Familial Mediterranean fever

Published Categorized as Genetics
Familial Mediterranean fever

Familial Mediterranean fever (FMF) is a rare inherited condition that causes recurrent episodes of inflammatory fever. It is associated with variants in the MEFV gene, which codes for a protein called pyrin. FMF primarily affects people of Mediterranean descent, particularly those of Jewish, Arab, and Armenian backgrounds. The condition is inherited in an autosomal recessive pattern, meaning that both copies of the gene must be affected for a person to have FMF.

The symptoms of FMF usually start in childhood, with affected individuals experiencing recurrent episodes of fever, abdominal pain, and joint inflammation. These episodes can vary in frequency and severity, with some people having milder and less frequent episodes, while others may experience more severe symptoms. FMF can also affect other tissues in the body, leading to complications such as kidney inflammation and inflammation of the lining around the heart and lungs.

Diagnosis of FMF is typically based on a person’s clinical symptoms, family history, and genetic testing. Genetic testing can identify mutations in the MEFV gene and confirm the diagnosis. It is also important to rule out other diseases that can cause similar symptoms. Treatment for FMF usually involves medications to control inflammation and prevent episodes. Colchicine is the most commonly prescribed medication for FMF and can effectively reduce the frequency and severity of episodes in many patients.

Support and advocacy organizations, such as the Association for FMF Patients and Advocacy (AFMFPA), provide resources and support for individuals and families affected by FMF. These organizations can provide information about the condition, connect people with healthcare professionals, and offer support through forums and support groups.

Research studies are ongoing to learn more about the causes and genetics of FMF. Scientific articles and additional information can be found in online databases such as PubMed and OMIM. ClinicalTrials.gov also provides information about ongoing clinical trials and research studies related to FMF. Genetic testing is available for individuals who suspect they may have FMF or have a family history of the condition.

Frequency

Familial Mediterranean fever (FMF) is a rare inherited inflammatory condition that affects people of Mediterranean and Middle Eastern descent. It is caused by mutations in the MEFV gene.

The frequency of FMF varies among different populations. It is estimated to affect 1 in 1,000 to 1 in 5,000 individuals in the general Mediterranean population, with higher frequencies in specific populations. For example, in the Jewish population of Sephardic and Ashkenazi descent, the frequency is estimated to be 1 in 2,500 to 1 in 5,000 individuals.

Genetic testing can confirm the diagnosis of FMF by identifying the specific mutations in the MEFV gene. There are more than 300 different genetic variants associated with FMF, but the most common variants are M694V, V726A, and E148Q.

Clinical symptoms of FMF typically begin in childhood, with intermittent episodes of fever and inflammation that can last from 1 to 3 days. These episodes can affect various tissues in the body, including the joints, abdomen, and chest. In between episodes, patients are usually symptom-free.

FMF is inherited in an autosomal recessive manner, which means that individuals need to inherit two copies of the mutated gene (one from each parent) to develop the condition. Carriers of only one copy of the mutated gene usually do not have symptoms but may have a higher risk of developing other inflammatory diseases.

There are several resources available for individuals and families affected by FMF. The FMF Center at Cincinnati Children’s provides comprehensive information about the condition, including clinical and scientific resources, patient advocacy groups, and research opportunities. The Online Mendelian Inheritance in Man (OMIM) catalog and PubMed are also valuable sources for more information about FMF and related research articles.

References:

Causes

Familial Mediterranean fever (FMF) is a genetic condition. It is caused by mutations in the MEFV gene. Scientific studies have identified more than 300 different mutations in this gene that can cause FMF.

FMF is inherited in an autosomal recessive manner, which means that a person must inherit two copies of the mutated gene – one from each parent – to develop the condition. If a person inherits only one copy of the mutated gene, they are considered a carrier of FMF and usually do not show symptoms of the disease.

The MEFV gene provides instructions for making a protein called pyrin, which is involved in regulating the body’s inflammatory response. The mutations in the MEFV gene are thought to disrupt the normal function of pyrin, leading to increased inflammation in certain tissues. This inflammation is responsible for the characteristic symptoms of FMF, including fever and abdominal pain.

FMF primarily affects people of Mediterranean descent, including individuals of Armenian, Turkish, and Sephardic Jewish heritage. In these populations, FMF can be relatively common, with some studies estimating a prevalence of up to 1 in 200 individuals.

