Figure 2

Haplotype-assisted noninvasive prenatal testing (NIPT) method. (a) Target region for enrichment and haplotyping. (b) The haplotype-assisted approach to NIPT for Duchenne muscular dystrophy (DMD). The fetal genome can be one of four combinations that result from the random assortment of parental haplotypes. If a male fetus inherits haplotype X_a (the same as the proband’s, which is the mutant allele) from the mother, this haplotype will be overrepresented in the plasma. By contrast, when haplotype X_u (wild-type allele) is inherited, it exists in greater proportion to haplotype X_a. If a female fetus inherits the maternal X_a haplotype, it would have excessive reads compared with haplotype X_u; by contrast, similar amounts of the two types of maternal haplotypes would exist. Because the father had only one X chromosome, the fetal inherited paternal haplotype can be clearly identified from paternal genotyping. The informative single-nucleotide polymorphisms that were used for analysis were maternal heterozygous sites (*). Based on the maternal haplotypes and maternal plasma sequencing data, the cumulative probability of each of the two possible haplotype combinations in males or females could be calculated using a hidden Markov model. The fetal genetic conditions were predicted by observing the inherited maternal mutant allele, which was then used for NIPTs for DMD.