OA1 Gene (Genbank ID: 4935)

Last update: 16.05.2010 OA1 gene (Genbank ID: 4935) Genbank Z48804, NM_000273 and sequencing results from the editors laboratory Codon usage adjusted according to (1) |-----> Primers as published for reference see list at bottom Nucleotide numbering is given in Blue Aminoacid numbering is given in green Colour coding of the mutations indicates the following disorders | OA1, | Polymorphisms, |X-linked nystagmus Numbers in brackets indicate the references at the end of the document Mutations have been adjusted to the most recent nucleodtide and codon numbering. Functional units A: Transcription start according to (2) T: TMD G: Glycosylation (5)

-760 -750 -740 -730 -720 -710 -700 -690 ctgcg acctt ctcgg ctgcc tgggg ggttt cgcca tgttg cccac gctgg tctcc aactc ttgag ctcaa gcgat gacgc tggaa gagcc gacgg acccc ccaaa gcggt acaac gggtg cgacc agagg ttgag aactc gagtt cgcta

-680 -670 -660 -650 -640 -630 -620 ctgcc tgcct cggcc tccca aggtg ctggg attac aggtg tgagc tactg ctctt tcttt aacat tgatc tgttt gacgg acgga gccgg agggt tccac gaccc taatg tccac actcg atgac gagaa agaaa ttgta actag acaaa

-610 -600 -590 -580 -570 -560 -550 -540 gtttc attca ttaat tgtaa acgaa aatcc tgcct ctgtg ggatt atatc catga atgag agagg ccata aaaaa caaag taagt aatta acatt tgctt ttagg acgga gacac cctaa tatag gtact tactc tctcc ggtat ttttt

-530 -520 -510 -500 -490 -480 -470 aagca ctaat tggac aacca tctct actta ggaaa aaagc agtta caggg atcag tcaca gttta tgaac atgtt ttcgt gatta acctg ttggt agaga tgaat ccttt tttcg tcaat gtccc tagtc agtgt caaat acttg tacaa

-460 -450 -440 -430 -420 -410 -400 -390 ctggc gcctt aaagg catca aaatc aggat gtcag agtcc caaat aggaa agatc tagtc cacga ggcct gtttc gaccg cggaa tttcc gtagt tttag tccta cagtc tcagg gttta tcctt tctag atcag gtgct ccgga caaag

-380 -370 -360 -350 -340 -330 -320 tctag aagac cagta aagat ggcag gtttg gcgct ctagg tggca gagaa accac cagga aggct tggtg aatgg agatc ttctg gtcat ttcta ccgtc caaac cgcga gatcc accgt ctctt tggtg gtcct tccga accac ttacc

t (24) -310 -300 -290 -280 -270 -260 | -250 -240 ggaga aaggt aacct tccca acctt tctgc ttctc cttcc acttc cctcc tcctc ctccc tcttc ctctc ctctc cctct ttcca ttgga agggt tggaa agacg aagag gaagg tgaag ggagg aggag gaggg agaag gagag gagag

-230 -220 -210 -200 -190 -180 -170 agccc tccct ctctc tgtcc tcctc ctccg cccgc ccaag catca cctcg tgagg cctcg tggcg ttagc ccagt tcggg aggga gagag acagg aggag gaggc gggcg ggttc gtagt ggagc actcc ggagc accgc aatcg ggtca

-160 -150 -140 -130 -120 -110 -100 -90 |------> (1) gctct cggcc cccac cgagc ctggc tctac tgcag gcgct ggggg ttggg gtggg ggaga ggccc agggc acatg cgaga gccgg gggtg gctcg gaccg agatg acgtc cgcga ccccc aaccc caccc cctct ccggg tcccg tgtac

-80 -70 -60 -50 -40 -30 -20 atgcc gcccc cagcc cgccc agcac atgac ccagg caggc cggcg gggtc ctggc acacc cgagc cgcgt ccgcg tacgg cgggg gtcgg gcggg tcgtg tactg ggtcc gtccg gccgc cccag gaccg tgtgg gctcg gcgca ggcgc AAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA

