Human tyrosinase
Yüklə 190,87 Kb.
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| Last update: 11.05.2010 Human tyrosinase GeneAccording to NW_001838029.2 and sequencing results from the editors laboratory Nucleotide numbering is given in Blue Aminoacid numbering is given in green Colour coding of the mutations indicates the following disorders |OCA1A |OCA1B |OCA2 |Polymorphism OCA1/2 OCA1A/B OCA1TS* OA/OCA Numbers in brackets indicate the references at the end of the document Mutations have been adjusted to the most recent nucleotide and codon numbering starting with 1 at the first nucleotide of the initiating Methionine. Functional units C =Copper-binding domain 1 K =Copper-binding domain 2 P =polymorphic di-nucleotide repeat (23) S =Signalpeptide *temperature sensitive -990 -980 -970 -960 -950 -940 -930 -920 tctag aattg atagg aaaaa caata tggct acagc attgg agaga gagag aaagg agaga ggaga aagga gagag agatc ttaac tatcc ttttt gttat accga tgtcg taacc tctct ctctc tttcc tctct cctct ttcct ctctc PPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPP del (22) -910 -900 -890 -880 -870 | -850 -840 agaga aagga gagag gagag agaca gagga gagag agaga ggata gaggg ggaga gagag agagg agaga gacag tctct ttcct ctctc ctctc tctgt ctcct ctctc tctct cctat ctccc cctct ctctc tctcc tctct ctgtc PPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPP
-830 -820 -810 |-800 -790 -780 -770 aggag agaga gagag gatag agggg agaga gaggg agagg gagag agagg gagag agagg gagag agaga gagag tcctc tctct ctctc ctatc tcccc tctct ctccc tctcc ctctc tctcc ctctc tctcc ctctc tctct ctctc PPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPP
-760 -750 -740 -730 -720 -710 -700 | agagg gagag agaga gagaa agaga gagag aggga gagag agaga gagag ctctt taacg tgaga tatcc cacaa tctcc ctctc tctct ctctt tctct ctctc tccct ctctc tctct ctctc gagaa attgc actct atagg gtgtt PPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPP (23)
| -680 -670 | -650 -640 -630 -620 tgaac aaatc gccca gttat caaag tgcag ctatc cttag gagtt gtcag aaaat gcatc aggat tatca gagaa acttg tttag cgggt caata gtttc acgtc gatag gaatc ctcaa cagtc tttta cgtag tccta atagt ctctt -610 -600 -590 -580 -570 -560 -550 -540 aagta tcaga aagat ttttt tttct gatac gttgt ataaa ataaa caaac tgaaa ttcaa taaca tataa ggaat ttcat agtct ttcta aaaaa aaaga ctatg caaca tattt tattt gtttg acttt aagtt attgt atatt cctta
tctgt ctggg ctctg aagac aatct ctctc tgcat attga ttctt caaac attgt agcct cttta tggtc tctga agaca gaccc gagac ttctg ttaga gagag acgta taact aagaa gtttg taaca tcgga gaaat accag agact
gaaat aacta cctta aaccc ataat cttta atact tccta aactt tctta ataag agaag ctcta ttcct gacac cttta ttgat ggaat ttggg tatta gaaat tatga aggat ttgaa agaat tattc tcttc gagat aagga ctgtg
tacct ctcat ttgca aggtc aaatc atcat tagtt ttgta gtcta ttaac tgggt ttgct taggt caggc attat atgga gagta aacgt tccag tttag tagta atcaa aacat cagat aattg accca aacga atcca gtccg taata
-310 | -300 -290 -280 -270 | -250 -240 tatta ctaac cttat tgtta atatt ctaac cataa gaatt aaact attaa tggtg aatag agttt ttcac tttaa ataat gattg gaata acaat tataa gattg gtatt cttaa tttga taatt accac ttatc tcaaa aagtg aaatt a (18,58) -230 -220 -210 | -190 -180 -170 catag gccta tccca ctggt gggat acgag ccaat tcgaa agaaa agtca gtcat gtgct tttca gagga tgaaa gtatc cggat agggt gacca cccta tgctc ggtta agctt tcttt tcagt cagta cacga aaagt ctcct acttt -160 -150 -140 -130 -120 -110 -100 -90 gctta agata aagac taaaa gtgtt tgatg ctgga ggtgg gagtg gtatt atata ggtct cagcc aagac atgtg cgaat tctat ttctg atttt cacaa actac gacct ccacc ctcac cataa tatat ccaga gtcgg ttctg tacac
ataat cactg tagta gtagc tggaa agaga aatct gtgac tccaa ttagc cagtt cctgc agacc ttgtg aggac tatta gtgac atcat catcg acctt tctct ttaga cactg aggtt aatcg gtcaa ggacg tctgg aacac tcctg
G=Val (21,25,33,50,30,92) | (2) Gln=A |C=Thr ( ) del (1,44) | (34) Arg=G| a (db)| T=Leu (db) |C=Pro (50) |(2) del || -10 | | | 15 || 30 45 | | || 60 tagag gaaga ATG CTC CTG GCT GTT TTG TAC TGC CTG CTG TGG AGT TTC CAG ACC TCC GCT GGC CAT TTC atctc cttct TAC GAG GAC CGA CAA AAC ATG ACG GAC GAC ACC TCA AAG GTC TGG AGG CGA CCG GTA AAG Met Leu Leu Ala Val Leu Tyr Cys Leu Leu Trp Ser Phe Gln Thr Ser Ala Gly His Phe M L L A V L Y C L L W S F Q T S A G H F SSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSS 1 5 10 15 20
(44) del| ((41) Asn=A| (93,50) Arg=A || (93) Cys=C | || (50) ter=A| | || T=Ser (3,4,18,28,33) (93) Arg=A|| | || | C=Arg (93) (db) Pro=A ||| | || | |A=Tyr (80,93) (db) Thr=A | ||| | || | || T=Phe (62) (5) Tyr=A | | ||| | || | || | insT (50,62,92) C=Thr (34) | | | ||| (50)| || | || | | 90 | 105 | | | ||| 120 | || CCT AGA GCC TGT GTC TCC TCT AAG AAC CTG ATG GAG AAG GAA TGC TGT CCA CCG TGG AGC GGG GAC AGG GGA TCT CGG ACA CAG AGG AGA TTC TTG GAC TAC CTC TTC CTT ACG ACA GGT GGC ACC TCG CCC CTG TCC Pro Arg Ala Cys Val Ser Ser Lys Asn Leu Met Glu Lys Glu Cys Cys Pro Pro Trp Ser Gly Asp Arg P R A C V S S K N L M E K E C C P P W S G D R 25 30 35 40
