CN101481741B - 一种新的突变的pah基因 - Google Patents
一种新的突变的pah基因 Download PDFInfo
- Publication number
- CN101481741B CN101481741B CN 200910046100 CN200910046100A CN101481741B CN 101481741 B CN101481741 B CN 101481741B CN 200910046100 CN200910046100 CN 200910046100 CN 200910046100 A CN200910046100 A CN 200910046100A CN 101481741 B CN101481741 B CN 101481741B
- Authority
- CN
- China
- Prior art keywords
- leu
- glu
- lys
- ala
- ile
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
Landscapes
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
Abstract
一种生物技术领域的PAH基因13种新突变的检测方法,步骤如下:步骤一,以GenBank数据库中PAH基因第4或5或6或7或10或11或12号外显子以及外显子与内含子接合部位序列为模板设计一对等位基因特异性的核酸引物,利用引物对来扩增PAH基因相应外显子的DNA序列,对扩增产物进行分离纯化,得到相应分离核酸;步骤二,对分离核酸的PAH基因外显子的核苷酸进行是否存在突变检测。本发明为进一步开发PKU基因突变种类及其频率的分子遗传技术提供了依据,具有重要的实用价值。
Description
技术领域
本发明涉及一种生物技术领域的基因突变检测方法,具体是一种PAH(苯丙氨酸羟化酶)基因13种新突变的检测方法。
背景技术
苯酮尿症(phenylketonuria,PKU)是一种可以造成儿童不同程度智力损害的常见的先代谢性疾病,属于常染色体隐性遗传,OMIM编号为261600。PKU的主要致病基因是PAH基因,1983年该基因被定位在2q22-24。随着PAH基因突变分子的不断深入研究,至2007年7月为止,http://www.pahdb.mcgill.ca/(国际PAH数据库)共记载513种突变。PAH基因定位于染色体12q24.1,大约由1.5Mb碱基组成。PAH基因的编码区包含13个外显子,被不编码的12个内含子分隔。转录剪接后形成长1353bp的mRNA,后者经翻译,形成含451个氨基酸的酶单体,单体聚会成有功能的PAH酶。我国自80年代初以来对PKU开展了系统研究,随着分子生物学技术的发展,至今已发现90余种突变,并不断有新突变发现。
经对现有文献的检索,未发现与PAH基因13种新突变的检测方法主题有关的报道。
发明内容
本发明的目的在于克服现有技术中的不足,提供一种PAH基因13种新突变的检测方法。本发明为进一步开发PKU基因突变种类及其频率的分子遗传技术提供了依据,具有实用价值。
本发明是通过以下技术方案实现的:
本发明包括步骤如下:
步骤一,以GenBank数据库中PAH基因第4或5或6或7或10或11或12号外显子以及外显子与内含子接合部位序列为模板设计一对等位基因特异性的核酸引物,利用引物对来扩增PAH基因相应外显子的DNA序列,对扩增产物进行 分离纯化,得到相应分离核酸;
步骤二,对分离核酸的PAH基因外显子的核苷酸进行是否存在突变结果的检测。
步骤一中,所述的特异性的核酸引物具体为:长度为15bp-25bp,且能特异性地杂交并扩增出含PAH基因外显子以及相应外显子与内含子接合部位的序列。
步骤一中,所述分离纯化具体为:在基因组DNA水平上,利用引物来扩增每个突变位点的基因序列和利用纯化试剂盒对扩增产物进行提纯。
步骤一中,所述分离核酸具体为:
当外显子为第4号时,该核酸具有序列表SEQ ID NO.3所示的序列;
当外显子为第5号时,该核酸具有序列表SEQ ID NO.4或SEQ ID NO.5所示的序列;
当外显子为第6号时,该核酸具有序列表SEQID NO.6或SEQID NO.7或SEQ ID NO.8所示的序列;
当外显子为第7号时,该核酸具有序列表SEQ ID NO.9或SEQ ID NO.10所示的序列;
当外显子为第10号时,该核酸具有序列表SEQ ID NO.11所示的序列;
当外显子为第11号时,该核酸具有序列表SEQ ID NO.12或SEQ ID NO.13或SEQ ID NO.14所示的序列;
当外显子为第12号时,该核酸具有序列表SEQ ID NO.15所示的序列。
步骤二中,所述检测,其方法包括:DNA测序法、杂交测序法、酶促错配切割法、异源双链分析法、点杂交法、寡核苷酸阵列法、微测序法、Taqman技术、分子信标法、变性高效液相色谱法的一种或者几种。
步骤二中,所述突变结果的检测是指:
当为第4号外显子时,检测SEQ ID NO.1所示序列的第361位核苷酸是否存在突变,即T→C;
当为第5号外显子时,检测SEQ ID NO.1所示序列的第461位核苷酸是否存在突变,即A→G;或检测SEQ ID NO.1所示序列的第466位核苷酸是否存在突变,即G→C;
当为第6号外显子时,检测SEQ ID NO.1所示序列的第548位核苷酸是否 存在突变,即A→G;或检测SEQ ID NO.1所示序列的第680位核苷酸是否存在突变,即T→A;或检测SEQ ID NO.1所示序列的第682位核苷酸是否存在突变,即G→T;
当为第7号外显子时,检测SEQ ID NO.1所示序列的第808位核苷酸是否存在突变,即A→G;或检测SEQ ID NO.1所示序列的第823位核苷酸是否存在突变,即C→G;
当为第10号外显子时,检测SEQ ID NO.1所示序列的第971位核苷酸是否存在突变,即T→A;
当为第11号外显子时,检测SEQ ID NO.1所示序列的第1070位核苷酸是否存在突变,即G→A;或检测SEQ ID NO.1所示序列的第1071位核苷酸是否存在突变,即C→A;或检测SEQ ID NO.1所示序列的第1085位核苷酸是否存在突变,即C→T;
当为第12号外显子时,检测SEQ ID NO.1所示序列的第1242位核苷酸是否存在突变,即C→A。
本发明以GenBank数据库中PAH基因第4或5或6或7或10或11或12号外显子以及外显子与内含子接合部位序列为模板设计一对等位基因特异性的核酸引物,利用引物对来扩增PAH基因相应外显子的DNA序列,对扩增产物进行分离纯化,得到相应分离核酸;对分离核酸的PAH基因外显子的核苷酸进行检测,确定其是否存在突变。用于本发明的测试样品对于检测突变和单核苷酸多态性而言,可以从测试样品中抽提的DNA或mRNA。对于PAH酶活性而言,可以是任何含有PAH基因的样品。
本发明通过对PAH基因测序结果分析,发现13种不同的突变,经功能分析,此13种突变都是改变了原有的氨基酸序列,导致了氨基酸的置换,最终导致了PAH基因编码的苯丙氨酸羟化酶活性的改变,影响氨基酸的正常代谢。本发明为进一步开发PKU基因突变种类及其频率的分子遗传技术提供了依据,具有重要的实用价值。
具体实施方式
下面结合具体实施例,进一步阐述本发明。应理解,这些实施例仅用于说明本发明而不用于限制本发明的范围。下列实施例中未注明具体条件的实验方 法,通常照常规条件,例如分子克隆,实验室手册(New York:Cold Spring HarborLaboratory Press,1989)中所述的条件,或按照制造厂商所建议的条件。
实施例
步骤一,以GenBank数据库中PAH基因第4或5或6或7或10或11或12号外显子以及外显子与内含子接合部位序列为模板设计一对等位基因特异性的核酸引物,利用引物对来扩增PAH基因相应外显子的DNA序列,对扩增产物进行分离纯化,得到相应分离核酸
引物设计:
通过Primer5.0软件,以Genebank数据库PAH基因(NM_000277)第4、5、6、7、10、11、12号外显子以及相应外显子与内含子接合部位序列为模板设计7对等位基因特异性的核酸引物,由上海生工生物技术有限公司合成。PAH基因序列可由GeneBank数据库中取得,PAH基因序列如SEQ NO.1所示,PAH基因的外显子的基因组序列可从Genebank中获得。
引物信息:
扩增PAH基因的第4号外显子突变位点的DNA序列引物:
正向引物5’-AGAGAACATCTCCAGGAAAGA-3’
反向引物5’-CCCAGCCCTCGTGTAAATAG-3’;
扩增PAH基因的第5号外显子突变位点的DNA序列引物:
正向引物5’-AGGGTATAACCAAGGGAAGG-3’
反向引物5’-ATGAGGGCAAGGGAGAAGC-3’;
扩增PAH基因的第6号外显子突变位点的DNA序列引物:
正向引物5’-CCCCGACTCCCTCTGCTAA-3’
反向引物5’-CCTCTGCCTCAATCCTCCC-3’;
扩增PAH基因的第7号外显子突变位点的DNA序列引物:
正向引物5’-CTGCCTAGCGTCAAAGCC-3’
反向引物5’-ECAGCCAGCAATGAACCCAAA-3’;
扩增PAH基因的第10号外显子突变位点的DNA序列引物:
正向引物5’-AGGTATCCCTTCATCCAGTC-3’
反向引物5’-CCCACAGCCATCATCAAATC-3’;
扩增PAH基因的第11号外显子突变位点的DNA序列引物:
正向引物5’-ATTTGGGCTGTGATGTAGAAG-3’
反向引物5’-TTCAGTGTCTTGACTTGGTGG-3’
扩增PAH基因的第12号外显子突变位点的DNA序列引物:
正向引物5’-CTAGGGAGGTGTCCGTGTT-3’
反向引物5’-GGCGATGGTAGGGAAAGAC-3’;
第4、7、10、11、12号外显子PCR扩增条件为:
体系各项试剂除DNA外均由Bio-Asia公司提供
反应体系总体积为15μl,其中
ddH2O 8.8μl
10 X Buffer 1.5μl,其中聚合反应缓冲液包含KCl Tris-HCl溶液
DMSO 0.6μl
2mM dNTP 1.5μl
10pM正反向引物各0.9μl
5U Taq 0.3μl
DNA 10ng/0.5ul
第5、6号外显子PCR扩增条件为:
体系各项试剂除DNA外均由Bio-Asia公司提供
反应体系总体积为15μl,其中:
ddH2O 8.8μl
10 X Buffer 1.5μl,其中聚合反应缓冲液包含KCl Tris-HCl溶液
DMSO 0.6μl
2mM dNTP 1.5μl
10pM正反向引物各0.9μl
5U Taq 0.3μl
DNA 10ng/0.5ul
上述外显子PCR反应条件为:
94℃ 3mins;94℃ 30 seconds;64℃ 30 seconds,-0.5℃/CYCLE;72℃1min;14 times to 2;30×(94℃ 30 seconds;57℃ 30 seconds;72℃ 1min;)72℃ 10mins。
测序反应均作正反向,条件如下:
扩增产物酶纯化法:PCR产物2μl,加入2μl纯化酶系,酶系内含SAP(Shrimpalkaline phosphatase,碱性磷酸酶)0.15u和Exo-nuclease I(核酸外切酶I)0.75u/ul,37℃ 30mins,85℃ 20mins,4℃保存备用。
测序采用ABI公司的Prism BigDye terminator(BDT)cycle sequencingreaction kit试剂盒进行测序,测序总体积为5μl,其中纯化后的PCR产物4μl,BDT 0.5μl,正向或反向引物0.5μl。反应条件是94℃ 2mins,35 X(94℃ 30seconds,55℃ 40 seconds,60℃,1.5mins),4℃保存备用。
上样前纯化:5μl测序产物中加入25μl无水乙醇和3.0mol/L醋酸钠混合液(V∶V=25∶1),室温、避光、静置15min,4000rpm/min 45mins,700rpm/min5 seconds,弃上清;2X(75%Alcohol 25μl,4000rpm/min 10mins,700rpm/min5 seconds,弃上清);室温、避光、静置、风干20mins;上样8μl于3100测序仪进行测序。
步骤二,对分离核酸的PAH基因外显子的核苷酸进行是否存在突变结果的检测
对PAH基因进行直接测序,将测定的各样本序列与GeneBank数据库PAH基因序列(NM 000277)进行比较,PAH基因序列如SEQ NO.1所示,对应编码的氨基酸序列如SEQ ID NO.2所示。
对样本的测序结果标明,在PAH基因第4、5、6、7、10、11、12号外显子中发现13种新突变,频率均为0.05%,PAH基因的上述外显子的基因组序列可从Genebank中获得。经功能分析,13种突变都改变了原有的氨基酸序列,导致了氨基酸的置换,具体为:
(1)SEQ ID NO.1所示序列的第361位核苷酸发生突变,即T→C;此时,SEQ ID NO.1所示序列编码的氨基酸序列SEQ ID NO.2第121位由Phe(F)→Leu(L),具体序列如SEQ ID NO.16所示;
(2)SEQ ID NO.1所示序列的第461位核苷酸发生突变,即A→G;此时,SEQ ID NO.1所示序列编码的氨基酸序列SEQID NO.2第154位由Tyr(Y)→Cys(C);具体序列如SEQ ID NO.17所示;
(3)SEQ ID NO.1所示序列的第466位核苷酸发生突变,即G→C;此时, SEQ ID NO.1所示序列编码的氨基酸序列SEQ ID NO.2第156位由Ala(A)→Pro(P);具体序列如SEQ ID NO.18所示;
(4)SEQ ID NO.1所示序列的第548位核苷酸发生突变,即A→G;此时,SEQ ID NO.1所示序列编码的氨基酸序列SEQ ID NO.2第183位由Glu(E)→Gly(G);具体序列如SEQ ID NO.19所示;
(5)SEQ ID NO.1所示序列的第680位核苷酸发生突变,即T→A;此时,SEQ ID NO.1所示序列编码的氨基酸序列SEQ ID NO.2第227位由Leu(L)→Gln(Q);具体序列如SEQ ID NO.20所示;
(6)SEQ ID NO.1所示序列的第682位核苷酸发生突变,即G→T;此时,SEQ ID NO.1所示序列编码的氨基酸序列SEQ ID NO.2第270位由Arg(R)→Gly(G);具体序列如SEQ ID NO.21所示;
(7)SEQ ID NO.1所示序列的第808位核苷酸发生突变,即A→G;此时,SEQ ID NO.1所示序列编码的氨基酸序列SEQ ID NO.2第275位由Pro(P)→Ala(A);具体序列如SEQ ID NO.22所示;
(8)SEQ ID NO.1所示序列的第823位核苷酸发生突变,即C→G;此时,SEQ ID NO.1所示序列编码的氨基酸序列SEQ ID NO.2第324位由Ile(I)→Asn(N);具体序列如SEQ ID NO.23所示;
(9)SEQ ID NO.1所示序列的第971位核苷酸发生突变,即T→A;此时,SEQ ID NO.1所示序列编码的氨基酸序列SEQ ID NO.2第357位由Cys(C)→Tyr(Y);具体序列如SEQ ID NO.24所示;
(10)SEQ ID NO.1所示序列的第1070位核苷酸发生突变,即G→A;此时,SEQ ID NO.1所示序列编码的氨基酸序列SEQ ID NO.2第362位由Pro(P)→Thr(T);具体序列如SEQ ID NO.25所示;
(11)SEQ ID NO.1所示序列的第1071位核苷酸发生突变,即C→A;此时,SEQ ID NO.1所示序列编码的氨基酸序列SEQ ID NO.2第228位氨基酸由Glu(E)→终止(X);具体序列如SEQ ID NO.26所示;
(12)SEQ ID NO.1所示序列的第1085位核苷酸发生突变,即C→T;此时,SEQ ID NO.1所示序列编码的氨基酸序列SEQ ID NO.2第357位氨基酸由Cys(C)→终止(X);具体序列如SEQ ID NO.27所示;
(13)SEQ ID NO.1所示序列的第1242位核苷酸发生突变,即C→A;此时,SEQ ID NO.1所示序列编码的氨基酸序列SEQ ID NO.2第414位氨基酸由Tyr(Y)→终止(X);具体序列如SEQ ID NO.28所示。
最终这些突变都导致了PAH基因编码的苯丙氨酸羟化酶活性的改变,影响体内氨基酸的正常代谢。
序列表
<110>上海交通大学
<120>PAH基因13种新突变的检测方法
<160>28
<210>1
<211>1359
<212>DNA
<213>人(Homo sapiens)
<400>1
atgtccactg cggtcctgga aaacccaggc ttgggcagga aactctctga 50
ctttggacag gaaacaagct atattgaaga caactgcaat caaaatggtg 100
ccatatcact gatcttctca ctcaaagaag aagttggtgc attggccaaa 150
gtattgcgct tatttgagga gaatgatgta aacctgaccc acattgaatc 200
tagaccttct cgtttaaaga aagatgagta tgaatttttc acccatttgg 250
ataaacgtag cctgcctgct ctgacaaaca tcatcaagat cttgaggcat 300
gacattggtg ccactgtcca tgagctttca cgagataaga agaaagacac 350
agtgccctgg ttcccaagaa ccattcaaga gctggacaga tttgccaatc 400
agattctcag ctatggagcg gaactggatg ctgaccaccc tggttttaaa 450
gatcctgtgt accgtgcaag acggaagcag tttgctgaca ttgcctacaa 500
ctaccgccat gggcagccca tccctcgagt ggaatacatg gaggaagaaa 550
agaaaacatg gggcacagtg ttcaagactc tgaagtcctt gtataaaacc 600
catgcttgct atgagtacaa tcacattttt ccacttcttg aaaagtactg 650
tggcttccat gaagataaca ttccccagct ggaagacgtt tctcagttcc 700
tgcagacttg cactggtttc cgcctccgac ctgtggctgg cctgctttcc 750
tctcgggatt tcttgggtgg cctggccttc cgagtcttcc actgcacaca 800
gtacatcaga catggatcca agcccatgta tacccccgaa cctgacatct 850
gccatgagct gttgggacat gtgcccttgt tttcagatcg cagctttgcc 900
cagttttccc aggaaattgg ccttgcctct ctgggtgcac ctgatgaata 950
