正常眼压性青光眼疾病易感性基因及其应用的制作方法.docx

文档介绍：该【正常眼压性青光眼疾病易感性基因及其应用的制作方法 】是由【开心果】上传分享，文档一共【230】页，该文档可以免费在线阅读，需要了解更多关于【正常眼压性青光眼疾病易感性基因及其应用的制作方法 】的内容，可以使用淘豆网的站内搜索功能，选择自己适合的文档，以下文字是截取该文章内的部分文字，如需要获得完整电子版，请下载此文档到您的设备，方便您编辑和打印。正常眼压性青光眼疾病易感性基因及其应用的制作方法
专利名称:正常眼压性青光眼疾病易感性基因及其应用的制作方法
技术领域:
本发明涉及正常眼压性青光眼疾病易感性基因及其应用。
背景技术:
青光眼是由于眼压升高至能够维持正常视功能的健康眼压以上的眼压而对视神经带来伤害的进行性的难治性疾病。如果任由该疾病继续发展,则视野狭窄会不断加剧,有时会导致失明,尽管目前其在日本的失明原因中占据首位,但其原因尚不明确,还没有准确的诊断方法、有效的治疗方法及预防方法。日本人中最多见的是其中虽然眼压在正常范围内但仍发生青光眼的正常眼压性青光眼(NTG),其发生频率在40岁以上的人群中约为4%。由于NTG的眼压在正常范围内,因此在眼压检查中很难发现,在健康体检或通常的眼科检查中容易疏漏。由于视神经的损伤不会恢复,因此对于NTG,早期发现/早期治疗是最重要的关键。但是,由于其进展缓慢且中心视野在晚期才会受到损害,因此,缺乏自觉症状,视神经损害在本人还未注意到时会逐渐进展。目前正在进行正常眼压性青光眼疾病易感性基因的探索,但是尚未发现与疾病关联的基因。已经进行了若干候选基因的分析。已经集中精力分别进行了高度疑似与青光眼相关的myocilin(非专利文献
1-15)以及optineurin(非专利文献16-30)、opticatrophy1(非专利文献31-41)基因的分析,但与NTG的相关性还不明确。另外,也进行了候选基因的分析,但仅仅得到相关的启示。
发明内容
本发明的目的在于发现正常眼压性青光眼疾病易感性基因并提供其应用方法。本发明人以正常眼压性青光眼患者和正常人为对象,对全基因组上的SNP进行了网罗性分析/比较,结果发现,多个基因存在差异。本发明是基于该见解而完成的。本发明的主旨如下所述。(1)一种正常眼压性青光眼的检查方法,其中,包括对多态性位点的碱基进行鉴定,所述多态性位点为选自由人第6号染色体的包含EL0VL5的区域、人第2号染色体的包含SRBDl的区域、人第3号染色体的包含ARPP-21的区域、人第4号染色体的包含EPHA5的区域、人第6号染色体的包含GMDS的区域、(包含HSPA1B)的区域、人第6号染色体的包含SYTL3的区域、人第7号染色体的包含NXPHl的区域、人第7号染色体的包含LHFPL3的区域、人第11号染色体的包含GLB1L3的区域、人第18号染色体的包含ZNF407的区域、人第1号染色体的包含PAX7的区域、人第1号染色体的包含PTPRF的区域、(包含CHDlL和/或FM05)的区域、(
包含FDPS和/或ASHlL和/或KCNN3)的区域、人第1号染色体的包含FAM5B和/或ASTm的区域、人第1号染色体的包含PKPl的区域、人第2号染色体的包含KLHL29和/或FLJ14126的区域、人第3号染色体的包含THRB的区域、人第3号染色体的包含MED12L和/或CLRN10S和/或GPR171的区域、人第4号染色体的包含S0RBS2的区域、人第5号染色体的包含MAST4的区域、人第5号染色体的包含GLRX和/或C5orf27的区域、人第5号染色体的包含EBFl的区域、人第5号染色体的包含D0CK2的区域、-(包含HLA-DPA1)的区域、人第6号染色体的包含L0C100132919的区域、人第号染色体的包含AAAl和/或NPSRl的区域、人第7号染色体的包含ELMOl的区域、人第8号染色体的包含TNKS的区域、人第8号染色体的包含ANGPTl的区域、人第9号染色体的包含PGM5的区域、人第9号染色体的包含TMCl的区域、人第9号染色体的包含R0R2的区域、人第9号染色体的包含PPP6C和/或C9orf126的区域、人第10号染色体的包含GRIDl的区域、(包含SPIl和/或SLC39A13和/或PSMC3和/或RAPSN和/或NUP160)的区域、人第11号染色体的包含0R5R1的区域、人第11号染色体的包含MS4A7和/或MS4A14的区域、人第11号染色体的包含MAP6和/或⑶PD5和/或SERPINH1的区域、人第11号染色体的包含
llq23_24(包含PCSK7和/或RNF214)的区域、人第12号染色体的包含TA0K3的区域、人第12号染色体的包含STX2的区域、人第13号染色体的包含CARS2的区域、人第15号染色体的包含CYP19A1的区域、人第17号染色体的包含CAlO的区域、人第18号染色体的包含L0C643542的区域、人第20号染色体的包含PTPRT的区域、人第21号染色体的包含ITSm的区域、人第2号染色体的包含LRP2的区域、人第11号染色体的包含APIP和/或PDHX的区域、人第12号染色体的包含CUX2的区域、以及人第17号染色体的包含T0M1L1的区域组成的组中的至少一个区域中的至少一个多态性位点。(2)如(1)所述的检查方法,其中,人第6号染色体的包含EL0VL5的区域中的多态性位点选自由单核苷酸多态性国际编号rs222450、rs9474394、rs2816344、rs2816341、rs2518579、rs2518578、rs9367511、rs6915699、rs6930045、rs9370188、rs9382180、rs9382181、rs4486010、rs2816379、rs6939730、rs2817088、rs2817090、rs2816372、rs2562895、rs2816364、rs2562893、rs281710Urs2816362、rs2816356、rsl0948744、rsl2183976、rs2562898、rs735860、rs715441、rs2057024、rsl429146、rs9463895、rs2235723、rsl346603、rs9474476、rs2294867、rs9349660、rs974323、rs6909592、rs9367520、rs9395854、rs209485、rs9395856
