ES2586153T3 - Predicción de nacimiento prematuro espontáneo mediante la medición de ácidos nucleicos libres de células en sangre materna - Google Patents
Predicción de nacimiento prematuro espontáneo mediante la medición de ácidos nucleicos libres de células en sangre materna Download PDFInfo
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- ES2586153T3 ES2586153T3 ES11845889.2T ES11845889T ES2586153T3 ES 2586153 T3 ES2586153 T3 ES 2586153T3 ES 11845889 T ES11845889 T ES 11845889T ES 2586153 T3 ES2586153 T3 ES 2586153T3
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Abstract
Uso de una composición que comprende un ácido nucleico que tiene una secuencia de biomarcador de nacimiento prematuro (PTB) en ARN de plasma libre de células (PLC) que incluye o es complementaria a una o más de las SEQ ID NOs: 5-300 o a una sonda o cebador específicos para ellas, el ácido nucleico que está presente en una cantidad suficiente para su uso en un protocolo de diagnóstico de ácido nucleico en el diagnóstico de susceptibilidad a PTB.
Description
tenido, o tendrán PTB con menos de 32 semanas; y la normalización de las secuencias de ARNm o miARN de PLC con las secuencias conocidas de ARNm o miARN de PLC inalteradas.
En una realización, un método de normalización de secuencias de ARNm o miARN de PLC puede incluir la 5 normalización con una o más de las SEQ ID NOs: 1-4 o un cebador y/o sonda de las mismas o las SEQ ID NOs: 301-303 mediante protocolos de normalización convencionales.
Los métodos descritos también pueden incluir la obtención de muestras que tienen ARN de un sujeto y el procesamiento de la muestra con el fin de obtener ARN de PLC.
Se puede utilizar la cuantificación de ácidos nucleicos biomarcadores de PTB (por ejemplo, ARN) extraídos de una muestra biológica con el fin de determinar si una mujer embarazada es susceptible, o no, de PTB. Por consiguiente, 15 la identificación de biomarcadores de PTB puede ser importante a fin de diagnosticar la susceptibilidad a PTB o predecir PTB. La presente invención en general incluye nuevos biomarcadores de ARN y procesos para identificar biomarcadores de ARN en plasma, y el uso de los biomarcadores de ARN para identificar estados previos a enfermedad relacionados con el PTB. La presente invención puede utilizar biomarcadores de ARN asociados a estados de enfermedad del embarazo con el fin de predecir si una mujer embarazada puede desarrollar o es 20 susceptible de desarrollar un estado de enfermedad particular que pueda causar parto prematuro. En general, los biomarcadores de PTB incluyen ácidos nucleicos que son ARN de PLC como se describe en el presente documento.
Los biomarcadores de ARN de PLC pueden incluir secuencias de ARN derivadas de la madre y del feto. Puesto que la activación del miometrio puede resultar en parto espontáneo, y puesto que la quiescencia del miometrio es un 25 período genómicamente rico, se pueden utilizar los cambios en el transcriptoma de PLC (por ejemplo, transcriptoma de ARN) para predecir PTB espontáneo. Dicho cambio en el transcriptoma de PLC puede ser indicativo de PTB, independientemente de si el estímulo se origina en los compartimentos de la madre o del feto. Ahora se han identificado los biomarcadores de PTB en ARN de PLC y se proporcionan en la Lista de secuencias como SEQ ID NOs: 5-300. Estas secuencias biomarcadoras de PTB en ARN de PLC están involucradas en el proceso biológico y
30 regulador del embarazo, y la modulación de estos biomarcadores de PTB en ARN de PLC puede ser un indicio de enfermedad. Además, la modulación de estos biomarcadores de PTB en ARN de PLC se puede usar para inhibir, prevenir o tratar una enfermedad asociada al ARNm o miARN particular del biomarcador de PTB en ARN de PLC.
Brevemente, se obtuvo ARNm de PLC a las 26-28 semanas de 5 mujeres seleccionadas al azar abocadas a PTB
35 (por ejemplo, nacimiento < 32 semanas) sin rotura prematura de las membranas (es decir, parto prematuro, rotura prematura de las membranas), y de 5 mujeres de control con parto a término. En una 'Fase de descubrimiento' de identificación de ARNm de PLC, el ARN extraído se analizó en la matriz de expresión de un transcrito humano completo Affymetrix Human Whole-Transcript Expression y las secuencias de ARNm alteradas en mujeres abocadas a PTB se identificaron en base a un factor de cambio (por ejemplo, ≥ 1,5x, un límite de corte convencional que se
40 utiliza en ciencia) y el valor p de control (p <0,01). El ARNm de PLC se ordenó por estrechez de la distribución (por ejemplo, el análisis Ingenuity Systems Pathway Analysis) puesto que una distribución estrecha es una característica muy deseable de la prueba para cualquier marcador seleccionado, en el que cuanto más estrecha sea la distribución de la enfermedad y la normal, menor es la superposición en las distribuciones de la población. De las 25.934 secuencias de ARN identificadas a formar parte del transcriptoma de PLC a las 26 semanas, 88 biomarcadores de
45 PTB en ARNm de PLC estaban alterados en mujeres abocadas a PTB; 22 biomarcadores de PTB en ARNm de PLC (SEQ ID NO: 19-41) estaban regulados por aumento y 66 ARNm de PLC (SEQ ID NO: 42-106) estaban regulados por disminución. El mapeo genómico reveló que las secuencias marcadoras de PTB en ARNm de PLC estaban asociadas a la expresión, el crecimiento y la proliferación celular, el ciclo celular, la muerte celular, y el ensamblaje y la organización celular.
