Genes
BRCA2
Overview
BRCA2 is a gene that everyone has, and its primary role is to help prevent cancer by repairing damaged DNA. However, some people inherit a faulty version of this gene, which can increase their risk of developing certain types of cancer, including breast and ovarian cancer. This is because the faulty gene is less effective at fixing damaged DNA, allowing potentially cancerous cells to multiply. Testing for changes in the BRCA2 gene can help identify individuals at a higher risk of developing these cancers. Despite the increased risk, not everyone with a faulty BRCA2 gene will develop cancer, as other genetic and environmental factors also play a role.
Short Overview
Conditions associated with BRCA2
BRCA2 is a gene that everyone has, and its primary role is to help prevent cancer by repairing damaged DNA. However, some people inherit a faulty version of this gene, which can increase their risk of developing certain types of cancer, including breast and ovarian cancer. This is because the faulty gene is less effective at fixing damaged DNA, allowing potentially cancerous cells to multiply. Testing for changes in the BRCA2 gene can help identify individuals at a higher risk of developing these cancers. Despite the increased risk, not everyone with a faulty BRCA2 gene will develop cancer, as other genetic and environmental factors also play a role.
Gene Function
BRCA2 is a key gene that helps maintain the stability of a cell's genetic information by aiding in the repair of damaged DNA, specifically through a process known as homologous recombination. It also plays a role in controlling the cell cycle, ensuring DNA is replicated only once per cycle to prevent the build-up of genetic errors and uncontrolled cell growth, a characteristic of cancer. Additionally, BRCA2 interacts with various other proteins to perform its functions, which can offer insights into its operation and how its malfunction can result in disease.
Mutation and Pathology
BRCA2 is a gene that, when functioning normally, helps suppress the growth of cancerous cells. However, mutations in this gene can lead to an increased risk of several types of cancer, most notably breast and ovarian cancer in women, and to a lesser extent, prostate and pancreatic cancer in men. Additionally, BRCA2 mutations can cause Fanconi anemia, a rare disorder that affects the body's ability to repair DNA damage, leading to various developmental problems and a higher risk of cancer.
Diagnostics
BRCA2 genetic testing is typically conducted when there is a family history of breast, ovarian, or related cancers. The decision to test is often guided by a healthcare provider, who takes into account the individual's personal and family medical history. While a positive result indicates an increased cancer risk, it does not guarantee the development of the disease.
Effect of Variations on the BRCA2
Variants are common variations in genes that can significantly impact the health and traits of an individual. This section shows all variants that are located on BRCA2 as well as their associated conditions, traits and drugs.
Did you know that gene anomalies are relatively common?
On average, each person has approximately 100 to 400 genes that are not normal (with different genes being affected in different people). However, usually, the matching gene on the other chromosome within the pair is normal, which helps prevent any potential negative consequences. In the broader population, the odds of someone having two copies of the same abnormal gene (and hence, a genetic disorder) are very low. However, this probability is higher for children whose parents are closely related by blood.
Dr. Wallerstorfer
Conditions caused and influenced by BRCA2
Genetic abnormalities can significantly influence the likelihood of developing a certain condition, either increasing or decreasing the risk. These mutations can alter gene function, which may result in protein malfunction or a lack of protein production. However, even if a genetic mutation increases the risk, it doesn't necessarily mean the condition will develop as environmental and lifestyle factors also play a role.
Did you know the difference between mutations, genetic variations, variants and haplotypes?
Mutations are random changes in the DNA and genetic variations are differences in the DNA among people. Variants are tiny changes in just one piece of the DNA while haplotypes are groups of these changes that usually come together.
Dr. Wallerstorfer
Traits caused and influenced by BRCA2
Abnormalities in genes can also have a significant impact on an individual's traits, or physical characteristics. These genetic mutations can affect the way certain traits are expressed by modifying the function of the related genes. However, the manifestation of these traits isn't determined by genetics alone. It's also influenced by a combination of environmental factors and interactions with other genes. Thus, while a gene mutation can potentially influence a trait, it doesn't necessarily dictate its final expression.
Did you know that Genes vary substantially in size?
In the human genome, there are approximately 21,000 protein-coding genes. Notably, 17,000 of these genes contain only a single variant. However, a small fraction, around 6%, contain more than 50 variants. One gene, CSMD1, stands out significantly with a total of 1008 variants. In terms of size, CSMD1 spans over 818 kilobases, making it considerably larger than TDF, which is one of the smallest genes in the human genome at just 35 kilobases.
Dr. Wallerstorfer
Variants located on BRCA2
A genetic code of a gene usually has many differences in individual genetic letters or tiny pices of the DNA.
Did you know variants may affect drugs?
Variants can influence how our body reacts to certain drugs. The presence of specific variants can increase or decrease the efficiency and effectiveness of a drug, impacting how well it works inside our system. Additionally, certain variants can heighten or lessen the toxicity of a drug, thereby affecting the risk of unwanted side effects. They can also alter how a drug is metabolized, which influences the appropriate dosage one should receive.
