Glossary (EN)

  • Amino acids: molecules with several distinct chemical properties that are combined in multiple sequences to generate proteins.

  • Codon: sets of three nucleotides that contain the information needed to match the right amino acid during the protein assembly. A nucleotide mismatch in the position 1138 of the FGFR3 gene leads to the placement of the wrong amino acid in the FGFR3 protein chain and causes achondroplasia.
 (from BioGem.Org)

  • Chondrocytes: the cells within the cartilage growth plates, the masters of bone growth. In achondroplasia, due to the excessive function of the FGFR3 mutation G380R, they are forced to reduce their multiplication and maturation rates, which in turn causes a significant loss of bone growth.

  • Exons and introns: exons are the parts of the gene sequence containing the codons that will be translated in amino acids to form proteins. Introns are the parts of the gene that do not have codons.

(from Wikipedia)

  • Fibroblast growth factor receptor type 3 (FGFR3): an enzyme responsible for the control of chondrocyte proliferation and maturation speed, working like a natural brake. When it works too much due to an activating mutation, it causes bone growth arrest. Achondroplasia, the most common cause of dwarfism, is caused by an activating mutation of FGFR3.

  • Growth plate cartilage: a thin band of cartilaginous tissue present in both extremities of long bones. Although relatively small, this tissue is key for the appropriate development and growth of the bones. The growth plate is organized in four layers of chondrocytes, the core cells of bone growth, in different stages of life cycle (figure). There is a resting layer, where chondrocytes are dormant. Triggered by several stimuli, chondrocytes start to proliferate (multiply) and are organized in quite straight piles in a longitudinal axis. Again responding to several local and systemic stimuli, chondrocytes stop to proliferate and start to enlarge (pre-hypertrophy), composing the third layer of the growth plate. When chondrocytes reach their maximum size (full hypertrophy) they die and are substituted by osteoblasts, cells responsible for the assembly of the bone tissue.
  • Nucleotides: they are the four basic molecules which, combined in sequences of three (the codons), will encode the information needed to the production of the proteins.

  •  Signaling pathway or cascade. This is the chemical chain reaction carrying a signal from one point to another inside the cell to generate a particular response from it. This response is frequently related to the production of proteins from the cellular DNA. Protein (s) produced due to the signal will be responsible for the kind of cell response. The signal may come from outside the cell, such as that produced by a hormone or a growth factor. In the case of achondroplasia, the signal starts when a fibroblast growth factor (FGF) couples to the FGFR3. This causes changes in the shape of FGFR3, leading to an electric discharge produced by the displacement of phosphorus ions. This chemical/electrical signal is then transmitted to other neighbor proteins until one or more of these enter the cell nucleus. The signal can be transmitted by several different proteins, and it is what will determine which of the genes in the DNA of the cell is (are) "read" to generate new proteins. Here is a 14 minute animation which shows the entire signaling process since the start signal to the generation of new protein. It is one of the most comprehensive animations on the subject I have ever encountered on the web:
DNA Learning Center by Cold Spring Harbor Laboratory
  • Transcription: the process through which a gene is read and a messenger RNA is created. It is the first main step for a protein to be produced.
  • Transcription factors: proteins capable to identify certain nucleotide sequences in the DNA and bind them.
  • Translation: This is the process through which a sequence of nucleotides present in the mRNA chain is translated into an amino acid sequence, creating a new protein.
  • Upstream sites: They mean sequences of nucleotides located before the gene sequence. There are at least two of these regions located before the gene sequence, the promoter and the enhancer sequences and they are very important to allow gene expression, like beacons for the protein complex that will read the gene (see text).

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