cattgaaaag ctcgccacaa tttactggtt tactgtggag tttgggctct 1000
gcaaacaagg agactccata aaggcatatg gtgctgggct cctgtcatcc 1050
tttggtgaat tacagtactg cttatcagag aagccaaagc ttctccccct 1100
ggagctggag aagacagcca tccaaaatta cactgtcacg gagttccagc 1150
ccctctatta cgtggcagag agttttaatg atgccaagga gaaagtaagg 1200
aactttgctg ccacaatacc tcggcccttc tcagttcgct acgacccata 1250
cacccaaagg attgaggtct tggacaatac ccagcagctt aagattttgg 1300
ctgattccat taacagtgaa attggaatcc tttgcagtgc cctccagaaa 1350
ataaagtaa 1359
<210>2
<211>452
<212>PRT
<213>人(Homo sapiens)
<400>2
Met Ser Thr Ala Val Leu Glu Asn Pro Gly Leu Gly Arg Lys Leu
1 5 10 15
Ser Asp Phe Gly Gln Glu Thr Ser Tyr Ile Glu Asp Asn Cys Asn
20 25 30
Gln Asn Gly Ala Ile Ser Leu Ile Phe Ser Leu Lys Glu Glu Val
35 40 45
Gly Ala Leu Ala Lys Val Leu Arg Leu Phe Glu Glu Asn Asp Val
50 55 60
Asn Leu Thr His Ile Glu Ser Arg Pro Ser Arg Leu Lys Lys Asp
65 70 75
Glu Tyr Glu Phe Phe Thr His Leu Asp Lys Arg Ser Leu Pro Ala
80 85 90
Leu Thr Asn Ile Ile Lys Ile Leu Arg His Asp Ile Gly Ala Thr
95 100 105
Val His Glu Leu Ser Arg Asp Lys Lys Lys Asp Thr Val Pro Trp
110 115 120
Phe Pro Arg Thr Ile Gln Glu Leu Asp Arg Phe Ala Asn Gln Ile
125 130 135
Leu Ser Tyr Gly Ala Glu Leu Asp Ala Asp His Pro Gly Phe Lys
140 145 150
Asp Pro Val Tyr Arg Ala Arg Arg Lys Gln Phe Ala Asp Ile Ala
155 160 165
Tyr Asn Tyr Arg His Gly Gln Pro Ile Pro Arg Val Glu Tyr Met
170 175 180
Glu Glu Glu Lys Lys Thr Trp Gly Thr Val Phe Lys Thr Leu Lys
185 190 195
Ser Leu Tyr Lys Thr His Ala Cys Tyr Glu Tyr Asn His Ile Phe
200 205 210
Pro Leu Leu Glu Lys Tyr Cys Gly Phe His Glu Asp Asn Ile Pro
215 220 225
Gln Leu Glu Asp Val Ser Gln Phe Leu Gln Thr Cys Thr Gly Phe
230 235 240
Arg Leu Arg Pro Val Ala Gly Leu Leu Ser Ser Arg Asp Phe Leu
245 250 255
Gly Gly Leu Ala Phe Arg Val Phe His Cys Thr Gln Tyr Ile Arg
260 265 270
His Gly Ser Lys Pro Met Tyr Thr Pro Glu Pro Asp Ile Cys His
275 280 285
Glu Leu Leu Gly His Val Pro Leu Phe Ser Asp Arg Ser Phe Ala
290 295 300
Gln Phe Ser Gln Glu Ile Gly Leu Ala Ser Leu Gly Ala Pro Asp
305 310 315
Glu Tyr Ile Glu Lys Leu Ala Thr Ile Tyr Trp Phe Thr Val Glu
320 325 330
Phe Gly Leu Cys Lys Gln Gly Asp Ser Ile Lys Ala Tyr Gly Ala
335 340 345
Gly Leu Leu Ser Ser Phe Gly Glu Leu Gln Tyr Cys Leu Ser Glu
350 355 360
Lys Pro Lys Leu Leu Pro Leu Glu Leu Glu Lys Thr Ala Ile Gln
365 370 375
Asn Tyr Thr Val Thr Glu Phe Gln Pro Leu Tyr Tyr Val Ala Glu
380 385 390
Ser Phe Asn Asp Ala Lys Glu Lys Val Arg Asn Phe Ala Ala Thr
395 400 405
Ile Pro Arg Pro Phe Ser Val Arg Tyr Asp Pro Tyr Thr Gln Arg
410 415 420
Ile Glu Val Leu Asp Asn Thr Gln Gln Leu Lys Ile Leu Ala Asp
425 430 435
Ser Ile Asn Ser Glu Ile Gly Ile Leu Cys Ser Ala Leu Gln Lys
440 445 450
Ile Lys
452
<210>3
<211>1359
<212>DNA
<213>人(Homo sapiens)
<220>
<221>mutation
<222>(361)
<223>n=t或c
<400>3
atgtccactg cggtcctgga aaacccaggc ttgggcagga aactctctga ctttggacag 60
gaaacaagct atattgaaga caactgcaat caaaatggtg ccatatcact gatcttctca 120
ctcaaagaag aagttggtgc attggccaaa gtattgcgct tatttgagga gaatgatgta 180
aacctgaccc acattgaatc tagaccttct cgtttaaaga aagatgagta tgaatttttc 240
acccatttgg ataaacgtag cctgcctgct ctgacaaaca tcatcaagat cttgaggcat 300
gacattggtg ccactgtcca tgagctttca cgagataaga agaaagacac agtgccctgg 360
ntcccaagaa ccattcaaga gctggacaga tttgccaatc agattctcag ctatggagcg 420
gaactggatg ctgaccaccc tggttttaaa gatcctgtgt accgtgcaag acggaagcag 480
tttgctgaca ttgcctacaa ctaccgccat gggcagccca tccctcgagt ggaatacatg 540
gaggaagaaa agaaaacatg gggcacagtg ttcaagactc tgaagtcctt gtataaaacc 600
catgcttgct atgagtacaa tcacattttt ccacttcttg aaaagtactg tggcttccat 660
gaagataaca ttccccagct ggaagacgtt tctcagttcc tgcagacttg cactggtttc 720
cgcctccgac ctgtggctgg cctgctttcc tctcgggatt tcttgggtgg cctggccttc 780
cgagtcttcc actgcacaca gtacatcaga catggatcca agcccatgta tacccccgaa 840
cctgacatct gccatgagct gttgggacat gtgcccttgt tttcagatcg cagctttgcc 900
cagttttccc aggaaattgg ccttgcctct ctgggtgcac ctgatgaata cattgaaaag 960
ctcgccacaa tttactggtt tactgtggag tttgggctct gcaaacaagg agactccata 1020
aaggcatatg gtgctgggct cctgtcatcc tttggtgaat tacagtactg cttatcagag 1080
aagccaaagc ttctccccct ggagctggag aagacagcca tccaaaatta cactgtcacg 1140
gagttccagc ccctctatta cgtggcagag agttttaatg atgccaagga gaaagtaagg 1200
aactttgctg ccacaatacc tcggcccttc tcagttcgct acgacccata cacccaaagg 1260
attgaggtct tggacaatac ccagcagctt aagattttgg ctgattccat taacagtgaa 1320
attggaatcc tttgcagtgc cctccagaaa ataaagtaa
<210>4
<211>1359
<212>DNA
<213>人(Homo sapiens)
<220>
<221>mutation
<222>(461)
<223>n=a或g
<400>4
atgtccactg cggtcctgga aaacccaggc ttgggcagga aactctctga ctttggacag 60
gaaacaagct atattgaaga caactgcaat caaaatggtg ccatatcact gatcttctca 120
ctcaaagaag aagttggtgc attggccaaa gtattgcgct tatttgagga gaatgatgta 180
aacctgaccc acattgaatc tagaccttct cgtttaaaga aagatgagta tgaatttttc 240
acccatttgg ataaacgtag cctgcctgct ctgacaaaca tcatcaagat cttgaggcat 300
gacattggtg ccactgtcca tgagctttca cgagataaga agaaagacac agtgccctgg 360
ttcccaagaa ccattcaaga gctggacaga tttgccaatc agattctcag ctatggagcg 420
gaactggatg ctgaccaccc tggttttaaa gatcctgtgt nccgtgcaag acggaagcag 480
tttgctgaca ttgcctacaa ctaccgccat gggcagccca tccctcgagt ggaatacatg 540
gaggaagaaa agaaaacatg gggcacagtg ttcaagactc tgaagtcctt gtataaaacc 600
catgcttgct atgagtacaa tcacattttt ccacttcttg aaaagtactg tggcttccat 660
gaagataaca ttccccagct ggaagacgtt tctcagttcc tgcagacttg cactggtttc 720
cgcctccgac ctgtggctgg cctgctttcc tctcgggatt tcttgggtgg cctggccttc 780
cgagtcttcc actgcacaca gtacatcaga catggatcca agcccatgta tacccccgaa 840
cctgacatct gccatgagct gttgggacat gtgcccttgt tttcagatcg cagctttgcc 900
cagttttccc aggaaattgg ccttgcctct ctgggtgcac ctgatgaata cattgaaaag 960
ctcgccacaa cttactggtt tactgtggag tttgggctct gcaaacaagg agactccata 1020
aaggcatatg gtgctgggct cctgtcatcc tttggtgaat tacagtactt gttatcagag 1080
aagccaaagc ttctccccct ggagctggag aagacagcca tccaaaatta cactgtcacg 1140
gagttccagc ccctctatta cgtggcagag agttttaatg atgccaagga gaaagtaagg 1200
aactttgctg ccacaatacc tcggcccttc tcagttcgct acgacccata cacccaaagg 1260
attgaggtct tggacaatac ccagcagctt aagattttgg ctgattccat taacagtgaa 1320
attggaatcc tttgcagtgc cctccagaaa ataaagtaa
<210>5
<211>1359
<212>DNA
<213>人(Homo sapiens)
<220>
<221>mutation
<222>(466)
<223>n=g或c
<400>5
atgtccactg cggtcctgga aaacccaggc ttgggcagga aactctctga ctttggacag 60
gaaacaagct atattgaaga caactgcaat caaaatggtg ccatatcact gatcttctca 120
ctcaaagaag aagttggtgc attggccaaa gtattgcgct tatttgagga gaatgatgta 180
aacctgaccc acattgaatc tagaccttct cgtttaaaga aagatgagta tgaatttttc 240
acccatttgg ataaacgtag cctgcctgct ctgacaaaca tcatcaagat cttgaggcat 300
gacattggtg ccactgtcca tgagctttca cgagataaga agaaagacac agtgccctgg 360
ttcccaagaa ccattcaaga gctggacaga tttgccaatc agattctcag ctatggagcg 420
gaactggatg ctgaccaccc tggttttaaa gatcctgtgt accgtncaag acggaagcag 480
tttgctgaca ttgcctacaa ctaccgccat gggcagccca tccctcgagt ggaatacatg 540
gaggaagaaa agaaaacatg gggcacagtg ttcaagactc tgaagtcctt gtataaaacc 600
catgcttgct atgagtacaa tcacattttt ccacttcttg aaaagtactg tggcttccat 660
gaagataaca ttccccagct ggaagacgtt tctcagttcc tgcagacttg cactggtttc 720
cgcctccgac ctgtggctgg cctgctttcc tctcgggatt tcttgggtgg cctggccttc 780
cgagtcttcc actgcacaca gtacatcaga catggatcca agcccatgta tacccccgaa 840
cctgacatct gccatgagct gttgggacat gtgcccttgt tttcagatcg cagctttgcc 900
cagttttccc aggaaattgg ccttgcctct ctgggtgcac ctgatgaata cattgaaaag 960
ctcgccacaa tttactggtt tactgtggag tttgggctct gcaaacaagg agactccata 1020
aaggcatatg gtgctgggct cctgtcatcc tttggtgaat tacagtactg cttatcagag 1080
aagccaaagc ttctccccct ggagctggag aagacagcca tccaaaatta cactgtcacg 1140
gagttccagc ccctctatta cgtggcagag agttttaatg atgccaagga gaaagtaagg 1200
aactttgctg ccacaatacc tcggcccttc tcagttcgct acgacccata cacccaaagg 1260
attgaggtct tggacaatac ccagcagctt aagattttgg ctgattccat taacagtgaa 1320
attggaatcc tttgcagtgc cctccagaaa ataaagtaa
<210>6
<211>1359
<212>DNA
<213>人(Homo sapiens)
<220>
<221>mutation
<222>(548)
<223>n=a或g
<400>6
atgtccactg cggtcctgga aaacccaggc ttgggcagga aactctctga ctttggacag 60
gaaacaagct atattgaaga caactgcaat caaaatggtg ccatatcact gatcttctca 120
ctcaaagaag aagttggtgc attggccaaa gtattgcgct tatttgagga gaatgatgta 180
aacctgaccc acattgaatc tagaccttct cgtttaaaga aagatgagta tgaatttttc 240
acccatttgg ataaacgtag cctgcctgct ctgacaaaca tcatcaagat cttgaggcat 300
gacattggtg ccactgtcca tgagctttca cgagataaga agaaagacac agtgccctgg 360
ttcccaagaa ccattcaaga gctggacaga tttgccaatc agattctcag ctatggagcg 420
