Chen Pin-Jung1, Teng Pai-Chi1, Yazhen Zhu1, Yu Jen Jan2, Matthew Smalley1, Yalda Afshar3, Chen Li-Ching4, Margareta D Pisarska3,5, Tseng Hsian-Rong1. 1. Department of Molecular and Medical Pharmacology, California NanoSystems Institute, Crump Institute for Molecular Imaging, University of California, Los Angeles, Los Angeles, CA, USA. 2. Urologic Oncology Program and Uro-Oncology Research Laboratories, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, Los Angeles, CA, USA. 3. Division of Maternal Fetal Medicine, Department of Obstetrics and Gynecology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA. 4. Department of Obstetrics and Gynecology, Cathay General Hospital, Taipei, Taiwan. 5. Department of Obstetrics and Gynecology, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Abstract
PURPOSE OF REVIEW: The purpose of this review is to highlight recent research advances in noninvasive prenatal diagnostic methods. RECENT FINDINGS: Recent studies developing noninvasive prenatal diagnostic (NIPD) methods have been focused on either fetal nucleated red blood cells (fNRBCs) or circulating trophoblasts (cTBs). Enriched cTBs were successfully utilized for whole genome profiling and short tandem repeat (STR) identification to confirm feto-maternal relationship. However, further analysis of isolated fNRBCs remains confined to examining fetal cytogenetics. SUMMARY: Invasive prenatal diagnostic procedures, amniocentesis and chorionic villus sampling, are the gold standard for the diagnosis of fetal chromosomal abnormalities and genetic disorders. Meanwhile, noninvasive techniques of analyzing circulating cell-free fetal DNA (cffDNA) have been limited to screening tools and are highly fragmented and confounded by maternal DNA. By detecting circulating fetal nucleated cells (CFNCs) we are able to noninvasively confirm fetal chromosomal abnormalities, truly realizing the concept of "noninvasive prenatal diagnostics". The primary technical challenge is the enrichment of the low abundance of CFNCs in maternal peripheral blood. For any cell-based NIPD method, both fetal whole genome profiling and confirmation of the feto-parental relationship are essential. This has been successfully performed using enriched and isolated cTBs, making cTB a better candidate for NIPD. cTB enumeration also correlates with abnormal fetal or placental development. On the other hand, downstream analysis of fNRBCs remains limited to examining fetal sex and aneuploidies. Furthermore, trophoblast-based NIPD via an endocervical sample is also promising because of reduced dilution from hematologic cells.
PURPOSE OF REVIEW: The purpose of this review is to highlight recent research advances in noninvasive prenatal diagnostic methods. RECENT FINDINGS: Recent studies developing noninvasive prenatal diagnostic (NIPD) methods have been focused on either fetal nucleated red blood cells (fNRBCs) or circulating trophoblasts (cTBs). Enriched cTBs were successfully utilized for whole genome profiling and short tandem repeat (STR) identification to confirm feto-maternal relationship. However, further analysis of isolated fNRBCs remains confined to examining fetal cytogenetics. SUMMARY: Invasive prenatal diagnostic procedures, amniocentesis and chorionic villus sampling, are the gold standard for the diagnosis of fetal chromosomal abnormalities and genetic disorders. Meanwhile, noninvasive techniques of analyzing circulating cell-free fetal DNA (cffDNA) have been limited to screening tools and are highly fragmented and confounded by maternal DNA. By detecting circulating fetal nucleated cells (CFNCs) we are able to noninvasively confirm fetal chromosomal abnormalities, truly realizing the concept of "noninvasive prenatal diagnostics". The primary technical challenge is the enrichment of the low abundance of CFNCs in maternal peripheral blood. For any cell-based NIPD method, both fetal whole genome profiling and confirmation of the feto-parental relationship are essential. This has been successfully performed using enriched and isolated cTBs, making cTB a better candidate for NIPD. cTB enumeration also correlates with abnormal fetal or placental development. On the other hand, downstream analysis of fNRBCs remains limited to examining fetal sex and aneuploidies. Furthermore, trophoblast-based NIPD via an endocervical sample is also promising because of reduced dilution from hematologic cells.
Entities:
Keywords:
Array Comparative Genomic Hybridization; Circulating Fetal Nucleated Red Blood Cell; Circulating Trophoblast; Noninvasive Prenatal Diagnostic; Short Tandem Repeat; Whole Genome Amplification
Authors: Steen Kølvraa; Ripudaman Singh; Elizabeth A Normand; Sadeem Qdaisat; Ignatia B van den Veyver; Laird Jackson; Lotte Hatt; Palle Schelde; Niels Uldbjerg; Else Marie Vestergaard; Li Zhao; Rui Chen; Chad A Shaw; Amy M Breman; Arthur L Beaudet Journal: Prenat Diagn Date: 2016-11-18 Impact factor: 3.050
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