                         SEQUENCE LISTING

<110>  INSTITUT PASTEUR
       CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE (CNRS)
       COMMISSARIAT A L'ENERGIE ATOMIQUE ET AUX ENERGIES 
       ALTERNATIVES (CEA)
 
<120>  METHODS FOR IN VITRO INVESTIGATING MITOCHONDRIAL REPLICATION 
       DYSFUNCTION IN A BIOLOGICAL SAMPLE, KITS AND USES THEREOF, 
       THERAPEUTIC METHODS AGAINST PROGEROID-LIKE SYNDROMES OR SYMPTOMES
        AND SCREENING METHOD FOR IDENTIFYING PARTICULAR PROTEASE 
       INHIBITOR(S)  AND/OR NITROSO-REDOX STRESS SCAVENGER COMPOUND(S).

<130>  B10292A_AD/AFL/KN

<140>  PCT/EP XXXXXX
<141>  2015-02-13

<150>  EP 14305203.3
<151>  2014-02-14

<160>  18    

<170>  PatentIn version 3.5

<210>  1
<211>  1239
<212>  PRT
<213>  Homo sapiens


<220>
<221>  MISC_FEATURE
<223>  PolG protein (access number NP_001119603.1)

<400>  1

Met Ser Arg Leu Leu Trp Arg Lys Val Ala Gly Ala Thr Val Gly Pro 
1               5                   10                  15      


Gly Pro Val Pro Ala Pro Gly Arg Trp Val Ser Ser Ser Val Pro Ala 
            20                  25                  30          


Ser Asp Pro Ser Asp Gly Gln Arg Arg Arg Gln Gln Gln Gln Gln Gln 
        35                  40                  45              


Gln Gln Gln Gln Gln Gln Gln Pro Gln Gln Pro Gln Val Leu Ser Ser 
    50                  55                  60                  


Glu Gly Gly Gln Leu Arg His Asn Pro Leu Asp Ile Gln Met Leu Ser 
65                  70                  75                  80  


Arg Gly Leu His Glu Gln Ile Phe Gly Gln Gly Gly Glu Met Pro Gly 
                85                  90                  95      


Glu Ala Ala Val Arg Arg Ser Val Glu His Leu Gln Lys His Gly Leu 
            100                 105                 110         


Trp Gly Gln Pro Ala Val Pro Leu Pro Asp Val Glu Leu Arg Leu Pro 
        115                 120                 125             


Pro Leu Tyr Gly Asp Asn Leu Asp Gln His Phe Arg Leu Leu Ala Gln 
    130                 135                 140                 


Lys Gln Ser Leu Pro Tyr Leu Glu Ala Ala Asn Leu Leu Leu Gln Ala 
145                 150                 155                 160 


Gln Leu Pro Pro Lys Pro Pro Ala Trp Ala Trp Ala Glu Gly Trp Thr 
                165                 170                 175     


Arg Tyr Gly Pro Glu Gly Glu Ala Val Pro Val Ala Ile Pro Glu Glu 
            180                 185                 190         


Arg Ala Leu Val Phe Asp Val Glu Val Cys Leu Ala Glu Gly Thr Cys 
        195                 200                 205             


Pro Thr Leu Ala Val Ala Ile Ser Pro Ser Ala Trp Tyr Ser Trp Cys 
    210                 215                 220                 


Ser Gln Arg Leu Val Glu Glu Arg Tyr Ser Trp Thr Ser Gln Leu Ser 
225                 230                 235                 240 


Pro Ala Asp Leu Ile Pro Leu Glu Val Pro Thr Gly Ala Ser Ser Pro 
                245                 250                 255     


Thr Gln Arg Asp Trp Gln Glu Gln Leu Val Val Gly His Asn Val Ser 
            260                 265                 270         


Phe Asp Arg Ala His Ile Arg Glu Gln Tyr Leu Ile Gln Gly Ser Arg 
        275                 280                 285             


Met Arg Phe Leu Asp Thr Met Ser Met His Met Ala Ile Ser Gly Leu 
    290                 295                 300                 


Ser Ser Phe Gln Arg Ser Leu Trp Ile Ala Ala Lys Gln Gly Lys His 
305                 310                 315                 320 


Lys Val Gln Pro Pro Thr Lys Gln Gly Gln Lys Ser Gln Arg Lys Ala 
                325                 330                 335     


Arg Arg Gly Pro Ala Ile Ser Ser Trp Asp Trp Leu Asp Ile Ser Ser 
            340                 345                 350         


Val Asn Ser Leu Ala Glu Val His Arg Leu Tyr Val Gly Gly Pro Pro 
        355                 360                 365             


Leu Glu Lys Glu Pro Arg Glu Leu Phe Val Lys Gly Thr Met Lys Asp 
    370                 375                 380                 


Ile Arg Glu Asn Phe Gln Asp Leu Met Gln Tyr Cys Ala Gln Asp Val 
385                 390                 395                 400 


Trp Ala Thr His Glu Val Phe Gln Gln Gln Leu Pro Leu Phe Leu Glu 
                405                 410                 415     


Arg Cys Pro His Pro Val Thr Leu Ala Gly Met Leu Glu Met Gly Val 
            420                 425                 430         


Ser Tyr Leu Pro Val Asn Gln Asn Trp Glu Arg Tyr Leu Ala Glu Ala 
        435                 440                 445             


Gln Gly Thr Tyr Glu Glu Leu Gln Arg Glu Met Lys Lys Ser Leu Met 
    450                 455                 460                 


Asp Leu Ala Asn Asp Ala Cys Gln Leu Leu Ser Gly Glu Arg Tyr Lys 
465                 470                 475                 480 


Glu Asp Pro Trp Leu Trp Asp Leu Glu Trp Asp Leu Gln Glu Phe Lys 
                485                 490                 495     


Gln Lys Lys Ala Lys Lys Val Lys Lys Glu Pro Ala Thr Ala Ser Lys 
            500                 505                 510         


Leu Pro Ile Glu Gly Ala Gly Ala Pro Gly Asp Pro Met Asp Gln Glu 
        515                 520                 525             


Asp Leu Gly Pro Cys Ser Glu Glu Glu Glu Phe Gln Gln Asp Val Met 
    530                 535                 540                 