50 Los biomarcadores de PTB en ARN de PLC pueden incluir, pero no se limitan a, ARN no codificante, tal como miARN y snARN y snoARN, y otros son ARNm. En una realización, los biomarcadores de PTB en ARN de PLC pueden incluir un biomarcador que indica susceptibilidad a PTB. Estos biomarcadores de PTB en ARN de PLC pueden incluir: (SEQ ID NO: 19) taspasa de Homo sapiens, aspartasa treonina, 1 (TASP1), ARNm, número de
55 acceso NM_017714; (SEQ ID NO: 20) proteína con dedos de zinc 99 de Homo sapiens (ZNF99), ARNm, números de acceso NM_001080409 y XM_001132267; (SEQ ID NO: 21) ADNc FLJ16171 fis de Homo sapiens, clon BRHIP2003272, número de acceso AK131247; (SEQ ID NO: 22) islotes de regeneración de derivadas de gamma 3 de Homo sapiens (REG3G), variante de transcripción 1, ARNm, número de acceso NM_001008387; (SEQ ID NO: 23) receptor olfativo de Homo sapiens, familia 51, subfamilia A, miembro 2 (OR51A2), ARNm, números de acceso
XM_376832; (SEQ ID NO: 70) marco de lectura abierto 95 del cromosoma 10 de Homo sapiens, ARNm (clon de ADNc MGC: 161737 IMAGE: 8992175), cds completos, número de acceso, BC126459; (SEQ ID NO: 71) nicotinamida fosforribosiltransferasa de Homo sapiens (NAMPT), ARNm, número de acceso NM_005746; (SEQ ID NO: 72) receptor 6 asociado a trazas de amina de Homo sapiens (TAAR6), ARNm, número de acceso, NM_175067; 5 (SEQ ID NO: 73) miosina de Homo sapiens, cadena ligera 6, alcalina, músculo liso y no muscular (MYL6), variante de transcripción 1, ARNm, números de acceso NM_021019 y NM_079424; (SEQ ID NO: 74) ATP sintasa de Homo sapiens, transporte de H+, complejo Fo mitocondrial, subunidad C2 (subunidad 9) (ATP5G2), gen nuclear que codifica la proteína mitocondrial, variante de transcripción 2, ARNm, número de acceso NM_005176; (SEQ ID NO: 75) familia 18 con similitud de secuencia de Homo sapiens, miembro B2 (FAM18B2), variante de transcripción 1, 10 ARNm, números de acceso NM_145301 y XM_936923; (SEQ ID NO: 76) factor de transcripción Sp6 de Homo sapiens (SP6), ARNm, números de acceso NM_199262 y XM_292621; (SEQ ID NO: 77) formina invertida de Homo sapiens, dominio que contiene FH2 y WH2 (INF2), variante de transcripción 1, ARNm, número de acceso NM_022489; (SEQ ID NO: 78) inhibidor de la disociación de Rho PIB de Homo sapiens (GDI) alfa (ARHGDIA), variante de transcripción 2, ARNm, número de acceso NM_004309; (SEQ ID NO: 79) dominio OTU que contiene 6A 15 de Homo sapiens (OTUD6A), ARNm, número de acceso NM_207320; (SEQ ID NO: 80) dominio BTB 12 y que contiene dedos de zinc de Homo sapiens (ZBTB12), ARNm, número de acceso NM_181842; (SEQ ID NO: 81) proteína 2B organizadora del huso mitótico de Homo sapiens (MZT2B), ARNm, número de acceso NM_025029; (SEQ ID NO: 82) receptor olfativo de Homo sapiens, familia 52, subfamilia E, miembro 2 (OR52E2), ARNm, número de acceso NM_001005164 y XM_061610; (SEQ ID NO: 83) LOC150622 hipotética de Homo sapiens (LOC150622), 20 ARN no codificante, número de acceso NR_026832, XR_041760, XR_041761, y XR_041762; (SEQ ID NO: 84) selenofosfato sintetasa 1 de Homo sapiens (SEPHS1), variante de transcripción 1, ARNm, número de acceso