KR20160029948A - Method for Imputing Classical Alleles of HLA-A, HLA-B, HLA-C, HLA-DPB1 or HLA-DQB1 Using Single Nucleotide Polymorphisms in East Asian Population - Google Patents

Abstract

The present invention relates to a genotype analysis method using a single base polymorphism combination capable of accurately predicting HLA-A, HLA-B, HLA-C, HLA-DPB1 or HLA-DQB1 genotypes of East Asian people with high accuracy. A, HLA-B, HLA-C, HLA-DPBl or HLA-DQB1 genotypes of East Asian can be predicted with high accuracy by using the composition of the present invention.

Description

Methods for Analysis of HLA-A, HLA-B, HLA-C, HLA-DPB1 or HLA-DQB1 Genotypes in East Asian Patients Using Single Base Polymorphism -DPB1 or HLA-DQB1 Using Single Nucleotide Polymorphisms in East Asian Population}

The present invention relates to a genotype analysis method using a single base polymorphism combination capable of accurately predicting HLA-A, HLA-B, HLA-C, HLA-DPB1 or HLA-DQB1 genotypes of East Asian people with high accuracy.

Human leukocyte antigen (HLA) genes present in the chromosome 6, major histocompatibility complex (MHC) locus, have a high level of genetic diversity [1]. Although the various genetic and heterozygosity of HLA molecules has been shown to contribute to defense of a wide range of foreign substances and pathogens [2], the genotypes of HLA genes have been implicated in susceptibility or prognosis to a variety of inflammatory diseases [3, 4 ].

 Despite this clinical significance, HLA genotyping for a large number of samples has been limited by the high cost and low processing efficiency of genotyping methods. Recently, it is possible to infer HLA alleles from single nucleotide polymorphisms in MHC locus using several HLA genotyping methods such as SNP2HLA and HLA * IMP [5, 6]. SNP2HLA has been successfully used in the study of complex diseases such as HIV infection, rheumatoid arthritis, multiple sclerosis and follicular lymphoma because this method was able to estimate the amino acid residues of the HLA gene as well as the classical HLA allele [ 7, 10]. SNP2HLA uses HLA reference panels containing single nucleotide polymorphism information in the MHC region, along with traditional HLA alleles and amino acid residues, as a reference for genotypic prediction [5]. However, since this HLA reference panel is manufactured from European genetic information, studying non-Europeans is very limited in their use because they can not guarantee prediction accuracy.

The present inventors have developed an HLA reference panel which can efficiently be used for prediction of HLA genotypes of East Asian people including Koreans, Japanese and Chinese, and can be used together with SNP2HLA, and developed a single nucleotide polymorphism required for accurate prediction.

Numerous papers and patent documents are referenced and cited throughout this specification. The disclosures of the cited papers and patent documents are incorporated herein by reference in their entirety to better understand the state of the art to which the present invention pertains and the content of the present invention.

The inventors of the present invention have developed a reference containing a single base polymorphism combination for the genotyping of HLA-A, HLA-B, HLA-C, HLA-DPB1 or HLA-DQB1 of East Asian people including Korean, Research efforts. HLA-B, HLA-C, HLA-DPB1, or HLA-DQB1 genotypes were determined with high accuracy by using a combination of 1778 single nucleotide polymorphisms. Thereby completing the present invention.

Accordingly, an object of the present invention is to provide a data collection method for genotyping HLA-A, HLA-B, HLA-C, HLA-DPB1 or HLA-DQB1 of East Asian people.

A further object of the present invention is East of the HLA-A, HLA-B, HLA-C, HLA-A of HLA-DPB1 or analyzed using the data collected for genotype determination of the HLA-DQB1 target, HLA-B , HLA-C, HLA-DPBl or HLA-DQB1 genotypes.

Other objects and advantages of the present invention will become more apparent from the following detailed description of the invention, claims and drawings.

According to one aspect of the present invention, the present invention provides a method of analyzing a single nucleotide polymorphism combination of SNP list 1 from a nucleic acid sample isolated from a biological sample derived from a subject to determine genotypes of the single nucleotide polymorphisms A , HLA-B, HLA-C, HLA-DPBl or HLA-DQB1 genotypes of the East Asian population including the human leukocyte antigen-

