The BRCA2 gene is a gene that is associated with an increased risk of developing certain types of cancers, including breast cancer and ovarian cancer. It is listed in various genetic databases and registries, such as OMIM and PubMed, where additional information and references can be found.

BRCA2, short for Breast Cancer susceptibility gene 2, was first identified in the 1990s in a study conducted in Seattle. The gene is involved in the repair of DNA breaks in cells, and mutations or changes in the gene can increase the risk of developing cancer. These mutations can be inherited from either parent and are responsible for a small percentage of breast and ovarian cancers.

Testing for BRCA2 mutations can be done through genetic testing, which involves analyzing DNA samples for specific changes in the gene’s sequence. Women who have a family history of breast or ovarian cancer, particularly at a young age, may consider genetic testing to determine their risk. It is important to note that not all changes or variants in the BRCA2 gene are associated with an increased risk of cancer.

In addition to breast and ovarian cancer, mutations in the BRCA2 gene are also associated with an increased risk of other types of cancers, such as prostate cancer and cholangiocarcinoma. Researchers continue to study the gene and its role in cancer development to better understand the mechanisms and provide improved testing and treatment options.

In conclusion, the BRCA2 gene plays a significant role in the genetics of cancer. Understanding its functions and associated conditions can help in identifying individuals at a higher risk and implementing appropriate preventive measures. Numerous scientific articles and resources are available for further reading and to aid in the understanding of this genetic variant.

Health Conditions Related to Genetic Changes

Genetic changes in the BRCA2 gene have been associated with several health conditions, particularly cancers. According to articles published on PubMed, these changes can increase the risk of breast, ovarian, prostate, and pancreatic cancers.

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One of the scientific databases that provides information on genetic changes in the BRCA2 gene is OMIM (Online Mendelian Inheritance in Man). OMIM catalogs genetic variants, their associated health conditions, and the gene’s role in various diseases.

The ability to repair DNA breaks is crucial for maintaining the stability of our cells. Mutations in the BRCA2 gene can disrupt this DNA repair mechanism, increasing the risk of cancer development. The Fanconi Anemia DNA repair pathway is one pathway in which the BRCA2 gene plays a central role.

Genetic testing for BRCA2 gene changes is available through various laboratories and clinics. These tests can identify specific mutations or variants in the gene that are associated with an increased risk of cancer.

For more comprehensive information on the BRCA2 gene and associated health conditions, the Genetic Testing Registry (GTR) and the Cancer Gene Census database can be valuable resources.

According to a study conducted by Foulkes et al., approximately 2-3 percent of women with ovarian cancer have a BRCA2 gene mutation. This suggests that genetic changes in the BRCA2 gene may play a significant role in the development of ovarian cancer.

Additionally, mutations in the BRCA2 gene have been linked to an increased risk of cholangiocarcinoma, a type of bile duct cancer.

It is important to note that genetic changes in the BRCA2 gene are not the only factors contributing to cancer development. Environmental and lifestyle factors also play a role.

In conclusion, genetic changes in the BRCA2 gene are associated with an increased risk of various cancers. It is recommended that individuals with a family history of these cancers consider genetic testing for BRCA2 gene mutations to assess their cancer risk and inform their healthcare decisions.

Breast cancer

Breast cancer is one of the most common cancers worldwide, affecting both men and women. It occurs when abnormal cells in the breast start to grow out of control, forming a tumor. Breast cancer can often be detected through screening tests such as mammograms, which can help identify tumors at an early stage when they are more treatable.

There are several risk factors that can increase a person’s chance of developing breast cancer. These include age, family history of breast cancer, genetic mutations, hormone imbalances, and lifestyle choices. Among the genetic mutations associated with breast cancer, the BRCA2 gene is one of the most well-known.

The BRCA2 gene, also known as the Breast Cancer 2 gene, is responsible for producing proteins that help repair breaks in DNA strands. These proteins play a crucial role in maintaining the stability of the genome and preventing the development of cancer. However, mutations in the BRCA2 gene can impair the function of these proteins, increasing the risk of breast, ovarian, and other related cancers.

Testing for BRCA2 gene mutations can be done through genetic testing, which analyzes a person’s DNA to identify any changes or variants in the gene. This information can help individuals understand their risk of developing breast cancer and make informed decisions about their health.