NM_012247; (SEQ ID NO: 85) barrera para el factor de autointegración 1 de Homo sapiens (BANF1), variante de transcripción 1, ARNm, número de acceso NM_003860; (SEQ ID NO: 86) factor de transcripción general IIB de Homo sapiens (GTF2B), ARNm, número de acceso NM_001514; (SEQ ID NO: 87) familia del dominio RGM de 25 Homo sapiens, miembro A (RGMA), variante de transcripción 4, ARNm, número de acceso NM_020211; (SEQ ID NO: 88) receptor de la hormona de liberación de prolactina de Homo sapiens (PRLHR), ARNm, número de acceso NM_004248 y NM_005287; (SEQ ID NO: 89) pseudogen 2 similar a dpy-19 de Homo sapiens (C. elegans) (DPY19L2P2), variante de transcripción 2, no codificante de ARN, número de acceso NR_003561; (SEQ ID NO: 90) regulador de la diferenciación celular glial, meteorina de Homo sapiens (METRN), ARNm, número de acceso 30 NM_024042; (SEQ ID NO: 91) receptor de ácido graso libre 1 de Homo sapiens (FFAR1), ARNm, número de acceso NM_005303; (SEQ ID NO: 92) péptido natriurético B de Homo sapiens (NPPB), ARNm, número de acceso NM_002521; (SEQ ID NO: 93) proteína 3 de interacción BCL2/adenovirus E1B de 19 kDa de Homo sapiens (BNIP3), gen nuclear que codifica la proteína mitocondrial, ARNm, número de acceso NM_004052; (SEQ ID NO: 94) familia hélice-bucle-hélice básica de Homo sapiens, miembro a15 (BHLHA15), ARNm, número de acceso NM_177455; 35 (SEQ ID NO: 95) virus del sarcoma murino Finkel-Biskis-Reilly de Homo sapiens (FBR-MuSV) expresado ubicuamente (FAU), ARNm, número de acceso NM_001997; (SEQ ID NO: 96) marco de lectura abierto 70 del cromosoma 9 de Homo sapiens (C9orf70), ARN no codificante, número de acceso NR_026663 y XM_001721481 XM_001723928 XM_001724353; (SEQ ID NO: 97) proteína ribosomal L30 de Homo sapiens (RPL30), ARNm, número de acceso NM_000989; (SEQ ID NO: 98) regulador semejante a la diferenciación celular glial, meteorina de 40 Homo sapiens (METRNL), ARNm, número de acceso NM_001004431 y XM_209073; (SEQ ID NO: 99) semejante a la ubiquitina 5 de Homo sapiens (UBL5), variante de transcripción 1, ARNm, número de acceso NM_024292; (SEQ ID NO: 100) canal de rectificación de potasio hacia el interior de Homo sapiens, subfamilia J, miembro 4, (KCNJ4), variante de transcripción 1, ARNm, número de acceso NM_152868; (SEQ ID NO: 101) polipéptido naciente asociado a la subunidad alfa del complejo de Homo sapiens (NACA), variante de transcripción 1, ARNm, número de acceso 45 NM_001113203; (SEQ ID NO: 102) factor 2 rico en EDRK pequeñas de Homo sapiens (SERF2), ARNm, número de acceso NM_001018108; (SEQ ID NO: 103) familia de sulfotransferasa citosólica 1A con preferencia por fenol, miembro 2, de Homo sapiens, (SULT1A2), variante de transcripción 2, ARNm, número de acceso NM_177528; (SEQ ID NO: 104) receptor olfativo de Homo sapiens, familia 51, subfamilia G, miembro 2 (OR51G2), ARNm, número de acceso NM_001005238; (SEQ ID NO: 105) factor de transcripción básico 3 de Homo sapiens (BTF3), variante de
50 transcripción 1, ARNm, número de acceso NM_001037637; y (SEQ ID NO: 106) LSM10 de Homo sapiens, asociado a ARN U7 nuclear pequeño (LSM10), ARNm, número de acceso NM_032881.