SNP list 1

rs7739830, rs1880271, rs11751616, rs6908645, rs522024, rs807213, rs807211, rs807203, rs1179007, rs707903, rs1183694, rs806972, rs2298090, rs2298091, rs806966, rs806978, rs806792, rs438534, rs3857549, rs6921148, rs13195509, rs4713002, rs13194984, rs7768682, rs9295700, rs7751878, rs7741445, rs6932003, rs6904071, rs6913660, rs6921711, rs17737028, rs13194053, rs12210982, rs9468019, rs9461345, rs7746199, rs9468031, rs11965377, rs2893912, rs9468058, rs11967073, rs9969094, rs11962403, rs2393997, rs6908615, rs4713119, rs7742752, rs12192568, rs6915101, rs9468227, rs9295749, rs2021835, rs11962868, rs9468236, rs11970638, rs7748520, rs7742529, rs10456357, rs6910968, rs6922530, rs7769416, rs7741570, rs6913038, rs10484404, rs3734572, rs7747772, rs9468293, rs6908414, rs6932313, rs1150671, rs6929559, rs1233667, rs1233698, rs1736892, rs3757183, rs6918043, rs2799076, rs11966237, rs11965542, rs1150725, rs7759855, rs6922161, rs6902583, rs6456812, rs9295769, rs6908459, rs7759845, rs6918631, rs6929449, rs94 68346, rs2859379, rs3757181, rs719370, rs2859367, rs2531808, rs2531810, rs2531816, rs6927023, rs722788, rs423118, rs11757235, rs426922, rs413488, rs422089, rs454746, rs449074, rs411538, rs420436, rs7738979, rs11969304, rs911178, rs4711176, rs7742658, rs6925972, rs1319076, rs6456832, rs9468413, rs6456834, rs11754985, rs11963531, rs209181, rs9501112, rs176461, rs7775657, rs209139, rs12386522, rs6934470, rs9468459, rs9295784, rs9468461, rs9468464, rs3129795, rs9468469, rs9468474, rs3129106, rs9468487, rs3129157, rs3130801, rs11962388, rs11964645, rs6899390, rs9468508, rs3117433, rs9348827, rs7761746, rs9257792, rs9257803, rs9257805, rs11969272, rs16894919, rs2073148, rs2746149, rs16894948, rs1362076, rs7771335, rs2107189, rs17415601, rs2066951, rs17184114, rs9393967, rs7767894, rs2294748, rs9461533, rs9391895, rs6930217, rs6935418, rs10484548, rs362541, rs3025657, rs6902738, rs7763501, rs16895058, rs6915177, rs2076486, rs64036, rs2272991, rs362532, rs459970, rs6912437, rs3025650, rs311707 3, rs17508548, rs3095273, rs362518, rs2267633, rs2076483, rs2076482, rs29267, rs29264, rs29230, rs29246, rs29243, rs29273, rs3131854, rs9257928, rs16895214, rs439812, rs29269, rs29272, rs29231, rs29235, rs9468571, rs3135050, rs2857783, rs2256266, rs2857784, rs6905408, rs3130253, rs2535250, rs2535248, rs2857771, rs2071652, rs1318631, rs2071653, rs2273192, rs2747419, rs9257940, rs378596, rs9257985, rs3117301, rs2747453, rs2747454, rs2747457, rs2747458, rs2747460, rs2747466, rs3129039, rs3129029, rs3129066, rs9258102, rs6911622, rs2107203, rs3129055, rs9258122, rs3116798, rs2394660, rs3131863, rs11962017, rs1476573, rs1476572, rs1610594, rs1611364, rs2735063, rs1632962, rs2517911, rs2517910, rs9258170, rs1362126, rs2076183, rs9258186, rs1736926, rs2235383, rs1736922, rs1628578, rs2523404, rs2735059, rs2272874, rs3736694, rs2743925, rs2523402, rs2523399, rs2735052, rs2844833, rs2523395, rs2394159, rs2394160, rs9258205, rs9258206, rs1736915, rs1736913, rs9258207, rs9258208, rs9258209, rs273 5051, rs9258211, rs2844831, rs9258213, rs932338, rs1633096, rs9258218, rs2743951, rs2517938, rs909732, rs4713240, rs2523386, rs9258225, rs2072894, rs2523385, rs34260811, rs1633085, rs733841, rs1610621, rs909728, rs909725, rs4713244, rs9391630, rs9258260, rs1633068, rs1737079, rs1633057, rs1633056, rs1610628, rs1633048, rs1737069, rs7759474, rs1611285, rs1626392, rs1625636, rs1737060, rs1633041, rs2735048, rs2735046, rs1737043, rs1737041, rs11753872, rs9258302, rs9258303, rs1615962, rs2844836, rs1633021, rs1002046, rs2743941, rs7758742, rs1610644, rs1633011, rs11758087, rs2523414, rs11752553, rs11751333, rs1611185, rs2017525, rs3891160, rs1610711, rs1736982, rs1736981, rs1611192, rs1632988, rs1632987, rs17178826, rs9258447, rs11757182, rs2523409, rs1736971, rs1736969, rs1610699, rs3926748, rs11753629, rs11753654, rs1077432, rs2735028, rs2743933, rs2743931, rs2394177, rs1611149, rs1736936, rs3115630, rs915669, rs1233330, rs11753296, rs16896052, rs2394180, rs2735014, rs9258525, rs2523779, rs2743937, rs2735003, rs9258537, rs2523777, rs2523776, rs1611133, rs2523774, rs2523769, rs2844827, rs16896081, rs2734994, rs2523767, rs2517879, rs9258557, rs2394185, rs2394186, rs9380146, rs3115628, rs2247504, rs2508050, rs3115627, rs2523756, rs9258631, rs2517862, rs3115626, rs2517855, rs2517854, rs3132726, rs6919513, rs1611684, rs9258738, rs17185692, rs2523822, rs9295822, rs3094170, rs1611717, rs9258766, rs9258771, rs765649, rs1611737, rs1611738, rs2524035, rs3094165, rs2734974, rs2734973, rs2517826, rs9258866, rs3132718, rs9258883, rs3094654, rs3132714, rs2523809, rs2523808, rs2517904, rs2524024, rs2860580, rs3823342, rs6921314, rs2735097, rs1655900, rs2523949, rs9260497, rs404046, rs429511, rs2523942, rs2517700, rs9260679, rs441808, rs9260722, rs9260734, rs3903160, rs6457109, rs2844806, rs3893259, rs4713270, rs3869062, rs3893464, rs9260759, rs9260761, rs17186496, rs2517673, rs4713275, rs1061535, rs6916422, rs2523969, rs2523961, rs2523960, rs2256902, rs2523946, rs3823355, rs2844804, rs3823358, rs2232238, rs2232239, rs2523943, rs6904029, rs2735076, rs2394250, rs2893999, rs3823374, rs2571375, rs3823384, rs9260860, rs2108691, rs9260915, rs423808, rs2571430, rs2246638, rs2394255, rs401618, rs2735067, rs11757750, rs17186937, rs11755961, rs3901554, rs5025708, rs12665186, rs9260930, rs12662611, rs9260967, rs9260984, rs6457121, rs6910898, rs9260997, rs9260998, rs9261040, rs6941318, rs6904120, rs9261079, rs9261081, rs9261091, rs11760176, rs9261093, rs11965524, rs2286405, rs2286404, rs9261105, rs356968, rs6940082, rs2240619, rs3765604, rs9261115, rs9261129, rs11753431, rs3734836, rs9261130, rs9261138, rs16896044, rs6457126, rs356954, rs9357092, rs9261145, rs6926792, rs6931776, rs165256, rs4711206, rs9261151, rs3891157, rs3129012, rs3891156, rs6919617, rs1150743, rs9261171, rs9261174, rs4448133, rs9261189, rs16896923, rs9261193, rs3121593, rs166327, rs3869067, rs3869068, rs9261203, rs259938, rs3910312, rs9261216, rs259939, rs259940, rs9261224, rs259942, rs3132128, rs6457138 , Rs7771476, rs6457140, rs28570682, rs7761314, rs9261257, rs9261258, rs3869070, rs9261261, rs9261263, rs6911724, rs259919, rs6917477, rs10484549, rs9261265, rs3757328, rs3757329, rs3757333, rs9295829, rs1150742, rs7770092, rs7770505, rs10745, rs9261269, rs9261270, rs1150740 , rs9261277, rs3188482, rs3807030, rs3807031, rs9261285, rs2074482, rs9261288, rs1245371, rs2301753, rs2301751, rs9393989, rs2074480, rs2074479, rs9261301, rs9261302, rs3807033, rs3132682, rs3807035, rs1150735, rs2394734, rs4711209, rs9261316, rs7382061, rs2057728, rs9261361 , rs9261371, rs17187805, rs9261387, rs6923832, rs7765810, rs9261394, rs1264702, rs916570, rs1264701, rs1264698, rs7763159, rs1108052, rs1110446, rs2240070, rs1116222, rs1116221, rs11964542, rs2844796, rs2248289, rs3132680, rs2523992, rs2523988, rs2523987, rs2517597, rs2523986 , rs2523981, rs2523979, rs9261434, rs17455565, rs10947056, rs2523995, rs3132676, rs9468693, rs3094134, rs3757334, rs12212092, rs9261536, rs2857449, rs17188127, rs2074475, rs10 63280, rs13212414, rs9261538, rs2517623, rs9261547, rs4476873, rs10947058, rs11967808, rs11961294, rs1345229, rs9295837, rs3094138, rs3094137, rs10456378, rs2508028, rs9261588, rs928824, rs28780093, rs1264622, rs8973, rs3094631, rs7758503, rs1264608, rs1264581, rs12663184, rs7767653, rs3129838, rs6931763, rs6905389, rs3132649, rs3094061, rs3130375, rs3130379, rs3094622, rs3094621, rs2057726, rs3129808, rs3129809, rs3130361, rs11759238, rs7772240, rs3129817, rs3129820, rs3132631, rs3132630, rs3129822, rs3132625, rs1245218, rs7744914, rs28780099, rs3094032, rs3130126, rs3094050, rs17475879, rs3130116, rs9261761, rs9261821, rs9261846, rs1573294, rs9261895, rs9261919, rs9261922, rs9261923, rs9261926, rs9261947, rs9501447, rs1079541, rs9295863, rs9295871, rs9295873, rs4947284, rs9295886, rs17411480, rs35407515, rs34101875, rs9501336, rs11966619, rs35792611, rs2524172, rs2516670, rs28780106, rs3757335, rs12192673, rs4713337, rs3132611, rs4148248, rs1264429, rs9348841, rs2517565, rs17195551, rs1079687, rs3094104, rs3132608, rs2269708, rs1076829, rs9262138, rs3130000, rs1076828, rs3094098, rs2285322, rs3094097, rs17189246, rs2285321, rs6937357, rs9468805, rs9262141, rs2269707, rs2239887, rs2394392, rs3129996, rs2249059, rs3094092, rs2269703, rs2239886, rs28994872, rs2269702, rs28986466, rs6929626, rs17189329, rs28986465, rs2075015, rs6924270, rs3132587, rs9461624, rs4713354, rs3132584, rs25527, rs8233, rs9500864, rs3095329, rs35580157, rs3094127, rs12179975, rs9501029, rs1064627, rs3909184, rs9969042, rs9968884, rs9380182, rs12111310, rs10947088, rs10947089, rs2301277, rs12210092, rs6926530, rs11757629, rs17189427, rs3131064, rs1264377, rs3129987, rs3094123, rs3094111, rs1264352, rs9262216, rs3130785, rs3130648, rs11757306, rs9262222, rs3095345, rs11759095, rs9262256, rs7746003, rs9262280, rs3131034, rs6457281, rs3132572, rs3130779, rs3130780, rs3218822, rs7766094, rs4678, rs3131787, rs3095151, rs7764239, rs2844649, rs6933400, rs6933909, rs4711248, rs2844648, rs2844701, rs2 844700, rs9391637, rs2517451, rs9368647, rs2247178, rs3094086, rs11970154, rs9368648, rs2429557, rs9295937, rs4711250, rs2844697, rs2530715, rs3095089, rs3132579, rs3131931, rs2517425, rs1634714, rs3873342, rs1634718, rs12528082, rs9262539, rs6903912, rs12198448, rs7768644, rs4711253, rs2517549, rs9262560, rs10947129, rs12528584, rs7756294, rs9295947, rs2394427, rs17190134, rs16898614, rs9262632, rs2517512, rs3906263, rs2523887, rs9380215, rs9263509, rs2894179, rs2517403, rs6919169, rs9263600, rs2844635, rs9391709, rs1265062, rs2233985, rs2233984, rs2233976, rs2233974, rs2270190, rs4495304, rs2233964, rs2233956, rs3823402, rs17190526, rs6917517, rs9295952, rs3130981, rs3132553, rs3132552, rs3132550, rs3130989, rs3132546, rs3095317, rs2239520, rs3095314, rs4410768, rs9295953, rs3778630, rs3778638, rs10947137, rs9263719, rs3130560, rs3734861, rs4959053, rs3130564, rs28732100, rs1265100, rs2233954, rs2233950, rs9263726, rs1265093, rs2233945, rs1966, rs9263733, rs2073718, rs9263739, rs1196 