The key difference between SMN1 and SMN2 gene is that a mutation in the SMN1 gene leads to spinal muscular atrophy, while a mutation in the SMN2 gene does not lead to spinal muscular atrophy.
SMN1 and SMN2 genes are two identical genes located within an inverted duplicated region on chromosome 5q13.2. They are 99% percent identical to each other. One of the main differences between these genes is the C to T transition in exon 7 of SMN2. Biallelic deletions or mutations in the SMN1 gene result in a deficiency of SMN1 protein, which lead to a neuromuscular disease called spinal muscular atrophy. Moreover, SMN2 is not associated with this disease. Rather, this gene may be a modifier of disease caused by mutations in the SMN1 gene.
CONTENTS
1. Overview and Key Difference
2. What is SMN1 Gene
3. What is SMN2 Gene
4. Similarities – SMN1 and SMN2 Gene
5. SMN1 vs SMN2 Gene in Tabular Form
6. Summary – SMN1 vs SMN2 Gene
What is SMN1 Gene?
SMN1 gene is generally called the survival of motor neuron gene. It is also known as a component of gems 1. This gene encodes a specific protein named SMN protein in humans. This gene is in the telomeric region of chromosome 5. Further, the SMN1 gene is also located in a part of chromosome 5 q13 called an inverted duplicated region, which is 500 kbp long. This duplicated region contains at least 4 genes (eg. SMN2 gene) and repetitive elements. Moreover, the inverted duplicated region is prone to rearrangements and deletion due to its complexity. SMN1 and SMN2 genes are nearly identical. But there is a critical sequence difference in the two genes, which is a single nucleotide transition (C to T) in exon 7.
Figure 01: SMN1 Gene
Mutations in the SMN1 gene lead to a neuromuscular disorder called spinal muscular atrophy. However, deletions in the SMN2 gene do not lead to this disease. Furthermore, mutations in both SMN1 and SMN2 genes together result in embryonic death.
What is SMN2 Gene?
SMN2 gene is normally called survival of motor neuron 2. This gene produced two types of proteins in humans; normal full-length SMN protein and truncated SMN protein. Due to the transition of C to T in exon 7 of the gene, there is a production of a truncated, non-functional SMN protein from the majority of SMN2 mRNA transcripts. However, 10 to 15% of SMN2 mRNA transcripts from the SMN2 gene can produce functional, full-length SMN protein. Therefore, the loss of function of the SMN1 gene by mutations is partially compensated by SMN protein synthesis through SMN 2 gene.
Furthermore, the nucleotide substitution in SMN 2 gene results in around 80-90% of truncated and unstable protein while 10-20% of the full-length protein, which is very similar to the protein made by the SMN1 gene. In addition to that, as this gene is a modifier of the disease, it is found the presence of three or more copies of SMN2 is associated with a milder phenotype of spinal muscular atrophy.
What are the Similarities Between SMN1 and SMN2 Gene?
- SMN1 and SMN2 genes are two identical genes located within an inverted duplicated region on chromosome 2.
- Both genes are 99% percent identical to each other.
- Both these genes are present in humans.
- They are capable of producing full-length SMN protein.
- Both genes are very important for mRNA synthesis in motor neurons and inhibit their apoptosis.
What is the Difference Between SMN1 and SMN2 Gene?
Mutation in the SMN1 gene does lead to spinal muscular atrophy, while a mutation in the SMN2 gene does not lead to spinal muscular atrophy. Thus, this is the key difference between SMN1 and SMN2 genes. Furthermore, SMN1 always produces full-length SMN protein, while SMN 2 gene produces around 80-90% of truncated and unstable SMN protein and 10-20% of full-length SMN protein.
The below infographic presents the differences between SMN1 and SMN2 gene in tabular form for side-by-side comparison.
Summary – SMN1 vs SMN2 Gene
SMN1 and SMN2 genes are two genes that are 99% identical to each other. They are located within an inverted duplicated region on chromosome 5q13.2, which is prone to rearrangements and deletion due to their complexity. However, a mutation in the SMN1 gene does lead to spinal muscular atrophy, while a mutation in the SMN2 gene does not lead to spinal muscular atrophy. So, this is the key difference between SMN1 and SMN2 genes.
Reference:
1. “SMN1 Survival of Motor Neuron 1, Telomeric [Homo Sapiens (Human)] – Gene – NCBI.” National Center for Biotechnology Information, U.S. National Library of Medicine.
2. “SMN2 Survival of Motor Neuron 2, Centromeric [Homo Sapiens (Human)] – Gene – NCBI.” National Center for Biotechnology Information, U.S. National Library of Medicine.
Image Courtesy:
1. “Cuerpos de Cajal” By Hao et al – Biomedical Central (CC BY 3.0) via Commons Wikimedia