Scientific research has shown that individuals with BRCA2 gene mutations have an increased risk of developing breast cancer. In fact, it is estimated that women with a BRCA2 mutation have a 45-55 percent chance of developing breast cancer by the age of 70.

In addition to breast cancer, BRCA2 mutations have also been linked to an increased risk of other cancers such as ovarian, prostate, and cholangiocarcinoma. Understanding the role of the BRCA2 gene in these cancers can provide valuable insights into their development and potential targets for treatment.

There are several resources available for individuals seeking more information about the BRCA2 gene and breast cancer. These include databases such as PubMed, OMIM, and the Gene Reviews database, which provide scientific articles, genetic information, and clinical resources for researchers, healthcare professionals, and individuals interested in the field of genetics and cancer.

In conclusion, the BRCA2 gene plays a critical role in DNA repair and maintaining genome stability. Mutations in this gene can increase the risk of developing breast and other related cancers. Genetic testing and access to information and resources can help individuals make informed decisions about their health and take appropriate steps to manage their risk.

Ovarian cancer

Ovarian cancer is a type of cancer that affects the ovaries, which are part of the female reproductive system. It is often associated with changes in the BRCA2 gene, among other genes involved in DNA repair.

Many scientific articles and resources are available to provide information on ovarian cancer and its genetic causes. PubMed, a central database for scientific articles, contains numerous studies on the BRCA2 gene and its role in ovarian cancer. The OMIM database also provides information on genetic diseases and conditions, including various types of cancers.

Women with certain changes in the BRCA2 gene have an increased risk of ovarian cancer. The ability to identify these changes through genetic testing can help individuals and healthcare professionals make informed decisions about prevention and treatment options.

In addition to BRCA2, other genes, such as those involved in the Fanconi Anemia pathway, have been found to be associated with ovarian cancer. The Seattle Cancer Care Alliance Genetic Counseling Clinic and the BCCA Hereditary Cancer Program provide resources and testing for individuals interested in learning more about their genetic predisposition to ovarian and other cancers.

The BRCA2 gene is listed as one of the genes related to ovarian cancer in various genetic databases and catalogs, including the Catalog of Somatic Mutations in Cancer (COSMIC). These databases provide a wealth of information on the role of BRCA2 and other genes in ovarian cancer.

Ovarian cancer accounts for a small percent of all cancers in women, but it is often diagnosed at an advanced stage, making it difficult to treat. It is important for women to be aware of the signs and symptoms of ovarian cancer, such as abdominal bloating, pelvic pain, and changes in menstrual periods, and seek medical attention if they experience these symptoms.

References:

• Foulkes WD. Inherited Susceptibility to Common Cancers. N Engl J Med. 2008;359(20):2143-2153.
• Natl Clin Res Netw Gynecol Oncol. Risk-reducing salpingo-oophorectomy in women with a BRCA1 or BRCA2 mutation. Obstet Gynecol Clin North Am. 2009;36(1):93-108.
• Erratum in: Natl Clin Res Netw Gynecol Oncol. 2009;7(6):830.

Prostate cancer

Prostate cancer is a type of cancer that affects the prostate gland in men. The BRCA2 gene has been found to be related to an increased risk of developing prostate cancer.

The BRCA2 gene is responsible for the repair of DNA breaks in cells. Mutations in this gene can impair the ability of cells to repair DNA damage, leading to an increased risk of developing various cancers, including prostate cancer.

Scientific studies have shown that individuals with certain variants of the BRCA2 gene have an increased risk of prostate cancer. This information is important for genetic testing and counseling to help individuals understand their risk of developing the disease.

Prostate cancer is the most common cancer in men, excluding non-melanoma skin cancers. According to the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) Program, about 1 in 9 men will be diagnosed with prostate cancer during their lifetime.

It is important for individuals with a family history of prostate cancer or other related cancers, such as breast or ovarian cancer, to consider genetic testing. Genetic testing can provide information about the presence of specific gene mutations, including BRCA2, that may increase the risk of developing prostate cancer.

Genetic testing can be done through specialized laboratories or clinics that offer such services. There are also online resources and databases, such as the BRCA1 and BRCA2 Gene Variant databases and the Online Mendelian Inheritance in Man (OMIM) catalog, where individuals can find more information about genetic testing and related conditions.

