Extended Data Fig. 2: Whole exome analysis of the patients.
From: A variant in human AIOLOS impairs adaptive immunity by interfering with IKAROS
a, Patients and healthy family members who were analyzed by whole-exome sequencing are indicated with an asterisk. b, Filtering strategy for whole-exome analysis. Patient-specific variants were selected by familial segregation. Variants resulting from sequencing errors were filtered out by ignoring the variants with high in-house frequency. Variants shared by the P1 and the P2 were selected and further narrowed down to rare variants by using cut-off as dbSNP minor allele frequency (MAF) of 0.0001. Candidate variants other than IKZF3 were BCL9 (NM_004326.2:c.3934delG, NP_004317.2:p.Gly1312Alafs, and NM_004326.2:c.3936_3937insTTT, NP_004317.2:p.Gly1311_His1312insGly), BMS1 (NM_014753.3:c.3557C>T, NP_055568.3:p.Ala1186Val), CCDC102A (NM_033212.3:c.1135C>T, NP_149989.2:p.Arg379Trp), DENND4B (NM_014856.2:c.307G>A, NP_055671.2:p.Val103Ile), KIAA1462 (NM_020848.2:c.2215G>A, NP_065899.1:p.Gly739Ser), KRTAP2-2 (NM_033032.2:c.333_334delGA, NP_149021.2:p.Thr112Profs), NCSTN (NM_015331.2:c.464A>G, NP_056146.1:p.Glu155Gly), TCHH (NM_007113.2:c.1072_1074delGAG, NP_009044.2:p.Glu358del), and TMEM129 (NM_138385.3:c.40G>C, NP_612394.1:p.Val14Leu). c, Alignment of amino acid sequences of the second zinc finger ___domain of AIOLOS orthologues from several species. Gray-shaded letters indicate identical amino acid in relation to human AIOLOS. Glycine residue at 159 position in human AILOS is well conserved beyond species. d, Expression pattern of IKZF family genes during human B cell development. CLP/Pre-pro-B cell (CD34+CD10+CD19−), pro-B cells (CD34+CD10+CD19+), large pre-B cells (CD34−CD10+CD19+CD79B+IgM−) and small pre-B cells (CD34−CD10+CD19+CD79B−IgM−) were isolated by FACS sorting from the bone marrow aspirate of a healthy donor. RNA was extracted and subjected to RNA-seq analysis. FPKM of IKZF genes in the indicated populations are shown.
