Spinal Muscular Atrophy

SMN1

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

Medline Plus (2009) Spinal Muscular Atrophy

retrieved Feb 3, 2009 from: http://www.nlm.nih.gov/medlineplus/spinalmuscularatrophy.html

Billy Baader - Genetics 677

 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
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Type IV Adult Onset - adulthood

1 in 35-40 Americans are carriers

Retrieved from: http://www.fsma.org/FSMACommunity/understandingsma

1 in 10,000 infants effected

Most deadly recessive genetic disease among infants

 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

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Retrieved from: http://student.britannica.com/comptons/art-66123/Section-of-a-spinal-cord

 SMN1 Gene + Protein
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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

• 28,050 base pairs

• 294 aa
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• 9 exons

• SMN2
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/

 Homologs
Homologs Percent Identity:
1. SMN1, Pan troglodytes (Chimpanzee) DNA: 99.4
survival of motor neuron 1, telomeric Protein:100

2. SMN, Canis lupus familiaris (Dog) DNA: 90.8

survival motor neuron Protein: 89.4

3. SMN, Bos taurus (Cow) DNA: 88.2

survival motor neuron Protein: 85.2

4. Smn1, Mus musculus (Mouse) DNA: 83.5

survival motor neuron 1 Protein: 83.3

5. Smn1, Rattus norvegicus (Rat) DNA: 82.1

survival motor neuron 1 Protein: 81.2

6. SMN, Gallus gallus (Rooster) DNA: 67.1

survival motor neuron Protein: 64.8

7. smn1, Danio rerio (Zebrafish) DNA: 61.2

survival motor neuron 1 Protein: 59.0
 Protein Domain: Tudor

Protein-protein
Interactions
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RNA metabolism

Not fully
understood

Retrieved from: Huang, Y. et al. (2006) Science. 312(5774): 748-51. PDB: 2GFA
 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 QuickTime™ and a
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Yeast Two Hybrid

Retrieved from:

– Neural vs. other tissues http://www.bio.davidson.edu/COURSES/genomics/2005/Durnbaugh/home.ht

Microarrays of gene expression in

different tissues
Mice should be good model organisms to
research SMA
Questions
 References
1. Spinal Muscular Atrophy Foundation (2009) About SMA retrieved
Feb 3, 2009 from:
http://www.smafoundation.org/index.php?option=com_faq&Itemi
d=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