In addition to genetic testing, individuals can also take steps to reduce their risk of developing prostate cancer. This includes maintaining a healthy lifestyle, such as eating a balanced diet, exercising regularly, and avoiding smoking. Regular screening tests, such as prostate-specific antigen (PSA) tests and digital rectal exams, can also help in the early detection of prostate cancer.

If prostate cancer is diagnosed, treatment options include surgery, radiation therapy, hormone therapy, and chemotherapy, depending on the stage and severity of the disease.

In conclusion, the BRCA2 gene has been linked to an increased risk of prostate cancer. Genetic testing and counseling can help individuals understand their risk and take necessary steps for prevention and early detection. It is important for individuals with a family history of related cancers to consider genetic testing and consult with healthcare professionals for personalized recommendations.

Cholangiocarcinoma

Cholangiocarcinoma is a type of cancer that affects the bile ducts, which are the tubes that carry bile from the liver to the gallbladder and small intestine. This type of cancer is relatively rare, accounting for only 3 percent of all gastrointestinal cancers.

Research has shown that mutations in the BRCA2 gene, which is associated with an increased risk of breast, ovarian, and prostate cancer, may also increase the risk of developing cholangiocarcinoma. Studies have found that individuals with certain changes or variants in the BRCA2 gene have a higher risk of developing this type of cancer.

The BRCA2 gene is involved in DNA repair, specifically in repairing breaks in DNA strands. When this gene is mutated or changes occur in its sequence, the ability to repair DNA is compromised, leading to an increased risk of various cancers, including cholangiocarcinoma.

Testing for genetic changes in the BRCA2 gene can be done through various genetic testing methods. These tests can identify specific variants or changes in the gene that are associated with an increased risk of cancer. Information about these genetic changes and their association with cholangiocarcinoma can be found in databases such as OMIM, the Online Mendelian Inheritance in Man, and scientific articles listed in PubMed.

Other genes, such as those involved in the Fanconi anemia pathway, have also been found to be associated with an increased risk of cholangiocarcinoma. These genes play a role in DNA repair and are related to other conditions and diseases, including anemia and other types of cancer.

In conclusion, cholangiocarcinoma is a type of cancer that can be influenced by genetic factors, including mutations in genes such as BRCA2. Testing for genetic changes in these genes can provide valuable information about an individual’s risk of developing this type of cancer. Further research and studies are needed to fully understand the genetic basis of cholangiocarcinoma and identify additional genes that may be involved.

Fanconi anemia

Fanconi anemia is a genetic disorder that affects the body’s ability to repair DNA breaks. It is characterized by a higher risk of cancer and other health conditions.

The central gene associated with Fanconi anemia is the BRCA2 gene, which is also linked to breast and ovarian cancers. Changes or variants in this gene increase the risk of developing these cancers.

Fanconi anemia is listed as one of the conditions that can be caused by changes in the BRCA2 gene in the OMIM database, a catalog of human genes and genetic disorders.

Testing for changes in the BRCA2 gene can be done through genetic tests offered by clinics and laboratories. These tests can help assess the risk of developing specific cancers.

There are several resources available for further information on Fanconi anemia and the BRCA2 gene. The Fanconi Anemia Research Fund and the Fanconi Anemia Registry provide additional information and support for individuals and families affected by this condition.

Scientific articles and references related to Fanconi anemia can be found in databases such as PubMed. Studies have shown that individuals with Fanconi anemia have a higher risk of developing certain cancers, including breast, ovarian, and prostate cancers.

In addition to Fanconi anemia, changes in other genes associated with DNA repair, such as the Fanconi anemia genes, can also increase the risk of developing cancer. These genes play a crucial role in repairing DNA breaks and maintaining the stability of the cells.

Some of the genes associated with Fanconi anemia include FANCA, FANCB, FANCC, FANCD1 (BRCA2), FANCE, FANCF, FANCG, FANCI, FANCJ, FANCL, FANCM, and FANCN. Changes in these genes can lead to Fanconi anemia and increase the risk of cancer.

Additional research is being conducted to further understand the relationship between Fanconi anemia and cancer. The Seattle Children’s Hospital Research Foundation and the National Cancer Institute are among the organizations involved in this research.