Ala Arg Ala Cys Leu Gln Lys Leu Lys Gly Thr Thr Glu Leu Leu Pro 
545                 550                 555                 560 


Lys Arg Pro Gln His Leu Pro Gly His Pro Gly Trp Tyr Arg Lys Leu 
                565                 570                 575     


Cys Pro Arg Leu Asp Asp Pro Ala Trp Thr Pro Gly Pro Ser Leu Leu 
            580                 585                 590         


Ser Leu Gln Met Arg Val Thr Pro Lys Leu Met Ala Leu Thr Trp Asp 
        595                 600                 605             


Gly Phe Pro Leu His Tyr Ser Glu Arg His Gly Trp Gly Tyr Leu Val 
    610                 615                 620                 


Pro Gly Arg Arg Asp Asn Leu Ala Lys Leu Pro Thr Gly Thr Thr Leu 
625                 630                 635                 640 


Glu Ser Ala Gly Val Val Cys Pro Tyr Arg Ala Ile Glu Ser Leu Tyr 
                645                 650                 655     


Arg Lys His Cys Leu Glu Gln Gly Lys Gln Gln Leu Met Pro Gln Glu 
            660                 665                 670         


Ala Gly Leu Ala Glu Glu Phe Leu Leu Thr Asp Asn Ser Ala Ile Trp 
        675                 680                 685             


Gln Thr Val Glu Glu Leu Asp Tyr Leu Glu Val Glu Ala Glu Ala Lys 
    690                 695                 700                 


Met Glu Asn Leu Arg Ala Ala Val Pro Gly Gln Pro Leu Ala Leu Thr 
705                 710                 715                 720 


Ala Arg Gly Gly Pro Lys Asp Thr Gln Pro Ser Tyr His His Gly Asn 
                725                 730                 735     


Gly Pro Tyr Asn Asp Val Asp Ile Pro Gly Cys Trp Phe Phe Lys Leu 
            740                 745                 750         


Pro His Lys Asp Gly Asn Ser Cys Asn Val Gly Ser Pro Phe Ala Lys 
        755                 760                 765             


Asp Phe Leu Pro Lys Met Glu Asp Gly Thr Leu Gln Ala Gly Pro Gly 
    770                 775                 780                 


Gly Ala Ser Gly Pro Arg Ala Leu Glu Ile Asn Lys Met Ile Ser Phe 
785                 790                 795                 800 


Trp Arg Asn Ala His Lys Arg Ile Ser Ser Gln Met Val Val Trp Leu 
                805                 810                 815     


Pro Arg Ser Ala Leu Pro Arg Ala Val Ile Arg His Pro Asp Tyr Asp 
            820                 825                 830         


Glu Glu Gly Leu Tyr Gly Ala Ile Leu Pro Gln Val Val Thr Ala Gly 
        835                 840                 845             


Thr Ile Thr Arg Arg Ala Val Glu Pro Thr Trp Leu Thr Ala Ser Asn 
    850                 855                 860                 


Ala Arg Pro Asp Arg Val Gly Ser Glu Leu Lys Ala Met Val Gln Ala 
865                 870                 875                 880 


Pro Pro Gly Tyr Thr Leu Val Gly Ala Asp Val Asp Ser Gln Glu Leu 
                885                 890                 895     


Trp Ile Ala Ala Val Leu Gly Asp Ala His Phe Ala Gly Met His Gly 
            900                 905                 910         


Cys Thr Ala Phe Gly Trp Met Thr Leu Gln Gly Arg Lys Ser Arg Gly 
        915                 920                 925             


Thr Asp Leu His Ser Lys Thr Ala Thr Thr Val Gly Ile Ser Arg Glu 
    930                 935                 940                 


His Ala Lys Ile Phe Asn Tyr Gly Arg Ile Tyr Gly Ala Gly Gln Pro 
945                 950                 955                 960 


Phe Ala Glu Arg Leu Leu Met Gln Phe Asn His Arg Leu Thr Gln Gln 
                965                 970                 975     


Glu Ala Ala Glu Lys Ala Gln Gln Met Tyr Ala Ala Thr Lys Gly Leu 
            980                 985                 990         


Arg Trp Tyr Arg Leu Ser Asp Glu  Gly Glu Trp Leu Val  Arg Glu Leu 
        995                 1000                 1005             


Asn Leu  Pro Val Asp Arg Thr  Glu Gly Gly Trp Ile  Ser Leu Gln 
    1010                 1015                 1020             


Asp Leu  Arg Lys Val Gln Arg  Glu Thr Ala Arg Lys  Ser Gln Trp 
    1025                 1030                 1035             


Lys Lys  Trp Glu Val Val Ala  Glu Arg Ala Trp Lys  Gly Gly Thr 
    1040                 1045                 1050             


Glu Ser  Glu Met Phe Asn Lys  Leu Glu Ser Ile Ala  Thr Ser Asp 
    1055                 1060                 1065             


Ile Pro  Arg Thr Pro Val Leu  Gly Cys Cys Ile Ser  Arg Ala Leu 
    1070                 1075                 1080             


Glu Pro  Ser Ala Val Gln Glu  Glu Phe Met Thr Ser  Arg Val Asn 
    1085                 1090                 1095             


Trp Val  Val Gln Ser Ser Ala  Val Asp Tyr Leu His  Leu Met Leu 
    1100                 1105                 1110             


Val Ala  Met Lys Trp Leu Phe  Glu Glu Phe Ala Ile  Asp Gly Arg 
    1115                 1120                 1125             


Phe Cys  Ile Ser Ile His Asp  Glu Val Arg Tyr Leu  Val Arg Glu 
    1130                 1135                 1140             


Glu Asp  Arg Tyr Arg Ala Ala  Leu Ala Leu Gln Ile  Thr Asn Leu 
    1145                 1150                 1155             


Leu Thr  Arg Cys Met Phe Ala  Tyr Lys Leu Gly Leu  Asn Asp Leu 
    1160                 1165                 1170             


Pro Gln  Ser Val Ala Phe Phe  Ser Ala Val Asp Ile  Asp Arg Cys 
    1175                 1180                 1185             