En una realización, los biomarcadores de PTB en ARN de PLC pueden incluir un marcador biológico que está regulado por aumento a fin de indicar la susceptibilidad al PTB con las SEQ ID NO: 107-142, en las que el Probeset
55 ID, los números de acceso, los símbolos de genes, y sus secuencias de inicio y detención se incorporan en este documento por referencia específica:
- SEQ ID NO:
- # Probeset ID Símbolo del gen RefSeq (Acceso) Seqname Inicio Detención
- SEQ ID NO:
- 107 2391026 C1orf159 BC008788 chr1 1020631 1020674
- SEQ ID NO:
- 108 2465373 AHCTF1 NM_015446 chr1 247063497 247063521
- SEQ ID NO:
- 109 2321026 C1orf158 NM_152290 chr1 12821062 12821086
- SEQ ID NO:
- 110 2370564 CACNA1E NM_000721 chr1 181705411 181705435
- SEQ ID NO:
- 111 2445415 ASTN1 NM_004319 chr1 176927594 176927618
- SEQ ID NO:
- 112 2383404 ADCK3 NM_020247 chr1 227165195 227165219
- SEQ ID NO:
- 113 3314648 C10orf92 BC034223 chr10 134628211 134628236
- SEQ ID NO:
- 114 3332991 C11orf66 NM_145017 chr11 61257978 61258037
- SEQ ID NO:
- 115 3377201 CDC42BPG NM_017525 chr11 64601758 64601797
- SEQ ID NO:
- 116 3381279 ARAP1 BC056401 chr11 72411090 72411124
- SEQ ID NO:
- 117 3403055 ATN1 NM_001007026 chr12 7045236 7045261
- SEQ ID NO:
- 118 3655114 CD19 NM_001178098 chr16 28943903 28943933
- SEQ ID NO:
- 119 3739970 ABR NM_021962 chr17 913969 913994
- SEQ ID NO:
- 120 3774020 C17orf70 NR_033338 chr17 79518798 79518881
- SEQ ID NO:
- 121 3774725 CCDC57 ENST00000324808 chr17 80109446 80109470
- SEQ ID
- 122 3741735 CAMKK1 AF370377 chr17 3773035 3773059
- NO:
- SEQ ID NO:
- 123 3830886 ARHGAP33 NM_052948 chr19 36273687 36273769
- SEQ ID NO:
- 124 3835887 APOE NM_000041 chr19 45412388 45412412
- SEQ ID NO:
- 125 3866306 AP2S1 NM_004069 chr19 47342008 47342032
- SEQ ID NO:
- 126 2546857 CAPN13 NM_144575 chr2 30993219 30993282
- SEQ ID NO:
- 127 2576644 C2orf27B BC043584 chr2 132552867 132552917
- EQ ID NO:
- 128 2546826 CAPN13 NM_144575 chr2 30961299 ..., 30961323
- SEQ ID NO:
- 129 2708707 C3orf70 NM_001025266 chr3 184870647 .., 184870677
- SEQ ID NO:
- 130 2622179 BSN NM_003458 chr3 49699843 49699867
- SEQ ID NO:
- 131 2870730 BCLAF1 NM_014739 chr5 110285528 110285604
- SEQ ID NO:
- 132 2902959 C4A ENST00000428956 chr6 31949811 31949835
- SEQ ID NO:
- 133 2953468 C6orf130 ENST00000488238 chr6 41043021 41043070
- SEQ ID NO:
- 134 3031798 ABCB8 NM_007188 chr7 150744493 150744517
- SEQ ID NO:
- 135 3039763 ANKMY2 NM_020319 chr7 16666684 16666799
- SEQ ID NO:
- 136 3023426 AHCYL2 NM_001130723 chr7 129008311 129008335
- SEQ ID NO:
- 137 3031951 AGAP3 NM_031946 chr7 150841064 150841088
- SEQ ID NO:
- 138 3031944 AGAP3 AL442089 chr7 150838958 150838982
- SEQ ID NO:
- 139 3206269 ATP5A1 NM_001001937 chr9 41799773 41799797
- SEQ ID NO:
- 140 4001353 BEND2 NM_153346 chrX 18221855 18222031
- SEQ ID NO:
- 141 3969900 CA5B ENST00000479740 chrX 15768063 15768093
- SEQ ID NO:
- 142 3966810 CD99P1 NR_033380 chrX 2541426 2541450
En una realización, los biomarcadores de PTB en ARN de PLC pueden incluir un marcador biológico que está regulado por disminución a fin de indicar la susceptibilidad al PTB.
- SEQ NO
- ID # Probeset ID Símbolo del gen RefSeq (Acceso) Seqname Inicio Detención
- SEQ NO:
- ID 143 2434348 APH1A AK125685 chr1 150239436 150239470
- SEQ NO:
- ID 144 2347527 ABCD3 NM_001122674 chr1 94944215 94944239
- SEQ NO:
- ID 145 2347504 ABCD3 NM_002858 chr1 194884035 94884129
- SEQ NO:
- ID 146 2347024 CCDC18 NM_206886 chr1 193645587 93645967
- SEQ NO:
- ID 147 2383766 ARF1 NM_001024227 chr1 228286406 228286440
- SEQ NO:
- ID 148 2411671 AGBL4 ENST00000411952 chur1 49052585 49052609
- SEQ NO:
