GBA - Glucosidase/Glucocerebrosidase
Basic Facts
GBA is the gene related to Gaucher’s Disease. Officially GBA stands for: glucosidase, beta, acid. More than 200 mutations of the gene were found in people with Gaucher’s Disease. The disease is characterized by the buildup of a fatty substance (glucocerebroside) in organs, commonly one’s spleen and liver. This causes the organs to enlarge and therefore, affects their function. The buildup of the same fatty substance can also occur in bones, causing them to become weak and fragile. In a person who did not carry the mutation, an enzyme called glucocerebrosidase breaks down glucocerebroside, a part of the cell membrane. Patients with Gaucher’s Disease cannot make enough glucocerebrosidase, leading to the buildup in one’s spleen, liver, and bones. These attributes cause an array of symptoms, including: skeletal abnormalities, painfully distended abdomen, and a decrease in healthy red blood cells, which can lead to fatigue. In more rare cases Gaucher’s Disease can affect the brain, causing abnormal eye movements, difficulty swallowing, muscle rigidity, and seizures. Treating Gaucher’s Disease often involves enzyme replacement therapy.
The GBA gene is located on chromosome one (1), and its cytogenetic location is 1q21.
Gene History
Professor Shafit-Zagardo, from Albert Einstein College of Medicine of Yeshiva University originally mapped the GBA gene to the chromosome 1p11-qter. Devine narrowed it down to 1q42-qter. Barneveld studied hamster-human somatic cell hybrids, assigning the gene to 1q21-q31. Through somatic cell hybridization and in situ hybridization, Ginns placed GBA at 1q21 in 1985.
Science Behind the Gene
Gene Expression:
The GBA gene is responsible for providing instructions to make beta-glucocerebrosidase, which is an enzyme active in lysozomes. Lysozomes are structures in the cells that act as “recycling centers” that attach and release enzymes to digest substances in the cells. They specifically use digestive enzymes to break down substances that are toxic.
The photo below is a GeneCard, which estimates the locations of GBA protein expression.
The GBA gene is responsible for providing instructions to make beta-glucocerebrosidase, which is an enzyme active in lysozomes. Lysozomes are structures in the cells that act as “recycling centers” that attach and release enzymes to digest substances in the cells. They specifically use digestive enzymes to break down substances that are toxic.
The photo below is a GeneCard, which estimates the locations of GBA protein expression.
GeneCard - http://www.genecards.org/cgi-bin/carddisp.pl?gene=GBA
PCR With GBA:
We ran PCR on our gene with primers that followed the following information:
We ran PCR on our gene with primers that followed the following information:
The results: (we are groups 4 & 5)
Although we were expecting a band of size 226, our band fell closer to the 300-400 range. There may have been other genetic information added during the PCR process that caused this result.
Although we were expecting a band of size 226, our band fell closer to the 300-400 range. There may have been other genetic information added during the PCR process that caused this result.
Affects on Other Genes:
Gaucher’s Disease has been found to increase the risk of growth delays in children, obstetric problems, cancers such as myeloma, leukemia, and lymphoma, as well as Parkinson’s Disease. Research has shown that carriers of GBA mutations have a higher propensity to develop Parkinson’s disease, meaning that gene mutations associated with Gaucher’s Disease leads to increased susceptibility for Parkinson’s Disease. In 2004 Goker-Alpan, co-author of a report in The Journal Of Medical Genetics reported that: “Observations indicate that mutant glucocerebrosidase, even in heterozygotes, may be a risk factor for the development of parkinsonism.” In summary, his findings concluded that heterozygosity for mutations in the GBA gene may be a risk factor for the development of Parkinson’s Disease.
Gaucher’s Disease has been found to increase the risk of growth delays in children, obstetric problems, cancers such as myeloma, leukemia, and lymphoma, as well as Parkinson’s Disease. Research has shown that carriers of GBA mutations have a higher propensity to develop Parkinson’s disease, meaning that gene mutations associated with Gaucher’s Disease leads to increased susceptibility for Parkinson’s Disease. In 2004 Goker-Alpan, co-author of a report in The Journal Of Medical Genetics reported that: “Observations indicate that mutant glucocerebrosidase, even in heterozygotes, may be a risk factor for the development of parkinsonism.” In summary, his findings concluded that heterozygosity for mutations in the GBA gene may be a risk factor for the development of Parkinson’s Disease.
