AU2018258580A1 - Methods for detecting alleles associated with keratoconus - Google Patents
Methods for detecting alleles associated with keratoconus Download PDFInfo
- Publication number
- AU2018258580A1 AU2018258580A1 AU2018258580A AU2018258580A AU2018258580A1 AU 2018258580 A1 AU2018258580 A1 AU 2018258580A1 AU 2018258580 A AU2018258580 A AU 2018258580A AU 2018258580 A AU2018258580 A AU 2018258580A AU 2018258580 A1 AU2018258580 A1 AU 2018258580A1
- Authority
- AU
- Australia
- Prior art keywords
- subject
- variants
- genetic variants
- genetic
- dna
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- 238000000034 method Methods 0.000 title claims abstract description 138
- 201000002287 Keratoconus Diseases 0.000 title abstract description 111
- 108700028369 Alleles Proteins 0.000 title description 24
- 239000002773 nucleotide Substances 0.000 claims abstract description 49
- 125000003729 nucleotide group Chemical group 0.000 claims abstract description 49
- 230000002068 genetic effect Effects 0.000 claims description 110
- 238000001514 detection method Methods 0.000 claims description 57
- 238000012163 sequencing technique Methods 0.000 claims description 36
- 238000011269 treatment regimen Methods 0.000 claims description 36
- 238000011282 treatment Methods 0.000 claims description 25
- 238000003745 diagnosis Methods 0.000 claims description 12
- 108091093088 Amplicon Proteins 0.000 claims description 9
- 238000004393 prognosis Methods 0.000 claims description 5
- 102000054765 polymorphisms of proteins Human genes 0.000 abstract description 6
- 239000000523 sample Substances 0.000 description 127
- 108020004414 DNA Proteins 0.000 description 61
- 150000007523 nucleic acids Chemical class 0.000 description 49
- 230000035772 mutation Effects 0.000 description 46
- 102000039446 nucleic acids Human genes 0.000 description 44
- 108020004707 nucleic acids Proteins 0.000 description 44
- 108090000623 proteins and genes Proteins 0.000 description 43
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 35
- 210000004027 cell Anatomy 0.000 description 34
- 210000004087 cornea Anatomy 0.000 description 30
- 239000000243 solution Substances 0.000 description 29
- 201000010099 disease Diseases 0.000 description 27
- 230000009089 cytolysis Effects 0.000 description 26
- 239000003153 chemical reaction reagent Substances 0.000 description 22
- 239000000203 mixture Substances 0.000 description 22
- 239000002585 base Substances 0.000 description 21
- 238000003752 polymerase chain reaction Methods 0.000 description 19
- 238000003753 real-time PCR Methods 0.000 description 18
- 238000012360 testing method Methods 0.000 description 18
- 108010035532 Collagen Proteins 0.000 description 17
- 238000004458 analytical method Methods 0.000 description 17
- 239000000758 substrate Substances 0.000 description 16
- 102000008186 Collagen Human genes 0.000 description 15
- 238000009396 hybridization Methods 0.000 description 15
- 229920001436 collagen Polymers 0.000 description 14
- 238000005516 engineering process Methods 0.000 description 14
- 210000001508 eye Anatomy 0.000 description 14
- 239000000975 dye Substances 0.000 description 13
- 238000012986 modification Methods 0.000 description 13
- 230000004048 modification Effects 0.000 description 13
- 201000009310 astigmatism Diseases 0.000 description 12
- 230000001965 increasing effect Effects 0.000 description 12
- 108091028043 Nucleic acid sequence Proteins 0.000 description 11
- 230000003321 amplification Effects 0.000 description 11
- VHRGRCVQAFMJIZ-UHFFFAOYSA-N cadaverine Chemical compound NCCCCCN VHRGRCVQAFMJIZ-UHFFFAOYSA-N 0.000 description 11
- 238000003199 nucleic acid amplification method Methods 0.000 description 11
- 230000002441 reversible effect Effects 0.000 description 11
- 239000011324 bead Substances 0.000 description 10
- 239000007790 solid phase Substances 0.000 description 10
- 239000000872 buffer Substances 0.000 description 9
- 238000004132 cross linking Methods 0.000 description 9
- 239000012634 fragment Substances 0.000 description 9
- 238000001356 surgical procedure Methods 0.000 description 9
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 8
- 238000003556 assay Methods 0.000 description 8
- 230000008859 change Effects 0.000 description 8
- 238000002405 diagnostic procedure Methods 0.000 description 8
- 238000010791 quenching Methods 0.000 description 8
- 230000000171 quenching effect Effects 0.000 description 8
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 8
- 238000006243 chemical reaction Methods 0.000 description 7
- 210000000349 chromosome Anatomy 0.000 description 7
- 208000035475 disorder Diseases 0.000 description 7
- 230000004438 eyesight Effects 0.000 description 7
- 239000007850 fluorescent dye Substances 0.000 description 7
- 239000011521 glass Substances 0.000 description 7
- 238000002844 melting Methods 0.000 description 7
- 230000008018 melting Effects 0.000 description 7
- 102000053602 DNA Human genes 0.000 description 6
- 208000026350 Inborn Genetic disease Diseases 0.000 description 6
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 238000000137 annealing Methods 0.000 description 6
- 238000013461 design Methods 0.000 description 6
- 210000002919 epithelial cell Anatomy 0.000 description 6
- 208000016361 genetic disease Diseases 0.000 description 6
- 230000007614 genetic variation Effects 0.000 description 6
- -1 organic solvents Chemical class 0.000 description 6
- 238000012216 screening Methods 0.000 description 6
- 102000004190 Enzymes Human genes 0.000 description 5
- 108090000790 Enzymes Proteins 0.000 description 5
- 206010064571 Gene mutation Diseases 0.000 description 5
- 241000521257 Hydrops Species 0.000 description 5
- 206010030113 Oedema Diseases 0.000 description 5
- 238000013459 approach Methods 0.000 description 5
- 230000000295 complement effect Effects 0.000 description 5
- 239000002131 composite material Substances 0.000 description 5
- 238000012217 deletion Methods 0.000 description 5
- 230000037430 deletion Effects 0.000 description 5