Leu Arg  Lys Glu Val Thr Met  Asp Cys Lys Thr Pro  Ser Asn Pro 
    1190                 1195                 1200             


Thr Gly  Met Glu Arg Arg Tyr  Gly Ile Pro Gln Gly  Glu Ala Leu 
    1205                 1210                 1215             


Asp Ile  Tyr Gln Ile Ile Glu  Leu Thr Lys Gly Ser  Leu Glu Lys 
    1220                 1225                 1230             


Arg Ser  Gln Pro Gly Pro 
    1235                 


<210>  2
<211>  4452
<212>  DNA
<213>  Homo sapiens


<220>
<221>  source
<222>  (1)..(4452)
<223>  POLG DNA sequence

<400>  2
gcggaccggc cgggtggagg ccacacgcta ccccgaggct gcgtaggccg cgcgaagggg       60

gacgccgtgc cgtgggcctg gggtcggggg agcagcagac cgggaagcac cgatttgggg      120

tggaaggcag gcatggtcaa acccatttca ctgacaggag agcagagaca ggacgtgtct      180

ctctccacgt cttccagcca gtaaaagaag ccaagctgga gcccaaagcc aggtgttctg      240

actcccagcg tgggggtccc tgcaccaacc atgagccgcc tgctctggag gaaggtggcc      300

ggcgccaccg tcgggccagg gccggttcca gctccggggc gctgggtctc cagctccgtc      360

cccgcgtccg accccagcga cgggcagcgg cggcggcagc agcagcagca gcagcagcag      420

cagcagcaac agcagcctca gcagccgcaa gtgctatcct cggagggcgg gcagctgcgg      480

cacaacccat tggacatcca gatgctctcg agagggctgc acgagcaaat cttcgggcaa      540

ggaggggaga tgcctggcga ggccgcggtg cgccgcagcg tcgagcacct gcagaagcac      600

gggctctggg ggcagccagc cgtgcccttg cccgacgtgg agctgcgcct gccgcccctc      660

tacggggaca acctggacca gcacttccgc ctcctggccc agaagcagag cctgccctac      720

ctggaggcgg ccaacttgct gttgcaggcc cagctgcccc cgaagccccc ggcttgggcc      780

tgggcggagg gctggacccg gtacggcccc gagggggagg ccgtacccgt ggccatcccc      840

gaggagcggg ccctggtgtt cgacgtggag gtctgcttgg cagagggaac ttgccccaca      900

ttggcggtgg ccatatcccc ctcggcctgg tattcctggt gcagccagcg gctggtggaa      960

gagcgttact cttggaccag ccagctgtcg ccggctgacc tcatccccct ggaggtccct     1020

actggtgcca gcagccccac ccagagagac tggcaggagc agttagtggt ggggcacaat     1080

gtttcctttg accgagctca tatcagggag cagtacctga tccagggttc ccgcatgcgt     1140

ttcctggaca ccatgagcat gcacatggcc atctcagggc taagcagctt ccagcgcagt     1200

ctgtggatag cagccaagca gggcaaacac aaggtccagc cccccacaaa gcaaggccag     1260

aagtcccaga ggaaagccag aagaggccca gcgatctcat cctgggactg gctggacatc     1320

agcagtgtca acagtctggc agaggtgcac agactttatg taggggggcc tcccttagag     1380

aaggagcctc gagaactgtt tgtgaagggc accatgaagg acattcgtga gaacttccag     1440

gacctgatgc agtactgtgc ccaggacgtg tgggccaccc atgaggtttt ccagcagcag     1500

ctaccgctct tcttggagag gtgtccccac ccagtgactc tggccggcat gctggagatg     1560

ggtgtctcct acctgcctgt caaccagaac tgggagcgtt acctggcaga ggcacagggc     1620

acttatgagg agctccagcg ggagatgaag aagtcgttga tggatctggc caatgatgcc     1680

tgccagctgc tctcaggaga gaggtacaaa gaagacccct ggctctggga cctggagtgg     1740

gacctgcaag aatttaagca gaagaaagct aagaaggtga agaaggaacc agccacagcc     1800

agcaagttgc ccatcgaggg ggctggggcc cctggtgatc ccatggatca ggaagacctc     1860

ggcccctgca gtgaggagga ggagtttcaa caagatgtca tggcccgcgc ctgcttgcag     1920

aagctgaagg ggaccacaga gctcctgccc aagcggcccc agcaccttcc tggacaccct     1980

ggatggtacc ggaagctctg cccccggcta gacgaccctg catggacccc gggccccagc     2040

ctcctcagcc tgcagatgcg ggtcacacct aaactcatgg cacttacctg ggatggcttc     2100

cctctgcact actcagagcg tcatggctgg ggctacttgg tgcctgggcg gcgggacaac     2160

ctggccaagc tgccgacagg taccaccctg gagtcagctg gggtggtctg cccctacaga     2220

gccatcgagt ccctgtacag gaagcactgt ctcgaacagg ggaagcagca gctgatgccc     2280

caggaggccg gcctggcgga ggagttcctg ctcactgaca atagtgccat atggcaaacg     2340

gtagaagaac tggattactt agaagtggag gctgaggcca agatggagaa cttgcgagct     2400

gcagtgccag gtcaacccct agctctgact gcccgtggtg gccccaagga cacccagccc     2460

agctatcacc atggcaatgg accttacaac gacgtggaca tccctggctg ctggtttttc     2520

aagctgcctc acaaggatgg taatagctgt aatgtgggaa gcccctttgc caaggacttc     2580

ctgcccaaga tggaggatgg caccctgcag gctggcccag gaggtgccag tgggccccgt     2640

gctctggaaa tcaacaaaat gatttctttc tggaggaacg cccataaacg tatcagctcc     2700

cagatggtgg tgtggctgcc caggtcagct ctgccccgtg ctgtgatcag gcaccccgac     2760

tatgatgagg aaggcctcta tggggccatc ctgccccaag tggtgactgc cggcaccatc     2820

actcgccggg ctgtggagcc cacatggctc accgccagca atgcccggcc tgaccgagta     2880

ggcagtgagt tgaaagccat ggtgcaggcc ccacctggct acacccttgt gggtgctgat     2940

gtggactccc aagagctgtg gattgcagct gtgcttggag acgcccactt tgccggcatg     3000

catggctgca cagcctttgg gtggatgaca ctgcagggca ggaagagcag gggcactgat     3060

ctacacagta agacagccac tactgtgggc atcagccgtg agcatgccaa aatcttcaac     3120

tacggccgca tctatggtgc tgggcagccc tttgctgagc gcttactaat gcagtttaac     3180

