CCGO awards exome sequencing to NIH intramural investigators

The awards are part of a two-year initiative, called the Clinical Center Genomics Opportunity (CCGO), which is encouraging NIH institutes to jumpstart genomic medicine by increasing the use of genomic data in clinical research. CCGO is co-sponsored by the National Human Genome Research Institute (NHGRI), the NIH Deputy Director for Intramural Research, and the NIH Clinical Center.

Using CCGO funds, the NIH Intramural Sequencing Center will sequence the exomes of 1,000 NIH Clinical Center patients. Exome sequencing explores the 1-2 percent of the genome that codes for proteins, the most likely place to find DNA differences that could cause or contribute to disease.

The selection committee, made up of NHGRI and Clinical Center researchers, chose projects that would take advantage of the NIH Clinical Center's resources, be likely to result in important scientific discovery and encourage the development of more resources for genome and exome sequencing within NIH.

In their grant applications, award recipients proposed to use exome sequencing in a range of clinical projects that include:

• Ilias Alevisos, D.M.D., M.M.Sc., National Institute of Dental and Craniofacial Research, will use exome sequencing data from 60 patients to characterize the rate of mutations that lead to Sjögren's syndrome. Sjögren's syndrome is a chronic autoimmune disease in which the body's white blood cells destroy the glands that produce saliva and tears.
• Jeff Baron, M.D., National Institute of Child Health and Human Development, will use exome sequence data from 90 patients for his research on genetic causes of childhood growth failure.
   
• Carsten Bönnemann, M.D., National Institute of Neurological Disorders and Stroke, will use exome sequencing of 150 patients to explore the diversity of gene mutations and phenotypes in a well-defined, pediatric, neuromuscular disorder cohort.
   
• Brian P. Brooks, M.D., Ph.D., National Eye Institute, will use exome sequence data from 75 patients with syndromic colobomas, which are malformations of the normal optic fissure closure process of the eye, including the iris, retina, choroid, or optic disc.
   
• Raphaela Goldbach-Mansky, M.D., M.H.S., National Institute of Arthritis and Musculoskeletal and Skin Diseases, will use exome sequencing of 89 patients to investigate the genetic causes and improve diagnostic techniques and treatments for severe early-onset autoinflammatory and autoimmune diseases.
   
• W. Marston Linehan, M.D., National Cancer Institute, will use exome sequencing data from 100 patients to identify novel cancer susceptibility genes in kidney cancer patients.
   
• Francis J. McMahon, M.D., National Institute of Mental Health, will use exome sequencing of 75 patients to study treatment-resistant depression.
   
• Joel Moss, M.D., Ph.D., National Heart, Lung, and Blood Institute (NHLBI), will use exome sequencing of 130 patients to research the genetic origins of lymphatic disorders.
   
• Alan T. Remaley, M.D., Ph.D., NHLBI, will use exome data from 75 patients in a study to identify the genetic determinants of extreme dyslipidemia. Dyslipidemia is a disorder caused by an abnormal amount of lipids (such as cholesterol and fat) in the blood.
   
• Helen Su, M.D., Ph.D., National Institute of Allergy and Infectious Diseases, will examine exome sequencing data from 150 patients to explore a number of immune system disorders. Some of the patients selected for exome sequencing will also participate in a pilot program at the National Institute of Allergy and Infectious Diseases (NIAID) on the management of incidental findings. An incidental finding is the discovery of a gene variant that is unrelated to the patient's primary disorder that could cause disease and require medical surveillance or treatment for a separate condition.

The cost of exome sequencing conducted through CCGO will be offset by a combination of funds from the Director's Challenge Innovation Award Program that is administered by the NIH Office of Intramural Research; sequencing discounts from the NIH Intramural Sequencing Center; NHGRI clinical support for incidental findings analysis and counseling; and NIH Clinical Center sample processing and informatics. CCGO will also leverage clinical, scientific and bioinformatics resources within participating institutes.