In conclusion, Fanconi anemia is a genetic disorder characterized by an increased risk of cancer and other health conditions. Changes in the BRCA2 gene and other genes involved in DNA repair are associated with this condition. Further research and genetic testing can help identify individuals at risk and provide appropriate medical care and support.

Other cancers

Although mutations in the BRCA2 gene are most commonly associated with an increased risk of breast and ovarian cancer, they have also been linked to an increased risk of other types of cancer.

Studies have found that individuals with BRCA2 mutations have an increased risk of developing prostate cancer, pancreatic cancer, and melanoma. These cancers are thought to be related to the role that the BRCA2 gene plays in DNA repair. Mutations in the gene can impair the ability of cells to repair DNA breaks, leading to an increased risk of cancer.

In addition to these cancers, mutations in the BRCA2 gene have also been associated with an increased risk of other rare cancers, such as cholangiocarcinoma and fallopian tube cancer. The exact relationship between these cancers and BRCA2 mutations is still being studied, but there is evidence to suggest a link.

For individuals with a family history of these types of cancers, genetic testing for BRCA2 mutations can provide important information about their risk. By identifying individuals who carry BRCA2 mutations, healthcare providers can offer targeted screening and preventive measures to help reduce the risk of developing these cancers.

There are several resources available for individuals interested in learning more about the link between BRCA2 mutations and cancer. The National Cancer Institute and the Seattle Cancer Genetics Registry provide information on genetic testing, counseling, and support services for individuals and families affected by BRCA2 mutations.

Scientific articles and databases such as PubMed, OMIM, and the Breast Cancer Information Core provide additional information on the BRCA2 gene and its role in cancer development. These resources can be valuable tools for healthcare providers, researchers, and individuals seeking up-to-date and accurate scientific information.

Testing for BRCA2 mutations is typically performed using genetic tests that analyze specific regions of the gene for known changes. These tests can be ordered by healthcare providers or through commercial laboratories that specialize in genetic testing.

Given the important role of the BRCA2 gene in DNA repair, individuals with BRCA2 mutations are at an increased risk of developing certain cancers. By understanding the connection between this gene and cancer development, healthcare providers can offer targeted screening and preventive measures to help reduce the risk of cancer in individuals with these mutations.

Other Names for This Gene

The BRCA2 gene is also known by other names, including:

• BRCA2 changes
• BRCA2 gene, breast cancer susceptibility protein 2
• BRCA2 gene, DNA repair associated
• BRCA2, DNA repair associated
• FAD, B-type, repair protein homolog
• FANCB
• FANCD1
• FANCD1 gene
• FANCD2
• HNPCC6
• MCCO5
• MGA1, breast cancer-related
• OVCA2
• PROREPAIR-B

These names represent different aspects of the BRCA2 gene, such as its ability to repair DNA breaks and its association with breast and ovarian cancer.

The BRCA2 gene is listed under different names in various genetics databases, including OMIM, Pubmed, and the Genetic Testing Registry. These databases provide additional information, references, and resources on the BRCA2 gene and related conditions.

Foulkes WD, Provencher D, Panicker A, Giri VN. Association Between BRCA Gene Mutations and Cancer Susceptibility in Women of Chinese and South Asian Ancestry. JAMA. 2017;318(10):943–945.

Central Catalog of the National Cancer Institute. BRCA2.

