Eukaryote chromosome mapping by recombination

Meiosis is the basis of transmission genetics. Recombination in a heterozygous individual is a useful tool for making linkage maps, and linkage maps help us understand evolution, synteny, and selection response.

I. Key terms

  1. Linkage refers to the association of two or more phenotypic characters in inheritance because the genes controlling these characters are located in the same chromosome. Genes carried by the same chromosome are members of the same linkage group; the number of linkage groups corresponds, therefore, to the basic number of chromosomes in the organism in question. The strength of linkage, or the amount of recombination, is dictated by the "distance" between genes in the same chromosome.

  2. Crossing over refers to the physical exchange between homologous chromosomes. As discussed in the previous class, meiotic crossing over is a potent source of genetic variability.

  3. Recombination is the genetic result of crossing over and is detected by new combinations of alleles at two or more loci.

  4. Linkage:
    1. Complete: Gene pairs are so close together that crossing over rarely occurs and recombinant types are generally not recovered.

    2. Partial: Gene pairs are sufficiently far apart that some recombinant types are recovered. The "distance" between genes ranges from a few percent recombination to 50% recombination.

 

  1. Terms describing the allelic condition at linked loci

II. More on the meiotic basis of recombination

At Pachynema, there can be breakage of chromatids, followed by their fusion with sister chromatids, or with non-sister chromatids. As long as orientation corresponds, reciprocal exchanges between sister chromatids will not be detected and will not lead to genetic variability. Keys points in non-sister chromatid exchange:

III. Factors affecting meiotic crossing over

 

IV. Types of Crossovers

V. Calculating linkage

Tracking recombination in the VVWWNNLL x vvnnll cross progeny
Point: Consequences of random alignment of non-homologs; Consequences of crossovers; Consequences of separation of sister chromatids; Consequences of crossover; calculating linkage

VI.. Looking at the consequences of recombination

VII. Building a genome-wide linkage map

Linkage analysis is now an "automated" procedure. Given that mapping now involves hundreds, if not thousands, of loci at a time, tools such as JoinMap are necessities. You will learn how to use these tools in other classes. For now, you should be aware that the underlying mathematics are considerably more complicated than what we have explored with our simple examples.

Key issues in linkage map construction are locus order and distance. A term you will see applied to linkage and ordering is the likelihood odds (LOD) score. The LOD score is a test statistic that is used to test the hypothesis that there is no linkage against the alternative hypothesis that there is linkage. A LOD of 3.00 is approximately equal to P.001, so if LOD > 3 then one concludes that two loci are indeed linked. Next, one exercises a number of options to arrive at what is the most likely locus order. This is not trivial, as a linkage group with 6 loci has about 360 possible orders, and a group with 100 loci has approximately 5 X 106 possible orders.



VIII. Genetic and physical maps: Perspectives on double crossovers: the coefficient of coincidence, interference, and centiMorgans

The centiMorgan is a unit of distance without a physical basis. This is readily apparent in organisms with large genomes, where the ratio of cM to base pairs can vary enormously across the genome. For example, in barley the average genome-wide ratio is 4.4Mb/cM. Kuenzel et al. (2000) presented an elegant piece of work defining regions of the genome where the ratio is considerably higher than this figure and regions of the genome with high recombination, where the ratio is < 1Mb/cM.

IX. Utility of linkage maps

  1. Establish evolutionary relationships: homoeology, synteny and orthology. Case study: vernalization genes in wheat and barley. See Yan et al. 2004a. Yan et al. 2004b
    Homoeology: Refers to chromosomes, or chromosome segments, and which are similar in terms of the order and function of the genetic loci. Homoeologous chromosomes may occur within a single allopolyploid individual (e.g. the A,B, and D, genomes in wheat), or they may be found in related species (e.g. the 1A, 1, B, 1D series and wheat and the 1H of barley).
    Orthology: Refers to genes in different species which are so similar in sequence that they are assumed to have originated from a single ancestral gene.
    Synteny: Refers to genetic loci that are linked on the same chromosome.
  2. Determine if trait associations are due to linkage or pleiotropy.
  3. Finding genes determining qualitative and quantitative phenotypes (Marker assisted selection for barley stripe rust)
  4. Map-based cloning (tomato; barley disease resistance; Vrs1).
Key concepts:

Text: Chapter 4

 

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