Noninvasive Whole-Genome Sequencing of a Human Fetus

摘要: Analysis of cell-free fetal DNA in maternal plasma holds promise for the development noninvasive prenatal genetic diagnostics. Previous studies have been restricted to detection trisomies, specific paternally inherited mutations, or genotyping common polymorphisms using material obtained invasively, example, through chorionic villus sampling. Here, we combine genome sequencing two parents, genome-wide haplotyping, and deep noninvasively determine sequence a human fetus at 18.5 weeks gestation. Inheritance was predicted 2.8 × 10(6) parental heterozygous sites with 98.1% accuracy. Furthermore, 39 44 de novo point mutations were detected, albeit limited specificity. Subsampling these data analyzing second family trio by same approach indicate that haplotype blocks ~300 kilo-base pairs combined shallow is sufficient substantially complement genome. However, ultradeep necessary practical genome-wide. Although technical analytical challenges remain, anticipate analysis variation genomes will facilitate diagnosis both recessive dominant Mendelian disorders.