(A) In in vitro differentiated human erythroblasts, three LGALS8 mRNA isoforms are expressed. Isoform 1 includes the “multiple of three nucleotides” exon 9 (in red, 126-bp), whereas isoforms 2 and 3 do not. The nonsense variant rs2273865 (p.Leu212Ter) is located in exon 9. At this variant, the minor A-allele has a frequency of 3.5% in populations of European ancestry (ExAC). (B) Eight erythroblast samples are heterozygous at rs2273865 and show strong allelic imbalance (binomial P<0.05 for all samples). Numbers in the bars indicate the numbers of reads carrying the T (green) or A (blue) allele. Differential expression of total LGALS8 (C), isoform 1 (D), isoform 2 (E), and isoform 3 (F) between erythroblast samples homozygous TT (n = 16) and heterozygous AT (n = 8) at rs2273865. No samples homozygous for the minor allele (AA) were available. (G) The ratio of LGALS8 transcripts without exon 9 over transcripts with exon 9 is higher in heterozygous AT than in homozygous TT erythroblast samples. P-values are calculated by linear regression correcting for cell developmental stage.