science overview

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The Human Neurogenetics team contributes to the description of 17 new patients.

The study of a micro-rearragement in a patient with polymicrogyria allows the Human Neurogenetics team to show that the...

Zaffran's Team published a new study in bicupsid aortic valve

It is the first knock-in model based on a recurrent pathogenic variant in Kcnq2.

Dr. Fabienne Lescroart started a new team in the DevCard department on the theme of early cardiac progenitor...

Our laboratory has just reported a very unusual and never described phenotype associated with a mutation of the GLE1...


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SELECTED PUBLICATIONS

Cerino, M.  et al. 2020

Extension of the phenotypic spectrum of GLE1-related disorders to a mild congenital form resembling congenital myopathy

BACKGROUND: GLE1 (GLE1, RNA Export Mediator, OMIM#603371) variants are associated with severe autosomal recessive motor neuron diseases, that are lethal congenital contracture syndrome 1 (LCCS1,...
Mol Genet Genomic Med - issue: - volume: - pages: e1277.

Milh, M.  et al. 2020

A knock-in mouse model for KCNQ2-related epileptic encephalopathy displays spontaneous generalized seizures and cognitive impairment

OBJECTIVE: Early onset epileptic encephalopathy with suppression-burst is one of the most severe epilepsy phenotypes in human patients. A significant proportion of cases have a genetic origin, and the...
Epilepsia - issue: 5 - volume: 61 - pages: 868-878.

Bizzari, S.  et al. 2020

Recessive marfanoid syndrome with herniation associated with a homozygous mutation in Fibulin-3

We have previously reported on a consanguineous family where 2 siblings, a girl and a boy, presented with tall stature, long and triangular faces, prominent forehead, telecanthus, ptosis, everted...
Eur J Med Genet - issue: 5 - volume: 63 - pages: 103869.

Gorokhov, M.  et al. 2020

A new tool CovReport generates easy-to-understand sequencing coverage summary for diagnostic reports

In order to properly interpret the results of a diagnostic gene panel sequencing test, gene coverage needs to be taken into consideration. If coverage is too low, an additional re-sequencing test is...
Sci Rep - issue: 1 - volume: 10 - pages: 6247.

Faucherre, A.  et al. 2020

Piezo1 is required for outflow tract and aortic valve development

AIMS: During embryogenesis, the onset of circulatory blood flow generates a variety of hemodynamic forces which reciprocally induce changes in cardiovascular development and performance. It has been...
J Mol Cell Cardio - issue: - volume: - pages: .

Ballouhey, O.  et al. 2020

[CRISPR-Cas9 for muscle dystrophies]

Muscular dystrophies are a group of rare muscular disorders characterized by weakness and progressive degeneration of the muscle. They are diseases of genetic origin caused by the mutation of one or...
Med Sci (Paris) - issue: 4 - volume: 36 - pages: 358-366.

Charfeddine, C.  et al. 2020

Identification of a CDH12 potential candidate genetic variant for an autosomal dominant form of transgrediens and progrediens palmoplantar keratoderma in a Tunisian family

Molecular diagnosis of rare inherited palmoplantar keratoderma (PPK) is still challenging. We investigated at the clinical and genetic level a consanguineous Tunisian family presenting an autosomal...
J. Hum. Genet. - issue: 4 - volume: 65 - pages: 397-410.

Mortreux, J.  et al. 2020

Identification of novel pathogenic copy number variations in Charcot-Marie-Tooth disease

Charcot-Marie-Tooth disease (CMT) is a hereditary sensory-motor neuropathy characterized by a strong clinical and genetic heterogeneity. Over the past few years, with the occurrence of whole-exome...
J. Hum. Genet. - issue: 3 - volume: 65 - pages: 313-323.

Ehinger, Y.  et al. 2020

Huntingtin phosphorylation governs BDNF homeostasis and improves the phenotype of Mecp2 knockout mice

Mutations in the X-linked MECP2 gene are responsible for Rett syndrome (RTT), a severe neurological disorder for which there is no treatment. Several studies have linked the loss of MeCP2 function to...
EMBO Mol Med - issue: 2 - volume: 12 - pages: e10889.

Jaouadi, H.  et al. 2020

Multiallelic rare variants support an oligogenic origin of sudden cardiac death in the young

Unexplained sudden death in the young is cardiovascular in most cases. Structural and conduction defects in cardiac-related genes can conspire to underlie sudden cardiac death. Here we report a...
Herz - issue: - volume: - pages: .

Human Genetics Timeline

  1. Discovery of Natural Selection

    1859

    Charles Darwin published "On The Origin of Species", a foundation to the understanding of biology and genetics.Service commun administratif

  2. Discovery of Heredity

    1865

    Working on pea plants, Gregor Mendel reports that the inheritance of certain traits follows a particular pattern, discovering the notion that heredity is transmitted in discrete units that will later be referred to as genes.

  3. Isolation of DNA

    1869

    Frederick Miescher isolates DNA from white blood cells and calls it nuclein. He was the first to identify DNA as a distinct unit.

  4. First sight of human chromosomes

    1882

    Walther Flemming produces the first illustration of a human chromosome.

