CN112442542A - Fetal paternity testing method - Google Patents
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- CN112442542A CN112442542A CN202011103020.3A CN202011103020A CN112442542A CN 112442542 A CN112442542 A CN 112442542A CN 202011103020 A CN202011103020 A CN 202011103020A CN 112442542 A CN112442542 A CN 112442542A
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- 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
- C12Q1/6888—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for detection or identification of organisms
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- G—PHYSICS
- G16—INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR SPECIFIC APPLICATION FIELDS
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- G16B20/00—ICT specially adapted for functional genomics or proteomics, e.g. genotype-phenotype associations
- G16B20/30—Detection of binding sites or motifs
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- 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
Abstract
The invention discloses a method for identifying the paternity relationship of a fetus, which comprises the steps of selecting a locus group with diversity difference; obtaining the depth distribution of each site in the peripheral blood free DNA, the genotype of each site in the leucocyte DNA and the genotype of each site in the father DNA to be suspected; obtaining the concentration of the fetal DNA in the peripheral blood DNA of the pregnant woman to be detected as P1 based on the random information site set G1; obtaining the concentration of the fetal DNA in the peripheral blood DNA of the pregnant woman to be detected as P2 based on the inevitable information site set G2; selecting N random male DNA samples which have no relationship with the pregnant woman to be detected and the father to be detected as Fi, and then calculating P2(i) corresponding to each random male; respectively calculating an H value and a Hi value according to H-P2/P1 and Hi-P2 (i)/P1, and determining the paternity of the father to be detected and the fetus of the pregnant woman to be detected according to the significance difference between the H value and { Hi }; the identification method does not depend on the typing of the fetus, is suitable for the free DNA sample of the pregnant woman with lower concentration, and has simple operation and high identification accuracy.
Description
Technical Field
The invention relates to the technical field of paternity test, in particular to a method for identifying paternity relationship of a fetus.
Background
At present, a paternity test method for a fetus generally obtains a sample through amniotic fluid puncture or chorionic biopsy after the fetus reaches 13-14 weeks, performs paternity test on a sperm supply side by using a paternity test kit, and judges the biological father of the fetus; however, this method requires the acquisition of amniotic fluid and a sample of fetal chorionic villus, which poses unnecessary medical risks to the pregnant woman or the fetus, and requires the fetus to reach a certain number of weeks when the sample is acquired, which limits the detection time.
Disclosure of Invention
The invention aims to provide a fetal paternity test method, which does not need to obtain amniotic fluid or fetal chorion and can avoid medical risks; in addition, the method does not need to type the fetus, and is suitable for the free DNA sample of the pregnant woman with lower concentration.
In order to achieve the above purpose of the present invention, the following technical solutions are adopted:
the invention provides a method for identifying the paternity relationship of a fetus, which comprises the following steps:
(a) selecting a locus group with diversity difference according to the gene sequence of the pregnant woman population, and recording as G;
(b) acquiring free DNA of peripheral blood of a pregnant woman to be detected, DNA of leucocytes and father DNA to be detected, performing high-depth sequencing on the free DNA of the peripheral blood of the pregnant woman to be detected, the DNA of the leucocytes and the same sites as G in the father DNA to be detected respectively, and acquiring the depth distribution of each site in the free DNA of the peripheral blood, the genotype of each site in the DNA of the leucocytes and the genotype of each site in the father DNA to be detected according to a sequencing result;
