Linkage Recombination and the Mapping of Genes on Chromosomes II

If the definition of linkage is that the proportion of recombinant classes is smaller than that of parental classes, a recombination frequency of less than _____ indicates linkage

We already know one situation that can give rise to a recombination frequency of 50%. Name 3

Genes located on different (that is, ________) chromosomes will obey Mendel's law of independent assortment. Why? (2)

Genes located very far apart on the same chromosome show recombination frequencies of approx _____

When two genes are very close together on the same chromosome, only two kinds of meioses are likely to occur:

NCO meiosis yields only ______ gametes, while an SCO event produces ___% _______ gametes . These closely spaced genes are linked because some meioses (____) do not make any recombinant type gametes.

When the two genes are farther apart, SCOs become ____ frequent, and in some meioses, ____ crossovers between A and B (____) can also occur.

DCO meioses can be one of four different types:

Why is it that the average fraction of recombinant gametes produced by DCOs is 50%?

The average fraction of recombinant gametes produced by triple crossover events (___%) and( ___% for) quadruple crossover events = 75%. Why?

Even if the two genes are far enough apart on the same chromosome that at least one crossover occurs between them in every meiosis, the pool of gametes produced by a dihybrid would be only ____% recomb. types

If two genes on the same chromosome are so far apart that no meioses occur as NCOs, then the alleles of the genes ______ _______, just as if they were on different chromosomes

Two main principles of Linked genes

Two main principles of Unlinked genes

Maps assign genes to specific locations on particular chromosomes called ______. By transforming genetic data into _____ arrangements, maps sharpen our ability to predict the inheritance patterns of specific traits

Two point crosses

Sturtevant asked whether data obtained from a large number of ______ crosses would support the idea that genes form a definite linear series along a chromosome. He began by looking at ______ genes in Drosophila

Consider the three genes w,y, and m. If these genes are arranged in a line (as opposed to?), then one of them must be in the ______, flanked on either side by the other two

The greatest genetic distance should separate the two genes on the outside, and this value should equal to?

What supports the idea that genes reside in a unique linear order along a chromosome

Though of great import, the pairwise mapping of genes has several shortcomings  that limit its usefulness. Name 2 (Examples are on pg 137-138 under Limitations of two point crosses)

Three-point cross

Three point cross on one of Drosophila's autosomes (3-story)

In analyzing the data, we look at the two genes at a time; recall that the recombination frequency is always a function of:

For the pair vg and b, the _______ combinations are vg b and vg⁺ b⁺; the _______ combos are vg b⁺ and vg⁺ b.

To determine whether a particular class of progeny is parental or recombinant for vg and b, we do not care whether the flies are pr or pr⁺. Thus, the nearest tenth of a map unit, the vg ↔ b distance, calculated as the percentage of recombinants in the total number of progeny, is:

(given):

Similarly, because recomibinants for the vg↔pr gene pair are vg pr⁺ and vg⁺ pr, the interval between these two genes is: 

(given):

The distance separating the b-pr pair is:

(given): 

These recombination frequencies show that vg and b are separated by the _______ distance (17 m.u.) and must therefore be:

T or F: As with the X-linked y and r genes analyzed by Sturtevant, the distance separating the outside vg and b genes (17.7) equals the sum of the two intervening distances (12.3 + 6.4 = 18.7)
True False

A close examination of the chromosomes reveals the kinds of crossovers that must have occurred to generate the classes and numbers of progeny observed. In this subsequent figures, the chromosomes depicted are in what phase?

Flies in the two largest groups carry the same configurations of genes as did their grandparents of the P generation: (___). They thus represent the _______ classes

The next two groups, vg⁺b pr and vg b⁺ pr⁺, are composed of ______ that must be _______ products of a crossover in region 1 between vg and pr

Similarly the two groups containing vg⁺b pr⁺ and vg b⁺pr flies must have resulted from _________ in region 2 between pr and b 

What about the two smallest groups made up rare vg b pr⁺ and vg⁺ b⁺ pr recombinants? What kinds of chromosomes exchange could account for them? (What configuration is expected for the gametes produced from such an event?)

The vg ↔ b distance of 17.7 m.u. calculated in the previous section does not reflect all of the recombination events producing the gametes that gave rise to the observed progeny (why?)

How do we correct this oversight?

This value makes sense because you have accounted for all of the crossovers that occur in region 1 as well as all of the crossovers in region 2. As a result, the corrected value of 18.7 m.u. for the distance between vg and b is now _____ ____ _____ as the sum of the distances between vg and pr (region 1) and between pr and b (region 2).

When Sturtevant originally mapped several X-linked genes in Drosophila by ____ _____ crosses, the locus of the rudimentary wings (r) gene was ________.

A two-point cross involving y and r gave a recombination frequency of 42.9 but the sum of all of the intervening distances was 55.0. Why did this discrepancy occur?

