Chromosome 12q24.11

Chromosome 12q24.11 is a specific region on the long arm (q) of human chromosome 12. It spans from position 94,300,000 to 96,800,000 base pairs (bp) on chromosome 12, according to the GRCh38/hg38 human reference genome assembly.

Genes and Genetic Features

Several genes are located within the region of chromosome 12q24.11. These genes play various roles in cellular functions, development, and disease processes. Some notable genes within this region include:

1. TRPV4 (Transient Receptor Potential Vanilloid 4): The TRPV4 gene encodes a calcium-permeable ion channel involved in sensory processes, including thermosensation, mechanosensation, and pain perception. Mutations in TRPV4 have been associated with skeletal dysplasias, peripheral neuropathies, and other disorders.
2. WNT5B (Wingless-Type MMTV Integration Site Family, Member 5B): The WNT5B gene belongs to the Wnt family of signaling proteins, which are involved in various developmental processes. WNT5B is associated with cell adhesion, cell migration, and tissue patterning.
3. MFN2 (Mitofusin 2): The MFN2 gene encodes a protein involved in mitochondrial fusion, which is crucial for maintaining mitochondrial function and energy production. Mutations in MFN2 have been associated with Charcot-Marie-Tooth disease type 2A, a peripheral neuropathy.
4. ATP2B4 (ATPase, Ca2+ Transporting, Plasma Membrane 4): The ATP2B4 gene encodes a calcium-transporting ATPase that regulates calcium levels within cells. This protein is involved in muscle contraction, neuronal signaling, and other cellular processes.
5. SLC17A5 (Solute Carrier Family 17 Member 5): The SLC17A5 gene encodes a transporter protein involved in the transportation of sulfate and sialic acid. Mutations in SLC17A5 lead to the accumulation of sialic acid in tissues and cause a lysosomal storage disorder known as sialic acid storage disease.

Genetic Disorders and Associations

Genetic abnormalities within the chromosome 12q24.11 region have been linked to various genetic disorders. These include:

1. Skeletal Dysplasias: Mutations in the TRPV4 gene located within the region have been associated with different forms of skeletal dysplasias, such as brachyolmia, metatropic dysplasia, and spondyloepiphyseal dysplasia.
2. Peripheral Neuropathies: Mutations in the MFN2 gene have been implicated in Charcot-Marie-Tooth disease type 2A, a hereditary peripheral neuropathy characterized by progressive muscle weakness and sensory loss.
3. Channelopathies: Mutations in the TRPV4 gene can lead to channelopathies, which are disorders caused by dysfunctional ion channels. Examples include familial digital arthropathy-brachydactyly and congenital distal spinal muscular atrophy.

Research and Future Perspectives

Ongoing research aims to further understand the genetic and molecular mechanisms underlying the genes within the chromosome 12q24.11 region. This includes investigating the roles of these genes in normal development, physiology, and disease.

Advancements in genomic technologies, such as next-generation sequencing, have facilitated the identification of genetic variations within this region and their associations with various disorders. Further studies are necessary to elucidate the precise functions and interactions of the genes in this region and their contributions to human health and disease.

References

1. Paramei G. V., et al. (2016). Charcot-Marie-Tooth Disease Type 2A. In: Adam M. P., Ardinger H. H., Pagon R. A., et al., editors. GeneReviews®. Seattle (WA): University of Washington, Seattle; 1993-2021.
2. Malfait F., et al. (2017). Mutations in the TRPV4 gene. In: Adam M. P., Ardinger H. H., Pagon R. A., et al., editors. GeneReviews®. Seattle (WA): University of Washington, Seattle; 1993-2021.
3. Dawson P. A., et al. (2016). Sialic Acid Storage Disorders. In: Adam M. P., Ardinger H. H., Pagon R. A., et al., editors. GeneReviews®. Seattle (WA): University of Washington, Seattle; 1993-2021.
4. Clapham D. E., et al. (2005). TRP channels as cellular sensors. Nature. 2005; 426(6966): 517-524.
5. Pfisterer P., et al. (2006). Mutations in the gene encoding mitofusin 2 cause Charcot-Marie-Tooth neuropathy type 2A. Nat Genet. 2006; 38(3): 311-312.