(c) selecting a site set based on the genotype of each site in leucocyte DNA of the pregnant woman to be detected and the depth distribution of each site in peripheral blood free DNA, and marking as G1, wherein the selection conditions of G1 are as follows: when the sequencing depth is higher than a threshold value, at least 2 polymorphic sites are located on the site, and homozygote is located on the corresponding leucocyte DNA; then, obtaining the concentration of the fetal DNA in the peripheral blood DNA of the pregnant woman to be detected by adopting a maximum likelihood method for the depth distribution of the polymorphic sites on the selected G1, and marking as P1, wherein P1 is a P value which enables the formula 1 to obtain the maximum value,
in the formula 1, p is the concentration of fetal DNA in the peripheral blood DNA of a pregnant woman to be detected, and Xi is the polymorphism depth distribution of corresponding sites;
(d) selecting a locus set based on the genotype of each locus in the leucocyte DNA of the pregnant woman to be detected and the genotype of each locus in the father DNA to be detected, and marking as G2, wherein the selection conditions of G2 are as follows: the leucocyte DNA of the pregnant woman to be detected and the father DNA to be suspected are loci of homozygotes with different genotypes; then, obtaining the concentration of the fetal DNA in the peripheral blood DNA of the pregnant woman to be detected by adopting a maximum likelihood method based on the depth distribution of the peripheral blood free DNA of the pregnant woman to be detected on the polymorphic site G2, and marking as P2, wherein P2 is a P value enabling formula 2 to obtain the maximum value,
(e) selecting N random male DNA samples which have no relationship with the pregnant woman to be detected and the father to be detected, marking as Fi, and calculating P2(i) corresponding to each random male according to the step (d), wherein i is 1, 2 or 3 … N;
(f) and respectively calculating an H value and a Hi value according to H-P2/P1 and Hi-P2 (i)/P1, and determining the paternity of the father to be detected and the fetus of the pregnant woman to be detected according to the significance difference between the H value and { Hi }.
Preferably, the step (f) of determining the paternity of the father to be suspected and the fetus of the pregnant woman to be suspected according to the significant difference between the H value and the { Hi } includes:
if the H value is obviously larger than { Hi }, the father to be suspected and the fetus born by the pregnant woman to be suspected are in paternity, and if the H value is not obviously different from { Hi }, the father to be suspected and the fetus born by the pregnant woman to be suspected are in non-paternity.
Preferably, in step (a), the number of pregnant women in the pregnant woman population is not less than 50.
Preferably, in step (b), the depth of high-depth sequencing is not less than 20 ×.
Preferably, in the step (c), the threshold is 20 ×.
Preferably, in said step (e), N is greater than 20.
Preferably, in the step (f), a t test is used to judge the significant difference between the H value and the { Hi }.
Compared with the prior art, the invention has the beneficial effects that at least:
the identification method comprises the steps of obtaining the fetal DNA concentration in free DNA of peripheral blood of a pregnant woman to be detected, quantifying by two different methods, and identifying the paternity and the child relationship by the difference of the quantitative concentrations; the identification method does not depend on the typing of the fetus, is suitable for the free DNA sample of the pregnant woman with lower concentration, and is simple to operate and high in identification accuracy.
Detailed Description
The following describes embodiments of the present invention in detail with reference to the following embodiments. The following examples are only for illustrating the technical solutions of the present invention more clearly, and therefore are only examples, and the protection scope of the present invention is not limited thereby.
It is to be noted that, unless otherwise specified, technical or scientific terms used herein shall have the ordinary meaning as understood by those skilled in the art to which the invention pertains.
