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Description of Strs in Trinucleotide-Repeat Diseases

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Description of Strs in Trinucleotide-Repeat Diseases Table S1: Description of STRs in trinucleotide-repeat diseases. Normal range or hg19 reference Symbol Disease Gene repeats Expansion DRPLA Dentatorubro-pallidoluysian atrophy ATN1 7-34 49 SCA2 Spinocerebellar ataxia 2 ATXN2 15-24 33 SCA8 Spinocerebellar ataxia 8 ATXN8OS 16-34 80 HPE5 Holoprosencephaly-5 ZIC2 15 25 OPMD Oculopharyngeal muscular dystrophy PABPN1 6-7 12 SCA3 Spinocerebellar ataxia 3 ATXN3 13-36 61 HDL Huntington disease-like 2 JPH3 7-28 40 SCA6 Spinocerebellar ataxia 6 CACNA1A 4-7 21 DM1 Myotonic dystrophy 1 DMPK 5-37 50 SD5 Syndactyly HOXD13 15 22 SCA10 Spinocerebellar ataxia 10 ATXN10 10-20 800 SCA7 Spinocerebellar ataxia 7 ATXN7 4-35 37 DM2 Myotonic dystrophy 2 ZNF9 10-26 75 Blepharophimosis, epicanthusinversus, BPES andptosis FOXL2 14 19 CCHS Central hypoventilation syndrome PHOX2B 20 24 SCA12 Spinocerebellara taxia12 PPP2R2B 7-45 55 SCA1 Spinocerebellar ataxia1 ATXN1 6-38 39 CCD Cleidocranial dysplasia RUNX2 17 27 SCA17 Spinocerebellar ataxia17 TBP 25-42 47 HFG Hand-foot-uterus syndrome HOXA13 14 22 ALS Amyotrophic lateral sclerosis C9orf72 3 31 FRDA Friedreich ataxia FXN 6-32 200 SBMA Spinal and bulbar muscular atrophy AR 9-35 36 XLMR Mental retardation, X-linked SOX3 15 22 FXS FragileX syndrome FMR1b 20 200 FXTAS FragileX-associated tremor/ataxia syndrome FMR1b 20 55 FRAXE Mental retardation, FRAXE type FMR2 4-39 200 HD Huntington disease HTT 6-34 40 SCA36 Spinocerebellar ataxia 36 NOP56 3-8 1500 Table S2 : Description of STRs that have been identified in epilepsy disorders. Reference Chr Start Stop Gene motif* Disease Ref Expansion chr2 96862805 96862859 STARD7 AAAAT FAME2 11 340 chr4 160263679 160263768 RAPGEF2 TTTTA BAFME7 18 60 chr5 10356451 10356519 MARCH6 TTTTA FAME3 12 791 chr8 119379052 119379357 SAMD12 TTTCA# FAME1 0 440 chr16 24624760 24624850 TNRC6A TTTTA BAFME6 18 22 CGCGGG chr21 45196326 45196360 CSTB GCGGGG ULD 3 30 chrX 25031779 25031808 ARX CGC EIEE1 10 20 Whenever the number of repeats of the expansion was not available, we inferred it using the minimum length of this expansion reported in the literature. *Expansion motifs are usually more complex than reference motif # This motif is not seen in the reference. Reference is TTTTA Table S3: Number of twin pairs matching for each STR expansion disease. Hg19 Trinucleotide reference disease Both twins same Twins ± 1 Twins ± 2 length SCA17 2 2 2 114 SCA1 3 8 8 87 FXS 4 5 6 60 FXTAS 4 5 6 60 SBMA 5 7 7 66 SCA2 6 8 9 69 DM2 6 9 9 80 HD 8 9 9 57 BPES 9 9 9 42 ALS 9 9 9 18 CCHS 9 9 10 60 HDL 9 9 10 42 SCA10 9 9 10 70 