caccggctca cacagcagga ggcagctgag aaggcccagc agatgtacgc tgccaccaag     3240

ggcctccgct ggtatcggct gtcggatgag ggcgagtggc tggtgaggga gttgaacctc     3300

ccagtggaca ggactgaggg tggctggatt tccctgcagg atctgcgcaa ggtccagaga     3360

gaaactgcaa ggaagtcaca gtggaagaag tgggaggtgg ttgctgaacg ggcatggaag     3420

gggggcacag agtcagaaat gttcaataag cttgagagca ttgctacgtc tgacatacca     3480

cgtaccccgg tgctgggctg ctgcatcagc cgagccctgg agccctcggc tgtccaggaa     3540

gagtttatga ccagccgtgt gaattgggtg gtacagagct ctgctgttga ctacttacac     3600

ctcatgcttg tggccatgaa gtggctgttt gaagagtttg ccatagatgg gcgcttctgc     3660

atcagcatcc atgacgaggt tcgctacctg gtgcgggagg aggaccgcta ccgcgctgcc     3720

ctggccttgc agatcaccaa cctcttgacc aggtgcatgt ttgcctacaa gctgggtctg     3780

aatgacttgc cccagtcagt cgcctttttc agtgcagtcg atattgaccg gtgcctcagg     3840

aaggaagtga ccatggattg taaaacccct tccaacccaa ctgggatgga aaggagatac     3900

gggattcccc agggtgaagc gctggatatt taccagataa ttgaactcac caaaggctcc     3960

ttggaaaaac gaagccagcc tggaccatag cactgcctgg aggctctgta tttgctcccg     4020

tggagcttca tcggggtggt gcaggctccc aaactcaggc tttcagctgt gctttttgca     4080

aaagggcttg cctaaggcca gccatttttc agtagcagga cctgccaaga agattccttc     4140

taactgaagg tgcagttgaa ttcagtgggt tcagaaccaa gatgccaaca tcggtgtgga     4200

ctacaggaca aggggcattg ttgcttgttg ggtaaaaatg aagcagaagc cccaaagttc     4260

acattaactc aggcatttca tttatttttt ccttttcttc ttggctggtt ctttgttctg     4320

tcccccatgc tctgatgcag tgccctagaa ggggaaagaa ttaatgctct aacgtgataa     4380

acctgctcca aggcagtgga aataaaaaga aggaaaaaaa agactctatc ttctcaaaaa     4440

aaaaaaaaaa aa                                                         4452


<210>  3
<211>  485
<212>  PRT
<213>  Homo sapiens


<220>
<221>  MISC_FEATURE
<223>  POLG2 protein (access number NP_009146.2)

<400>  3

Met Arg Ser Arg Val Ala Val Arg Ala Cys His Lys Val Cys Arg Cys 
1               5                   10                  15      


Leu Leu Ser Gly Phe Gly Gly Arg Val Asp Ala Gly Gln Pro Glu Leu 
            20                  25                  30          


Leu Thr Glu Arg Ser Ser Pro Lys Gly Gly His Val Lys Ser His Ala 
        35                  40                  45              


Glu Leu Glu Gly Asn Gly Glu His Pro Glu Ala Pro Gly Ser Gly Glu 
    50                  55                  60                  


Gly Ser Glu Ala Leu Leu Glu Ile Cys Gln Arg Arg His Phe Leu Ser 
65                  70                  75                  80  


Gly Ser Lys Gln Gln Leu Ser Arg Asp Ser Leu Leu Ser Gly Cys His 
                85                  90                  95      


Pro Gly Phe Gly Pro Leu Gly Val Glu Leu Arg Lys Asn Leu Ala Ala 
            100                 105                 110         


Glu Trp Trp Thr Ser Val Val Val Phe Arg Glu Gln Val Phe Pro Val 
        115                 120                 125             


Asp Ala Leu His His Lys Pro Gly Pro Leu Leu Pro Gly Asp Ser Ala 
    130                 135                 140                 


Phe Arg Leu Val Ser Ala Glu Thr Leu Arg Glu Ile Leu Gln Asp Lys 
145                 150                 155                 160 


Glu Leu Ser Lys Glu Gln Leu Val Ala Phe Leu Glu Asn Val Leu Lys 
                165                 170                 175     


Thr Ser Gly Lys Leu Arg Glu Asn Leu Leu His Gly Ala Leu Glu His 
            180                 185                 190         


Tyr Val Asn Cys Leu Asp Leu Val Asn Lys Arg Leu Pro Tyr Gly Leu 
        195                 200                 205             


Ala Gln Ile Gly Val Cys Phe His Pro Val Phe Asp Thr Lys Gln Ile 
    210                 215                 220                 


Arg Asn Gly Val Lys Ser Ile Gly Glu Lys Thr Glu Ala Ser Leu Val 
225                 230                 235                 240 


Trp Phe Thr Pro Pro Arg Thr Ser Asn Gln Trp Leu Asp Phe Trp Leu 
                245                 250                 255     


Arg His Arg Leu Gln Trp Trp Arg Lys Phe Ala Met Ser Pro Ser Asn 
            260                 265                 270         


Phe Ser Ser Ser Asp Cys Gln Asp Glu Glu Gly Arg Lys Gly Asn Lys 
        275                 280                 285             


Leu Tyr Tyr Asn Phe Pro Trp Gly Lys Glu Leu Ile Glu Thr Leu Trp 
    290                 295                 300                 


Asn Leu Gly Asp His Glu Leu Leu His Met Tyr Pro Gly Asn Val Ser 
305                 310                 315                 320 


Lys Leu His Gly Arg Asp Gly Arg Lys Asn Val Val Pro Cys Val Leu 
                325                 330                 335     