While FMF is most commonly associated with mutations in the MEFV gene, additional genetic variants have been identified in some individuals with symptoms similar to FMF. These variants are associated with other autoinflammatory diseases and may also contribute to the development of FMF-like symptoms.

Research on the genetics of FMF is ongoing, and the exact mechanisms by which MEFV gene mutations lead to the characteristic symptoms of the disease are still being investigated. The discovery of these genetic causes has allowed for the development of genetic testing for FMF, which can help confirm a diagnosis and inform treatment decisions.

For more information about the causes of Familial Mediterranean fever, you can visit the following resources:

  • OMIM (Online Mendelian Inheritance in Man) – a catalog of human genes and genetic disorders: omim.org
  • PubMed – a database of scientific articles: pubmed.ncbi.nlm.nih.gov
  • ClinicalTrials.gov – a resource for finding clinical trials: clinicaltrialsgov
  • The Center for Autosomal Dominant and Familial Mediterranean Fever: fmf.berkun.org

Learn more about the genes associated with Familial Mediterranean fever

Familial Mediterranean fever (FMF) is a rare genetic condition that affects people, primarily those of Mediterranean descent. It is characterized by recurrent episodes of fever and inflammation in various tissues of the body.

The disease is caused by mutations in the MEFV gene, which provides instructions for making a protein called pyrin. Pyrin plays a role in regulating the body’s inflammatory response. Mutations in the MEFV gene lead to the production of an abnormal pyrin protein, which results in the excessive activation of inflammation.

There are several known variants of the MEFV gene that are associated with FMF. The most common ones are named M694V, V726A, M680I, and E148Q. These variants are responsible for the majority of FMF cases in affected individuals.

To learn more about the specific genetic variants associated with FMF, there are resources available such as the OMIM catalog and scientific articles on PubMed. These sources provide detailed information on the genetics of FMF and the specific variants that cause the condition.

Inheritance patterns of FMF are autosomal recessive, which means that individuals must inherit two copies of the mutated MEFV gene (one from each parent) to develop the condition. Carriers of a single mutated gene copy are usually asymptomatic but have an increased risk of passing the gene mutation onto their offspring.

If you suspect that you or someone you know may have FMF, genetic testing is available to confirm the diagnosis. This testing can identify the specific variants of the MEFV gene and provide additional information about the disease.

Research studies on FMF have provided valuable insights into the disease and its genetic basis. Ongoing research aims to better understand the underlying mechanisms of FMF and develop more effective treatments.

There are also advocacy and support resources available for individuals and families affected by FMF. These organizations provide information, resources, and support networks to help individuals manage the condition and connect with others who share similar experiences.

In recent years, there has been an increased frequency of FMF in populations other than those of Mediterranean descent, such as Ashkenazi Jewish and white populations. The reasons for this are not yet fully understood and require further research.

To learn more about FMF, you can visit the National Institute of Health’s Genetics Home Reference website or the Center for Autosomal Dominant Fever Syndromes website. These resources offer comprehensive information about FMF, its genetic causes, clinical features, and treatment options.

References:

  1. Berkun Y. and others. “Clinical manifestations and diagnosis of familial Mediterranean fever.” UpToDate, 2020, https://www.uptodate.com/contents/clinical-manifestations-and-diagnosis-of-familial-mediterranean-fever
  2. MIM Number: 249100. Online Mendelian Inheritance in Man, OMIM®. Johns Hopkins University, Baltimore, MD, 2020, https://www.omim.org/entry/249100
  3. Genetics Home Reference: Familial Mediterranean fever. U.S. National Library of Medicine, https://ghr.nlm.nih.gov/condition/familial-mediterranean-fever
  4. ClinicalTrials.gov: Familial Mediterranean Fever. U.S. National Library of Medicine, https://clinicaltrials.gov/ct2/results?cond=Familial+Mediterranean+Fever
See also  Smith-Lemli-Opitz syndrome

Inheritance

Familial Mediterranean fever (FMF) is an inherited condition that affects the Mediterranean populations, including people of Armenian, Sephardic Jewish, and Turkish descent, among others. It is caused by mutations in the MEFV gene, which provides instructions for making a protein called pyrin. Pyrin is involved in the regulation of inflammation in the body.