  5. The name “chromosome” is invented by Heinrich von Waldeyer.

    1888
  6. Chromosome Theory of Inheritance

    1902

    Walter Sutton and Theodor Boveri independently observe that Mendel’s inheritance pattern corresponds to chromosome inheritance during meiosis, the cell division that produces reproductive cells, i.e. the sperm and egg cells.

  7. First condition ascribed to a genetic cause

    1902

    Research conducted by William Bateson, Elizabeth Saunders and Archibald Garrod shows that alkaptonuria, also known as black bone disease, is inherited according to Mendelian rules.

  8. William Bateson invents the term “Genetics”

    1905
  9. First major interaction between geneticists and clinicians

    1908

    The “Debate On Heredity And Disease” organized by the Royal Society of Medicine takes place in London.

  10. The word “gene”

    1909

    is first formulated by Wilhelm Johannsen, who also defines the terms genotype and phenotype, referring respectively to the hereditary information and to the observed properties of an organism.

  11. Genes lie within chromosomes

    1911

    Working on the fruit fly Drosophila melanogaster, Thomas Hunt Morgan demonstrates that genes are carried by chromosomes and are the mechanical basis of heredity.

  12. Concept of Multifactorial Inheritance

    1931

    Archibald Garrod publishes his second book, “Inborn Factors in Disease” where he discusses the idea of inherited predisposition to a disease, setting the foundations for modern concepts of multifactorial inheritance.

  13. First estimation of a mutation rate in humans

    1935

    JBS Haldane provides an estimate of the frequency at which mutations that cause haemophilia arise.

  14. Development of genetic linkage

    1935

    Ronald Fisher, among others, suggests the tracing of linked genetic markers to predict a disease.

  15. First human genetic linkage

    1937

    Julia Bell and JBS Haldane demonstrate the linkage between genes for colour-blindness and haemophilia.

  16. One Gene, One Enzyme Hypothesis

    1941

    In their experiments using the red bread mold, Neurospora crassa, George Beadle and Edward Tatum’s show that genes act by regulating distinct chemical events. They propose that each gene directs the formation of one enzyme.

  17. First glimpse at the structure of DNA

    1943

    William Astbury obtains the first X-ray diffraction pattern of DNA, which reveals that DNA has a regular periodic structure. He suggests that nucleotide bases are stacked on top of each other.

  18. The chemical nature of genes

    1944

    Oswald Avery, Colin MacLeod, and Maclyn McCarty show that DNA, not proteins, can transform the properties of cells, thus clarifying the chemical nature of genes.

  19. First genetic disease known to result from an enzyme deficiency

    1952

    Carl Cori and Gerty Cori discover the Glycogen storage disease type 1 results form a deficiency in the enzyme glucose-6-phosphatase.

  20. Model structure of DNA as a double helix

    1953

    Based on the X-ray crystallography studies of DNA by Rosalind Franklin, Francis Crick and James Watson describe the double helix structure of DNA. They received the Nobel Prize for their work in 1962.

  21. Human Chromosomes Numbered

    1955

    Joe Hin Tjio defines 46 as the exact number of chromosomes in human cells.

  22. Discovery of DNA Polymerase

    1955

    Arthur Kornberg and colleagues isolated DNA polymerase, an enzyme that catalyzes the template-directed synthesis of DNA that would later be used for DNA sequencing.

  23. First human chromosome abnormalities identified

    1959

    In the same year, three groups discover that anomalies in chromosome numbers lead to Down, Turner and Klinefelter syndromes (discovered by Jérôme Lejeune, Charles Ford and Patricia Jacobs and John Strong, respectively).

  24. First Screen for Metabolic Defect in Newborns

    1961

    Robert Guthrie develops a method to test newborns for the metabolic defect, phenylketonuria (PKU).

  25. The Genetic Code is cracked

    1961

    Marshall Nirenberg and Heinrich Matthaei figure out the genetic code that allows nucleic acids with their 4-letter alphabet to determine the order of 20 kinds of amino acids in proteins.

  26. First chromosomal prenatal diagnosis

    1966

    Mark Steele and Roy Breg use cells obtained form amniotic fluid to perform fetal chromosome evaluation.

  27. First Restriction Enzyme Described

    1968

    Scientists describe restriction nucleases, enzymes that recognize and cut specific short sequences of DNA. The resulting fragments can be used to analyze DNA, and these enzymes later became an important tool for mapping genomes.

  28. Unique identification of all human chromosomes

    1970

    Lore Zech, Torbjörn Caspersson and colleagues develop the use of quinacrine, a fluorescent dye that intercalates into DNA, to visualize dark and light bands on chromosomes. These bands form unique patterns for each chromosome that makes them discernable from one another.

  29. Idea of gene therapy as a treatment for genetic disorders

    1972

    Theodor Friedmann and Richard Roblin suggest the use of exogenous DNA to replace the defective DNA in patients suffering from genetic defects.

  30. DNA sequencing

    1975

    Two groups, Frederick Sanger and colleagues, and Alan Maxam and Walter Gilbert, both develop rapid DNA sequencing methods.