Ser Val Asn Gly Asp Leu Asp Arg Gly Met Leu Ala Tyr Leu Tyr Asp 
            340                 345                 350         


Ser Phe Gln Leu Thr Glu Asn Ser Phe Thr Arg Lys Lys Asn Leu His 
        355                 360                 365             


Arg Lys Val Leu Lys Leu His Pro Cys Leu Ala Pro Ile Lys Val Ala 
    370                 375                 380                 


Leu Asp Val Gly Arg Gly Pro Thr Leu Glu Leu Arg Gln Val Cys Gln 
385                 390                 395                 400 


Gly Leu Phe Asn Glu Leu Leu Glu Asn Gly Ile Ser Val Trp Pro Gly 
                405                 410                 415     


Tyr Leu Glu Thr Met Gln Ser Ser Leu Glu Gln Leu Tyr Ser Lys Tyr 
            420                 425                 430         


Asp Glu Met Ser Ile Leu Phe Thr Val Leu Val Thr Glu Thr Thr Leu 
        435                 440                 445             


Glu Asn Gly Leu Ile His Leu Arg Ser Arg Asp Thr Thr Met Lys Glu 
    450                 455                 460                 


Met Met His Ile Ser Lys Leu Lys Asp Phe Leu Ile Lys Tyr Ile Ser 
465                 470                 475                 480 


Ser Ala Lys Asn Val 
                485 


<210>  4
<211>  1607
<212>  DNA
<213>  Homo sapiens


<220>
<221>  source
<222>  (1)..(1607)
<223>  POLG2 DNA sequence

<400>  4
gcctgcgccg tggcctctcc ggattctgtt aacggtagtg gtggcttgtt gggatccgtt       60

gagtgatggg agagtgtgct ctttaacttc ggagagagat gcgctctcgt gtagccgtca      120

gggcctgcca taaggtctgc aggtgcctgt tgtctgggtt tgggggtcga gtagatgcgg      180

ggcagccgga gctgttgacg gaaaggagta gccccaaagg agggcatgtg aagtcgcacg      240

cggagctcga ggggaacggc gagcacccag aagcccccgg gtctggagag ggaagcgagg      300

cgctgttaga gatctgtcag agaaggcatt tcctaagtgg aagcaagcag cagcttagcc      360

gggattctct tctgagtggg tgccaccccg gcttcggacc cttgggcgta gagttgcgga      420

agaacctggc cgcagaatgg tggacctcgg tggtggtgtt cagggagcag gtattcccgg      480

tggacgccct ccaccacaaa ccaggccctt tgctacccgg ggacagtgcc ttcaggttag      540

tttctgcaga aactctacgc gaaatcttgc aagacaaaga gctgagtaag gaacagctag      600

tagcatttct tgagaacgta ttaaaaactt ctgggaaact acgggagaac cttcttcacg      660

gtgccttgga acactatgtt aattgcctgg atctggtaaa caagaggcta ccttatggcc      720

ttgctcagat tggagtgtgt tttcatcctg tttttgacac taagcagata cgaaatggtg      780

ttaaaagtat tggtgagaag actgaagctt cgttagtatg gtttactcct ccgagaactt      840

caaaccagtg gcttgatttc tggttacgtc atcgactcca gtggtggaga aagtttgcca      900

tgagtccatc taacttcagc agcagtgact gtcaggatga agaaggccgg aaaggaaaca      960

aactttacta caattttccc tggggaaagg agttaataga aaccctgtgg aacctaggag     1020

atcacgaact tttacacatg tatcctggca atgtgtctaa attacatggc cgagatggac     1080

gaaaaaatgt ggttccttgt gttctctctg taaatgggga cctagaccga ggcatgctgg     1140

cctacctcta tgattctttc cagctgacag agaactcctt tacaagaaag aaaaatcttc     1200

atagaaaggt acttaaactt cacccttgtt tagcccctat taaggttgct ttggatgtag     1260

gaagaggccc cacattggaa ctaagacagg tttgtcaagg gctatttaat gagttactag     1320

aaaatgggat ttctgtgtgg cctggttatt tggaaactat gcagtcctca ttggaacaac     1380

tttattcgaa gtatgatgaa atgagtattc tcttcacagt tttggttact gaaactactt     1440

tggagaatgg attaatacat ctgagaagca gagacaccac aatgaaggaa atgatgcata     1500

tatccaaatt aaaagacttt ttgattaagt atatatcatc agctaagaat gtatagattt     1560

ttatatttgt ataataaata ttcttctctc ctaaaaaaaa aaaaaaa                   1607


<210>  5
<211>  453
<212>  PRT
<213>  Homo sapiens


<220>
<221>  MISC_FEATURE
<223>  HTRA3 protein (access number NP_444272.1)

<400>  5

Met Gln Ala Arg Ala Leu Leu Leu Ala Ala Leu Ala Ala Leu Ala Leu 
1               5                   10                  15      


Ala Arg Glu Pro Pro Ala Ala Pro Cys Pro Ala Arg Cys Asp Val Ser 
            20                  25                  30          


Arg Cys Pro Ser Pro Arg Cys Pro Gly Gly Tyr Val Pro Asp Leu Cys 
        35                  40                  45              


Asn Cys Cys Leu Val Cys Ala Ala Ser Glu Gly Glu Pro Cys Gly Gly 
    50                  55                  60                  


Pro Leu Asp Ser Pro Cys Gly Glu Ser Leu Glu Cys Val Arg Gly Leu 
65                  70                  75                  80  


Cys Arg Cys Arg Trp Ser His Ala Val Cys Gly Thr Asp Gly His Thr 
                85                  90                  95      


Tyr Ala Asn Val Cys Ala Leu Gln Ala Ala Ser Arg Arg Ala Leu Gln 
            100                 105                 110         


Leu Ser Gly Thr Pro Val Arg Gln Leu Gln Lys Gly Ala Cys Pro Leu 
        115                 120                 125             


Gly Leu His Gln Leu Ser Ser Pro Arg Tyr Lys Phe Asn Phe Ile Ala 
    130                 135                 140                 


Asp Val Val Glu Lys Ile Ala Pro Ala Val Val His Ile Glu Leu Phe 
145                 150                 155                 160 


