Connecting Concepts Across Chapters

The principle of independent assortment states that alleles at different loci assort (separate) independently in meiosis but only if the genes are located on different chromosomes or are far apart on the same chromosome. This chapter has focused on the inheritance of genes that are physically linked on the same chromosome and do not assort independently. To predict the outcome of crosses entailing linked genes, we must consider not only the genotypes of the parents but also the physical arrangement of the alleles on the chromosomes.

An important principle learned in this chapter is that rates of recombination are related to the physical distances between genes. Crossing over is more frequent between genes that are far apart than between genes that lie close together. This fact provides the foundation for gene mapping in eukaryotic organisms: recombination frequencies are used to determine the relative order and distances between linked genes. Gene mapping therefore requires the setting up of crosses in which recombinant progeny can be detected.

This chapter also examined several methods of physical mapping that do not rely on recombination rates but use methods to directly observe the association between genes and particular chromosomes or to position genes by determining the nucleotide sequences. Although genetic and physical distances are correlated, they are not identical, because factors other than the distances between genes can influence rates of crossing over.

Gene mapping requires a firm understanding of the behavior of chromosomes (Chapter 2) and basic principles of heredity (Chapters 3 through 5). The discussion of gene mapping with pedigrees assumes knowledge of how families are displayed in pedigrees (Chapter 6). In Chapter 8, we will consider specialized mapping techniques used in bacteria and viruses; in Chapter 18, techniques for detecting molecular markers used in gene mapping are examined in more detail. Techniques for mapping whole genomes are discussed in Chapter 19. Chromosome mutations that play a role in deletion mapping and somatic-cell hybridization are considered in more detail in Chapter 9.

CONCEPTS SUMMARY]_

• Soon after Mendel's principles were rediscovered, examples of genes that did not assort independently were discovered. These genes were subsequently shown to be linked on the same chromosome.

• In a testcross for two completely linked genes (which exhibit no crossing over), only nonrecombinant progeny containing the original combinations of alleles present in the parents are produced. When two genes assort independently, recombinant progeny and nonrecombinant progeny are produced in equal proportions. When two genes are linked with some crossing over between them, more nonrecombinant progeny than recombinant progeny are produced.

• Because a single crossover between two linked genes produces two recombinant gametes and two nonrecombinant gametes, crossing over and independent assortment produce the same results.

• Recombination frequency is calculated by summing the number of recombinant progeny, dividing by the total number of progeny produced in the cross, and multiplying by 100%.

• The recombination frequency is half the frequency of crossing over, and the maximum frequency of recombinant gametes is 50%.

• When two wild-type alleles are found on one homologous chromosome and their mutant alleles are found on the other chromosome, the genes are said to be in coupling configuration. When one wild-type allele and one mutant allele are found on each homologous chromosome, the genes are said to be in repulsion. Whether genes are in coupling configuration or in repulsion determines which combination of phenotypes will be most frequent in the progeny of a testcross.

• Linkage and crossing over are two opposing forces: linkage keeps alleles at different loci together, whereas crossing over breaks up linkage and allows alleles to recombine into new associations.

• Interchromosomal recombination takes place among genes located on different chromosomes and occurs through the random segregation of chromosomes in meiosis. Intrachromosomal recombination takes place among genes located on the same chromosome and occurs through crossing over.

• Testing for independent assortment between genes requires a series of chi-square tests, in which segregation is first tested at each locus individually, followed by testing for independent assortment among genes at the different loci.

• Recombination rates can be used to determine the relative order of genes and distances between them on a chromosome. Maps based on recombination rates are called genetic maps; maps based on physical distances are called physical maps.

• One percent recombination equals one map unit, which is also a centiMorgan.

• When genes exhibit 50% recombination, they belong to different linkage groups, which may be either on different chromosomes or far apart on the same chromosome.

• Recombination rates between two genes will underestimate the true distance between them because double crossovers cannot be detected.

• Genetic maps can be constructed by examining recombination rates from a series of two-point crosses or by examining the progeny of a three-point testcross.

• Gene mapping in humans can be accomplished by examining the cosegregation of traits in pedigrees, although the inability to control crosses and the small number of progeny in many families limit mapping with this technique.

• A lod score is obtained by calculating the logarithm of the ratio of the probability of obtaining the observed progeny with a specified degree of linkage to the probability of obtaining the observed progeny with independent assortment. A lod score of 3 or higher is usually considered evidence for linkage.

• Molecular techniques that allow the detection of variable differences in DNA sequence have greatly facilitated gene mapping.

• In deletion mapping, genes are physically associated with particular chromosomes by studying the expression of recessive mutations in heterozygotes that possess chromosome deletions.

• In somatic-cell hybridization, cells from two different cell lines (human and rodent) are fused. The resulting hybrid cells initially contain chromosomes from both species but randomly lose different human chromosomes. The hybrid cells are examined for the presence of specific genes; if a human gene is present in the hybrid cell, it must be present on one of the human chromosomes in that the cell line.

• With in situ hybridization, a radioactive or fluorescence label is added to a fragment of DNA that is complementary to a specific gene. This probe is then added to specially prepared chromosomes, where it pairs with the gene of interest. The presence of the label on a particular chromosome reveals the physical location of the gene.

• Nucleotide sequencing is another method of physically mapping genes.

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