G=Gly (62) | A=Thr(43) | | T=Val (62) | | |A=Asp(3,4,6,18,28,62,44,67,92) | | || G=ter (7) A=Tyr (3,4,8,26,21,18,28,44,50,93) | | || | | | | || | T=Ile (2) | T=His (db) T=Leu (db) | | || | | | | | 195 AGT CCC TGT GGC CAG CTT TCA GGC AGA GGT TCC TGT CAG AAT ATC CTT CTG TCC AAT GCA CCA CTT GGG TCA GGG ACA CCG GTC GAA AGT CCG TCT CCA AGG ACA GTC TTA TAG GAA GAC AGG TTA CGT GGT GAA CCC Ser Pro Cys Gly Gln Leu Ser Gly Arg Gly Ser Cys Gln Asn Ile Leu Leu Ser Asn Ala Pro Leu Gly S P C G Q L S G R G S C Q N I L L S N A P L G 45 50 55 60 65 del (2) | G=Glu (33) | | T=Trp (1,2,50,44,5,93) | | G=Gly (93) | | |A=Gln (3,4,5,9,18,28,30,33,8,84,93) | | |insGGG (8,80,93) | | || T=ter (1) | | || | C= Pro (50) | | || | |T=Leu (62) | | || | || C=Arg (1,50,44) (28,18,3,4,16) Arg=C | | || | || | A=ter (2,20) | | | || | || | | T=Ser (50) | | | || | || | | |T=Leu (1,6,10,18,28,34,54,84) | | | || | || | | || G=Val (44) | T=His (62) | | || | || | | || | G=ter (81,84) | | 210 | | || | || | | || | | | CCT CAA TTT CCC TTC ACA GGG GTG GAT GAC CGG GAG TCG TGG CCT TCC GTC TTT TAT AAT AGG ACC TGC GGA GTT AAA GGG AAG TGT CCC CAC CTA CTG GCC CTC AGC ACC GGA AGG CAG AAA ATA TTA TCC TGG ACG Pro Gln Phe Pro Phe Thr Gly Val Asp Asp Arg Glu Ser Trp Pro Ser Val Phe Tyr Asn Arg Thr Cys P Q F P F T G V D D R E S W P S V F Y N R T C 70 75 80 85
G=Arg (db) | A=Arg (2,5) T=Phe (93) | C=Ser (30,41) | |T=Val (90) |G=Trp (93) A=Arg (50) A=Arg (20) | | 285 | || || 315 | | 330 CAG TGC TCT GGC AAC TTC ATG GGA TTC AAC TGT GGA AAC TGC AAG TTT GGC TTT TGG GGA CCA AAC TGC GTC ACG AGA CCG TTG AAG TAC CCT AAG TTG ACA CCT TTG ACG TTC AAA CCG AAA ACC CCT GGT TTG ACG Gln Cys Ser Gly Asn Phe Met Gly Phe Asn Cys Gly Asn Cys Lys Phe Gly Phe Trp Gly Pro Asn Cys Q C S G N F M G F N C G N C K F G F W G P N C 90 95 100 105 110
|| del (2-5) | A=Gly (84) G=Glu (30) || || T=ter (2,50,62,80,93) | T=Tyr ( ) A=Ala (db)| A=Lys (db)G=Cys(db) || || | 360 | | | 390 | | | 405 ACA GAG AGA CGA CTC TTG GTG AGA AGA AAC ATC TTC GAT TTG AGT GCC CCA GAG AAG GAC AAA TTT TTT TGT CTC TCT GCT GAG AAC CAC TCT TCT TTG TAG AAG CTA AAC TCA CGG GGT CTC TTC CTG TTT AAA AAA Thr Glu Arg Arg Leu Leu Val Arg Arg Asn Ile Phe Asp Leu Ser Ala Pro Glu Lys Asp Lys Phe Phe T E R R L L V R R N I F D L S A P E K D K F F 115 120 125 130 135
T=Met (93) | insT (5) |T=Asn (db) G=Cys (44) | | T=Ser (62) 420 || 435 | 450 | | | GCC TAC CTC ACT TTA GCA AAG CAT ACC ATC AGC TCA GAC TAT GTC ATC CCC ATA GGG ACC TAT GGC CAA CGG ATG GAG TGA AAT CGT TTC GTA TGG TAG TCG AGT CTG ATA CAG TAG GGG TAT CCC TGG ATA CCG GTT Ala Tyr Leu Thr Leu Ala Lys His Thr Ile Ser Ser Asp Tyr Val Ile Pro Ile Gly Thr Tyr Gly Gln A Y L T L A K H T I S S D Y V I P I G T Y G Q 140 145 150 155
(62) Asn=A | (62) Leu=C | | (3,4,14,18) ter=A | | | (62) Phe=T | | | | (3,4,6,18) Ile=A | | | | | G=ter (34) del (34) | | | | | | 480 | 495 |-| 510 525 | | | | | | ATG AAA AAT GGA TCA ACA CCC ATG TTT AAC GAC ATC AAT ATT TAT GAC CTC TTT GTC TGG ATG CAT TAT TAC TTT TTA CCT AGT TGT GGG TAC AAA TTG CTG TAG TTA TAA ATA CTG GAG AAA CAG ACC TAC GTA ATA Met Lys Asn Gly Ser Thr Pro Met Phe Asn Asp Ile Asn Ile Tyr Asp Leu Phe Val Trp Met His Tyr M K N G S T P M F N D I N I Y D L F V W M H Y 160 165 170 175 180
|del(34,50) || A=Tyr (3,4,5,18,21,28,84 || | del (50) || | || A=Asn (62) || | || | del (62) G=Val (93) || | || | T=Ser (62) | || | 585 || | 600 | TAT GTG TCA ATG GAT GCA CTG CTT GGG GGA TCT GAA ATC TGG AGA GAC ATT GAT TTT GCC CAT GAA GCA ATA CAC AGT TAC CTA CGT GAC GAA CCC CCT AGA CTT TAG ACC TCT CTG TAA CTA AAA CGG GTA CTT CGT Tyr Val Ser Met Asp Ala Leu Leu Gly Gly Ser Glu Ile Trp Arg Asp Ile Asp Phe Ala His Glu Ala Y V S M D A L L G G S E I W R D I D F A H E A CCCCCCCCCCCCCCCCCCCCCCCCCCCCCCC 185 190 195 200 A=Met (3,4,6,18,28) | T=Trp (3,4,5,13,18,28,92) | G=Gly (1,17,44) A=Thr (20,44,50) | TC=Ser (62) | A=Thr (3,4,11,18,28,33) | del (4,5,7,44,92) | | G=Thr (50) | |A=Gln (3,4,5,18,33) | | T=Leu (44) | || T=ter (34) | | | G=Arg (93) | || A=Lys (41) | | | | C=Thr (93) | || | A=Lys (50) (33,20) del | | | | A=Lys (50) | || | | C=Thr (33) | | | | | 630 | | 645 | || | 660 | | 675 |--| CCA GCT TTT CTG CCT TGG CAT AGA CTC TTC TTG TTG CGG TGG GAA CAA GAA ATC CAG AAG CTG ACA GGA GGT CGA AAA GAC GGA ACC GTA TCT GAG AAG AAC AAC GCC ACC CTT GTT CTT TAG GTC TTC GAC TGT CCT Pro Ala Phe Leu Pro Trp His Arg Leu Phe Leu Leu Arg Trp Glu Gln Glu Ile Gln Lys Leu Thr Gly P A F L P W H R L F L L R W E Q E I Q K L T G CCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCC 205 210 215 220 225
| C=Arg (93) | |T=Leu (62) | |C=Ser (5) | |A=ter (3,4,6,18,28) | || T=Trp (31,50,74,84) | || |A=Gln (db) | || || T=Val (62) | || || | C=Thr (2) | || || | | del (3,4,5,24,18,28,34) | || || | | | | (93) Gly=G 690 | || || | | | | | 750 GAT GAA AAC TTC ACT ATT CCA TAT TGG GAC TGG CGG GAT GCA GAA AAG TGT GAC ATT TGC ACA GAT GAG CTA CTT TTG AAG TGA TAA GGT ATA ACC CTG ACC GCC CTA CGT CTT TTC ACA CTG TAA ACG TGT CTA CTC Asp Glu Asn Phe Thr Ile Pro Tyr Trp Asp Trp Arg Asp Ala Glu Lys Cys Asp Ile Cys Thr Asp Glu D E N F T I P Y W D W R D A E K C D I C T D E CCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCC 230 235 240 245 250 A=Arg (1) |A=Glu (50,93) (84,42,5) Cys=C || T=ter (33) A=Thr (db) | || | T=Tyr (20,62,80) T=Leu (db) A=Ile (db) | Pro (92?) | || | | | | 795 | | 810 | 819 TAC ATG GGA GGT CAG CAC CCC ACA AAT CCT AAC TTA CTC AGC CCA GCA TCA TTC TTC TCC TCT TGG CAG ATG TAC CCT CCA GTC GTG GGG TGT TTA GGA TTG AAT GAG TCG GGT CGT AGT AAG AAG AGG AGA ACC GTC Tyr Met Gly Gly Gln His Pro Thr Asn Pro Asn Leu Leu Ser Pro Ala Ser Phe Phe Ser Ser Trp Gln Y M G G Q H P T N P N L L S P A S F F S S W Q CCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCC 255 260 265 270 273
