MCDB 1041
Class 10: Linked genes (Linkage)
Reading: Chp 5: 101-106
Learning Goals
You should be able to:
Contrast the inheritance of linked genes with unlinked genes.
Calculate probability of inheritance of linked and unlinked genes
Explain several possible reasons why a given genotype does not always result in the same phenotype.
Linkage
So far, if we have considered the inheritance of two genes at the same time, they have been located on different chromosomes. Sometimes, of course, scientists will study the inheritance of two genes on the SAME chromosome. This has been particularly true when studying non-human systems such as yeast, the common fruit fly, and a small roundworm called C. elegans. These organisms have all been studied using genetic approaches to find out what their genes do. For humans, it is less common to follow the inheritance of two genes on the same chromosome, just because it's less likely that somebody will actually have two diseases caused by genes on the same chromosome. Nevertheless, it can be done!
lWhen looking at genes that are located on the same chromosome, the segregation of alleles *appears* to break Mendel's rules of independent assortment (it doesn’t actually break the rule). This is because genes that are closely linked on the same chromosome are usually inherited together simply because they are on the same chromosome. In the case of tight linkage (very close together on the chromosome), the two genes act as if they are one unit. Thus, rather than 4 possible gametes (e.g. PL, Pl, pL and pl) from a cross in which both parents are heterozygous PpLl ), there would only be 2 gametes (eg. PL and pl). This makes the ratio of dominant to recessive phenotypes 3:1, as if we were only looking at the transmission of a single gene.
PL pl
PL PPLL PpLl
pl PpLl ppll
However, if the genes are not actually immediately adjacent, there will be more than just 3 genotypes (2 phenotypes) produced in the offspring, because of the phenomenon of crossing over between homologous chromosomes prophase of meiosis I. Crossing over, or recombination, between homologous chromosomes allows disruption of this linkage (fig 5.12), returning the possibility of getting 4 different gametes from a heterozygous individual. The key difference in thinking about linked genes is that the frequency of the gametes and genotypes is no longer EQUAL as it was with unlinked genes.
When genes are on different chromosomes, the frequency of any allele combination is equal (the rule of independent assortment). When genes are linked, and there is recombination, the frequencies are different. There are two names for the kinds of gametes produced when looking at linked genes: "parental" and "recombinant." The parental gametes show the organization that was present in the parent. Recombinant gametes show the "new" arrangement that results from crossing over between the two genes.
If we are looking at two genes, R and E, and an individual is heterozygous for both, they might have the R and E alleles on one homolog and the r and e alleles on the other homolog. For this arrangement, the parental gametes are RE and re (the gametes that would be made without recombination), and the recombinant are Re and rE.
How to determine the frequency of recombinant classes (also shown in a figure in your book). Once it’s known that two genes are on the same chromosome, one can figure out how far apart they are by looking at the number of recombinants. Little by little, genes can be placed on the genetic map of a chromosome. This is known for many genes now that the human genome has been sequenced. However, it is still a tedious process, and the distance between individual genes is not always known. A linkage map is a diagram that indicates relative distance between genes of interest. By convention, one map unit is defined as : the distance between gene pairs for which one product of meisois out of 100 is recombinant. Thus, a recombinant frequency of 1% determines the two genes to be1 m.u. apart. 1 m.u. is equal to about 1 centimorgan, which is then related to an actual number of base pairs dependent upon the organism. Each time a crossing over event occurs between two genes, TWO recombinant chromosomes are produced as a result.
If the genetic map distance between two linked genes has already been determined, you can look at the parental genotypes involved in a mating and predict the % chance of certain classes of recombinants. There are always going to be TWO possible recombinant genotypes if there has been a recombination event. These two recombinant genotypes together will appear at a frequency of 5 % if the two genes are 5 m.u. apart. So, each genotype will appear at a frequency of 2.5%.
Independent vs. dependent events (again)
If you are calculating the frequency of a particular genotype from the merging of two gametes from two different people, it is always an independent event! However, if you are asked to find the frequency of a particular phenotype, and there are MULTIPLE genotypes that produce that phenotype, then these are dependent events, and you have to calculate the total possibility of seeing that phenotype by ADDING the possibilities of seeing each individual genotype.