Lysyl hydroxylase is an enzyme that is required for modification of collagens and consequently, for mechanical strength of connective tissue. The normal gene contains 17 exons. Two Alu, elements are known to exist in this gene, one in the intron between exons 9 and 10, and the other in the intron between exons 16 and 17.
One disease-causing allele of this gene contains extra exons, specifically, a tandem duplication of exons 10 through 16. Thus, the mutant gene contains exons 1 through 16, followed by another 10 through 17.
Please diagram how recombination between the Alu elements mentioned above could (probably did) lead to the creation of this unusual allele.
Hint: Write out the introns and exons, with the Alus in the correct locations.
THEN: Align them so that the Alus are aligned for recombination.
THEN: Do the crossover, connecting the two Alus to each other. Follow the crossover to see what the outcomes are for the two chromatids that are involved in the exchange.
Voila, a deletion and a duplication on the two chromatids.
The diagram below shows the factor VIII gene. The small boxes represent some of the exons and the arrow below the diagram indicates the direction of transcription of this gene. (This gene actually has 26 exons but we'll pretend there are only 6 as shown).
One of the factor VIII introns contains a gene, F8A indicated by the left-pointing arrow in the diagram. Another copy of this gene exists upstream of the promoter, indicated by the right-pointing arrow.
In one form of hemophilia, there has been an intrastrand recombination event involving the two copies of the F8A gene, with disastrous consequences for the factor VIII gene (and the person carrying this allele.) The normal arrangement is diagrammed below. Please diagram the recombination event and its outcome. Describe the effect on the factor VIII gene as clearly as possible.
Please consider the portion of the alpha globin gene cluster shown below. The leftmost gene is an inactive pseudogene and the other two are functional alpha genes, alpha 2 and alpha2. (We are going to ignore the remaining genes in this cluster.) The three genes are very similar in sequence, with the similarity extending up and downstream of the coding regions.
As might be expected, illegitimate recombination is frequent in this region, with the result that many variant chromosomes are present in the human population.
Please diagram recombination events that could produce the following:
a. a chromosome with three active alpha genes
b. an alpha2/alpha I fusion gene (not necessarily alone)
c. a chromosome with no active alpha genes.