CN1995381A - HLA-A resolution match chip preparation and uses - Google Patents
HLA-A resolution match chip preparation and uses Download PDFInfo
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- CN1995381A CN1995381A CNA2006100130123A CN200610013012A CN1995381A CN 1995381 A CN1995381 A CN 1995381A CN A2006100130123 A CNA2006100130123 A CN A2006100130123A CN 200610013012 A CN200610013012 A CN 200610013012A CN 1995381 A CN1995381 A CN 1995381A
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Abstract
The invention discloses a gene parting chip, which is characterized by the following: designing resolving typed probe in the atopic oligonucleotide according to gene point of common HLA-A of Chinese human populations according to real need; adopting primer marked by fluorescence; augumenting HLA-A on the multi-pattern area through fitful PCR method; crossing product and probe on the chip; scanning and analyzing the positive probe; affirming sample genetype; fitting for clinical and scientific study.
Description
Background technology
HLA antigen is positioned at a narrow zone of people's No. 6 the short arm of a chromosome, is genetic polymorphism system the most complicated in the human body, plays a significant role in the immunoregulation process.The HLA polymorphism detects and is of great significance in medical practice and scientific research, for type is joined in organ, tissue transplantation, and the disease-related Journal of Sex Research, the development in the fields such as application on anthropology and the medical jurisprudence provides reliable technique method and valued data.Serological method is the traditional classical classifying method of HLA-B antigen, but along with going deep into and improving constantly to HLA research to the typing method requirement, and more and more allelotrope is found successively and names, serological method can't obtain enough monospecific antibody, can not tell all specificitys, and the sero-fast triage techniques complexity of standard, difficulty is big, manpower and materials consumption is big, exist more in addition between the serological method, stronger cross reaction makes the resolution of HLA-A class antigenic subtype comparatively difficult.
Along with the continuous development of biology techniques, gene type has become the main method of HLA somatotype.Antigenic gene type research has obtained bigger progress to category-A in recent years.PCR-SSP wherein, PCR-SSO, 3 kinds of classifying methods of PCR-SSCP (single chain conformation polymorphism analysis) are all succeedd to antigenic somatotype. but these methods also exist some significantly not enough, as the PCR-SSP method, mainly depend on round pcr, when being carried out somatotype, a certain gene individuality often to design a large amount of primers, this will be difficult to be avoided the pollution problem in the ensuing PCR process and the false positive that causes, and complicated operation, need judge last result by electrophoresis repeatedly, be not suitable for the somatotype of sample in enormous quantities, its application clinically is restricted; The PCR-SSCP method is very effective less than the 400bpPCR amplified production to analyzing, but this method only can be found out the existence of genovariation, and definite position and content that can't definitive variation be general only as the analysis of HLA matching degree, and are not used for carrying out the concrete somatotype of HLA.
Gene chip is a forward position biotechnology of rising in recent years, be as detection, DNA hybridization, somatotype and great leap and the innovation of sequencing technologies to the traditional biological technology, relate to information biology, microelectronics, computer science, the integrated technology of many natural subjects such as semiconductor technology has been showed huge potential and tempting prospect in life science.Gene chip be meant with many specific widows examine former times acid fragment or gene fragment as probe, clocklike arrange and be fixed on the upholder, the sample gene of crossing with mark to be measured carries out specific hybrid then, by the laser co-focusing fluorescence detecting system chip is scanned, and be equipped with computer system the fluorescent signal on each probe is detected, thereby draw bulk information.Gene chip has highly integrated and characteristics parallel processing, and required reagent and sample size are few, and the result is analyzed automatically by computer software, is the effective ways that solve the numerous allelic gene typings of HLA.Because the essence of HLA idiogenetics difference is on the gene level of its antigen product of coding, so analyze the method the most accurately that the HLA genotype is analyzed the HLA type beyond doubt, its accuracy is far above serum and cytology somatotype, and replaced the above two position gradually, so the antigenic dna typing of HLA becomes inexorable trend.
