Figure 4

Expression skewing across the X chromosome and recombination mapping. (A,B) mRNA expression bias of the X chromosome inherited from the mother to the proband analyzed by comparing heterozygous SNPs detected both by WGS and RNA sequencing. Each black dot represents each informative heterozygous SNP. The grey dots are SNPs of genes known to escape XCI. (A) SNPs in the proband demonstrate that most genes across the entire X chromosome were expressed almost exclusively from the maternal allele. (B) SNPs in the mother revealed that most genes inside the central region from the short arm (p21.2) to the long arm (q26.3) were suppressed and that genes outside the central region were highly expressed from the inherited allele in the mother’s leukocytes. Because XCI of the mother’s leukocytes was extremely skewed, the points where expression bias patterns were inverted are regarded as the positions of meiotic recombination. The lower panel shows the X chromosome and the red triangles indicate the locations of AR at Xq12, XIST at Xq13.2, and ATP7A at Xq21.1. PAR, pseudoautosomal region. (C) A schematic diagram depicting the inheritance pattern of this family. The deleted ATP7A locus (del, red) is received from her grandmother (GrM) and her mother (Mo) to the proband (P) and inactivated in the mother, but activated in the proband. The central chromosomal region of the proband was from her mother’s inactivated X chromosome (Xi, light green) derived from her grandmother, and two other distal regions (red arrows, putative XCI control loci) were from her mother’s activated X chromosome (pink) derived from her grandfather (GrF). The X chromosome from the father (Fa) is shown in light blue. wt, wild-type.