Dr. Wallerstorfer
Pharmacogenetics
Variants can significantly influence how our body processes and reacts to drugs. The presence of specific variants can determine the efficiency and effectiveness of a medication, influencing its performance within our system. Additionally, certain variants can modify the drug's toxicity, thereby affecting the likelihood of unwanted side effects. They can also impact how a drug is metabolized, which in turn determines the ideal dosage one should receive. Every individual's response to medication can vary, largely dictated by their genetic makeup. Variations in genes can influence the functions of enzymes, transporters, receptors, and other proteins that interact with drugs. For example, certain genetic variants can alter an enzyme's function, causing it to metabolize a drug too quickly or too slowly. Such variations can either render a treatment ineffective or heighten the risk of side effects.
Gene Function & Mechanism
BRCA2 is a crucial player in the maintenance of genomic stability, which is vital for the prevention of diseases such as cancer. It is involved in several key biological processes, including DNA repair, cell cycle control, and protein interactions. The protein encoded by the BRCA2 gene is a part of the complex machinery that ensures the integrity of our genetic material. Here are some of the specific functions and processes associated with BRCA2.
DNA Repair: It is instrumental in the repair of damaged DNA. BRCA2 plays a key role in a process called homologous recombination, which is a high-fidelity method for fixing DNA double-strand breaks. In this process, it helps to guide the repair machinery to the site of damage and ensures the correct sequence is used for repair.
Cell Cycle Control: It also participates in the control of the cell cycle. BRCA2 helps to ensure that DNA is only replicated once per cell cycle, preventing the accumulation of genetic errors. This function is crucial for preventing uncontrolled cell growth, a hallmark of cancer.
Protein Interactions: It interacts with a variety of other proteins to carry out its functions. These interactions allow BRCA2 to recruit and position the necessary repair proteins at the site of DNA damage. Understanding these interactions can provide insights into how it functions and how its dysfunction can lead to disease.
Gene expression
BRCA2 is a gene that instructs the body to produce a protein that helps repair damaged DNA. This protein plays a crucial role in maintaining the stability of a cell's genetic information. When the BRCA2 gene is functioning properly, it helps prevent cells from growing and dividing too rapidly or in an uncontrolled way. However, if mutations occur in the BRCA2 gene, it can lead to problems with DNA repair, which can increase the risk of developing certain types of cancer. The expression of BRCA2 is therefore vital for maintaining the health and normal function of cells.
Prompoters and Inhibitors
BRCA2, a crucial gene in our bodies, is regulated by both promoters and inhibitors. Promoters are like the gas pedal in a car, they help speed up the production of BRCA2. On the other hand, inhibitors act like the brakes, slowing down or stopping the production. Some key promoters for BRCA2 include E2F1 and p53, while inhibitors include miR-19a and miR-19b. Understanding these elements can help us better comprehend how our bodies prevent diseases like cancer.
Protein Structure
BRCA2 proteins are like a toolbox, each with different tools or "domains" that perform specific tasks. The first domain, the N-terminal, is like a key, helping the protein to interact with others. The BRC repeats, another domain, are like a magnet, attracting and binding to other proteins. The DNA binding domain is like a pair of tweezers, grabbing onto DNA to repair it. Lastly, the C-terminal domain is like a switch, turning on the protein's ability to interact with DNA and other proteins.
Protein Interactions
The proteins made by the BRCA2 gene work like a team, interacting with other proteins in our cells. Their main job is to help repair damaged DNA, the blueprint for everything our bodies do. They do this by joining forces with a protein called RAD51. Together, they fix the DNA, ensuring our cells grow and divide properly. If this teamwork is disrupted, it can lead to problems like cancer.
Similar Genes
Similar to BRCA2, genes such as PALB2, CHEK2, and ATM also play a crucial role in maintaining the stability of a cell's genetic information. These genes are involved in repairing damaged DNA, a process vital for preventing the growth of cancer cells. Mutations in these genes can increase the risk of developing certain types of cancer, much like BRCA2. For instance, changes in PALB2 have been linked to breast cancer and pancreatic cancer, while alterations in CHEK2 and ATM are associated with an increased risk of breast cancer. Therefore, these genes share a similar function and potential risk factor with BRCA2.
Gene interaction
BRCA2, a crucial player in our body's DNA repair system, interacts with several other genes to maintain the integrity of our genetic material. These interactions are vital for preventing errors that could lead to diseases like cancer. The way BRCA2 interacts with other genes is a fascinating example of the complexity and precision of our genetic machinery. Let's delve into some of these interactions.
PALB2: This gene is a partner and localizer of BRCA2. It helps BRCA2 to reach the sites of DNA damage and participate in the repair process. Without this gene, BRCA2 cannot perform its function effectively.
RAD51: This gene works closely with BRCA2 in the repair of DNA double-strand breaks. BRCA2 helps to recruit and stabilize this gene at the sites of DNA damage, facilitating the repair process.
