| Journal: | Genetics and molecular biology |
| Database: | PERIÓDICA |
| System number: | 000419974 |
| ISSN: | 1415-4757 |
| Authors: | Malcher, Carolina1 Yamamoto, Guilherme L1 Burnham, Philip2 Ezquina, Suzana A.M1 Lourenço, Naila C.V1 Balkassmi, Sahilla4 Antonio, David S. Marco1 Hsia, Gabriella S.P1 Gollop, Thomaz3 Pavanello, Rita C1 Lopes, Marco Antonio5 Bakker, Egbert4 Zatz, Mayana1 Bertola, Debora1 Vlaminck, Iwijn De;2 Passos-Bueno, Maria Rita1 |
| Institutions: | 1Leiden University Medical Center, Department of Clinical Genetics, Leiden, Zuid Holland. Países Bajos |
| Year: | 2018 |
| Season: | Sep |
| Volumen: | 41 |
| Number: | 3 |
| Pages: | 545-554 |
| Country: | Brasil |
| Language: | Inglés |
| Document type: | Artículo |
| Approach: | Caso clínico |
| English abstract | Our aim was to develop and apply a comprehensive noninvasive prenatal test (NIPT) by using high-coverage tar- geted 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 sin- gle 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 vali- dation 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 per- formed 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 dis - eases |
| Disciplines: | Biología |
| Keyword: | Biología celular, Genética, Diagnóstico, ADN libre de células, Secuenciación de próxima generación (NGS), Trisomía, Prueba prenatal no invasiva, Fracción fetal |
| Keyword: | Cell biology, Genetics, Diagnosis, Cell-free DNA, Next Generation Sequencing (NGS), Trisomy, Noninvasive prenatal test, Fetal fraction |
| Full text: | Texto completo (Ver PDF) |