- 229940088598 enzyme Drugs 0.000 description 5
- 238000003205 genotyping method Methods 0.000 description 5
- 238000000126 in silico method Methods 0.000 description 5
- 238000003780 insertion Methods 0.000 description 5
- 230000037431 insertion Effects 0.000 description 5
- 150000002500 ions Chemical class 0.000 description 5
- 238000005259 measurement Methods 0.000 description 5
- 238000010369 molecular cloning Methods 0.000 description 5
- 230000000149 penetrating effect Effects 0.000 description 5
- 238000012175 pyrosequencing Methods 0.000 description 5
- 230000037390 scarring Effects 0.000 description 5
- 238000012876 topography Methods 0.000 description 5
- 230000004304 visual acuity Effects 0.000 description 5
- 238000007482 whole exome sequencing Methods 0.000 description 5
- 102100022145 Collagen alpha-1(IV) chain Human genes 0.000 description 4
- 102000004163 DNA-directed RNA polymerases Human genes 0.000 description 4
- 108090000626 DNA-directed RNA polymerases Proteins 0.000 description 4
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 4
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 4
- 101000901150 Homo sapiens Collagen alpha-1(IV) chain Proteins 0.000 description 4
- 101000710876 Homo sapiens Collagen alpha-2(IV) chain Proteins 0.000 description 4
- PEEHTFAAVSWFBL-UHFFFAOYSA-N Maleimide Chemical compound O=C1NC(=O)C=C1 PEEHTFAAVSWFBL-UHFFFAOYSA-N 0.000 description 4
- 108091034117 Oligonucleotide Proteins 0.000 description 4
- 108091093037 Peptide nucleic acid Proteins 0.000 description 4
- AUNGANRZJHBGPY-SCRDCRAPSA-N Riboflavin Chemical compound OC[C@@H](O)[C@@H](O)[C@@H](O)CN1C=2C=C(C)C(C)=CC=2N=C2C1=NC(=O)NC2=O AUNGANRZJHBGPY-SCRDCRAPSA-N 0.000 description 4
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
- 208000037065 Subacute sclerosing leukoencephalitis Diseases 0.000 description 4
- 206010042297 Subacute sclerosing panencephalitis Diseases 0.000 description 4
- 101150112441 Vsx1 gene Proteins 0.000 description 4
- 230000002776 aggregation Effects 0.000 description 4
- 238000004220 aggregation Methods 0.000 description 4
- 210000004369 blood Anatomy 0.000 description 4
- 239000008280 blood Substances 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 210000000981 epithelium Anatomy 0.000 description 4
- MHMNJMPURVTYEJ-UHFFFAOYSA-N fluorescein-5-isothiocyanate Chemical compound O1C(=O)C2=CC(N=C=S)=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 MHMNJMPURVTYEJ-UHFFFAOYSA-N 0.000 description 4
- 201000000766 irregular astigmatism Diseases 0.000 description 4
- 239000012139 lysis buffer Substances 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- 239000011807 nanoball Substances 0.000 description 4
- 230000007170 pathology Effects 0.000 description 4
- 230000008569 process Effects 0.000 description 4
- 235000018102 proteins Nutrition 0.000 description 4
- 102000004169 proteins and genes Human genes 0.000 description 4
- 230000001850 reproductive effect Effects 0.000 description 4
- 150000003839 salts Chemical class 0.000 description 4
- 230000001568 sexual effect Effects 0.000 description 4
- 208000024891 symptom Diseases 0.000 description 4
- 230000000007 visual effect Effects 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- COCMHKNAGZHBDZ-UHFFFAOYSA-N 4-carboxy-3-[3-(dimethylamino)-6-dimethylazaniumylidenexanthen-9-yl]benzoate Chemical compound C=12C=CC(=[N+](C)C)C=C2OC2=CC(N(C)C)=CC=C2C=1C1=CC(C([O-])=O)=CC=C1C(O)=O COCMHKNAGZHBDZ-UHFFFAOYSA-N 0.000 description 3
- YMZMTOFQCVHHFB-UHFFFAOYSA-N 5-carboxytetramethylrhodamine Chemical compound C=12C=CC(N(C)C)=CC2=[O+]C2=CC(N(C)C)=CC=C2C=1C1=CC=C(C(O)=O)C=C1C([O-])=O YMZMTOFQCVHHFB-UHFFFAOYSA-N 0.000 description 3
- BZTDTCNHAFUJOG-UHFFFAOYSA-N 6-carboxyfluorescein Chemical group C12=CC=C(O)C=C2OC2=CC(O)=CC=C2C11OC(=O)C2=CC=C(C(=O)O)C=C21 BZTDTCNHAFUJOG-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- 102100033780 Collagen alpha-3(IV) chain Human genes 0.000 description 3
- 238000001712 DNA sequencing Methods 0.000 description 3
- 108010014303 DNA-directed DNA polymerase Proteins 0.000 description 3
- 102000016928 DNA-directed DNA polymerase Human genes 0.000 description 3
- 101000710873 Homo sapiens Collagen alpha-3(IV) chain Proteins 0.000 description 3
- 101000710870 Homo sapiens Collagen alpha-4(IV) chain Proteins 0.000 description 3
- 101000713590 Homo sapiens T-box transcription factor TBX1 Proteins 0.000 description 3
- 108091092878 Microsatellite Proteins 0.000 description 3
- 101710163270 Nuclease Proteins 0.000 description 3
- 108020005187 Oligonucleotide Probes Proteins 0.000 description 3
- 102100036771 T-box transcription factor TBX1 Human genes 0.000 description 3
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 3
- 230000001154 acute effect Effects 0.000 description 3
- 230000008901 benefit Effects 0.000 description 3
- 230000015556 catabolic process Effects 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- 230000002939 deleterious effect Effects 0.000 description 3
- 239000003599 detergent Substances 0.000 description 3
- 238000011161 development Methods 0.000 description 3
- 230000018109 developmental process Effects 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 239000000839 emulsion Substances 0.000 description 3
- 210000003038 endothelium Anatomy 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 239000007789 gas Substances 0.000 description 3
- 238000010348 incorporation Methods 0.000 description 3
- 238000002955 isolation Methods 0.000 description 3
- 230000000670 limiting effect Effects 0.000 description 3
- 210000004379 membrane Anatomy 0.000 description 3
- 239000012528 membrane Substances 0.000 description 3
- YACKEPLHDIMKIO-UHFFFAOYSA-N methylphosphonic acid Chemical group CP(O)(O)=O YACKEPLHDIMKIO-UHFFFAOYSA-N 0.000 description 3
- 238000012544 monitoring process Methods 0.000 description 3
- 238000007481 next generation sequencing Methods 0.000 description 3
- 239000002751 oligonucleotide probe Substances 0.000 description 3
- 230000003287 optical effect Effects 0.000 description 3