Summary of the invention
The present invention adopts the oligonucleotide chip classifying method, according to the 13 international organization's consistency working conference report and pertinent literature, consider the linkage disequilibrium of heredity simultaneously, and ankylosing spondylitis, juvenile onset diabetes etc. and factors such as the closely-related inherited disease of HLA, selected the higher allelotrope of Chinese population gene frequency, unique sequences according to HLA-A different genes hypotype, the design and the screening of probe have been finished, design HLA-A56 bar probe at last and made gene typing chips, resolution was differentiated during these probes can be finished, and can satisfy the clinical type requirements of one's work of joining fully.By with fluorescently-labeled primer with sample to be tested fluorescent mark on the sheet broken belt of institute's syllabus behind the pcr amplification, have the probe hybridization on fluorescently-labeled PCR product and the chip, determine the genotype of sample according to hybridization signal power and position.The present invention is stationary probe on slide, and the HLA that can finish HLA gene type, bone marrow transplantation organ transplantation fully joins type, with HLA crowd's examination of the legacy disease of substantial connection arranged.
The objective of the invention is at the HLA-A gene design one cover probe (seeing Table 1).These probe stationary on the chip slapper base of epoxy finishes, are made complete HLA-A genoid oligonucleotide chip, and provide and comprise the necessary all components of experimental implementation, formed the complete test kit of a cover.The HLA that can be used for HLA gene type, bone marrow transplantation organ transplantation joins type, with HLA crowd's examination of the legacy disease of substantial connection is arranged.
Advantage and effect
Enforcement of the present invention has realized, high-pass typing quick, accurate to the HLA-A gene, can realize the many person-portions of chip, that satisfies clinical organ transplantation joins the type requirement, is suitable for clinical expansion, and can be used for other association areas, have important social and economic benefit.
Implementation method
Below in conjunction with description of drawings specific implementation method of the present invention:
Fig. 1 chip outward appearance:
1 surface of glass slide is handled:
The epoxy slide is handled:
Common slide, washing lotion soak, flushing with clean water, and distilled water is given a baby a bath on the third day after its birth time, dries standby.
The ultrasonic 2min of 2%3-glycidoxypropyltriethoxysilane ethanolic soln mixes, and puts into slide 1hr and soaks, and 95% ethanol is washed 5min twice, dries naturally.
2 design of primers and PCR condition
HLA-A selects meaningful exon fragment, designs the primer of oneself.The upstream and downstream primer is designed in exon2 and exon3 zone at the HLA-A seat respectively, for two downstreams and two upstream primers carry out Qian Taoshi PCR, product length is about 800bp, sequence is as follows: normal chain: 5 '-GGCCTCTGT/CGGGGAGAAGCAA-3 ', 5 '-GTCCCAATTGTCTCCCCTCCTT-3 ', anti-chain: 5 '-AGCCGCGCCG/TGGAAGAGGGTCG-3 ', 5 '-GGCCCCTGGTACCCGTGCGCTG-3 '.Amplification condition is: PCR:96 ℃ of 3min for the first time; 96 ℃ of 25s, 65 ℃ of 45s, 72 ℃ of 30s, 26 circulations; 96 ℃ of 25s, 55 ℃ of 1min, 72 ℃ of 2min, 4 circulations; 72 ℃ of 5min.PCR (Nested PCR) for the second time: 96 ℃ of 3min; 96 ℃ of 30s, 56 ℃ of 30s, 72 ℃ of 30s, 30 circulations; 96 ℃ of 30s, 56 ℃ of 1min, 72 ℃ of 2min, 4 circulations; 72 ℃ of 5min.Method is ditto selected top condition, sets up the fluorescently-labeled PCR system of introducing.
3 probes are handled
Probe is through NH
2 -Be used for the chip point sample after the modification.By the Chemical bond of NH2 and epoxy group(ing), probe stationary is on the epoxy sheet base.Be that the oligonucleotide probe of 100umol/L mixes with point sample damping fluid (0.2M NaOH) and is added in 96 orifice plates at 1: 1 with concentration, become required matrix (see figure 1) with the point sample instrument point.From left to right, per five points are represented a probe, are divided into three matrixes, are respectively positive controls, HLA-A, three groups of probes of negative control.The point sample rear enclosed spends the night, treat its seasoning after, 130 ℃ of baking 30min, 95 ℃ of water-bath 1min, sealings treat that its seasoning ,-20 ℃ of preservations are standby.
4 hybridization
10ul is hybridized buffer, 18ulPCR product and 1ul salmon sperm DNA (salmon sperm DNA is used for reducing hybrid context) thorough mixing, positive control with same sample, three kinds of different PCR products of HLA-A negative control arrive corresponding point sample zone with the pipettor application of sample, select the cover glass of suitable size, covered according to area size.Put into Hybridization Oven hybridization, hybridization conditions is 40 ℃, 1 hour.
