spinal muscular atrophy smn1 billy baader - genetics 677 medline plus (2009) spinal muscular atrophy...
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Spinal Muscular AtrophySMN1
Billy Baader - Genetics 677
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Medline Plus (2009) Spinal Muscular Atrophy retrieved Feb 3, 2009 from: http://www.nlm.nih.gov/medlineplus/spinalmuscularatrophy.html
Gubitz et al. The SMN Complex. Experimental Cell Research(2004) 296: 51-56
What is SMA?
• Neuromuscular Disease• Inactivated Muscle Communication
Weak and eventually atrophied muscles
• Death is inevitable
• Characterized by time of onset and severity
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Severity and Statistics
Type I Acute - <6 months after birth
Type II Intermediate - age 6 - 18 months
Type III Mild - 18 months - early adulthood
Type IV Adult Onset - adulthood
1 in 35-40 Americans are carriers
1 in 10,000 infants effected
Most deadly recessive genetic disease among infants
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Retrieved from: http://www.fsma.org/FSMACommunity/understandingsma/
Cause of SMA - SMN1
• Deletion or a mutation of the SMN1 gene leads to SMA
• SMN1 encodes Survival of motor neuron protein 1
• Functions in snRNP biogenesis and mRNA processing
• Problem is in the anterior horn cells
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Spinal Cord
Retrieved from: http://student.britannica.com/comptons/art-66123/Section-of-a-spinal-cord
SMN1 Gene + Protein
• 28,050 base pairs• 294 aa• 9 exons
• SMN2
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Spinal Muscular Atrophy Foundation (2009) About SMA retrieved from: http://www.smafoundation.org/index.php?option=com_faq&Itemid=32&Itemid=32
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Retrieved from: http://www.ebi.ac.uk/msd-srv/msdlite/atlas/visualization/1g5v.html
SMN Complex
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Gubitz et al. The SMN Complex. Experimental Cell Research(2004) 296: 51-56
Protein Network (Homo Sapiens)
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Retrieved from: http://string.embl.de/newstring_cgi/show_network_section.pl Retrieved from: http://string.embl.de/newstring_cgi/show_network_section.pl
Protein Network (Mus Musculus)
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Retrieved from: http://string.embl.de/newstring_cgi/show_network_section.pl
Phylogeny
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Retrieved from: http://www.phylogeny.fr/
HomologsHomologs1. SMN1, Pan troglodytes (Chimpanzee)survival of motor neuron 1, telomeric
2. SMN, Canis lupus familiaris (Dog)survival motor neuron
3. SMN, Bos taurus (Cow)survival motor neuron
4. Smn1, Mus musculus (Mouse)survival motor neuron 1
5. Smn1, Rattus norvegicus (Rat)survival motor neuron 1
6. SMN, Gallus gallus (Rooster)survival motor neuron
7. smn1, Danio rerio (Zebrafish)survival motor neuron 1
Percent Identity:DNA: 99.4Protein:100
DNA: 90.8Protein: 89.4
DNA: 88.2Protein: 85.2
DNA: 83.5Protein: 83.3
DNA: 82.1Protein: 81.2
DNA: 67.1Protein: 64.8
DNA: 61.2Protein: 59.0
Protein Domain: Tudor
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Retrieved from: Huang, Y. et al. (2006) Science. 312(5774): 748-51. PDB: 2GFA
Protein-protein Interactions
RNA metabolism
Not fullyunderstood
Mystery of SMA
Why low levels of SMN protein in the cells of SMA patients lead to the specific loss of motor neurons remains a central question in this field.
SMN may be involved in the transport of specific mRNA molecules in motor axon.
However, whether the clinical symptoms of SMA are caused by deficiencies in functions of SMN that are specific to the motor neuron or common to all cells but at higher demand in this cell type must still be resolved.
Future Possibilities
Yeast Two Hybrid– Neural vs. other tissues
Microarrays of gene expression in different tissues
Mice should be good model organisms to research SMA
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Retrieved from: http://www.bio.davidson.edu/COURSES/genomics/2005/Durnbaugh/home.html
Questions
References
1. Spinal Muscular Atrophy Foundation (2009) About SMA retrieved Feb 3, 2009 from: http://www.smafoundation.org/index.php?option=com_faq&Itemid=32&Itemid=32
2.Medline Plus (2009) Spinal Muscular Atrophy retrieved Feb 3, 2009 from: http://www.nlm.nih.gov/medlineplus/spinalmuscularatrophy.html
3.eMedicine (2009) Spinal Muscular Atrophy retrieved Feb 3, 2009 from: http://emedicine.medscape.com/article/1181436-overview
4.Fight SMA What is Spinal Muscular Atrophy retrieved Feb 3, 2009 from: http://www.fightsma.org/index.php?what_is_sma