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Use of whole exome and genome sequencing in the identification of genetic causes of primary immunodeficiencies

Chou, Janet; Ohsumi, Toshiro K.; Geha, Raif S.

Current Opinion in Allergy and Clinical Immunology: December 2012 - Volume 12 - Issue 6 - p 623–628
doi: 10.1097/ACI.0b013e3283588ca6
PRIMARY IMMUNE DEFICIENCY DISEASE: Edited by Amos Etzioni and Ramsey L. Fuleihan

Purpose of review This review discusses the strengths and challenges of using whole genome sequencing (WGS)/whole exome sequencing (WES) for identifying novel genetic causes of primary immunodeficiencies.

Recent findings WGS permits comprehensive sequencing of introns and exons, whereas WES allows deeper sequencing of exonic regions at a lower cost. Due to the large number of genetic variants found in each genome, it is necessary to use filtering approaches to distinguish deleterious from benign variants. WES has been used successfully to identify novel genetic causes of primary immunodeficiency. Complex structural variations and non-Mendelian disorders remain challenges for WGS/WES.

Summary WGS/WES is a powerful screening tool with great potential to identify genetic causes of primary immunodeficiencies for research and clinical applications. To use WGS/WES effectively, it is necessary to understand how to filter the sequencing data and to realize its limitations as well as its strengths.

aDivision of Immunology, Boston Children's Hospital

bDepartment of Pediatrics, Harvard Medical School

cDepartment of Molecular Biology, Massachusetts General Hospital

dDepartment of Genetics, Harvard Medical School, Boston, Massachusetts, USA

Correspondence to Raif S. Geha, MD, Division of Immunology, Boston Children's Hospital, Karp building 10th floor, One Blackfan Circle, Boston, MA 02115, USA. Tel: +1 617 919 2483; e-mail:

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