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A Genomic Approach to Two Related Human Scourges
John Ferguson, Scott H. Harrison and Mary Spratt
Introduction
[see uploaded content; PPT file]
Materials
Databases: IMG, NCBI and KEGG
Questions after Introduction
1) TB thrives in crowded conditions lacking in sanitary conditions. Would this favor
a quick cycle of infection and transmission?
2) The symptoms of leprosy take years to emerge in terms of deformation of bones
and tissues, first infecting the extremities such as ears and toes. Would you expect
this to be a slow or fast-reproducing bacteria?
3) If a bacteria was being destroyed quickly by other competing bacteria or the
immune system, would it be advantageous for it to grow fast or slow?
4) If a bacteria in the human body did not experience competition or effective
challenge
5) from the immune system, would a bacteria lose unnecessary content in its
genome?
6) Is an alternative possibility that genes acquire mutations and become nonfunctional outside the force of selection?
Laboratory Exercise Module #1:
Profiling the genomic complexity of tuberculosis and leprae
Go to NCBI web site and find the sizes of the two genomes.
Go to this web site and find the number of ORFs of the two genomes
What is the density of ORFs on these genomes?
Laboratory Exercise Module #2:
Investigating genes and pathways across four Actinobacteria
genomes
IGM and pathway analysis
Two from our menu list and choose your own ORF
Look at these four genomes
Based on BLAST scores between the conserved set of ORFs across these four genomes,
which two genomes are most closely related?
Go to IGM.
Do all four genomes have high similarity matches for your ORF?
Are the highest similarity matches for ORFs of the same length?
Looking at the provided phylogenetic tree, are there ORFs that are present
For only three of the genomes and not four, and may this imply a loss of an ORF.
Look at the following trees. If ORFs are present in only two genomes, does this mean
loss of ORF in the other two genomes or gaining of ORF in the other two genomes?
Is your ORF functional? Is it conserved across two or more genomes? Is its length
conserved? If it is on only one genome, does it occur elsewhere in phylogeny (use IGM)?
Codon usage? Pathway analysis?
Interesting articles/References:
“Leprosy as a model for genetic susceptibility”
Fuxelius et al
Visualization of pseudogenes in intracellular bacteria reveals the different tracks to gene
destruction
Concha et al
Hanesen’s disease: case report and review of literature
Alter et al
Leprosy as a genetic model for susceptibility to common infectious diseases