5 washings
Take out chip, 5 * elutriant (20*SSC) wash-out soaked 5 minutes; Take out chip, put into 3 * elutriant and soaked 5 minutes: ddH
2O washes (after each step soaking and washing, must be centrifugal rapidly) 2 times.Place room temperature to dry naturally the chip of washing, use ScanarryG after the drying
XScanning.
6 scannings
By analysis software, the signal power is converted into signal ratio intuitively, according to the probe sequence of mark on ratio and the particular location, can determine the genotype of sample.In Fig. 2, Far Left is positive locating point, and rightmost is negative locating point, is used for analysis software identification ranks and location.When with the probe hybridization on fluorescently-labeled PCR product and the chip, if probe and PCR product are complementary fully, the hybridization signal that then scans is strong, and color is between yellowish-white; If not complementary fully with the PCR product, a little less than the signal that scans, color is blue or colourless; If complementary with PCR product part, the signal and the color that then scan fall between.By particular analysis software, color power intuitively is converted into the ratio of signal, can draw the somatotype result easily.HLA joins cake core and has designed positive control and negative control and each probe 5 repetitions are arranged, and reliability, stability, the science of system are effectively guaranteed.
Fig. 2 results of hybridization shows
7 results
Chip detection result is with the Micro SSPTM Class I﹠amp of internationally recognizable one lambda company; II Generic Tray carries out parallel check experiment.Gene type result and the gene type that is drawn with internationally recognized one lambda test kit be basically identical as a result.
Inconsistent sample has been carried out the order-checking contrast, and sequencing result and chip analysis result are in full accord.1HLA joins 21 of the distinguishable HLA-A antigen-specifiies of cake core, 196 in allelotrope (seeing Table 6).
Table 6 gene chip is differentiated HLA-A site allelotrope and corresponding antigen-specific thereof
| A*01xx(9) A*02xx(51) A*03xx(9) A*11xx(9) A*23xx(6) A*24xx(30) A*25xx(3) A*26xx(15) | ?A1 ?A2 ?A3 ?A11 ?A23 ?A24 ?A25 ?A26 | A*29xx(4) A*30xx(8) A*31xx(5) A*32xx(6) A*33xx(5) A*34xx(3) A*36xx(2) A*43xx(1) | ?A29 ?A30 ?A31 ?A32 ?A33 ?A34 ?A36 ?A43 | A*80xx(1) A*66xx(3) A*68xx(21) A*69xx(1) A*74xx(4) | A80 A66 A68 A69 A74 |
Annotate: in () is distinguishable allelotrope number.
Sequence table 1:
＜110〉Medical University Of Tianjin
＜120〉resolution is joined the preparation and the application of cake core among the HLA-A
<160>56
<210>1
<211>19
<212>DNA
＜213〉artificial sequence
<220>
＜223〉according to pleomorphism site and the design of Tm value
<400>1
TATTTCTTCA?CATCCGTGT?19
<210>2
<211>19
<212>DNA
＜213〉artificial sequence
<220>
＜223〉according to pleomorphism site and the design of Tm value
<400>2
TATTTCTACA?CCTCCGTGT?19
<210>3
<211>18
<212>DNA
＜213〉artificial sequence
<220>
＜223〉according to pleomorphism site and the design of Tm value
<400>3
TCTACACTTC?CGTGTCCCG?19
<210>4
<211>18
<212>DNA
＜213〉artificial sequence
<220>
＜223〉according to pleomorphism site and the design of Tm value
<400>4
TACACCTCCA?TGTCCCGGC?19
<210>5
<211>19
<212>DNA
＜213〉artificial sequence
<220>
＜223〉according to pleomorphism site and the design of Tm value
<400>5
CAGGAGAGGC?CTGAGTATT?19
<210>6
<211>19
<212>DNA
＜213〉artificial sequence
<220>
＜223〉according to pleomorphism site and the design of Tm value
<400>6
GACGAGGAGA?CAGGGAAAG?19
<210>7
<211>19
<212>DNA
＜213〉artificial sequence
<220>
＜223〉according to pleomorphism site and the design of Tm value
<400>7
GGGACCGGAA?CACACGGAA?19
<210>8
<211>19
<212>DNA