gaactggatg ctgaccaccc tggttttaaa gatcctgtgt accgtgcaag acggaagcag 480
tttgctgaca ttgcctacaa ctaccgccat gggcagccca tccctcgagt ggaatacatg 540
gaggaagnaa agaaaacatg gggcacagtg ttcaagactc tgaagtcctt gtataaaacc 600
catgcttgct atgagtacaa tcacattttt ccacttcttg aaaagtactg tggcttccat 660
gaagataaca ttccccagct ggaagacgtt tctcagttcc tgcagacttg cactggtttc 720
cgcctccgac ctgtggctgg cctgctttcc tctcgggatt tcttgggtgg cctggccttc 780
cgagtcttcc actgcacaca gtacatcaga catggatcca agcccatgta tacccccgaa 840
cctgacatct gccatgagct gttgggacat gtgcccttgt tttcagatcg cagctttgcc 900
cagttttccc aggaaattgg ccttgcctct ctgggtgcac ctgatgaata cattgaaaag 960
ctcgccacaa tttactggtt tactgtggag tttgggctct gcaaacaagg agactccata 1020
aaggcatatg gtgctgggct cctgtcatcc tttggtgaat tacagtactg cttatcagag 1080
aagccaaagc ttctccccct ggagctggag aagacagcca tccaaaatta cactgtcacg 1140
gagttccagc ccctctatta cgtggcagag agttttaatg atgccaagga gaaagtaagg 1200
aactttgctg ccacaatacc tcggcccttc tcagttcgct acgacccata cacccaaagg 1260
attgaggtct tggacaatac ccagcagctt aagattttgg ctgattccat taacagtgaa 1320
attggaatcc tttgcagtgc cctccagaaa ataaagtaa
<210>7
<211>1359
<212>DNA
<213>人(Homo sapiens)
<220>
<221>mutation
<222>(680)
<223>n=t或a
<400>7
atgtccactg cggtcctgga aaacccaggc ttgggcagga aactctctga ctttggacag 60
gaaacaagct atattgaaga caactgcaat caaaatggtg ccatatcact gatcttctca 120
ctcaaagaag aagttggtgc attggccaaa gtattgcgct tatttgagga gaatgatgta 180
aacctgaccc acattgaatc tagaccttct cgtttaaaga aagatgagta tgaatttttc 240
acccatttgg ataaacgtag cctgcctgct ctgacaaaca tcatcaagat cttgaggcat 300
gacattggtg ccactgtcca tgagctttca cgagataaga agaaagacac agtgccctgg 360
ttcccaagaa ccattcaaga gctggacaga tttgccaatc agattctcag ctatggagcg 420
gaactggatg ctgaccaccc tggttttaaa gatcctgtgt accgtgcaag acggaagcag 480
tttgctgaca ttgcctacaa ctaccgccat gggcagccca tccctcgagt ggaatacatg 540
gaggaagaaa agaaaacatg gggcacagtg ttcaagactc tgaagtcctt gtataaaacc 600
catgcttgct atgagtacaa tcacattttt ccacttcttg aaaagtactg tggcttccat 660
gaagataaca ttccccagcn ggaagacgtt tctcagttcc tgcagacttg cactggtttc 720
cgcctccgac ctgtggctgg cctgctttcc tctcgggatt tcttgggtgg cctggccttc 780
cgagtcttcc actgcacaca gtacatcaga catggatcca agcccatgta tacccccgaa 840
cctgacatct gccatgagct gttgggacat gtgcccttgt tttcagatcg cagctttgcc 900
cagttttccc aggaaattgg ccttgcctct ctgggtgcac ctgatgaata cattgaaaag 960
ctcgccacaa tttactggtt tactgtggag tttgggctct gcaaacaagg agactccata 1020
aaggcatatg gtgctgggct cctgtcatcc tttggtgaat tacagtactg cttatcagag 1080
aagccaaagc ttctccccct ggagctggag aagacagcca tccaaaatta cactgtcacg 1140
gagttccagc ccctctatta cgtggcagag agttttaatg atgccaagga gaaagtaagg 1200
aactttgctg ccacaatacc tcggcccttc tcagttcgct acgacccata cacccaaagg 1260
attgaggtct tggacaatac ccagcagctt aagattttgg ctgattccat taacagtgaa 1320
attggaatcc tttgcagtgc cctccagaaa ataaagtaa
<210>8
<211>1359
<212>DNA
<213>人(Homo sapiens)
<220>
<221>mutation
<222>(682)
<223>n=g或t
<400>8
atgtccactg cggtcctgga aaacccaggc ttgggcagga aactctctga ctttggacag 60
gaaacaagct atattgaaga caactgcaat caaaatggtg ccatatcact gatcttctca 120
ctcaaagaag aagttggtgc attggccaaa gtattgcgct tatttgagga gaatgatgta 180
aacctgaccc acattgaatc tagaccttct cgtttaaaga aagatgagta tgaatttttc 240
acccatttgg ataaacgtag cctgcctgct ctgacaaaca tcatcaagat cttgaggcat 300
gacattggtg ccactgtcca tgagctttca cgagataaga agaaagacac agtgccctgg 360
ntcccaagaa ccattcaaga gctggacaga tttgccaatc agattctcag ctatggagcg 420
gaactggatg ctgaccaccc tggttttaaa gatcctgtgt accgtgcaag acggaagcag 480
tttgctgaca ttgcctacaa ctaccgccat gggcagccca tccctcgagt ggaatacatg 540
gaggaagaaa agaaaacatg gggcacagtg ttcaagactc tgaagtcctt gtataaaacc 600
catgcttgct atgagtacaa tcacattttt ccacttcttg aaaagtactg tggcttccat 660
gaagataaca ttccccagct gnaagacgtt tctcagttcc tgcagacttg cactggtttc 720
cgcctccgac ctgtggctgg cctgctttcc tctcgggatt tcttgggtgg cctggccttc 780
cgagtcttcc actgcacaca gtacatcaga catggatcca agcccatgta tacccccgaa 840
cctgacatct gccatgagct gttgggacat gtgcccttgt tttcagatcg cagctttgcc 900
cagttttccc aggaaattgg ccttgcctct ctgggtgcac ctgatgaata cattgaaaag 960
ctcgccacaa tttactggtt tactgtggag tttgggctct gcaaacaagg agactccata 1020
aaggcatatg gtgctgggct cctgtcatcc tttggtgaat tacagtactg cttatcagag 1080
aagccaaagc ttctccccct ggagctggag aagacagcca tccaaaatta cactgtcacg 1140
gagttccagc ccctctatta cgtggcagag agttttaatg atgccaagga gaaagtaagg 1200
aactttgctg ccacaatacc tcggcccttc tcagttcgct acgacccata cacccaaagg 1260
attgaggtct tggacaatac ccagcagctt aagattttgg ctgattccat taacagtgaa 1320
attggaatcc tttgcagtgc cctccagaaa ataaagtaa
<210>9
<211>1359
<212>DNA
<213>人(Homo sapiens)
<220>
<221>mutation
<222>(808)
<223>n=a或g
<400>9
atgtccactg cggtcctgga aaacccaggc ttgggcagga aactctctga ctttggacag 60
gaaacaagct atattgaaga caactgcaat caaaatggtg ccatatcact gatcttctca 120
ctcaaagaag aagttggtgc attggccaaa gtattgcgct tatttgagga gaatgatgta 180
aacctgaccc acattgaatc tagaccttct cgtttaaaga aagatgagta tgaatttttc 240
acccatttgg ataaacgtag cctgcctgct ctgacaaaca tcatcaagat cttgaggcat 300
gacattggtg ccactgtcca tgagctttca cgagataaga agaaagacac agtgccctgg 360
ttcccaagaa ccattcaaga gctggacaga tttgccaatc agattctcag ctatggagcg 420
gaactggatg ctgaccaccc tggttttaaa gatcctgtgt accgtgcaag acggaagcag 480
tttgctgaca ttgcctacaa ctaccgccat gggcagccca tccctcgagt ggaatacatg 540
gaggaagaaa agaaaacatg gggcacagtg ttcaagactc tgaagtcctt gtataaaacc 600
catgcttgct atgagtacaa tcacattttt ccacttcttg aaaagtactg tggcttccat 660
gaagataaca ttccccagct ggaagacgtt tctcagttcc tgcagacttg cactggtttc 720
cgcctccgac ctgtggctgg cctgctttcc tctcgggatt tcttgggtgg cctggccttc 780
cgagtcttcc actgcacaca gtacatcnga catggatcca agcccatgta tacccccgaa 840
cctgacatct gccatgagct gttgggacat gtgcccttgt tttcagatcg cagctttgcc 900
cagttttccc aggaaattgg ccttgcctct ctgggtgcac ctgatgaata cattgaaaag 960
ctcgccacaa tttactggtt tactgtggag tttgggctct gcaaacaagg agactccata 1020
aaggcatatg gtgctgggct cctgtcatcc tttggtgaat tacagtactg cttatcagag 1080
aagccaaagc ttctccccct ggagctggag aagacagcca tccaaaatta cactgtcacg 1140
gagttccagc ccctctatta cgtggcagag agttttaatg atgccaagga gaaagtaagg 1200
aactttgctg ccacaatacc tcggcccttc tcagttcgct acgacccata cacccaaagg 1260
attgaggtct tggacaatac ccagcagctt aagattttgg ctgattccat taacagtgaa 1320
attggaatcc tttgcagtgc cctccagaaa ataaagtaa
<210>10
<211>1359
<212>DNA
<213>人(Homo sapiens)
<220>
<221>mutation
<222>(823)
<223>n=c或g
<400>10
atgtccactg cggtcctgga aaacccaggc ttgggcagga aactctctga ctttggacag 60
gaaacaagct atattgaaga caactgcaat caaaatggtg ccatatcact gatcttctca 120
ctcaaagaag aagttggtgc attggccaaa gtattgcgct tatttgagga gaatgatgta 180
aacctgaccc acattgaatc tagaccttct cgtttaaaga aagatgagta tgaatttttc 240
acccatttgg ataaacgtag cctgcctgct ctgacaaaca tcatcaagat cttgaggcat 300
gacattggtg ccactgtcca tgagctttca cgagataaga agaaagacac agtgccctgg 360
ntcccaagaa ccattcaaga gctggacaga tttgccaatc agattctcag ctatggagcg 420
gaactggatg ctgaccaccc tggttttaaa gatcctgtgt accgtgcaag acggaagcag 480
tttgctgaca ttgcctacaa ctaccgccat gggcagccca tccctcgagt ggaatacatg 540
gaggaagaaa agaaaacatg gggcacagtg ttcaagactc tgaagtcctt gtataaaacc 600
catgcttgct atgagtacaa tcacattttt ccacttcttg aaaagtactg tggcttccat 660
gaagataaca ttccccagct ggaagacgtt tctcagttcc tgcagacttg cactggtttc 720
cgcctccgac ctgtggctgg cctgctttcc tctcgggatt tcttgggtgg cctggccttc 780
cgagtcttcc actgcacaca gtacatcaga catggatcca agnccatgta tacccccgaa 840
cctgacatct gccatgagct gttgggacat gtgcccttgt tttcagatcg cagctttgcc 900
cagttttccc aggaaattgg ccttgcctct ctgggtgcac ctgatgaata cattgaaaag 960
ctcgccacaa tttactggtt tactgtggag tttgggctct gcaaacaagg agactccata 1020
aaggcatatg gtgctgggct cctgtcatcc tttggtgaat tacagtactg cttatcagag 1080
aagccaaagc ttctccccct ggagctggag aagacagcca tccaaaatta cactgtcacg 1140
gagttccagc ccctctatta cgtggcagag agttttaatg atgccaagga gaaagtaagg 1200
aactttgctg ccacaatacc tcggcccttc tcagttcgct acgacccata cacccaaagg 1260
attgaggtct tggacaatac ccagcagctt aagattttgg ctgattccat taacagtgaa 1320
attggaatcc tttgcagtgc cctccagaaa ataaagtaa
<210>11
<211>1359
<212>DNA
<213>人(Homo sapiens)
<220>
<221>mutation
<222>(971)
<223>n=t或a
<400>11
atgtccactg cggtcctgga aaacccaggc ttgggcagga aactctctga ctttggacag 60
gaaacaagct atattgaaga caactgcaat caaaatggtg ccatatcact gatcttctca 120
ctcaaagaag aagttggtgc attggccaaa gtattgcgct tatttgagga gaatgatgta 180
aacctgaccc acattgaatc tagaccttct cgtttaaaga aagatgagta tgaatttttc 240
acccatttgg ataaacgtag cctgcctgct ctgacaaaca tcatcaagat cttgaggcat 300
gacattggtg ccactgtcca tgagctttca cgagataaga agaaagacac agtgccctgg 360
ntcccaagaa ccattcaaga gctggacaga tttgccaatc agattctcag ctatggagcg 420
