Figure 3: Principles of haplotype analysis.

A family-specific haplotype analysis based on SNP genotyping of the parents and the paternal grandmother. “P” represents “paternal grandmother”, “F” represents “father”, “M” represents “mother”, “F1” represents “haplotype 1 of the father”, “F2” represents “haplotype 2 of the father”, “M1” represents “haplotype 1 of the mother” and “M2” represents “haplotype 2 of the mother”. The seven closely linked SNPs were selected from the NGS SNP loci and were coded 1 to 7. The SNP genotype of the father was heterozygous, and both the paternal grandmother and the mother were homozygous. The proband and his mother were both affected by PKD, while the proband’s wife was normal. By Mendelian analysis of the SNP genotypes of the parents and the paternal grandmother, it is possible to identify the four parental haplotypes. Furthermore, it is easy to determine F1 as a mutation haplotype and a disease-causing haplotype and F2 as a normal haplotype. The SNP loci colored in red represent the informative SNPs in F1 that can determine the unique haplotype of F1. The SNP loci colored in green represent the informative SNPs in F2 that can determine the unique haplotype of F2. By contrast, the SNP loci colored in black are defined as invalid SNPs (A). “E” represents “embryo”. According to the SNP genotypes of E and E*, we can infer that E inherited haplotype 1 of the father because it carried the informative SNPs of F1. Similarly, we can infer that E* inherited haplotype 2 of the father because it carried the informative SNPs of F2. Therefore, we can define E as abnormal and E* as normal (B).