T=Cys (5,20,22) -10 1 |15 30 45 |------aACAC AGCCC ATG GCC TCC CCG CGC CTA GGG ACC TTC TGC TGC CCC ACG CGG GAC GCA GCC ACG CAG tTGTG TCGGG TAC CGG AGG GGC GCG GAT CCC TGG AAG ACG ACG GGG TGC GCC CTG CGT CGG TGC GTC AAAAAAAAAAA Met Ala Ser Pro Arg Leu Gly Thr Phe Cys Cys Pro Thr Arg Asp Ala Ala Thr Gln M A S P R L G T F C C P T R D A A T Q 1 5 10 15 Last update: 16.05.2010 G=Asp (21) G=Arg (7,8) 60 75 |90 A=Asp (1,5) | 120 ------> (1) | | | CTC GTG CTG AGC TTC CAG CCG CGG GCC TTC CAC GCG CTC TGC CTG GGC AGC GGC GGG CTC CGC TTG GAG CAC GAC TCG AAG GTC GGC GCC CGG AAG GTG CGC GAG ACG GAC CCG TCG CCG CCC GAG GCG AAC Leu Val Leu Ser Phe Gln Pro Arg Ala Phe His Ala Leu Cys Leu Gly Ser Gly Gly Leu Arg Leu L V L S F Q P R A F H A L C L G S G G L R L <------| (1) TTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTT 20 25 30 35 40

|del (13)------| del (6) del (2,15) | ins C (6) |------| | |------|-del (7,9,21)----- 135 150 | | | |-dup (11)| | 180 GCG CTG GGC CTT CTG CAG CTG CTG CCC GGC CGC CGG CCC GCG GGC CCC GGG TCC CCC GCG ACG TCC CGC GAC CCG GAA GAC GTC GAC GAC GGG CCG GCG GCC GGG CGC CCG GGG CCC AGG GGG CGC TGC AGG Ala Leu Gly Leu Leu Gln Leu Leu Pro Gly Arg Arg Pro Ala Gly Pro Gly Ser Pro Ala Thr Ser A L G L L Q L L P G R R P A G P G S P A T S TTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTT 45 50 55 60

------| | |------del exon 2 (15) ------| |------del (13)------| | |dup (22)------| | | | A=Asn (5) | del (18) | | | |T=Val (7,8) | | | | | || del (16) | ---| |---| del (15) |----del (1,4,6,15)--| || |---| T=Val (11)| C=Arg(4) | |195 | 210 | | | 225 | || | 240 | | | 250 CCG CCG GCC TCG GTC CGC ATC CTG CGC GCT GCC GCT GCC TGC GAC CTT CTC GGC TGC CTG G gtaag GGC GGC CGG AGC CAG GCG TAG GAC GCG CGA CGG CGA CGG ACG CTG GAA GAG CCG ACG GAC C cattc Pro Pro Ala Ser Val Arg Ile Leu Arg Ala Ala Ala Ala Cys Asp Leu Leu Gly Cys Leu Gly P P A S V R I L R A A A A C D L L G C L G TTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTT 65 70 75 80 84

------| (13) | ggcgc gcgcg gcccg cgggt tggaa tctga tcagc gcctg ggtga gggcg cgtgg cccgc aggtt gagac ccgac ccgcg cgcgc cgggc gccca acctt agact agtcg cggac ccact cccgc gcacc gggcg tccaa ctctg ggctg <------| (1)

------tggtg cccgg ataag ggcgc acggc ctgtg gattt ggacc tgttc cgtga tggag tgagg acgag aggcc cgcgg accac gggcc tattc ccgcg tgccg gacac ctaaa cctgg acaag gcact acctc actcc tgctc tccgg gcgcc

------ctttt tctct ctctg cacac acaaa tatgt atgtt ttttc ttcct ttctt ccttt tccct ccttg tcttt ttccc gaaaa agaga gagac gtgtg tgttt ataca tacaa aaaag aagga aagaa ggaaa aggga ggaac agaaa aaggg

------tccct ctctc cctcc ctcct ttcct tcctt ccttc ttcct tcctc tcttc ctatc tctat ctatt atgta tctat aggga gagag ggagg gagga aagga aggaa ggaag aagga aggag agaag gatag agata gataa tacat agata