cattc tatac gatct atatgc tacag tctca tccct ccttg gaatt gttag tgaag aagtc cgtcc catat ttgaa IVS 1 (12277 bp) gaagt ctaac aacga taatt aggag ttcca acatt tctgc cttct cctac tgact cagtg gtggt gacaa tttgt cttca gattg ttgct attaa tcctc aaggt tgtaa agacg gaaga ggatg actga gtcac cacca ctgtt aaaca g (8,50,52,80,93) |del (62 ) ||TG(34) (50) Tyr=A ||| | del (34,62) (62,8,2,5) Arg=C| ||| | T=Phe (1,3,14,18,28,34,20,50) (8) Gly=G| ||| | | A=Tyr (33) (29) Ser=C || ||| | | | T=ter (4,7,13,28,30,36,41,50,74,89,90) | || ||| | | | | C=Leu (db) | || ||| | | | | | del (5) (8) del || ||| | | | | | |del (62) || || ||| | | | | | || T=Ile (db)(28,15) del || ||820 | | | | || | 865 || || ttaac atgag ggtgt tttgt acag ATT GTC TGT AGC CGA TTG GAG GAG TAC AAC AGC CAT CAG TCT TTA TGC aattg tactc ccaca aaaca tgtc TAA CAG ACA TCG GCT AAC CTC CTC ATG TTG TCG GTA GTC AGA AAT ACG Ile Val Cys Ser Arg Leu Glu Glu Tyr Asn Ser His Gln Ser Leu Cys I V C S R L E E Y N S H Q S L C CCCCCCCCCCCCCCCCCCC 274 275 280 285 T=Met (db) | A=Lys (5,7,20,92) | G=Gly (5) | | A=Arg (30) | | | G=Leu (db) | | | | T=Cys (33,93) | | | | A=Ser (1,8,18,18,50,93) | | | | |A=His (3,4,7,12,15,18,28,44,80,81,93) | | | | || (2) Val=G | | | | || (93,80,90,74,31,28,18,3,4,8,12,15,19)insC | | | | | || A=Glu (33) | | | | | | || (50) del | | | | | | | || |---|| (db) Thr=C | | 870 | | | | || 900 | || | | | AAT GGA ACG CCC GAG GGA CCT TTA CGG CGT AAT CCT GGA AAC CAT GAC AAA TCC AGA ACC CCA AGG CTC TTA CCT TGC GGG CTC CCT GGA AAT GCC GCA TTA GGA CCT TTG GTA CTG TTT AGG TCT TGG GGT TCC GAG Asn Gly Thr Pro Glu Gly Pro Leu Arg Arg Asn Pro Gly Asn His Asp Lys Ser Arg Thr Pro Arg Leu N G T P E G P L R R N P G N H D K S R T P R L 290 295 300 305 310
| T=ter (41) | | G=Cys (50) | | | C=Gln (4,13,28) G=Arg (2) | | | | C=Pro (84,81,62) |--del---| (72) A=Glu (62) | | | | | G=Thr (50,62) || | | T=Phe (84) | | | | | |A=Ile (33) || | | 960 | | | | | | 990 || 1005 CCC TCT TCA GCT GAT GTA GAA TTT TGC CTG AGT TTG ACC CAA TAT GAA TCT GGT TCC ATG GAT AAA GCT GGG AGA AGT CGA CTA CAT CTT AAA ACG GAC TCA AAC TGG GTT ATA CTT AGA CCA AGG TAC CTA TTT CGA Pro Ser Ser Ala Asp Val Glu Phe Cys Leu Ser Leu Thr Gln Tyr Glu Ser Gly Ser Met Asp Lys Ala P S S A D V E F C L S L T Q Y E S G S M D K A 315 320 325 330 335
G=Gly (1,20) | T=ter (29,50,84) | C=Leu (2) A=Asn (81) | | g (50) | | | | |1036 GCC AAT TTC AGC TTT AGA AAT ACA CTG GAA G gtaat ctctt tcttt tcact tttaa ttttt tttct gaatt CGG TTA AAG TCG AAA TCT TTA TGT GAC CTT C catta gagaa agaaa agtga aaatt aaaaa aaaga cttaa Ala Asn Phe Ser Phe Arg Asn Thr Leu Glu Gly A N F S F R N T L E G 340 345 346
gtata aatgt cagag aatag gtttc aggat cctcc ataaa ctctt aagtc ttaaa agact caact ggttc ttata IVS 2 (36158 bp) ataat tataa ctcaa tacgg aatga atttt atttt tgatt ttata ttttg aaaca gtctt caagt tatag ttata aatca aatgg gagtt atgcc ttact taaaa taaaa actaa aatat aaaac tttgt cagaa gttca atatc aatat ttagt ttacc (92,1,5,7,33,28,43,44,68,74) a (93,15,55,90) del—t| |-| | | | | a (1,43) | | | | T=Val (30) | | | | A=Glu (29,81) atc | | | | | gataa tcaca taggt tttca gtcat taaag taaac atatt ttttt cattt ttttt taatg aacag GA TTT GCT ctatt agtgt atcca aaagt cagta atttc atttg tataa aaaaa gtaaa aaaaa attac ttgtc CT AAA CGA Gly Phe Ala G F A 346
C=Pro (1,4,5,28,20) | T=ter (1,62,44) (28,18,3,4,6) Thr=C | |T=Leu (33,81) (27,18,5)Tyr=T| | || A=Gly (81) (84) Ile=A || | || | C=Arg (62) (25) Thr=C| || | || | | T=Tyr (62) (50) Cys=G || || |A=Glu (29) || | | | (3) Arg=G | || || ||A=Ala (29) || | | | (25) Tyr=T| | || || 1050 ||| || | | | 1095 || | || || AGT CCA CTT ACT GGG ATA GCG GAT GCC TCT CAA AGC AGC ATG CAC AAT GCC TTG CAC ATC TAT ATG AAT TCA GGT GAA TGA CCC TAT CGC CTA CGG AGA GTT TCG TCG TAC GTG TTA CGG AAC GTG TAG ATA TAC TTA Ser Pro Leu Thr Gly Ile Ala Asp Ala Ser Gln Ser Ser Met His Asn Ala Leu His Ile Tyr Met Asn S P L T G I A D A S Q S S M H N A L H I Y M N KKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKK 350 355 360 365 370
| A=Lys (1,3-5,7,28,33,34,43,44,50,57,62,70,92) | | T=ter (4,28,13) | | | C=Ala (84) | | | | A=Lys (62) | | | | T=ter (3,18,28,88) | | | | | T=Gly (62) | | | | | | C=Pro (1,28,44,59) | | | | | | | A=Lys (3,4,18,28,93) | | | | | | | | A=Asn (3,4,15,,18,20,28,33,43,50,62,70,74,84) | | | | | | | | | del (3) | | | | | | | | | | del (5,12,28,62,44) | | | | | | | | | | | T=His (db) | | | | | | | | | | | |ins T (62) | | | | | | | | | | | ||G=Asp (1,4,28,43) | | | | | | | | | | | ||| (62) del | | | | | | | | | | | |||62,29) Phe=T | | | | | | | | | | | | ||| G=Glu 50| | | | | | | | | | | | | ||| | 50 del| | | | 1125 | | | | | | | 1155 | | ||| | | | | GGA ACA ATG TCC CAG GTA CAG GGA TCT GCC AAC GAT CCT ATC TTC CTT CTT CAC CAT GCA TTT GTT GAC CCT TGT TAC AGG GTC CAT GTC CCT AGA CGG TTG CTA GGA TAG AAG GAA GAA GTG GTA CGT AAA CAA CTG Gly Thr Met Ser Gln Val Gln Gly Ser Ala Asn Asp Pro Ile Phe Leu Leu His His Ala Phe Val Asp G T M S Q V Q G S A N D P I F L L H H A F V D KKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKK 375 380 385 390 C=Arg (44) |A=Asn (1,44) || g (62) ||1184
AG gttgg ttaat atttc tttat aaata acgtg ctcat tggat ttaaa tagaa ggtgc ctatc aaatg tgatt taagt TC caacc aatta taaag aaata tttat tgcac gagta accta aattt atctt ccacg gatag tttac actaa attca Ser S
395 IVS 3 (53131 bp) del exon 4-5 (41) tatgc cttat tttac tttaa aaatt ttcaa atgtt tcttt atacg gaata aaatg aaatt tttaa aagtt tacaa agaaa (93,2) Pro=C (62) Asn =A (62,28,18,3,4,5) Ser=T || (81) del | || (92,91,84,78,77,56,44,27,25,34,28,18,21,3,4) Gln=A | | || (62) Arg=C | | || (62) Leu=T | | || (29) Gly=G| | | || (93,92,43,44,84,81,62,28,4,5,7,) ter=T| | | || (34) Cys=T || | | || (93,8,80,62) Leu=T| || | | || t (34) || || | | || | (62) Val=T || || | | || | (44) Ala=C || || | | || | (30) Gly=G || || | | || | | || || | | || 1185 | || || | | || tatac acaat atgtt tctta gtctg aataa ccttt tcctc tgcag T ATT TTT GAG CAG TGG CTC CGA AGG CAC atatg tgtta tacaa agaat cagac ttatt ggaaa aggag acgtc A TAA AAA CTC GTC ACC GAG GCT TCC GTG Ser Ile Phe Glu Gln Trp Leu Arg Arg His S I F E Q W L R R H KKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKK 395 400
