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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Development of a comprehensive noninvasive prenatal test

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Author(s):
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Malcher, Carolina [1] ; Yamamoto, Guilherme L. [1] ; Burnham, Philip [2] ; Ezquina, Suzana A. M. [1] ; Lourenco, V, Naila C. ; Balkassmi, Sahilla [3] ; Marco Antonio, David S. [4] ; Hsia, Gabriella S. P. [4] ; Gollop, Thomaz [5] ; Pavanello, Rita C. [4] ; Lopes, Marco Antonio [6] ; Bakker, Egbert [3] ; Zatz, Mayana [4] ; Bertola, Debora [4] ; De Vlaminck, Iwijn [2] ; Passos-Bueno, Maria Rita [4]
Total Authors: 16
Affiliation:
[1] Univ Sao Paulo, Inst Biociencias, Ctr Pesquisa Genoma Humano & Celulas Tronco, Dept Genet & Biol Evolut, Rua Matao 277, BR-05508090 Sao Paulo, SP - Brazil
[2] Cornell Univ, Meinig Sch Biomed Engn, Ithaca, NY - USA
[3] Leiden Univ, Med Ctr, LDGA, Dept Clin Genet, Leiden - Netherlands
[4] Lourenco, Naila C., V, Univ Sao Paulo, Inst Biociencias, Ctr Pesquisa Genoma Humano & Celulas Tronco, Dept Genet & Biol Evolut, Rua Matao 277, BR-05508090 Sao Paulo, SP - Brazil
[5] Fac Med Jundiai, Jundiai, SP - Brazil
[6] Univ Sao Paulo, Fac Med, Dept Obstet & Ginecol, Sao Paulo, SP - Brazil
Total Affiliations: 6
Document type: Journal article
Source: GENETICS AND MOLECULAR BIOLOGY; v. 41, n. 3, p. 545-554, JUL-SEP 2018.
Web of Science Citations: 2
Abstract

Our aim was to develop and apply a comprehensive noninvasive prenatal test (NIPT) by using high-coverage targeted next-generation sequencing to estimate fetal fraction, determine fetal sex, and detect trisomy and monogenic disease without parental genotype information. We analyzed 45 pregnancies, 40 mock samples, and eight mother-child pairs to generate 35 simulated datasets. Fetal fraction (FF) was estimated based on analysis of the single nucleotide polymorphism (SNP) allele fraction distribution. A Z-score was calculated for trisomy of chromosome 21 (T21), and fetal sex detection. Monogenic disease detection was performed through variant analysis. Model validation was performed using the simulated datasets. The novel model to estimate FF was robust and accurate (r(2)= 0.994, p-value < 2.2e-16). For samples with FF > 0.04, T21 detection had 100% sensitivity (95% CI: 63.06 to 100%) and 98.53% specificity (95% CI: 92.08 to 99.96%). Fetal sex was determined with 100% accuracy. We later performed a proof of concept for monogenic disease diagnosis of 5/7 skeletal dysplasia cases. In conclusion, it is feasible to perform a comprehensive NIPT by using only data from high coverage targeted sequencing, which, in addition to detecting trisomies, also make it possible to identify pathogenic variants of the candidate genes for monogenic diseases. (AU)

FAPESP's process: 13/08028-1 - CEGH-CEL - Human Genome and Stem Cell Research Center
Grantee:Mayana Zatz
Support type: Research Grants - Research, Innovation and Dissemination Centers - RIDC
FAPESP's process: 13/14996-0 - Detection of fetal genetic disorders through non-invasive prenatal testing using next-generation sequencing
Grantee:Carolina Malcher Amorim de Carvalho Silva
Support type: Scholarships in Brazil - Doctorate
FAPESP's process: 15/11998-8 - Analysis of cell-free DNA sequencing data in order to infer the fetal fraction of cell-free DNA in maternal plasma
Grantee:Carolina Malcher Amorim de Carvalho Silva
Support type: Scholarships abroad - Research Internship - Doctorate