gaactggatg ctgaccaccc tggttttaaa gatcctgtgt accgtgcaag acggaagcag 480
tttgctgaca ttgcctacaa ctaccgccat gggcagccca tccctcgagt ggaatacatg 540
gaggaagaaa agaaaacatg gggcacagtg ttcaagactc tgaagtcctt gtataaaacc 600
catgcttgct atgagtacaa tcacattttt ccacttcttg aaaagtactg tggcttccat 660
gaagataaca ttccccagct ggaagacgtt tctcagttcc tgcagacttg cactggtttc 720
cgcctccgac ctgtggctgg cctgctttcc tctcgggatt tcttgggtgg cctggccttc 780
cgagtcttcc actgcacaca gtacatcaga catggatcca agcccatgta tacccccgaa 840
cctgacatct gccatgagct gttgggacat gtgcccttgt tttcagatcg cagctttgcc 900
cagttttccc aggaaattgg ccttgcctct ctgggtgcac ctgatgaata cattgaaaag 960
ctcgccacaa nttactggtt tactgtggag tttgggctct gcaaacaagg agactccata 1020
aaggcatatg gtgctgggct cctgtcatcc tttggtgaat tacagtactg cttatcagag 1080
aagccaaagc ttctccccct ggagctggag aagacagcca tccaaaatta cactgtcacg 1140
gagttccagc ccctctatta cgtggcagag agttttaatg atgccaagga gaaagtaagg 1200
aactttgctg ccacaatacc tcggcccttc tcagttcgct acgacccata cacccaaagg 1260
attgaggtct tggacaatac ccagcagctt aagattttgg ctgattccat taacagtgaa 1320
attggaatcc tttgcagtgc cctccagaaa ataaagtaa
<210>12
<211>1359
<212>DNA
<213>人(Homo sapiens)
<220>
<221>mutation
<222>(1070)
<223>n=g或a
<400>12
atgtccactg cggtcctgga aaacccaggc ttgggcagga aactctctga ctttggacag 60
gaaacaagct atattgaaga caactgcaat caaaatggtg ccatatcact gatcttctca 120
ctcaaagaag aagttggtgc attggccaaa gtattgcgct tatttgagga gaatgatgta 180
aacctgaccc acattgaatc tagaccttct cgtttaaaga aagatgagta tgaatttttc 240
acccatttgg ataaacgtag cctgcctgct ctgacaaaca tcatcaagat cttgaggcat 300
gacattggtg ccactgtcca tgagctttca cgagataaga agaaagacac agtgccctgg 360
ttcccaagaa ccattcaaga gctggacaga tttgccaatc agattctcag ctatggagcg 420
gaactggatg ctgaccaccc tggttttaaa gatcctgtgt accgtgcaag acggaagcag 480
tttgctgaca ttgcctacaa ctaccgccat gggcagccca tccctcgagt ggaatacatg 540
gaggaagaaa agaaaacatg gggcacagtg ttcaagactc tgaagtcctt gtataaaacc 600
catgcttgct atgagtacaa tcacattttt ccacttcttg aaaagtactg tggcttccat 660
gaagataaca ttccccagct ggaagacgtt tctcagttcc tgcagacttg cactggtttc 720
cgcctccgac ctgtggctgg cctgctttcc tctcgggatt tcttgggtgg cctggccttc 780
cgagtcttcc actgcacaca gtacatcaga catggatcca agcccatgta tacccccgaa 840
cctgacatct gccatgagct gttgggacat gtgcccttgt tttcagatcg cagctttgcc 900
cagttttccc aggaaattgg ccttgcctct ctgggtgcac ctgatgaata cattgaaaag 960
ctcgccacaa tttactggtt tactgtggag tttgggctct gcaaacaagg agactccata 1020
aaggcatatg gtgctgggct cctgtcatcc tttggtgaat tacagtactn cttatcagag 1080
aagccaaagc ttctccccct ggagctggag aagacagcca tccaaaatta cactgtcacg 1140
gagttccagc ccctctatta cgtggcagag agttttaatg atgccaagga gaaagtaagg 1200
aactttgctg ccacaatacc tcggcccttc tcagttcgct acgacccata cacccaaagg 1260
attgaggtct tggacaatac ccagcagctt aagattttgg ctgattccat taacagtgaa 1320
attggaatcc tttgcagtgc cctccagaaa ataaagtaa
<210>13
<211>1359
<212>DNA
<213>人(Homo sapiens)
<220>
<221>mutation
<222>(1071)
<223>n=c或g
<400>13
atgtccactg cggtcctgga aaacccaggc ttgggcagga aactctctga ctttggacag 60
gaaacaagct atattgaaga caactgcaat caaaatggtg ccatatcact gatcttctca 120
ctcaaagaag aagttggtgc attggccaaa gtattgcgct tatttgagga gaatgatgta 180
aacctgaccc acattgaatc tagaccttct cgtttaaaga aagatgagta tgaatttttc 240
acccatttgg ataaacgtag cctgcctgct ctgacaaaca tcatcaagat cttgaggcat 300
gacattggtg ccactgtcca tgagctttca cgagataaga agaaagacac agtgccctgg 360
ttcccaagaa ccattcaaga gctggacaga tttgccaatc agattctcag ctatggagcg 420
gaactggatg ctgaccaccc tggttttaaa gatcctgtgt accgtgcaag acggaagcag 480
tttgctgaca ttgcctacaa ctaccgccat gggcagccca tccctcgagt ggaatacatg 540
gaggaagaaa agaaaacatg gggcacagtg ttcaagactc tgaagtcctt gtataaaacc 600
catgcttgct atgagtacaa tcacattttt ccacttcttg aaaagtactg tggcttccat 660
gaagataaca ttccccagct ggaagacgtt tctcagttcc tgcagacttg cactggtttc 720
cgcctccgac ctgtggctgg cctgctttcc tctcgggatt tcttgggtgg cctggccttc 780
cgagtcttcc actgcacaca gtacatcaga catggatcca agcccatgta tacccccgaa 840
cctgacatct gccatgagct gttgggacat gtgcccttgt tttcagatcg cagctttgcc 900
cagttttccc aggaaattgg ccttgcctct ctgggtgcac ctgatgaata cattgaaaag 960
ctcgccacaa tttactggtt tactgtggag tttgggctct gcaaacaagg agactccata 1020
aaggcatatg gtgctgggct cctgtcatcc tttggtgaat tacagtactg nttatcagag 1080
aagccaaagc ttctccccct ggagctggag aagacagcca tccaaaatta cactgtcacg 1140
gagttccagc ccctctatta cgtggcagag agttttaatg atgccaagga gaaagtaagg 1200
aactttgctg ccacaatacc tcggcccttc tcagttcgct acgacccata cacccaaagg 1260
attgaggtct tggacaatac ccagcagctt aagattttgg ctgattccat taacagtgaa 1320
attggaatcc tttgcagtgc cctccagaaa ataaagtaa
<210>14
<211>1359
<212>DNA
<213>人(Homo sapiens)
<220>
<221>mutation
<222>(1085)
<223>n=c或t
<400>14
atgtccactg cggtcctgga aaacccaggc ttgggcagga aactctctga ctttggacag 60
gaaacaagct atattgaaga caactgcaat caaaatggtg ccatatcact gatcttctca 120
ctcaaagaag aagttggtgc attggccaaa gtattgcgct tatttgagga gaatgatgta 180
aacctgaccc acattgaatc tagaccttct cgtttaaaga aagatgagta tgaatttttc 240
acccatttgg ataaacgtag cctgcctgct ctgacaaaca tcatcaagat cttgaggcat 300
gacattggtg ccactgtcca tgagctttca cgagataaga agaaagacac agtgccctgg 360
ttcccaagaa ccattcaaga gctggacaga tttgccaatc agattctcag ctatggagcg 420
gaactggatg ctgaccaccc tggttttaaa gatcctgtgt accgtgcaag acggaagcag 480
tttgctgaca ttgcctacaa ctaccgccat gggcagccca tccctcgagt ggaatacatg 540
gaggaagaaa agaaaacatg gggcacagtg ttcaagactc tgaagtcctt gtataaaacc 600
catgcttgct atgagtacaa tcacattttt ccacttcttg aaaagtactg tggcttccat 660
gaagataaca ttccccagct ggaagacgtt tctcagttcc tgcagacttg cactggtttc 720
cgcctccgac ctgtggctgg cctgctttcc tctcgggatt tcttgggtgg cctggccttc 780
cgagtcttcc actgcacaca gtacatcaga catggatcca agcccatgta tacccccgaa 840
cctgacatct gccatgagct gttgggacat gtgcccttgt tttcagatcg cagctttgcc 900
cagttttccc aggaaattgg ccttgcctct ctgggtgcac ctgatgaata cattgaaaag 960
ctcgccacaa tttactggtt tactgtggag tttgggctct gcaaacaagg agactccata 1020
aaggcatatg gtgctgggct cctgtcatcc tttggtgaat tacagtactg cttatcagag 1080
aagcnaaagc ttctccccct ggagctggag aagacagcca tccaaaatta cactgtcacg 1140
gagttccagc ccctctatta cgtggcagag agttttaatg atgccaagga gaaagtaagg 1200
aactttgctg ccacaatacc tcggcccttc tcagttcgct acgacccata cacccaaagg 1260
attgaggtct tggacaatac ccagcagctt aagattttgg ctgattccat taacagtgaa 1320
attggaatcc tttgcagtgc cctccagaaa ataaagtaa
<210>15
<211>1359
<212>DNA
<213>人(Homo sapiens)
<220>
<221>mutation
<222>(1242)
<223>n=c或a
<400>15
atgtccactg cggtcctgga aaacccaggc ttgggcagga aactctctga ctttggacag 60
gaaacaagct atattgaaga caactgcaat caaaatggtg ccatatcact gatcttctca 120
ctcaaagaag aagttggtgc attggccaaa gtattgcgct tatttgagga gaatgatgta 180
aacctgaccc acattgaatc tagaccttct cgtttaaaga aagatgagta tgaatttttc 240
acccatttgg ataaacgtag cctgcctgct ctgacaaaca tcatcaagat cttgaggcat 300
gacattggtg ccactgtcca tgagctttca cgagataaga agaaagacac agtgccctgg 360
ttcccaagaa ccattcaaga gctggacaga tttgccaatc agattctcag ctatggagcg 420
gaactggatg ctgaccaccc tggttttaaa gatcctgtgt accgtgcaag acggaagcag 480
tttgctgaca ttgcctacaa ctaccgccat gggcagccca tccctcgagt ggaatacatg 540
gaggaagaaa agaaaacatg gggcacagtg ttcaagactc tgaagtcctt gtataaaacc 600
catgcttgct atgagtacaa tcacattttt ccacttcttg aaaagtactg tggcttccat 660
gaagataaca ttccccagct ggaagacgtt tctcagttcc tgcagacttg cactggtttc 720
cgcctccgac ctgtggctgg cctgctttcc tctcgggatt tcttgggtgg cctggccttc 780
cgagtcttcc actgcacaca gtacatcaga catggatcca agcccatgta tacccccgaa 840
cctgacatct gccatgagct gttgggacat gtgcccttgt tttcagatcg cagctttgcc 900
cagttttccc aggaaattgg ccttgcctct ctgggtgcac ctgatgaata cattgaaaag 960
ctcgccacaa tttactggtt tactgtggag tttgggctct gcaaacaagg agactccata 1020
aaggcatatg gtgctgggct cctgtcatcc tttggtgaat tacagtactg cttatcagag 1080
aagccaaagc ttctccccct ggagctggag aagacagcca tccaaaatta cactgtcacg 1140
gagttccagc ccctctatta cgtggcagag agttttaatg atgccaagga gaaagtaagg 1200
aactttgctg ccacaatacc tcggcccttc tcagttcgct angacccata cacccaaagg 1260
attgaggtct tggacaatac ccagcagctt aagattttgg ctgattccat taacagtgaa 1320
attggaatcc tttgcagtgc cctccagaaa ataaagtaa
<210>16
<211>452
<212>PRT
<213>人(Homo sapiens)
<220>
<221>VARIANT
<222>121
<223>Xaa=Phe或Leu
<400>16
Met Ser Thr Ala Val Leu Glu Asn Pro Gly Leu Gly Arg Lys Leu
1 5 10 15
Ser Asp Phe Gly Gln Glu Thr Ser Tyr Ile Glu Asp Asn Cys Asn
20 25 30
Gln Asn Gly Ala Ile Ser Leu Ile Phe Ser Leu Lys Glu Glu Val
35 40 45
Gly Ala Leu Ala Lys Val Leu Arg Leu Phe Glu Glu Asn Asp Val
50 55 60
Asn Leu Thr His Ile Glu Ser Arg Pro Ser Arg Leu Lys Lys Asp
65 70 75
Glu Tyr Glu Phe Phe Thr His Leu Asp Lys Arg Ser Leu Pro Ala