- 239000012071 phase Substances 0.000 description 3
- 108091033319 polynucleotide Proteins 0.000 description 3
- 102000040430 polynucleotide Human genes 0.000 description 3
- 239000002157 polynucleotide Substances 0.000 description 3
- 238000012545 processing Methods 0.000 description 3
- 230000000750 progressive effect Effects 0.000 description 3
- 238000011002 quantification Methods 0.000 description 3
- 239000004065 semiconductor Substances 0.000 description 3
- 239000011780 sodium chloride Substances 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- 238000011477 surgical intervention Methods 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- 210000001519 tissue Anatomy 0.000 description 3
- 238000005406 washing Methods 0.000 description 3
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 2
- OBYNJKLOYWCXEP-UHFFFAOYSA-N 2-[3-(dimethylamino)-6-dimethylazaniumylidenexanthen-9-yl]-4-isothiocyanatobenzoate Chemical compound C=12C=CC(=[N+](C)C)C=C2OC2=CC(N(C)C)=CC=C2C=1C1=CC(N=C=S)=CC=C1C([O-])=O OBYNJKLOYWCXEP-UHFFFAOYSA-N 0.000 description 2
- IJSMFQNTEUNRPY-UHFFFAOYSA-N 2-[3-(dimethylamino)-6-dimethylazaniumylidenexanthen-9-yl]-5-isothiocyanatobenzoate Chemical compound C=12C=CC(=[N+](C)C)C=C2OC2=CC(N(C)C)=CC=C2C=1C1=CC=C(N=C=S)C=C1C([O-])=O IJSMFQNTEUNRPY-UHFFFAOYSA-N 0.000 description 2
- ONTCUDVUGYVDSS-UHFFFAOYSA-N 4-(3-amino-6-iminoxanthen-9-yl)benzene-1,3-dicarboxylic acid Chemical compound C=12C=CC(=N)C=C2OC2=CC(N)=CC=C2C=1C1=CC=C(C(O)=O)C=C1C(O)=O ONTCUDVUGYVDSS-UHFFFAOYSA-N 0.000 description 2
- BPVHBBXCESDRKW-UHFFFAOYSA-N 5(6)-carboxyfluorescein Chemical compound C12=CC=C(O)C=C2OC2=CC(O)=CC=C2C21OC(=O)C1=CC(C(=O)O)=CC=C21.C12=CC=C(O)C=C2OC2=CC(O)=CC=C2C11OC(=O)C2=CC=C(C(=O)O)C=C21 BPVHBBXCESDRKW-UHFFFAOYSA-N 0.000 description 2
- NJYVEMPWNAYQQN-UHFFFAOYSA-N 5-carboxyfluorescein Chemical compound C12=CC=C(O)C=C2OC2=CC(O)=CC=C2C21OC(=O)C1=CC(C(=O)O)=CC=C21 NJYVEMPWNAYQQN-UHFFFAOYSA-N 0.000 description 2
- IDLISIVVYLGCKO-UHFFFAOYSA-N 6-carboxy-4',5'-dichloro-2',7'-dimethoxyfluorescein Chemical compound O1C(=O)C2=CC=C(C(O)=O)C=C2C21C1=CC(OC)=C(O)C(Cl)=C1OC1=C2C=C(OC)C(O)=C1Cl IDLISIVVYLGCKO-UHFFFAOYSA-N 0.000 description 2
- WQZIDRAQTRIQDX-UHFFFAOYSA-N 6-carboxy-x-rhodamine Chemical compound OC(=O)C1=CC=C(C([O-])=O)C=C1C(C1=CC=2CCCN3CCCC(C=23)=C1O1)=C2C1=C(CCC1)C3=[N+]1CCCC3=C2 WQZIDRAQTRIQDX-UHFFFAOYSA-N 0.000 description 2
- VWOLRKMFAJUZGM-UHFFFAOYSA-N 6-carboxyrhodamine 6G Chemical compound [Cl-].C=12C=C(C)C(NCC)=CC2=[O+]C=2C=C(NCC)C(C)=CC=2C=1C1=CC(C(O)=O)=CC=C1C(=O)OCC VWOLRKMFAJUZGM-UHFFFAOYSA-N 0.000 description 2
- ZEKAXIFHLIITGV-UHFFFAOYSA-N 7-methoxycoumarin-4-acetic acid Chemical compound OC(=O)CC1=CC(=O)OC2=CC(OC)=CC=C21 ZEKAXIFHLIITGV-UHFFFAOYSA-N 0.000 description 2
- 241000972773 Aulopiformes Species 0.000 description 2
- 108091026890 Coding region Proteins 0.000 description 2
- 229920000742 Cotton Polymers 0.000 description 2
- AUNGANRZJHBGPY-UHFFFAOYSA-N D-Lyxoflavin Natural products OCC(O)C(O)C(O)CN1C=2C=C(C)C(C)=CC=2N=C2C1=NC(=O)NC2=O AUNGANRZJHBGPY-UHFFFAOYSA-N 0.000 description 2
- 238000007400 DNA extraction Methods 0.000 description 2
- 238000009007 Diagnostic Kit Methods 0.000 description 2
- 108060002716 Exonuclease Proteins 0.000 description 2
- 206010020751 Hypersensitivity Diseases 0.000 description 2
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
- 241000124008 Mammalia Species 0.000 description 2
- 108091005461 Nucleic proteins Proteins 0.000 description 2
- 239000004793 Polystyrene Substances 0.000 description 2
- 229920000297 Rayon Polymers 0.000 description 2
- 241000239226 Scorpiones Species 0.000 description 2
- 229920002125 Sokalan® Polymers 0.000 description 2
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
- 229930006000 Sucrose Natural products 0.000 description 2
- JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 description 2
- 239000012670 alkaline solution Substances 0.000 description 2
- 125000003275 alpha amino acid group Chemical group 0.000 description 2
- 238000004422 calculation algorithm Methods 0.000 description 2
- 238000004364 calculation method Methods 0.000 description 2
- 239000002738 chelating agent Substances 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 238000012937 correction Methods 0.000 description 2
- 239000000634 cycloplegic agent Substances 0.000 description 2
- 229940124570 cycloplegic agent Drugs 0.000 description 2
- 230000004452 decreased vision Effects 0.000 description 2
- 238000006731 degradation reaction Methods 0.000 description 2
- 210000002555 descemet membrane Anatomy 0.000 description 2
- 239000012153 distilled water Substances 0.000 description 2
- 230000009977 dual effect Effects 0.000 description 2
- DEFVIWRASFVYLL-UHFFFAOYSA-N ethylene glycol bis(2-aminoethyl)tetraacetic acid Chemical compound OC(=O)CN(CC(O)=O)CCOCCOCCN(CC(O)=O)CC(O)=O DEFVIWRASFVYLL-UHFFFAOYSA-N 0.000 description 2
- 102000013165 exonuclease Human genes 0.000 description 2
- 208000030533 eye disease Diseases 0.000 description 2
- 230000037433 frameshift Effects 0.000 description 2
- UYTPUPDQBNUYGX-UHFFFAOYSA-N guanine Chemical class O=C1NC(N)=NC2=C1N=CN2 UYTPUPDQBNUYGX-UHFFFAOYSA-N 0.000 description 2
- 238000012165 high-throughput sequencing Methods 0.000 description 2
- 229920001519 homopolymer Polymers 0.000 description 2
- 230000003100 immobilizing effect Effects 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 230000000977 initiatory effect Effects 0.000 description 2
- 208000014674 injury Diseases 0.000 description 2
- 230000003993 interaction Effects 0.000 description 2
- 230000004410 intraocular pressure Effects 0.000 description 2
- 230000001788 irregular Effects 0.000 description 2
- 238000013532 laser treatment Methods 0.000 description 2
- 101150070593 lox gene Proteins 0.000 description 2
- 235000019689 luncheon sausage Nutrition 0.000 description 2
- 239000008176 lyophilized powder Substances 0.000 description 2
- 238000004949 mass spectrometry Methods 0.000 description 2
