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Table 1 Schematics of the filtering steps used for WES-data. The procedure used to find heterozygous candidate variants in whole-exome data from four affected siblings and one unaffected sibling in a family with early onset AD (PED.25)

From: Identification and description of three families with familial Alzheimer disease that segregate variants in the SORL1 gene

Step Criteria Description Number of variations passed Genes with excluded variants (number of variants)
1 Rare and novel variants segregating with disease CLC Genomic Workbench pipeline to extract shared variants in cases, not found in healthy sibling and with MAF < 1% in dbSNP138 1511 for gene names, see Additional file 5: Table S3
2 Non-synonymous or in splice-site region Information annotated in CLC Genomic Workbench to include missense, nonsense, and variants in ± 2 nt of splice-site region 109 for gene names, see Additional file 5: Table S3
(1402)
3 Rare and novel variants in relevant populations Excluded variants with MAF ≥ 1% found in either 1000G EUR, 1000G FIN, or in HBVDB Swedes/Danes 74 RAD54L, MROH7, CENPF, TMEM63A, COCL6A6, TOPBP1, SLC17A4, TNXB, HLA-DPA1, CAPZA3, ABCC3, PRTN3, NOTCH2, PDE4DIP, PLEKHB2, MUC4, OR4C5, KCNJ12, TBC1D3, RP11-1407015.2, KRTAP-9, CDC27, EME1, SSC5D, C1orf94, XCR1, PIGZ, BTN1A1, TGFB2
(35)
4 Predicted to be deleterious, disease causing or to affect splicing Alamut v.2.3 used for in-silico analysis of missense prediction to be either Deleterious (SIFT), to be Disease Causing (Mutation Taster) or being nonsense variations predicted to impact splicing by MaxEnt/NNSPLICE/HSF 45 DMAP1, NBPF14, IGFN1, OBSCN, DNAH1, MUC4, TXNDC5, SLC17A3, MDC1, PRSS3, MUC6, PRR4, PRB1, C17orf74, CCDC144CP, MPP3, ZSCAN5A, SLC9B1P4, PLA2G3, C22orf42
(29)
5 Quality control of variant calls Variants with low freq. (<20%), unbalanced F/R ratio (>0,1) and within repetitive sequence were removed 13 SRGAP2, OBSCN, ANKRD36C, MUC4, FRG1, AP3S1, HLA-G, PFDN6, PRSS1, KMT2C, MUC6, SLC2A3, PRR4, PRB3, FAM186A, HNF1A, AC087499.7, RP11-1407O15.2, KRTAP1-3, KRTAP4-5, ANKFN1, ROCK1, CGB1, SPIB, FRG1B
(32)
6 Knowledge based prioritization BioGSP to value expression profile and Ingenuity Pathway analysis to search for relevant processes 7 PLSCR2, AOC2, AOC1, MYO7A, AQPR
(6)
7 Segregation analysis Sanger sequencing in WES individuals and affected parent 6 SLFNL1
(1)
8 Passed variations in genes: LTF, MME, FAM221A, UBE4A, SORL1, KDM2B