80 85 90
Leu Thr Asn Ile Ile Lys Ile Leu Arg His Asp Ile Gly Ala Thr
95 100 105
Val His Glu Leu Ser Arg Asp Lys Lys Lys Asp Thr Val Pro Trp
110 115 120
Xaa Pro Arg Thr Ile Gln Glu Leu Asp Arg Phe Ala Asn Gln Ile
125 130 135
Leu Ser Tyr Gly Ala Glu Leu Asp Ala Asp His Pro Gly Phe Lys
140 145 150
Asp Pro Val Tyr Arg Ala Arg Arg Lys Gln Phe Ala Asp Ile Ala
155 160 165
Tyr Asn Tyr Arg His Gly Gln Pro Ile Pro Arg Val Glu Tyr Met
170 175 180
Glu Glu Glu Lys Lys Thr Trp Gly Thr Val Phe Lys Thr Leu Lys
185 190 195
Ser Leu Tyr Lys Thr His Ala Cys Tyr Glu Tyr Asn His Ile Phe
200 205 210
Pro Leu Leu Glu Lys Tyr Cys Gly Phe His Glu Asp Asn Ile Pro
215 220 225
Gln Leu Glu Asp Val Ser Gln Phe Leu Gln Thr Cys Thr Gly Phe
230 235 240
Arg Leu Arg Pro Val Ala Gly Leu Leu Ser Ser Arg Asp Phe Leu
245 250 255
Gly Gly Leu Ala Phe Arg Val Phe His Cys Thr Gln Tyr Ile Arg
260 265 270
His Gly Ser Lys Pro Met Tyr Thr Pro Glu Pro Asp Ile Cys His
275 280 285
Glu Leu Leu Gly His Val Pro Leu Phe Ser Asp Arg Ser Phe Ala
290 295 300
Gln Phe Ser Gln Glu Ile Gly Leu Ala Ser Leu Gly Ala Pro Asp
305 310 315
Glu Tyr Ile Glu Lys Leu Ala Thr Ile Tyr Trp Phe Thr Val Glu
320 325 330
Phe Gly Leu Cys Lys Gln Gly Asp Ser Ile Lys Ala Tyr Gly Ala
335 340 345
Gly Leu Leu Ser Ser Phe Gly Glu Leu Gln Tyr Cys Leu Ser Glu
350 355 360
Lys Pro Lys Leu Leu Pro Leu Glu Leu Glu Lys Thr Ala Ile Gln
365 370 375
Asn Tyr Thr Val Thr Glu Phe Gln Pro Leu Tyr Tyr Val Ala Glu
380 385 390
Ser Phe Asn Asp Ala Lys Glu Lys Val Arg Asn Phe Ala Ala Thr
395 400 405
Ile Pro Arg Pro Phe Ser Val Arg Tyr Asp Pro Tyr Thr Gln Arg
410 415 420
Ile Glu Val Leu Asp Asn Thr Gln Gln Leu Lys Ile Leu Ala Asp
425 430 435
Ser Ile Asn Ser Glu Ile Gly Ile Leu Cys Ser Ala Leu Gln Lys
440 445 450
Ile Lys
452
<210>17
<211>452
<212>PRT
<213>人(Homo sapiens)
<220>
<221>VARIANT
<222>154
<223>Xaa=Tyr或Cys
<400>17
Met Ser Thr Ala Val Leu Glu Asn Pro Gly Leu Gly Arg Lys Leu
1 5 10 15
Ser Asp Phe Gly Gln Glu Thr Ser Tyr Ile Glu Asp Asn Cys Asn
20 25 30
Gln Asn Gly Ala Ile Ser Leu Ile Phe Ser Leu Lys Glu Glu Val
35 40 45
Gly Ala Leu Ala Lys Val Leu Arg Leu Phe Glu Glu Asn Asp Val
50 55 60
Asn Leu Thr His Ile Glu Ser Arg Pro Ser Arg Leu Lys Lys Asp
65 70 75
Glu Tyr Glu Phe Phe Thr His Leu Asp Lys Arg Ser Leu Pro Ala
80 85 90
Leu Thr Asn Ile Ile Lys Ile Leu Arg His Asp Ile Gly Ala Thr
95 100 105
Val His Glu Leu Ser Arg Asp Lys Lys Lys Asp Thr Val Pro Trp
110 115 120
Phe Pro Arg Thr Ile Gln Glu Leu Asp Arg Phe Ala Asn Gln Ile
125 130 135
Leu Ser Tyr Gly Ala Glu Leu Asp Ala Asp His Pro Gly Phe Lys
140 145 150
Asp Pro Val Xaa Arg Ala Arg Arg Lys Gln Phe Ala Asp Ile Ala
155 160 165
Tyr Asn Tyr Arg His Gly Gln Pro Ile Pro Arg Val Glu Tyr Met
170 175 180
Glu Glu Glu Lys Lys Thr Trp Gly Thr Val Phe Lys Thr Leu Lys
185 190 195
Ser Leu Tyr Lys Thr His Ala Cys Tyr Glu Tyr Asn His Ile Phe
200 205 210
Pro Leu Leu Glu Lys Tyr Cys Gly Phe His Glu Asp Asn Ile Pro
215 220 225
Gln Leu Glu Asp Val Ser Gln Phe Leu Gln Thr Cys Thr Gly Phe
230 235 240
Arg Leu Arg Pro Val Ala Gly Leu Leu Ser Ser Arg Asp Phe Leu
245 250 255
Gly Gly Leu Ala Phe Arg Val Phe His Cys Thr Gln Tyr Ile Arg
260 265 270
His Gly Ser Lys Pro Met Tyr Thr Pro Glu Pro Asp Ile Cys His
275 280 285
Glu Leu Leu Gly His Val Pro Leu Phe Ser Asp Arg Ser Phe Ala
290 295 300
Gln Phe Ser Gln Glu Ile Gly Leu Ala Ser Leu Gly Ala Pro Asp
305 310 315
Glu Tyr Ile Glu Lys Leu Ala Thr Ile Tyr Trp Phe Thr Val Glu
320 325 330
Phe Gly Leu Cys Lys Gln Gly Asp Ser Ile Lys Ala Tyr Gly Ala
335 340 345
Gly Leu Leu Ser Ser Phe Gly Glu Leu Gln Tyr Cys Leu Ser Glu
350 355 360
Lys Pro Lys Leu Leu Pro Leu Glu Leu Glu Lys Thr Ala Ile Gln
365 370 375
Asn Tyr Thr Val Thr Glu Phe Gln Pro Leu Tyr Tyr Val Ala Glu
380 385 390
Ser Phe Asn Asp Ala Lys Glu Lys Val Arg Asn Phe Ala Ala Thr
395 400 405
Ile Pro Arg Pro Phe Ser Val Arg Tyr Asp Pro Tyr Thr Gln Arg
410 415 420
Ile Glu Val Leu Asp Asn Thr Gln Gln Leu Lys Ile Leu Ala Asp
425 430 435
Ser Ile Asn Ser Glu Ile Gly Ile Leu Cys Ser Ala Leu Gln Lys
440 445 450
Ile Lys
452
<210>18
<211>452
<212>PRT
<213>人(Homo sapiens)
<220>
<221>VARIANT
<222>156
<223>Xaa=Ala或Pro
<400>18
Met Ser Thr Ala Val Leu Glu Asn Pro Gly Leu Gly Arg Lys Leu
1 5 10 15
Ser Asp Phe Gly Gln Glu Thr Ser Tyr Ile Glu Asp Asn Cys Asn
20 25 30
Gln Asn Gly Ala Ile Ser Leu Ile Phe Ser Leu Lys Glu Glu Val
35 40 45
Gly Ala Leu Ala Lys Val Leu Arg Leu Phe Glu Glu Asn Asp Val
50 55 60
Asn Leu Thr His Ile Glu Ser Arg Pro Ser Arg Leu Lys Lys Asp
65 70 75
Glu Tyr Glu Phe Phe Thr His Leu Asp Lys Arg Ser Leu Pro Ala
80 85 90
Leu Thr Asn Ile Ile Lys Ile Leu Arg His Asp Ile Gly Ala Thr
95 100 105
Val His Glu Leu Ser Arg Asp Lys Lys Lys Asp Thr Val Pro Trp
110 115 120
Phe Pro Arg Thr Ile Gln Glu Leu Asp Arg Phe Ala Asn Gln Ile
125 130 135
Leu Ser Tyr Gly Ala Glu Leu Asp Ala Asp His Pro Gly Phe Lys
140 145 150
Asp Pro Val Tyr Arg Xaa Arg Arg Lys Gln Phe Ala Asp Ile Ala
155 160 165
Tyr Asn Tyr Arg His Gly Gln Pro Ile Pro Arg Val Glu Tyr Met
170 175 180
Glu Glu Glu Lys Lys Thr Trp Gly Thr Val Phe Lys Thr Leu Lys
185 190 195
Ser Leu Tyr Lys Thr His Ala Cys Tyr Glu Tyr Asn His Ile Phe
200 205 210
Pro Leu Leu Glu Lys Tyr Cys Gly Phe His Glu Asp Asn Ile Pro
215 220 225
Gln Leu Glu Asp Val Ser Gln Phe Leu Gln Thr Cys Thr Gly Phe
230 235 240
Arg Leu Arg Pro Val Ala Gly Leu Leu Ser Ser Arg Asp Phe Leu
245 250 255
Gly Gly Leu Ala Phe Arg Val Phe His Cys Thr Gln Tyr Ile Arg
260 265 270
His Gly Ser Lys Pro Met Tyr Thr Pro Glu Pro Asp Ile Cys His
275 280 285
Glu Leu Leu Gly His Val Pro Leu Phe Ser Asp Arg Ser Phe Ala
290 295 300
Gln Phe Ser Gln Glu Ile Gly Leu Ala Ser Leu Gly Ala Pro Asp
305 310 315
Glu Tyr Ile Glu Lys Leu Ala Thr Ile Tyr Trp Phe Thr Val Glu
320 325 330
Phe Gly Leu Cys Lys Gln Gly Asp Ser Ile Lys Ala Tyr Gly Ala
335 340 345
Gly Leu Leu Ser Ser Phe Gly Glu Leu Gln Tyr Cys Leu Ser Glu
350 355 360
Lys Pro Lys Leu Leu Pro Leu Glu Leu Glu Lys Thr Ala Ile Gln
365 370 375
Asn Tyr Thr Val Thr Glu Phe Gln Pro Leu Tyr Tyr Val Ala Glu
380 385 390
Ser Phe Asn Asp Ala Lys Glu Lys Val Arg Asn Phe Ala Ala Thr
395 400 405
Ile Pro Arg Pro Phe Ser Val Arg Tyr Asp Pro Tyr Thr Gln Arg
410 415 420
Ile Glu Val Leu Asp Asn Thr Gln Gln Leu Lys Ile Leu Ala Asp
425 430 435
Ser Ile Asn Ser Glu Ile Gly Ile Leu Cys Ser Ala Leu Gln Lys
440 445 450
Ile Lys
452
<210>19
<211>452
<212>PRT
<213>人(Homo sapiens)
<220>
<221>VARIANT
<222>183
<223>Xaa=Glu或Gly
<400>19
Met Ser Thr Ala Val Leu Glu Asn Pro Gly Leu Gly Arg Lys Leu
1 5 10 15
Ser Asp Phe Gly Gln Glu Thr Ser Tyr Ile Glu Asp Asn Cys Asn
20 25 30
Gln Asn Gly Ala Ile Ser Leu Ile Phe Ser Leu Lys Glu Glu Val
35 40 45
Gly Ala Leu Ala Lys Val Leu Arg Leu Phe Glu Glu Asn Asp Val
50 55 60
Asn Leu Thr His Ile Glu Ser Arg Pro Ser Arg Leu Lys Lys Asp
65 70 75
Glu Tyr Glu Phe Phe Thr His Leu Asp Lys Arg Ser Leu Pro Ala
80 85 90
Leu Thr Asn Ile Ile Lys Ile Leu Arg His Asp Ile Gly Ala Thr
95 100 105
Val His Glu Leu Ser Arg Asp Lys Lys Lys Asp Thr Val Pro Trp
110 115 120
Phe Pro Arg Thr Ile Gln Glu Leu Asp Arg Phe Ala Asn Gln Ile
125 130 135
Leu Ser Tyr Gly Ala Glu Leu Asp Ala Asp His Pro Gly Phe Lys
140 145 150
Asp Pro Val Tyr Arg Ala Arg Arg Lys Gln Phe Ala Asp Ile Ala
155 160 165
Tyr Asn Tyr Arg His Gly Gln Pro Ile Pro Arg Val Glu Tyr Met
170 175 180
Glu Glu Xaa Lys Lys Thr Trp Gly Thr Val Phe Lys Thr Leu Lys
185 190 195
Ser Leu Tyr Lys Thr His Ala Cys Tyr Glu Tyr Asn His Ile Phe
200 205 210
Pro Leu Leu Glu Lys Tyr Cys Gly Phe His Glu Asp Asn Ile Pro
215 220 225
Gln Leu Glu Asp Val Ser Gln Phe Leu Gln Thr Cys Thr Gly Phe
230 235 240
Arg Leu Arg Pro Val Ala Gly Leu Leu Ser Ser Arg Asp Phe Leu
245 250 255
Gly Gly Leu Ala Phe Arg Val Phe His Cys Thr Gln Tyr Ile Arg
260 265 270
His Gly Ser Lys Pro Met Tyr Thr Pro Glu Pro Asp Ile Cys His
275 280 285
Glu Leu Leu Gly His Val Pro Leu Phe Ser Asp Arg Ser Phe Ala
290 295 300
Gln Phe Ser Gln Glu Ile Gly Leu Ala Ser Leu Gly Ala Pro Asp
305 310 315
Glu Tyr Ile Glu Lys Leu Ala Thr Ile Tyr Trp Phe Thr Val Glu
320 325 330
Phe Gly Leu Cys Lys Gln Gly Asp Ser Ile Lys Ala Tyr Gly Ala
335 340 345
Gly Leu Leu Ser Ser Phe Gly Glu Leu Gln Tyr Cys Leu Ser Glu
350 355 360
Lys Pro Lys Leu Leu Pro Leu Glu Leu Glu Lys Thr Ala Ile Gln
365 370 375
Asn Tyr Thr Val Thr Glu Phe Gln Pro Leu Tyr Tyr Val Ala Glu
380 385 390
Ser Phe Asn Asp Ala Lys Glu Lys Val Arg Asn Phe Ala Ala Thr
395 400 405
Ile Pro Arg Pro Phe Ser Val Arg Tyr Asp Pro Tyr Thr Gln Arg
410 415 420