The embodiment of the invention provides a method for identifying the paternity relationship of a fetus, which comprises the following steps:
(a) selecting a locus group with diversity difference according to the gene sequence of the pregnant woman population, and recording as G;
(b) acquiring free DNA of peripheral blood of a pregnant woman to be detected, DNA of leucocytes and father DNA to be detected, performing high-depth sequencing (the depth is more than 20 x) on the free DNA of the peripheral blood of the pregnant woman to be detected, the DNA of the leucocytes and the same sites as G in the father DNA to be detected respectively, and acquiring the depth distribution of each site in the free DNA of the peripheral blood, the genotype of each site in the DNA of the leucocytes and the genotype of each site in the father DNA to be detected according to a sequencing result;
(c) selecting a site set based on the genotype of each site in leucocyte DNA of the pregnant woman to be detected and the depth distribution of each site in peripheral blood free DNA, and marking as G1, wherein the selection conditions of G1 are as follows: when the sequencing depth is higher than 20 multiplied, at least 2 polymorphic sites are positioned on the site, and homozygote is positioned on the corresponding leucocyte DNA; then, obtaining the concentration of the fetal DNA in the peripheral blood DNA of the pregnant woman to be detected by adopting a maximum likelihood method for the depth distribution of the polymorphic sites on the selected G1, and marking as P1, wherein P1 is a P value which enables the formula 1 to obtain the maximum value,
in the formula 1, p is the concentration of fetal DNA in the peripheral blood DNA of a pregnant woman to be detected, and Xi is the polymorphism depth distribution of corresponding sites;
(d) selecting a locus set based on the genotype of each locus in the leucocyte DNA of the pregnant woman to be detected and the genotype of each locus in the father DNA to be detected, and marking as G2, wherein the selection conditions of G2 are as follows: the leucocyte DNA of the pregnant woman to be detected and the father DNA to be suspected are loci of homozygotes with different genotypes; then, obtaining the concentration of the fetal DNA in the peripheral blood DNA of the pregnant woman to be detected by adopting a maximum likelihood method based on the depth distribution of the peripheral blood free DNA of the pregnant woman to be detected on the polymorphic site G2, and marking as P2, wherein P2 is a P value enabling formula 2 to obtain the maximum value,
(e) selecting N random male DNA samples which have no relationship with the pregnant woman to be detected and the father to be detected, marking as Fi, and calculating P2(i) corresponding to each random male according to the step (d), wherein i is 1, 2 or 3 … N;
(f) and respectively calculating an H value and a Hi value according to H-P2/P1 and Hi-P2 (i)/P1, wherein if the H value is obviously greater than { Hi }, the father to be detected and the fetus born by the pregnant woman to be detected are in paternity relationship, and if the H value is not obviously different from { Hi }, the father to be detected and the fetus born by the pregnant woman to be detected are in non-paternity relationship.
The identification method of the invention comprises the steps of obtaining the fetal DNA concentration in free DNA of peripheral blood of a pregnant woman to be detected, quantifying by two different methods, and identifying the paternity relationship by the difference of the quantitative concentrations; the identification method does not depend on the typing of the fetus, is suitable for the free DNA sample of the pregnant woman with lower concentration, and is simple to operate and high in identification accuracy.
In the present invention, the number of the pregnant woman group is not strictly limited, for example, in the step (a), the number of pregnant women in the pregnant woman group is not less than 100; in one embodiment, the population of pregnant women has a population of 100 pregnant women. By limiting the number of pregnant women in the pregnant woman group, the site groups with diversity differences can be fully and completely acquired, and the accuracy of the identification method can be better improved.
The number of random male DNA samples is not strictly limited in the present invention, preferably, the number of random male DNA samples is more than 20 persons; in step (e), N is greater than 20. The accuracy of the identification method can be better improved by selecting the random male DNA sample number.
In one embodiment, in step (f), t.test (H-Hi) in R language is used to determine the significance difference between H and { Hi }.
The technical solution claimed by the present invention is further described in detail by the following specific examples.
Example 1