BRCA1: This gene and BRCA2 work together in the repair of DNA damage. They both play a role in the same DNA repair pathway, and their functions are complementary to each other.
FANCD2: This gene interacts with BRCA2 in a pathway called Fanconi anemia pathway, which is involved in the repair of DNA interstrand crosslinks. This interaction is crucial for maintaining the stability of our genome.
Did you know that proteins and genes can have the same name?
In most cases, a gene codes for a specific protein, meaning the primary function of a gene is to provide instructions for producing a protein. Due to this intimate relationship, scientists often use the same name for both the gene and the protein it codes for.
Dr. Wallerstorfer
Diagnostics
BRCA2 is typically diagnosed through a genetic test, which involves analyzing a sample of blood or saliva in a laboratory. This test is often recommended for individuals with a family history of breast, ovarian, or related cancers. The timing of the test is usually determined by a healthcare provider, based on the individual's personal and family medical history. It's important to note that a positive test result doesn't necessarily mean a person will develop cancer, but it does indicate a higher risk. Genetic counseling is often recommended before and after testing to help individuals understand and cope with the potential results.
Living with
Variations in the BRCA2 gene can significantly increase the risk of developing certain types of cancer, most notably breast and ovarian cancer. These variations, or mutations, can be passed down through generations, making it a familial concern. For carriers, this means a higher likelihood of early cancer detection and the need for regular screenings. Additionally, lifestyle modifications and preventive surgeries may be considered to reduce the risk. Despite these challenges, carriers can lead fulfilling lives with appropriate medical guidance and support.
Did you know genetic tests are affordable?
Genetic tests, once regarded as a luxury due to their high costs, have become significantly more affordable. This change has been made possible through advancements in technology and increased competition in the market. Now, anyone curious about their genetic makeup and potential health risks can access this information at an affordable price. This development provides unprecedented insights into individual genetics.
Dr. Wallerstorfer
When to test BRCA2
A test for BRCA2 is typically conducted when there is a family history of breast or ovarian cancer, especially if these cancers developed at a young age or if the same person had both types of cancer. The test may also be recommended if a close relative has a known BRCA2 mutation. The goal of the test is to identify any changes in the BRCA2 gene that might increase the risk of developing these cancers.
Did you know the common mutations?
Mutations in the BRCA2 gene are relatively rare, affecting about 1 in 400 to 1 in 800 people in the general population. However, the prevalence can be significantly higher in certain ethnic groups, such as Ashkenazi Jews. It's important to note that having a BRCA2 mutation does not guarantee the development of cancer, but it does increase the risk.
Dr. Wallerstorfer
Genes tested together with
In genetic testing, several genes are often examined in conjunction with BRCA2 to provide a more comprehensive understanding of an individual's genetic risk profile. These genes, like BRCA2, are associated with an increased risk of certain types of cancer. The testing of these genes together can help in early detection, prevention strategies, and personalized treatment plans. Here are some of the genes commonly tested alongside BRCA2:
BRCA1: This is another gene that is frequently tested with BRCA2. Mutations in it can also increase the risk of breast and ovarian cancer. Testing for both can provide a more complete picture of an individual's genetic risk.
PALB2: This is a gene that works with BRCA2 to repair damaged DNA and stop tumor growth. Mutations in it can increase the risk of breast cancer. Testing for it along with BRCA2 can help identify additional genetic risk factors.
ATM: This is a gene that helps control cell division. Mutations in it can lead to cells dividing in an uncontrolled way, which can result in cancer. Testing for it along with BRCA2 can provide additional information about an individual's cancer risk.
CHEK2: This is a gene that produces a protein involved in preventing cells from growing and dividing too rapidly or in an uncontrolled way. Mutations in it can increase the risk of several types of cancer. Testing for it along with BRCA2 can help identify additional genetic risk factors.
Each of these genes can contribute to an individual's overall risk profile for developing breast and ovarian cancer, and understanding these risks can be crucial in the management of one's health. It is important to consult a healthcare professional to discuss any concerns related to genetic testing and cancer risk.
Did you know that pharmacogenomics is a thing?
Genetic testing can offer insights into how your body metabolizes specific medications, leading to more personalized and effective treatment plans. The genetic tests designed for this purpose are known as pharmacogenomic tests. Pharmacogenomics is the study of how genes influence an individual's response to drugs.
Dr. Wallerstorfer
History
The discovery of BRCA2, a gene linked to breast cancer, dates back to 1994. This breakthrough was made by a team of researchers led by Michael Stratton at the Institute of Cancer Research in London. The discovery was significant because it provided a deeper understanding of the genetic factors that contribute to breast cancer. Over the years, studies have shown that mutations in the BRCA2 gene increase the risk of both breast and ovarian cancer. In the late 1990s, the first tests to identify these mutations became available, offering a way for individuals to learn about their genetic risk. Since then, research has continued to explore the role of BRCA2 in cancer development and ways to target it for treatment. Today, BRCA2 is considered a key player in the field of cancer genetics, with its discovery marking a major milestone in our understanding of the disease.