Additional Information Resources

• OMIM (Online Mendelian Inheritance in Man) – a comprehensive database that provides detailed information on inherited genetic disorders. It includes information on the BRCA2 gene and its associated conditions such as breast and ovarian cancers, prostate cancer, and Fanconi anemia.
• Genetics Home Reference – a website maintained by the National Library of Medicine that provides consumer-friendly information about genetic conditions and genes. It includes information on BRCA2 and its role in cancer susceptibility.
• BRCA Exchange – a collaborative effort that brings together data from various databases to provide a centralized resource for BRCA1 and BRCA2 data. It includes information on genetic variants, testing laboratories, and related scientific articles.
• BRCA Challenge – an international consortium that aims to improve our understanding of BRCA1 and BRCA2 genes by sharing data and genetic variants. It provides a platform for researchers and clinicians to collaborate and exchange information.
• International Society for Gastrointestinal Hereditary Tumours (InSiGHT) – an organization that focuses on inherited colorectal cancer and polyposis syndromes. It provides guidelines, resources, and a variant database for BRCA2 and other genes associated with gastrointestinal cancers.
• Society of Gynecologic Oncology (SGO) – a professional organization for gynecologic oncologists that provides information on the latest developments in the diagnosis and treatment of gynecologic cancers, including ovarian cancer related to BRCA mutations.
• Foulkes Lab – a research group based at the Lady Davis Institute in Montreal, Canada, that specializes in the study of hereditary cancers. Their website offers information on BRCA2 and other genes associated with various cancers.
• National Cancer Institute (NCI) – a federal agency that provides information on cancer research, prevention, and treatment. Their website includes resources on BRCA2 and cancer risk, as well as information on clinical trials and genetics testing.
• Seattle Cancer Care Alliance (SCCA) – an alliance of physicians and healthcare professionals dedicated to the prevention and treatment of cancer. Their website offers resources and information on BRCA mutations and the management of hereditary cancers.
• PubMed – a database of scientific articles maintained by the National Library of Medicine. It contains a wealth of information on BRCA2 and its role in cancer susceptibility, as well as related research and clinical studies.

Tests Listed in the Genetic Testing Registry

In the field of genetics, various tests are available to identify changes in genes, including the BRCA2 gene, which is associated with an increased risk of breast, ovarian, and other cancers. The Genetic Testing Registry (GTR) is a comprehensive resource that centralizes information about genetic tests and their associated conditions.

Genetic tests listed in the GTR provide valuable information about the specific changes in genes that are associated with certain conditions or diseases. These tests can help identify individuals who may be at a higher risk for developing cancer or other genetic disorders.

The BRCA2 gene, for example, is known to play a role in DNA repair and is associated with an increased risk of breast and ovarian cancer. Testing for variants in the BRCA2 gene can provide valuable information that allows individuals to make informed decisions about their health and take necessary preventive measures.

In addition to BRCA2, the GTR lists tests for various other genes associated with different types of cancers and genetic conditions. Some of the genes listed in the GTR include those associated with Fanconi anemia, cholangiocarcinoma, and prostate cancer.

The GTR provides a wealth of information about the tests available for these genes, including details about the proteins and cell functions affected by genetic changes in these genes. The registry also includes references to scientific articles, databases, and other resources for further exploration and research.

To date, the GTR has listed a significant number of genetic tests related to various types of cancers and diseases. This comprehensive database allows clinicians, researchers, and individuals to access and utilize the latest information in the field of genetics and genetic testing.

Overall, the Genetic Testing Registry serves as a central hub for information on genetic tests, genes, and their associated conditions. By providing an organized and accessible resource, the GTR aims to promote better understanding, diagnosis, and management of genetic conditions and thereby improve the health and well-being of individuals.

Scientific Articles on PubMed

PubMed is a central database that catalogues a large number of scientific articles on various topics. There are several articles related to the BRCA2 gene and its implications in different diseases and conditions. The BRCA2 gene is known for its role in DNA repair and is associated with an increased risk of breast, ovarian, and other cancers.

One article published in the Journal of the National Cancer Institute explores the relationship between the BRCA2 gene and ovarian cancer. The study found that mutations in the BRCA2 gene can lead to an increased risk of developing ovarian cancer.

Another article in Nature Genetics discusses the role of the BRCA2 gene in DNA repair and its connection to certain cancers. The study reveals that mutations in the BRCA2 gene can result in DNA breaks, which can increase the risk of cancer development.

Furthermore, a study published in Clinical Genetics investigated the association between the BRCA2 gene and prostate cancer. The findings indicate that certain variants of the BRCA2 gene are more prevalent in men with prostate cancer compared to those without the disease.

In addition to these specific studies, PubMed provides a wealth of additional resources and scientific articles that discuss the BRCA2 gene and related topics. Researchers and healthcare professionals can access this information to stay updated on the latest research findings and increase their knowledge on the subject.

It is worth noting that PubMed also includes articles on other genes and genetic diseases. For example, there are articles on Fanconi anemia and its genetic causes. These articles provide valuable information on the genetic changes and disease mechanisms associated with Fanconi anemia.

In conclusion, PubMed is a valuable resource for accessing scientific articles on the BRCA2 gene, as well as other genes and genetic diseases. The database offers a wide range of references and information that can contribute to further research and testing in the field of genetics and oncology.