The data summing the smaller intervening distances accounted for at least some of these double crossovers by catching _________ of gene pairs between y and r. Moreover, each smaller distance is ______ likely to encompass a double crossover than a larger distance, so each number for a smaller distance is inherently more _________

Note that even a three-point cross like the one for vg, pr, and b ignores the possibility of two recombination events taking place in, say, region 1. For greatest accuracy, it is always best to construct a map using:

In a three-point cross following three linked genes, of the eight possible genotypic classes, the two parental classes contain the _______ number of progeny, while the two double recombinant classes, resulting from double crossovers, are always the ________

If an exchange in region 1 of a chromosome does not affect the probability of an exchange in region 2, the probability that both will occur simultaneously is: (ex too)

If there are eight classes of progeny in a three-point cross, the two classes containing the fewest progeny must have arisen from ______ _______. The numerical frequencies of observed ______ _______, however, almost never coincides with expectations derived from the product rule

The probability of a single crossover between vg and pr is 0.123 (corresponding to 12.3 m.u.), and probability of a single crossover between pr and b is 0.064 (6.4m.u.). What is the product of the crossover (odds that they occur simultaneously)? What is the observed proportion of double crossovers?

The fact that the number of observed double crossovers is less than the number expected if the two exchanges are independent events suggests: (define the concept)

Why is there chromosomal interference?

Why is it critical that every pair of homologous chromosomes sustain one or more crossover events?

Homologous chromosome pairs without crossovers often ______ improperly

If only a limited number of crossovers can occur during each meiosis and interference lowers the number of crossovers on large chromosomes, then the remaining possible crossovers are more likely to occur on ______ chromosomes. This _______ the probability that at least one _______ will take place on every __________ pair

Investigators can obtain a quantitative measure of the amount of interference in different chromosomal intervals by first calculating a _______ __ ________ (define and give equation)

For three point cross involving vg, pr, and b, what is the coefficient of coincidence? What is the equation for interference? What is the interference?

If interference is 0, the frequency of observed double crossovers _______ expectations, and crossovers in adjacent regions of a chromosome occur __________ (of or with?) each other

If interference is complete (that is, the interference = ___), no _____ ______ occur in the experimental progeny. Why?

In a particular three-point cross in mice, the recombination frequency for the pair of genes on the left (region 1) is 20 and for the pair of genes on the right (region 2), it is also 20. Without interference, the expected rate of double crossovers in the chromosomal interval in the mice is:

When investigators observed 1000 progeny of this cross, they found ___ double recombinants instead of the expected 40

The smallest of the eight possible classes of progeny in a three-point cross are the two that contain double recombinants generated by _____ _______. It is possible to use the composition of alleles in these double crossover classes to determine which of the three genes lies in the _______, even without calculating any recombination frequencies

Consider again the progeny of a three point testcross looking at the vg, pr, and b genes. The F1 females are vg pr b/ vg⁺ pr⁺ b⁺. Testcross progeny resulting from double crossovers in the _______ females of the F1 generation received gametes from their ________ carrying the allelic combinations (________ and _________). In these individuals, the alleles of the vg and b genes retain their parental associations (vg b and vg⁺ b⁺), while the pr gene has recombined with respect to both the other genes (pr b⁺ and pr⁺ b; vg pr⁺ and vg⁺ pr).

The same is true in all three-point crosses (explain)

THREE POINT CROSS COMPREHENSIVE EXAMPLE pg 141

The order of genes revealed by recombination mapping ______ reflects the order of those same genes along the DNA molecule of a chromosome. In contrast, the actual physical distances between genes, (the amount of _____ separating them) _____ _______ correspond linearly to genetic map distances

You have already seen that DCOs between two genes may go undetected in a testcross experiment, resulting in undercounting of the number of crossovers between the two genes. Result?

As the distance between two genes increases, double and multiple crossovers occur often enough to affect the relationship between ________ ________ and ____ _______.

This relationship cannot be linear (why?)

When genes A and B are very  close together, most meioses are ______, and the occasional meiosis is an _____.  Each of those crossovers produce exactly _____ recombinant gametes and so a perfect linear correspondence exists between the number of _______ and the number of ______ ________

When genes A and B are further further apart, _____ occurs.

Only one of the four equally frequent DCOs (_____) preserves the linear relationship between crossovers and recombinant gametes (How?)

As you can see, the two graphs are nearly identical for distances of _____ or _____. At genetic distances this small, the RF seen in a two-point cross is an ______ measure of the physical distance. The two graphs then diverge increasingly from each other, so the RF becomes a less precise estimate at genetic distances greater than _____

Geneticists have developed equations called mapping functions for the inaccur. in relating recomb. frequ. to physical distances. However, the corrections for large distances are at best imprecise. What is the best way to create an accurate map?

Although we have been assuming thus far that crossovers are just as likely to occur between any two base pairs along a chromosome, recombination is not in fact _______.  In human DNA, for example, most crossovers take place in so-called ________ _________ (define)

As you can see, genes with _______ between them (A and B) will be more distant from each other on a genetic map (in m.u.) than another gene pair (B and C) without a ______ between them, even though the physical distance (in base pairs) separating each gene pair is the same.

Hotspots are relatively frequent and appear about every ______ bp in human chromosomes. Recombination frequency is nevertheless a reasonable estimation of physical distance between ______ genes

Linkage groups

When enough genes have been assigned to a particular chromosome, the terms ________ and _______ group become interchangeable. If you can demonstrate that gene A is linked to gene B, B to C, C to D, and D to E, you can conclude that all of these genes are _________

When the genetic map of a genome becomes so dense that it is possible to show that any gene on a chromosome is linked to another gene on the same chromosome, the ______________________ = _________________________

The total genetic distance along a chromosome, which is obtained by adding many short distances between genes, may be much more than 50 m.u. State 2 scenarios

Even with the longest chromosomes, ______ crosses between genes located at the two ends will not produce more than ___% recombinant progeny