- 238000002493 microarray Methods 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 description 2
- 230000003472 neutralizing effect Effects 0.000 description 2
- 238000007899 nucleic acid hybridization Methods 0.000 description 2
- 239000002777 nucleoside Substances 0.000 description 2
- 239000002674 ointment Substances 0.000 description 2
- 230000036407 pain Effects 0.000 description 2
- 230000001717 pathogenic effect Effects 0.000 description 2
- 230000002974 pharmacogenomic effect Effects 0.000 description 2
- 150000008298 phosphoramidates Chemical class 0.000 description 2
- 230000010399 physical interaction Effects 0.000 description 2
- 229920005862 polyol Polymers 0.000 description 2
- 150000003077 polyols Chemical class 0.000 description 2
- 229920002223 polystyrene Polymers 0.000 description 2
- 239000011148 porous material Substances 0.000 description 2
- 230000003449 preventive effect Effects 0.000 description 2
- BBEAQIROQSPTKN-UHFFFAOYSA-N pyrene Chemical compound C1=CC=C2C=CC3=CC=CC4=CC=C1C2=C43 BBEAQIROQSPTKN-UHFFFAOYSA-N 0.000 description 2
- 239000002964 rayon Substances 0.000 description 2
- 230000003362 replicative effect Effects 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 235000019192 riboflavin Nutrition 0.000 description 2
- 229960002477 riboflavin Drugs 0.000 description 2
- 239000002151 riboflavin Substances 0.000 description 2
- 235000019515 salmon Nutrition 0.000 description 2
- 238000007480 sanger sequencing Methods 0.000 description 2
- 230000035945 sensitivity Effects 0.000 description 2
- 238000007841 sequencing by ligation Methods 0.000 description 2
- 210000002966 serum Anatomy 0.000 description 2
- 239000000377 silicon dioxide Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- 239000004094 surface-active agent Substances 0.000 description 2
- 230000002194 synthesizing effect Effects 0.000 description 2
- UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 description 2
- 238000003325 tomography Methods 0.000 description 2
- 238000013518 transcription Methods 0.000 description 2
- 230000035897 transcription Effects 0.000 description 2
- 230000007704 transition Effects 0.000 description 2
- 230000008733 trauma Effects 0.000 description 2
- 230000000472 traumatic effect Effects 0.000 description 2
- 238000002604 ultrasonography Methods 0.000 description 2
- 239000013598 vector Substances 0.000 description 2
- AYDAHOIUHVUJHQ-UHFFFAOYSA-N 1-(3',6'-dihydroxy-3-oxospiro[2-benzofuran-1,9'-xanthene]-5-yl)pyrrole-2,5-dione Chemical compound C=1C(O)=CC=C2C=1OC1=CC(O)=CC=C1C2(C1=CC=2)OC(=O)C1=CC=2N1C(=O)C=CC1=O AYDAHOIUHVUJHQ-UHFFFAOYSA-N 0.000 description 1
- SERLAGPUMNYUCK-DCUALPFSSA-N 1-O-alpha-D-glucopyranosyl-D-mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO[C@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O SERLAGPUMNYUCK-DCUALPFSSA-N 0.000 description 1
- DAKRRPZULHQSKP-UHFFFAOYSA-N 1-oxospiro[2-benzofuran-3,16'-3-oxa-9,23-diazaheptacyclo[17.7.1.15,9.02,17.04,15.023,27.013,28]octacosa-1(27),2(17),4(15),5(28),13,18-hexaene]-5-carboxylic acid Chemical compound C1CCN2CCCC(C=C3C4(OC(=O)C5=CC=C(C=C54)C(=O)O)C4=C5)=C2C1=C3OC4=C1CCCN2CCCC5=C12 DAKRRPZULHQSKP-UHFFFAOYSA-N 0.000 description 1
- UMCMPZBLKLEWAF-BCTGSCMUSA-N 3-[(3-cholamidopropyl)dimethylammonio]propane-1-sulfonate Chemical compound C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(=O)NCCC[N+](C)(C)CCCS([O-])(=O)=O)C)[C@@]2(C)[C@@H](O)C1 UMCMPZBLKLEWAF-BCTGSCMUSA-N 0.000 description 1
- SJQRQOKXQKVJGJ-UHFFFAOYSA-N 5-(2-aminoethylamino)naphthalene-1-sulfonic acid Chemical compound C1=CC=C2C(NCCN)=CC=CC2=C1S(O)(=O)=O SJQRQOKXQKVJGJ-UHFFFAOYSA-N 0.000 description 1
- GGMFTOCYWNYUSU-UHFFFAOYSA-N 5-(5-aminopentylcarbamoyl)-2-[3-(dimethylamino)-6-dimethylazaniumylidenexanthen-9-yl]benzoate Chemical compound C=12C=CC(=[N+](C)C)C=C2OC2=CC(N(C)C)=CC=C2C=1C1=CC=C(C(=O)NCCCCCN)C=C1C([O-])=O GGMFTOCYWNYUSU-UHFFFAOYSA-N 0.000 description 1
- MDGNQWAJTIGWLE-UHFFFAOYSA-N 5-[(4,6-dichloro-1,3,5-triazin-2-yl)amino]-3',6'-dihydroxyspiro[2-benzofuran-3,9'-xanthene]-1-one Chemical compound C=1C(O)=CC=C2C=1OC1=CC(O)=CC=C1C2(C1=C2)OC(=O)C1=CC=C2NC1=NC(Cl)=NC(Cl)=N1 MDGNQWAJTIGWLE-UHFFFAOYSA-N 0.000 description 1
- HWQQCFPHXPNXHC-UHFFFAOYSA-N 6-[(4,6-dichloro-1,3,5-triazin-2-yl)amino]-3',6'-dihydroxyspiro[2-benzofuran-3,9'-xanthene]-1-one Chemical compound C=1C(O)=CC=C2C=1OC1=CC(O)=CC=C1C2(C1=CC=2)OC(=O)C1=CC=2NC1=NC(Cl)=NC(Cl)=N1 HWQQCFPHXPNXHC-UHFFFAOYSA-N 0.000 description 1
- CZVCGJBESNRLEQ-UHFFFAOYSA-N 7h-purine;pyrimidine Chemical compound C1=CN=CN=C1.C1=NC=C2NC=NC2=N1 CZVCGJBESNRLEQ-UHFFFAOYSA-N 0.000 description 1
- 101710092462 Alpha-hemolysin Proteins 0.000 description 1
- 229920001342 Bakelite® Polymers 0.000 description 1
- 201000004569 Blindness Diseases 0.000 description 1
- 101150066399 COL4A1 gene Proteins 0.000 description 1
- 101150057990 COL4A4 gene Proteins 0.000 description 1
- LZZYPRNAOMGNLH-UHFFFAOYSA-M Cetrimonium bromide Chemical compound [Br-].CCCCCCCCCCCCCCCC[N+](C)(C)C LZZYPRNAOMGNLH-UHFFFAOYSA-M 0.000 description 1
- 102100033781 Collagen alpha-2(IV) chain Human genes 0.000 description 1
- 102100033779 Collagen alpha-4(IV) chain Human genes 0.000 description 1
- 206010010510 Congenital hypothyroidism Diseases 0.000 description 1
- 108091035707 Consensus sequence Proteins 0.000 description 1
- 229920000858 Cyclodextrin Polymers 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- 102000012410 DNA Ligases Human genes 0.000 description 1
- 108010061982 DNA Ligases Proteins 0.000 description 1
- 108020003215 DNA Probes Proteins 0.000 description 1
- 239000003298 DNA probe Substances 0.000 description 1
- 230000006820 DNA synthesis Effects 0.000 description 1
- 102100024353 Dedicator of cytokinesis protein 9 Human genes 0.000 description 1
- BVTJGGGYKAMDBN-UHFFFAOYSA-N Dioxetane Chemical class C1COO1 BVTJGGGYKAMDBN-UHFFFAOYSA-N 0.000 description 1
- 102100029671 E3 ubiquitin-protein ligase TRIM8 Human genes 0.000 description 1
- 108010014258 Elastin Proteins 0.000 description 1
- 102000016942 Elastin Human genes 0.000 description 1