| A=His (62) | | A=Arg (3,4,5,18,30,93) T=Leu (62) | | | T=Trp (50) | Pseudogene? | | | |A=Gln (3-5,16,18,28,33, | T=Leu(3,4,5,18,28,33,34,40,77,50,37,84)| | | || 44,62,93) | | C=His (62) G=Ala (50) | | | || (62) Gly=G | | | C=Asp (62)| Pseudogene? | | | || (62) Lys=A | | | | | | T=ter (62) | | | || (62) T=Phe | | | | | |1230 | | 1245 | | | 1260 || | 1275 | | CGT CCT CTT CAA GAA GTT TAT CCA GAA GCC AAT GCA CCC ATT GGA CAT AAC CGG GAA TCC TAC ATG GTT GCA GGA GAA GTT CTT CAA ATA GGT CTT CGG TTA CGT GGG TAA CCT GTA TTG GCC CTT AGG ATG TAC CAA Arg Pro Leu Gln Glu Val Tyr Pro Glu Ala Asn Ala Pro Ile Gly His Asn Arg Glu Ser Tyr Met Val R P L Q E V Y P E A N A P I G H N R E S Y M V KKKKKKK 405 410 415 420 425 (93,80) insGG A=Thr (50,28) (50) Asn=G | |T=Leu (4,13,28,53,74) (81,62,44,50,12,10,28,3,4,5,18) Asn=A | | || G=Val (84) || | G=Cys (81,68) (62) Gly=G | | | || | |G=ter (65) (12,44,50,1,3-5,18,28,33) Ser=A | | | | || | || T=Ile (62) del (18,3,4,88) | | | | | || | || | Pseudogene | G=Val(5) (62) Gly=G | | | | | || | || | G=Asp (62) | | ins C (26) | | | | | | || | || | | C=Arg (50)| |-| C=Pro(84)| | | | | | 1290 || | || | | | |---|1320 | | 1335 | | | | | CCT TTT ATA CCA CTG TAC AGA AAT GGT GAT TTC TTT ATT TCA TCC AAA GAT CTG GGC TAT GAC TAT AGC GGA AAA TAT GGT GAC ATG TCT TTA CCA CTA AAG AAA TAA AGT AGG TTT CTA GAC CCG ATA CTG ATA TCG Pro Phe Ile Pro Leu Tyr Arg Asn Gly Asp Phe Phe Ile Ser Ser Lys Asp Leu Gly Tyr Asp Tyr Ser P F I P L Y R N G D F F I S S K D L G Y D Y S 430 435 440 445 450 T=ter (3,18,88) | a (34)
| | g (28) | | |g (1,44) | 1366 | || TAT CTA CAA GAT TCA G gtaaa gttta cttt ctttc agagg aattg ctgaa tctag tgtta ccaat ttatt ttgag ATA GAT GTT CTA AGT C cattt caaat gaaa gaaag tctcc ttaac gactt agatc acaat ggtta aataa aactc Tyr Leu Gln Asp Ser Asp Y L Q D S D 455 456
tattg tgttt tgaaa
tctcg accgg aagtt tgggt ccaca gatga ggttt cctga cactt tccta cttct actac cacta gcatt gttac C=Ser (db) del (62,41) insT (34) T=Gly (62) || |T=ter(34) 1367 || || gtggt aacaa taaaa acaat gggat gtctt tttat ttcag AC CCA GAC TCT TTT CAA GAC TAC ATT AAG TCC cacca ttgtt atttt tgtta cccta cagaa aaata aagtc TG GGT CTG AGA AAA GTT CTG ATG TAA TTC AGG Asp Pro Asp Ser Phe Gln Asp Tyr Ile Lys Ser D P D S F Q D Y I K S 456 460 465
A=Ala (37,62) |del(50)-----| | C=Ala (62) | 1410 | || | 1440 | | 1455 | TAT TTG GAA CAA GCG AGT CGG ATC TGG TCA TGG CTC CTT GGG GCG GCG ATG GTA GGG GCC GTC CTC ACT ATA AAC CTT GTT CGC TCA GCC TAG ACC AGT ACC GAG GAA CCC CGC CGC TAC CAT CCC CGG CAG GAG TGA Tyr Leu Glu Gln Ala Ser Arg Ile Trp Ser Trp Leu Leu Gly Ala Ala Met Val Gly Ala Val Leu Thr Y L E Q A S R I W S W L L G A A M V G A V L T 470 475 480 485 insT (49,43,44,62,50,34,33,28,18,3,4) |G=Gly (50,33) insC (3,4,18,28,40) T=ter (93) || 14855 1500 | 1515 | 1530 GCC CTG CTG GCA GGG CTT GTG AGC TTG CTG TGT CGT CAC AAG AGA AAG CAG CTT CCT GAA GAA AAG CAG CGG GAC GAC CGT CCC GAA CAC TCG AAC GAC ACA GCA GTG TTC TCT TTC GTC GAA GGA CTT CTT TTC GTC Ala Leu Leu Ala Gly Leu Val Ser Leu Leu Cys Arg His Lys Arg Lys Gln Leu Pro Glu Glu Lys Gln A L L A G L V S L L C R H K R K Q L P E E K Q 490 495 500 505 510 1545 1560 1575 1590 1600 CCA CTC CTC ATG GAG AAA GAG GAT TAC CAC AGC TTG TAT CAG AGC CAT TTA TAA aaggc ttagg caata GGT GAG GAG TAC CTC TTT CTC CTA ATG GTG TCG AAC ATA GTC TCG GTA AAT ATT ttccg aatcc gttat Pro Leu Leu Met Glu Lys Glu Asp Tyr His Ser Leu Tyr Gln Ser His Leu ter P L L M E K E D Y H S L Y Q S H L X 515 520 525 530 1610 1620 1630 1640 1650 1660 1670 1680 gagta gggcc aaaaa gcctg acctc actct aactc aaagt aatgt ccagg ttccc agaga atatc tgctg gtatt ctcat cccgg ttttt cggac tggag tgaga ttgag tttca ttaca ggtcc aaggg tctct tatag acgac cataa
tttct gtaaa gacca tttgc aaaat tgtaa cctaa tacaa agtgt agcct tcttc caact caggt agaac acacc aaaga cattt ctggt aaacg tttta acatt ggatt atgtt tcaca tcgga agaag gttga gtcca tcttg tgtgg
tgtct ttgtc ttgct gtttt cactc agccc tttta acatt ttccc cctaa gccat atgtc taagg aaagg atgct acaga aacag aacga caaaa gtgag tcggg aaaat tgtaa aaggg ggatt cggta tacag attcc tttcc tacga
atttg gtaat gagga actgt tattt gtatg tgaat taaag tgctc ttatt ttaaa aaatt gaaat aattt tgatt taaac catta ctcct tgaca ataaa catac actta atttc acgag aataa aattt tttaa cttta ttaaa actaa
tttgc cttct gatta tttaa agatc tatat atgtt ttatt ggccc cttct ttatt ttaat aaaac agtga gaaat aaacg gaaga ctaat aaatt tctag atata tacaa aataa ccggg gaaga aataa aatta ttttg tcact cttta
ctaca ttaac tgact ccttt aggct tcaga aacac atttt tattc tcttc agaaa ggatg atatt ccc gatgt aattg actga ggaaa tccga agtct ttgtg taaaa ataag agaag tcttt cctac tataa ggg
