and C+)

for the segment containing the mutant alleles (B- and C-) on the homologous

chromosome.

• This could be explained by breaking and rejoining of the two homologous

chromosomes during meiosis.

• This process resulting in new DNA molecules that carry genetic information

derived from both parental DNA molecules is called reciprocal recombination.

The number of alleles for each gene remains the same in the products of this

recombination, only their arrangement has changed.

Reciprocal recombination

Single-strand break model

Mechanism (Holliday Model)

Mechanism..cont

Double-strand break model

• General recombination can also result in a one-

way transfer of genetic information, resulting

in an allele of a gene on one chromosome

being changed to the allele on the homologous

chromosome.

• Recombination between two homologous

chromosomes A+B+C+ and A-B-C- can result in

a new arrangement, A-B+C-, without a change

in the parental A+B+C+.

• In this case, the allele of gene B on the bottom

chromosome has changed from B- to B+

without a reciprocal change on the other

chromosome.

Non-reciprocal recombination

• Major pathway for the repair of chromosomal double-

strand breaks in the DNA of somatic cells, V(D)J recombination of antibody.

• This pathway is often used when the cell is in G1 and a

sister chromatid is not available for repair through homologous recombination.

• Non-homologous end joining uses proteins that

recognize the broken ends of DNA, bind to the ends, and then joins them together.

• It is more error prone than homologous recombination

and often leads to deletions, insertions, and translocations.

Non-homologous recombination

• Site-specific recombination occurs between particular short sequences (about 12 to 24 bp) present on otherwise dissimilar parental molecules. Site-specific recombination requires a special enzymatic machinery, basically one enzyme or enzyme system for each particular site. Good examples are the systems for integration of some bacteriophage, such as λ, into a bacterial chromosome and the rearrangement of immunoglobulin genes in vertebrate animals.
• Unlike general recombination, site specific recombination is guided by a recombination enzyme that recognizes specific nucleotide sequences present on one of both recombining DNA molecules.

Site-specific recombination

Leads to the combination of two different DNA molecules, illustrated here for a bacteriophage integrating into the E. coli chromosome, catalyzed by a specific enzyme that recognizes a short sequence present in both the phage DNA and the target site in the bacterial chromosome, called att

• Bacterial recombination is a type of genetic recombination in bacteria characterized by DNA transfer from one organism called donor to another organism as recipient. This process occurs in three main ways: - Transformation - Transduction - Conjugation
• The final result of conjugation, transduction, and/or transformation is the production of genetic recombinants, individuals that carry not only the genes they inherited from their parent cells but also the genes introduced to their genomes by conjugation, transduction, and/or transformation.
• Recombination in bacteria is ordinarily catalyzed by a RecA type of recombinase.
• These recombinases promote repair of DNA damages by homologous recombination.
• In the archaea, the ortholog of the bacterial RecA protein is RadA.

Bacterial recombination

Number of chromosomes in most organisms is limited and

that there are certain to be more genes than chromosomes;

so some genes must be present on the same chromosome and

should not assort independently.

Genes located close together on the same chromosome are

called linked genes and belong to the same linkage group.

Linked genes travel together in meiosis, eventually arriving

at the same destination (the same gamete), and are not

expected to assort independently.

Linkage

History of Linkage

establishment

One of the first cases was reported in sweet peas by William Bateson, Edith Rebecca Saunders, and Reginald C. Punnett in 1905.

They crossed a homozygous strain of peas having purple flowers and long pollen grains with a homozygous strain having red flowers and round pollen grains.

All the F1 had purple flowers and long pollen grains, indicating that purple was dominant over red and long was dominant over round.

When they intercrossed the F1, the resulting F progeny did not appear in the 9 : 3 : 3 : 1 ratio expected with independent assortment. An excess of F2 plants had purple flowers and long pollen or red flowers and round pollen (the parental phenotypes).

In the light of linkage we now can explain that the two loci that they examined lie close together on the same chromosome and therefore do not assort independently.

• Genes are rarely completely linked but, by assuming that

no crossing over occurs, we can see the effect of linkage more clearly. We will then consider what happens when genes assort independently. Finally, we will consider the results obtained if the genes are linked but exhibit some crossing over.

• A testcross reveals the effects of linkage.
• Consider a pair of linked genes in tomato plants. One of

the genes affects the type of leaf: an allele for mottled leaves (m) is recessive to an allele that produces normal leaves (M). Nearby on the same chromosome the other gene determines the height of the plant: an allele for dwarf (d) is recessive to an allele for tall (D).

Linkage Vs. Independent Assortment