Figure 1

Schematic location of rare CLU coding variants identified in stage I, II and III resequencing. (A) Schematic presentation of CLU gene structure, CLU transcript 1 [NM_001831.2] and CLU protein [NP_001822.2]. Coding variants observed in AD patients only are indicated in red, variants observed in patients and controls in blue, variants detected in control individuals only in green. All predicted pathogenic variants are indicated in bold. After cleavage of the signal peptide, the secreted CLU form (449 AA) contains two coiled-coiled domains (pink), three amphipathic domains (blue) and a cysteine rich region (yellow) with 5 disulfide bridges (grey). Six N-glycosylation sites are marked in purple. For ease of interpretation, amino acids are given for specific CLU domains and for detected protein variants only. (B) Conservation alignment of amino acids of CLU beta-chain variants is shown in different species; Homo sapiens (ENSP00000315130), Gorilla gorilla (ENSGGOP00000016521), Pan troglodytes (ENSPTRP00000034423), Pongo abelii (ENSPPYP00000020696), Macaca mulata (ENSMMUP0000003216), Nomascus leucogenys (ENSNLEP00000020015), Tarsius syrichta (ENSTSYP00000001230), Mus musculus (ENSMUSP00000022616), Rattus norvegicus (ENSRNOP00000022095), Canis lupus familiaris (ENSCAFP00000012350) and Bos taurus (ENSBTAP00000007324). Similar to panel A, patient specific variants are marked in red, variants observed in patients and controls in blue and variants in control individuals in green. All predicted pathogenic variants are marked in bold.