(2)=[2] (3)=[3] (4)=[4] (5)=[5] (6)=[6] (7)=[7] (8)=[8]sg (9)=[9] (10)=[10] (11)=[11] (12)=[12] (13)=[13] (14)=[14] (15)=[15] (16)=[16] (17)=[17] (18)=[18] (19)=[19] (20)=[20] (21)=[21] (22)=[22] (23)=[23] (24)=[24] (25)=[25] (26)=[26] (27)=[27] (28)=[28] (29)=[29] (30)=[30] (31)=[31] (32)=[32] (33)=[33] (34)=[34] (35)=[35] (36)=[36] (37)=[37] (38)=[38] (39)=[39] (40)=[40] (41)=[41] (42)=[42] (43)=[43] (44)=[44] (45)=[45] (46)=[46] (47)=[47] (48)=[48] (49)=[49] (50)=[50] (51)=[51] (52)=[52] (53)=[53] (54)=[54] (55)=[55] (56)=[56] (57)=[57] (58)=[58] (59)=[59] (60)=[60] (61)=[61] (62)=[62] (63)=[63] (64)=[15] (65)=[64] (66)=[65] (67)=[66] (68)=[67] (69)=[68] (70)=[69] (71)=[70] (72)=[71] (72)=[72] (73)=[73] (74)=[74] (75)=[75] (76)=[76] (77)=[77] (78)=[78] (79)=[79] (80)=[80] (81)=[81] (82)=[82] (83)=[83] (84)=[84] (85)=[85] (86)=[86] (87)=[87] (88)=[88] (89)=[89] (90)=[90] (91)=[91] (92)=[92] (93)=[93] 1. Spritz,R.A., Oh,J., Fukai,K., Holmes,S.A., Ho,L., Chitayat,D., France,T.D., Musarella,M.A., Orlow,S.J., Schnur,R.E., Weleber,R.G., and Levin,A.V. Novel mutations of the tyrosinase (TYR) gene in type I oculocutaneous albinism (OCA1). 1997; Hum.Mutat. 10: 171-174. PMID: 9259202 2. Oetting,W.S., Fryer,J.P., and King,R.A. Mutations of the human tyrosinase gene associated with tyrosinase related oculocutaneous albinism (OCA1). 1998; Hum.Mutat. 12: 433-434. PMID: 10671066 3. Oetting,W.S. and King,R.A. Analysis of tyrosinase mutations associated with tyrosinase- related oculocutaneous albinism (OCA1). 1994; Pigment Cell Res. 7: 285-290. PMID: 7886000 4. Spritz,R.A. Molecular genetics of oculocutaneous albinism. 1994; Hum.Mol.Genet. 3 Spec No: 1469-1475. PMID: 7849740 5. Passmore,L., Käsmann-Kellner,B., and Weber,B.H.F. Novel and recurrent mutations in the tyrosinase gene and the P gene in the German albino population. 1999; Hum.Genet. 105: 200-210. PMID: 10987646 6. Oetting,W.S., Fryer,J.P., and King,R.A. A dinucleotide deletion (-delta GA115) in the tyrosinase gene responsible for type I-A (tyrosinase negative) oculocutaneous albinism in a Pakistani individual. 1993; Hum.Mol.Genet. 2: 1047-1048. PMID: 8364542 7. Gershoni Baruch,R., Rosenmann,A., Droetto,S., Holmes,S., Tripathi,R.K., and Spritz,R.A. Mutations of the tyrosinase gene in patients with oculocutaneous albinism from various ethnic groups in Israel. 1994; Am.J.Hum.Genet. 54: 586-594. PMID: 8128955 8. Tsai,C.H., Tsai,F.J., Wu,J.Y., Lin,S.P., Chang,J.G., Yang,C.F., and Lee,C.C. Insertion/deletion mutations of type I oculocutaneous albinism in chinese patients from Taiwan. 1999; Hum.Mutat.Online. 14: 542 PMID: 10571953 9. Takeda,A., Tomita,Y., Matsunaga,J., Tagami,H., and Shibahara,S. Molecular basis of tyrosinase-negative oculocutaneous albinism. A single base mutation in the tyrosinase gene causing arginine to glutamine substitution at position 59. 1990; J.Biol.Chem. 265: 17792-17797. PMID: 2120217 10. Giebel,L.B. and Spritz,R.A. RFLP for MboI in the human tyrosinase (TYR) gene detected by PCR. 1990; Nucleic.Acids.Res. 18: 3103 PMID: 1971925 11. King,R.A., Mentink,M.M., and Oetting,W.S. Non-random distribution of missense mutations within the human tyrosinase gene in type I (tyrosinase-related) oculocutaneous albinism. 1991; Mol.Biol.Med. 8: 19-29. PMID: 1943686 12. Tripathi,R.K., Strunk,K.M., Giebel,L.B., Weleber,R.G., and Spritz,R.A. Tyrosinase gene mutations in type I (tyrosinase-deficient) oculocutaneous albinism define two clusters of missense substitutions. 1992; Am.J.Med.Genet. 43: 865-871. PMID: 1642278 13. Tripathi,R.K., Bundey,S., Musarella,M.A., Droetto,S., Strunk,K.M., Holmes,S.A., and Spritz,R.A. Mutations of the tyrosinase gene in Indo-Pakistani patients with type I (tyrosinase-deficient) oculocutaneous albinism (OCA). 1993; Am.J.Hum.Genet. 53: 1173-1179. PMID: 7902671 14. Giebel,L.B., Musarella,M.A., and Spritz,R.A. A nonsense mutation in the tyrosinase gene of Afghan patients with tyrosinase negative (type IA) oculocutaneous albinism. 1991; J.Med.Genet. 28: 464-467. PMID: 1832718 15. Park,S.K., Lee,K.H., Park,K.C., Lee,J.S., Spritz,R.A., and Lee,S.T. Prevalent and novel mutations of the tyrosinase gene in Korean patients with tyrosinase-deficient oculocutaneous albinism. 1997; Mol.Cells. 7: 187-191. PMID: 9163730 16. Giebel,L.B., Tripathi,R.K., King,R.A., and Spritz,R.A. A tyrosinase gene missense mutation in temperature-sensitive type I oculocutaneous albinism. A human homologue to the Siamese cat and the Himalayan mouse. 1991; J.Clin.Invest. 87: 1119-1122. PMID: 1900309 17. Spritz,R.A., Lee,S.T., Fukai,K., Brondum Nielsen,K., Chitayat,D., Lipson,M.H., Musarella,M.A., Rosenmann,A., and Weleber,R.G. Novel mutations of the P gene in type II oculocutaneous albinism (OCA2). 1997; Hum.Mutat. 10: 175-177. PMID: 9259203 18. Oetting,W.S. and King,R.A. Molecular basis of type I (tyrosinase-related) oculocutaneous albinism: mutations and polymorphisms of the human tyrosinase gene. 1993; Hum.Mutat. 2: 1-6. PMID: 8477259 19. Tomita,Y., Takeda,A., Okinaga,S., Tagami,H., and Shibahara,S. Human oculocutaneous albinism caused by single base insertion in the tyrosinase gene. 1989; Biochem.Biophys.Res.Commun. 164: 990-996. PMID: 2511845 20. Camand,O., Marchant,D., Boutboul,S., Pequignot,M., Odent,S., Dollfus,H., Sutherland,J., Levin,A., Menasche,M., Marsac,C., Dufier,J.L., Heon,E., and Abitbol,M. Mutation analysis of the tyrosinase gene in oculocutaneous albinism. 2001; Hum.Mutat. 17: 352 PMID: 11295837 21. Fukai,K., Holmes,S.A., Lucchese,N.J., Siu,V.M., Weleber,R.G., Schnur,R.E., and Spritz,R.A. Autosomal recessive ocular albinism associated with a functionally significant tyrosinase gene polymorphism. 1995; Nat.Genet. 9: 92-95. PMID: 7704033 22. Matsunaga,J., Dakeishi,M., Miyamura,Y., and Tomita,Y. Sequence analysis of the human tyrosinase promoter from a patient with tyrosinase-negative oculocutaneous albinism. 