Ile Glu Val Leu Asp Asn Thr Gln Gln Leu Lys Ile Leu Ala Asp
425 430 435
Ser Ile Asn Ser Glu Ile Gly Ile Leu Cys Ser Ala Leu Gln Lys
440 445 450
Ile Lys
452
<210>20
<211>452
<212>PRT
<213>人(Homo sapiens)
<220>
<221>VARIANT
<222>227
<223>Xaa=Leu或Gln
<400>20
Met Ser Thr Ala Val Leu Glu Asn Pro Gly Leu Gly Arg Lys Leu
1 5 10 15
Ser Asp Phe Gly Gln Glu Thr Ser Tyr Ile Glu Asp Asn Cys Asn
20 25 30
Gln Asn Gly Ala Ile Ser Leu Ile Phe Ser Leu Lys Glu Glu Val
35 40 45
Gly Ala Leu Ala Lys Val Leu Arg Leu Phe Glu Glu Asn Asp Val
50 55 60
Asn Leu Thr His Ile Glu Ser Arg Pro Ser Arg Leu Lys Lys Asp
65 70 75
Glu Tyr Glu Phe Phe Thr His Leu Asp Lys Arg Ser Leu Pro Ala
80 85 90
Leu Thr Asn Ile Ile Lys Ile Leu Arg His Asp Ile Gly Ala Thr
95 100 105
Val His Glu Leu Ser Arg Asp Lys Lys Lys Asp Thr Val Pro Trp
110 115 120
Phe Pro Arg Thr Ile Gln Glu Leu Asp Arg Phe Ala Asn Gln Ile
125 130 135
Leu Ser Tyr Gly Ala Glu Leu Asp Ala Asp His Pro Gly Phe Lys
140 145 150
Asp Pro Val Tyr Arg Ala Arg Arg Lys Gln Phe Ala Asp Ile Ala
155 160 165
Tyr Asn Tyr Arg His Gly Gln Pro Ile Pro Arg Val Glu Tyr Met
170 175 180
Glu Glu Glu Lys Lys Thr Trp Gly Thr Val Phe Lys Thr Leu Lys
185 190 195
Ser Leu Tyr Lys Thr His Ala Cys Tyr Glu Tyr Asn His Ile Phe
200 205 210
Pro Leu Leu Glu Lys Tyr Cys Gly Phe His Glu Asp Asn Ile Pro
215 220 225
Gln Xaa Glu Asp Val Ser Gln Phe Leu Gln Thr Cys Thr Gly Phe
230 235 240
Arg Leu Arg Pro Val Ala Gly Leu Leu Ser Ser Arg Asp Phe Leu
245 250 255
Gly Gly Leu Ala Phe Arg Val Phe His Cys Thr Gln Tyr Ile Arg
260 265 270
His Gly Ser Lys Pro Met Tyr Thr Pro Glu Pro Asp Ile Cys His
275 280 285
Glu Leu Leu Gly His Val Pro Leu Phe Ser Asp Arg Ser Phe Ala
290 295 300
Gln Phe Ser Gln Glu Ile Gly Leu Ala Ser Leu Gly Ala Pro Asp
305 310 315
Glu Tyr Ile Glu Lys Leu Ala Thr Ile Tyr Trp Phe Thr Val Glu
320 325 330
Phe Gly Leu Cys Lys Gln Gly Asp Ser Ile Lys Ala Tyr Gly Ala
335 340 345
Gly Leu Leu Ser Ser Phe Gly Glu Leu Gln Tyr Cys Leu Ser Glu
350 355 360
Lys Pro Lys Leu Leu Pro Leu Glu Leu Glu Lys Thr Ala Ile Gln
365 370 375
Asn Tyr Thr Val Thr Glu Phe Gln Pro Leu Tyr Tyr Val Ala Glu
380 385 390
Ser Phe Asn Asp Ala Lys Glu Lys Val Arg Asn Phe Ala Ala Thr
395 400 405
Ile Pro Arg Pro Phe Ser Val Arg Tyr Asp Pro Tyr Thr Gln Arg
410 415 420
Ile Glu Val Leu Asp Asn Thr Gln Gln Leu Lys Ile Leu Ala Asp
425 430 435
Ser Ile Asn Ser Glu Ile Gly Ile Leu Cys Ser Ala Leu Gln Lys
440 445 450
Ile Lys
452
<210>21
<211>452
<212>PRT
<213>人(Homo sapiens)
<220>
<221>VARIANT
<222>228
<223>Xaa=Glu或X
<400>21
Met Ser Thr Ala Val Leu Glu Asn Pro Gly Leu Gly Arg Lys Leu
1 5 10 15
Ser Asp Phe Gly Gln Glu Thr Ser Tyr Ile Glu Asp Asn Cys Asn
20 25 30
Gln Asn Gly Ala Ile Ser Leu Ile Phe Ser Leu Lys Glu Glu Val
35 40 45
Gly Ala Leu Ala Lys Val Leu Arg Leu Phe Glu Glu Asn Asp Val
50 55 60
Asn Leu Thr His Ile Glu Ser Arg Pro Ser Arg Leu Lys Lys Asp
65 70 75
Glu Tyr Glu Phe Phe Thr His Leu Asp Lys Arg Ser Leu Pro Ala
80 85 90
Leu Thr Asn Ile Ile Lys Ile Leu Arg His Asp Ile Gly Ala Thr
95 100 105
Val His Glu Leu Ser Arg Asp Lys Lys Lys Asp Thr Val Pro Trp
110 115 120
Phe Pro Arg Thr Ile Gln Glu Leu Asp Arg Phe Ala Asn Gln Ile
125 130 135
Leu Ser Tyr Gly Ala Glu Leu Asp Ala Asp His Pro Gly Phe Lys
140 145 150
Asp Pro Val Tyr Arg Ala Arg Arg Lys Gln Phe Ala Asp Ile Ala
155 160 165
Tyr Asn Tyr Arg His Gly Gln Pro Ile Pro Arg Val Glu Tyr Met
170 175 180
Glu Glu Glu Lys Lys Thr Trp Gly Thr Val Phe Lys Thr Leu Lys
185 190 195
Ser Leu Tyr Lys Thr His Ala Cys Tyr Glu Tyr Asn His Ile Phe
200 205 210
Pro Leu Leu Glu Lys Tyr Cys Gly Phe His Glu Asp Asn Ile Pro
215 220 225
Gln Leu Xaa Asp Val Ser Gln Phe Leu Gln Thr Cys Thr Gly Phe
230 235 240
Arg Leu Arg Pro Val Ala Gly Leu Leu Ser Ser Arg Asp Phe Leu
245 250 255
Gly Gly Leu Ala Phe Arg ValPhe His Cys Thr Gln Tyr Ile Arg
260 265 270
His Gly Ser Lys Pro Met Tyr Thr Pro Glu Pro Asp Ile Cys His
275 280 285
Glu Leu Leu Gly His Val Pro Leu Phe Ser Asp Arg Ser Phe Ala
290 295 300
Gln Phe Ser Gln Glu Ile Gly Leu Ala Ser Leu Gly Ala Pro Asp
305 310 315
Glu Tyr Ile Glu Lys Leu Ala Thr Ile Tyr Trp Phe Thr Val Glu
320 325 330
Phe Gly Leu Cys Lys Gln Gly Asp Ser Ile Lys Ala Tyr Gly Ala
335 340 345
Gly Leu Leu Ser Ser Phe Gly Glu Leu Gln Tyr Cys Leu Ser Glu
350 355 360
Lys Pro Lys Leu Leu Pro Leu Glu Leu Glu Lys Thr Ala Ile Gln
365 370 375
Asn Tyr Thr Val Thr Glu Phe Gln Pro Leu Tyr Tyr Val Ala Glu
380 385 390
Ser Phe Asn Asp Ala Lys Glu Lys Val Arg Asn Phe Ala Ala Thr
395 400 405
Ile Pro Arg Pro Phe Ser Val Arg Tyr Asp Pro Tyr Thr Gln Arg
410 415 420
Ile Glu Val Leu Asp Asn Thr Gln Gln Leu Lys Ile Leu Ala Asp
425 430 435
Ser Ile Asn Ser Glu Ile Gly Ile Leu Cys Ser Ala Leu Gln Lys
440 445 450
Ile Lys
452
<210>22
<211>452
<212>PRT
<213>人(Homo sapiens)
<220>
<221>VARIANT
<222>270
<223>Xaa=Arg或Gly
<400>22
Met Ser Thr Ala Val Leu Glu Asn Pro Gly Leu Gly Arg Lys Leu
1 5 10 15
Ser Asp Phe Gly Gln Glu Thr Ser Tyr Ile Glu Asp Asn Cys Asn
20 25 30
Gln Asn Gly Ala Ile Ser Leu Ile Phe Ser Leu Lys Glu Glu Val
35 40 45
Gly Ala Leu Ala Lys Val Leu Arg Leu Phe Glu Glu Asn Asp Val
50 55 60
Asn Leu Thr His Ile Glu Ser Arg Pro Ser Arg Leu Lys Lys Asp
65 70 75
Glu Tyr Glu Phe Phe Thr His Leu Asp Lys Arg Ser Leu Pro Ala
80 85 90
Leu Thr Asn Ile Ile Lys Ile Leu Arg His Asp Ile Gly Ala Thr
95 100 105
Val His Glu Leu Ser Arg Asp Lys Lys Lys Asp Thr Val Pro Trp
110 115 120
Phe Pro Arg Thr Ile Gln Glu Leu Asp Arg Phe Ala Asn Gln Ile
125 130 135
Leu Ser Tyr Gly Ala Glu Leu Asp Ala Asp His Pro Gly Phe Lys
140 145 150
Asp Pro Val Tyr Arg Ala Arg Arg Lys Gln Phe Ala Asp Ile Ala
155 160 165
Tyr Asn Tyr Arg His Gly Gln Pro Ile Pro Arg Val Glu Tyr Met
170 175 180
Glu Glu Glu Lys Lys Thr Trp Gly Thr Val Phe Lys Thr Leu Lys
185 190 195
Ser Leu Tyr Lys Thr His Ala Cys Tyr Glu Tyr Asn His Ile Phe
200 205 210
Pro Leu Leu Glu Lys Tyr Cys Gly Phe His Glu Asp Asn Ile Pro
215 220 225
Gln Leu Glu Asp Val Ser Gln Phe Leu Gln Thr Cys Thr Gly Phe
230 235 240
Arg Leu Arg Pro Val Ala Gly Leu Leu Ser Ser Arg Asp Phe Leu
245 250 255
Gly Gly Leu Ala Phe Arg Val Phe His Cys Thr Gln Tyr Ile Xaa
260 265 270
His Gly Ser Lys Pro Met Tyr Thr Pro Glu Pro Asp Ile Cys His
275 280 285
Glu Leu Leu Gly His Val Pro Leu Phe Ser Asp Arg Ser Phe Ala
290 295 300
Gln Phe Ser Gln Glu Ile Gly Leu Ala Ser Leu Gly Ala Pro Asp
305 310 315
Glu Tyr Ile Glu Lys Leu Ala Thr Ile Tyr Trp Phe Thr Val Glu
320 325 330
Phe Gly Leu Cys Lys Gln Gly Asp Ser Ile Lys Ala Tyr Gly Ala
335 340 345
Gly Leu Leu Ser Ser Phe Gly Glu Leu Gln Tyr Cys Leu Ser Glu
350 355 360
Lys Pro Lys Leu Leu Pro Leu Glu Leu Glu Lys Thr Ala Ile Gln
365 370 375
Asn Tyr Thr Val Thr Glu Phe Gln Pro Leu Tyr Tyr Val Ala Glu
380 385 390
Ser Phe Asn Asp Ala Lys Glu Lys Val Arg Asn Phe Ala Ala Thr
395 400 405
Ile Pro Arg Pro Phe Ser Val Arg Tyr Asp Pro Tyr Thr Gln Arg
410 415 420
Ile Glu Val Leu Asp Asn Thr Gln Gln Leu Lys Ile Leu Ala Asp
425 430 435
Ser Ile Asn Ser Glu Ile Gly Ile Leu Cys Ser Ala Leu Gln Lys
440 445 450
Ile Lys
452
<210>23
<211>452
<212>PRT
<213>人(Homo sapiens)
<220>
<221>VARIANT
<222>275
<223>Xaa=Pro或Ala
<400>23
Met Ser Thr Ala Val Leu Glu Asn Pro Gly Leu Gly Arg Lys Leu
1 5 10 15
Ser Asp Phe Gly Gln Glu Thr Ser Tyr Ile Glu Asp Asn Cys Asn
20 25 30
Gln Asn Gly Ala Ile Ser Leu Ile Phe Ser Leu Lys Glu Glu Val
35 40 45
Gly Ala Leu Ala Lys Val Leu Arg Leu Phe Glu Glu Asn Asp Val
50 55 60
Asn Leu Thr His Ile Glu Ser Arg Pro Ser Arg Leu Lys Lys Asp
65 70 75
Glu Tyr Glu Phe Phe Thr His Leu Asp Lys Arg Ser Leu Pro Ala
80 85 90
Leu Thr Asn Ile Ile Lys Ile Leu Arg His Asp Ile Gly Ala Thr
95 100 105
Val His Glu Leu Ser Arg Asp Lys Lys Lys Asp Thr Val Pro Trp
110 115 120
Phe Pro Arg Thr Ile Gln Glu Leu Asp Arg Phe Ala Asn Gln Ile
125 130 135
Leu Ser Tyr Gly Ala Glu Leu Asp Ala Asp His Pro Gly Phe Lys
140 145 150
Asp Pro Val Tyr Arg Ala Arg Arg Lys Gln Phe Ala Asp Ile Ala
155 160 165
Tyr Asn Tyr Arg His Gly Gln Pro Ile Pro Arg Val Glu Tyr Met
170 175 180
Glu Glu Glu Lys Lys Thr Trp Gly Thr Val Phe Lys Thr Leu Lys
185 190 195
Ser Leu Tyr Lys Thr His Ala Cys Tyr Glu Tyr Asn His Ile Phe
200 205 210
Pro Leu Leu Glu Lys Tyr Cys Gly Phe His Glu Asp Asn Ile Pro
215 220 225
Gln Leu Glu Asp Val Ser Gln Phe Leu Gln Thr Cys Thr Gly Phe
230 235 240
Arg Leu Arg Pro Val Ala Gly Leu Leu Ser Ser Arg Asp Phe Leu
245 250 255
Gly Gly Leu Ala Phe Arg Val Phe His Cys Thr Gln Tyr Ile Arg
260 265 270
His Gly Ser Lys Xaa Met Tyr Thr Pro Glu Pro Asp Ile Cys His
275 280 285