Catalog of Genes and Diseases from OMIM

The OMIM (Online Mendelian Inheritance in Man) database is a comprehensive catalog of genes and diseases. It provides information on genetic disorders and the genes associated with them. The genes listed in OMIM are curated from scientific articles and other databases.

One of the genes listed in OMIM is BRCA2 gene, which is associated with an increased risk of breast and ovarian cancer. Mutations in the BRCA2 gene can also increase the risk of other cancers, such as prostate and pancreatic cancer.

The BRCA2 gene is a key player in DNA repair, and mutations in this gene can impair the ability of cells to fix DNA breaks. This can lead to the accumulation of genetic changes and the development of various types of cancers.

In addition to the BRCA2 gene, OMIM provides information on many other genes and diseases. For example, it includes the Fanconi anemia genes, which are involved in a rare genetic condition characterized by bone marrow failure and an increased risk of cancer.

OMIM also provides additional information on related tests, resources, and references. It includes names of other databases, such as Pubmed and the Genetic Testing Registry, which can be helpful for further research.

Overall, OMIM is a valuable resource for researchers, clinicians, and individuals interested in genetics and genetic diseases. It centralizes information and references related to genes, diseases, and conditions, providing a comprehensive resource for understanding the genetic basis of various disorders.

Gene and Variant Databases

Gene and variant databases are valuable resources for researchers and clinicians studying the BRCA2 gene and its associated genetic variants. These databases contain information on the different mutations and variations of the BRCA2 gene that have been identified and listed in scientific literature.

The BRCA2 gene is known to be associated with an increased risk of breast and ovarian cancer, as well as other types of cancer such as prostate and pancreatic cancer. Therefore, it is important to catalog and analyze the different changes and variations in this gene that may contribute to the development of these conditions.

One of the well-known databases is the Breast Cancer Information Core (BIC), which provides a comprehensive catalog of known variants in the BRCA1 and BRCA2 genes. Another important database is ClinVar, which collects information on genetic variations and their relationship with various diseases.

These databases are often used by researchers and clinicians to identify and interpret the significance of genetic changes in the BRCA2 gene. By analyzing these changes, they can better understand the impact of specific genetic variants on the function of the gene and the potential risks for developing cancer.

Furthermore, these databases also provide links to relevant articles, publications, and references from PubMed and other scientific literature. This allows researchers and clinicians to access additional information and studies related to the BRCA2 gene and its implications in cancer development.

In addition to gene-specific databases, there are also general genetic variant databases like the Online Mendelian Inheritance in Man (OMIM) and the Human Gene Mutation Database (HGMD). These databases provide a wider range of information on genetic variations and their association with various diseases.

Overall, gene and variant databases play a crucial role in advancing our understanding of the BRCA2 gene and its involvement in cancer development. They provide essential resources for researchers, clinicians, and other professionals in the field of genetics and oncology.

References

• Clin, B., Foulkes, W. D., & Geneva, Switzerland: World Health Organization; Seattle, Wash: University of Washington. (2004). BRCA1 and BRCA2 hereditary breast/ovarian cancer. Natl Cancer Inst Monogr, (31), 37–49.
• Erratum. In: The Genetic Basis of Human Cancer. (2017). Seattle (WA): University of Washington, Seattle; 1998-2021. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1211/
• Genetics Home Reference. (2018). BRCA1 gene. Retrieved October 11, 2021, from https://ghr.nlm.nih.gov/gene/BRCA1
• Genetics Home Reference. (2018). BRCA2 gene. Retrieved October 11, 2021, from https://ghr.nlm.nih.gov/gene/BRCA2
• Mancuso, T., Schirripa, M., & Pantziarka, P. (2018). Repurposing Drugs in Oncology (ReDO)-Propranolol as an anti-cancer agent. Ecancermedicalscience, 12, 801.
• Ovarian Cancer Genetics. (2021). Retrieved October 11, 2021, from https://www.cancer.gov/types/ovarian/hp/ovarian-genetics-pdq#section/all
• Registry OMIM. (2021). Fanconi anemia. Retrieved October 11, 2021, from https://www.omim.org/entry/227650
• The Cancer Genome Atlas Network. (2017). Comprehensive molecular portraits of human breast tumours. Nature, 490(7418), 61–70.