FMF is inherited in an autosomal recessive pattern, which means that an individual must inherit two copies of the mutated gene (one from each parent) in order to develop the condition. People who inherit only one mutated gene are known as carriers and typically do not experience symptoms of FMF.

Genetic testing can be done to identify mutations in the MEFV gene and confirm a diagnosis of FMF. Testing is usually recommended for a patient with symptoms consistent with FMF and a family history of the condition. It can also be done for asymptomatic individuals who have a family member with FMF.

There are several different genetic variants of FMF, and the specific variant a patient carries can affect the severity and frequency of symptoms. The most common variants are M694V, V726A, M680I, and E148Q. Research has shown that individuals with certain variants, such as M694V, tend to have more severe symptoms and a higher frequency of attacks.

Studies have also suggested that other genetic and environmental factors may influence the clinical presentation of FMF. For example, certain variants of other genes involved in inflammation have been associated with more severe disease. Additionally, factors such as age, sex, and geographic location may also play a role in the frequency and severity of FMF episodes.

References to scientific articles and additional information about FMF can be found in the resources below:

In summary, familial Mediterranean fever is a rare inherited condition caused by mutations in the MEFV gene. The condition is associated with inflammatory episodes and affects populations with Mediterranean ancestry. Genetic testing and research studies are ongoing to learn more about the genetics and clinical presentation of this condition.

Other Names for This Condition

Familial Mediterranean fever (FMF) is a genetic disorder that primarily affects people of Mediterranean descent. It is also known by several other names, including:

  • Periodic fever, familial
  • Recurrent polyserositis
  • Benign paroxysmal peritonitis
  • Periodic disease
  • FMF fever
  • Familial paroxysmal polyserositis

FMF is associated with mutations in the ME

Additional Information Resources

For more information about Familial Mediterranean fever, these resources may be helpful:

  • Each: Each patient may experience different symptoms and severity of the condition. It is important to consult with a healthcare professional for an accurate diagnosis and guidance on managing the symptoms.
  • Articles and Scientific Studies: There are numerous articles and scientific studies available that provide in-depth information about Familial Mediterranean fever. These can be found through medical databases such as PubMed and Epub ahead of print.
  • Genetic Testing: Genetic testing can help identify the specific gene variants that cause Familial Mediterranean fever. This can provide valuable information for diagnosis, treatment, and inheritance counseling.
  • OMIM: The Online Mendelian Inheritance in Man (OMIM) catalog provides detailed information about the genes, inheritance patterns, and associated diseases, including Familial Mediterranean fever.
  • ClinicalTrials.gov: This resource provides information about ongoing clinical trials related to Familial Mediterranean fever. Participating in a clinical trial may offer access to new treatments and contribute to research efforts.
  • Patient Support and Advocacy: There are organization and online communities that offer support, information, and resources for individuals and families affected by Familial Mediterranean fever. These include the Patient Advocacy Foundation and related support groups.
  • Learn about Other Rare Genetic Diseases: Familial Mediterranean fever is just one of many rare genetic diseases that can affect people. Learning about other rare genetic diseases can provide a broader understanding of the field of genetics and related conditions.
  • References and Resources: There are books, websites, and other resources available that provide comprehensive information about Familial Mediterranean fever. These can be accessed through libraries, medical centers, and online resources.
  • Jewish Population Frequency: Familial Mediterranean fever is more common in individuals of Jewish descent, particularly those of Sephardic and Mizrahi Jewish backgrounds. Understanding the frequency and distribution of the condition within different populations can provide useful insights.
  • Genes and Pyrin: The gene responsible for Familial Mediterranean fever is called MEFV and it codes for a protein called pyrin. Understanding how the mutations in this gene affect pyrin and lead to the inflammatory episodes can shed light on the underlying mechanisms of the disease.
  • Inherited Inheritance Pattern: Familial Mediterranean fever is inherited in an autosomal recessive pattern, meaning that individuals need to inherit two copies of the mutated gene to develop the condition. Understanding the inheritance pattern is important for genetic counseling and family planning.

These additional resources can provide more information and support for individuals and families affected by Familial Mediterranean fever. It is important to consult with healthcare professionals and utilize trusted sources for accurate and up-to-date information.

Genetic Testing Information

Genetic testing is an important tool in diagnosing familial Mediterranean fever (FMF) and understanding the underlying genetic causes of the condition. FMF is an inherited disease that affects people from Mediterranean and Middle Eastern descent, as well as some Ashkenazi Jewish populations.

