Bayesian-based noninvasive prenatal diagnosis of single-gene disorders

Tom Rabinowitz, Avital Polsky, David Golan, Artem Danilevsky, Guy Shapira, Chen Raff, Lina Basel-Salmon, Reut Tomashov Matar, Noam Shomron*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

28 Scopus citations


In the last decade, noninvasive prenatal diagnosis (NIPD) has emerged as an effective procedure for early detection of inherited diseases during pregnancy. This technique is based on using cell-free DNA (cfDNA) and fetal cfDNA (cffDNA) in maternal blood, and hence, has minimal risk for the mother and fetus compared with invasive techniques. NIPD is currently used for identifying chromosomal abnormalities (in some instances) and for single-gene disorders (SGDs) of paternal origin. However, for SGDs of maternal origin, sensitivity poses a challenge that limits the testing to one genetic disorder at a time. Here, we present a Bayesian method for the NIPD of monogenic diseases that is independent of the mode of inheritance and parental origin. Furthermore, we show that accounting for differences in the length distribution of fetal- and maternal-derived cfDNA fragments results in increased accuracy. Our model is the first to predict inherited insertions-deletions (indels). The method described can serve as a general framework for the NIPD of SGDs; this will facilitate easy integration of further improvements. One such improvement that is presented in the current study is a machine learning model that corrects errors based on patterns found in previously processed data. Overall, we show that next-generation sequencing (NGS) can be used for the NIPD of a wide range of monogenic diseases, simultaneously. We believe that our study will lead to the achievement of a comprehensive NIPD for monogenic diseases.

Original languageEnglish
Pages (from-to)428-438
Number of pages11
JournalGenome Research
Issue number3
StatePublished - Mar 2019


FundersFunder number
Adelis Foundation
Israeli Ministry of Defense
Office of Assistant Minister of Defense for Chemical, Biological, Radiological and Nuclear
National Institutes of Health
National Human Genome Research InstituteR01HG006283
Achelis Foundation
Edmond J. Safra Center for Ethics, Harvard University
Canadian Friends of Tel Aviv University
Breakthrough Institute
Foundation Fighting Blindness
Israel Science Foundation1852/16
Tel Aviv University
Chinese University of Hong Kong
Shun Hing Institute of Advanced Engineering
Ministry of Defense
Circulatory Disorders Research Fund
Istituto Oncologico Veneto


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