FRAXE 9 10 10 45 DM1 10 10 10 60 CCD 10 10 10 51 DRPLA 10 10 10 45 SCA8 10 10 10 45 HPE5 10 10 10 45 SD5 10 10 10 45 XLMR 10 10 10 45 HFG 10 10 10 42 SCA6 10 10 10 39 OPMD 10 10 10 30 SCA7 10 10 10 30 SCA12 10 10 10 30 SCA3 10 10 10 24 FRDA 10 10 10 18 SCA36 10 10 10 24 Number of twin pairs (total of 10 twin pairs) that have the exact same repeat number for both alleles, same or ± one repeat difference for one or both alleles and same or ± two repeats difference for one or both alleles for each STR expansion disease. Table S4: Number of twin pairs matching for each STR expansion related to an increased risk of epilepsy Hg19 STR reference expansion Both twins same Twins ± 1 Twins ± 2 length SAMD12 0 4 4 105 RAPGEF2 1 5 7 90 TNRC6A 3 8 8 90 STARD7 2 6 9 55 MARCH6 3 7 9 70 ARX 9 9 10 30 CSTB 10 10 10 36 Number of twin pairs (total of 10 twin pairs) that have the exact same repeat number for both alleles, same or ± one repeat difference for one or both alleles and same or ± two repeats difference for one or both alleles for each STR expansion related to an increased risk of epilepsy. Table S5: Information on genes identified in table 3 Gene Function Disease(s) Function: Transcription factor that plays a key role in neuronal Intellectual differentiation by specifically repressing expression of non- MYT1L disability, neuronal genes during neuron differentiation autism Phenotype (GWAS): cognitive impairment or decline Function: Putative adapter protein involved in asymmetrical cell PARD3B division and cell polarization processes. May play a role in the ALS2 formation of epithelial tight junctions Cms1 Ribosomal Small Subunit Homolog CMSS1 Function: Acts as a regulator of the antiangiogenic activity on FILIP1L endothelial cells Function: Non-catalytic subunit of the queuine tRNA- ribosyltransferase that catalyzes the base-exchange of a guanine QTRT2 residue with queuine Gene ontology: metal ion binding (GO:0046872) Phenotype (GWAS): unipolar depression, schizophrenia, bipolar ADAMTS16 disorder, functional impairment measurement Gene ontology: metal ion binding (GO:0046872) Microcephaly, seizures, CDH18 Function: Cadherins are calcium-dependent cell adhesion proteins developmental delay Function: Subunit of non-clathrin- and clathrin-associated adaptor AP3B1 protein complex 3 (AP-3) that plays a role in protein sorting in the late-Golgi/trans-Golgi network and/or endosomes ATXN7L1 Ataxin 7 Like 1 Function: Transcription factor involved in unfolded protein CREB3L2 response Function: Calcium-regulated non-lysosomal thiol-protease Muscular CAPN3 Gene ontology: calcium ion binding (GO:0005509) dystrophy Function: As a component of the GATOR subcomplex GATOR2, WDR59 functions within the amino acid-sensing branch of