Glu Leu Leu Gly His Val Pro Leu Phe Ser Asp Arg Ser Phe Ala
290 295 300
Gln Phe Ser Gln Glu Ile Gly Leu Ala Ser Leu Gly Ala Pro Asp
305 310 315
Glu Tyr Ile Glu Lys Leu Ala Thr Ile Tyr Trp Phe Thr Val Glu
320 325 330
Phe Gly Leu Cys Lys Gln Gly Asp Ser Ile Lys Ala Tyr Gly Ala
335 340 345
Gly Leu Leu Ser Ser Phe Gly Glu Leu Gln Tyr Cys Leu Ser Glu
350 355 360
Lys Pro Lys Leu Leu Pro Leu Glu Leu Glu Lys Thr Ala Ile Gln
365 370 375
Asn Tyr Thr Val Thr Glu Phe Gln Pro Leu Tyr Tyr Val Ala Glu
380 385 390
Ser Phe Asn Asp Ala Lys Glu Lys ValArg Asn Phe Ala Ala Thr
395 400 405
Ile Pro Arg Pro Phe Ser Val Arg Tyr Asp Pro Tyr Thr Gln Arg
410 415 420
Ile Glu Val Leu Asp Asn Thr Gln Gln Leu Lys Ile Leu Ala Asp
425 430 435
Ser Ile Asn Ser Glu Ile Gly Ile Leu Cys Ser Ala Leu Gln Lys
440 445 450
Ile Lys
452
<210>24
<211>452
<212>PRT
<213>人(Homo sapiens)
<220>
<221>VARIANT
<222>324
<223>Xaa=Ile或Asn
<400>24
Met Ser Thr Ala Val Leu Glu Asn Pro Gly Leu Gly Arg Lys Leu
1 5 10 15
Ser Asp Phe Gly Gln Glu Thr Ser Tyr Ile Glu Asp Asn Cys Asn
20 25 30
Gln Asn Gly Ala Ile Ser Leu Ile Phe Ser Leu Lys Glu Glu Val
35 40 45
Gly Ala Leu Ala Lys Val Leu Arg Leu Phe Glu Glu Asn Asp Val
50 55 60
Asn Leu Thr His Ile Glu Ser Arg Pro Ser Arg Leu Lys Lys Asp
65 70 75
Glu Tyr Glu Phe Phe Thr His Leu Asp Lys Arg Ser Leu Pro Ala
80 85 90
Leu Thr Asn Ile Ile Lys Ile Leu Arg His Asp Ile Gly Ala Thr
95 100 105
Val His Glu Leu Ser Arg Asp Lys Lys Lys Asp Thr Val Pro Trp
110 115 120
Phe Pro Arg Thr Ile Gln Glu Leu Asp Arg Phe Ala Asn Gln Ile
125 130 135
Leu Ser Tyr Gly Ala Glu Leu Asp Ala Asp His Pro Gly Phe Lys
140 145 150
Asp Pro Val Tyr Arg Ala Arg Arg Lys Gln Phe Ala Asp Ile Ala
155 160 165
Tyr Asn Tyr Arg His Gly Gln Pro Ile Pro Arg Val Glu Tyr Met
170 175 180
Glu Glu Glu Lys Lys Thr Trp Gly Thr Val Phe Lys Thr Leu Lys
185 190 195
Ser Leu Tyr Lys Thr His Ala Cys Tyr Glu Tyr Asn His Ile Phe
200 205 210
Pro Leu Leu Glu Lys Tyr Cys Gly Phe His Glu Asp Asn Ile Pro
215 220 225
Gln Leu Glu Asp Val Ser Gln Phe Leu Gln Thr Cys Thr Gly Phe
230 235 240
Arg Leu Arg Pro Val Ala Gly Leu Leu Ser Ser Arg Asp Phe Leu
245 250 255
Gly Gly Leu Ala Phe Arg Val Phe His Cys Thr Gln Tyr Ile Arg
260 265 270
His Gly Ser Lys Pro Met Tyr Thr Pro Glu Pro Asp Ile Cys His
275 280 285
Glu Leu Leu Gly His Val Pro Leu Phe Ser Asp Arg Ser Phe Ala
290 295 300
Gln Phe Ser Gln Glu Ile Gly Leu Ala Ser Leu Gly Ala Pro Asp
305 310 315
Glu Tyr Ile Glu Lys Leu Ala Thr Xaa Tyr Trp Phe Thr Val Glu
320 325 330
Phe Gly Leu Cys Lys Gln Gly Asp Ser Ile Lys Ala Tyr Gly Ala
335 340 345
Gly Leu Leu Ser Ser Phe Gly Glu Leu Gln Tyr Cys Leu Ser Glu
350 355 360
Lys Pro Lys Leu Leu Pro Leu Glu Leu Glu Lys Thr Ala Ile Gln
365 370 375
Asn Tyr Thr Val Thr Glu Phe Gln Pro Leu Tyr Tyr Val Ala Glu
380 385 390
Ser Phe Asn Asp Ala Lys Glu Lys Val Arg Asn Phe Ala Ala Thr
395 400 405
Ile Pro Arg Pro Phe Ser Val Arg Tyr Asp Pro Tyr Thr Gln Arg
410 415 420
Ile Glu Val Leu Asp Asn Thr Gln Gln Leu Lys Ile Leu Ala Asp
425 430 435
Ser Ile Asn Ser Glu Ile Gly Ile Leu Cys Ser Ala Leu Gln Lys
440 445 450
Ile Lys
452
<210>25
<211>452
<212>PRT
<213>人(Homo sapiens)
<220>
<221>VARIANT
<222>357
<223>Xaa=Cys或Tyr
<400>25
Met Ser Thr Ala Val Leu Glu Asn Pro Gly Leu Gly Arg Lys Leu
1 5 10 15
Ser Asp Phe Gly Gln Glu Thr Ser Tyr Ile Glu Asp Asn Cys Asn
20 25 30
Gln Asn Gly Ala Ile Ser Leu Ile Phe Ser Leu Lys Glu Glu Val
35 40 45
Gly Ala Leu Ala Lys Val Leu Arg Leu Phe Glu Glu Asn Asp Val
50 55 60
Asn Leu Thr His Ile Glu Ser Arg Pro Ser Arg Leu Lys Lys Asp
65 70 75
Glu Tyr Glu Phe Phe Thr His Leu Asp Lys Arg Ser Leu Pro Ala
80 85 90
Leu Thr Asn Ile Ile Lys Ile Leu Arg His Asp Ile Gly Ala Thr
95 100 105
Val His Glu Leu Ser Arg Asp Lys Lys Lys Asp Thr Val Pro Trp
110 115 120
Phe Pro Arg Thr Ile Gln Glu Leu Asp Arg Phe Ala Asn Gln Ile
125 130 135
Leu Ser Tyr Gly Ala Glu Leu Asp Ala Asp His Pro Gly Phe Lys
140 145 150
Asp Pro Val Tyr Arg Ala Arg Arg Lys Gln Phe Ala Asp Ile Ala
155 160 165
Tyr Asn Tyr Arg His Gly Gln Pro Ile Pro Arg Val Glu Tyr Met
170 175 180
Glu Glu Glu Lys Lys Thr Trp Gly Thr Val Phe Lys Thr Leu Lys
185 190 195
Ser Leu Tyr Lys Thr His Ala Cys Tyr Glu Tyr Asn His Ile Phe
200 205 210
Pro Leu Leu Glu Lys Tyr Cys Gly Phe His Glu Asp Asn Ile Pro
215 220 225
Gln Leu Glu Asp Val Ser Gln Phe Leu Gln Thr Cys Thr Gly Phe
230 235 240
Arg Leu Arg Pro Val Ala Gly Leu Leu Ser Ser Arg Asp Phe Leu
245 250 255
Gly Gly Leu Ala Phe Arg Val Phe His Cys Thr Gln Tyr Ile Arg
260 265 270
His Gly Ser Lys Pro Met Tyr Thr Pro Glu Pro Asp Ile Cys His
275 280 285
Glu Leu Leu Gly His Val Pro Leu Phe Ser Asp Arg Ser Phe Ala
290 295 300
Gln Phe Ser Gln Glu Ile Gly Leu Ala Ser Leu Gly Ala Pro Asp
305 310 315
Glu Tyr Ile Glu Lys Leu Ala Thr Ile Tyr Trp Phe Thr Val Glu
320 325 330
Phe Gly Leu Cys Lys Gln Gly Asp Ser Ile Lys Ala Tyr Gly Ala
335 340 345
Gly Leu Leu Ser Ser Phe Gly Glu Leu Gln Tyr Xaa Leu Ser Glu
350 355 360
Lys Pro Lys Leu Leu Pro Leu Glu Leu Glu Lys Thr Ala Ile Gln
365 370 375
Asn Tyr Thr Val Thr Glu Phe Gln Pro Leu Tyr Tyr Val Ala Glu
380 385 390
Ser Phe Asn Asp Ala Lys Glu Lys Val Arg Asn Phe Ala Ala Thr
395 400 405
Ile Pro Arg Pro Phe Ser Val Arg Tyr Asp Pro Tyr Thr Gln Arg
410 415 420
Ile Glu Val Leu Asp Asn Thr Gln Gln Leu Lys Ile Leu Ala Asp
425 430 435
Ser Ile Asn Ser Glu Ile Gly Ile Leu Cys Ser Ala Leu Gln Lys
440 445 450
Ile Lys
452
<210>26
<211>452
<212>PRT
<213>人(Homo sapiens)
<220>
<221>VARIANT
<222>357
<223>Xaa=Cys或X
<400>26
Met Ser Thr Ala Val Leu Glu Asn Pro Gly Leu Gly Arg Lys Leu
1 5 10 15
Ser Asp Phe Gly Gln Glu Thr Ser Tyr Ile Glu Asp Asn Cys Asn
20 25 30
Gln Asn Gly Ala Ile Ser Leu Ile Phe Ser Leu Lys Glu Glu Val
35 40 45
Gly Ala Leu Ala Lys Val Leu Arg Leu Phe Glu Glu Asn Asp Val
50 55 60
Asn Leu Thr His Ile Glu Ser Arg Pro Ser Arg Leu Lys Lys Asp
65 70 75
Glu Tyr Glu Phe Phe Thr His Leu Asp Lys Arg Ser Leu Pro Ala
80 85 90
Leu Thr Asn Ile Ile Lys Ile Leu Arg His Asp Ile Gly Ala Thr
95 100 105
Val His Glu Leu Ser Arg Asp Lys Lys Lys Asp Thr Val Pro Trp
110 115 120
Phe Pro Arg Thr Ile Gln Glu Leu Asp Arg Phe Ala Ash Gln Ile
125 130 135
Leu Ser Tyr Gly Ala Glu Leu Asp Ala Asp His Pro Gly Phe Lys
140 145 150
Asp Pro Val Tyr Arg Ala Arg Arg Lys Gln Phe Ala Asp Ile Ala
155 160 165
Tyr Asn Tyr Arg His Gly Gln Pro Ile Pro Arg Val Glu Tyr Met
170 175 180
Glu Glu Glu Lys Lys Thr Trp Gly Thr Val Phe Lys Thr Leu Lys
185 190 195
Ser Leu Tyr Lys Thr His Ala Cys Tyr Glu Tyr Asn His Ile Phe
200 205 210
Pro Leu Leu Glu Lys Tyr Cys Gly Phe His Glu Asp Asn Ile Pro
215 220 225
Gln Leu Glu Asp Val Ser Gln Phe Leu Gln Thr Cys Thr Gly Phe
230 235 240
Arg Leu Arg Pro Val Ala Gly Leu Leu Ser Ser Arg Asp Phe Leu
245 250 255
Gly Gly Leu Ala Phe Arg Val Phe His Cys Thr Gln Tyr Ile Arg
260 265 270
His Gly Ser Lys Pro Met Tyr Thr Pro Glu Pro Asp Ile Cys His
275 280 285
Glu Leu Leu Gly His Val Pro Leu Phe Ser Asp Arg Ser Phe Ala
290 295 300
Gln Phe Ser Gln Glu Ile Gly Leu Ala Ser Leu Gly Ala Pro Asp
305 310 315
Glu Tyr Ile Glu Lys Leu Ala Thr Ile Tyr Trp Phe Thr Val Glu
320 325 330
Phe Gly Leu Cys Lys Gln Gly Asp Ser Ile Lys Ala Tyr Gly Ala
335 340 345
Gly Leu Leu Ser Ser Phe Gly Glu Leu Gln Tyr Xaa Leu Ser Glu
350 355 360
Lys Pro Lys Leu Leu Pro Leu Glu Leu Glu Lys Thr Ala Ile Gln
365 370 375
Asn Tyr Thr Val Thr Glu Phe Gln Pro Leu Tyr Tyr Val Ala Glu
380 385 390
Ser Phe Asn Asp Ala Lys Glu Lys Val Arg Asn Phe Ala Ala Thr
395 400 405
Ile Pro Arg Pro Phe Ser Val Arg Tyr Asp Pro Tyr Thr Gln Arg
410 415 420
Ile Glu Val Leu Asp Asn Thr Gln Gln Leu Lys Ile Leu Ala Asp
425 430 435
Ser Ile Asn Ser Glu Ile Gly Ile Leu Cys Ser Ala Leu Gln Lys
440 445 450
Ile Lys
452
<210>27
<211>452
<212>PRT
<213>人(Homo sapiens)
<220>
<221>VARIANT
<222>362
<223>Xaa=Pro或Thr
<400>27
Met Ser Thr Ala Val Leu Glu Asn Pro Gly Leu Gly Arg Lys Leu
1 5 10 15
Ser Asp Phe Gly Gln Glu Thr Ser Tyr Ile Glu Asp Asn Cys Asn
20 25 30
Gln Asn Gly Ala Ile Ser Leu Ile Phe Ser Leu Lys Glu Glu Val
35 40 45
Gly Ala Leu Ala Lys Val Leu Arg Leu Phe Glu Glu Asn Asp Val
50 55 60
Asn Leu Thr His Ile Glu Ser Arg Pro Ser Arg Leu Lys Lys Asp
65 70 75
Glu Tyr Glu Phe Phe Thr His Leu Asp Lys Arg Ser Leu Pro Ala
80 85 90
Leu Thr Asn Ile Ile Lys Ile Leu Arg His Asp Ile Gly Ala Thr
95 100 105
Val His Glu Leu Ser Arg Asp Lys Lys Lys Asp Thr Val Pro Trp
110 115 120
Phe Pro Arg Thr Ile Gln Glu Leu Asp Arg Phe Ala Asn Gln Ile
125 130 135
Leu Ser Tyr Gly Ala Glu Leu Asp Ala Asp His Pro Gly Phe Lys
140 145 150