、rs7747926、rs7738788、rs209500、rs9357760、rs9370196、rs209512、rs209517、rs937020Urs9367529、rsl2209741、rs7744451、rs6904083、rs6904376、rs9367532、rs2067833、rs9382212、rs2139077、rs2397146、rs7742367、rs9474576、rs622447、rs3736729、rsl3212365和rs761141组成的组,人第2号染色体的包含SRBDl的区域中的多态性位点选自由单核苷酸多态性国际编号rsll686431、rs7580559、rs3908093、rs2343412、rsl2623996、rs7573149、rs918810、rs6721199、rs7579209、rsl0194925、rsl7033378、rs2343466、rsl7033398、rs6737172、rs4953226、rs3851333、rsl2473388、rsll681887、rs35608719、rsll888802、rsll678872、rs2343468、rsl3003019、rs6760244、rsl2471726、rs2081297、rsl0460504、rs7562458、rs4953230、rs4952763、rs6719211、rsl014454、rs3755070、rs3213787、rsl0210691、rs377025Urs4455206、rs3755076、rs3770254、rslll25017、rs3770264、rsl0205197、rsl0427308、rsl7033745、rs3770278、rsl7322370、rs6736954、rsl0427402、rs4476395、rsl3023749、rsl7033801、rs755652、rs748573、rs6708810、rs6710581、rsl2712945、rsl7033871、rs3755082、rs6544840、rs7599740、rsll884064、rs7596942、rs7565326、rsl7323037
、rsl916231、rsl517001、rsl522988、rs614281、rs582213、rs650508、rs666334、rsl7033965、rs556650、rs2204204、rs3795863、rs2285024、rs505310、rsl0490342、rs612717、rsl0490341、rs656823、rs563601、rs609573、rs6746467、rs637889、rsl0495926、rsl522986、rsl522987、rs6544843和rs6724488组成的组,人第3号染色体的包含ARPP-21的区域中的多态性位点选自由单核苷酸多态性国际编号rsl523048、rsl523029、rsl2487524、rsl403468、rs872133、rsl523040、rsl523041、rsl306945Ursl2629480,rsl357449、rs6801949、rsl7033355、rs9873254、rs9839823、rs6794354,rs6794373、rsl2637211、rs9855328、rs2037538、rs2037539、rsl523038、rsll718271、rsl608314、rs2197728、rs9311101、rsl0490870、rsl7033506、rsl2634096、rs2359774、rs9860326、rs4678788、rs3213953、rs6799641、rsl7201627、rs4678789、rsl2632607,rslll29660、rslll29662、rsl7033672、rsl728020Urs677909Urs3772395、rs9872664、rsl963934、rs35102908、rs4678802、rs4678803、rs6550367、rsl7033738、rs6801590、rsl7033748、rs9865772、rsl7033755、rsl7228111、rs2016955、rs2016975、rs735353、rsll920715、rsl378481、rsl7814981、rsl455489