＜213〉artificial sequence
<220>
＜223〉according to pleomorphism site and the design of Tm value
<400>8
GGGACCTGCA?GACACGGAA?19
<210>9
<211>19
<212>DNA
＜213〉artificial sequence
<220>
＜223〉according to pleomorphism site and the design of Tm value
<400>9
GGAACACACG?GAAAGTGAA?19
<210>10
<211>19
<212>DNA
＜213〉artificial sequence
<220>
＜223〉according to pleomorphism site and the design of Tm value
<400>10
GGGACGGGGA?GACACGGAA?19
<210>11
<211>19
<212>DNA
＜213〉artificial sequence
<220>
＜223〉according to pleomorphism site and the design of Tm value
<400>11
ACACGGAATA?TGAAGGCCC?19
<210>12
<211>19
<212>DNA
＜213〉artificial sequence
<220>
＜223〉according to pleomorphism site and the design of Tm value
<400>12
GACACGGAAT?GTGAAGGCC?19
<210>13
<211>15
<212>DNA
＜213〉artificial sequence
<220>
＜223〉according to pleomorphism site and the design of Tm value
<400>13
TCTGTGACTG?GGCCT?15
<210>14
<211>18
<212>DNA
＜213〉artificial sequence
<220>
＜223〉according to pleomorphism site and the design of Tm value
<400>14
TGAAGGCCCA?CTCACAGA?18
<210>15
<211>16
<212>DNA
＜213〉artificial sequence
<220>
＜223〉according to pleomorphism site and the design of Tm value
<400>15
GTCAGTCTGT?GAGTGG?16
<210>16
<211>19
<212>DNA
＜213〉artificial sequence
<220>
＜223〉according to pleomorphism site and the design of Tm value
<400>16
TCACAGACTC?ACCGAGTGG?19
<210>17
<211>19
<212>DNA
＜213〉artificial sequence
<220>
＜223〉according to pleomorphism site and the design of Tm value
<400>17
CACAGATTGA?CCGAGTGGA?19
<210>18
<211>19
<212>DNA
＜213〉artificial sequence
<220>
＜223〉according to pleomorphism site and the design of Tm value
<400>18
ACAGACTGAC?CGAGTGGAC?19
<210>19
<211>19
<212>DNA
＜213〉artificial sequence
<220>
＜223〉according to pleomorphism site and the design of Tm value
<400>19
CCGAGCGAAC?CTGGGGACC?19
<210>20
<211>18
<212>DNA
＜213〉artificial sequence
<220>
＜223〉according to pleomorphism site and the design of Tm value
<400>20
CCGAGTGGAC?CTGGGGAC?18
<210>21
<211>18
<212>DNA
＜213〉artificial sequence
<220>
＜223〉according to pleomorphism site and the design of Tm value
<400>21
CCGAGAGAAC?CTGCGGAT?18
<210>22
<211>19
<212>DNA
＜213〉artificial sequence
<220>
＜223〉according to pleomorphism site and the design of Tm value
<400>22
ACCGAGAGAG?CCTGCGGAT?19
<210>23
<211>19
<212>DNA
＜213〉artificial sequence
<220>
＜223〉according to pleomorphism site and the design of Tm value
<400>23
CCGAGAGAAC?CTGGGGACC?19
<210>24
<211>19
<212>DNA
＜213〉artificial sequence
<220>
＜223〉according to pleomorphism site and the design of Tm value
<400>24
GTGGACCTGG?CGACCCTGC?19
<210>25
<211>19
<212>DNA
＜213〉artificial sequence
<220>
＜223〉according to pleomorphism site and the design of Tm value
<400>25
CACACCATCC?AGATAATGT?19
<210>26
<211>19
<212>DNA
＜213〉artificial sequence
<220>
＜223〉according to pleomorphism site and the design of Tm value
<400>26
CACACCGTCC?AGAGGATGT?19
<210>27
<211>19
<212>DNA
＜213〉artificial sequence
<220>
＜223〉according to pleomorphism site and the design of Tm value
<400>27
TACCGGCAGG?ACGCCTACG?19
<210>28
<211>19
<212>DNA
＜213〉artificial sequence
<220>
＜223〉according to pleomorphism site and the design of Tm value
<400>28
TACCAGCAGGACGCTTACG?19
<210>29
<211>19
<212>DNA
＜213〉artificial sequence
<220>
＜223〉according to pleomorphism site and the design of Tm value
<400>29
TATGAACAGC?ACGCCTACG?19
<210>30
<211>19
<212>DNA
＜213〉artificial sequence
<220>
＜223〉according to pleomorphism site and the design of Tm value
<400>30
TACCACCAGT?ACGCCTACG?19
<210>31
<211>19
<212>DNA
＜213〉artificial sequence
<220>
＜223〉according to pleomorphism site and the design of Tm value
<400>31
TACCAGCAGG?ACGCCTACG?19
<210>32
<211>18
<212>DNA
＜213〉artificial sequence
<220>
＜223〉according to pleomorphism site and the design of Tm value
<400>32
TCGCCTTGAA?CGAGGACC?18
<210>33
<211>18
