Fig. 3.

Phenotype and genotype of pedigree. (A) Sanger sequence chromatographs showing the prostaglandin synthase-1 (PTGS-1) variants in eight pedigree members spanning three generations. Pedigree members with impaired platelet aggregation and excessive hemorrhage all had heterozygosity of the PTGS-1 c.50C>T variant (P17L, rs3842787; yellow box). A second known variant in PTGS-1 (c.22T>C, rs1236913; blue box) was also present in some family members but did not segregate with the platelet disorder phenotype. (B) Pedigree for affected family. Black arrowhead indicates proband. Filled symbols represent individuals with an inherited platelet function disorder (IPFD) and hashed symbols represent individuals with hemophilia A. WES was performed on the following six pedigree members: II.1, II.2, III.1, III.2, III.3 and III.4 (*not sequenced). (C) Principle components analysis (PCA) of the exome-sequenced individuals from the analyzed pedigree. PCA was performed on variants from these individuals and from select populations of the 1000 Genomes phase 3 dataset (CEU, Utah Residents [CEPH] with Northern and Western European Ancestry; JPT, Japanese in Tokyo, Japan; CHB, Han Chinese in Beijing, China; YRI, Yoruba in Ibadan, Nigeria.). This analysis shows that all sequenced individuals are of European descent and high-quality sequencing and variant calling was achieved.