A universal carrier test for the long tail of Mendelian disease

Srinivasan, Balaji S.; Evans, Eric A.; Flannick, Jason; Patterson, A. Scott; Chang, Christopher C.; Pham, Tuan; Young, Sharon; Kaushal, Amit; Lee, James; Jacobson, Jessica L.; Patrizio, Pasquale

doi:10.1016/j.rbmo.2010.05.012

« Previous Next »Reproductive BioMedicine Online
Volume 21, Issue 4 , Pages 537-551, October 2010

A universal carrier test for the long tail of Mendelian disease

Balaji S. Srinivasan
- Counsyl, Redwood Shores, CA, USA
- Department of Computer Science, Stanford University, Stanford, CA, USA
- Department of Statistics, Stanford University, Stanford, CA, USA
- Corresponding author.
- These authors contributed equally to this work.
Eric A. Evans
- Counsyl, Redwood Shores, CA, USA
- These authors contributed equally to this work.
Jason Flannick
- Counsyl, Redwood Shores, CA, USA
- Current affiliation: Broad Institute of Harvard and MIT, Cambridge, MA, USA
A. Scott Patterson
- Counsyl, Redwood Shores, CA, USA
Christopher C. Chang
- Counsyl, Redwood Shores, CA, USA
- Department of Mathematics, UCSD, La Jolla, CA, USA
Tuan Pham
- Counsyl, Redwood Shores, CA, USA
Sharon Young
- Counsyl, Redwood Shores, CA, USA
Amit Kaushal
- Counsyl, Redwood Shores, CA, USA
- Stanford Medical School, Stanford University, Stanford, CA, USA
- Stanford Genome Technology Center, Stanford University, Stanford, CA, USA
- Program in Biomedical Informatics, Stanford University, Stanford, CA, USA
James Lee
- Counsyl, Redwood Shores, CA, USA
- The Personal Genome Project, Harvard University, Cambridge, MA, USA
- Department of Psycology, Harvard University, Cambridge, MA, USA
Jessica L. Jacobson
- Counsyl, Redwood Shores, CA, USA
- Department of Pathology, New York University School of Medicine, New York, NY, USA
Pasquale Patrizio
- Counsyl, Redwood Shores, CA, USA
- Yale University Fertility Center, Yale University, New Haven, CT, USA

Received 22 March 2010; received in revised form 22 May 2010; accepted 24 May 2010. published online 23 August 2010.

Declaration: All authors are consultants or employees of Counsyl. Seed funding for this study was provided by a group of anonymous philanthropists and families with genetic disease.

Abstract

Mendelian disorders are individually rare but collectively common, forming a ‘long tail’ of genetic disease. A single highly accurate assay for this long tail would allow the scaling up of the Jewish community’s successful campaign of population screening for Tay–Sachs disease to the general population, thereby improving millions of lives, greatly benefiting minority health and saving billions of dollars. This need has been addressed by designing a universal carrier test: a non-invasive, saliva-based assay for more than 100 Mendelian diseases across all major population groups. The test has been exhaustively validated with a median of 147 positive and 525 negative samples per variant, demonstrating a multiplex assay whose performance compares favourably with the previous standard of care, namely blood-based single-gene carrier tests. Because the test represents a dramatic reduction in the cost and complexity of large-scale population screening, an end to many preventable genetic diseases is now in sight. Moreover, given that the assay is inexpensive and requires only a saliva sample, it is now increasingly feasible to make carrier testing a routine part of preconception care.

Keywords: carrier testing, Mendelian disease, population screening, preconception, preventive medicine, reproductive health

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Balaji S Srinivasan taught computational genomics and statistics at Stanford before becoming Chief Technology Officer (CTO) of Counsyl. His research interests include machine learning, personalized medicine and the biology and diagnosis of rare genetic variants.