Leu Arg His Pro Leu Phe Gly Arg Asn Val Pro Leu Ser Ser Gly Ser 
                165                 170                 175     


Gly Phe Ile Met Ser Glu Ala Gly Leu Ile Ile Thr Asn Ala His Val 
            180                 185                 190         


Val Ser Ser Asn Ser Ala Ala Pro Gly Arg Gln Gln Leu Lys Val Gln 
        195                 200                 205             


Leu Gln Asn Gly Asp Ser Tyr Glu Ala Thr Ile Lys Asp Ile Asp Lys 
    210                 215                 220                 


Lys Ser Asp Ile Ala Thr Ile Lys Ile His Pro Lys Lys Lys Leu Pro 
225                 230                 235                 240 


Val Leu Leu Leu Gly His Ser Ala Asp Leu Arg Pro Gly Glu Phe Val 
                245                 250                 255     


Val Ala Ile Gly Ser Pro Phe Ala Leu Gln Asn Thr Val Thr Thr Gly 
            260                 265                 270         


Ile Val Ser Thr Ala Gln Arg Glu Gly Arg Glu Leu Gly Leu Arg Asp 
        275                 280                 285             


Ser Asp Met Asp Tyr Ile Gln Thr Asp Ala Ile Ile Asn Tyr Gly Asn 
    290                 295                 300                 


Ser Gly Gly Pro Leu Val Asn Leu Asp Gly Glu Val Ile Gly Ile Asn 
305                 310                 315                 320 


Thr Leu Lys Val Thr Ala Gly Ile Ser Phe Ala Ile Pro Ser Asp Arg 
                325                 330                 335     


Ile Thr Arg Phe Leu Thr Glu Phe Gln Asp Lys Gln Ile Lys Asp Trp 
            340                 345                 350         


Lys Lys Arg Phe Ile Gly Ile Arg Met Arg Thr Ile Thr Pro Ser Leu 
        355                 360                 365             


Val Asp Glu Leu Lys Ala Ser Asn Pro Asp Phe Pro Glu Val Ser Ser 
    370                 375                 380                 


Gly Ile Tyr Val Gln Glu Val Ala Pro Asn Ser Pro Ser Gln Arg Gly 
385                 390                 395                 400 


Gly Ile Gln Asp Gly Asp Ile Ile Val Lys Val Asn Gly Arg Pro Leu 
                405                 410                 415     


Val Asp Ser Ser Glu Leu Gln Glu Ala Val Leu Thr Glu Ser Pro Leu 
            420                 425                 430         


Leu Leu Glu Val Arg Arg Gly Asn Asp Asp Leu Leu Phe Ser Ile Ala 
        435                 440                 445             


Pro Glu Val Val Met 
    450             


<210>  6
<211>  2589
<212>  DNA
<213>  Homo sapiens


<220>
<221>  source
<222>  (1)..(2589)
<223>  HTRA3 DNA sequence

<400>  6
ggagggagct ggtccctgcg ctccctgcgc cctggggatg cccctgccgc cctgacgccc       60

