Fetal genome profiling at 5 weeks of gestation after noninvasive isolation of trophoblast cells from the endocervical canal.
Single-gene mutations account for more than 6000 diseases, 10% of all pediatric hospital admissions, and 20% of infant deaths. Down syndrome and other aneuploidies occur in more than 0.2% of births worldwide and are on the rise because of advanced reproductive age. Birth defects of genetic origin can be diagnosed in utero after invasive extraction of fetal tissues. Noninvasive testing with circulating cell-free fetal DNA is limited by a low fetal DNA fraction. Both modalities are unavailable until the end of the first trimester. We have isolated intact trophoblast cells from Papanicolaou smears collected noninvasively at 5 to 19 weeks of gestation for next-generation sequencing of fetal DNA. Consecutive matched maternal, placental, and fetal samples (n = 20) were profiled by multiplex targeted DNA sequencing of 59 short tandem repeat and 94 single-nucleotide variant sites across all 24 chromosomes. The data revealed fetal DNA fractions of 85 to 99.9%, with 100% correct fetal haplotyping. This noninvasive platform has the potential to provide comprehensive fetal genomic profiling as early as 5 weeks of gestation.
Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI 48201, USA.|Department of Physiology, Wayne State University School of Medicine, Detroit, MI 48201, USA.
Chandni V
CV
Jain
Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI 48201, USA.|Department of Physiology, Wayne State University School of Medicine, Detroit, MI 48201, USA.
Leena
L
Kadam
Department of Clinical Chemistry, VU University Medical Center, Amsterdam, Netherlands.
Marie
M
van Dijk
Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI 48201, USA.
Hamid-Reza
HR
Kohan-Ghadr
Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI 48201, USA.
Brian A
BA
Kilburn
Safe and Sound for Women, 3131 La Canada Street, Las Vegas, NV 89169, USA.
Craig
C
Hartman
Safe and Sound for Women, 3131 La Canada Street, Las Vegas, NV 89169, USA.
Vicki
V
Mazzorana
Department of Clinical Chemistry, VU University Medical Center, Amsterdam, Netherlands.
Allerdien
A
Visser
Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI 48201, USA.
Michael
M
Hertz
Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI 48201, USA.
Alan D
AD
Bolnick
Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI 48201, USA.
Rani
R
Fritz
Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI 48201, USA.|Department of Anatomy and Cell Biology, Wayne State University School of Medicine, Detroit, MI 48201, USA.|Program in Reproductive and Adult Endocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.
D Randall
DR
Armant
Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI 48201, USA. sdrewlo@med.wayne.edu.
Sascha
S
Drewlo
D000073888:Cell-Free Nucleic Acids / Q000032:analysis; D004252:DNA Mutational Analysis; D005260:Female; D005333:Fetus / Q000473:pathology*; D005838:Genotype; D005865:Gestational Age; D006239:Haplotypes; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D018895:Microsatellite Repeats; D009154:Mutation; D010920:Placenta / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D011295:Prenatal Care; D011296:Prenatal Diagnosis / Q000379:methods*; D014327:Trophoblasts / Q000166:cytology*
D000073888:Cell-Free Nucleic Acids