------(4) c |------> (1) | cattt ttcca aagca agaag tcagc tttat atttg attag gatca gatac aaagt attat ccaat tctct cttag gtaaa aaggt ttcgt tcttc agtcg aaata taaac taatc ctagt ctatg tttca taata ggtta agaga gaatc Last update: 16.05.2010 ------<------del exon 2 (23)------del (db) |-| del (21) |del (22)------| del(7,25, A=Asp (1,5,6,10,15) T=Phe (12) | | | ,8) | 255 | 270 285 | 300 | | 315 GT ATG GTG ATC CGG TCC ACC GTG TGG TTA GGA TTC CCA AAT TTT GTT GAC AGC GTC TCG GAT ATG CA TAC CAC TAG GCC AGG TGG CAC ACC AAT CCT AAG GGT TTA AAA CAA CTG TCG CAG AGC CTA TAC Gly Met Val Ile Arg Ser Thr Val Trp Leu Gly Phe Pro Asn Phe Val Asp Ser Val Ser Asp Met G M V I R S T V W L G F P N F V D S V S D M TTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTT 84 85 90 95 100 105

------> G=Gly (18) C=Arg (4) |C=Ser (5,6) ||T=Trp (11) ||| A=Glu (4,5,6,16) A=ter (21) ||| | A=Ala (7,8) | insC (21) ||| | | c (1,6) 330 | | 345 ||| | |360 | AAC CAC ACG GAA ATT TGG CCT GCT GCT TTC TGC GTG GGG AGT GCG gtgag tccac cccct ctgca tgccc TTG GTG TGC CTT TAA ACC GGA CGA CGA AAG ACG CAC CCC TCA CGC cactc aggtg gggga gacgt acggg Asn His Thr Glu Ile Trp Pro Ala Ala Phe Cys Val Gly Ser Ala N H T E I W P A A F C V G S A GGG TTTTTTTTTTTTTTT 110 115 120

------del exon 2 (15)------> tctcc tccct actta tgctc ctcaa atcgc agcag cagca aaccc tggga gtctg ttaga aatgc aggtt ctcac agagg aggga tgaat acgag gagtt tagcg tcgtc gtcgt ttggg accct cagac aatct ttacg tccaa gagtg <------| (1) gtcct gcccc atcct gctga tcagg aaccc agccc tctct gtttt aacaa aaccc cagga cgggg tagga cgact agtcc ttggg tcggg agaga caaaa ttgtt ttggg

IVS 2 agtgg agcag aaggc atagt tcctt agtca aatct gaatg cctac accta tccca ggcca caccc tcctt ggtcc tcacc tcgtc ttccg tatca aggaa tcagt ttaga cttac ggatg tggat agggt ccggt gtggg aggaa ccagg cagga actgt gccca cttgt gtccc gagag ctgtc acgtg cggct tcctg acgtc agagg aagcc agtgt ctacc gtcct tgaca cgggt gaaca caggg ctctc gacag tgcac gccga aggac tgcag tctcc ttcgg tcaca gatgg

|------> (1) ctgcc gtctc aagga tgggc tgggc ttctt gtacc tgttt ccaga cattt tgatg caggc tcttc ccgat tgcag gacgg cagag ttcct acccg acccg aagaa catgg acaaa ggtct gtaaa actac gtccg agaag ggcta acgtc

C=Arg (14) | A=Arg (7,8) | C=Arg (4,5) | | insG (db) | | | C=Pro (10,11) G=Arg (5,6) | | | |del (4) T=Val (4,5) | 375 390 | | | || 405 | 420 ATG TGG ATC CAG CTG TTG TAC AGT GCC TGC TTC TGG TGG CTG TTT TGC TAT GCA GTG GAT GCT TAT TAC ACC TAG GTC GAC AAC ATG TCA CGG ACG AAG ACC ACC GAC AAA ACG ATA CGT CAC CTA CGA ATA Met Trp Ile Gln Leu Leu Tyr Ser Ala Cys Phe Trp Trp Leu Phe Cys Tyr Ala Val Asp Ala Tyr M W I Q L L Y S A C F W W L F C Y A V D A Y TTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTT 121 125 130 135 140 Last update: 16.05.2010 A=Lys (db) | ins AGATCGG (1,6) | | A=Asn (4,5) | | | c (6,15) 435 | | 450 | | CTG GTG ATC CGG AGA TCG GCA GGA CTG AG gtatt caccg aggaa atggg atttc tgccc tagtt ctatt GAC CAC TAG GCC TCT AGC CGT CCT GAC TC cataa gtggc tcctt taccc taaag acggg atcaa gataa Leu Val Ile Arg Arg Ser Ala Gly Leu Ser L V I R R S A G L S 145 150 152 ttaga gggaa gataa gagat ggcac tgagc gttta aaagt atttt gcagt gttgc agaca ccgtc attca gaatc aatct ccctt ctatt ctcta ccgtg actcg caaat tttca taaaa cgtca caacg tctgt ggcag taagt cttag <------| (1) tgtca gctgg cccct ccgcc tagaa acatc cacag cagct cattt ttata agagg ccaaa ggcac attta aaata acagt cgacc gggga ggcgg atctt tgtag gtgtc gtcga gtaaa aatat tctcc ggttt ccgtg taaat tttat