gccagcctga gccaccggcg catgtgaccg cgcgtccgcc ccagtcccat ccgtaggcgc      120

ccggcgcccg gccccgcagc ggcctcgttg tccccgccgg cccccgcccg gtctcccgcg      180

ctgccacccg ccgccggccc tgccgccatg caggcgcgag cgctgctcct ggccgcgttg      240

gccgcgctgg cgctggcccg ggagccccct gcggcgccgt gtcccgcgcg ctgcgacgtg      300

tcgcggtgtc ccagcccccg ctgccccggc ggctacgtgc ccgacctctg caactgctgc      360

ctggtgtgcg ccgccagcga gggcgagccc tgtggcggcc ctctggactc gccttgcggc      420

gagagcctgg agtgcgtgcg cggcctatgc cgctgccgct ggtcgcacgc cgtgtgtggc      480

accgacgggc acacctatgc caacgtgtgc gcgctgcagg cggccagccg ccgcgcgctg      540

cagctctccg ggacgcccgt gcgccagctg cagaagggcg cctgcccgtt gggtctccac      600

cagctgagca gcccgcgcta caagttcaac ttcattgctg acgtggtgga gaagatcgca      660

ccagccgtgg tccacataga gctcttcctg agacacccgc tgtttggccg caacgtgccc      720

ctgtccagcg gttctggctt catcatgtca gaggccggcc tgatcatcac caatgcccac      780

gtggtgtcca gcaacagtgc tgccccgggc aggcagcagc tcaaggtgca gctacagaat      840

ggggactcct atgaggccac catcaaagac atcgacaaga agtcggacat tgccaccatc      900

aagatccatc ccaagaaaaa gctccctgtg ttgttgctgg gtcactcggc cgacctgcgg      960

cctggggagt ttgtggtggc catcggcagt cccttcgccc tacagaacac agtgacaacg     1020

ggcatcgtca gcactgccca gcgggagggc agggagctgg gcctccggga ctccgacatg     1080

gactacatcc agacggatgc catcatcaac tacgggaact ccgggggacc actggtgaac     1140

ctggatggcg aggtcattgg catcaacacg ctcaaggtca cggctggcat ctcctttgcc     1200

atcccctcag accgcatcac acggttcctc acagagttcc aagacaagca gatcaaagac     1260

tggaagaagc gcttcatcgg catacggatg cggacgatca caccaagcct ggtggatgag     1320

ctgaaggcca gcaacccgga cttcccagag gtcagcagtg gaatttatgt gcaagaggtt     1380

gcgccgaatt caccttctca gagaggcggc atccaagatg gtgacatcat cgtcaaggtc     1440

aacgggcgtc ctctagtgga ctcgagtgag ctgcaggagg ccgtgctgac cgagtctcct     1500

ctcctactgg aggtgcggcg ggggaacgac gacctcctct tcagcatcgc acctgaggtg     1560

gtcatgtgag gggcgcattc ctccagcgcc aagcgtcaga gcctgcagac aacggagggc     1620

agcgcccccc cgagatcagg acgaaggacc accgtcggtc ctcagcaggg cggcagcctc     1680

ctcctggctg tccggggcag agcggaggct gggcttggcc aggggcccga atttccgcct     1740

ggggagtgtt ggatccacat cccggtgccg gggagggaag cccaacatcc ccttgtacag     1800

atgatcctga aagtcacttc caagttctcc ggatattcac aaaactgcct tccatggagg     1860

tcccctcctc tcctagcttc ccgcctctgc ccctgtgaac acccatctgc agtatcccct     1920

gctcctgccc ctcctactgc aggtctgggc tgccaagctt cttcccccct gacaaacgcc     1980

cacctgacct gaggccccag cttccctctg ccctaggact taccaagctg tagggccagg     2040

gctgctgcct gccagcctgg ggtccctgga ggacaggtca catctgatcc ctttggggtg     2100

cgggggtggg gtccagccca gagcaggcac tgagtgaatg ccccctggct gcggagctga     2160

gccccgccct gccatgaggt tttcctcccc aggcaggcag gaggccgcgg ggagcacgtg     2220

gaaagttggc tgctgcctgg ggaagcttct cctccccaag gcggccatgg ggcagcctgc     2280

agaggacagt ggacgtggag ctgcggggtg tgaggactga gccggcttcc ccttcccacg     2340

cagctctggg atgcagcagc cgctcgcatg gaagtgccgc ccagaggcat gcaggctgct     2400

gggcaccacc ccctcatcca gggaacgagt gtgtctcaag gggcatttgt gagctttgct     2460

gtaaatggat tcccagtgtt gcttgtactg tatgtttctc tactgtatgg aaaataaagt     2520

ttacaagcac acggttctca gccaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa     2580

aaaaaaaaa                                                             2589


<210>  7
<211>  458
<212>  PRT
<213>  Homo sapiens


<220>
<221>  MISC_FEATURE
<223>  HTRA2 PROTEIN (access number NP_037379.1)

<400>  7

Met Ala Ala Pro Arg Ala Gly Arg Gly Ala Gly Trp Ser Leu Arg Ala 
1               5                   10                  15      


Trp Arg Ala Leu Gly Gly Ile Arg Trp Gly Arg Arg Pro Arg Leu Thr 
            20                  25                  30          


Pro Asp Leu Arg Ala Leu Leu Thr Ser Gly Thr Ser Asp Pro Arg Ala 
        35                  40                  45              


Arg Val Thr Tyr Gly Thr Pro Ser Leu Trp Ala Arg Leu Ser Val Gly 
    50                  55                  60                  


Val Thr Glu Pro Arg Ala Cys Leu Thr Ser Gly Thr Pro Gly Pro Arg 
65                  70                  75                  80  


Ala Gln Leu Thr Ala Val Thr Pro Asp Thr Arg Thr Arg Glu Ala Ser 
                85                  90                  95      


Glu Asn Ser Gly Thr Arg Ser Arg Ala Trp Leu Ala Val Ala Leu Gly 
            100                 105                 110         


Ala Gly Gly Ala Val Leu Leu Leu Leu Trp Gly Gly Gly Arg Gly Pro 
        115                 120                 125             


Pro Ala Val Leu Ala Ala Val Pro Ser Pro Pro Pro Ala Ser Pro Arg 
    130                 135                 140                 


Ser Gln Tyr Asn Phe Ile Ala Asp Val Val Glu Lys Thr Ala Pro Ala 
145                 150                 155                 160 


Val Val Tyr Ile Glu Ile Leu Asp Arg His Pro Phe Leu Gly Arg Glu 
                165                 170                 175     


Val Pro Ile Ser Asn Gly Ser Gly Phe Val Val Ala Ala Asp Gly Leu 
            180                 185                 190         


Ile Val Thr Asn Ala His Val Val Ala Asp Arg Arg Arg Val Arg Val 
        195                 200                 205             


Arg Leu Leu Ser Gly Asp Thr Tyr Glu Ala Val Val Thr Ala Val Asp 
    210                 215                 220                 


Pro Val Ala Asp Ile Ala Thr Leu Arg Ile Gln Thr Lys Glu Pro Leu 
225                 230                 235                 240 


Pro Thr Leu Pro Leu Gly Arg Ser Ala Asp Val Arg Gln Gly Glu Phe 
                245                 250                 255     


Val Val Ala Met Gly Ser Pro Phe Ala Leu Gln Asn Thr Ile Thr Ser 
            260                 265                 270         


Gly Ile Val Ser Ser Ala Gln Arg Pro Ala Arg Asp Leu Gly Leu Pro 
        275                 280                 285             


Gln Thr Asn Val Glu Tyr Ile Gln Thr Asp Ala Ala Ile Asp Phe Gly 
    290                 295                 300                 


Asn Ser Gly Gly Pro Leu Val Asn Leu Asp Gly Glu Val Ile Gly Val 
305                 310                 315                 320 


Asn Thr Met Lys Val Thr Ala Gly Ile Ser Phe Ala Ile Pro Ser Asp 
                325                 330                 335     


Arg Leu Arg Glu Phe Leu His Arg Gly Glu Lys Lys Asn Ser Ser Ser 
            340                 345                 350         


Gly Ile Ser Gly Ser Gln Arg Arg Tyr Ile Gly Val Met Met Leu Thr 
        355                 360                 365             


Leu Ser Pro Ser Ile Leu Ala Glu Leu Gln Leu Arg Glu Pro Ser Phe 
    370                 375                 380                 


Pro Asp Val Gln His Gly Val Leu Ile His Lys Val Ile Leu Gly Ser 
385                 390                 395                 400 


Pro Ala His Arg Ala Gly Leu Arg Pro Gly Asp Val Ile Leu Ala Ile 
                405                 410                 415     


Gly Glu Gln Met Val Gln Asn Ala Glu Asp Val Tyr Glu Ala Val Arg 
            420                 425                 430         


Thr Gln Ser Gln Leu Ala Val Gln Ile Arg Arg Gly Arg Glu Thr Leu 
        435                 440                 445             