- 239000004386 Erythritol Substances 0.000 description 1
- UNXHWFMMPAWVPI-UHFFFAOYSA-N Erythritol Natural products OCC(O)C(O)CO UNXHWFMMPAWVPI-UHFFFAOYSA-N 0.000 description 1
- 241000588724 Escherichia coli Species 0.000 description 1
- 206010015946 Eye irritation Diseases 0.000 description 1
- 102100027267 FERM, ARHGEF and pleckstrin domain-containing protein 1 Human genes 0.000 description 1
- 229920001917 Ficoll Polymers 0.000 description 1
- 208000034826 Genetic Predisposition to Disease Diseases 0.000 description 1
- 108700005087 Homeobox Genes Proteins 0.000 description 1
- 101001052948 Homo sapiens Dedicator of cytokinesis protein 9 Proteins 0.000 description 1
- 101000795300 Homo sapiens E3 ubiquitin-protein ligase TRIM8 Proteins 0.000 description 1
- 101000914701 Homo sapiens FERM, ARHGEF and pleckstrin domain-containing protein 1 Proteins 0.000 description 1
- 101000852539 Homo sapiens Importin-5 Proteins 0.000 description 1
- 101000583839 Homo sapiens Muscleblind-like protein 1 Proteins 0.000 description 1
- 101001079155 Homo sapiens RING finger protein 113B Proteins 0.000 description 1
- 101000628647 Homo sapiens Serine/threonine-protein kinase 24 Proteins 0.000 description 1
- 101000976643 Homo sapiens Zinc finger protein ZIC 2 Proteins 0.000 description 1
- 101000976649 Homo sapiens Zinc finger protein ZIC 5 Proteins 0.000 description 1
- 102100036340 Importin-5 Human genes 0.000 description 1
- 241001071864 Lethrinus laticaudis Species 0.000 description 1
- 108060001084 Luciferase Proteins 0.000 description 1
- 239000005089 Luciferase Substances 0.000 description 1
- 206010025421 Macule Diseases 0.000 description 1
- 102000016943 Muramidase Human genes 0.000 description 1
- 108010014251 Muramidase Proteins 0.000 description 1
- 102100030965 Muscleblind-like protein 1 Human genes 0.000 description 1
- 108010062010 N-Acetylmuramoyl-L-alanine Amidase Proteins 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 108091092724 Noncoding DNA Proteins 0.000 description 1
- 239000004677 Nylon Substances 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 208000031816 Pathologic Dilatation Diseases 0.000 description 1
- 201000011252 Phenylketonuria Diseases 0.000 description 1
- 108010010677 Phosphodiesterase I Proteins 0.000 description 1
- 239000004698 Polyethylene Substances 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 239000004743 Polypropylene Substances 0.000 description 1
- 102100028136 RING finger protein 113B Human genes 0.000 description 1
- 238000011529 RT qPCR Methods 0.000 description 1
- 108091028664 Ribonucleotide Proteins 0.000 description 1
- 238000012300 Sequence Analysis Methods 0.000 description 1
- 102100026764 Serine/threonine-protein kinase 24 Human genes 0.000 description 1
- 229920001800 Shellac Polymers 0.000 description 1
- 206010040925 Skin striae Diseases 0.000 description 1
- 238000002105 Southern blotting Methods 0.000 description 1
- 108010006785 Taq Polymerase Proteins 0.000 description 1
- RYYWUUFWQRZTIU-UHFFFAOYSA-N Thiophosphoric acid Chemical group OP(O)(S)=O RYYWUUFWQRZTIU-UHFFFAOYSA-N 0.000 description 1
- GYDJEQRTZSCIOI-UHFFFAOYSA-N Tranexamic acid Chemical compound NCC1CCC(C(O)=O)CC1 GYDJEQRTZSCIOI-UHFFFAOYSA-N 0.000 description 1
- 206010052779 Transplant rejections Diseases 0.000 description 1
- 239000013504 Triton X-100 Substances 0.000 description 1
- 229920004890 Triton X-100 Polymers 0.000 description 1
- 241000251539 Vertebrata <Metazoa> Species 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 206010052428 Wound Diseases 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 description 1
- 101150013194 ZNF469 gene Proteins 0.000 description 1
- 102100023492 Zinc finger protein ZIC 2 Human genes 0.000 description 1
- 102100023494 Zinc finger protein ZIC 5 Human genes 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 238000003916 acid precipitation Methods 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- DZBUGLKDJFMEHC-UHFFFAOYSA-N acridine Chemical class C1=CC=CC2=CC3=CC=CC=C3N=C21 DZBUGLKDJFMEHC-UHFFFAOYSA-N 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 239000013566 allergen Substances 0.000 description 1
- 230000007815 allergy Effects 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 238000005571 anion exchange chromatography Methods 0.000 description 1
- 239000012062 aqueous buffer Substances 0.000 description 1
- 238000003491 array Methods 0.000 description 1
- 230000003190 augmentative effect Effects 0.000 description 1
- 239000004637 bakelite Substances 0.000 description 1
- 238000012042 bayesian logistic regression model Methods 0.000 description 1
- 230000002146 bilateral effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 210000000601 blood cell Anatomy 0.000 description 1
- 210000004045 bowman membrane Anatomy 0.000 description 1
- 230000001680 brushing effect Effects 0.000 description 1
- 239000000337 buffer salt Substances 0.000 description 1
- 239000006172 buffering agent Substances 0.000 description 1
- 210000005252 bulbus oculi Anatomy 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 239000004202 carbamide Substances 0.000 description 1
- 125000002091 cationic group Chemical group 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 230000006037 cell lysis Effects 0.000 description 1
- 239000006285 cell suspension Substances 0.000 description 1
- 210000002421 cell wall Anatomy 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 230000003196 chaotropic effect Effects 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 229920001429 chelating resin Polymers 0.000 description 1
- 238000007385 chemical modification Methods 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 238000010367 cloning Methods 0.000 description 1
- 229910017052 cobalt Inorganic materials 0.000 description 1
- 239000010941 cobalt Substances 0.000 description 1
- GUTLYIVDDKVIGB-UHFFFAOYSA-N cobalt atom Chemical compound [Co] GUTLYIVDDKVIGB-UHFFFAOYSA-N 0.000 description 1
- 239000002299 complementary DNA Substances 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 230000021615 conjugation Effects 0.000 description 1