IVS 3 tgcca ctttg ttgtt cactt taaaa tagtt aattt tatgt gatgt gaatt tcacc tcaat ggaaa acaac caacc acggt gaaac aacaa gtgaa atttt atcaa ttaaa ataca ctaca cttaa agtgg agtta ccttt tgttg gttgg aacct cagca gcacg aggaa actct ttgcc gaggg gcttt cctct gtgta cattt tcctg acctt tccag agcgc ttgga gtcgt cgtgc tcctt tgaga aacgg ctccc cgaaa ggaga cacat gtaaa aggac tggaa aggtc tcgcg

|------> (1) aggag ctggc ctggc agttc caggc aggcc tctgt gcccc actga gctgt ggctg ctgtt gtgct tgtcc cctag tcctc gaccg gaccg tcaag gtccg tccgg agaca cgggg tgact cgaca ccgac gacaa cacga acagg ggatc

A=Asn (11) A=Asp (10) | del(11)(15,5,1)Asp=A 456 465 480 | | |-| 510 |- C ACC ATC CTG CTG TAT CAC ATC ATG GCG TGG GGC CTG GCC ACC CTG CTC TGT GTG GAG GGA GCC G TGG TAG GAC GAC ATA GTG TAG TAC CGC ACC CCG GAC CGG TGG GAC GAG ACA CAC CTC CCT CGG Ser Thr Ile Leu Leu Tyr His Ile Met Ala Trp Gly Leu Ala Thr Leu Leu Cys Val Glu Gly Ala S T I L L Y H I M A W G L A T L L C V E G A TTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTT 152 155 160 165 170

525 540 548 a (11) ------> (3) | GCC ATG CTC TAC TAC CCT TCC GTG TCC AG gtaag ttggg actcc agcgc cccag gcagc cccat ccttg GCC TAC GAG ATG ATG GGA AGG CAC AGG TC cattc aaccc tgagg tcgcg gggtc cgtcg gggta ggaac Ala Met Leu Tyr Tyr Pro Ser Val Ser Arg A M L Y Y P S V S R TTTTTTTTTTTTTTTTTTT 175 180 183 gctca taatg tgttg tcttg caggg aatac atgag ccccg accca cagag tgggt gcctt ggagg ttagg ccgtt cgagt attac acaac agaac gtccc ttatg tactc ggggc tgggt gtctc accca cggaa cctcc aatcc ggcaa <------| (1) gtctc agggc cacat gaggc catgc tcacg gccca gcccc agagg gctga ctaca atagc ttgga gaatg accct cagag tcccg gtgta ctccg gtacg agtgc cgggt cgggg tctcc cgact gatgt tatcg aacct cttac tggga

IVS 4 ccagg gtgtt tttct ttccg atctt ttccc agcag gaacc tttaa aagct tcctc cagtg gaatg cctta ggggt ggtcc cacaa aaaga aaggc tagaa aaggg tcgtc cttgg aaatt ttcga aggag gtcac cttac ggaat cccca cctcc cattt ctgag acaga aacat ggttg atctc cctta ctctc ctgca attta tggct tgttc cagac atgag ggagg gtaaa gactc tgtct ttgta ccaac tagag ggaat gagag gacgt taaat accga acaag gtctg tactc

|------aaatg actca cattt ccttt gggca gtcag cagca gattt atgca tttcc ctttt tgttc tcatc ctctt atctt tttac tgagt gtaaa ggaaa cccgt cagtc gtcgt ctaaa tacgt aaagg gaaaa acaag agtag gagaa tagaa Last update: 16.05.2010 Last update: 16.05.2010 ------> (1) gactt ccaga taagt agatg tcttt tagcc aaaac tttgc ttttg agaag aatga ctttg gtttt cctct ctcag ctgaa ggtct attca tctac agaaa atcgg ttttg aaacg aaaac tcttc ttact gaaac caaaa ggaga gagtc

