The genome data you will be investigating was collected as part of the 1000 genomes project. It is from an apparently healthy British female (number 121 out of the XXXXXXXXXXYou will be provided, via...

The genome data you will be investigating was collected as part of the 1000 genomes project. It is from an apparently healthy British female (number 121 out of the 1000). You will be provided, via an email link to Dropbox, with exome data for chromosome 11 from this individual. The sequencing reads have been previously aligned to Human Genome Feb 2009 reference hg19. The alignments are in BAM format prepared using as was described in the Galaxy tutorial. Remember that you must keep the ‘index’ BAI file in the same folder ('directory') as the BAM file as both are required for programs to access the alignment data.


You will be examining an amino acid position in the DLAT gene of this individual. You will be describing what you see at the DNA level and what the effect of this is on the protein produced. Remember that the individual may be heterozygous for the mutation.


You will need to be able to run the Integrated Genome Viewer program described in the IGV tutorial. Refer back to that for guidance. Remember that IGV only colours and labels nucleotides in the aligned reads that differ from the reference genome. The default loaded into IGV is hg19 which is the correct one for your work. Figures for your report can be generated from IGV by using the File>Save Image> menu item, then selecting a name for your snapshot.


Figures of the protein structure involved can be made using an online display program Jolecule  https://jolecule.appspot.com/ or the online ICM browser program  https://www.molsoft.com/pdbv.html to look at where the variation is in the protein structure with variation.


Make sure you write a clear and explanatory legend for these figures and mention them at the appropriate point when you include them in your report.
Laboratory report instructions


Write a laboratory report (up to 2000 words, excluding references, tables and figures) on the resit bioinformatics problem entitled, ‘Analysis of a missense variant in the DLAT gene of a British human exome’. Draw upon the bioinformatics tutorials given during the module, and the information here, to help you. Your report should be structured as follows:


1.     Introduction (20 marks). State why this study is being done - mentioning some background to the subject(s) involved and their health.



2.     Materials and Methods (5 marks). Briefly describe the advantages of exome sequencing compared with full genome sequencing.



3.     Results and Discussion (40 marks). You should prepare a figure displaying the positions of the variant in the allelic variation on chromosome 11 in the IGV program. You should indicate whether the individual is homozygous or heterozygous for the variant and other positions in the gene. You should indicate where the effect of the mutation will be in the protein and what the effect is on the predicted amino acid. You can speculate on whether the amino acid change is large enough to de-stabilize the protein. Finally, prepare a figure displaying the amino acid position on the protein that is affected by the variation. Optionally you can also display a mutation close by that is known to have a large pathological effect.



4.     Conclusion (15 marks). Is this individual’s mutation likely to cause a loss of the protein



activity and lead to disease? Explain your answers.


5.     Report Structure (10 marks). Easy-to-read; logical flow and order with appropriate headings or subheadings as needed; tables and figures numbered with appropriate legends; graphics appropriately prepared for clarity.



6.     References (5 marks). No more than 10 papers. List, in addition, the databases and reference id numbers for syndromes and SNP variation you identify.



7.     Supplementary Information (5 marks). Any additional figures with descriptive legends