1997; Pigment Cell Res. 10: 64-67. PMID: 9170165 23. Morris,S.W., Muir,W., and St Clair,D. Dinucleotide repeat polymorphism at the human tyrosinase gene. 1991; Nucleic.Acids.Res. 19: 6968 PMID: 1762935 24. Coupry,I., Taine,L., Goizet,C., Soriano,C., Mortemousque,B., Arveiler,B., and Lacombe,D. Leucodystrophy and oculocutaneous albinism in a child with an 11q14 deletion. 2001; J.Med.Genet. 38: 35-38. PMID: 11134238 25. Breimer,L.H., Winder,A.F., Jay,B., and Jay,M. Initiation codon mutation of the tyrosinase gene as a cause of human albinism. 1994; Clin.Chim.Acta. 227: 17-22. PMID: 7955413 26. Breimer,L.H., Winder,A.F., Panayiotidis,P., Jay,M., Moore,A., and Jay,B. A trinucleotide deletion together with a base duplication event at codon 439 in the human tyrosinase gene identifies a mutational hotspot. 1995; Clin.Chim.Acta. 243: 35-42. PMID: 8747512 27. Summers,C.G. Vision in albinism. 1996; Trans.Am.Ophthalmol.Soc. 94: 1095-1155. PMID: 8981720 28. Spritz,R.A. Molecular genetics of oculocutaneous albinism. 1993; Semin.Dermatol. 12: 167-172. PMID: 8217557 29. Oetting,W.S. and King,R.A. Molecular basis of albinism: mutations and polymorphisms of pigmentation genes associated with albinism. 1999; Hum.Mutat. 13: 99-115. PMID: 10094567 30. Miyamura,Y., Verma,I.C., Saxena,R., Hoshi,M., Murase,A., Nakamura,E., Kono,M., Suzuki,T., Yasue,S., Shibata,S., Sakakibara,A., and Tomita,Y. Five novel mutations in tyrosinase gene of Japanese and Indian patients with oculocutaneous albinism type I (OCA1). 2005; J Invest Dermatol. 125: 397-398. PMID: 16098056 31. Nakamura,E., Miyamura,Y., Matsunaga,J., Kano,Y., keishi-Hara,M., Tanita,M., Kono,M., and Tomita,Y. A novel mutation of the tyrosinase gene causing oculocutaneous albinism type 1 (OCA1). 2002; J.Dermatol.Sci. 28: 102-105. PMID: 11858948 32. Hewitt,C., Wu,C.L., Hattab,F.N., Amin,W., Ghaffar,K.A., Toomes,C., Sloan,P., Read,A.P., James,J.A., and Thakker,N.S. Coinheritance of two rare genodermatoses (Papillon-Lefevre syndrome and oculocutaneous albinism type 1) in two families: a genetic study. 2004; Br.J.Dermatol. 151: 1261-1265. PMID: 15606524 33. Gronskov,K., Ek,J., Sand,A., Scheller,R., Bygum,A., Brixen,K., Brondum-Nielsen,K., and Rosenberg,T. Birth prevalence and mutation spectrum in danish patients with autosomal recessive albinism. 2009; Invest Ophthalmol Vis.Sci. 50: 1058-1064. PMID: 19060277 34. Rooryck,C., Morice-Picard,F., Elcioglu,N.H., Lacombe,D., Taieb,A., and Arveiler,B. Molecular diagnosis of oculocutaneous albinism: new mutations in the OCA1-4 genes and practical aspects. 2008; Pigment Cell Melanoma Res. 21: 583-587. PMID: 18821858 35. Aquaron,R. L'albinisme oculocutane humain. De l'observation clinique a la biologie moleculaire. 1993; Bull.Soc Pathol.Exot. 86: 313-326. PMID: 8124097 36. Chaki,M., Mukhopadhyay,A., Chatterjee,S., Das,M., Samanta,S., and Ray,K. Higher prevalence of OCA1 in an ethnic group of eastern India is due to a founder mutation in the tyrosinase gene. 2005; Mol.Vis. 11:531-4.: 531-534. PMID: 16056219 37. Chaki,M., Mukhopadhyay,A., and Ray,K. Determination of variants in the 3'-region of the Tyrosinase gene requires locus specific amplification. 2005; Hum.Mutat. 26: 53-58. PMID: 15895460 38. Chintamaneni,C.D., Halaban,R., Kobayashi,Y., Witkop,C.J., Jr., and Kwon,B.S. A single base insertion in the putative transmembrane domain of the tyrosinase gene as a cause for tyrosinase-negative oculocutaneous albinism. 1991; Proc.Natl.Acad.Sci.U.S.A. 88: 5272-5276. PMID: 1711223 39. Giebel,L.B., Strunk,K.M., King,R.A., Hanifin,J.M., and Spritz,R.A. A frequent tyrosinase gene mutation in classic, tyrosinase- negative (type IA) oculocutaneous albinism. 1990; Proc.Natl.Acad.Sci.U.S.A. 87: 3255-3258. PMID: 1970634 40. Giebel,L.B., Tripathi,R.K., Strunk,K.M., Hanifin,J.M., Jackson,C.E., King,R.A., and Spritz,R.A. Tyrosinase gene mutations associated with type IB ("yellow") oculocutaneous albinism. 1991; Am.J.Hum.Genet. 48: 1159-1167. PMID: 1903591 41. Chaki,M., Sengupta,M., Mukhopadhyay,A., Subba,R., I, Majumder,P.P., Das,M., Samanta,S., and Ray,K. OCA1 in different ethnic groups of india is primarily due to founder mutations in the tyrosinase gene. 2006; Ann.Hum.Genet. 70: 623-630. PMID: 16907708 42. Hattab,F.N. and Amin,W.M. Papillon-Lefevre syndrome with albinism: a review of the literature and report of 2 brothers. 2005; Oral Surg.Oral Med.Oral Pathol.Oral Radiol.Endod. 100: 709-716. PMID: 16301152 43. Hutton,S.M. and Spritz,R.A. A comprehensive genetic study of autosomal recessive ocular albinism in Caucasian patients. 2008; Invest Ophthalmol.Vis.Sci. 49: 868-872. PMID: 18326704 44. Hutton,S.M. and Spritz,R.A. Comprehensive analysis of oculocutaneous albinism among non-Hispanic caucasians shows that OCA1 is the most prevalent OCA type. 2008; J.Invest Dermatol. 128: 2442-2450. PMID: 18463683 45. Hsieh,Y.Y., Wu,J.Y., Chang,C.C., Tsai,F.J., Lee,C.C., Tsai,H.D., and Tsai,C.H. Prenatal diagnosis of oculocutaneous albinism two mutations located at the same allele. 2001; Prenat.Diagn. 21: 200-201. PMID: 11260608 46. Kikuchi,H., Hara,S., Ishiguro,S., Tamai,M., and Watanabe,M. Detection of point mutation in the tyrosinase gene of a Japanese albino patient by a direct sequencing of amplified DNA. 1990; Hum.Genet. 85: 123-124. PMID: 2113511 47. Kim,D.K., Kang,K.H., and Choi,I.J. One-allele system in the Korean for MboI-RFLP in exon 1 of the human tyrosinase (TYR) gene. 2000; J.Dermatol.Sci. 24: 1-3. PMID: 10960773 48. King,R.A., Townsend,D., Oetting,W., Summers,C.G., Olds,D.P., White,J.G., and Spritz,R.A. Temperature-sensitive tyrosinase associated with peripheral pigmentation in oculocutaneous albinism. 