This embodiment is a method for identifying paternity relationships of a fetus, comprising the steps of:
(a) selecting a locus group with diversity difference according to the gene sequence of the pregnant woman (50 persons) and recording as G, wherein G comprises 2736 polymorphic SNP loci;
(b) acquiring free DNA (number 2015986S) of peripheral blood of a pregnant woman to be detected, DNA (number 2015986M) of white blood cells and father DNA (number 2015986F) to be detected, respectively carrying out high-depth sequencing (depth 20 x) on the free DNA of the peripheral blood of the pregnant woman to be detected, the DNA of the white blood cells and the same sites as G in the father DNA to be detected, and obtaining the depth distribution of each site in the free DNA of the peripheral blood, the genotype of each site in the DNA of the white blood cells and the genotype of each site in the father DNA to be detected according to a sequencing result;
(c) selecting a site set based on the genotype of each site in leucocyte DNA of the pregnant woman to be detected and the depth distribution of each site in peripheral blood free DNA, and marking as G1, wherein the selection conditions of G1 are as follows: when the sequencing depth is higher than 20 multiplied, at least 2 polymorphic sites are positioned on the site, and homozygote is positioned on the corresponding leucocyte DNA; then, obtaining the concentration of the fetal DNA in the peripheral blood DNA of the pregnant woman to be detected by adopting a maximum likelihood method for the depth distribution of the polymorphic sites on the selected G1, and marking as P1, wherein P1 is a P value which enables the formula 1 to obtain the maximum value,
in the formula 1, P is the concentration of fetal DNA in peripheral blood DNA of a pregnant woman to be detected, Xi is the polymorphism depth distribution of a corresponding site, and P1 is calculated to be 0.0445;
(d) selecting a locus set based on the genotype of each locus in the leucocyte DNA of the pregnant woman to be detected and the genotype of each locus in the father DNA to be detected, and marking as G2, wherein the selection conditions of G2 are as follows: the leucocyte DNA of the pregnant woman to be detected and the father DNA to be suspected are loci of homozygotes with different genotypes; then, obtaining the concentration of the fetal DNA in the peripheral blood DNA of the pregnant woman to be detected by adopting a maximum likelihood method based on the depth distribution of the peripheral blood free DNA of the pregnant woman to be detected on the polymorphic site G2, and marking as P2, wherein P2 is a P value enabling formula 2 to obtain the maximum value,
calculating P2-0.0389;
(e) selecting 29 random male DNA samples which have no relationship with the pregnant woman to be detected and the father to be detected, marking as Fi, and calculating P2(i) corresponding to each random male according to the step (d), wherein i is 1, 2 or 3 … N; when i is 1, 2, 3 … N, the corresponding P2(i) is 0.02, 0.019, 0.02, 0.021, 0.024, 0.022, 0.021, 0.023, 0.023, 0.02, 0.02, 0.022, 0.023, 0.025, 0.021, 0.023, 0.02, 0.02, 0.018, 0.016, 0.022, 0.017, 0.022, 0.021, 0.017, 0.017, 0.02, 0.022 in sequence;
(f) calculating H and Hi values according to H-P2/P1 and Hi-P2 (i)/P1, respectively, wherein H-0.8742;
judging the significance difference between the H value and { Hi } by using t.test (H-Hi) of the R language, wherein the judgment result is that H is significantly larger than { Hi }, and p-value is less than 2.2 e-16; and judging that the father (2015986F) to be suspected is in parentage with the fetus born by the pregnant woman (2015986S) to be suspected.
Based on the locus set G1, calculating to obtain 0% locus proportion of the fetal genotype and the paternal genotype which do not accord with the paternity relationship by judging the fetal genotype, the maternal genotype and the paternal genotype and 1.1 x 10 CPI index77The paternity relationship between the fetus and the male parent can be determined, and the identification result is the same as that of the application.
Example 2
This embodiment is a method for identifying paternity relationships of a fetus, comprising the steps of:
(a) selecting a locus group with diversity difference according to the gene sequence of a pregnant woman (5000 persons) and recording as G, wherein G comprises 2738 polymorphic SNP loci;
(b) acquiring free DNA (number 2015938S) of peripheral blood of a pregnant woman to be detected, DNA (number 2015938M) of white blood cells and father DNA (number 2015938F) to be detected, respectively carrying out high-depth sequencing (depth 20 x) on the free DNA of the peripheral blood of the pregnant woman to be detected, the DNA of the white blood cells and the same sites as G in the father DNA to be detected, and obtaining the depth distribution of each site in the free DNA of the peripheral blood, the genotype of each site in the DNA of the white blood cells and the genotype of each site in the father DNA to be detected according to a sequencing result;
(c) selecting a site set based on the genotype of each site in leucocyte DNA of the pregnant woman to be detected and the depth distribution of each site in peripheral blood free DNA, and marking as G1, wherein the selection conditions of G1 are as follows: when the sequencing depth is higher than 20 multiplied, at least 2 polymorphic sites are positioned on the site, and homozygote is positioned on the corresponding leucocyte DNA; then, obtaining the concentration of the fetal DNA in the peripheral blood DNA of the pregnant woman to be detected by adopting a maximum likelihood method for the depth distribution of the polymorphic sites on the selected G1, and marking as P1, wherein P1 is a P value which enables the formula 1 to obtain the maximum value,
in the formula 1, P is the concentration of fetal DNA in peripheral blood DNA of a pregnant woman to be detected, Xi is the polymorphism depth distribution of a corresponding site, and P1 is calculated to be 0.0707;
(d) selecting a locus set based on the genotype of each locus in the leucocyte DNA of the pregnant woman to be detected and the genotype of each locus in the father DNA to be detected, and marking as G2, wherein the selection conditions of G2 are as follows: the leucocyte DNA of the pregnant woman to be detected and the father DNA to be suspected are loci of homozygotes with different genotypes; then, obtaining the concentration of the fetal DNA in the peripheral blood DNA of the pregnant woman to be detected by adopting a maximum likelihood method based on the depth distribution of the peripheral blood free DNA of the pregnant woman to be detected on the polymorphic site G2, and marking as P2, wherein P2 is a P value enabling formula 2 to obtain the maximum value,
calculating P2-0.0319;
(e) selecting 29 random male DNA samples which have no relationship with the pregnant woman to be detected and the father to be detected, marking as Fi, and calculating P2(i) corresponding to each random male according to the step (d), wherein i is 1, 2 or 3 … N; when i is 1, 2, 3 … N, the corresponding P2(i) is 0.036,0.032,0.033, 0.029,0.035,0.033,0.032,0.034,0.038,0.032,0.035,0.029,0.033, 0.033,0.031, 0.036,0.035,0.031,0.029,0.03,0.033,0.028, 0.033,0.031,0.034,0.035, 0.032;
(f) calculating H and Hi values according to H-P2/P1 and Hi-P2 (i)/P1, respectively, wherein H is 0.451;
judging the significance difference between the H value and { Hi } by using t.test (H-Hi) of an R language, wherein the judgment result shows that the difference between the H value and { Hi } is not significant, and p-value is 0.09003; the paternity of the fetus born by the father (2015938F) to be detected and the pregnant woman (2015938S) to be detected is judged.
Based on the site set G1, by judging the fetal genotype, the maternal genotype and the paternal genotype, the site proportion of the fetal genotype and the paternal genotype which do not accord with the paternal relationship is calculated to be 23.85 percent, and the CPI index is 5.89 x 10-111The non-paternity relationship between the fetus and the male parent can be determinedThe results were the same as the results identified in the present application.
Finally, it should be noted that: the above embodiments are only used to illustrate the technical solution of the present invention, and not to limit the same; while the invention has been described in detail and with reference to the foregoing embodiments, it will be understood by those skilled in the art that: the technical solutions described in the foregoing embodiments may still be modified, or some or all of the technical features may be equivalently replaced; the modifications and the substitutions do not cause the essence of the corresponding technical solutions to depart from the scope of the technical solutions of the embodiments of the present invention, and the corresponding technical solutions are all covered in the claims and the specification of the present invention.
Claims (7)
1. A method for identifying fetal paternity, comprising the steps of:
(a) selecting a locus group with diversity difference according to the gene sequence of the pregnant woman population, and recording as G;
(b) acquiring free DNA of peripheral blood of a pregnant woman to be detected, DNA of leucocytes and father DNA to be detected, performing high-depth sequencing on the free DNA of the peripheral blood of the pregnant woman to be detected, the DNA of the leucocytes and the same sites as G in the father DNA to be detected respectively, and acquiring the depth distribution of each site in the free DNA of the peripheral blood, the genotype of each site in the DNA of the leucocytes and the genotype of each site in the father DNA to be detected according to a sequencing result;
