While most of us recover from influenza after a week, it can be a very severe disease, and even fatal in rare cases, with no reason for physicians to have expected such an outcome. By analysing the genome of a little girl who contracted a severe form of influenza at the age of two and a half years, researchers at the Laboratory of Human Genetics of Infectious Diseases (a joint French-American international laboratory), which brings together researchers from Inserm, Paris Descartes University, and physicians from the Paris public hospitals (AP-HP; Necker Hospital for Sick Children), working at the Imagine Institute, and from The Rockefeller University in New York, have discovered that she has a genetic mutation, unknown until now, that causes a subtle dysfunction in her immune system. More generally, these results show that genetic mutations could be the root cause of some severe forms of influenza in children, and indicate in any event that immune mechanisms missing in this little girl are needed for protection against this virus in humans. These results are published in the journal Science.
Seasonal influenza is an acute viral infection caused by the influenza virus. It is characterised by high fever, headaches, sore muscles, etc. Apart from vaccination, there is no treatment for it other than symptomatic (pain) treatment. In most cases, patients recover after a week, but in more vulnerable people influenza can cause acute respiratory distress, which is potentially fatal.
The main known risk factors for severe forms of influenza are some acquired comorbidities, such as chronic lung disease. However, the cause of most fatal cases remains unexplained, especially in children.
The absence of cases of severe influenza in patients with known acquired immunodeficiencies, which usually increase susceptibility to infections, is also surprising.
Given these different observations, the researchers at Jean-Laurent Cassanova's and Laurent Abel's laboratory, in Paris and New York, therefore formulated a hypothesis whereby severe influenza in healthy children might be the result of genetic errors.
To test this hypothesis, they sequenced the entire genome of a 7-year-old child who had contracted a severe form of influenza (influenza A virus strain H1N1), requiring her admission to a paediatric intensive care unit in January 2011, at the age of two and a half years. At the time, she showed no other known pathology that might have suggested greater vulnerability to the virus than that of other children.
This analysis, combined with analysis of her parents' genomes, made it possible to show that the little girl had inherited a mutated allele of the gene encoding interferon regulatory factor (IRF7) from both of her parents. The latter is a transcription factor known to amplify the production of interferons in response to viral infection in mice and humans.
In contrast to her parents, in whom the mutation of a single allele of the gene is of no consequence, in the little girl, mutation of both alleles of the gene encoding IRF7 has led to its inactivation. The result: failure to produce interferons, disrupting her system of defence against influenza virus infection in a cascading manner.
By carrying out a comprehensive series of experiments on blood cells, particularly dendritic cells, and by generating lung cells from stem cells taken from the young girl, the researchers provided proof that the mutations observed in this little girl explain the development of severe influenza. Furthermore, this discovery demonstrates that interferon amplification dependent on IRF7 expression is needed for protection against influenza virus in humans. They now need to search for mutations in this or other genes in other children recruited following an episode of unexplained severe influenza.
Based on these initial observations, the researchers at Inserm believe that therapeutic strategies based on recombinant interferons, available in the pharmacopoeia, could help to combat severe forms of influenza in children.
Link:
What if the severity of our seasonal influenza were related to our genetic background?