<212>DNA
＜213〉artificial sequence
<220>
＜223〉according to pleomorphism site and the design of Tm value
<400>33
TCGCCCTGAA?AGAGGACC?18
<210>34
<211>19
<212>DNA
＜213〉artificial sequence
<220>
＜223〉according to pleomorphism site and the design of Tm value
<400>34
CCTGCGCTCT?TGGACCGCG?19
<210>35
<211>19
<212>DNA
＜213〉artificial sequence
<220>
＜223〉according to pleomorphism site and the design of Tm value
<400>35
TCAGATCACC?CAGCGCAAG?19
<210>36
<211>19
<212>DNA
＜213〉artificial sequence
<220>
＜223〉according to pleomorphism site and the design of Tm value
<400>36
TCAGARCACC?AAGCGCAAG?19
<210>37
<211>19
<212>DNA
＜213〉artificial sequence
<220>
＜223〉according to pleomorphism site and the design of Tm value
<400>37
TCAGACCACC?AAGCACAAG?19
<210>38
<211>19
<212>DNA
＜213〉artificial sequence
<220>
＜223〉according to pleomorphism site and the design of Tm value
<400>38
GGAGGCGGCC?CATGTGGCG?19
<210>39
<211>19
<212>DNA
＜213〉artificial sequence
<220>
＜223〉according to pleomorphism site and the design of Tm value
<400>39
GGAGACGGCC?CATGAGGCG?19
<210>40
<211>19
<212>DNA
＜213〉artificial sequence
<220>
＜223〉according to pleomorphism site and the design of Tm value
<400>40
GGAGGCGGCC?CATGAGGCG?19
<210>41
<211>14
<212>DNA
＜213〉artificial sequence
<220>
＜223〉according to pleomorphism site and the design of Tm value
<400>41
CCTCATGGGC?CGCC?14
<210>42
<211>19
<212>DNA
＜213〉artificial sequence
<220>
＜223〉according to pleomorphism site and the design of Tm value
<400>42
AGGCGGCCCA?TGCGGCGGA?19
<210>43
<211>19
<212>DNA
＜213〉artificial sequence
<220>
＜223〉according to pleomorphism site and the design of Tm value
<400>43
AGGCGGCCCG?TCGGGCGGA?19
<210>44
<211>19
<212>DNA
＜213〉artificial sequence
<220>
＜223〉according to pleomorphism site and the design of Tm value
<400>44
AGGCGGCCCG?TGTGGCGGA?19
<210>45
<211>19
<212>DNA
＜213〉artificial sequence
<220>
＜223〉according to pleomorphism site and the design of Tm value
<400>45
GGAGCAGCGG?AGAGTCTAC?19
<210>46
<211>19
<212>DNA
＜213〉artificial sequence
<220>
＜223〉according to pleomorphism site and the design of Tm value
<400>46
GGCGGAGCAG?TTGAGAGCC?19
<210>47
<211>19
<212>DNA
＜213〉artificial sequence
<220>
＜223〉according to pleomorphism site and the design of Tm value
<400>47
GGCGGAGCAG?TGGAGAGCC?19
<210>48
<211>19
<212>DNA
＜213〉artificial sequence
<220>
＜223〉according to pleomorphism site and the design of Tm value
<400>48
GGCGGAGCAG?CAGAGAGCC?19
<210>49
<211>19
<212>DNA
＜213〉artificial sequence
<220>
＜223〉according to pleomorphism site and the design of Tm value
<400>49
CCTGGATGGC?ACGTGCGTG?19
<210>50
<211>18
<212>DNA
＜213〉artificial sequence
<220>
＜223〉according to pleomorphism site and the design of Tm value
<400>50
GCACGTGCGT?GGAGTGGC?18
<210>51
<211>18
<212>DNA
＜213〉artificial sequence
<220>
＜223〉according to pleomorphism site and the design of Tm value
<400>51
GCCGGTGCGT?GGACGGGC?18
<210>52
<211>19
<212>DNA
＜213〉artificial sequence
<220>
＜223〉according to pleomorphism site and the design of Tm value
<400>52
GGCGAGTGCG?TGGAGTGGC?19
<210>53
<211>18
<212>DNA
＜213〉artificial sequence
<220>
＜223〉according to pleomorphism site and the design of Tm value
<400>53
GCACGTGCGT?GGACGGGC?18
<210>54
<211>18
<212>DNA
＜213〉artificial sequence
<220>
＜223〉according to pleomorphism site and the design of Tm value
<400>54
GCCGGTGCGT?GGAGTGGC?18
<210>55
<211>19
<212>DNA
＜213〉artificial sequence
<220>
＜223〉according to pleomorphism site and the design of Tm value
<400>55
GGCGAGTGCG?TGGACGGGC?19
<210>56
<211>19
<212>DNA
＜213〉artificial sequence
<220>
＜223〉according to pleomorphism site and the design of Tm value
<400>56
TGCGTGGACG?GGCTCCGCA?19。
Claims (6)
