NIH Exome Sequencing of Familial Amyotrophic Lateral Sclerosis Project

The purpose of this project was to perform exome sequencing of DNA samples obtained from patients diagnosed with familial amyotrophic lateral sclerosis (ALS) to search for the genetic factors that predispose to this fatal neurodegenerative disease. Understanding the genetic architecture of familial ALS will provide fundamental insight into the cellular processes that lead to motor neuron death, facilitate animal and in vitro disease modeling, and will provide focus for research aimed at developing therapies that alter the natural course of the disease.

Samples were collected from patients diagnosed with familial ALS in the United States, Italy, Germany, Finland and Israel. Relevant clinical data was collected for each patient, including age of onset, site of symptom onset, gender, and survival. Exome sequencing was performed in the Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD using a variety of exome capture technologies and next generation sequencing on the Illumina sequence-by-synthesis platform.

• Study Weblinks:
  • NINDS Amyotrophic Lateral Sclerosis
• Study Design:
  • Case-Control
• Study Type:
  • Case-Control
  • Case Set
• dbGaP estimated ancestry using GRAF-pop
• Total number of consented subjects: 3161
• Subject Sample Telemetry Report (SSTR)

Inclusion criteria

• Diagnosed as having familial amyotrophic lateral sclerosis by a neurologist.
• Onset of symptoms after 18 years of age.
• Non-Hispanic Caucasian ethnicity.

Exclusion Criteria

• Diagnosis of another condition that could mimic amyotrophic lateral sclerosis.
• Onset of symptoms before 18 years of age.
• Non-Caucasian ethnicity.

Case cohort exome sequencing data of n=247 subjects were submitted to dbGaP in December 2013. Additional phenotype and genotype data of genome-wide association studies of ALS may be viewed and accessed through releases of previous study versions (phs000101.v3.p1; phs000101.v2.p1; phs000101.v1.p1)

• Primary Phenotype: Amyotrophic Lateral Sclerosis
• Frontotemporal Dementia

• Principal Investigators
  • Bryan J. Traynor. National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.
  • Adriano Chiò. University of Turin, Turin, Italy.
• Co-Investigators
  • Gabriella Restagno. A.S.O. O.I.R.M.-S. Anna, Turin, Italy.
  • Mario Sabatelli. Catholic University Rome, Rome, Italy.
  • Michael Sendtner. University of Würzburg, Würzburg, Germany.
  • Vivian E. Drory. Tel-Aviv Sourasky Medical Center, Tel-Aviv, Israel.
  • Jessica Mandrioli. S. Agostino-Estense Hospital and University of Modena, Modena, Italy.
  • Michael Benatar. Department of Neurology, Emory University School of Medicine, Atlanta, GA, USA.
  • Yevgeniya Abramzon. National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.
  • Vivianna M. Van Deerlin. University of Pennsylvania, Philadelphia, PA, USA.
  • John Q. Trojanowski. University of Pennsylvania, Philadelphia, PA, USA.
  • J. Raphael Gibbs. National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.
  • Maura Brunetti. A.S.O. O.I.R.M.-S. Anna, Turin, Italy.
  • Susan Gronka. Emory University School of Medicine, Atlanta, GA, USA.
  • Joanne Wuu. Emory University School of Medicine, Atlanta, GA, USA.
  • Jinhui Ding. National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.
  • Leo McCluskey. University of Pennsylvania, Philadelphia, PA, USA.
  • Maria Martinez-Lage. University of Pennsylvania, Philadelphia, PA, USA.
  • Dana Falcone. University of Pennsylvania, Philadelphia, PA, USA.
  • Dena G. Hernandez. National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.
  • Sampath Arepalli. National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.
  • Sean Chong. National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.
  • Jennifer C. Schymick. National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.
  • Jeffrey Rothstein. Johns Hopkins Hospital, Baltimore, MD, USA.
  • Francesco Landi. Catholic University of Sacred Heart, Rome, Italy.
  • Yong-Dong Wang. St. Jude Children's Research Hospital, Memphis, TN, USA.
  • Andrea Calvo. University of Turin, Turin, Italy.
  • Gabriele Mora. Salvatore Maugeri Foundation, Milan, Italy.
  • Maria Rosaria Monsurro. Second University of Naples, Naples, Italy.
  • Stefania Battistini. University of Siena, Siena, Italy.
  • Fabrizio Salvi. Bellaria Hospital, Bologna, Italy.
  • Rossella Spataro. University of Palermo, Palermo, Italy.
  • Patrizia Sola. S. Agostino-Estense Hospital and University of Modena, Modena, Italy.
  • Giuseppe Borghero. Azienda Hospital, University of Cagliari, Monserrato-Cagliari, Italy.
  • The ITALSGEN Consortium.
  • Giuliana Galassi. S. Agostino-Estense Hospital and University of Modena, Modena, Italy.
  • Sonja W. Scholz. National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.
  • J. Paul Taylor. St. Jude Children's Research Hospital, Memphis, TN, USA.
  • Erik P. Pioro. Cleveland Clinic, Cleveland, OH, USA.
  • Ashley Boehringer. Barrow Neurological Institute, Phoenix, AZ, USA.
  • Ruth Chia. National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.
  • Howard Feit. Henry Ford Hospital, Detroit, MI, USA.
  • Alan E. Renton. National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.
  • Hannah A. Pliner. National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.
  • Giuseppe Marangi. National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.
  • Brett J. Winborn. St. Jude Children's Research Hospital, Memphis, TN, USA.
  • Michael A. Nalls. National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.
  • Sarah Morgan. Institute of Neurology, University College London, Queen Square, London, UK.
  • John Hardy. Institute of Neurology, University College London, Queen Square, London, UK.
  • Alan Pittman. Institute of Neurology, University College London, Queen Square, London, UK.
  • Richard W. Orrell. Institute of Neurology, University College London, Queen Square, London, UK.
  • Andrea Malaspina. Queen Mary University of London, UK.
  • Katie C. Sidle. Institute of Neurology, University College London, Queen Square, London, UK.
  • Pietro Fratta. Institute of Neurology, University College London, Queen Square, London, UK.
  • Matthew B. Harms. Washington University School of Medicine, St. Louis, MO, USA.
  • Robert H. Baloh. Cedars-Sinai Medical Center, Los Angeles, CA, USA.
  • Alan Pestronk. Washington University School of Medicine, St. Louis, MO, USA.
  • Conrad C. Weihl. Washington University School of Medicine, St. Louis, MO, USA.
  • Ekaterina Rogaeva. University of Toronto, Toronto, ON, Canada.
  • Lorne Zinman. University of Toronto, Toronto, ON, Canada.
  • Carsten Drepper. University of Würzburg, Würzburg, Germany.
  • Andrew B. Singleton. National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.
  • Mark R. Cookson. National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.
  • Robert Bowser. Barrow Neurological Institute, Phoenix, AZ, USA.
  • Janel O. Johnson. National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.
• Funding Sources
  • Federazione Italiana Giuoco Calcio (Italian Football Federation).
  • The Packard Center for ALS Research at Johns Hopkins, Johns Hopkins University, Baltimore, MD, USA.
  • The ALS Association USA, Washington D.C., USA.
  • Intramural Research Program of the National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.
  • Intramural Research Program, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.