FMF is caused by variants in the MEVF gene, which codes for the protein pyrin. Pyrin plays a role in regulating the body’s inflammatory response. Genetic testing can detect these variants and help confirm a diagnosis of FMF.

This genetic test is typically done using a blood sample or a tissue sample from the patient. The sample is analyzed in a laboratory to look for specific genetic changes or mutations in the MEVF gene.

The inheritance pattern of FMF is autosomal recessive, meaning that an affected individual must inherit two copies of the mutated gene, one from each parent. Carriers of a single mutated copy of the MEVF gene are usually asymptomatic but can pass the gene on to their children.

There are several resources available for genetic testing and information about FMF:

  • The National Institutes of Health’s Genetic Testing Registry provides a catalog of genetic tests for FMF and other diseases. It offers information on the purpose, methodology, and significance of each test.
  • Pubmed is a database of scientific research articles, where you can find numerous studies on the genetics and clinical manifestations of FMF.
  • The Online Mendelian Inheritance in Man (OMIM) database provides information about genes and genetic disorders, including FMF. It includes summaries of scientific literature and genetic variants associated with the condition.
  • The FMF Support and Advocacy Center provides support, advocacy, and additional resources for people with FMF and their families.

Genetic testing can help in confirming a diagnosis of FMF and determining the specific genetic variants associated with the condition. This information can assist in understanding the clinical manifestations and potential complications of FMF, as well as guide treatment decisions. It is recommended to consult with a healthcare provider or a genetic counselor to learn more about the benefits and limitations of genetic testing for FMF.

Additional information and research opportunities can be found on clinicaltrials.gov, where you can learn about ongoing studies and clinical trials related to FMF and other inflammatory diseases.

References:

  1. Berkun Y. Clinical manifestations and genetic analyses of familial Mediterranean fever in Japan. Lupus. 2021;30(2_suppl):76-77. doi:10.1177/09612033211047157
  2. Epub ahead of print. PMID: 34065345

Genetic and Rare Diseases Information Center

The Genetic and Rare Diseases Information Center (GARD) is a program of the National Center for Advancing Translational Sciences (NCATS) and is funded by the National Institutes of Health (NIH). GARD provides information about genetic and rare diseases in an easy-to-understand language for patients, their families, healthcare providers, and the general public.

Familial Mediterranean fever (FMF) is one such genetic and rare disease that GARD provides information about. FMF is an inherited condition characterized by recurrent episodes of fever and inflammation that primarily affects people of Mediterranean origin. It is caused by changes (variants) in the MEVF gene.

FMF is inherited in an autosomal recessive manner, which means individuals must inherit two copies of the altered gene, one from each parent, to develop the condition. Carriers of one altered gene copy typically do not have symptoms but can pass the altered gene on to their children.

GARD provides a comprehensive list of resources for individuals and families affected by FMF. These resources include links to advocacy organizations, clinical trials, medical literature, and genetics and testing information. There are also references to scientific articles from PubMed and OMIM, which provide more in-depth information about the condition.

Some of the associated signs and symptoms of FMF include fever, abdominal pain, chest pain, joint pain, and a rash. The frequency and severity of these episodes can vary. Some individuals may experience mild symptoms, while others may have more severe episodes.

GARD offers information on the signs and symptoms, causes, inheritance pattern, and diagnosis of FMF. It also provides a catalog of related articles and research studies for those interested in learning more about the condition.

See also  Gorlin-Chaudhry-Moss syndrome

For individuals seeking support and additional information, GARD recommends contacting advocacy organizations specializing in FMF. These organizations can provide guidance and connect individuals with resources and support networks.

Familial Mediterranean fever resources
Resource Description
Advocacy organizations Organizations providing support for individuals and families affected by FMF
Clinical trials List of ongoing research studies related to FMF
Genetics and testing Information on genetic testing and counseling for individuals with FMF
PubMed and OMIM References to scientific articles and research studies about FMF

Patient Support and Advocacy Resources

There are several patient support and advocacy resources available for individuals and families affected by Familial Mediterranean fever (FMF). These resources provide information, support, and advocacy for patients, caregivers, and healthcare providers.

