Spinal Muscular Atrophy SMN1 Billy Baader - Genetics 677 Medline Plus (2009) Spinal Muscular Atrophy retrieved Feb 3, 2009 from:

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



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



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



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



Spinal Muscular Atrophy Foundation (2009) About SMA retrieved from: http://www.smafoundation.org/index.php?option=com_faq&Itemid=32&Itemid=32



Retrieved from: http://www.ebi.ac.uk/msd-srv/msdlite/atlas/visualization/1g5v.html

SMN Complex



Gubitz et al. The SMN Complex. Experimental Cell Research(2004) 296: 51-56

Protein Network (Homo Sapiens)





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)



Retrieved from: http://string.embl.de/newstring_cgi/show_network_section.pl

Phylogeny



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






Protein Domain: Tudor



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



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

Documents

Spinal Muscular Atrophy SMN1 Billy Baader - Genetics 677 Medline Plus (2009) Spinal Muscular Atrophy retrieved Feb 3, 2009 from: