DK2728014T3 - Ikke-invasiv fremgangsmåde til detektering af føtal kromosomal aneuploidi - Google Patents
Ikke-invasiv fremgangsmåde til detektering af føtal kromosomal aneuploidi Download PDFInfo
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- DK2728014T3 DK2728014T3 DK12190844.6T DK12190844T DK2728014T3 DK 2728014 T3 DK2728014 T3 DK 2728014T3 DK 12190844 T DK12190844 T DK 12190844T DK 2728014 T3 DK2728014 T3 DK 2728014T3
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- C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
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- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
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- C12Q2600/00—Oligonucleotides characterized by their use
- C12Q2600/166—Oligonucleotides used as internal standards, controls or normalisation probes
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Claims (15)
1. Fremgangsmåde til opnåelse af et sæt referenceprøver til diagnosticering af føtal aneuploidi fra en maternal biologisk prøve, som indeholder cellefrit DNA, omfattende: (i) ekstraktion af cellefrit DNA fra et sæt biologiske prøver, der er opnået fra et sæt af euploide gravide kvinder, som bærer et euploid foster; (ii) forsekvensering af DNA af hver prøve; (iii) mapning af de sekvenser, der opnås i trin (ii) til det menneskelige genom; (iv) udvælgelse af et sæt af prøver på grundlag af mængden af enestående eksakte sekvenser, der er mappede på det menneskelige genom i trin (iii); (v) massiv parallel sekvensering af DNA fra hver prøve fra sættet af prøver, der er udvalgt i trin (iv); (vi) mapning af de sekvenser, der opnås i trin (v) til det menneskelige genom; (vii) udvælgelse af et sæt referenceprøver på grundlag af antallet af enestående eksakte sekvenser, der er mappede på det menneskelige genom i trin (vi);
2. Fremgangsmåde ifølge krav 1, yderligere omfattende, mellem trinnet med ekstraktion af cellefrit DNA og trinnet med forsekvensering: - analysering af størrelsesfordelingen af DNA-molekyler i hver prøve; - udvælgelse af et sæt prøver på grundlag af størrelsesfordelingen af DNA-molekylerne i prøverne.
3. Fremgangsmåde ifølge krav 1 eller 2, hvor ekstraktionen af cellefrit DNA fra hver prøve af sættet af biologiske prøver omfatter: - blanding af den biologiske prøve med en sammensætning, som omfatter kloroform og fenol; - ekstraktion af den vandige fase fra blandingen; - bundfældning af DNA fra den vandige fase.
4. Fremgangsmåde ifølge krav 2 til 3, hvor trinnet med udvælgelse af et sæt prøver på grundlag af størrelsesfordelingen af DNA-molekylerne omfatter udvælgelse af prøver, hvor mindst 90 vægt%, fortrinsvis mere end 95 vægt% af DNA-molekylerne har en størrelse fra 156 bp til 176 bp.
5. Fremgangsmåde ifølge krav 2 til 4, hvor trinnet med udvælgelse af et sæt prøver på grundlag af størrelsesfordelingen af DNA-molekylerne omfatter udvælgelse af prøver med mindst 0,88 ng/μΙ DNA-molekyler med en størrelse fra 156 bp til 176 bp.
6. Fremgangsmåde ifølge krav 1 til 5, hvor trin (ii) omfatter sekvensering fra 1000 til 100000 sekvenser i hver prøve.
7. Fremgangsmåde ifølge krav 1 til 6, hvor trin (iv) omfatter udvælgelse af prøver, som har mindst 70 % enestående eksakte sekvenser i forhold til det samlede antal sekvenser, der er opnået i trin (ii).
8. Fremgangsmåde ifølge krav 1 til 7, hvor trin (v) omfatter sekvensering af mindst 25 millioner sekvenser for hver prøve.
9. Fremgangsmåde ifølge krav 1 til 8, hvor trin (vii) omfatter udvælgelse af prøver, som har mere end 15 millioner enestående eksakte sekvenslæsninger.
10. Fremgangsmåde til diagnosticering af føtal aneuploidi fra en maternal biologisk testprøve, omfattende: (a) ekstraktion af cellefrit DNA fra en maternal biologisk testprøve, der opnås fra en gravid kvinde; (b) massiv parallel sekvensering af cellefrit DNA, der er ekstraheret fra testprøven; (c) mapning af de sekvenser, der opnås i trin (b) til det menneskelige genom; (d) beregning af en testparameter, som angiver antallet af enestående eksakte sekvenser, der er mappede på et kromosom eller kromosomalt interesseområde; (e) beregning af et sæt referenceparametre, hvor hver referenceparameter angiver antallet af enestående eksakte sekvenser, der er mappede på et kromosom eller kromosomalt interesseområde for en prøve af et sæt af referenceprøver, som er opnået i krav 1 til 8; (f) sammenligne testparameteren, der er beregnet i trin (d) med sættet af referenceparametre, der er beregnet i trin (e); (g) diagnosticering af føtal aneuploidi på basis af sammenligningen.
11. Fremgangsmåde ifølge krav 10, hvor ekstraktionen af cellefrit DNA fra den maternale biologiske testprøve omfatter: - blanding af den biologiske prøve med en sammensætning, som omfatter kloroform og fenol; - ekstraktion af den vandige fase fra blandingen; - bundfældning af DNA fra den vandige fase.
12. Fremgangsmåde ifølge krav 10 eller 11, hvor testparameteren er den enestående sekvens-tag-densitet af kromosomet eller det kromosomale interesseområde, normaliseret til den gennemsnitlige enestående sekvens-tag-densitet af alle autosomer.
13. Fremgangsmåde ifølge krav 10 til 12, hvor sammenligningen i trin (f) udføres ved beregning af z-score af testparameteren i forhold til sættet af referenceparametre.
14. Fremgangsmåde ifølge krav 10 til 13, hvor det interessante kromosom er kromosom 21, kromosom 18 eller kromosom 13.
15. Fremgangsmåde ifølge krav 13, hvor det interessante kromosom er kromosom 21, og z-score af en trisomi-21-prøve er mindst 4,4, mens den absolutte værdi af z-score af en prøve, der er euploid for kromosom 21, er mindre end 4,4.
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|---|---|---|---|
| EP12190844.6A EP2728014B1 (en) | 2012-10-31 | 2012-10-31 | Non-invasive method for detecting a fetal chromosomal aneuploidy |
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| DK2728014T3 true DK2728014T3 (da) | 2016-01-25 |
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2012
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2013
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| EP2728014B1 (en) | 2015-10-07 |
| HK1208708A1 (en) | 2016-04-15 |
| US20150275290A1 (en) | 2015-10-01 |
| WO2014068075A1 (en) | 2014-05-08 |
| IL238426A0 (en) | 2015-06-30 |
| CN105074004A (zh) | 2015-11-18 |
| EP2914738A1 (en) | 2015-09-09 |
| EP2728014A1 (en) | 2014-05-07 |
| AU2013340795A1 (en) | 2015-05-14 |
| EP3026124A1 (en) | 2016-06-01 |
| CA2888906A1 (en) | 2014-05-08 |
| JP2015534807A (ja) | 2015-12-07 |
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