BI0-333 Biomedical Research Paper Mutations in BICD2 Cause Dominant Congenital Spinal Muscular Atrophy and Hereditary Spastic Paraplegia By Oates,...

BI0-333 Biomedical Research Paper

Mutations in BICD2 Cause Dominant Congenital Spinal Muscular Atrophy and Hereditary Spastic Paraplegia

By Oates, E., Rossor, A.M., Hafezparast, M. et al.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3675232/

Mutations in BICD2, which Encodes a Golgin and Important Motor Adaptor, Cause Congenital Autosomal-Dominant Spinal Muscular Atrophy

By Kornelia, N., Martinez-Carrera, L.A., Holker, I. et al.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3675237/

Read both papers and answer the following questions:

1.    Using full sentences, compose at least two paragraphs to describe how BICD2 mutations can cause defects in the function of spinal motor neurons.

2.    In "Mutations in BICD2 Cause Dominant Congenital Spinal Muscular Atrophy and Hereditary Spastic Paraplegia" a genome-wide linkage study was performed using four affected family members and five unaffected family members from a dominant congenital spinal muscular atrophy kindred.

a.     What variants of BICD2 were found to be likely to cause the clinical phenotypes found in the affected family?

b.    Describe the recombinant DNA technologies used to demonstrate the in vitro effects on neuronal cell function of two of the isolated BICD2 variants.

c.     In this research paper both Sanger DNA sequencing and whole exome sequencing were used. Describe the differences between these two DNA sequencing methods.

3.    You have been assigned an unknown DNA sequence from a family with a young boy showing signs of Spinal muscle atrophy (Refer to "Unknown DNA Sequence "). Using the online NCBI tools we have been learning about in class (GENE, OMIM, BLAST, and BLASTX). State which unknown sequence you were assigned and then determine:

a.     The gene this unknown sequence represents based on highest similarity match.

b.    Using the two research articles you were assigned and the NCBI tools. Is this gene that you identified based on similarity to your unknown DNA sequence identified to be involved in Spinal Muscular Atrophy? Can this young boy be classified as having a form of Spinal Muscular Atrophy (SMA)? 

c.     Use BLASTX to translate this DNA sequence and search a protein database to find the best protein sequence match. Display a screenshot of the best protein sequence alignment. Is this protein sequence alignment consistent with the results of the of the DNA alignment? Discuss any changes that have occurred in the unknown DNA sequence query from this young patient. Where these changes deletions, missense mutations, insertions? How might these changes to this protein sequence affect the function of this protein?

4.    Consider that this young boy's family is told of an experimental stem cell treatment that can potentially alleviate some or all of the symptoms with which this boy is experiencing. From a Christian World View perspective, should the researchers or the family  "play God " and try to correct the neuronal cells that are affected in Spinal Muscular Atrophy? Discuss your views on this potential stem cell therapy and discuss the ethical questions that you think need to be considered when developing new DNA based medical treatments.