Parkinson's Disease
The National Human Genome Research Institute, and the National Institute on aging, which are both branches of the National Institutes of Health discovered GBA’s link to Gaucher Disease. They collaborated with scientists from 16 research centers across 4 continents.
Beyond Gaucher's disease, mutations in the GBA gene have been linked to Parkinson’s disease, a neurological condition typically characterized by shaking and difficulty with movement. Research has shown that patients with the Parkinson’s disease condition possessed a larger frequency of mutations in the GBA gene compared to the control group. Additionally, research has indicated that patients whose parkinsonism is associated with the GBA gene develop Parkinson’s at an earlier age, with more cognitive changes, compared to patients without GBA mutations. For example, Parkinson’s patients with GBA mutations developed symptoms of the condition four years earlier (on average) than other patients. The link between Parkinson’s and GBA has not been connected to any specific ethnicities or mutations, but some research has shown gene alterations to be more frequent in specific populations. To this day, scientists are still conducting research to further explore the specific alterations prompting the onset of Parkinson’s.
Beyond Gaucher's disease, mutations in the GBA gene have been linked to Parkinson’s disease, a neurological condition typically characterized by shaking and difficulty with movement. Research has shown that patients with the Parkinson’s disease condition possessed a larger frequency of mutations in the GBA gene compared to the control group. Additionally, research has indicated that patients whose parkinsonism is associated with the GBA gene develop Parkinson’s at an earlier age, with more cognitive changes, compared to patients without GBA mutations. For example, Parkinson’s patients with GBA mutations developed symptoms of the condition four years earlier (on average) than other patients. The link between Parkinson’s and GBA has not been connected to any specific ethnicities or mutations, but some research has shown gene alterations to be more frequent in specific populations. To this day, scientists are still conducting research to further explore the specific alterations prompting the onset of Parkinson’s.
Inheritance
GBA is inherited through an autosomal recessive pattern. In this situation both parents must be carriers of a Gaucher’s genetic mutation for the child to potentially inherit the condition. Each parent must have one recessive gene (mutated), and one dominant gene (normal) for Gaucher’s. In an autosomal recessive pattern there is a 25% chance that they will have a child with two dominant, normal genes, a 50% chance that they will carry the gene but never experience the symptoms, and a 25% chance that their child will inherit two recessive genes and become affected by the gene mutations.
A Take Away:
”Understanding the relationship between altered glucocerebrosidase and the development of parkinsonian manifestations will provide insights into the genetics, pathogenesis, and treatment of Parkinson disease.” - Goker-Alpan
Links Used:
http://www.omim.org/entry/606463 http://omim.org/entry/168600.
http://ghr.nlm.nih.gov/gene/GBA.
http://www.genome.gov/25521505.
http://www.mayoclinic.org/autosomal-recessive-inheritance-pattern/img-20007457.
http://jmg.bmj.com/content/41/12/937.long.
http://www.childrensgaucher.org/recent-news/study-conclusively-linksgba-gene-to-parkinsons/
http://www.genecards.org/info.shtml#expression_images
https://www.youtube.com/watch?v=Q4WKt57Q0js
http://www.ncbi.nlm.nih.gov/IEB/Research/Acembly/av.cgi?d
http://www.omim.org/entry/606463 http://omim.org/entry/168600.
http://ghr.nlm.nih.gov/gene/GBA.
http://www.genome.gov/25521505.
http://www.mayoclinic.org/autosomal-recessive-inheritance-pattern/img-20007457.
http://jmg.bmj.com/content/41/12/937.long.
http://www.childrensgaucher.org/recent-news/study-conclusively-linksgba-gene-to-parkinsons/
http://www.genecards.org/info.shtml#expression_images
https://www.youtube.com/watch?v=Q4WKt57Q0js
http://www.ncbi.nlm.nih.gov/IEB/Research/Acembly/av.cgi?d