7883, rs130072, rs1265076, rs3132538, rs746647, rs9263749, rs1265114, rs1265112, rs130067, rs2517985, rs1265110, rs130077, rs130076, rs9263781, rs720465, rs9263785, rs6905862, rs6929434, rs2073724, rs9263794, rs1044870, rs17190776, rs9263796, rs3757349, rs9263800, rs12215963, rs885952, rs1108746, rs1265159, rs2269713, rs887468, rs3132517, rs3094188, rs1265156, rs9468877, rs4713438, rs9263823, rs9263846, rs9405015, rs1265178, rs28362332, rs28362343, rs3094609, rs6903896, rs10807081, rs9263870, rs6921948, rs4446605, rs3094606, rs2894181, rs9263911, rs3132506, rs9263916, rs3132505, rs35718543, rs3130952, rs3132503, rs9263948, rs9468898, rs28360990, rs3132501, rs9263979, rs12662501, rs9263993, rs3130521, rs28397289, rs6908994, rs3130473, rs3130528, rs7745906, rs2394892, rs3130685, rs2394895, rs28397299, rs3132499, rs6901869, rs3130695, rs4332019, rs9357117, rs2394950, rs2245822, rs2853961, rs3130542, rs9264532, rs9394047, rs34131062, rs9264602, rs9366775, rs2074488, rs9357121, rs2249742, r s7759127, rs5010528, rs6923313, rs2844613, rs3130696, rs2524074, rs9264731, rs2524073, rs9468913, rs2524068, rs9391714, rs6906846, rs17198616, rs9468914, rs2844603, rs9461684, rs2853935, rs2853933, rs2853930, rs2524048, rs2524044, rs9468924, rs2524043, rs3900938, rs2524040, rs9468925, rs2256583, rs2524163, rs2524162, rs2524160, rs9357122, rs2524156, rs3873380, rs9348863, rs3873381, rs2524132, rs2853925, rs2247056, rs3905495, rs2524115, rs17192463, rs13191519, rs2853922, rs2524089, rs9380238, rs9380240, rs2524066, rs9366778, rs3873385, rs3915971, rs9468935, rs7750269, rs9264851, rs9264869, rs9264870, rs9368675, rs9368677, rs9264904, rs9264916, rs7760988, rs364415, rs3873386, rs9500887, rs28380796, rs2844586, rs2523619, rs4394275, rs2523618, rs9391846, rs2596503, rs1058026, rs2596487, rs2523573, rs2596548, rs2596549, rs2523557, rs2523554, rs2523544, rs9266395, rs2523537, rs9266409, rs2844567, rs2253908, rs9266433, rs4358666, rs2844556, rs2254556, rs6933050, rs13202464, rs4959069, rs95015 87, rs3094600, rs9266669, rs4143334, rs9266722, rs3016014, rs2442749, rs9266772, rs9266773, rs9266774, rs2523477, rs2523476, rs2523464, rs2523454, rs2844523, rs2844519, rs2263313, rs2857281, rs12174396, rs6910087, rs3828875, rs2256028, rs2848713, rs10223568, rs4418214, rs9501109, rs2524279, rs4346874, rs9501595, rs2524277, rs9469003, rs6938674, rs2524276, rs9267084, rs28575156, rs2844510, rs9765960, rs12206131, rs16899646, rs3128982, rs2596460, rs2596458, rs2395028, rs2596480, rs2523684, rs6930572, rs2255001, rs2255221, rs11752262, rs2395030, rs11757571, rs3094604, rs3094013, rs2516518, rs4713466, rs2395031, rs9267137, rs7758090, rs2844505, rs6940467, rs3131643, rs3828893, rs3749945, rs3749946, rs3099844, rs2905722, rs2905747, rs3094011, rs9267280, rs2904783, rs3130922, rs2395043, rs3134899, rs3131638, rs3131633, rs3067945, rs3094001, rs3131630, rs3130636, rs3093993, rs9469021, rs3095227, rs3093992, rs3093988, rs2516482, rs3093983, rs3093981, rs3093980, rs3115537, rs3219190, rs3093978, rs3130056, rs3093948, rs3131628, rs3093976, rs2734583, rs3130058, rs1129640, rs2516393, rs2523511, rs2523508, rs7738430, rs2239528, rs2523504, rs3219183, rs35969216, rs2255798, rs13192469, rs9469024, rs2857709, rs2857708, rs3093542, rs4248157, rs1800629, rs3093671, rs3093672, rs3093561, rs9267503, rs13211368, rs28732144, rs34816476, rs11575839, rs11755226, rs2509217, rs17200810, rs2857700, rs3132451, rs28732150, rs2736182, rs2736177, rs3130070, rs2280801, rs17200837, rs1046080, rs3130623, rs17207225, rs2736161, rs3130626, rs2736157, rs2272593, rs11538263, rs11538264, rs9267522, rs10885, rs9267525, rs3130628, rs7770976, rs35843778, rs2844463, rs10484558, rs3130050, rs3117583, rs805264, rs2273612, rs707921, rs28732157, rs707974, rs805259, rs928814, rs3130618, rs805258, rs9267529, rs3117578, rs805268, rs805267, rs11758242, rs805272, rs3115667, rs805269, rs9267533, rs9267534, rs9267536, rs10573, rs1475865, rs805283, rs1266071, rs9267545, rs34406901, rs805295, rs3793125, rs9469040, rs94690 41, rs9469042, rs3749952, rs4713479, rs453098, rs3101018, rs28381339, rs28381346, rs707915, rs3117572, rs1150793, rs9296001, rs11754464, rs9461718, rs28399987, rs707936, rs707934, rs9461721, rs9461725, rs34585796, rs2273613, rs11751198, rs9296002, rs17201171, rs34636308, rs2227955, rs2227956, rs481825, rs16867582, rs34378923, rs13217108, rs35987121, rs9368699, rs9368700, rs17207629, rs11968400, rs9267577, rs9501157, rs13191375, rs9267649, rs13118, rs35092817, rs4947332, rs11966200, rs13192107, rs9267659, rs36097221, rs589428, rs486416, rs35875104, rs9267661, rs9469069, rs28732165, rs28435656, rs9267673, rs644045, rs511294, rs498240, rs9267677, rs9332705, rs11752672, rs2257331, rs9332735, rs635348, rs12614, rs9501161, rs9267785, rs34555781, rs9296003, rs492899, rs2280773, rs13217120, rs34241101, rs2075702, rs2854432, rs2746394, rs9391732, rs11757034, rs34214527, rs10046127, rs2077580, rs12198173, rs3749963, rs11751545, rs34878747, rs11756755, rs13199524, rs1269854, rs4713503, rs12153855 , Rs13196724, rs28732175, rs204892, rs4713504, rs11753510, rs13211318, rs388629, rs204999, rs28732178, rs3134608, rs34129552, rs3096697, rs3130347, rs34280838, rs3130284, rs2071290, rs3134947, rs3134945, rs3130349, rs12663103, rs9267820, rs2114437, rs3134942, rs3132935, rs6907458 , rs17604492, rs3132956, rs2269418, rs3213468, rs8192591, rs430916, rs2071282, rs8192584, rs8192565, rs483574, rs482759, rs511027, rs28895018, rs28366174, rs6906662, rs9268199, rs6910071, rs498422, rs3132958, rs3132959, rs28732193, rs9469099, rs3117133, rs910049, rs12662503 , rs2395148, rs3129907, rs2894249, rs2143462, rs3129931, rs3129937, rs3129939, rs3129941, rs2076535, rs2073045, rs9391858, rs3129945, rs9268425, rs9268428, rs2894252, rs2894253, rs8180664, rs9268454, rs9268456, rs28732201, rs6930777, rs9268461, rs9268474, rs28366191, rs2076528 , rs2076527, rs3763305, rs2076525, rs2076524, rs3793127, rs3763309, rs3763310, rs3763312, rs3763315, rs3763316, rs9380293, rs9268516, rs9405098, rs3129963, rs2395163, rs 2395165, rs2395166, rs9268557, rs6457580, rs3135344, rs9501626, rs11759143, rs3129860, rs7356880, rs2027856, rs3129868, rs6911777, rs3129883, rs3129886, rs3129887, rs2239805, rs11544315, rs2239802, rs2395182, rs3763326, rs28895103, rs28895187, rs7763262, rs28732227, rs9268831, rs9268926, rs7748472, rs3830135, rs9270665, rs28605404, rs2858870, rs602457, rs9270986, rs9271055, rs9271100, rs660895, rs9271170, rs35759989, rs4530903, rs642093, rs13204672, rs9271348, rs3135005, rs9271366, rs17533090, rs2097431, rs3129763, rs9271588, rs35399661, rs9271775, rs9272219, rs3104369, rs2187668, rs9273012, rs17843604, rs9273327, rs9273349, rs6906021, rs1063355, rs9273448, rs2854275, rs7775228, rs9275224, rs2858324, rs9275245, rs5000634, rs17427431, rs6457617, rs6457622, rs2647003, rs9357152, rs9275312, rs2856725, rs9275330, rs9275333, rs35998847, rs3135006, rs17427599, rs2858308, rs2856717, rs2858305, rs2856705, rs13192471, rs1794275, rs4947344, rs9275572, rs3129727, rs7765379, rs2858332, rs9275595, rs7454108, rs3957146, rs9275596, rs3998159, rs3957148, rs3873444, rs3892710, rs3997854, rs6915986, rs6936707, rs9275659, rs9275686, rs9275698, rs763026, rs2859099, rs9276310, rs7773068, rs7773694, rs7755597, rs9276399, rs17500468, rs2213565, rs9276435, rs28986337, rs28986338, rs28986359, rs28986364, rs10484564, rs28986373, rs13204139, rs28986396, rs7758736, rs9276722, rs11967235, rs2071471, rs3763355, rs3763354, rs9784876, rs16870907, rs13209654, rs10484565, rs9380326, rs4148872, rs4148871, rs241428, rs13215, rs17213812, rs16871027, rs2071538, rs4148878, rs28724900, rs35571244, rs10214510, rs9469311, rs35599935, rs6934645, rs12206377, rs1480380, rs6906517, rs11757089, rs2894311, rs9276969, rs3128933, rs3129304, rs3129303, rs3129302, rs3130603, rs9276992, rs3130604, rs3130607, rs423639, rs17214311, rs3130609, rs397576, rs6933319, rs34493748, rs763469, rs7738815, rs376877, rs2395309, rs3077, rs2301226, rs1054025, rs1042190, rs10214910, rs2301220, rs9277341, rs6914849, rs1431399, rs143140 0, rs1431401, rs2051548, rs9380340, rs2071349, rs2071351, rs2071353, rs3135021, rs1042151, rs2856826, rs9378177, rs9277378, rs9277396, rs9277464, rs9277469, rs3097675, rs9277471, rs9277533, rs9277555, rs3117229, rs3117228, rs9277557, rs9277565, rs3130188, rs3091282, rs3117226, rs3117225, rs3097652, rs2068204, rs3128972, rs2179920, rs10484569, rs2179919, rs2281390, rs2281389, rs3128917, rs2281388, rs7763822, rs3117222, rs3128918, rs3130190, rs3130191, rs3117221, rs3130198, rs3117213, rs2395319, rs3117239, rs2064479, rs2064478, rs2064476, rs3117234, rs3117231, rs3130215, rs3117230, rs3128930, rs6457713, rs9380342, rs9380343, rs6937034, rs6937061, rs9348906, rs9277629, rs1810472, rs2395349, rs3117039, rs3117038, rs3117035, rs1883414, rs9277682, rs4713607, rs9277723, rs3117021, rs6913896, rs3129275, rs3117016, rs3117008, rs3117004, rs3116998, rs3130235, rs3130237, rs6901221, rs9277768, rs2294472, rs2395352, rs7756467, rs3129264, rs7750000, rs9366816, rs13437000, rs4713610, rs926421, rs3129 249, rs9296086, rs7754200, rs3129234, rs3129231, rs3129228, rs3129223, rs3130151, rs2395365, rs3129214, rs721394, rs756441, rs756440, rs9277912, rs3129207, rs3129206, rs9277920, rs9368757, rs9380351, rs2235499, rs734181, rs2235498, rs986522, rs2855441, rs9368758, rs2855440, rs2855437, rs2855430, rs16868943, rs2269346, rs9469378, rs9277935, rs2076310, rs110662, rs439205, rs383711, rs421446, rs107822, rs213210, rs213208, rs1567464, rs213213, rs9277937, rs28892580, rs386084, rs17215210, rs12664430, rs6923740, rs761583, rs7752625, rs1755044, rs2772385, rs2772372, rs2772374, rs68191, rs169737, rs2296340, rs11753634 and rs11758326.

