Genetics 3301

Chapter 4: Chromosome Mapping

Detecting Linkage:

Ä Inheritance of linked genes (4-2); Linkage terminology; Crossing-over during meiosis (4-3); Crossing-over during the 4-chromatid stage (4-4); Multiple crossovers (4-5).

Ä Meiotic recombination generates allelic combinations that differ from those that made either parent (4-6); the product of meiotic recombination is called a recombinant; a test cross can determine whether genes are independently assorting (which would be a 50% recombination frequency or 1:1:1:1 ratio) (4-8) or linked (which would give >50% parental phenotypes and <50% non-parental phenotypes) (4-9, 4-10); recombination frequencies can never be more than 50% since that is equal to random assortment.

Ä Recombination on the X chromosome occurs in the homogametic sex and can be detected in the heterogametic sex; X recombination occurs in female Drosophila and is detected in her sons.

Linkage Mapping:

Ä The magnitude of recombination between two linked genes is a measure of their distance apart ≠ the closer two genes are, the smaller the recombination frequency; A linkage map of genes along the chromosome can be generated by determining their recombination frequencies; a recombination frequency (RF) of 1% equals 1 genetic map unit (m.u.); to obtain a map of linked genes A, B and C you must determine the recombination frequency of A-B, B-C and A-C (4-11).

Ä A three point test cross can detect linkage and produce a map of the genes along the chromosome in one cross; double recombinant classes are the smallest and show which genes are furthest apart (4-12); double recombinants do not appear as recombinants for the genes furthest apart, which leads to an underestimate of distance between these genes compared to adding the single recombinant classes (4-12); deducing gene order by inspection (4-13).

Ä One cross over will interfere with or inhibit another crossover nearby; expected recombinants is the product of the RFs in the adjacent regions; coefficient of coincidence calculates amount of interference.

Ä Five steps for recombinant analysis in 3-point test crosses:

1) calculate recombination frequency for each pair of genes

2) make a linkage map

3) determine the double crossover classes

4) calculate the expected frequency of double crossovers assuming no interference

5) calculate the intereference

Ä Mapping with molecular markers; RFLPs and VNTRs.

Analyzing single meioses:

Ä In some haploid organisms you can look at the products of single meioses because the meiosis products (spores) are arranged in tetrads and octads within the ascus (3-37a); Neurospora is a beneficial model system because segregate in a linear order (3-37b); one can follow chromosome segregation after the first division (M₁) or second division (M₂) (3-37); M₂ segregation can lead to four ascus patterns because of random chromosome segregation (4-15, 4-16).

Ä RF between the centromere and a gene locus equals the number of M₂ ascus patterns ˜ 2 since only half the chromatids from a meiosis are recombinant (4-15).

Statistical analysis of linkage:

Ä Determining whether two genes are linked via chi-square analysis; Null hypothesis; Assessing linkage in humans using Lod scores (4-17).

Accounting for unseen multiple crossovers:

Ä The average RF is 50% for meioses in which crossing over occurs (4-18); Mapping genes in relation to each other; classifying tetrads ≠ PD, NPD and T; RF=1/2(T)+NPD.

Key terms: Know all of these except mapping function and Poisson distribution.

Problems: 1, 2, 3, 5, 6, 7, 8, 10, 11, 13, 15, 19, 22, 28, 29, 35, 37, 42.