- 210000001608 connective tissue cell Anatomy 0.000 description 1
- 230000000875 corresponding effect Effects 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 229960000633 dextran sulfate Drugs 0.000 description 1
- 238000012631 diagnostic technique Methods 0.000 description 1
- 238000003748 differential diagnosis Methods 0.000 description 1
- 238000006471 dimerization reaction Methods 0.000 description 1
- 231100000676 disease causative agent Toxicity 0.000 description 1
- BFMYDTVEBKDAKJ-UHFFFAOYSA-L disodium;(2',7'-dibromo-3',6'-dioxido-3-oxospiro[2-benzofuran-1,9'-xanthene]-4'-yl)mercury;hydrate Chemical compound O.[Na+].[Na+].O1C(=O)C2=CC=CC=C2C21C1=CC(Br)=C([O-])C([Hg])=C1OC1=C2C=C(Br)C([O-])=C1 BFMYDTVEBKDAKJ-UHFFFAOYSA-L 0.000 description 1
- 238000006073 displacement reaction Methods 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- NAGJZTKCGNOGPW-UHFFFAOYSA-N dithiophosphoric acid Chemical group OP(O)(S)=S NAGJZTKCGNOGPW-UHFFFAOYSA-N 0.000 description 1
- 239000006196 drop Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 229920002549 elastin Polymers 0.000 description 1
- 229920001971 elastomer Polymers 0.000 description 1
- 239000000806 elastomer Substances 0.000 description 1
- 239000012149 elution buffer Substances 0.000 description 1
- 210000003890 endocrine cell Anatomy 0.000 description 1
- 210000002889 endothelial cell Anatomy 0.000 description 1
- 230000003511 endothelial effect Effects 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 235000019414 erythritol Nutrition 0.000 description 1
- UNXHWFMMPAWVPI-ZXZARUISSA-N erythritol Chemical compound OC[C@H](O)[C@H](O)CO UNXHWFMMPAWVPI-ZXZARUISSA-N 0.000 description 1
- 229940009714 erythritol Drugs 0.000 description 1
- VYXSBFYARXAAKO-UHFFFAOYSA-N ethyl 2-[3-(ethylamino)-6-ethylimino-2,7-dimethylxanthen-9-yl]benzoate;hydron;chloride Chemical compound [Cl-].C1=2C=C(C)C(NCC)=CC=2OC2=CC(=[NH+]CC)C(C)=CC2=C1C1=CC=CC=C1C(=O)OCC VYXSBFYARXAAKO-UHFFFAOYSA-N 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 239000003889 eye drop Substances 0.000 description 1
- 229940012356 eye drops Drugs 0.000 description 1
- 231100000013 eye irritation Toxicity 0.000 description 1
- 210000000744 eyelid Anatomy 0.000 description 1
- 239000000835 fiber Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- GVEPBJHOBDJJJI-UHFFFAOYSA-N fluoranthrene Natural products C1=CC(C2=CC=CC=C22)=C3C2=CC=CC3=C1 GVEPBJHOBDJJJI-UHFFFAOYSA-N 0.000 description 1
- ZFKJVJIDPQDDFY-UHFFFAOYSA-N fluorescamine Chemical compound C12=CC=CC=C2C(=O)OC1(C1=O)OC=C1C1=CC=CC=C1 ZFKJVJIDPQDDFY-UHFFFAOYSA-N 0.000 description 1
- GNBHRKFJIUUOQI-UHFFFAOYSA-N fluorescein Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 GNBHRKFJIUUOQI-UHFFFAOYSA-N 0.000 description 1
- 238000002866 fluorescence resonance energy transfer Methods 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 238000007672 fourth generation sequencing Methods 0.000 description 1
- 238000013467 fragmentation Methods 0.000 description 1
- 238000006062 fragmentation reaction Methods 0.000 description 1
- 238000002523 gelfiltration Methods 0.000 description 1
- 238000010199 gene set enrichment analysis Methods 0.000 description 1
- 238000012252 genetic analysis Methods 0.000 description 1
- 238000010448 genetic screening Methods 0.000 description 1
- 238000013412 genome amplification Methods 0.000 description 1
- 210000002768 hair cell Anatomy 0.000 description 1
- 210000002064 heart cell Anatomy 0.000 description 1
- 230000004402 high myopia Effects 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- GPRLSGONYQIRFK-UHFFFAOYSA-N hydron Chemical compound [H+] GPRLSGONYQIRFK-UHFFFAOYSA-N 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 239000007943 implant Substances 0.000 description 1
- 230000001976 improved effect Effects 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000012405 in silico analysis Methods 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000010921 in-depth analysis Methods 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 238000011221 initial treatment Methods 0.000 description 1
- 238000005342 ion exchange Methods 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- 239000000905 isomalt Substances 0.000 description 1
- 235000010439 isomalt Nutrition 0.000 description 1
- HPIGCVXMBGOWTF-UHFFFAOYSA-N isomaltol Natural products CC(=O)C=1OC=CC=1O HPIGCVXMBGOWTF-UHFFFAOYSA-N 0.000 description 1
- 210000002510 keratinocyte Anatomy 0.000 description 1
- 238000002372 labelling Methods 0.000 description 1
- 210000004561 lacrimal apparatus Anatomy 0.000 description 1
- 210000000265 leukocyte Anatomy 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 238000007477 logistic regression Methods 0.000 description 1
- 229960000274 lysozyme Drugs 0.000 description 1
- 239000004325 lysozyme Substances 0.000 description 1
- 235000010335 lysozyme Nutrition 0.000 description 1
- 230000002101 lytic effect Effects 0.000 description 1
- 239000000845 maltitol Substances 0.000 description 1
- 235000010449 maltitol Nutrition 0.000 description 1
- VQHSOMBJVWLPSR-WUJBLJFYSA-N maltitol Chemical compound OC[C@H](O)[C@@H](O)[C@@H]([C@H](O)CO)O[C@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O VQHSOMBJVWLPSR-WUJBLJFYSA-N 0.000 description 1
- 229940035436 maltitol Drugs 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000013160 medical therapy Methods 0.000 description 1
- 210000002752 melanocyte Anatomy 0.000 description 1
- 238000011880 melting curve analysis Methods 0.000 description 1
- 230000003340 mental effect Effects 0.000 description 1
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 description 1
- 238000010208 microarray analysis Methods 0.000 description 1
- 230000003990 molecular pathway Effects 0.000 description 1
- MLEBFEHOJICQQS-UHFFFAOYSA-N monodansylcadaverine Chemical compound C1=CC=C2C(N(C)C)=CC=CC2=C1S(=O)(=O)NCCCCCN MLEBFEHOJICQQS-UHFFFAOYSA-N 0.000 description 1
- 230000004899 motility Effects 0.000 description 1