The present inventors sought to develop a reference containing a single base polymorphism combination for the genotyping of HLA-A, HLA-B, HLA-C, HLA-DPB1 or HLA-DQB1 of East Asian people. HLA-B, HLA-C, HLA-DPB1, or HLA-DQB1 genotypes were determined with high accuracy by using a combination of 1778 single nucleotide polymorphisms. Respectively.

The subject "subject" in this specification means human, and more specifically, East Asian. East Asian people in this specification include Koreans, Chinese and Japanese, and include people of the same genetic origin as Koreans, Chinese or Japanese.

A feature of the present invention is that a genotype of HLA-A, HLA-B, HLA-C, HLA-DPB1 or HLA-DQB1 can be analyzed with high accuracy using a combination of genotypes of specific single nucleotide polymorphisms selected by the present inventors have.

The term " single nucleotide polymorphism " (SNP) in the present specification refers to a part of the entire human genome that changes in the order of bases, and may cause differences in the phenotype of a race or an individual, Section. The present inventors East Asians of HLA-A, HLA-B, HLA-C, HLA-DPB1 , or the most efficient of the SNP associated with HLA-DQB1 genotype HLA-A, HLA-B, HLA-C, HLA-DPB1 or A combination of 1778 SNPs of the present invention capable of performing genotyping of HLA-DQB1 was first discovered. The 1778 SNP sequences can be obtained from the National Center for Bioinformatics (http://www.ncbi.nlm.nih.gov/).

In one embodiment of the present invention, step (a) of the present invention comprises hybridization by a microarray, allele-specific probe hybridization, allele specific amplification amplification, sequencing, 5 'nuclease digestion, molecular beacon assay, oligonucleotide ligation assay, size analysis Quot;) and single-stranded conformation polymorphism. ≪ / RTI >

In one embodiment of the present invention, the biological sample of the present invention is any one selected from the group consisting of blood, tissue, cells, serum, plasma, saliva, sputum and urine.

According to another aspect of the present invention, the present invention provides a method for analyzing human leukocyte antigen (HLA) -A, HLA-B, HLA-C, HLA-DPB1 or HLA-DQB1 of East Asian people comprising the following steps :

(a) the above-mentioned HLA (human leukocyte antigen) -A, HLA-B, HLA-C, HLA-DPB1 or from the analyte by the methods of data collection method for the HLA-DQB1 genotype determination HLA (human leukocyte antigen) - A , HLA-B, HLA-C, HLA-DPBl or HLA-DQB1 genotyping; And

(b) comparing the genotypes of the single nucleotide polymorphism combinations obtained from step (a) with the genotypes of the single nucleotide polymorphism combinations and the genotypes of HLA-A, HLA-B, HLA-C, HLA-DPB1 or HLA-DQB1 A, HLA-B, HLA-C, HLA-DPB1 or HLA-DQB1 to be analyzed in comparison with a reference providing predetermined information about the genotype.

The reference in step (b) is a database originally constructed by using the information on the single nucleotide polymorphism combination of SNP list 1 described above by the method described in the embodiments of the present invention. The reference information for this invention is available at http://sites.google.com/site/KwangwooKimPhD. The calculation program for prediction is performed with the reference information constructed by the present inventors through SNP2HLA.

In one embodiment of the present invention, the genotypes of HLA-A, HLA-B, HLA-C, HLA-DPB1 or HLA-DQB1 of the present invention are classical 2-digit, -digit) resolution. In the case of predicting the HLA-A, HLA-B, HLA-C, HLA-DPB1 and HLA-DQB1 genotypes using the single nucleotide polymorphism combination of the present invention , 88.1% (standard deviation: 3.4% , And 92.0% (standard deviation: 2.4%) and 91.0% (standard deviation: 3.1%), respectively, and the CHB (HanChinese A, HLA-B, HLA-C and HLA-DQB1 genotypes were predicted for 89.3%, 85.2%, 98.4% and 90.2%, respectively, 4-digit genotype agreement. This is a much higher accuracy than with conventional reference panels for Europeans (see Table 3).

In one embodiment, the polymorphism of the SNP list 1 are HLA-A, HLA-B, HLA-C, HLA-DPB1 or HLA-DQB1 genotypes associated with uneven (linkage disequilibrium) index (r ²⁾ is 0.3 or more. As used herein, the term "association disequilibrium" refers to a measure of the genetic association of alleles at two or more genetic displacement deviations with a higher frequency than is expected randomly. The present inventors have associated uneven index (r ²⁾ is as least 0.3, HLA-A, HLA- B, HLA-C, HLA-DPB1 or analyze the HLA-DQB1 genotype case of using the combination of the 1778 polymorphism in the present invention The most accurate and the most accurate.

In accordance with another aspect of the present invention, the present invention relates to a single nucleotide polymorphism combination of SNP list 1 , or a human leukocyte antigen (HLA) of an East Asian gene comprising an oligonucleotide having a sequence complementary to a single nucleotide polymorphism of each of said combinations , -A, HLA-B, HLA-C, HLA-DPB1 or HLA-DQB1 genotype analysis kit.

A, HLA-B, HLA-C, HLA-DPB1 and HLA-DQB1 genotypes at low cost by using an assay kit containing oligonucleotides having a single nucleotide polymorphism combining sequence or a complementary sequence can do.

According to another aspect of the present invention , there is provided a method for determining HLA (human leukocyte antigen) -A, HLA-B, HLA-C, HLA-DPBl and HLA-DQB1 genotypes of East Asian people comprising the following steps A computer program for running on a computer is provided:

(a) receiving genotype information of a single nucleotide polymorphism combination of SNP list 1 obtained from a nucleic acid sample isolated from a biological sample derived from a subject; And

(b) comparing the genotype information of the single nucleotide polymorphism combination obtained from step (a) with the genotypes of the single nucleotide polymorphism combination and the genotype of HLA-A, HLA-B, HLA-C, HLA-DPB1 or HLA- A, HLA-B, HLA-C, HLA-DPB1 or HLA-DQB1 to be analyzed in comparison with a reference database providing predetermined information on the HLA-

Specifically, the computer program of the present invention can be applied, for example, by applying a reference database related to HLA-A, HLA-B, HLA-C, HLA-DPB1 or HLA-DQB1 of the present invention to SNP2HLA have.

The computer program of the present invention is a method for collecting data for determination of HLA- HLA-B, HLA-C, HLA-DPB1 or HLA-DQB1 genotypes of East Asian people as another aspect of the present invention , HLA-B, HLA-C, HLA-DPB1, or HLA-DQB1 genotyping methods are used to avoid redundancy in order to avoid the excessive complexity described herein.

According to another aspect of the present invention, there is provided a method for determining a human leukocyte antigen (HLA) -A, HLA-B, HLA-C, HLA-DPB1 or HLA- A computer program, and a computer-readable recording medium for executing the program on a computer.

Since the recording medium of the present invention relates to a storage medium for storing a computer program, which is another aspect of the present invention, redundant contents are omitted in order to avoid excessive complexity described in the present specification.

The features and advantages of the present invention are summarized as follows:

(a) The present invention provides a genotyping method using a reference suitable for analyzing genotypes of HLA-A, HLA-B, HLA-C, HLA-DPB1 or HLA-DQB1 of East Asian people.

(b) The present invention provides a kit for genotype analysis using a single base polymorphism combination suitable for analyzing genotypes of HLA-A, HLA-B, HLA-C, HLA-DPB1 or HLA-DQB1 of East Asian people.