、rs4678509、rsl0510667、rs6799649、rs6799609、rsl7033836、rs4234248、rs6770245、rsl0865865、rs7615307、rs9845811、rsl7033961、rsl488092、rsl0461001和rsl7033999组成的组,人第4号染色体的包含EPHA5的区域中的多态性位点选自由单核苷酸多态性国际编号rs371925、rs4241661、rsl70654、rsl514271、rs2063419、rsl3102419、rslll31589、rs2167320、rsll59057、rsl2501311、rsl7086016、rs961489、rs7684130、rs3749526、rs486065Ursll938753、rsl376417、rsl0025570、rsl376416、rs2084682、rs7658065、rs9312144、rsl376412、rsl7086181、rsl7086185、rs6847413、rs2198103、rsl2509018、rsl7082122、rs6823779、rsl7086224、rsl451170、rs4289492、rs4371663、rs9986026、rs9991256、rs4267782、rs7660334、rs6815080、rsll737314、rs4365778、rs7673091、rs4320185、rs4604104、rs7684022、rs4860679、rs6844942、rsl2644315、rs4599467、rs6834811、rs4320186、rs4487412、rs7667410、rs4611975、rs437020Urs4438803和rs4608860组成的组,人第6号染色体的包含GMDS的区域中的多态性位点选自由单核苷酸多态性国际编号rsll966212、rs2143396、rs6911992、rs9378593、rs9392253、rs9378594、rs2050158、rs9391900
、rs6596786、rs2235706、rs9378596、rsl997773、rs6926322、rs7754106、rs7750178、rs742520、rs2210370、rs6940618、rs349100、rs9405444、rs6932005、rs4959523、rsl0484953、rs464778、rsll5705、rsl013185、rsll242672、rs463641、rs4959525、rs369656、rs459162、rsl27091、rs4959530、rs463264、rs7757477、rs448915、rs444018、rs443971、rs9391913、rs238048、rs238050、rs9378605、rs2459602、rs2438074、rsl2191625、rs2438077、rs2496292、rs2496301、rs2438083、rs977674、rs977673、rsl7259747、rsl437288、rs7772349、rs6596805、rsl347656、rs6925983、rsl550199、rsll242676、rs7744559、rsll966550、rs9378290、rs9405136、rs9405470、rs9392285、rs9405137、rs9405471、rs746095、rs9378623、rs9378292、rsl711957、rs7742720、rs9378629、rs7741690、rs9328052、rs9328053、rsl922938、rs2745636、rs2816242、rs932410、rsl474721、rs9392296、rs9502950、rs6907725、rs9405484、rs4443540、rs4355648、rs9328058、rs9328059、rs2569866、rs6935712、rs6935896、rs6937266、rs6925228、rsll242704、rs2816286、rs2816287、rs6596833、rs2317965、rs2873591、rs2569835、rs2745567、rs2493160、rs2317966、rs9392305、rs9501738、rs2569
839、rs932806Urs9378300、rs2816221、rs6916316、rs2281272、rs2569824、rs9405496、rsl810496、rs2814827、rs7759035、rs9502997、rs281481Urs2317964、rs9378304、rs2569854、rsl2206340、rs4538755、rs9378305、rs9503011、rs9405505、rs9503015、rs9501762、rs9405506、rsl2197419、rs7765344、rs7765461、rsl013303、rs3800046、rs689035、rs2318108、rs6919059、rs6928276、rs226456、rs9378314、rsll57673、rsll57675、rs9391933、rs9328071、rs3778533、rsl028714、rs3800094、rs3778539、rs6596857、rs7776397、rs6596858、rs9378661,rs3823279、rs3800122、rsl0484693、rsl7772389、rs4959160、rs3778555、rs4463305、rs3800140、rsl7134506、rs3800142、rs3800143、rs3800144、rs3800146、rs2761234、rs9405156、rsl7134549、rsl408002、rsl830733、rsl830734、rsl0223785、rs9405157、rs7772545、rs6596866、rs4959621、rs4412249、rs4367413、rsll242729、rs6925298、rsl2212324、rs9392353、rsll242730、rs4580917、rs6910252、rsll242733、rs9503080、rsll242735、rs476594、rs9378676、rs676015、rs2026446、rs4959631、rsl7134693、rs3800156、rsll242740、rs4959635、rs3800159、