- 229920003052 natural elastomer Polymers 0.000 description 1
- 229920001194 natural rubber Polymers 0.000 description 1
- 238000003203 nucleic acid sequencing method Methods 0.000 description 1
- 229920001778 nylon Polymers 0.000 description 1
- 238000002577 ophthalmoscopy Methods 0.000 description 1
- 210000001328 optic nerve Anatomy 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 208000025896 pellucid marginal degeneration Diseases 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 description 1
- PTMHPRAIXMAOOB-UHFFFAOYSA-N phosphoramidic acid Chemical group NP(O)(O)=O PTMHPRAIXMAOOB-UHFFFAOYSA-N 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 229920001467 poly(styrenesulfonates) Polymers 0.000 description 1
- 229920002239 polyacrylonitrile Polymers 0.000 description 1
- 229920000573 polyethylene Polymers 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 238000006116 polymerization reaction Methods 0.000 description 1
- 229920001155 polypropylene Polymers 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 239000013615 primer Substances 0.000 description 1
- 239000002987 primer (paints) Substances 0.000 description 1
- 235000004252 protein component Nutrition 0.000 description 1
- 230000004853 protein function Effects 0.000 description 1
- 230000001179 pupillary effect Effects 0.000 description 1
- 238000010926 purge Methods 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 230000011514 reflex Effects 0.000 description 1
- 208000014733 refractive error Diseases 0.000 description 1
- 238000000611 regression analysis Methods 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 230000010076 replication Effects 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 108091008146 restriction endonucleases Proteins 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 210000001525 retina Anatomy 0.000 description 1
- 238000004366 reverse phase liquid chromatography Methods 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 239000002336 ribonucleotide Substances 0.000 description 1
- 238000005096 rolling process Methods 0.000 description 1
- 102200011997 rs3812954 Human genes 0.000 description 1
- HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 238000013515 script Methods 0.000 description 1
- 238000011451 sequencing strategy Methods 0.000 description 1
- 239000004208 shellac Substances 0.000 description 1
- ZLGIYFNHBLSMPS-ATJNOEHPSA-N shellac Chemical compound OCCCCCC(O)C(O)CCCCCCCC(O)=O.C1C23[C@H](C(O)=O)CCC2[C@](C)(CO)[C@@H]1C(C(O)=O)=C[C@@H]3O ZLGIYFNHBLSMPS-ATJNOEHPSA-N 0.000 description 1
- 229940113147 shellac Drugs 0.000 description 1
- 235000013874 shellac Nutrition 0.000 description 1
- 210000002363 skeletal muscle cell Anatomy 0.000 description 1
- AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 description 1
- 229910000162 sodium phosphate Inorganic materials 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 229960002920 sorbitol Drugs 0.000 description 1
- 235000010356 sorbitol Nutrition 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000012066 statistical methodology Methods 0.000 description 1
- 238000005728 strengthening Methods 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 150000005846 sugar alcohols Chemical class 0.000 description 1
- 229940124530 sulfonamide Drugs 0.000 description 1
- 150000003456 sulfonamides Chemical class 0.000 description 1
- 230000008961 swelling Effects 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 229920003051 synthetic elastomer Polymers 0.000 description 1
- 239000005061 synthetic rubber Substances 0.000 description 1
- 108091035539 telomere Proteins 0.000 description 1
- 102000055501 telomere Human genes 0.000 description 1
- 230000002123 temporal effect Effects 0.000 description 1
- 230000008719 thickening Effects 0.000 description 1
- OVTCUIZCVUGJHS-VQHVLOKHSA-N trans-dipyrrin Chemical compound C=1C=CNC=1/C=C1\C=CC=N1 OVTCUIZCVUGJHS-VQHVLOKHSA-N 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 230000002485 urinary effect Effects 0.000 description 1
- 230000004393 visual impairment Effects 0.000 description 1
- 238000012800 visualization Methods 0.000 description 1
- 238000001262 western blot Methods 0.000 description 1
- 239000000811 xylitol Substances 0.000 description 1
- 235000010447 xylitol Nutrition 0.000 description 1
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 description 1
- 229960002675 xylitol Drugs 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
- C12Q1/6876—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
- C12Q1/6883—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q2600/00—Oligonucleotides characterized by their use
- C12Q2600/118—Prognosis of disease development
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q2600/00—Oligonucleotides characterized by their use
- C12Q2600/156—Polymorphic or mutational markers
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2800/00—Detection or diagnosis of diseases
- G01N2800/16—Ophthalmology
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2800/00—Detection or diagnosis of diseases
- G01N2800/50—Determining the risk of developing a disease
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Organic Chemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Analytical Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Zoology (AREA)
- Genetics & Genomics (AREA)
- Wood Science & Technology (AREA)
- Immunology (AREA)
- Molecular Biology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biotechnology (AREA)
- Biochemistry (AREA)
- Physics & Mathematics (AREA)
- Pathology (AREA)
- Microbiology (AREA)
- Medicinal Chemistry (AREA)
- Biophysics (AREA)
- General Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Urology & Nephrology (AREA)
- Hematology (AREA)
- Ophthalmology & Optometry (AREA)
- General Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Cell Biology (AREA)
- Food Science & Technology (AREA)
- General Physics & Mathematics (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
- Peptides Or Proteins (AREA)
- Investigating Or Analysing Biological Materials (AREA)