(c) The present invention provides a computer program for genotyping using single base polymorphism combinations suitable for analyzing genotypes of HLA-A, HLA-B, HLA-C, HLA-DPB1 or HLA-DQB1 of East Asian people.

(d) Using the present invention, HLA-A, HLA-B, HLA-C, HLA-DPB1 or HLA-DQB1 genotypes of East Asian people can be easily analyzed compared to the conventional method.

(e) Using the present invention, HLA-A, HLA-B, HLA-C, HLA-DPB1 or HLA-DQB1 genotypes of East Asian people can be analyzed with high accuracy.

FIG. 1 shows the results of confirming the agreement between the actual HLA-A genotype and the predicted HLA-A genotype.
FIG. 2 shows the results of confirming the agreement between the actual HLA-B genotype and the predicted HLA-B genotype.
FIG. 3 shows the results of confirming the agreement between the actual HLA-C genotype and the predicted HLA-C genotype.
Fig. 4 shows the results of confirming the agreement between the actual HLA-DPB1 genotype and the predicted HLA-DPB1 genotype.
FIG. 5 shows the results of confirming the agreement between the actual HLA-DQB1 genotype and the predicted HLA-DQB1 genotype.

Hereinafter, the present invention will be described in more detail with reference to Examples. It is to be understood by those skilled in the art that these embodiments are only for describing the present invention in more detail and that the scope of the present invention is not limited by these embodiments in accordance with the gist of the present invention .

Example

Example 1: Using 1778 single nucleotide polymorphisms HLA-A, HLA-B, HLA-C, HLA-DPB1 or  HLA-DQB1  Confirm Genetic Prediction

The classical HLA alleles of HLA-A, HLA-B, HLA-C, HLA-DPB1 or HLA-DQB1 were randomly selected from the blood DNA of 413 Koreans in the Immunology and Infectious Diseases laboratory Murdoch WA, Australia) using Roche's GS 454 sequencing. Institutional calling algorithms for HLA alleles have been approved by the American Society for Histocompatibility and Immunogenetics (ASHI). The SNPs of the samples were tested using an Illumina's HumanOmni Express array of SNPgenetics (Seoul, Korea). The general quality control criteria were minor allele frequency (MAF; MAF> 0.5%), Hardy-Weinberg equilibrium (HWE; HWE p-value <5 x 10 ^-7 ) It has been suggested that the call rate (> 98%), the call rate per individual (> 98%), heterozygosity rate, population stratification, Consistency between sexes, and cryptic relatedness (duplicate and cryptic 1st degree relatives). For HLA reference prediction, 5858 SNPs between MHCs of chromosome 6 and 25 Mb to 33 Mb were extracted.

Subsequently, 20% of the 413 groups were categorized into a subset of the reference group (330 subjects) and the test group (83 subjects) to be designated as test samples. The test group of HLA-A, HLA-B, HLA-C, HLA-DPB1 and HLA-DQB1 genotype information according to the polymorphism data from the test group based on the genotype data for the reference group in the non-visibility of HLA- A, HLA-B, HLA-C, HLA-DPB1 and HLA-DQB1 . However, the single nucleotide polymorphisms in the reference group produced 10 sets according to the association inequality index (r ² ) (see Table 1).

The association inequality index (r ² ) Single nucleotide polymorphic number 0.0 5858 ≥ 0.1 3854 ≥ 0.2 2537 ≥ 0.3 1778 ≥ 0.4 1309 ≥ 0.5 979 ≥ 0.6 673 ≥ 0.7 524 ≥ 0.8 372 ≥ 0.9 209 = 1 86

HLA-B, HLA-C, HLA-DPB1 and HLA-DQB1 genotypes were compared with the genotype of predicted HLA-A, HLA-B, HLA-C, HLA-DPB1 and HLA- Respectively.

A, HLA-B, HLA-C, HLA-DPB1 and HLA-DQB1 genotypes and predicted HLA-A, HLA-B and HLA-C genotype by performing random assignment of the reference group and the test group 100 times. , HLA-DPB1 and HLA-DQB1 genotypes were confirmed 100 times and the average predictive power was calculated and shown in FIGS. 1 to 5, respectively. Figures 1 to 5 show that 1778 single nucleotide polymorphisms of the SNP list 1 of the invention showing a linkage inequality index (r ² ) of 0.3 or more show high accuracy with a small number.

It was confirmed that 1778 SNPs in the SNP list 1 of the present invention showing a linkage inequality index (r ² ) of 0.3 or more show a high accuracy with a small number of SNPs (see Table 2). The two-digit genotype agreement was 98.2% (standard deviation: 1.2%), 90.1% (standard deviation: 2.9%), and 96.1% (standard deviation) for HLA-A, HLA-B, HLA-C, HLA-DPB1 and HLA- A, HLA-B, HLA-C, HLA-DPB1, and HLA -B were found to be statistically significant (P <.05 ), 95.4% (standard deviation: 2.7%) and 95.2% respectively, 88.1% based on the -DQB1 (standard deviation: 3.4%), 84.3% (standard deviation: 4.1%), 92.9% (standard deviation: 2.7%), 92.9% (standard deviation: 2.4%) and 91.0% (standard deviation : 3.1%).

Example 2: Genetic prediction of Japanese and Chinese

The international HapMap project (HapMap3 r2 data set; http://hapmap.ncbi.nlm.nih.gov/) based on the 413 Korean HLA-DRB1 genotype information in Example 1 and the single nucleotide polymorphism information of the SNP list 1 of the present invention A, HLA-B, HLA-C and HLA-DQB1 genotypes were analyzed using 61 single nucleotide polymorphisms of Japanese or Chinese who were analyzed in HLA-A, HLA-C and HLA- B, HLA-C and HLA-DQB1 genotypes. HLA-A, HLA-B, HLA-B and HLA-DQB1 were 96.7%, 90.2%, 99.2% and 100%, respectively, and the four-spot genotypic agreement was HLA-A, 89.3%, 85.2%, 98.4% and 90.2% for C and HLA-DQB1 , respectively (see Table 2). The two-tailed genotype agreement was 91.1%, 28.3%, 66.8% and 79.4% for HLA-A, HLA-B, HLA-C and HLA-DQB1 , respectively, Were significantly higher than those of HLA-A, HLA-B, HLA-C, and HLA-DQB1 , respectively, compared to those of 82.9%, 23.3%, 60.2% and 65.9%, respectively (Table 2). For reference, in order to avoid errors in the interpretation of results due to the difference in the number of samples for European reference and Korean reference, a reference containing only 413 information was arbitrarily selected from the European reference, and the genotypic agreement was analyzed. The results are shown in Table 2.

While the present invention has been particularly shown and described with reference to exemplary embodiments thereof, it is to be understood that the same is by way of illustration and example only and is not to be construed as limiting the scope of the present invention. Accordingly, the actual scope of the present invention will be defined by the appended claims and their equivalents.

references

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2. Apanius V, Penn D, Slev PR, Ruff L R, Potts WK (1997). The nature of selection is the major histocompatibility complex. Crit Rev Immunol 17: 179-224.

3. Ahn S, Choi HB, Kim TG (2011) HLA and Disease Associations in Koreans. Immune Netw 11: 324-335.

4. Shiina T, Hosomichi K, Inoko H, Kulski JK (2009) The HLA genomic loci map: expression, interaction, diversity and disease. J Hum Genet 54: 15-39.

5. Jia X, Han B, Onengut-Gumuscu S, Chen WM, Concannon PJ, et al. (2013) Imputing amino acid polymorphisms in human leukocyte antigens. PLoS One 8: e64683.

6. Dilthey AT, Moutsianas L, Leslie S, McVean G (2011) HLA * IMP-an integrated framework for imputing classical HLA alleles from SNP genotypes. Bioinformatics 27: 968-972.

7. International HIVCS, Pereyra F, Jia X, McLaren PJ, Telentia, et al. (2010) The major genetic determinants of HIV-1 control affect HLA class I peptide presentation. Science 330: 1551-1557.

8. Raychaudhuri S, Sandor C, Stahl EA, Freudenberg J, Lee HS, et al. (2012) Five amino acids in three HLA proteins explain most of the association between MHC and seropositive rheumatoid arthritis. Nat Genet 44: 291-296.

9. Patsopoulos NA, Barcellos LF, Hintzen RQ, Schaefer C, van Duijn CM, et al. (2013) Fine-mapping of the major histocompatibility complex in multiple sclerosis: HLA and non-HLA effects. PLoS Genet 9: e1003926.

10. Foo JN, Smedby KE, Akers NK, Berglund M, Irwan ID, et al. (2013) Coding variants at hexa-allelic amino acid 13 of HLA-DRB1 explain independent SNP associations with follicular lymphoma risk. Am J Hum Genet 93: 167-172.