  31. First transgenic mice and fruit flies

    1981

    Scientists successfully add stably inherited genes to laboratory animals. The resulting transgenic animals provide a new way to test the functions of genes.

  32. GenBank database formed

    1982

    Scientists begin to submit DNA sequence data to a National Institutes of Health (NIH) database that is open to the public.

  33. First linkage of DNA markers to a disease

    1982

    Murray and colleagues link the locus responsible for Duchenne muscular dystrophy to genetic markers on the short arm of the X chromosome.

  34. First positional cloning of a disease gene

    1986

    A method for finding a gene without the knowledge of the protein it encodes is developed. The first human disease gene identified by positional cloning is responsible for chronic granulomatous disease (CGD), an inherited immunodeficiency.

  35. Invention of the Polymerase Chain Reaction (PCR)

    1986

    Kary Mullis develops the PCR technique to amplify DNA, rapidly generating billions of copies of a specific sequence thus facilitating its study. Mullis was awarded the Nobel Prize in Chemistry in 1993 for his work on the PCR technique.

  36. First Human Genetic map

    1987

    The first comprehensive genetic map is based on variations in DNA sequence that can be observed by digesting DNA with restriction enzymes.

  37. Launch of the Human Genome Project

    1990

    The US Department of Energy and the National Institute of Health announce a plan for a 15-year project to sequence the human genome. This will eventually result in sequencing all 3.2 billion letters of the human genome.

  38. First attempt at gene therapy

    1990

    A four-year-old girl with severe immunodeficiency became the first patient to undergo gene therapy in the United States. The effect of the therapy were temporary, but successful.

  39. First disease gene identified

    1993

    With a combination of fine genetic mapping and DNA sequencing, the gene responsible for Huntington’s disease is cloned, and mutations within it are identified.

  40. First cloned animal

    1997

    ‘Dolly the sheep’ is the first animal ever cloned in the Roslin Institute, Edinburgh.

  41. Chromosome 22 Sequenced

    1999

    The first finished, full-length sequence of a human chromosome is produced. Chromosome 22 was chosen to be first because it is relatively small and had a highly detailed map already available. Such a map is necessary for the clone by clone sequencing approach.

  42. Human genome working draft completed

    2000

    ‘Draft sequence’ of human genome announced jointly by International Human Genome Consortium and by Celera. By the end of Spring 2000, HGP researchers sequence 90% of the human genome with 4-fold redundancy.

  43. Progressing on gene therapy

    2003

    Gene therapy trial for the treatment of severe combined immune deficiency (SCID). But 2 out of the 10 boys that entered the trial in Paris developed leukemia-like disorders.

  44. Completion of the Human Genome Sequencing

    2003

    The finished sequence covers 99% of the human genome and is 99.99% accurate.

  45. First gene therapy approved

    2003

    The world's first gene therapy is approved in China for the treatment of head and neck cancer.

  46. LMNA is mutated in Hutchinson-Guilford Progeria Syndrome

    2003

    Nicolas Lévy and his colleagues identify mutations in the LMNA gene in patients suffering from progeria, a condition linked to premature aging

  47. First reports of next-generation sequencing technologies

    2005

    Development of high-throughput sequencing platforms that allow fast and cost-competitive DNA sequencing.

  48. First genome wide association studies (GWAS)

    2005

    A GWA study proves efficient in finding a common variant in complement factor H gene (CFH) to be strongly associated with age-related macular degeneration, the major cause of blindness in the elderly.

    Since 2005, thousands of GWAS studies have provided robust genetic associations to common multifactorial disorders.

  49. Towards gene therapy for pituitary tumors

    2006

    Anne Barlier and Thierry Brue demonstrate the efficiency of a gene therapy approach using a mutated version of the PIT-1 gene to treat neuroendocrine tumours in mice

  50. First individual human genome sequenced by next-generation sequencing

    2008

    The whole sequence is completed in two months at approximately one-hundredth of the cost of traditional, first-generation sequencing methods.

  51. Launch of the 1000 Genomes Project

    2008

    The project ran from 2008 to 2015, to build the largest catalog of human variation and genotype data. The final dataset contains data for 2,504 individuals from 26 populations around the world.

  52. First use of exome sequencing in diagnostics

    2009

    A patient with a suspected Bartter syndrome (a renal salt-wasting disease) is effectively diagnosed by exome sequencing. This technique makes use of next-generation sequencing technologies and was designed to identify variants that alter expressed genes.

  53. Identification of a gene involved in intellectual deficiency

    2013

    Using exome sequencing, the laboratory of Laurent Villard identifies a mutation in the BCAP31 gene in patients suffering from an X-linked immune deficiency and motor impairment.

  54. CRISPR-Cas9 first used to edit the human genome

    2013

    Work from the laboratories of Feng Zhang and George Church demonstrates that the CRISPR-Cas9 technology can be used to edit the human genome.

  55. Towards gene therapy for dysferlinopathies

    2015

    Marc Bartoli and his colleagues develop a gene therapy approach based on exon-skipping within the DYSF gene to treat a subset of dysferlinopathies with encouraging results on patient cells.

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