- Avera Medical Minute AMcK: Researching the human genome - April 10th, 2014 [April 10th, 2014]
- Artificial Reproductive Technology: Constructing a Dystopia - April 10th, 2014 [April 10th, 2014]
- Human genetics - Wikipedia, the free encyclopedia - April 10th, 2014 [April 10th, 2014]
- Wellcome Trust Centre for Human Genetics - Video - April 10th, 2014 [April 10th, 2014]
- Human Genetics Biology Project - Video - April 10th, 2014 [April 10th, 2014]
- Dame Bridget Ogilvie: Women in Science - Video - April 15th, 2014 [April 15th, 2014]
- Human Genetics | Buzzle.com - April 16th, 2014 [April 16th, 2014]
- Refining language for chromosomes - April 17th, 2014 [April 17th, 2014]
- Refining the language for chromosomes - April 17th, 2014 [April 17th, 2014]
- CU system resets health care with $63M personalized medicine division - April 21st, 2014 [April 21st, 2014]
- Human Genetics and Personalized Medicine, Dr. David Cox - Video - April 21st, 2014 [April 21st, 2014]
- Applying math to biology: Software identifies disease-causing mutations in undiagnosed illnesses - April 22nd, 2014 [April 22nd, 2014]
- Software Identifies Gene Mutations in 3 Undiagnosed Children - April 22nd, 2014 [April 22nd, 2014]
- International collaboration unravels novel mechanism for neurological disorder - April 25th, 2014 [April 25th, 2014]
- Mount Sinai Researchers Identify Genetic Alterations in Shared Biological Pathways as Major Risk Factor for Autism ... - April 25th, 2014 [April 25th, 2014]
- Dive into Human Genetics - Video - April 26th, 2014 [April 26th, 2014]
- A new syndrome caused by mutations in AHDC1 - May 2nd, 2014 [May 2nd, 2014]
- Exploring genetics behind Alzheimer's resiliency - May 3rd, 2014 [May 3rd, 2014]
- Human genetics - An Introduction to Genetic Analysis ... - May 4th, 2014 [May 4th, 2014]
- Human Genetics - Estrella Mountain Community College - May 5th, 2014 [May 5th, 2014]
- What Is Human Genetics: How Important Is It To Science Today? - May 9th, 2014 [May 9th, 2014]
- Human Genetics Project - Video - May 9th, 2014 [May 9th, 2014]
- Journal of Human Genetics - Nature - May 16th, 2014 [May 16th, 2014]
- CSHL Keynote: Dr. Peter Donnelly, Wellcome Trust Centre for Human Genetics - Video - May 16th, 2014 [May 16th, 2014]
- New genetic sequencing methods mean quicker, cheaper, and accurate embryo screening - May 31st, 2014 [May 31st, 2014]
- Researchers take a major step towards better diagnosis and treatment of osteoporosis - May 31st, 2014 [May 31st, 2014]
- Poor coverage of specific gene sets in exome sequencing gives cause for concern - June 2nd, 2014 [June 2nd, 2014]
- Osteoporosis: Genetic researchers take major step towards better diagnosis, treatment - June 2nd, 2014 [June 2nd, 2014]
- Deletions and duplications in the exome can help pinpoint cause of unexplained genetic diseases - June 2nd, 2014 [June 2nd, 2014]
- New genes involved in food preferences will revolutionize diets and improve health - June 2nd, 2014 [June 2nd, 2014]
- ESHG14 Update on Ion PII and Ion Chef from Andy Felton - Video - June 4th, 2014 [June 4th, 2014]
- Ancient Human-Chimp Link Pushed Back Millions of Years - June 22nd, 2014 [June 22nd, 2014]
- Chinakov Vs. The Hidden Ep 4: Lets Play Some Xbox - Video - June 22nd, 2014 [June 22nd, 2014]
- Reaction to the $1,000 Genome - June 26th, 2014 [June 26th, 2014]
- Tragicom Studios Movie Explores Link between the Technology Industry and the Rise in Autism with Futuristic Eugenics ... - June 26th, 2014 [June 26th, 2014]
- 09 Prof. Richard Gold, Esq. - Video - June 29th, 2014 [June 29th, 2014]
- John Maunsell Takes Helm of Neuroscience Institute at University of Chicago - July 2nd, 2014 [July 2nd, 2014]
- Illumina Expands in Europe on 3 NIPT Deals - Analyst Blog - July 2nd, 2014 [July 2nd, 2014]
- GHOST STORY (The Hidden) - Video - July 6th, 2014 [July 6th, 2014]
- HOW TO MOONSHINE (The Hidden) - Video - July 9th, 2014 [July 9th, 2014]
- Will Genomics Soon Explain the Human Brain Gain? - July 11th, 2014 [July 11th, 2014]
- WIGGLE WIGGLE WIGGLE (The Hidden) - Video - July 11th, 2014 [July 11th, 2014]
- The Hidden Source : Beta - 1 V.S.1 me Brah! - w/ Friend (Short footage) - Video - July 18th, 2014 [July 18th, 2014]