Claims (9)

Analyzing a single nucleotide polymorphism combination of SNP listing 1 from a nucleic acid sample isolated from a biological sample derived from a subject to determine the genotypes of the single nucleotide polymorphisms to identify a human leukocyte antigen (HLA) ) -A, HLA-B, HLA-C, HLA-DPB1 or HLA-
SNP list 1
rs7739830, rs1880271, rs11751616, rs6908645, rs522024, rs807213, rs807211, rs807203, rs1179007, rs707903, rs1183694, rs806972, rs2298090, rs2298091, rs806966, rs806978, rs806792, rs438534, rs3857549, rs6921148, rs13195509, rs4713002, rs13194984, rs7768682, rs9295700, rs7751878, rs7741445, rs6932003, rs6904071, rs6913660, rs6921711, rs17737028, rs13194053, rs12210982, rs9468019, rs9461345, rs7746199, rs9468031, rs11965377, rs2893912, rs9468058, rs11967073, rs9969094, rs11962403, rs2393997, rs6908615, rs4713119, rs7742752, rs12192568, rs6915101, rs9468227, rs9295749, rs2021835, rs11962868, rs9468236, rs11970638, rs7748520, rs7742529, rs10456357, rs6910968, rs6922530, rs7769416, rs7741570, rs6913038, rs10484404, rs3734572, rs7747772, rs9468293, rs6908414, rs6932313, rs1150671, rs6929559, rs1233667, rs1233698, rs1736892, rs3757183, rs6918043, rs2799076, rs11966237, rs11965542, rs1150725, rs7759855, rs6922161, rs6902583, rs6456812, rs9295769, rs6908459, rs7759845, rs6918631, rs6929449, rs94 68346, rs2859379, rs3757181, rs719370, rs2859367, rs2531808, rs2531810, rs2531816, rs6927023, rs722788, rs423118, rs11757235, rs426922, rs413488, rs422089, rs454746, rs449074, rs411538, rs420436, rs7738979, rs11969304, rs911178, rs4711176, rs7742658, rs6925972, rs1319076, rs6456832, rs9468413, rs6456834, rs11754985, rs11963531, rs209181, rs9501112, rs176461, rs7775657, rs209139, rs12386522, rs6934470, rs9468459, rs9295784, rs9468461, rs9468464, rs3129795, rs9468469, rs9468474, rs3129106, rs9468487, rs3129157, rs3130801, rs11962388, rs11964645, rs6899390, rs9468508, rs3117433, rs9348827, rs7761746, rs9257792, rs9257803, rs9257805, rs11969272, rs16894919, rs2073148, rs2746149, rs16894948, rs1362076, rs7771335, rs2107189, rs17415601, rs2066951, rs17184114, rs9393967, rs7767894, rs2294748, rs9461533, rs9391895, rs6930217, rs6935418, rs10484548, rs362541, rs3025657, rs6902738, rs7763501, rs16895058, rs6915177, rs2076486, rs64036, rs2272991, rs362532, rs459970, rs6912437, rs3025650, rs311707 3, rs17508548, rs3095273, rs362518, rs2267633, rs2076483, rs2076482, rs29267, rs29264, rs29230, rs29246, rs29243, rs29273, rs3131854, rs9257928, rs16895214, rs439812, rs29269, rs29272, rs29231, rs29235, rs9468571, rs3135050, rs2857783, rs2256266, rs2857784, rs6905408, rs3130253, rs2535250, rs2535248, rs2857771, rs2071652, rs1318631, rs2071653, rs2273192, rs2747419, rs9257940, rs378596, rs9257985, rs3117301, rs2747453, rs2747454, rs2747457, rs2747458, rs2747460, rs2747466, rs3129039, rs3129029, rs3129066, rs9258102, rs6911622, rs2107203, rs3129055, rs9258122, rs3116798, rs2394660, rs3131863, rs11962017, rs1476573, rs1476572, rs1610594, rs1611364, rs2735063, rs1632962, rs2517911, rs2517910, rs9258170, rs1362126, rs2076183, rs9258186, rs1736926, rs2235383, rs1736922, rs1628578, rs2523404, rs2735059, rs2272874, rs3736694, rs2743925, rs2523402, rs2523399, rs2735052, rs2844833, rs2523395, rs2394159, rs2394160, rs9258205, rs9258206, rs1736915, rs1736913, rs9258207, rs9258208, rs9258209, rs273 5051, rs9258211, rs2844831, rs9258213, rs932338, rs1633096, rs9258218, rs2743951, rs2517938, rs909732, rs4713240, rs2523386, rs9258225, rs2072894, rs2523385, rs34260811, rs1633085, rs733841, rs1610621, rs909728, rs909725, rs4713244, rs9391630, rs9258260, rs1633068, rs1737079, rs1633057, rs1633056, rs1610628, rs1633048, rs1737069, rs7759474, rs1611285, rs1626392, rs1625636, rs1737060, rs1633041, rs2735048, rs2735046, rs1737043, rs1737041, rs11753872, rs9258302, rs9258303, rs1615962, rs2844836, rs1633021, rs1002046, rs2743941, rs7758742, rs1610644, rs1633011, rs11758087, rs2523414, rs11752553, rs11751333, rs1611185, rs2017525, rs3891160, rs1610711, rs1736982, rs1736981, rs1611192, rs1632988, rs1632987, rs17178826, rs9258447, rs11757182, rs2523409, rs1736971, rs1736969, rs1610699, rs3926748, rs11753629, rs11753654, rs1077432, rs2735028, rs2743933, rs2743931, rs2394177, rs1611149, rs1736936, rs3115630, rs915669, rs1233330, rs11753296, rs16896052, rs2394180, rs2735014, rs9258525, rs2523779, rs2743937, rs2735003, rs9258537, rs2523777, rs2523776, rs1611133, rs2523774, rs2523769, rs2844827, rs16896081, rs2734994, rs2523767, rs2517879, rs9258557, rs2394185, rs2394186, rs9380146, rs3115628, rs2247504, rs2508050, rs3115627, rs2523756, rs9258631, rs2517862, rs3115626, rs2517855, rs2517854, rs3132726, rs6919513, rs1611684, rs9258738, rs17185692, rs2523822, rs9295822, rs3094170, rs1611717, rs9258766, rs9258771, rs765649, rs1611737, rs1611738, rs2524035, rs3094165, rs2734974, rs2734973, rs2517826, rs9258866, rs3132718, rs9258883, rs3094654, rs3132714, rs2523809, rs2523808, rs2517904, rs2524024, rs2860580, rs3823342, rs6921314, rs2735097, rs1655900, rs2523949, rs9260497, rs404046, rs429511, rs2523942, rs2517700, rs9260679, rs441808, rs9260722, rs9260734, rs3903160, rs6457109, rs2844806, rs3893259, rs4713270, rs3869062, rs3893464, rs9260759, rs9260761, rs17186496, rs2517673, rs4713275, rs1061535, rs6916422, rs2523969, rs2523961, rs2523960, rs2256902, rs2523946, rs3823355, rs2844804, rs3823358, rs2232238, rs2232239, rs2523943, rs6904029, rs2735076, rs2394250, rs2893999, rs3823374, rs2571375, rs3823384, rs9260860, rs2108691, rs9260915, rs423808, rs2571430, rs2246638, rs2394255, rs401618, rs2735067, rs11757750, rs17186937, rs11755961, rs3901554, rs5025708, rs12665186, rs9260930, rs12662611, rs9260967, rs9260984, rs6457121, rs6910898, rs9260997, rs9260998, rs9261040, rs6941318, rs6904120, rs9261079, rs9261081, rs9261091, rs11760176, rs9261093, rs11965524, rs2286405, rs2286404, rs9261105, rs356968, rs6940082, rs2240619, rs3765604, rs9261115, rs9261129, rs11753431, rs3734836, rs9261130, rs9261138, rs16896044, rs6457126, rs356954, rs9357092, rs9261145, rs6926792, rs6931776, rs165256, rs4711206, rs9261151, rs3891157, rs3129012, rs3891156, rs6919617, rs1150743, rs9261171, rs9261174, rs4448133, rs9261189, rs16896923, rs9261193, rs3121593, rs166327, rs3869067, rs3869068, rs9261203, rs259938, rs3910312, rs9261216, rs259939, rs259940, rs9261224, rs259942, rs3132128, rs6457138 , Rs7771476, rs6457140, rs28570682, rs7761314, rs9261257, rs9261258, rs3869070, rs9261261, rs9261263, rs6911724, rs259919, rs6917477, rs10484549, rs9261265, rs3757328, rs3757329, rs3757333, rs9295829, rs1150742, rs7770092, rs7770505, rs10745, rs9261269, rs9261270, rs1150740 , rs9261277, rs3188482, rs3807030, rs3807031, rs9261285, rs2074482, rs9261288, rs1245371, rs2301753, rs2301751, rs9393989, rs2074480, rs2074479, rs9261301, rs9261302, rs3807033, rs3132682, rs3807035, rs1150735, rs2394734, rs4711209, rs9261316, rs7382061, rs2057728, rs9261361 , rs9261371, rs17187805, rs9261387, rs6923832, rs7765810, rs9261394, rs1264702, rs916570, rs1264701, rs1264698, rs7763159, rs1108052, rs1110446, rs2240070, rs1116222, rs1116221, rs11964542, rs2844796, rs2248289, rs3132680, rs2523992, rs2523988, rs2523987, rs2517597, rs2523986 , rs2523981, rs2523979, rs9261434, rs17455565, rs10947056, rs2523995, rs3132676, rs9468693, rs3094134, rs3757334, rs12212092, rs9261536, rs2857449, rs17188127, rs2074475, rs10 