(c) selecting a site set based on the genotype of each site in leucocyte DNA of the pregnant woman to be detected and the depth distribution of each site in peripheral blood free DNA, and marking as G1, wherein the selection conditions of G1 are as follows: when the sequencing depth is higher than a threshold value, at least 2 polymorphic sites are located on the site, and homozygote is located on the corresponding leucocyte DNA; then, obtaining the concentration of the fetal DNA in the peripheral blood DNA of the pregnant woman to be detected by adopting a maximum likelihood method for the depth distribution of the polymorphic sites on the selected G1, and marking as P1, wherein P1 is a P value which enables the formula 1 to obtain the maximum value,
in the formula 1, p is the concentration of fetal DNA in the peripheral blood DNA of a pregnant woman to be detected, and Xi is the polymorphism depth distribution of corresponding sites;
(d) based on the genotype of each site in the leucocyte DNA of the pregnant woman to be detected and the genotype of each site in the father DNA to be detected, a site set is selected and marked as G2, and the selection conditions of G2 are as follows: the leucocyte DNA of the pregnant woman to be detected and the father DNA to be suspected are loci of homozygotes with different genotypes; then, obtaining the concentration of the fetal DNA in the peripheral blood DNA of the pregnant woman to be detected by adopting a maximum likelihood method based on the depth distribution of the peripheral blood free DNA of the pregnant woman to be detected on the polymorphic site G2, and marking as P2, wherein P2 is a P value enabling formula 2 to obtain the maximum value,
(e) selecting N random male DNA samples which have no relationship with the pregnant woman to be detected and the father to be detected, marking as Fi, and calculating P2(i) corresponding to each random male according to the step (d), wherein i is 1, 2 or 3 … N;
(f) and respectively calculating an H value and a Hi value according to H-P2/P1 and Hi-P2 (i)/P1, and determining the paternity of the father to be detected and the fetus of the pregnant woman to be detected according to the significance difference between the H value and { Hi }.
2. The method as claimed in claim 1, wherein said step (f) of determining the paternity of the father to be suspected with the fetus carried by the pregnant woman to be suspected based on the significant difference between the H value and { Hi } comprises:
if the H value is obviously larger than { Hi }, the father to be suspected and the fetus born by the pregnant woman to be suspected are in paternity, and if the H value is not obviously different from { Hi }, the father to be suspected and the fetus born by the pregnant woman to be suspected are in non-paternity.
3. The identification method according to claim 1, wherein in the step (a), the number of pregnant women in the pregnant woman population is not less than 50.
4. The method of claim 1, wherein in step (b), the depth of the high-depth sequencing is not less than 20 x.
5. The method of claim 1, wherein in step (c) the threshold is 20 x.
6. The method of claim 1, wherein in step (e), N is greater than 20.
7. The method according to claim 1 or 2, wherein in the step (f), a significant difference between the H value and { Hi } is judged by using a t-test.
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113969310A (en) * | 2021-10-14 | 2022-01-25 | 武汉蓝沙医学检验实验室有限公司 | Fetal DNA concentration evaluation method and application |
| CN113981062A (en) * | 2021-10-14 | 2022-01-28 | 武汉蓝沙医学检验实验室有限公司 | Method for evaluating fetal DNA concentration by using DNA of non-biotics father and mother and application |
| CN113999900A (en) * | 2021-10-14 | 2022-02-01 | 武汉蓝沙医学检验实验室有限公司 | Method for evaluating fetal DNA concentration by using free DNA of pregnant woman and application |
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2020
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Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113969310A (en) * | 2021-10-14 | 2022-01-25 | 武汉蓝沙医学检验实验室有限公司 | Fetal DNA concentration evaluation method and application |
| CN113981062A (en) * | 2021-10-14 | 2022-01-28 | 武汉蓝沙医学检验实验室有限公司 | Method for evaluating fetal DNA concentration by using DNA of non-biotics father and mother and application |
| CN113999900A (en) * | 2021-10-14 | 2022-02-01 | 武汉蓝沙医学检验实验室有限公司 | Method for evaluating fetal DNA concentration by using free DNA of pregnant woman and application |
| CN113999900B (en) * | 2021-10-14 | 2024-02-20 | 武汉蓝沙医学检验实验室有限公司 | Method for evaluating fetal DNA concentration by using free DNA of pregnant woman and application |
| CN113981062B (en) * | 2021-10-14 | 2024-02-20 | 武汉蓝沙医学检验实验室有限公司 | Method for evaluating fetal DNA concentration by non-maternal and maternal DNA and application |
| CN113969310B (en) * | 2021-10-14 | 2024-02-20 | 武汉蓝沙医学检验实验室有限公司 | Fetal DNA concentration evaluation method and application |
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