A=Lys (14) | T=Trp (14) | |C=Pro (14) T=His (db) | |ins C (14) G=Gln (db) | || del (23) A=Gln (db) insT (11) 549 | || || | 585 600 | G TGT GAG CGG GGC CTG GAC CAC GCC ATC CCC CAC TAT GTC ACC ATG TAC CTG CCC CTG CTG CTG C ACA CTC GCC CCG GAC CTG GTG CGG TAG GGG GTG ATA CAG TGG TAC ATG GAC GGG GAC GAC GAC Arg Cys Glu Arg Gly Leu Asp His Ala Ile Pro His Tyr Val Thr Met Tyr Leu Pro Leu Leu Leu R C E R G L D H A I P H Y V T M Y L P L L L TTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTT 183 185 190 195 200

a (16) 615 630 645 658 | GTT CTC GTG GCG AAC CCC ATC CTG TTC CAA AAG ACA GTG ACT GCA G gtaaa tacta gggaa gctct CAA GAG CAC CGC TTG GGG TAG GAC AAG GTT TTC TGT CAC TGA CGT C cattt atgat ccctt cgaga Val Leu Val Ala Asn Pro Ile Leu Phe Gln Lys Thr Val Thr Ala Val <------V L V A N P I L F Q K T V T A V TTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTT 205 210 215 220 ctggg tacac ggcca ctggg agcgg cccca tgcct cgggc tcaga cagtg acaca tgttg tcctg gaatt ctcca gaccc atgtg ccggt gaccc tcgcc ggggt acgga gcccg agtct gtcac tgtgt acaac aggac cttaa gaggt ------| (1) ggaca gttga cctca tttgt catcc tccag agaca tcagc agaac acagc tgcag aaagt aagca ggttc aataa cctgt caact ggagt aaaca gtagg aggtc tctgt agtcg tcttg tgtcg acgtc tttca ttcgt ccaag ttatt

IVS 5 tgtaa atcta aaatt atttc aaagc agaag tttaa aaata tgtat attcc ttagg gtcta tgagg actcc aacct acatt tagat tttaa taaag tttcg tcttc aaatt tttat acata taagg aatcc cagat actcc tgagg ttgga ggaag ttgtg aggaa tgaat gtcag tgact tgctt tgctt cctgc ccctc tggcc ttgct tgtgg gctca cacct ccttc aacac tcctt actta cagtc actga acgaa acgaa ggacg gggag accgg aacga acacc cgagt gtgga

|------> (1) gcttc cattg ccttc tctgt cactc cgtaa acatg aataa tgaac accat acata gttcc ttctg ttctt cacag cgaag gtaac ggaag agaca gtgag gcatt tgtac ttatt acttg tggta tgtat caagg aagac aagaa gtgtc

<------del exon 6 (25)------del (16,14,15) | T=Val (5,6,21) | | A=Lys (4,5) | | | A=Lys (7,8) | | | | A=Lys (4,5) (21,14) del 660 675 | | 690 | | | | TG GCC TCT TTA CTT AAA GGA AGA CAA GGC ATT TAC ACG GAG AAC GAG AGG AGG ATG GGA GCC GTG AC CGG AGA AAT GAA TTT CCT TCT GTT CCG TAA ATG TGC CTC TTG CTC TCC TCC TAC CCT CGG CAC Val Ala Ser Leu Leu Lys Gly Arg Gln Gly Ile Tyr Thr Glu Asn Glu Arg Arg Met Gly Ala Val V A S L L K G R Q G I Y T E N E R R M G A V 220 225 230 235 240