- Resolution classifying method in 1 one kinds of HLA-A genes, it is characterized in that according in common gene locus of Chinese population HLA-A class and the clinical application to the actual needs of somatotype resolution, resolution typing probes in the design specific oligonucleotide is made gene typing chips.Fluorescently-labeled primer is with in employing, with the polymorphic regions on the suitable PCR method amplification HLA-A class antigen, probe hybridization on product and the chip.Results of hybridization determine the sample gene type with this, and the reagent of this method is formed and the application in clinical and scientific research through fluorescent scanning and with the positive probe of specific software analysis and judgement.The chip agent box component is as follows: detect with sheet base, signal Mk system, oligonucleotide probe, primer, washings, sampling liquid.
- 2 methods according to claim 1, the immobilised probe in every hole is an oligonucleotide probe on the sheet base, its sequence is according to the 13 international organization's consistency working conference report and pertinent literature, consider the linkage disequilibrium of heredity simultaneously, and ankylosing spondylitis, juvenile onset diabetes etc. and factors such as the closely-related inherited disease of HLA, selected the higher allelotrope of Chinese population gene frequency, unique sequences according to HLA-A different genes hypotype, the design and the screening of probe have been finished, design 56 probes of HLA-A at last and made gene typing chips, its length range is 14-30 base, be generally 18 bases, its Tm value is satisfying the medium resolution somatotype of said gene needs.
- 3 ways according to claim 1, its various primers are to design according to HLA-A gene order characteristics, the upstream and downstream primer is designed in exon2 and exon3 zone at the HLA-A seat respectively, for two downstreams and two upstream primers carry out Qian Taoshi PCR, primer length is respectively applied for the amplification of said gene between 18-25 base.
- 4 according to claims 1 described way, and the signaling molecule mark that is used for the signal demonstration is the primer at the amplification of HLA-A gene order.
- 5 according to claims 4, and the signaling molecule that is used for the signal demonstration is CY3.
- 6 according to claims 1 described method, can be applicable to: somatotype is carried out to all seats of crowd HLA-A gene in hospital or blood station, for tissue matching and stem cell transplantation provide foundation.Also can be applicable to R﹠D institution, legal medical expert field for analyzing the genetic diseases relevant and individual identification provides foundation with HLA-A.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA2006100130123A CN1995381A (en) | 2006-01-06 | 2006-01-06 | HLA-A resolution match chip preparation and uses |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA2006100130123A CN1995381A (en) | 2006-01-06 | 2006-01-06 | HLA-A resolution match chip preparation and uses |
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| Publication Number | Publication Date |
|---|---|
| CN1995381A true CN1995381A (en) | 2007-07-11 |
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| CNA2006100130123A Pending CN1995381A (en) | 2006-01-06 | 2006-01-06 | HLA-A resolution match chip preparation and uses |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102209791B (en) * | 2008-11-12 | 2014-02-12 | 香港中文大学 | Detection of HLA genotype |
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2006
- 2006-01-06 CN CNA2006100130123A patent/CN1995381A/en active Pending
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102209791B (en) * | 2008-11-12 | 2014-02-12 | 香港中文大学 | Detection of HLA genotype |
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