Anatomy of a Gene

There are over twenty thousand genes in the human genome, and a substantial fraction of these genes code for proteins involved in the development and function of the brain. Genes are spaced at varying intervals along the strands of DNA, much as songs or other files are arranged on a magnetic tape. The DNA is then tightly packed into chromosomes. The fragile X mental retardation 1 (FMR1) gene is located hear the end of the long arm of the X chromosome.

Figure 1

Genes provide all of the information needed to produce the proteins required for cell growth and development. For most genes that code for proteins, this process fundamentally involves two (very complex) steps. The following diagram will allow you to become familiar with these steps. To learn a bit more about the processing of genetic information, move your cursor over the specific location in the figure.

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The fragile X gene - The most common mutation of the fragile X mental retardation 1 (FMR1) gene is an expansion of a CGG repeat (gold) in a portion of the mRNA that is not translated into protein (FMRP).

figure 3

For "premutation" CGG-repeat expansions (between 55 and 200 repeats), the gene produces excess mRNA, and this excess RNA is believed to result in FXTAS. For "full mutation" expansions (> 200 CGG repeats), the FMR1 gene promoter region is methylated, which shuts down (silences) the gene, so little/no mRNA is produced and therefore no protein is available for proper brain development. The absence of FMRP is responsible for fragile X syndrome.

 

The Promoter is the controller of gene activity - it tells the gene when and in which cell types it should be active. The fragile X (FMR1) gene is "on" throughout life and is most active in cells of the brain.

The coding portion of the gene (maroon) contains the information necessary to produce the protein product of the gene; in the case of the FMR1 gene, the protein is designated FMRP. The coding portion of the gene is normally broken up into separate portions of the gene (not shown), which are spliced back together at the RNA level.

The gene (DNA) is first transcribed into messenger (m)RNA ("message"), much as a set of house plans is copied into blueprints - the process is called transcription

The messenger (m)RNA ("message"), contains all of the protein coding information as well as additional leader and trailer sequence (pink) that controls the translation of the mRNA into protein. In the fragile X (FMR1) gene, the CGG repeat is in the non-coding leader region (gold triangle)

The mRNA molecules are then exported from (move out of) the nucleus of the cell into the cytoplasm, where they are translated into proteins that carry out various cellular functions. In the case of FMRP, these functions include binding to a number of mRNA molecules and regulating their translation.

The mRNA molecules are translated into proteins that carry out various cellular functions. In the case of FMRP, these functions include binding to a number of mRNA molecules and regulating their translation.

The CGG repeat region of the FMR1 gene. In the general population, most individuals carry fewer than ~40 repeats; those who carry premutation expansions have between 55 and 200 repeats, and those who carry full mutation expansions have greater than 200 CGG repeats.