------> G=Val (5,6,15) | T=ter (4,6,10,15,21) |----del (3)-----| g (24) | | 750 | 767 | | ATC AAG ATC CGA TTT TTC AAA ATC ATG CTG GTT TTA ATT ATT TG gtaac ctttc ttcta tatat gtgta TAG TTC TAG GCT AAA AAG TTT TAG TAC GAC CAA AAT TAA TAA AC cattg gaaag aagat atata cacat Ile Lys Ile Arg Phe Phe Lys Ile Met Leu Val Leu Ile Ile Cys I K I R F F K I M L V L I I C TTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTT Last update: 16.05.2010 245 250 256 ttttt attgc cagtg ggaag ggcta tggaa acaac ttgcc atgtt gcatg cgtga ccaga agttc caaag ggaag aaaaa taacg gtcac ccttc ccgat acctt tgttg aacgg tacaa cgtac gcact ggtct tcaag gtttc ccttc <------| (1) agcct ttggg aagga aatct ttgag actgt gctag gtgcc ctttg aggaa aggca cagag gacag gggag caagt tcgga aaccc ttcct ttaga aactc tgaca cgatc cacgg gaaac tcctt tccgt gtctc ctgtc ccctc gttca

IVS 6 cctgg gctca agcaa tcctc ctgcc tcagc ctccc aaagt gctgg gatta cagga gggag ccatt gcacc tggcc ggacc cgagt tcgtt aggag gacgg agtcg gaggg tttca cgacc ctaat gtcct ccctc ggtaa cgtgg accgg ctctt agttt cttac tgcag aagtg gccat gtcta taccg ggagt tggta ctttt aggtc ttggt agaaa ttctt gagaa tcaaa gaatg acgtc ttcac cggta cagat atggc cctca accat gaaaa tccag aacca tcttt aagaa

|- |------> (1) | ctctg actct ccagc attta aaaac gagtt tcatt gcatg ttctc tttac ctgct gccat tttct ttcta acag gagac tgaga ggtcg taaat ttttg ctcaa agtaa cgtac aagag aaatg gacga cggta aaaga aagat tgtc

<------del exon 7 – 8 (25)------del (21) A=Asn (5,6) ----| | G=Lys (21) G=Gly (5,6) (21) G=Val 768 | 780 | | 795 810 | 825 | T TGG TTG TCG AAT ATC ATC AAT GAA AGC CTT TTA TTC TAT CTT GAG ATG CAA ACA GAT ATC AAT A ACC AAC AGC TTA TAG TAG TTA CTT TCG GAA AAT AAG ATA GAA CTC TAC GTT TGT CTA TAG TTA Cys Trp Leu Ser Asn Ile Ile Asn Glu Ser Leu Leu Phe Tyr Leu Glu Met Gln Thr Asp Ile Asn C W L S N I I N E S L L F Y L E M Q T D I N TTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTT 256 260 265 270 275

------del (1,5,6) |-| G=Gly (1,5,6) del (16) | | | T=Cys (6,15) | T=ter (10,11) | | | A=ter (6) a (6) 840 | | | | | | 885 | GGA GGT TCT TTG AAA CCT GTC AGA ACT GCA GCC AAG ACC ACA TGG TTT ATT ATG gtagg tcaat ctata CCT CCA AGA AAC TTT GGA CAG TCT TGA CGT CGG TTC TGG TGT ACC AAA TAA TAC catcc agtta gatat <------| (3) Gly Gly Ser Leu Lys Pro Val Arg Thr Ala Ala Lys Thr Thr Trp Phe Ile Met G G S L K P V R T A A K T T W F I M TTTTTTTTTTTTTTT 280 285 290 294

------del exon 7 – 8 (25)------tttta tttta attag ttaat tattt aatta atttg cttca gagac aaggt ctcac tctgt caccc aggct ggaaa aaaat aaaat taatc aatta ataaa ttaat taaac gaagt ctctg ttcca gagtg agaca gtggg tccga ccttt <------| (1)

------del exon 7 – 8 (25)------gcggt ggcat gatca tagct cactg cagcc ttaaa ctcct gggct caagc aatcc tctgt cttgg cctcc tgagt cgcca ccgta ctagt atcga gtgac gtcgg aattt gagga cccga gttcg ttagg agaca gaacc ggagg actca

------del exon 7 – 8 (25)---// aactg ggact acagg tgtat gcctc caccc tgggc aatgt aggga gaccc catct ctttt tttaa ttatc ttgac cctga tgtcc acata cggag gtggg acccg ttaca tccct ctggg gtaga gaaaa aaatt aatag

IVS 7 IVS+748g>a (20)