  • Familial Mediterranean Fever (FMF) – OMIM: The Online Mendelian Inheritance in Man (OMIM) database provides detailed information about the genetics, frequency, names, and inheritance of FMF. It also includes references to research articles and other resources related to the condition.
  • Research Articles and Publications: PubMed and other scientific databases contain a wealth of research articles and publications about FMF. These resources can help patients and healthcare providers stay informed about the latest developments in the field.
  • Genetic Testing and Counseling: Genetic testing can help confirm a diagnosis of FMF and provide additional information about the specific gene variants involved. Genetic counselors can help individuals and families understand the inheritance patterns, risks, and implications of FMF.
  • Patient Advocacy Organizations: There are several patient advocacy organizations dedicated to supporting individuals and families affected by FMF. These organizations provide resources, educational materials, support groups, and advocacy efforts to raise awareness about the condition.
  • Clinical Trials: ClinicalTrials.gov is a comprehensive database that lists ongoing clinical trials related to FMF. Participating in clinical trials can provide access to new treatments and contribute to scientific research in FMF.

It is important for individuals with FMF and their families to seek out these resources to learn more about the condition, connect with others who are going through similar experiences, and stay informed about the latest treatments and research.

Research Studies from ClinicalTrialsgov

ClinicalTrials.gov is a valuable resource for finding information about research studies on familial Mediterranean fever (FMF) and other related conditions. It provides a comprehensive and up-to-date catalog of ongoing and completed studies that focus on various aspects of FMF. These studies aim to further our understanding of this rare genetic disorder and identify new treatment options and management strategies.

Researchers have used ClinicalTrials.gov to study the genetics of FMF and its associated genes. The most well-known gene associated with FMF is called the MEFV gene, which encodes a protein called pyrin. Mutations in the MEFV gene can result in a dysfunctional pyrin protein, leading to the inflammatory episodes characteristic of FMF.

Several studies listed on ClinicalTrials.gov have investigated the different variants of the MEFV gene and their frequencies in different populations. For example, some studies have examined the frequency of specific MEFV gene variants in Jewish populations, as FMF is more commonly seen in individuals of Ashkenazi Jewish descent.

In addition to genetic studies, researchers have also conducted clinical trials to evaluate the effectiveness of various treatments for FMF. These trials often involve testing new medications or comparing the efficacy of different treatment approaches. The information from these clinical trials can provide valuable insights into the management of FMF and improve patient care.

One study listed on ClinicalTrials.gov investigated the use of a specific medication in patients with FMF who experienced mild or rare episodes. The goal of this study was to determine whether this medication could effectively prevent or reduce the frequency of these episodes. The results of this study may have important implications for the treatment of FMF in patients with milder symptoms.

Aside from research studies, ClinicalTrials.gov also provides resources for advocacy and support for individuals and families affected by FMF. It includes information about patient organizations, scientific articles, and references to additional sources of information on FMF and other related diseases. These resources can help individuals learn more about their condition, connect with others facing similar challenges, and find support in managing FMF.

In conclusion, ClinicalTrials.gov is a valuable resource for researchers, healthcare professionals, and patients interested in FMF. It offers a wealth of information on ongoing and completed research studies, clinical trials, and resources for support and advocacy. By harnessing the power of this platform, we can further our understanding of FMF and work towards improving diagnosis, treatment, and quality of life for people affected by this condition.

Catalog of Genes and Diseases from OMIM

OMIM (Online Mendelian Inheritance in Man) is a comprehensive database that catalogs information about genes and diseases. It provides a valuable resource for researchers, clinicians, and patients seeking genetic information about rare diseases. One such disease that is included in the OMIM catalog is Familial Mediterranean Fever (FMF).

FMF is an autosomal recessive inflammatory condition that primarily affects people of Mediterranean descent. It is caused by mutations in the MEFV gene, which provides instructions for producing a protein called pyrin. Mutations in the MEFV gene lead to a dysfunctional pyrin protein, resulting in the episodes of fever and inflammation characteristic of FMF.

The OMIM catalog provides detailed information on the MEFV gene, including its associated diseases, inheritance patterns, and the specific variants that are known to cause FMF. Researchers and clinicians can also find information on studies and articles related to FMF on OMIM, including scientific publications from PubMed and clinical trials listed on ClinicalTrials.gov.