- ID 149 2316059 ATAD3A NM_018188 chur1 1469347 1469376
- SEQ NO:
- ID 150 2391349 ACAP3 AB051503 chur1 1240376 1240469
- SEQ NO:
- ID 151 2385702 C1orf57 NM_032324 chur1 233086457 233086481
- SEQ NO:
- ID 152 2393833 C1orf174 NM_207356 chr1 3816811 3816835
- SEQ
- ID 153 2440696 B4GALT3 NM_003779 chr1 161147290 161147314
- NO:
- SEQ NO:
- ID 154 2383363 ADCK3 ENST00000366779 chr1 227096295 227096344
- SEQ NO:
- ID 155 2318458 CAMTA1 NM_015215 chr1 6845541 6845635
- SEQ NO:
- ID 156 2392132 C1orf86 ENST00000378545 chr1 2130199 2130245
- SEQ NO:
- ID 157 2399312 ALDH4A1 NM_003748 chr1 19199312 19199336
- SEQ NO:
- ID 158 3286039 CCNYL2 ENST00000345581 chr10 42965620 42965646
- SEQ NO:
- ID 159 3282296 ACBD5 ENST00000375888 chr10 27529434 27529579
- SEQ NO:
- ID 160 3261217 BTRC NM_033637 chr10 103285926 103285955
- SEQ NO:
- ID 161 3284165 C1D NM_173177 chr10 32800666 32800698
- SEQ NO:
- ID 162 3245187 ANXA8L2 NM_001630 chr10 47747028 47747107
- SEQ NO:
- ID 163 3251356 ANAPC16 NM_173473 chr10 73975872 73975896
- SEQ NO:
- ID 164 3380994 C11orf59 NM_017907 chr11 71814234 71814263
- SEQ NO:
- ID 165 3353451 C11orf63 NM_024806 chr11 122774660 122774979
- SEQ NO:
- ID 166 3370889 ALX4 NM_021926 chr11 44296901 44297069
- SEQ NO:
- ID 167 3364964 ABCC8 NM_000352 chr11 17453766 17453791
- SEQ NO:
- ID 168 3377365 BATF2 NM_138456 chr11 64757241 64757266
- SEQ NO:
- ID 169 3351287 CD3E NM_000733 chr11 118175668 118175692
- SEQ NO:
- ID 170 3323765 ANO5 NM_213599 chr11 22215039 22215069
- SEQ NO:
- ID 171 3352074 CBL NM_005188 chr11 119077128 119077154
- SEQ NO:
- ID 172 3332702 CD6 NM_006725 chr11 60785827 60785851
- SEQ NO:
- ID 173 3378518 C1QBP NM_001212 chr11 66529422 66529450
- SEQ NO:
- ID 174 3334998 CAPN1 NM_005186 chr11 64978760 64978949
- SEQ NO:
- ID 175 3316546 AP2A2 NM_012305 chr11 1010548 1010572
- SEQ NO:
- ID 176 3358122 C11orf35 NM_173573 chr11 556268 556374
- SEQ NO:
- ID 177 3457551 ANKRD52 NM_173595 chr12 56631722 56631752
- SEQ NO:
- ID 178 3440081 CACNA2D4 NM_172364 chr12 1909167 1909199
- SEQ NO:
- ID 179 3431564 C12orf24 AK297684 chr12 110924538. 110924563
- SEQ NO:
- ID 180 3434501 CABP1 NM_031205 chr12 121088358 121088431
- SEQ NO:
- ID 181 3435685 ARL61P4 NM_018694 chr12 123466154 123466179
- SEQ NO:
- ID 182 3413611 CACNB3 NM_000725 chr12 49212713 49212756
- SEQ NO:
- ID 183 3523859 C13orf27 NM_138779 chr13 103418821 103418856
- SEQ NO:
- ID 184 3573232 ALKBH1 NM_006020 chr14 78140155 78140183
- SEQ NO:
- ID 185 3563711 C14orf138 NM_024558 chr14 50583243 50583268
- SEQ
- ID 186 3543628 C14orf169 NM_024644 chr14 73957998 73958031
- NO:
- SEQ NO:
- ID 187 3576909 ATXN3 NR_028453 chr14 92547321 92547345
- SEQ NO:
- ID 188 3557166 ACIN1 NM_014977 chr14 23564322 23564348
- SEQ NO:
- ID 189 3604597 ADAMTS7 NM_014272 chr15 82611989 82612090
- SEQ NO:
- ID 190 3601544 CCDC33 NM_025055 chr15 74536429 74536486
- SEQ NO:
- ID 191 3605931 ALPK3 NM_020778 chr15 85411431 85411647
- SEQ NO:
- ID 192 3619410 C15orf52 NM_207380 chr15 40627985 40628027
- SEQ NO:
- ID 193 3605398 ADAMTSL3 NM_207517 chr15 84324481 84324513
- SEQ NO:
- ID 194 3636496 BTBD1 NM_025238 chr15 83735879 83735903
- SEQ NO:
- ID 195 3628544 CA12 NM_001218 chr15 63637686 63637806
- SEQ NO:
- ID 196 3601237 CD276 NM_001024736 chr15 73992032 73992056
- SEQ NO:
- ID 197 3607736 C15orf42 NM_152259 chr15 90167064 90167094
- SEQ NO:
- ID 198 3620776 CDAN1 NM_138477 chr15 43026443 43026535
- SEQ NO:
- ID 199 3619407 C15orf52 NM_207380 chr15 40627389 40627585
- SEQ NO:
- ID 200 3617732 ACT1 NM_005159 chr15 35084610 35084634
- SEQ NO:
- ID 201 3619427 C15orf52 AK126485 chr15 40631674 40631701