------del exon 7 – 8 (25)------ctttc aggca ccctt gaagg tacag cacct actgt ggcca atctt catct tgccc caaac caacc cacca accag gaaag tccgt gggaa cttcc atgtc gtgga tgaca ccggt tagaa gtaga acggg gtttg gttgg gtggt tggtc Last update: 16.05.2010 ------del exon 7 – 8 (25)------tcaac cagcc accag ccaac ccatg gtccc ttcca agcga gtcca gccct gtggg catcc tgggg ggagt gtgtc agttg gtcgg tggtc ggttg ggtac caggg aaggt tcgct caggt cggga caccc gtagg acccc cctca cacag

------del exon 7 – 8 (25)------(11) a |------> (1) | actct gtgac agccc agggc tctga cttct gctac gctgc actga ctgcc atgtg tcttt ctgtc ctctc tccag tgaga cactg tcggg tcccg agact gaaga cgatg cgacg tgact gacgg tacac agaaa gacag gagag aggtc

------del exon 7 – 8 (25)------G=ter (14) | T=Val (21) | ins CG (1) T=ter (17) 900 915 930 | | | GGA ATC CTG AAT CCA GCC CAG GGA TTT CTC TTG TCT TTG GCC TTC TAC GGC TGG ACA GGA TGC AGC CCT TAG GAC TTA GGT CGG GTC CCT AAA GAG AAC AGA AAC CGG AAG ATG CCG ACC TGT CCT ACG TCG Gly Ile Leu Asn Pro Ala Gln Gly Phe Leu Leu Ser Leu Ala Phe Tyr Gly Trp Thr Gly Cys Ser G I L N P A Q G F L L S L A F Y G W T G C S TTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTT 296 300 305 310 315

------960 975 990 1005 |------> (1) CTG GGT TTT CAG TCT CCC AGG AAG GAG ATC CAG TGG GAA TCA CTG ACC ACC TCG GCT GCT GAG GGG GAC CCA AAA GTC AGA GGG TCC TTC CTC TAG GTC ACC CTT AGT GAC TGG TGG AGC CGA CGA CTC CCC <------| (1) Leu Gly Phe Gln Ser Pro Arg Lys Glu Ile Gln Trp Glu Ser Leu Thr Thr Ser Ala Ala Glu Gly L G F Q S P R K E I Q W E S L T T S A A E G 320 325 330 335

------G=Val (db) 1020 1035 | 1050 1065 1080 GCT CAC CCA TCC CCA CTG ATG CCC CAT GAA AAC CCT GCT TCC GGG AAG GTG TCT CAA GTG GGT GGG CGA GTG GGT AGG GGT GAC TAC GGG GTA CTT TTG GGA CGA AGG CCC TTC CAC AGA GTT CAC CCA CCC Ala His Pro Ser Pro Leu Met Pro His Glu Asn Pro Ala Ser Gly Lys Val Ser Gln Val Gly Gly A H P S P L M P H E N P A S G K V S Q V G G 340 345 350 355 360

------del exon 7 – 8 (25)------> 1095 1110 1120 CAG ACT TCT GAC GAA GCC CTG AGC ATG CTG TCT GAA G gtaat gccct gtctg ccaca gcagg tagac GTC TGA AGA CTG CTT CGG GAC TCG TAC GAC AGA CTT C catta cggga cagac ggtgt cgtcc atctg Gln Thr Ser Asp Glu Ala Leu Ser Met Leu Ser Glu Gly <------Q T S D E A L S M L S E G 365 370 374 ttcgg ggtcc caggg ctccc cttgg aaagc cttag aggat tcttt gtccc ggggg ctgtc ctgtg catgg cgggg aagcc ccagg gtccc gaggg gaacc tttcg gaatc tccta agaaa caggg ccccc gacag gacac gtacc gcccc --| (1) tgttc agcag cacct ctcat gtgaa ctcac tagct tccag ttgca cctcc ccaat tgtga caacc acaag tcgtc gtgga gagta cactt gagtg atcga aggtc aacgt ggagg ggtta acact gttgg

IVS 8 gttgt aatga tttaa taaaa tgtag atgga aagtt gatgt agatt tccac ccctc ccacc ttttt ttttt ttttt caaca ttact aaatt atttt acatc tacct ttcaa ctaca tctaa aggtg gggag ggtgg aaaaa aaaaa aaaaa ttttt ttttt gcaga tgaga tgaat gctag gactt tgacc aaagt tggtc catga aaaac tccat gcact gaata aaaaa aaaaa cgtct actct actta cgatc ctgaa actgg tttca accag gtact ttttg aggta cgtga cttat

|------> (1) ctgag cattt tctga agctg atgac aaacc tgcta ggaca cagac acagt cagtc ttttg tcttt tcctc tccag gactc gtaaa agact tcgac tactg tttgg acgat cctgt gtctg tgtca gtcag aaaac agaaa aggag aggtc Last update: 16.05.2010

