Suzanne de Bruijn

87 Homozygous KIAA1549 variants are associated with retinitis pigmentosa 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 NM_001164665 1950 aa (6283 bp) XM_935390 734 aa (2652 bp) 8a Transmembrane domain (p.998-1018 and p.1299-1319) p.(Arg18Alafs*64) p.(Glu801Metfs*9) p.(His1562Gln) NM_001164665 XM_935390 Bone marrow Brain Duodenum Heart Kidney Liver Lung Retina Skeletal muscle Spleen Stomach Testis Thymus 0 20 40 60 80 100 Relative expression to GUSB Bone marrow Brain Duodenum Heart Kidney Liver Lung Retina Skeletal muscle Spleen Stomach Testis Thymus 0 100 200 300 Serine-rich domain (p.494-764) Extracellular Extracellular Intracellular B A Figure 3. Expression of KIAA1549 transcripts in human tissues. (A) Schematic representation of the major long and short KIAA1549 transcripts and identified segregating variants. A previously reported KIAA1549 variant by Abu-Safieh et al. is depicted in italics. 4 The short transcript is transcribed from an alternative promoter sequence present in intron 8, and includes a transcript-specific exon referred to as exon 8a. (B) Relative KIAA1549 expression in human tissues determined by qPCR. Expression of the transcript encoding the long isoform (NM_001164555) is depicted in the left panel, and expression of the transcript encoding the short isoform (XM_935390) is depicted in the right panel. The long transcript is predominantly expressed in the brain, whereas expression of the short transcript is significantly increased in the retina compared to other tissues. Expression of KIAA1549 transcripts in human tissues To gain knowledge on the specific role of KIAA1549 , its relative expression was determined in a set of human adult tissues. Two major KIAA1549 isoforms have been identified (Uniprot: Q9HCM3), a long primary isoform (NM_001164665) of 1950 amino acids (aa) and a short isoform (XM_935390) of 734 aa ( Figure 3A ). The shorter isoform is produced from an alternative transcript transcribed from an alternative promoter sequence located in intron 8. The nomenclature of all genetic or protein elements is based on the long isoform. The expression of both KIAA1549 transcripts and of the reference gene GUSB was evaluated in cDNA of human tissues by qPCR ( Figure 3B ). The