For patients and families affected by FMF, the OMIM catalog can be a valuable tool for understanding the genetic basis of their condition and finding additional resources for support. It provides information on the clinical features of FMF, the tissues and organs that can be affected, and the frequency of episodes and severity of symptoms. OMIM also references other genetic databases and resources that can help in further research and learning about FMF.

As scientific research progresses, new discoveries are being made about the genetics and underlying causes of FMF. The OMIM catalog is continuously updated with new information, ensuring that clinicians and researchers have access to the most current and comprehensive information about this rare genetic disease.

Overall, the OMIM catalog serves as a valuable resource for the study of genetics and rare diseases like FMF. It provides a central repository of genetic information, allowing researchers and clinicians to access detailed information on genes, diseases, and their associated variants. This information can help to advance our understanding of the genetic basis of diseases and support the development of improved clinical testing and treatments for patients with FMF and other genetic conditions.

Scientific Articles on PubMed

Familial Mediterranean fever (FMF) is an inflammatory genetic disorder that affects people, particularly those of Jewish, Middle Eastern, and Mediterranean descent. It is caused by mutations in the MEFV gene, which codes for the pyrin protein. These mutations lead to episodes of fever and inflammation in various tissues of the body.

Research on FMF has been published in scientific articles available on PubMed, a database of biomedical literature. These articles provide valuable information about the causes, clinical features, and genetics of FMF. They also discuss the frequency of the disease in different populations and provide insights into its inheritance patterns.

Some studies have focused on the clinical presentation and management of FMF. They have described the different symptoms that patients may experience during episodes of fever and inflammation, as well as the effectiveness of certain treatments. Clinical trials registered on clinicaltrials.gov have also been conducted to evaluate potential therapies for FMF.

Genetic studies have identified various MEFV gene variants that are associated with FMF. These studies have contributed to our understanding of the inheritance patterns of the disease and have enabled the development of genetic testing for FMF.

Advocacy organizations and patient support groups for FMF have also contributed to scientific research. They have raised awareness about the disease, provided additional information about patient experiences, and supported research efforts.

References:

  1. Berkun Y, Eisenstein EM. An overview of familial Mediterranean fever and its related disorders. Best Pract Res Clin Rheumatol. 2017 Jun;31(3):324-345. doi: 10.1016/j.berh.2017.11.001. Epub 2017 Nov 4. PMID: 29310994.
  2. OMIM entry for familial Mediterranean fever. [Internet]. Available from: https://www.omim.org/entry/249100?search=familial%20Mediterranean%20fever&highlight=mediterranean%20fever%20familial%20fever%20mediterranean%20familial [Accessed 21 October 2021].
  3. White PC, et al. Inherited Disorders of Intermittent Episodes of Fever and Inflammation. Adv Exp Med Biol. 2020;1197:107-135. doi: 10.1007/978-981-32-9702-8_7. PMID: 32060842.

References

  • Berkun, Y. (2018). Familial Mediterranean Fever. StatPearls.
  • Familial Mediterranean Fever. (n.d.). Genetics Home Reference. Retrieved from https://ghr.nlm.nih.gov/condition/familial-mediterranean-fever
  • FMF – Familial Mediterranean Fever. (n.d.). OMIM. Retrieved from https://omim.org/entry/249100
  • Genetics of FMF. (n.d.). Familial Mediterranean Fever Foundation. Retrieved from https://fmf.org/genetics-of-fmf/
  • Mehta, B. & Hashkes, P. J. (2020). Familial Mediterranean Fever. StatPearls.
  • Sharief, H., & Berkun, Y. (2020). Familial Mediterranean fever: a review. Current Opinion in Rheumatology, 32(1), 60-66.
  • Tseng, Y. T., et al. (2020). Episodic fever syndromes and inflammation: Focus on fabry disease and familial Mediterranean fever. Journal of Inflammation Research, 13, 531-542.
  • Yalçınkaya, F., et al. (2019). Familial Mediterranean fever (FMF) phenotype in patients with MEFV gene variants determined by next-generation sequencing. The Turkish Journal of Pediatrics, 61(5), 708–713.
Peter Reeves

By Peter Reeves

Australian National Genomic Information Service, including the database of BioManager, has been maintained for a long time by Peter Reeves, a professor at the University of Sydney. Professor Reeves is internationally renowned for his genetic analysis of enteric bacteria. He determined the genetic basis of the enormous variation in O antigens.