1125 1140 1155 1170 1185 GT TCT GAT GCC AGC ACA ATT GAA ATT CAC ACT GCA AGT GAA TCC TGC AAC AAA AAT GAG GGT GAC CA AGA CTA CGG TCG TGT TAA CTT TAA GTG TGA CGT TCA CTT AGG ACG TTG TTT TTA CTC CCA CTG Gly Ser Asp Ala Ser Thr Ile Glu Ile His Thr Ala Ser Glu Ser Cys Asn Lys Asn Glu Gly Asp G S D A S T I E I H T A S E S C N K N E G D 374 375 380 385 390 395

1200 1215 1225 1235 1245 1255 |------CCT GCT CTC CCA ACC CAT GGA GAC CTA TGA agggg atgtg ctggg ggtcc agacc ccata ttcct cagac GGA CGA GAG GGT TGG GTA CCT CTG GAT ACT tcccc tacac gaccc ccagg tctgg ggtat aagga gtctg Pro Ala Leu Pro Thr His Gly Asp Leu ter <------P A L P T H G D L X 400 404

1265 1275 1285 1295 1305 1315 1325 ------> (1) tcaac aattc ttgtt cttta gaact gtgtt ctcac cttcc caaca ctgca ctgcc gaagt gtagc ggccc ccaaa agttg ttaag aacaa gaaat cttga cacaa gagtg gaagg gttgt gacgt gacgg cttca catcg ccggg ggttt ----| (1)

t (8) 1335 1345 | 1355 1365 1375 1385 1395 1405 | |------> (1) ccttg ctctc atcac cagct agagc ttctt cccga agggc cttta ggata ggaga aaggg ttcat gcaca cacgt ggaac gagag tagtg gtcga tctcg aagaa gggct tcccg gaaat cctat cctct ttccc aagta cgtgt gtgca

1415 1425 1435 1445 1455 1465 1475 gtgag aatgg aagag ccccc tccag accac tctac agctg ctcta gcctt agttg ccact aggaa gtttt ctgag cactc ttacc ttctc ggggg aggtc tggtg agatg tcgac gagat cggaa tcaac ggtga tcctt caaaa gactc <------| (1)

1485 1495 1505 1515 1525 1535 1545 1555 gctgg ctgta aagta agtgt aaggt ccaca tcctt gggga agtag ttaaa taaaa tagtt atgac tgagc tctca cgacc gacat ttcat tcaca ttcca ggtgt aggaa cccct tcatc aattt atttt atcaa tactg actcg agagt

1565 1575 1585 1595 1605 1615 1625 gcctg acttg gattc tgtct taaca cttct agcaa aagaa aataa ataca tgtac agtta tgcat tgctt aatga cggac tgaac ctaag acaga attgt gaaga tcgtt ttctt ttatt tatgt acatg tcaat acgta acgaa ttact <------| (1)

1635 1645 1655 1665 1675 1685 1695 1705 tgggg atgag ttctg agaaa tatat cgcta ggtgg tatca ctgtt gtgtg aatac catag agcac agtta cacaa acccc tactc aagac tcttt atata gcgat ccacc atagt gacaa cacac ttatg gtatc tcgtg tcaat gtgtt

1715 1725 1735 1745 1755 1765 1775 accta gatgg tacag gctac agcac actta tgcta tacgg tagag cctat ggctc ctatg ctaca aacct gaaca tggat ctacc atgtc cgatg tcgtg tgaat acgat atgcc atctc ggata ccgag gatac gatgt ttgga cttgt http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?locusId=4935 (7)=[7] (14)=[14] (21)=[21] (1)=[1] (8)=[8] (15)=[15] (22)=[22] (2)=[2] (9)=[9] (16)=[16] (23)=[23] (3)=[3] (10)=[10] (17)=[17] (24)=[24] (4)=[4] (11)=[11] (18)=[18] (25)=[25] (5)=[5] (12)=[12] (19)=[19] (6)=[6] (13)=[13] (20)=[20]

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