63280, rs13212414, rs9261538, rs2517623, rs9261547, rs4476873, rs10947058, rs11967808, rs11961294, rs1345229, rs9295837, rs3094138, rs3094137, rs10456378, rs2508028, rs9261588, rs928824, rs28780093, rs1264622, rs8973, rs3094631, rs7758503, rs1264608, rs1264581, rs12663184, rs7767653, rs3129838, rs6931763, rs6905389, rs3132649, rs3094061, rs3130375, rs3130379, rs3094622, rs3094621, rs2057726, rs3129808, rs3129809, rs3130361, rs11759238, rs7772240, rs3129817, rs3129820, rs3132631, rs3132630, rs3129822, rs3132625, rs1245218, rs7744914, rs28780099, rs3094032, rs3130126, rs3094050, rs17475879, rs3130116, rs9261761, rs9261821, rs9261846, rs1573294, rs9261895, rs9261919, rs9261922, rs9261923, rs9261926, rs9261947, rs9501447, rs1079541, rs9295863, rs9295871, rs9295873, rs4947284, rs9295886, rs17411480, rs35407515, rs34101875, rs9501336, rs11966619, rs35792611, rs2524172, rs2516670, rs28780106, rs3757335, rs12192673, rs4713337, rs3132611, rs4148248, rs1264429, rs9348841, rs2517565, rs17195551, rs1079687, rs3094104, rs3132608, rs2269708, rs1076829, rs9262138, rs3130000, rs1076828, rs3094098, rs2285322, rs3094097, rs17189246, rs2285321, rs6937357, rs9468805, rs9262141, rs2269707, rs2239887, rs2394392, rs3129996, rs2249059, rs3094092, rs2269703, rs2239886, rs28994872, rs2269702, rs28986466, rs6929626, rs17189329, rs28986465, rs2075015, rs6924270, rs3132587, rs9461624, rs4713354, rs3132584, rs25527, rs8233, rs9500864, rs3095329, rs35580157, rs3094127, rs12179975, rs9501029, rs1064627, rs3909184, rs9969042, rs9968884, rs9380182, rs12111310, rs10947088, rs10947089, rs2301277, rs12210092, rs6926530, rs11757629, rs17189427, rs3131064, rs1264377, rs3129987, rs3094123, rs3094111, rs1264352, rs9262216, rs3130785, rs3130648, rs11757306, rs9262222, rs3095345, rs11759095, rs9262256, rs7746003, rs9262280, rs3131034, rs6457281, rs3132572, rs3130779, rs3130780, rs3218822, rs7766094, rs4678, rs3131787, rs3095151, rs7764239, rs2844649, rs6933400, rs6933909, rs4711248, rs2844648, rs2844701, rs2 844700, rs9391637, rs2517451, rs9368647, rs2247178, rs3094086, rs11970154, rs9368648, rs2429557, rs9295937, rs4711250, rs2844697, rs2530715, rs3095089, rs3132579, rs3131931, rs2517425, rs1634714, rs3873342, rs1634718, rs12528082, rs9262539, rs6903912, rs12198448, rs7768644, rs4711253, rs2517549, rs9262560, rs10947129, rs12528584, rs7756294, rs9295947, rs2394427, rs17190134, rs16898614, rs9262632, rs2517512, rs3906263, rs2523887, rs9380215, rs9263509, rs2894179, rs2517403, rs6919169, rs9263600, rs2844635, rs9391709, rs1265062, rs2233985, rs2233984, rs2233976, rs2233974, rs2270190, rs4495304, rs2233964, rs2233956, rs3823402, rs17190526, rs6917517, rs9295952, rs3130981, rs3132553, rs3132552, rs3132550, rs3130989, rs3132546, rs3095317, rs2239520, rs3095314, rs4410768, rs9295953, rs3778630, rs3778638, rs10947137, rs9263719, rs3130560, rs3734861, rs4959053, rs3130564, rs28732100, rs1265100, rs2233954, rs2233950, rs9263726, rs1265093, rs2233945, rs1966, rs9263733, rs2073718, rs9263739, rs1196 7883, rs130072, rs1265076, rs3132538, rs746647, rs9263749, rs1265114, rs1265112, rs130067, rs2517985, rs1265110, rs130077, rs130076, rs9263781, rs720465, rs9263785, rs6905862, rs6929434, rs2073724, rs9263794, rs1044870, rs17190776, rs9263796, rs3757349, rs9263800, rs12215963, rs885952, rs1108746, rs1265159, rs2269713, rs887468, rs3132517, rs3094188, rs1265156, rs9468877, rs4713438, rs9263823, rs9263846, rs9405015, rs1265178, rs28362332, rs28362343, rs3094609, rs6903896, rs10807081, rs9263870, rs6921948, rs4446605, rs3094606, rs2894181, rs9263911, rs3132506, rs9263916, rs3132505, rs35718543, rs3130952, rs3132503, rs9263948, rs9468898, rs28360990, rs3132501, rs9263979, rs12662501, rs9263993, rs3130521, rs28397289, rs6908994, rs3130473, rs3130528, rs7745906, rs2394892, rs3130685, rs2394895, rs28397299, rs3132499, rs6901869, rs3130695, rs4332019, rs9357117, rs2394950, rs2245822, rs2853961, rs3130542, rs9264532, rs9394047, rs34131062, rs9264602, rs9366775, rs2074488, rs9357121, rs2249742, r s7759127, rs5010528, rs6923313, rs2844613, rs3130696, rs2524074, rs9264731, rs2524073, rs9468913, rs2524068, rs9391714, rs6906846, rs17198616, rs9468914, rs2844603, rs9461684, rs2853935, rs2853933, rs2853930, rs2524048, rs2524044, rs9468924, rs2524043, rs3900938, rs2524040, rs9468925, rs2256583, rs2524163, rs2524162, rs2524160, rs9357122, rs2524156, rs3873380, rs9348863, rs3873381, rs2524132, rs2853925, rs2247056, rs3905495, rs2524115, rs17192463, rs13191519, rs2853922, rs2524089, rs9380238, rs9380240, rs2524066, rs9366778, rs3873385, rs3915971, rs9468935, rs7750269, rs9264851, rs9264869, rs9264870, rs9368675, rs9368677, rs9264904, rs9264916, rs7760988, rs364415, rs3873386, rs9500887, rs28380796, rs2844586, rs2523619, rs4394275, rs2523618, rs9391846, rs2596503, rs1058026, rs2596487, rs2523573, rs2596548, rs2596549, rs2523557, rs2523554, rs2523544, rs9266395, rs2523537, rs9266409, rs2844567, rs2253908, rs9266433, rs4358666, rs2844556, rs2254556, rs6933050, rs13202464, rs4959069, rs95015 87, rs3094600, rs9266669, rs4143334, rs9266722, rs3016014, rs2442749, rs9266772, rs9266773, rs9266774, rs2523477, rs2523476, rs2523464, rs2523454, rs2844523, rs2844519, rs2263313, rs2857281, rs12174396, rs6910087, rs3828875, rs2256028, rs2848713, rs10223568, rs4418214, rs9501109, rs2524279, rs4346874, rs9501595, rs2524277, rs9469003, rs6938674, rs2524276, rs9267084, rs28575156, rs2844510, rs9765960, rs12206131, rs16899646, rs3128982, rs2596460, rs2596458, rs2395028, rs2596480, rs2523684, rs6930572, rs2255001, rs2255221, rs11752262, rs2395030, rs11757571, rs3094604, rs3094013, rs2516518, rs4713466, rs2395031, rs9267137, rs7758090, rs2844505, rs6940467, rs3131643, rs3828893, rs3749945, rs3749946, rs3099844, rs2905722, rs2905747, rs3094011, rs9267280, rs2904783, rs3130922, rs2395043, rs3134899, rs3131638, rs3131633, rs3067945, rs3094001, rs3131630, rs3130636, rs3093993, rs9469021, rs3095227, rs3093992, rs3093988, rs2516482, rs3093983, rs3093981, rs3093980, rs3115537, rs3219190, rs3093978, rs3130056, rs3093948, rs3131628, rs3093976, rs2734583, rs3130058, rs1129640, rs2516393, rs2523511, rs2523508, rs7738430, rs2239528, rs2523504, rs3219183, rs35969216, rs2255798, rs13192469, rs9469024, rs2857709, rs2857708, rs3093542, rs4248157, rs1800629, rs3093671, rs3093672, rs3093561, rs9267503, rs13211368, rs28732144, rs34816476, rs11575839, rs11755226, rs2509217, rs17200810, rs2857700, rs3132451, rs28732150, rs2736182, rs2736177, rs3130070, rs2280801, rs17200837, rs1046080, rs3130623, rs17207225, rs2736161, rs3130626, rs2736157, rs2272593, rs11538263, rs11538264, rs9267522, rs10885, rs9267525, rs3130628, rs7770976, rs35843778, rs2844463, rs10484558, rs3130050, rs3117583, rs805264, rs2273612, rs707921, rs28732157, rs707974, rs805259, rs928814, rs3130618, rs805258, rs9267529, rs3117578, rs805268, rs805267, rs11758242, rs805272, rs3115667, rs805269, rs9267533, rs9267534, rs9267536, rs10573, rs1475865, rs805283, rs1266071, rs9267545, rs34406901, rs805295, rs3793125, rs9469040, rs94690 41, rs9469042, rs3749952, rs4713479, rs453098, rs3101018, rs28381339, rs28381346, rs707915, rs3117572, rs1150793, rs9296001, rs11754464, rs9461718, rs28399987, rs707936, rs707934, rs9461721, rs9461725, rs34585796, rs2273613, rs11751198, rs9296002, rs17201171, rs34636308, rs2227955, rs2227956, rs481825, rs16867582, rs34378923, rs13217108, rs35987121, rs9368699, rs9368700, rs17207629, rs11968400, rs9267577, rs9501157, rs13191375, rs9267649, rs13118, rs35092817, rs4947332, rs11966200, rs13192107, rs9267659, rs36097221, rs589428, rs486416, rs35875104, rs9267661, rs9469069, rs28732165, rs28435656, rs9267673, rs644045, rs511294, rs498240, rs9267677, rs9332705, rs11752672, rs2257331, rs9332735, rs635348, rs12614, rs9501161, rs9267785, rs34555781, rs9296003, rs492899, rs2280773, rs13217120, rs34241101, rs2075702, rs2854432, rs2746394, rs9391732, rs11757034, rs34214527, rs10046127, rs2077580, rs12198173, rs3749963, rs11751545, rs34878747, rs11756755, rs13199524, rs1269854, rs4713503, rs12153855 , Rs13196724, rs28732175, rs204892, rs4713504, rs11753510, rs13211318, rs388629, rs204999, rs28732178, rs3134608, rs34129552, rs3096697, rs3130347, rs34280838, rs3130284, rs2071290, rs3134947, rs3134945, rs3130349, rs12663103, rs9267820, rs2114437, rs3134942, rs3132935, rs6907458 , rs17604492, rs3132956, rs2269418, rs3213468, rs8192591, rs430916, rs2071282, rs8192584, rs8192565, rs483574, rs482759, rs511027, rs28895018, rs28366174, rs6906662, rs9268199, rs6910071, rs498422, rs3132958, rs3132959, rs28732193, rs9469099, rs3117133, rs910049, rs12662503 , rs2395148, rs3129907, rs2894249, rs2143462, rs3129931, rs3129937, rs3129939, rs3129941, rs2076535, rs2073045, rs9391858, rs3129945, rs9268425, rs9268428, rs2894252, rs2894253, rs8180664, rs9268454, rs9268456, rs28732201, rs6930777, rs9268461, rs9268474, rs28366191, rs2076528 , rs2076527, rs3763305, rs2076525, rs2076524, rs3793127, rs3763309, rs3763310, rs3763312, rs3763315, rs3763316, rs9380293, rs9268516, rs9405098, rs3129963, rs2395163, rs 2395165, rs2395166, rs9268557, rs6457580, rs3135344, rs9501626, rs11759143, rs3129860, rs7356880, rs2027856, rs3129868, rs6911777, rs3129883, rs3129886, rs3129887, rs2239805, rs11544315, rs2239802, rs2395182, rs3763326, rs28895103, rs28895187, rs7763262, rs28732227, rs9268831, rs9268926, rs7748472, rs3830135, rs9270665, rs28605404, rs2858870, rs602457, rs9270986, rs9271055, rs9271100, rs660895, rs9271170, rs35759989, rs4530903, rs642093, rs13204672, rs9271348, rs3135005, rs9271366, rs17533090, rs2097431, rs3129763, rs9271588, rs35399661, rs9271775, rs9272219, rs3104369, rs2187668, rs9273012, rs17843604, rs9273327, rs9273349, rs6906021, rs1063355, rs9273448, rs2854275, rs7775228, rs9275224, rs2858324, rs9275245, rs5000634, rs17427431, rs6457617, rs6457622, rs2647003, rs9357152, rs9275312, rs2856725, rs9275330, rs9275333, rs35998847, rs3135006, rs17427599, rs2858308, rs2856717, rs2858305, rs2856705, rs13192471, rs1794275, rs4947344, rs9275572, rs3129727, rs7765379, rs2858332, rs9275595, rs7454108, rs3957146, rs9275596, rs3998159, rs3957148, rs3873444, rs3892710, rs3997854, rs6915986, rs6936707, rs9275659, rs9275686, rs9275698, rs763026, rs2859099, rs9276310, rs7773068, rs7773694, rs7755597, rs9276399, rs17500468, rs2213565, rs9276435, rs28986337, rs28986338, rs28986359, rs28986364, rs10484564, rs28986373, rs13204139, rs28986396, rs7758736, rs9276722, rs11967235, rs2071471, rs3763355, rs3763354, rs9784876, rs16870907, rs13209654, rs10484565, rs9380326, rs4148872, rs4148871, rs241428, rs13215, rs17213812, rs16871027, rs2071538, rs4148878, rs28724900, rs35571244, rs10214510, rs9469311, rs35599935, rs6934645, rs12206377, rs1480380, rs6906517, rs11757089, rs2894311, rs9276969, rs3128933, rs3129304, rs3129303, rs3129302, rs3130603, rs9276992, rs3130604, rs3130607, rs423639, rs17214311, rs3130609, rs397576, rs6933319, rs34493748, rs763469, rs7738815, rs376877, rs2395309, rs3077, rs2301226, rs1054025, rs1042190, rs10214910, rs2301220, rs9277341, rs6914849, rs1431399, rs143140 0, rs1431401, rs2051548, rs9380340, rs2071349, rs2071351, rs2071353, rs3135021, rs1042151, rs2856826, rs9378177, rs9277378, rs9277396, rs9277464, rs9277469, rs3097675, rs9277471, rs9277533, rs9277555, rs3117229, rs3117228, rs9277557, rs9277565, rs3130188, rs3091282, rs3117226, rs3117225, rs3097652, rs2068204, rs3128972, rs2179920, rs10484569, rs2179919, rs2281390, rs2281389, rs3128917, rs2281388, rs7763822, rs3117222, rs3128918, rs3130190, rs3130191, rs3117221, rs3130198, rs3117213, rs2395319, rs3117239, rs2064479, rs2064478, rs2064476, rs3117234, rs3117231, rs3130215, rs3117230, rs3128930, rs6457713, rs9380342, rs9380343, rs6937034, rs6937061, rs9348906, rs9277629, rs1810472, rs2395349, rs3117039, rs3117038, rs3117035, rs1883414, rs9277682, rs4713607, rs9277723, rs3117021, rs6913896, rs3129275, rs3117016, rs3117008, rs3117004, rs3116998, rs3130235, rs3130237, rs6901221, rs9277768, rs2294472, rs2395352, rs7756467, rs3129264, rs7750000, rs9366816, rs13437000, rs4713610, rs926421, rs3129 249, rs9296086, rs7754200, rs3129234, rs3129231, rs3129228, rs3129223, rs3130151, rs2395365, rs3129214, rs721394, rs756441, rs756440, rs9277912, rs3129207, rs3129206, rs9277920, rs9368757, rs9380351, rs2235499, rs734181, rs2235498, rs986522, rs2855441, rs9368758, rs2855440, rs2855437, rs2855430, rs16868943, rs2269346, rs9469378, rs9277935, rs2076310, rs110662, rs439205, rs383711, rs421446, rs107822, rs213210, rs213208, rs1567464, rs213213, rs9277937, rs28892580, rs386084, rs17215210, rs12664430, rs6923740, rs761583, rs7752625, rs1755044, rs2772385, rs2772372, rs2772374, rs68191, rs169737, rs2296340, rs11753634 and rs11758326.
The method according to claim 1, wherein step (a) comprises the steps of: hybridization by microarray; allele-specific probe hybridization; allele specific amplification; sequencing, 5 'nuclease digestion, molecular beacon assay, oligonucleotide ligation assay, size analysis and single-strand conformation polymorphism A single-stranded conformation polymorphism. &Lt; Desc / Clms Page number 13 &gt;
The method according to claim 1, wherein the biological sample is any one selected from the group consisting of blood, tissue, cells, serum, plasma, saliva, sputum and urine.
HLA-A, HLA-B, HLA-C, HLA-DPB1 or HLA-DQB1 genotypes of East Asian people including the following steps:
(a) collecting data for HLA-A, HLA-B, HLA-C, HLA-DPB1 or HLA-DQB1 genotyping from an assay by the method of claim 1; And
(b) comparing the genotypes of the single nucleotide polymorphism combinations obtained from step (a) with the genotypes of the single nucleotide polymorphism combinations and the genotypes of HLA-A, HLA-B, HLA-C, HLA-DPB1 or HLA-DQB1 A, HLA-B, HLA-C, HLA-DPB1 or HLA-DQB1 to be analyzed in comparison with a reference providing predetermined information about the genotype.
5. The method according to claim 4, wherein the genotype of the HLA-A, HLA-B, HLA-C, HLA-DPB1 or HLA-DQB1 is determined by a four-digit allele resolution.
5. The method according to claim 4, wherein the SNP 1 polymorphisms have HLA-A, HLA-B, HLA-C, HLA-DPB1 or HLA- DQB1 genotypes and a linkage disequilibrium index (r ² ) &Lt; / RTI &gt;
Single nucleotide polymorphism SNP combinations in the list 1, or HLA-A of East Asians containing oligonucleotides having a sequence complementary to each of the single nucleotide polymorphism of the combination, HLA-B, HLA-C, HLA-DPB1 or HLA- DQB1 genotype analysis kit.
A computer program for performing on a computer a method of determining a HLA-A, HLA-B, HLA-C, HLA-DPB1 or HLA-DQB1 genotype in an East Asian population comprising the steps of:
(a) receiving genotype information of a single nucleotide polymorphism combination of SNP list 1 obtained from a nucleic acid sample isolated from a biological sample derived from a subject; And
(b) comparing the genotype information of the single nucleotide polymorphism combination obtained from step (a) with the genotypes of the single nucleotide polymorphism combination and the genotype of HLA-A, HLA-B, HLA-C, HLA-DPB1 or HLA- A, HLA-B, HLA-C, HLA-DPB1 or HLA-DQB1 to be analyzed in comparison with a reference database providing predetermined information on the HLA-
9. A computer-readable recording medium containing the computer program of claim 8 for executing the program on a computer.

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