- Materials For Medical Uses (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201762492060P | 2017-04-28 | 2017-04-28 | |
| US62/492,060 | 2017-04-28 | ||
| US201762570620P | 2017-10-10 | 2017-10-10 | |
| US62/570,620 | 2017-10-10 | ||
| PCT/US2018/029836 WO2018200980A1 (en) | 2017-04-28 | 2018-04-27 | Methods for detecting alleles associated with keratoconus |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| AU2018258580A1 true AU2018258580A1 (en) | 2019-11-21 |
Family
ID=63918944
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU2018258580A Abandoned AU2018258580A1 (en) | 2017-04-28 | 2018-04-27 | Methods for detecting alleles associated with keratoconus |
Country Status (8)
| Country | Link |
|---|---|
| US (1) | US20200190587A1 (enExample) |
| EP (1) | EP3628056A4 (enExample) |
| JP (2) | JP7244437B2 (enExample) |
| KR (1) | KR102602627B1 (enExample) |
| CN (1) | CN110997940A (enExample) |
| AU (1) | AU2018258580A1 (enExample) |
| CA (1) | CA3061620A1 (enExample) |
| WO (1) | WO2018200980A1 (enExample) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP4036228A1 (en) | 2015-11-13 | 2022-08-03 | Avellino Lab USA, Inc. | Methods for the treatment of corneal dystrophies |
| JP7097850B2 (ja) * | 2019-04-23 | 2022-07-08 | ジェネシスヘルスケア株式会社 | 遠視のリスクを判定する方法 |
| JP7097851B2 (ja) * | 2019-04-23 | 2022-07-08 | ジェネシスヘルスケア株式会社 | 乱視のリスクを判定する方法 |
| EP4355338A4 (en) * | 2021-06-18 | 2025-12-24 | Ionis Pharmaceuticals Inc | COMPOUNDS AND METHODS FOR REDUCING THE EXPRESSION OF IFNAR1 |
| WO2023004189A1 (en) * | 2021-07-23 | 2023-01-26 | Avellino Lab Usa, Inc. | Method for detecting alleles associated with keratoconus |
Family Cites Families (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5210015A (en) | 1990-08-06 | 1993-05-11 | Hoffman-La Roche Inc. | Homogeneous assay system using the nuclease activity of a nucleic acid polymerase |
| US5925517A (en) | 1993-11-12 | 1999-07-20 | The Public Health Research Institute Of The City Of New York, Inc. | Detectably labeled dual conformation oligonucleotide probes, assays and kits |
| DE69739357D1 (de) | 1996-06-04 | 2009-05-28 | Univ Utah Res Found | Überwachung der hybridisierung während pcr |
| US6117635A (en) | 1996-07-16 | 2000-09-12 | Intergen Company | Nucleic acid amplification oligonucleotides with molecular energy transfer labels and methods based thereon |
| GB9812768D0 (en) | 1998-06-13 | 1998-08-12 | Zeneca Ltd | Methods |
| US6270970B1 (en) | 1999-05-14 | 2001-08-07 | Promega Corporation | Mixed-bed solid phase and its use in the isolation of nucleic acids |
| KR20130027281A (ko) * | 2011-09-07 | 2013-03-15 | (주)에스엘에스 | 원추각막 검사 방법 및 키트 |
| SG11201701693RA (en) * | 2014-09-05 | 2017-04-27 | Univ Osaka | Corneal endothelial cell marker |
| CN105256059B (zh) * | 2015-11-20 | 2019-01-18 | 山东省眼科研究所 | Tuba3d基因在制备圆锥角膜诊断制品中的应用 |
| CN106282383B (zh) | 2016-10-08 | 2019-05-31 | 山东省眼科研究所 | Krt12基因在检测圆锥角膜中的应用 |
-
2018
- 2018-04-27 US US16/609,039 patent/US20200190587A1/en not_active Abandoned
- 2018-04-27 KR KR1020197034634A patent/KR102602627B1/ko active Active
- 2018-04-27 CA CA3061620A patent/CA3061620A1/en active Pending
- 2018-04-27 JP JP2019558671A patent/JP7244437B2/ja active Active
- 2018-04-27 CN CN201880040439.3A patent/CN110997940A/zh active Pending
- 2018-04-27 WO PCT/US2018/029836 patent/WO2018200980A1/en not_active Ceased
- 2018-04-27 EP EP18790019.6A patent/EP3628056A4/en not_active Withdrawn
- 2018-04-27 AU AU2018258580A patent/AU2018258580A1/en not_active Abandoned
-
2023
- 2023-03-09 JP JP2023036246A patent/JP2023085286A/ja active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| JP2023085286A (ja) | 2023-06-20 |
| WO2018200980A1 (en) | 2018-11-01 |
| CA3061620A1 (en) | 2018-11-01 |
| KR20200017392A (ko) | 2020-02-18 |
| EP3628056A1 (en) | 2020-04-01 |
| KR102602627B1 (ko) | 2023-11-16 |
| JP2020517296A (ja) | 2020-06-18 |
| EP3628056A4 (en) | 2021-03-03 |
| CN110997940A (zh) | 2020-04-10 |
| JP7244437B2 (ja) | 2023-03-22 |
| US20200190587A1 (en) | 2020-06-18 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP2023085286A (ja) | 円錐角膜に関連する対立遺伝子を検出する方法 | |
| EP3068908B1 (en) | Methods for multiplex detection of alleles associated with ophthalmic conditions | |
| US20240182969A1 (en) | Method for detecting alleles associated with keratoconus | |
| Bua et al. | Diagnostic markers for glaucoma: a patent and literature review (2013-2019) | |
| WO2010075519A2 (en) | Allelic variants associated with advanced age-related macular degeneration | |
| CN114574574B (zh) | 一组右眼等效球镜数量性状相关的snp标志物及其应用 | |
| CN114525336A (zh) | 一组用于近视诊断及右眼柱镜筛查的snp组合标志物及其应用 | |
| US20210180131A1 (en) | Methods for detecting and treating atopic dermatitis | |
| JP6412101B2 (ja) | アレル検出用ゲノムｄｎａテンプレートの改良された単離方法 | |
| US20210115499A1 (en) | Methods for Improved Isolation of Genomic DNA Templates for Allele Detection | |
| WO2014031079A1 (en) | Method and/or probe for determining glaucoma susceptibility | |
| HK40053535A (en) | Methods for improved isolation of genomic dna templates for allele detection | |
| Oliver | Pectinate ligament dysplasia and primary glaucoma in dogs: investigating prevalence and identifying genetic risk factors | |
| CN114606313A (zh) | 一组用于检测最差眼等效球镜的snp标志物及其应用 | |
| CN114592055A (zh) | 一组两眼等效球镜差相关的snp标志物及其应用 | |
| Awadalla | A Genetic Study of Primary Angle-Closure Glaucoma and Nanophthalmos | |
| Rong | Molecular Genomics of Primary Open Angle Glaucoma | |
| HK40009141A (en) | Methods for improved isolation of genomic dna templates for allele detection | |
| HK40009141B (en) | Methods for improved isolation of genomic dna templates for allele detection | |
| HK1216034B (en) | Methods for improved isolation of genomic dna templates for allele detection | |
| CN104450871A (zh) | 小眼畸形和无眼畸形相关基因突变、其检测方法及其用途 | |
| HK1228464B (en) | Methods for multiplex detection of alleles associated with ophthalmic conditions |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MK5 | Application lapsed section 142(2)(e) - patent request and compl. specification not accepted |