Linkage, Recombination and Eukaryotic Gene Mapping

Mendel's work focused on gene pairs that assorted independently.
Discovery by William Bateson, Edith Rebecca Saunders, and Reginald C. Punnett in 1905 of gene pairs that did not appear to assort independently.
Example of experiment: Crossing peas with purple flowers and long pollen grains to red flowers with round pollen grains.
F1 progeny were heterozygous at both loci resulting in purple flowers with long pollen grains.
F2 progeny did not conform to expected 9:3:3:1 ratio:
- Majority were purple and long (dominant) or red and round.

Distribution of phenotypes in the F2 generation was as follows:
- Purple flowers, long pollen: 284
- Purple flowers, round pollen: 21
- Red flowers, long pollen: 21
- Red flowers, round pollen: 55
Conclusion: F2 progeny do not appear in the 9:3:3:1 ratio indicative of independent assortment.

Genetic recombination: Sorting of alleles into new combinations during gamete formation.
- Gametes can be described as:
- Non-recombinant: Gametes with the same allele combinations as the parental gametes.
- Recombinant: Gametes with different allele combinations than parental gametes.

Independent assortment: Random arrangement of chromosomes during meiosis.
Genetic recombination also occurs through crossing over during meiosis I.
Genes that are farther apart on the chromosome are more likely to undergo recombination.

Linkage Group: All of the genes located on a single chromosome that are inherited together.
- Chromosome 1: Genes include traits like bent wing and yellow body.
- Distance between genes is expressed in map units (m.u.).

Linked Genes: Genes that are located close together on the same chromosome.
Complete linkage: No crossing over occurs between closely spaced genes on the same chromosome.
Incomplete linkage: Occurs when genes are sufficiently far apart to allow crossing over between them.

Cross between genotypes is often denoted as:
- AB or ab denoting combinations of dominant and recessive alleles.

Example with alleles for leaf color and plant height:
- M = normal leaves, m = mottled leaves.
- D = tall plant, d = dwarf plant.
Gamete formation forms only nonrecombinant gametes (e.g., MD or md) due to complete linkage.
- Resulting progeny show traits corresponding to nonrecombinant gametes (normal leaves, tall plants).

If crossing over occurs:
- Fewer than 50% of progeny will show recombinant phenotypes.
- Example calculations show distributions of traits resulting from both crossing over and non-crossing over events.

Calculation of the recombination frequency:
- Recombination \, frequency = \frac{\text{no. of recombinant progeny}}{\text{total number of progeny}}
- This is standardized as map units (1 m.u. = 1% recombination).

Example with genes for eye color and wing phenotype demonstrates allele combinations.
Through phenotypic analysis, frequencies of traits in progeny are assessed to determine linkage.

Mechanism to map three genes simultaneously on a chromosome.
- Different crossover types (single and double) can be distinguished in progeny from these crossings.

Interference: One crossover may inhibit the occurrence of a second crossover near it on the chromosome, resulting in fewer observed double crossovers.

More complex due to fewer progeny and inability to conduct controlled crosses.
Utilization of pedigree analysis and molecular markers to determine location and function of traits such as Nail-Patella syndrome.

RFLPs: Variations in length of fragments produced by restriction enzymes.
Microsatellites: Repeating sequences that can serve as genetic markers.
SNP: Single nucleotide changes between different strains serving as important markers.

Examining nonrandom associations between traits and genotypes across populations to identify linked genetic variants.

Linkage Disequilibrium: Nonrandom associations between alleles at different loci.
Stability and persistence of alleles over time reveal their proximity (linkage) on chromosomes.

Identification of gene locations relative to markers (deletions, chromosomal bands).
Helps outline genetic paths and connections between phenotypic traits and genetic locations.

Method to determine if mutations are at the same locus or different loci.
Deletion Mapping: Mapping genes by examining effects of deletions on phenotypes.

Techniques include various forms of mapping that encompass both statistical and mechanistic approaches of determining genetic linkage and trait manifestation.
Understanding of these principles enables breeding programs, disease identification, and evolutionary studies in various organisms.