Chapter 9 Flashcards
Define the terms “parental” and recombinant” as they pertain to linkage.
In a linkage problem, true-breeding parents are mated to produce heterozygous F1 offspring, which are then test-crossed to produce an F2 generation. Among the F2, parental phenotypes are those observed in the F2 that are the same as the original parents, while recombinant phenotypes are those that differ from the original parents. Recombinant phenotypes are less frequent than parental phenotypes. These terms can also be applied to the underlying genotypes of the organisms.
For X-linked genes, a F1 heterozygous female might be mated to a wild-type male rather than test-crossed to a mutant male.
How is this conceptually similar to a test-cross, and what has to be changed about how the data are collected?
A test cross is used for autosomal genes since one parent does not contribute any dominant alleles. If a female heterozygous for an X-linked trait is mated to a wild-type male, all F1 females will show the wild-type phenotype (if wild-type is dominant). In this case, only the F2 males should be counted. This is similar to a test-cross in that the male offspring must have a Y chromosome, which does not contribute to the phenotype of interest.
For X-linked genes, a F1 heterozygous female might be mated to a wild-type male rather than test-crossed to a mutant male.
What might be an advantage to using a wild-type male for mapping X-linked genes rather than a mutant male?
Wild-type males are likely to mate better than a mutant male that cannot move well or that are a less attractive mate than a wild-type male (for instance, female flies will preferentially mate with wild-type males rather than white males).
In a two factor cross, the longest possible map distance is 50 map units.
Explain why this is true.
How then can genetic maps show two genes that are 70 map units or more apart?
Map distances are defined as the percentage of recombinants observed. Since recombinants are always less frequent than parental combinations, the number of recombinants cannot exceed 50%.
Genes that are closer together (within the 70 map unit distance) are used to establish smaller distances, and then added together to obtain map distances greater than 50 map units.
What is the difference between “linked” genes and “syntenic” genes and how are both important in genetic analysis?
Linked genes are close enough together that they are likely to be inherited together. Syntenic genes are located on the same chromosome. Syntenic genes may segregate independently if they are far enough apart.
What is interference and what does that tell us about crossing over?
Interference is a measure of the extent to which a crossover in one region of the chromosome prevents the occurrence of a crossover in a nearby region. It is defined as 1- (number of observed double crossovers/number of expected double crossovers) in a three-factor cross. It tells us that the positions of crossovers are not random but are instead controlled somehow.
Define the term haplotype.
Polymorphisms in a region of the genome that continue to be inherited together as a unit, as they are linked to each other on the chromosome.
What roles do genetic and physical maps play in genetic experiments?
Genetic maps are important tools for understanding structure of the genome, for finding genes that give rise to mutant phenotypes, and for predicting how often particular traits are inherited together. A physical map shows where the genes are location in terms of the DNA molecule. This can be of use in making synthetic constructs to study the functions of particular genes or how changes in the DNA result in differences in protein products made.
For the past two decades, genetic mapping has usually involved genetic markers with molecular phenotypes than genes with more “traditional” phenotypes. Discuss some of the advantages of using molecular markers for mapping that have made them the pre-dominant ones used for mapping. Besides the assay used to determine the phenotype, what other part of the standard mapping procedure might be different when molecular markers are used?
Some advantages of using molecular markers rather than phenotypic traits include: more molecular markers are available, covering many more regions of the genome; a similar assay can often be used to score several different markers simultaneously; regardless of the assay used, multiple markers can be scored together since the phenotype of one does not obscure or alter the phenotype of another; molecular markers can often be scored without the need for a test cross, which allows them to assessed one generation sooner; and molecular markers are much less likely to affect viability and fertility than a phenotypic marker. The main differences with molecular markers are the lack of a test-cross and possibly in the order in which the steps are done. With traditional phenotypic markers, the outcome of crossing over is observed first and then the appropriate number of each offspring is determined; with molecular markers, the recombinants and parentals often cannot be distinguished easily at the outset so all of the offspring are collected and enumerated, and then the locations of the crossovers are determined.
For some organisms, linkage is often done using an F2 ratio from two heterozygotes rather than doing a test-cross. Consider a recombination experiment that mates F1 offspring among themselves to produce an F2 rather than uses a test-cross.
Which classes of offspring would be more and less common in such an experiment?
Here is a way to solve this problem. Imagine a heterozygote with the chromosome configuration A B/a b—that is, with the dominant alleles in cis and the recessive alleles in cis. The genes are p map units apart. The recombinant gametes (A b and a B) occur at a frequency of p, so each of them occurs at a frequency of p/2.
For some organisms, linkage is often done using an F2 ratio from two heterozygotes rather than doing a test-cross. Consider a recombination experiment that mates F1 offspring among themselves to produce an F2 rather than uses a test-cross. Can you think of one reason that an investigator would use an F2 ratio rather than a test-cross? (Hint: This is commonly done with C. elegans and plants such as Arabidopsis but rarely done with Drosophila or mice.)
F2 ratios like this are more commonly used in organisms that self-fertilize like C. elegans and Arabidopsis since it is simpler to allow the heterozygous F1 to self-fertilize than it is to do a test-cross.
In many organisms, it is possible to see the chiasmata that form during meiosis I. Suppose that a chromosome has two easily observed physical landmarks such as a knob at one end and a constriction that forms nearby. When the gametes are examined cytologically, 10% of them have a chiasma between the knob and the constriction. What is the approximate map distance between the knob and the constriction? (Be careful—the answer is not 10 map units.)
If 10% of the gametes have a chiasma in the area, then 5% of the gametes are recombinant. Remember that even when recombination is known to have occurred, only half of the gametes arise from the crossover. So the map distance is 5 map units.
How are balancer chromosomes (discussed in Tool Box 9-3) and haplotypes related to each other? What are some ways that they are different?
Balancer chromosomes are laboratory stocks that help to ensure that certain combinations of alleles will be inherited together without recombination. Although the terminology is not used in laboratory organisms, the combination of alleles that is inherited together is a haplotype. The main differences are that haplotypes are usually only assessed with molecular markers while balancer chromosomes use morphological phenotypes (and often lethal combinations); that, depending on the balancer chromosome and the organism, balancer chromosomes usually ensure co-inheritance of markers over a much longer region of the chromosome than does a haplotype; and that balancer chromosomes are induced in the laboratory in experimental organisms while haplotypes are found in nature.
(Looking ahead). dpy-18 and unc-32 are closely linked autosomal genes in C. elegans. A student crosses dpy-18 males to unc-32 hermaphrodites and then picks and cultures the wild-type F1 hermaphrodites. She has no time to finish the experiment before the term ends, so her plates sit in the incubator for several weeks. What will be the most common phenotypes when she returns? Assume that all genotypes and phenotypes have equal numbers of offspring. The parental types are dpy-18 unc-32+ and dpy-18+ unc-32.
Parental combinations are always more common than recombinants, so the most common phenotypes are expected to be Dumpy non-Uncoordinated and non-Dumpy Uncoordinated. The alleles exhibit the phenomenon of linkage disequilibrium, which is defined and discussed in Chapter 10
Recombination mapping was a common procedure in model organisms such as flies, worms, mice, and Arabidopsis about 20 years ago, and nearly all genetics graduate students mapped at least one gene in the course of their thesis. Nowadays most genetics graduate students working with these model organisms do not map genes. Why is mapping no longer a common laboratory practice?
Since the genomes of these model organisms have been sequenced and the locations of the genes have been determined from the sequence, there is less need to map genes.