- SEQ NO:
- ID 202 3655082 ATP2A1 NM_173201 chr16 28909568 28909754
- SEQ NO:
- ID 203 3656848 BCKDK NM_001122957 chr16 31123381 31123415
- SEQ NO:
- ID 204 3695322 CDH16 NM_004062 chr16 66944302 66944327
- SEQ NO:
- ID 205 3704743 ANKRD11 NM_013275 chr16 89351849 89352020
- SEQ NO:
- ID 206 3662891 CCDC135 NM_032269 chr16 57738788 57738820
- SEQ NO:
- ID 207 3687096 BOLA2 NM_001031827 chr16 30204743 30204770
- SEQ NO:
- ID 208 3686627 APOB48R NM_018690 chr16 28507548 28507572
- SEQ NO:
- ID 209 3770812 CASKIN2 NM_020753 chr17 73499499 73499557
- SEQ NO:
- ID 210 3767486 AXIN2 NM_004655 chr17 63533032 63533167
- SEQ NO:
- ID 211 3742217 ALOX15 NM_001140 chr17 4535481 4535558
- SEQ NO:
- ID 212 3742483 CAMTA2 NM_015099 chr17 4876890 4877042
- SEQ NO:
- ID 213 3764300 BZRAP1 BX648763 chr17 56382268 56382298
- SEQ NO:
- ID 214 3722682 C17orf88 NK_026770 chr17 41994608 41994632
- SEQ NO:
- ID 215 3766544 CDd79B NM_000626 chr17 62008702 62008726
- SEQ NO:
- ID 216 3748962 ALDH3A1 NM_001135168 chr17 19641470 19641494
- SEQ NO:
- ID 217 3774985 C17orf101 NR_033265 chr17 80350291 80350395
- SEQ NO:
- ID 218 3764359 BZRAP1 NM_004758 chr17 56404109 56404137
- SEQ
- ID 219 3774706 CCDC57 NM_198082 chr17 80059693 80059731
- NO:
- SEQ NO:
- ID 220 3773685 AZI1 NM_014984 chr17 79172707 79172736
- SEQ NO:
- ID 221 3773633 AATK ENST00000417379 chr17 79105718 79105746
- SEQ NO:
- ID 222 3848059 C3 NM_000064 chr19 6684786 6684810
- SEQ NO:
- ID 223 3866980 CARD8 NM_001184900 chr19 48715191 48715220
- SEQ NO:
- ID 224 3850462 AP1M2 NM_005498 chr19 10685580 10685611
- SEQ NO:
- ID 225 3854387 ANO8 NM_020959 chr19 17439225 17439281
- SEQ NO:
- ID 226 3837683 C19orf68 BC043386 chr19 48700487 48700516
- SEQ NO:
- ID 227 3867278 CA11 NM_001217 chr19 49143358 49143452
- SEQ NO:
- ID 228 3865986 CCDC8 NM_032040 chr19 46916087 46916262
- SEQ NO:
- ID 229 3846260 C19orf28 NM_021731 chr19 3557104 3557128
- SEQ NO:
- ID 230 3868520 ASPDH NM_001114598 chr19 51014987 51015030
- SEQ NO:
- ID 231 3860221 ALKBH6 NM_198867 chr19 36502307 36502333
- SEQ NO:
- ID 232 3815214 AZU1 NM_001700 chr19 828320 82837371
- SEQ NO:
- ID 233 3817205 ATCAY NM_033064 chr19 3917745 3917775
- SEQ NO:
- ID 234 3846377 APBA3 NM_004886 chr19 3754199 3754228
- SEQ NO:
- ID 235 3830369 CD22 NM_001771 chr19 35823497 35823523
- SEQ NO:
- ID 236 3842076 BRSK1 NM_032430 chr19 55805471 5805501
- SEQ NO:
- ID 237 3852137 CACNA1A NM_000068 chr19 13318294 13318431
- SEQ NO:
- ID 238 3824734 ARRDC2 NM_015683 chr19 18121452 18121479
- SEQ NO:
- ID 239 3834055 AXL NM_021913 chr19 41737096 41737140
- SEQ NO:
- ID 240 3846299 C19orf29 NM_001080543 chr19 3613163 3613278
- SEQ NO:
- ID 241 3836141 BLOC1S3 NM_212550 chr19 45683121 45683155
- SEQ NO:
- ID 242 3832352 CATSPERG NM_021185 chr19 38852853 38852886
- SEQ NO:
- ID 243 3843980 A1BG-AS BC040926 chr19 58864701 58864725
- SEQ NO:
- ID 244 3846310 C19orf29 NM_001080543 chr19 3620730 3620754
- SEQ NO:
- ID 245 3839117 ATF5 NM_012068 chr19 50436321 50436349
- SEQ NO:
- ID 246 2521240 CCDC150 NM_001080539 chr2 197504344 197504405
- SEQ NO:
- ID 247 2474325 C2orf28 NM_016085 chr2 27435237 27435334
- SEQ NO:
- ID 248 2574650 BIN1 NM_139343 chr2 127808045 127808098
- SEQ NO:
- ID 249 2473975 C2orf18 NM_017877 chr2 27001867 27001894
- SEQ NO:
- ID 250 2500292 BCL2L11 AB071199 chr2 111887709 111887791
- SEQ NO:
- ID 251 2505925 ARHGEF4 NM_015320 chr2 131804327 131804358
- SEQ
- ID 252 2532302 ALPPL2 NM_031313 chr2 233272604 233272635
- NO:
- SEQ NO:
- ID 253 2536644 BOK NM_032515 chr2 242512472 242512497
- SEQ NO:
- ID 254 2566556 C2orf55 NM_207362 chr2 99454585 99454610
- SEQ NO:
