GENE EXPRESSION:  WHAT IS PELIZAEUS- MERZBACHER DISEASE?

Pelizaeus-Merzbacher disease is a genetic disorder that affects the brain and spinal cord (central nervous system), and is a part of the genetic disorder group Leukodystrophy. Leukodystrophies are conditions that affect the brain's white matter, which are areas of the brain that contain myelinated axons. These axons are covered with myelin, a sheath that has a white color, hence the name "white matter." Pelizaeus-Merzbacher is an X-linked disease; thus, males are primarily affected, as they only have one X chromosome and an error in one copy is never obscured by a second, unaltered copy. Those with Pelizaeus-Merzbacher disease often have delayed development of motor skills, speech difficulties, seizures, jerking movements, and experience weak muscle tone. However, the severity of these symptoms depend on whether the individual has the classic or connatal type; the classic type often develops within the first year of life and progresses slowly over time while the connatal type has symptoms since birth and has a much quicker progressiveness.    

PLP1 AND PELIZAEUS- MERZBACHER DISEASE

Based on studies, mutations in the gene PLP1 cause Pelizaeus-Merzbacher disease. PLP1 encodes a proteolipid protein that is responsible for a number of roles in the central nervous system, such as the maintenance of myelin. The mutations in the gene that can cause the disease lead to an increased or abnormal production of the protein; when this happens, the protein is unable to travel to the cell membrane and form the myelin sheath. Thus, the nervous system functions are impaired and nerve fibers are damaged, leading to the symptoms of Pelizaeus-Merzbacher disease. Figure 1 shows a section of the details page in the Genome summarizing information from the RefSeq project at NCBI.

Figure 1. Information regarding PLP1   http://genome.ucsc.edu/cgi-bin/hgGene?db=hg19&hgg_gene=PLP1 

Some genetic variants in PLP1 result in a disorder called spastic paraplegia, also the result of demyelinization. (https://omim.org/entry/300401#0020).  Figure 2 shows a Browser view of PLP1 with the OMIM Allelic Variants data track turned on.  Two different mouseovers were superimposed to show different phenotypes associated with different variants.

Figure 2. Different variants of PLP1 are associated with different disease states
http://genome.ucsc.edu/s/education/hg19_PLP1

VIEWING PLP1 IN THE GENOME BROWSER

Through the UCSC Genome Browser, one can view information regarding the PLP1 gene ( http://genome.ucsc.edu/s/education/hg19_pelizaeus).

In this session, we will be mainly looking at the GTEx Gene Expression track. 

On the hg19 human genome assembly, the GTEx Gene track displays the median gene expression levels in 51 tissues and 2 cell lines based on RNA-seq data. It can be accessed on the main browser page of the gene or when you scroll down on the details page after clicking into the gene in the UCSC Genes track. 

Figure 3 shows the GTEx gene expression profile of PLP1.  The expression profile shows that PLP1 is mostly expressed in the brain and the spinal cord. This is a good example of a gene that is expressed in specific cells or organs and whose expression is consistent with an observable phenotype. Many other genes display similar tissue-specific expression patterns, not all of which have an obvious relationship to phenotypes.

Figure 3. Gene expression, by tissue, of PLP1
http://genome.ucsc.edu/cgi-bin/hgGene?db=hg19&hgg_gene=PLP1#gtex. Links on that page lead to the original GTEx project data.

Written by Callie Lin, UCSC.  Majors:  BS, Biomolecular Engineering & Bioinformatics; BS, Neuroscience