Thr Leu Tyr Val Thr Pro Glu Val Thr Glu 
    450                 455             


<210>  8
<211>  2550
<212>  DNA
<213>  Homo sapiens


<220>
<221>  source
<222>  (1)..(2550)
<223>  HTRA2 DNA sequence

<400>  8
cgtggatccc gagaaagagg cgcaggacga ggaggcagaa cccgactggc gcgtagagca       60

gcagcacgag cagtaggaag cagtcacccg gaagcctggg ggcgagaggc gaagtggtca      120

ggcgccgaag gccgagagca cgcggggatc ggtctcttcc cgccgggtct cttaccggtg      180

cgagtcaaag agccgctccg gccccggccc tgagggaagc tccataactg ctgcttcagg      240

agcgcccggc cgtcgccgcc gccgccattt tcgcgcccgg ccgcaggggc tcttgggaag      300

gcggagtctt tgggcatccg cccggggtga ggggacccga agtcctgagg cgcgccggaa      360

gggctagcgg tcccagcata ccccgcggcc ccttgggccg tctcacaact cgcgtccggc      420

ggagaccaca attcccggca ttcgtggggc agggaggagt cggcctcccg gaatcctggt      480

cccggcgtgc acttctgaag gacttcaggt accggcgtgc cccgcgtcct actgtccgcc      540

tgctcgcgtc ctgggtgccg cctctgagta gggcgggcga ggaggcagcc aaggcggagc      600

tgatggctgc gccgagggcg gggcggggtg caggctggag ccttcgggca tggcgggctt      660

tggggggcat tcgctggggg aggagacccc gtttgacccc tgacctccgg gccctgctga      720

cgtcaggaac ttctgacccc cgggcccgag tgacttatgg gacccccagt ctctgggccc      780

ggttgtctgt tggggtcact gaaccccgag catgcctgac gtctgggacc ccgggtcccc      840

gggcacaact gactgcggtg accccagata ccaggacccg ggaggcctca gagaactctg      900

gaacccgttc gcgcgcgtgg ctggcggtgg cgctgggcgc tgggggggca gtgctgttgt      960

tgttgtgggg cgggggtcgg ggtcctccgg ccgtcctcgc cgccgtccct agcccgccgc     1020

ccgcttctcc ccggagtcag tacaacttca tcgcagatgt ggtggagaag acagcacctg     1080

ccgtggtcta tatcgagatc ctggaccggc accctttctt gggccgcgag gtccctatct     1140

cgaacggctc aggattcgtg gtggctgccg atgggctcat tgtcaccaac gcccatgtgg     1200

tggctgatcg gcgcagagtc cgtgtgagac tgctaagcgg cgacacgtat gaggccgtgg     1260

tcacagctgt ggatcccgtg gcagacatcg caacgctgag gattcagact aaggagcctc     1320

tccccacgct gcctctggga cgctcagctg atgtccggca aggggagttt gttgttgcca     1380

tgggaagtcc ctttgcactg cagaacacga tcacatccgg cattgttagc tctgctcagc     1440

gtccagccag agacctggga ctcccccaaa ccaatgtgga atacattcaa actgatgcag     1500

ctattgattt tggaaactct ggaggtcccc tggttaacct ggatggggag gtgattggag     1560

tgaacaccat gaaggtcaca gctggaatct cctttgccat cccttctgat cgtcttcgag     1620

agtttctgca tcgtggggaa aagaagaatt cctcctccgg aatcagtggg tcccagcggc     1680

gctacattgg ggtgatgatg ctgaccctga gtcccagcat ccttgctgaa ctacagcttc     1740

gagaaccaag ctttcccgat gttcagcatg gtgtactcat ccataaagtc atcctgggct     1800

cccctgcaca ccgggctggt ctgcggcctg gtgatgtgat tttggccatt ggggagcaga     1860

tggtacaaaa tgctgaagat gtttatgaag ctgttcgaac ccaatcccag ttggcagtgc     1920

agatccggcg gggacgagaa acactgacct tatatgtgac ccctgaggtc acagaatgaa     1980

tagatcacca agagtatgag gctcctgctc tgatttcctc cttgcctttc tggctgaggt     2040

tctgagggca ccgagacaga gggttaaatg aaccagtggg ggcaggtccc tccaaccacc     2100

agcactgact cctgggctct gaagaatcac agaaacactt tttatataaa ataaaattat     2160

acctagcaac atattatagt aaaaaatgag gtgggagggc tggatctttt cccccaccaa     2220

aaggctagag gtaaagctgt atccccctaa acttagggga gatactggag ctgaccatcc     2280

tgacctccta ttaaagaaaa tgagctgctg ccatcttttg tgggcagtta gtcaggtgct     2340

gctctttgtg gtgtggtggg ctctggtctg ttctgctcgg tgctgggcct gggagcaaag     2400

attcccatgc ttggctacag atactgacag ctggcctctg aaggagggtg aaaacttctg     2460

cttgacagtt ccacatccat agtgcatggt ctgatgagtg cggttgctga catgggtttc     2520

ttggtaagct cctgaggtaa tggcagcctc                                      2550


<210>  9
<211>  20
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  POLG forward primer

<400>  9
gagaaggccc agcagatgta                                                   20


<210>  10
<211>  18
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  POLG reverse primer

<400>  10
atccgacagc cgatacca                                                     18


<210>  11
<211>  20
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  POLG2 forward primer

<400>  11
gagctgttga cggaaaggag                                                   20


<210>  12
<211>  20
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  POLG2 reverse primer

<400>  12
gttcttccgc aactctacgc                                                   20


<210>  13
<211>  20
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Long HTRA3 reverse primer

<400>  13
atgcggacga tcacaccaag                                                   20


<210>  14
<211>  19
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Long HTRA3 reverse primer

<400>  14
cgctgccctc cgttgtctg                                                    19


<210>  15
<211>  20
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Short HTRA3 forward primer

<400>  15
gagggctggt cacatgaaga                                                   20


<210>  16
<211>  18
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Short HTRA3 reverse primer

<400>  16
gctccgctaa tttccagt                                                     18


<210>  17
<211>  20
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  HTRA2 forward primer

<400>  17
tttgccatcc cttctgatcg                                                   20


<210>  18
<211>  20
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  HTRA2 reverse primer

<400>  18
acaccatgct gaacatcggg                                                   20