- ID 255 2532289 ALPP NM_001632 chr2 233246242 233246266
- SEQ NO:
- ID 256 2604401 ARL4C NM_005737 chr2 235404210 235404234
- SEQ NO:
- ID 257 3874441 CDC25B NM_021873 chr20 3776391 3776523
- SEQ NO:
- ID 258 3882227 BPIL3 NM_174897 chr20 31625440 31625473
- SEQ NO:
- ID 259 3894422 ANGPT4 NM_015985 chr20 865725 865751
- SEQ NO:
- ID 260 3874383 ATRN NM_139321 chr20 3614963 3615036
- SEQ NO:
- ID 261 3892803 C20orf200 NR_033263 chr20 61142540 61142567
- SEQ NO:
- ID 262 3914081 ARFRP1 NM_001134758 chr20 62331883 62331908
- SEQ NO:
- ID 263 3882563 CBFA2T2 NM_005093 chr20 32194762 32194787
- SEQ NO:
- ID 264 3907034 ADA NM_000022 chr20 43280223 43280248
- SEQ NO:
- ID 265 3926166 C21orf91 ENST00000405964 chr21 19191195 19191284
- SEQ NO:
- ID 266 3932407 C21orf88 NR_026542 chr21 40984265 40984292
- SEQ NO:
- ID 267 3922457 ABCG1 NM_016818 chr21 43639267 43639291
- SEQ NO:
- ID 268 3918143 C21orf63 AK126660 chr21 33829548 33829572
- SEQ NO:
- ID 269 3951118 ACR ENST00000216139 chr22 51176638 51176663
- SEQ NO:
- ID 270 3946042 CACNA1l NM_021096 chr22 40081973 40082331
- SEQ NO:
- ID 271 3955347 C22orf13 ENST00000407973 chr22 24951587 24951829
- SEQ NO:
- ID 272 2644874 BPESC1 NR_026783 chr3 138824138 138824168
- SEQ NO:
- ID 273 2641457 CCDC48 NM_024768 chr3 128751742 128751767
- SEQ NO:
- ID 274 2627379 C3orf49 NR_026866 chr3 63830699 63830723
- SEQ NO:
- ID 275 2624738 CACNA2D3 NM_018398 chr3 54913057 54913081
- SEQ NO:
- ID 276 2681152 C3orf64 AK304102 chr3 69062765 69062816
- SEQ NO:
- ID 277 2687780 CD47 NM_001777 chr3 107769425 107769449
- SEQ NO:
- ID 278 2719502 CC2D2A NM_001080522 chr4 15504114 15504140
- SEQ NO:
- ID 279 2852783 C1QTNF3 NM_030945 chr5 34033484 34033517
- SEQ NO:
- ID 280 2881766 ANXA6 NM_001155 chr5 150496698 150496722
- SEQ NO:
- ID 281 2842463 C5orf25 AK126204 chr5 175721931 175722032
- SEQ NO:
- ID 282 2878396 APBB3 AK125244 chr5 139943698 139943736
- SEQ NO:
- ID 283 4047621 BTNL8 NM_024850 chr5 180375920 180375946
- SEQ NO:
- ID 284 2901692 ABCF1 NM_001025091 chr6 3 30545599 30545665
- SEQ
- ID 285 2973284 C6orf174 NM_001012279 chr61 127837554 127837578
- NO:
- SEQ NO:
- ID 286 2937603 C6orf70 NM_018341 chr6 170175406 170175442
- SEQ NO:
- ID 287 2999777 AEBP1 NM_001129 chr7 44148891 44148940
- SEQ NO:
- ID 288 3001005 ABCA13 NM_152701 chr7 18285460 48285484
- SEQ NO:
- ID 289 3017084 ARMC10 NM_031905 chr7 102716226 102716250
- SEQ NO:
- ID 290 3006668 AUTS2 NM_015570 chr7 69599533 69599557
- SEQ NO:
- ID 291 3158462 C8ORFK29 NR_015428 chr8 145577092 145577180
- SEQ NO:
- ID 292 3121027 C8orf33 NM_023080 chr8 146278059 146278089
- SEQ NO:
- ID 293 3105606 CA2 ENST00000285379 chr8 86376123 86376148
- SEQ NO:
- ID 294 3204670 CD72 ENST00000396759 chr9 35618756 35618361
- SEQ NO:
- ID 295 3221925 AKNA NM_030767 chr9 117103978 117104002
- SEQ NO:
- ID 296 3223849 C5 NM_001735 chr9 123812463 123812487
- SEQ NO:
- ID 297 3190991 C9orf106 NM_001012715 chr9 132083295 132083325
- SEQ NO:
- ID 298 3222599 ASTN2 NM_198186 chr9 119449350 119449382
- SEQ NO:
- ID 299 3229062 BRD3 NM_007371 chr9 136905156 136905186
- SEQ NO:
- ID 300 3986675 ATG4A ENST00000457035 chrx 107335082 107335109
Se llevó a cabo una investigación para determinar si los biomarcadores de PTB podrían ser específicos de miARN o no. El mismo ARN total extraído de las muestras de la semana 26-28, descritas anteriormente, se analizó en la matriz de ARN pequeño no codificante Affymetrix GeneChip (por ejemplo, 847 ARN humanos pequeños no
Claims (1)
-
imagen1 imagen2
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US41836810P | 2010-11-30 | 2010-11-30 | |