1991; J.Clin.Invest. 87: 1046-1053. PMID: 1900307 49. King,R.A. and Oetting,W.S. Molecular basis of type IA (tyrosinase negative) oculocutaneous albinism. 1992; Pigment Cell Res. Suppl 2: 249-253. PMID: 1409426 50. King,R.A., Pietsch,J., Fryer,J.P., Savage,S., Brott,M.J., Russell-Eggitt,I., Summers,C.G., and Oetting,W.S. Tyrosinase gene mutations in oculocutaneous albinism 1 (OCA1): definition of the phenotype. 2003; Hum.Genet. 113: 502-513. PMID: 13680365 51. Lee,S.T., Park,S.K., Lee,H., Lee,J.S., and Park,Y.W. DNA-based prenatal diagnosis of a Korean family with tyrosinase- related oculocutaneous albinism (OCA1). 1997; Jpn.J.Hum.Genet. 42: 499-505. PMID: 52. Lin,S.Y., Chien,S.C., Su,Y.N., Lee,C.N., and Chen,C.P. Rapid genetic analysis of oculocutaneous albinism (OCA1) using denaturing high performance liquid chromatography (DHPLC) system. 2006; Prenat.Diagn. 26: 466-470. PMID: 16570240 53. Matsunaga,J., Dakeishi,M., Shimizu,H., and Tomita,Y. R278TER and P431L mutations of the tyrosinase gene exist in Japanese patients with tyrosinase-negative oculocutaneous albinism. 1996; J.Dermatol.Sci. 13: 134-139. PMID: 8953413 54. Matsunaga,J., Takeda,A., Tomita,Y., Hara,M., Shibahara,S., and Tagami,H. Cloning and sequence analysis of the tyrosinase gene from a patient with tyrosinase-positive oculocutaneous albinism. 1992; J.Dermatol.Sci. 3: 181-185. PMID: 1498098 55. Matsunaga,J., Dakeishi-Hara,M., Tanita,M., Nindl,M., Nagata,Y., Nakamura,E., Miyamura,Y., Kikuchi,K., Furue,M., and Tomita,Y. A splicing mutation of the tyrosinase gene causes yellow oculocutaneous albinism in a Japanese patient with a pigmented phenotype. 1999; Dermatology. 199: 124-129. PMID: 10559577 56. Morell,R., Spritz,R.A., Ho,L., Pierpont,J., Guo,W., Friedman,T.B., and Asher,J.H., Jr. Apparent digenic inheritance of Waardenburg syndrome type 2 (WS2) and autosomal recessive ocular albinism (AROA). 1997; Hum.Mol.Genet. 6: 659-664. PMID: 9158138 57. Oetting,W.S., Handoko,H.Y., Mentink,M.M., Paller,A.S., White,J.G., and King,R.A. Molecular analysis of an extended family with type IA (tyrosinase-negative) oculocutaneous albinism. 1991; J.Invest.Dermatol. 97: 15-19. PMID: 1676041 58. Oetting,W.S., Roed,C.M., Mentink,M.M., and King,R.A. PCR detection of a TaqI polymorphism at the CCAATT box of the human tyrosinase (TYR) gene. 1991; Nucleic.Acids.Res. 19: 5800 PMID: 1682887 59. Oetting,W.S., Mentink,M.M., Summers,C.G., Lewis,R.A., White,J.G., and King,R.A. Three different frameshift mutations of the tyrosinase gene in type IA oculocutaneous albinism. 1991; Am.J.Hum.Genet. 49: 199-206. PMID: 1905879 60. Oetting,W.S., Witkop,C.J., Jr., Brown,S.A., Colomer,R., Fryer,J.P., Bloom,K.E., and King,R.A. A frequent tyrosinase gene mutation associated with type I-A (tyrosinase-negative) oculocutaneous albinism in Puerto Rico. 1993; Am.J.Hum.Genet. 52: 17-23. PMID: 8434585 61. Oetting,W.S., Skach,W.R., Fryer,J.P., and King,R.A. Unusual tyrosinase mutations associated with OCA1. 1993; Am.J.Hum.Genet. 53: 935 PMID: 62. Opitz,S., Kasmann-Kellner,B., Kaufmann,M., Schwinger,E., and Zuhlke,C. Detection of 53 novel DNA variations within the tyrosinase gene and accumulation of mutations in 17 patients with albinism. 2004; Hum.Mutat. 23: 630-631. PMID: 15146472 63. Park,K.C., Chintamaneni,C.D., Halaban,R., Witkop,C.J., Jr., and Kwon,B.S. Molecular analyses of a tyrosinase-negative albino family. 1993; Am.J.Hum.Genet. 52: 406-413. PMID: 843070 64. Park,K.C., Kim,K.H., Lee,Y.S., and Kwon,B.S. Single-strand conformation polymorphism analysis of point mutation in a tyrosinase-negative oculocutaneous albinism. 1994; J.Inherit.Metab Dis. 17: 123-126. PMID: 8051921 65. Ray,K., Chaki,M., and Sengupta,M. Gene symbol: TYR. Disease: albinism, oculocutaneous 1. 2006; Hum.Genet. 119: 675 PMID: 17128464 66. Ray,K., Chaki,M., and Sengupta,M. Tyrosinase and ocular diseases: some novel thoughts on the molecular basis of oculocutaneous albinism type 1. 2007; Prog.Retin.Eye Res. 26: 323-358. PMID: 17355913 67. Santiago Borrero,P.J., Rodriguez-Perez,Y., Renta,J.Y., Izquierdo,N.J., Del,F.L., Munoz,D., Molina,N.L., Ramirez,S., Pagan-Mercado,G., Ortiz,I., Rivera-Caragol,E., Spritz,R.A., and Cadilla,C.L. Genetic testing for oculocutaneous albinism type 1 and 2 and Hermansky-Pudlak syndrome type 1 and 3 mutations in Puerto Rico. 2006; J.Invest Dermatol. 126: 85-90. PMID: 16417222 68. Schnur,R.E., Sellinger,B.T., Holmes,S.A., Wick,P.A., Tatsumura,Y.O., and Spritz,R.A. Type I oculocutaneous albinism associated with a full-length deletion of the tyrosinase gene. 1996; J.Invest Dermatol. 106: 1137-1140. PMID: 8618053 69. Takeda,A., Tomita,Y., Okinaga,S., Tagami,H., and Shibahara,S. Functional analysis of the cDNA encoding human tyrosinase precursor. 1989; Biochem.Biophys.Res.Commun. 162: 984-990. PMID: 70. Spritz,R.A., Strunk,K.M., Giebel,L.B., and King,R.A. Detection of mutations in the tyrosinase gene in a patient with type IA oculocutaneous albinism. 1990; N.Engl.J.Med. 322: 1724-1728. PMID: 2342539 71. Spritz,R.A., Strunk,K.M., Hsieh,C.L., Sekhon,G.S., and Francke,U. Homozygous tyrosinase gene mutation in an American black with tyrosinase-negative (type IA) oculocutaneous albinism. 1991; Am.J.Hum.Genet. 