the TORC1 signaling pathway Function: Receptor tyrosine kinase which mediates the pleiotropic INSR actions of insulin Brief summary of function, gene ontology, phenotype and diseases for genes in table 3. In this table we focused specifically on information related to neurodevelopmental conditions. Information comes from https://www.genecards.org/. Supporting Text 1 365 epilepsy related gene list AARS,ABAT,ABCC8,ACTB,ACY1,ADCK3,ADSL,ALDH7A1,ALG1,ALG11,ALG13, ALG3,ALG6,AMACR,AMT,ANKRD11,AP3BP2,APOPT1,ARFGEF2,ARHGEF9,ARI D1B,ARX,ASAH1,ASNS,ATP1A2,ATP1A3,ATP2A2,ATP6AP2,ATP6V0A2,ATP7A,A TRX,AUTS2,BOLA3,BRAT1,BTD,CACNA1A,CACNA1E,CACNA1H,CACNA2D2,C ASK,CASR,CCDC88C,CDKL5,CHD2,CHRNA2,CHRNA4,CHRNB2,CLCN2,CLCN4, CLCNKA,CLCNKB,CLDN16,CLDN19,CLN3,CLN5,CLN6,CLN8,CLTC,CNNM2,CN TN2,CNTNAP2,COL18A1,COL4A1,COL4A3BP,COL6A2,COQ2,COQ4,CPA6,CPS1, CPT2,CSTB,CTSD,CTSF,CUL4B,D2HGDH,DCX,DDX3X,DENND5A,DEPDC5,DHD DS,DLAT,DNAJC5,DNM1,DOCK7,DPAGT1,DPM1,DPM2,DPYD,DYNC1H1,DYRK 1A,EEF1A2,EFHC1,EGF,EHMT1,EMX2,EPM2A,FA2H,FARS2,FASN,FGD1,FGF12,F GFR3,FIG4,FKRP,FKTN,FLNA,FOLR1,FOXG1,FOXRED1,FRRS1L,FXYD2,GABBR 2,GABRA1,GABRB2,GABRB3,GABRD,GABRG2,GAMT,GATM,GCK,GCSH,GLDC ,GLRA1,GLRB,GLUD1,GNAO,GNAO1,GNB1,GOSR2,GPC3,GPHN,GPR56,GRIA3, GRIN1,GRIN2A,GRIN2B,GRIN2D,GRN,HADH,HCN1,HCN2,HDAC4,HIP1,HIVEP2, HLCS,HNRNPU,HSD17B10,HSD17B4,IDH2,IER3IP1,IFIH1,IQSEC2,JAM3,KANSL1, KCNA1,KCNA2,KCNAB2,KCNB1,KCNC1,KCND2,KCNH1,KCNJ1,KCNJ10,KCNJ1 1,KCNMA1,KCNQ2,KCNQ2(1),KCNQ3,KCNT1,KCNV2,KCTD7,KDM5C,KIAA1279 ,KIAA2022,KMT2D,KPTN,L1CAM,LAMA2,LARGE,LBR,LGI1,LIAS,MBD5,ME2,M ECP2,MED12,MED13L,MEF2C,MFSD8,MOCS1,MOCS2,MPDU1,MTHFR,MTOR,N AA10,NAGA,NCKAP5,NDE1,NDUFA1,NDUFA11,NDUFAF1,NDUFAF2,NDUFAF3, NDUFAF4,NDUFAF5,NDUFB3,NDUFB9,NDUFS1,NDUFS2,NDUFS3,NDUFS4,ND UFS6,NDUFV1,NDUFV2,NECAP1,NEDD4L,NF1,NGLY1,NHLRC1,NIPBL,NOTCH3 ,NR2F1,NRXN1,NTRK2,NUBPL,NUS1,OFD1,OPHN1,OPRM1,PAFAH1B1,PAK3,PA NK2,PAX6,PC,PCDH19,PDHA1,PDHB,PDP1,PDX1,PET100,PEX1,PEX10,PEX12,PE X13,PEX14,PEX16,PEX19,PEX26,PEX3,PEX5,PEX6,PEX7,PGAP3,PHF6,PHGDH,PI GA,PIGN,PIGO,PIGT,PIGV,PLA2G6,PLCB1,PLP1,PMM2,PNKP,PNPO,POLG,POMG NT1,POMT1,POMT2,PPP2R1A,PPT1,PQBP1,PRICKLE1,PRICKLE2,PRRT2,PURA,P YCR2,QARS,RAB39B,RAB3GAP1,RAI1,RARS2,RBFOX1,RBFOX3,RELN,RNASEH 2A,RNASEH2B,RNASEH2C,ROGDI,RPS6KA3,RRM2B,SAMHD1,SCARB2,SCN1A, SCN1B,SCN2A,SCN3A,SCN8A,SCN9A,SERPINI1,SETBP1,SIAT9,SIK1,SLC12A5,S LC13A5,SLC16A1,SLC19A3,SLC1A2,SLC1A4,SLC25A1,SLC25A15,SLC25A22,SLC 2A1,SLC35A2,SLC4A10,SLC4A3,SLC6A1,SLC6A8,SLC9A6,SMARCA2,SMC1A,SM C3,SMS,SNAP25,SNAP29,SNIP1,SPTAN1,SRPX2,ST3GAL3,ST3GAL5,STRADA,ST X1B,STXBP1,SUOX,SYN1,SYN2,SYNGAP1,SYP,SZT2,TBC1D24,TBCE,TBX1,TCF 4,TDP2,TNK2,TPP1,TREX1,TRPM6,TSC1,TSC2,TUBA1A,TUBA8,TUBB2A,TUBB2 B,TUBG1,UBE3A,VPS13A,VPS13B,VPS35,WDR45,WDR62,WWOX,ZEB2,ZNF44 .
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