Figure 3.
Fetal inheritance of parental mutations in family A. A, For paternal inheritance, SNPs that were homozygous in the mother and heterozygous in the father were selected. The paternal-specific SNP alleles transmitted to the proband belonged to the haplotype linked with the proband's mutation (Mpa, red). The paternal-specific SNP alleles not present in the proband belonged to the haplotype not linked with the proband's mutation (Npa, blue). B, For maternal inheritance, SNPs that were heterozygous in the mother and homozygous in the father were classified into type α- or type β-SNPs. For type α-SNPs, the paternal alleles were the same as those on Mma (red). The equal representation of Mma and Nma alleles in the maternal plasma indicated that the fetus had inherited Nma from the mother. For type β-SNPs, the paternal alleles were the same as those of Nma (blue). The overrepresentation of Nma alleles in the maternal plasma also indicated that the fetus had inherited Nma from the mother. C, Parental haplotype blocks are denoted by arrows along the entire targeted region. The tail and tip of an arrow denote the start and end, respectively, of a RHDO block, established analytically from the telomeric to the centromeric end. Left, Paternal inheritance analysis resulted in 14 paternal haplotype blocks, represented by red arrows, all indicating the inheritance of Mpa. Prenatal determination of the fetal inheritance status was made according to the haplotype block spanning the CYP21A2 gene, indicated with a thick red arrow. Right, Maternal inheritance analysis resulted in six and one SPRT classifications using type α- and type β-SNPs, respectively. The haplotypes established by the type α- and β-SNPs are represented by upper and lower half-arrows, respectively. The fetus had inherited Nma from the mother by both type α- and β-SNPs. The SPRT classification near the centromeric end indicated that a recombination event had occurred. Grey line, targeted region spanning chromosome 6: 24,954,958–38,933,706. Dotted line and green box, CYP21A2 gene on chromosome 6: 32,006,093–32,009,447. D, RHDO analysis showing SPRT classification process using type α-SNPs on chromosome 6: 31,161,210–33,431,319 (i) or type β-SNPs on chromosome 6: 24,958,935–32,972,690 (ii). For details, please refer to Supplemental Methods.