48: 318-324. PMID: 1899321 72. Sundaresan,P., Sil,A.K., Philp,A.R., Randolph,M.A., Natchiar,G., and Namperumalsamy,P. Genetic analysis of oculocutaneous albinism type 1 (OCA1) in Indian families: two novel frameshift mutations in the TYR Gene. 2004; Mol.Vis. 10:1005-10.: 1005-1010. PMID: 15635296 73. Takizawa,Y., Kato,S., Matsunaga,J., Aozaki,R., Tomita,Y., Nishikawa,T., and Shimizu,H. Electron microscopic DOPA reaction test for oculocutaneous albinism. 2000; Arch Dermatol.Res. 292: 301-305. PMID: 10929771 74. Tanita,M., Matsunaga,J., Miyamura,Y., Dakeishi,M., Nakamura,E., Kono,M., Shimizu,H., Tagami,H., and Tomita,Y. Polymorphic sequences of the tyrosinase gene: allele analysis on 16 OCA1 patients in Japan indicate that three polymorphic sequences in the tyrosinase gene promoter could be powerful markers for indirect gene diagnosis. 2002; J.Hum.Genet. 47: 1-6. PMID: 11829136 75. Tomita,Y. and Miyamura,Y. Oculocutaneous albinism and analysis of tyrosinase gene in Japanese patients. 1998; Nagoya J.Med.Sci. 61: 97-102. PMID: 9879192 76. Toyofuku,K., Wada,I., Valencia,J.C., Kushimoto,T., Ferrans,V.J., and Hearing,V.J. Oculocutaneous albinism types 1 and 3 are ER retention diseases: mutation of tyrosinase or Tyrp1 can affect the processing of both mutant and wild-type proteins. 2001; FASEB J. 15: 2149-2161. PMID: 11641241 77. Toyofuku,K., Wada,I., Spritz,R.A., and Hearing,V.J. The molecular basis of oculocutaneous albinism type 1 (OCA1): sorting failure and degradation of mutant tyrosinases results in a lack of pigmentation. 2001; Biochem.J. 355: 259-269. PMID: 11284711 78. Tripathi,R.K., Giebel,L.B., Strunk,K.M., and Spritz,R.A. A polymorphism of the human tyrosinase gene is associated with temperature-sensitive enzymatic activity. 1991; Gene Expr. 1: 103-110. PMID: 1820207 79. Tripathi,R.K., Hearing,V.J., Urabe,K., Aroca,P., and Spritz,R.A. Mutational mapping of the catalytic activities of human tyrosinase. 1992; J.Biol.Chem. 267: 23707-23712. PMID: 1429711 80. Wang,Y., Guo,X., Li,W., and Lian,S. Four novel mutations of TYR gene in Chinese OCA1 patients. 2009; J.Dermatol.Sci. 53: 80-81. PMID: 18701257 81. Zahed,L., Zahreddine,H., Noureddine,B., Rebeiz,N., Shakar,N., Zalloua,P., and Haddad,F. Molecular basis of oculocutaneous albinism type 1 in Lebanese patients. 2005; J.Hum.Genet. 50: 317-319. PMID: 15937636 82. Zuhlke,C., Criee,C., Gemoll,T., Schillinger,T., and Kaesmann-Kellner,B. Polymorphisms in the genes for oculocutaneous albinism type 1 and type 4 in the German population. 2007; Pigment Cell Res. 20: 225-227. PMID: 17516931 83. Ziakas,N.G., Jogiya,A., and Michaelides,M. A case of familial trichomegaly in association with oculocutaneous albinism type 1. 2004; Eye (Lond). 18: 863-864. PMID: 14752500 84. Preising,M.N., Forster,H., Lorenz,B. Mutations screening of TYR, OCA2, GPR143, and MC1R in Patients Identified by Congenital Nystagmus, Macular Hypoplasia and Hypopiogmentatof the Fundus; the Classical Features of Ocular and Oculocutaneous Albinism. - submitted 2010; Goto Top 85. Aquaron,R., Hesse,S., Badens,C., and Bonerandi,J.J. Nouvelle mutation non sens (p.E250X) du gene de la tyrosinase chez un homme atteint d'albinisme de type 1A. 2009; Ann.Dermatol.Venereol. 136: 57-59. PMID: 19171234 86. Aquaron,R., Soufir,N., Berge-Lefranc,J.L., Badens,C., Austerlitz,F., and Grandchamp,B. Oculocutaneous albinism type 2 (OCA2) with homozygous 2.7-kb deletion of the P gene and sickle cell disease in a Cameroonian family. Identification of a common TAG haplotype in the mutated P gene. 2007; J.Hum.Genet. 52: 771-780. PMID: 17767372 87. Aquaron,R., Berge-Lefranc,J.L., Badens,C., Roche,J., Fite,A., Sainte-Marie,D., Piquion,N., and Cartault,F. L'albinisme oculocutane dans les departements francais d'Outre-Mer (Reunion, Guyane, Martinique) et a Mayotte: a propos de 21 observations dans 16 familles. 2005; Med.Trop.(Mars.). 65: 584-591. PMID: 16555521 88. Oetting,W.S. and King,R.A. Molecular analysis of type I-A (tyrosinase negative) oculocutaneous albinism. 1992; Hum.Genet. 90: 258-262. PMID: 1487241 89. Matsunaga,J., Dakeishi Hara,M., Miyamura,Y., Nakamura,E., Tanita,M., Satomura,K., and Tomita,Y. Sequence-based diagnosis of tyrosinase-related oculocutaneous albinism: successful sequence analysis of the tyrosinase gene from blood spots dried on filter paper. 1998; Dermatology. 196: 189-193. PMID: 9568405 90. Goto,M., Sato-Matsumura,K.C., Sawamura,D., Yokota,K., Nakamura,H., and Shimizu,H. Tyrosinase gene analysis in Japanese patients with oculocutaneous albinism. 2004; J.Dermatol.Sci. 35: 215-220. PMID: 15381243 91. Oetting,W.S., Pietsch,J., Brott,M.J., Savage,S., Fryer,J.P., Summers,C.G., and King,R.A. The R402Q tyrosinase variant does not cause autosomal recessive ocular albinism. 2009; Am.J.Med.Genet.A. 149A: 466-469. PMID: 19208379 92. Rosenmann,A., Bejarano-Achache,I., Eli,D., Maftsir,G., Mizrahi-Meissonnier,L., and Blumenfeld,A. Prenatal molecular diagnosis of oculocutaneous albinism (OCA) in a large cohort of Israeli families. 2009; Prenat.Diagn. 29: 939-946. PMID: 19626598 93. Wei,A., Wang,Y., Long,Y., Wang,Y., Guo,X., Zhou,Z., Zhu,W., Liu,J., Bian,X., Lian,S., and Li,W. A comprehensive analysis reveals mutational spectra and common alleles in Chinese patients with oculocutaneous albinism. 2010; J.Invest Dermatol. 130: 716-724. PMID: 19865097 Yüklə 190,87 Kb. Dostları ilə paylaş:
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