Asp Pro Val Tyr Arg Ala Arg Arg Lys Gln Phe Ala Asp Ile Ala
155 160 165
Tyr Asn Tyr Arg His Gly Gln Pro Ile Pro Arg Val Glu Tyr Met
170 175 180
Glu Glu Glu Lys Lys Thr Trp Gly Thr Val Phe Lys Thr Leu Lys
185 190 195
Ser Leu Tyr Lys Thr His Ala Cys Tyr Glu Tyr Asn His Ile Phe
200 205 210
Pro Leu Leu Glu Lys Tyr Cys Gly Phe His Glu Asp Asn Ile Pro
215 220 225
Gln Leu Glu Asp Val Ser Gln Phe Leu Gln Thr Cys Thr Gly Phe
230 235 240
Arg Leu Arg Pro Val Ala Gly Leu Leu Ser Ser Arg Asp Phe Leu
245 250 255
Gly Gly Leu Ala Phe Arg Val Phe His Cys Thr Gln Tyr Ile Arg
260 265 270
His Gly Ser Lys Pro Met Tyr Thr Pro Glu Pro Asp Ile Cys His
275 280 285
Glu Leu Leu Gly His Val Pro Leu Phe Ser Asp Arg Ser Phe Ala
290 295 300
Gln Phe Ser Gln Glu Ile Gly Leu Ala Ser Leu Gly Ala Pro Asp
305 310 315
Glu Tyr Ile Glu Lys Leu Ala Thr Ile Tyr Trp Phe Thr Val Glu
320 325 330
Phe Gly Leu Cys Lys Gln Gly Asp Ser Ile Lys Ala Tyr Gly Ala
335 340 345
Gly Leu Leu Ser Ser Phe Gly Glu Leu Gln Tyr Cys Leu Ser Glu
350 355 360
Lys Xaa Lys Leu Leu Pro Leu Glu Leu Glu Lys Thr Ala Ile Gln
365 370 375
Asn Tyr Thr Val Thr Glu Phe Gln Pro Leu Tyr Tyr Val Ala Glu
380 385 390
Ser Phe Asn Asp Ala Lys Glu Lys Val Arg Asn Phe Ala Ala Thr
395 400 405
Ile Pro Arg Pro Phe Ser Val Arg Tyr Asp Pro Tyr Thr Gln Arg
410 415 420
Ile Glu Val Leu Asp Asn Thr Gln Gln Leu Lys Ile Leu Ala Asp
425 430 435
Ser Ile Asn Ser Glu Ile Gly Ile Leu Cys Ser Ala Leu Gln Lys
440 445 450
Ile Lys
452
<210>28
<211>452
<212>PRT
<213>人(Homo sapiens)
<220>
<221>VARIANT
<222>414
<223>Xaa=Tyr或X
<400>28
Met Ser Thr Ala Val Leu Glu Asn Pro Gly Leu Gly Arg Lys Leu
1 5 10 15
Ser Asp Phe Gly Gln Glu Thr Ser Tyr Ile Glu Asp Asn Cys Asn
20 25 30
Gln Asn Gly Ala Ile Ser Leu Ile Phe Ser Leu Lys Glu Glu Val
35 40 45
Gly Ala Leu Ala Lys Val Leu Arg Leu Phe Glu Glu Asn Asp Val
50 55 60
Asn Leu Thr His Ile Glu Ser Arg Pro Ser Arg Leu Lys Lys Asp
65 70 75
Glu Tyr Glu Phe Phe Thr His Leu Asp Lys Arg Ser Leu Pro Ala
80 85 90
Leu Thr Asn Ile Ile Lys Ile Leu Arg His Asp Ile Gly Ala Thr
95 100 105
Val His Glu Leu Ser Arg Asp Lys Lys Lys Asp Thr Val Pro Trp
110 115 120
Phe Pro Arg Thr Ile Gln Glu Leu Asp Arg Phe Ala Asn Gln Ile
125 130 135
Leu Ser Tyr Gly Ala Glu Leu Asp Ala Asp His Pro Gly Phe Lys
140 145 150
Asp Pro Val Tyr Arg Ala Arg Arg Lys Gln Phe Ala Asp Ile Ala
155 160 165
Tyr Asn Tyr Arg His Gly Gln Pro Ile Pro Arg Val Glu Tyr Met
170 175 180
Glu Glu Glu Lys Lys Thr Trp Gly Thr Val Phe Lys Thr Leu Lys
185 190 195
Ser Leu Tyr Lys Thr His Ala Cys Tyr Glu Tyr Asn His Ile Phe
200 205 210
Pro Leu Leu Glu Lys Tyr Cys Gly Phe His Glu Asp Asn Ile Pro
215 220 225
Gln Leu Glu Asp Val Ser Gln Phe Leu Gln Thr Cys Thr Gly Phe
230 235 240
Arg Leu Arg Pro Val Ala Gly Leu Leu Ser Ser Arg Asp Phe Leu
245 250 255
Gly Gly Leu Ala Phe Arg Val Phe His Cys Thr Gln Tyr Ile Arg
260 265 270
His Gly Ser Lys Pro Met Tyr Thr Pro Glu Pro Asp Ile Cys His
275 280 285
Glu Leu Leu Gly His Val Pro Leu Phe Ser Asp Arg Ser Phe Ala
290 295 300
Gln Phe Ser Gln Glu Ile Gly Leu Ala Ser Leu Gly Ala Pro Asp
305 310 315
Glu Tyr Ile Glu Lys Leu Ala Thr Ile Tyr Trp Phe Thr Val Glu
320 325 330
Phe Gly Leu Cys Lys Gln Gly Asp Ser Ile Lys Ala Tyr Gly Ala
335 340 345
Gly Leu Leu Ser Ser Phe Gly Glu Leu Gln Tyr Cys Leu Ser Glu
350 355 360
Lys Pro Lys Leu Leu Pro Leu Glu Leu Glu Lys Thr Ala Ile Gln
365 370 375
Asn Tyr Thr Val Thr Glu Phe Gln Pro Leu Tyr Tyr Val Ala Glu
380 385 390
Ser Phe Asn Asp Ala Lys Glu Lys Val Arg Asn Phe Ala Ala Thr
395 400 405
Ile Pro Arg Pro Phe Ser Val Arg Xaa Asp Pro Tyr Thr Gln Arg
410 415 420
Ile Glu Val Leu Asp Asn Thr Gln Gln Leu Lys Ile Leu Ala Asp
425 430 435
Ser Ile Asn Ser Glu Ile Gly Ile Leu Cys Ser Ala Leu Gln Lys
440 445 450
Ile Lys
452
Claims (1)
1.一种PAH基因的突变体,其特征在于,该突变体具体为SEQ ID NO.1所示序列的第548位核苷酸由A→G,该突变体的氨基酸序列如SEQ ID NO.19所示;
所述的突变体通过以下方式检测得到:
步骤一,以GenBank数据库中PAH基因第6号外显子以及外显子与内含子接合部位序列为模板设计一对等位基因特异性的核酸引物,利用引物对来扩增PAH基因相应外显子的DNA序列,对扩增产物进行分离纯化,得到相应分离核酸;
步骤二,对分离核酸的PAH基因外显子的核苷酸进行是否存在突变结果的检测;
所述突变结果的检测是指:当为第6号外显子时,检测SEQ ID NO.1所示序列的第548位核苷酸是否存在突变,即A→G;此时,SEQ ID NO.1所示序列编码的氨基酸序列SEQ ID NO.2第183位由Glu(E)→Gly(G),如SEQ IDNO.19所示。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN 200910046100 CN101481741B (zh) | 2009-02-12 | 2009-02-12 | 一种新的突变的pah基因 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN 200910046100 CN101481741B (zh) | 2009-02-12 | 2009-02-12 | 一种新的突变的pah基因 |
Publications (2)
Publication Number | Publication Date |
---|---|
CN101481741A CN101481741A (zh) | 2009-07-15 |
CN101481741B true CN101481741B (zh) | 2012-01-25 |
Family
ID=40879031
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN 200910046100 Expired - Fee Related CN101481741B (zh) | 2009-02-12 | 2009-02-12 | 一种新的突变的pah基因 |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN101481741B (zh) |
Families Citing this family (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN101899518B (zh) * | 2010-07-23 | 2012-07-25 | 苏州大学 | 检测苯丙酮尿症pah基因7个热点突变位点的试剂盒及其pcr扩增方法 |
CN107523608A (zh) * | 2016-06-22 | 2017-12-29 | 海门中科基因生物科技有限公司 | 一种检测苯丙酮尿症致病基因突变的试剂盒 |
CN111073884A (zh) * | 2020-02-14 | 2020-04-28 | 昆明理工大学 | 提高非编码区域距离<50bp的SNP中具有功能效应的SNP位点检测准确率的方法 |
CN115772503B (zh) * | 2022-08-16 | 2023-10-17 | 广东省南山医药创新研究院 | 一种表达pah的基因修饰细胞药物及其制备方法与应用 |
-
2009
- 2009-02-12 CN CN 200910046100 patent/CN101481741B/zh not_active Expired - Fee Related
Non-Patent Citations (3)
Title |
---|
Fang Song,et al.Phenylketonuria mutations in Northern China.《Molecular Genetics and Metabolism》.2005,107-118. * |
宋昉,等.联合应用STR 连锁分析与多重等位基因特异PCR 进行PKU 基因诊断.《中华医学遗传学杂志》.1997,9-12. * |
瞿宇晋.苯酮尿症的分子研究及其基因型-表型相关性的研究进展.《国际儿科学杂志》.2006,23-26. * |
Also Published As
Publication number | Publication date |
---|---|
CN101481741A (zh) | 2009-07-15 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
Akey et al. | Melting curve analysis of SNPs (McSNP®): A gel-free and inexpensive approach for SNP genotyping | |
CN101481741B (zh) | 一种新的突变的pah基因 | |
Wang et al. | Analysis of molecular inversion probe performance for allele copy number determination | |
Lee et al. | Selection of twenty-four highly informative SNP markers for human identification and paternity analysis in Koreans | |
AU4002900A (en) | Thermostable nucleoside diphosphate kinase for nucleic acid detection | |
US20160076089A1 (en) | A method for dna amplification with a blocking oligonucleotide | |
Tzvetkov et al. | Genome‐wide single‐nucleotide polymorphism arrays demonstrate high fidelity of multiple displacement‐based whole‐genome amplification | |
CN104212904A (zh) | 一种用于快速检测人类cyp2c19基因多态性的试剂盒及其使用方法 | |
CN101434994A (zh) | Cyp2c9基因第九号外显子单核苷酸多态性的检测方法 | |
CN101109018A (zh) | Cyp2d6基因第九号外显子的单核苷酸多态性的检测方法 | |
Oka et al. | Genotyping of 38 insertion/deletion polymorphisms for human identification using universal fluorescent PCR | |
CN112980933A (zh) | 一种基于CRISPR-Cas体系的SNP分型检测方法及其应用 | |
CA3069580A1 (en) | Dna polymerase with increased gene mutation specificity and pcr buffer composition for increasing activity thereof | |
KR101147277B1 (ko) | Jak2 유전자의 변이 검출용 프로브 및 그 용도 | |
Berger et al. | Molecular characterization and Austrian Caucasian population data of the multi-copy Y-chromosomal STR DYS464 | |
US11268140B2 (en) | Delayed pyrophosphorolysis activated polymerization | |
CN104818340A (zh) | 检测jak2基因v617f位点多态性的引物、试剂盒及其pcr方法 | |
CN108624652B (zh) | 多重焦磷酸化激活性聚合反应在一个反应内扩增单位点多个序列几乎完全相同的模板 | |
CA2611188A1 (en) | Mdr1 snp in acute rejection | |
KR100818276B1 (ko) | 알콜 분해 능력과 숙취 발생 여부를 예측하기 위한프라이머 세트, 프로브 세트, 방법 및 키트 | |
JP2008545444A (ja) | 急性拒絶反応に関連するil10snp | |
US20180155793A1 (en) | Method, sequences, compositions and kit for detection of changes in the promoter of the gene htert | |
Silander et al. | Evaluating whole genome amplification via multiply-primed rolling circle amplification for SNP genotyping of samples with low DNA yield | |
Chen et al. | Natural haplotypes in the regulatory sequences affect human alcohol dehydrogenase 1C (ADH1C) gene expression | |
Ho et al. | Novel cytochrome P450-2D6 promoter sequence variations in hepatitis C positive and negative subjects |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
C06 | Publication | ||
PB01 | Publication | ||
C10 | Entry into substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
C14 | Grant of patent or utility model | ||
GR01 | Patent grant | ||
C17 | Cessation of patent right | ||
CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20120125 Termination date: 20130212 |