- Three parent babies banned from knowing 'second mothers' - July 23rd, 2014 [July 23rd, 2014]
- 2014 ASHG Annual Meeting Schedule Overview - Video - July 24th, 2014 [July 24th, 2014]
- Pinpointing genetic links to schizophrenia may open doors to better treatment - July 26th, 2014 [July 26th, 2014]
- Factoring in Mendel and Human Genetics - Video - July 27th, 2014 [July 27th, 2014]
- University of Maryland Schools of Dentistry and Medicine receive NIH grant - July 29th, 2014 [July 29th, 2014]
- Mosaicism: Study clarifies parents as source of new disease mutations - July 31st, 2014 [July 31st, 2014]
- Human Genetics and the Image of God - Video - August 7th, 2014 [August 7th, 2014]
- Bigfoot and yeti, as elusive as ever - August 8th, 2014 [August 8th, 2014]
- Fruit Flies Used To Unlock Mysteries Of Human Diabetes - August 11th, 2014 [August 11th, 2014]
- 23andMe Announces Agreement with Pfizer Inc. to Research Genetics of Ulcerative Colitis and Crohn's Disease - August 12th, 2014 [August 12th, 2014]
- Penn's Basser Research Center for BRCA Names BRCA1 Founder Mary-Claire King Winner of the 2014 Basser Global Prize - August 12th, 2014 [August 12th, 2014]
- Announcing Speakers at BioConference Live Genetics and Genomics 2014 - August 19th, 2014 [August 19th, 2014]
- MARC travel awards announced for: American Society of Human Genetics 2014 Annual Meeting - August 28th, 2014 [August 28th, 2014]
- Human Genetics - The Complexity of Living Cells Debunks Evolution. - Video - September 1st, 2014 [September 1st, 2014]
- ASHG and NHGRI award first genetics and education fellowship - September 2nd, 2014 [September 2nd, 2014]
- ASHG and NHGRI award genetics and public policy fellowship - September 2nd, 2014 [September 2nd, 2014]
- Mapping the DNA Sequence of Ashkenazi Jews - September 10th, 2014 [September 10th, 2014]
- Google Continues To Build Upon Its Life Sciences Ecosystem - September 12th, 2014 [September 12th, 2014]
- Scientists discover genetic link to autism, developmental disorders - September 15th, 2014 [September 15th, 2014]
- Scientists discover possible genetic link to autism, developmental disorders - September 15th, 2014 [September 15th, 2014]
- Human Genetics DNA and RNA.mp4 - Video - September 18th, 2014 [September 18th, 2014]
- Dogs, humans attack cancer together - September 19th, 2014 [September 19th, 2014]
- Cancer treatment for dogs could one day save humans - September 19th, 2014 [September 19th, 2014]
- Synthetic sperm protein raises the chance for successful in vitro fertilization - September 30th, 2014 [September 30th, 2014]
- Gene Interacts with Stress and Leads to Heart Disease in Some People - October 1st, 2014 [October 1st, 2014]
- ASHG Launches Scientific EventPilot Meeting App with 3,500 Offline Abstracts for the Largest Human Genetics Meeting ... - October 1st, 2014 [October 1st, 2014]
- Human genetics of malaria has uncovered some new clues about susceptibility to severe malaria - Video - October 4th, 2014 [October 4th, 2014]
- How Iceland's Genealogy Obsession Leads to Scientific Breakthroughs - October 8th, 2014 [October 8th, 2014]
- Dartmouth Researchers Develop Reproducibility Score for SNPs Associated with Human Disease in GWAS - October 8th, 2014 [October 8th, 2014]
- Researchers develop reproducibility score for SNPs associated with human disease in GWAS - October 8th, 2014 [October 8th, 2014]
- Moore Foundation Selects Matthew Stephens for Data-Driven-Discovery Grant - October 9th, 2014 [October 9th, 2014]
- Reproducibility score for SNPs associated with human disease in GWAS - October 9th, 2014 [October 9th, 2014]
- Multiple neurodevelopmental disorders have a common molecular cause - October 9th, 2014 [October 9th, 2014]
- Human Genetics Molecular Biology of Gene - Video - October 10th, 2014 [October 10th, 2014]
- Human genetics : gel electrophoresis - Video - October 11th, 2014 [October 11th, 2014]
- Giant gene banks take on disease - October 14th, 2014 [October 14th, 2014]
- Gene duplications associated with autism evolved recently in human history - October 19th, 2014 [October 19th, 2014]