| US41837510P | 2010-11-30 | 2010-11-30 | |
| US418368P | 2010-11-30 | ||
| US418375P | 2010-11-30 | ||
| PCT/US2011/062661 WO2012075150A2 (en) | 2010-11-30 | 2011-11-30 | Prediction of spontaneous preterm birth by measuring cell free nucleic acids in maternal blood |
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|---|---|
| ES2586153T3 true ES2586153T3 (es) | 2016-10-11 |
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| US (2) | US20130296190A1 (es) |
| EP (1) | EP2646554B1 (es) |
| ES (1) | ES2586153T3 (es) |
| WO (1) | WO2012075150A2 (es) |
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| US20150038358A1 (en) | 2011-12-01 | 2015-02-05 | University Of Kansas | Methods for detecting trisomy 21 |
| KR20160027212A (ko) * | 2013-07-24 | 2016-03-09 | 더 차이니즈 유니버시티 오브 홍콩 | 조산에 대한 바이오 마커 |
| GB201503792D0 (en) * | 2015-03-06 | 2015-04-22 | Imp Innovations Ltd | Method |
| US11293931B2 (en) | 2016-05-05 | 2022-04-05 | Indiana University Research And Technology Corporation | Quantitative profiling of progesterone metabolites for the prediction of spontaneous preterm delivery |
| EP3452491B1 (en) * | 2016-05-05 | 2021-07-07 | Indiana University Research & Technology Corporation | Quantitative profiling of progesterone metabolites for the prediction of spontaneous preterm delivery |
| CN106381339B (zh) * | 2016-10-31 | 2018-10-26 | 中南大学 | 长链非编码rna linc00152原位杂交探针的应用方法 |
| CN106511368B (zh) * | 2016-10-31 | 2018-10-26 | 中南大学 | 长链非编码RNA LINC00152的siRNA的应用及抑制制剂 |
| CN106480196B (zh) * | 2016-10-31 | 2018-10-26 | 中南大学 | 一种长链非编码rna linc00152的应用 |
| EP3861340A4 (en) | 2019-12-04 | 2022-08-10 | Garbha Health, Inc | ANALYSIS OF HORMONE PROFILES ALLOWING THE PREDICTION OF SPONTANEOUS PREMATURE CHILDBIRTH |
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| US20070037165A1 (en) * | 2000-09-08 | 2007-02-15 | Applera Corporation | Polymorphisms in known genes associated with human disease, methods of detection and uses thereof |
| US20040142325A1 (en) * | 2001-09-14 | 2004-07-22 | Liat Mintz | Methods and systems for annotating biomolecular sequences |
| US20080090759A1 (en) * | 2004-08-30 | 2008-04-17 | Robert Kokenyesi | Methods and kits for predicting risk for preterm labor |
| US20060223066A1 (en) * | 2005-03-29 | 2006-10-05 | Applera Corporation | Methods for normalizing and for identifying small nucleic acids |
| US7807366B2 (en) * | 2007-04-12 | 2010-10-05 | Virginia Commonwealth University | Genetic markers for assessing risk of premature birth resulting from preterm premature rupture of membranes |
| WO2008155397A2 (en) * | 2007-06-20 | 2008-12-24 | Galapagos N.V. | Molecular targets and compounds, and methods to identify the same, useful in the treatment of bone and joint degenerative diseases |
| EP2234483A4 (en) | 2008-01-27 | 2011-04-27 | Rosetta Genomics Ltd | METHOD AND COMPOSITIONS FOR DIAGNOSIS OF PREGNANCY COMPLICATIONS |
| WO2011029899A1 (en) * | 2009-09-11 | 2011-03-17 | The Chinese University Of Hong Kong | Methods for assessing liver pathologies |
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- 2011-11-30 WO PCT/US2011/062661 patent/WO2012075150A2/en not_active Ceased
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- 2011-11-30 EP EP11845889.2A patent/EP2646554B1/en active Active
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| WO2012075150A3 (en) | 2012-08-09 |
| US20130296190A1 (en) | 2013-11-07 |
| EP2646554A2 (en) | 2013-10-09 |
| EP2646554B1 (en) | 2016-06-08 |
| EP2646554A4 (en) | 2014-10-29 |
| US20150376709A1 (en) | 2015-12-31 |
| WO2012075150A2 (en) | 2012-06-07 |
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