Method for judging the parent-child relationship between pregnant woman and fetus by calculating fetal concentration

Abstract

The present invention discloses a method for judging the parent-child relationship between a pregnant woman and a fetus by calculating the fetal concentration, and belongs to the technical field of parent-child identification. The method comprises: S101: obtaining DNA data S and F' of dimorphic sites of a pregnant woman's free DNA sample and a random paternal DNA sample; S102: obtaining site sets X1 and X' that meet the requirements in S; S103: calculating the probability P of a certain site on the site sets X1 and X' respectively according to formula I; S104: using the point sets X1 and X' to respectively calculate the fetal concentrations p1 and p2 by using the maximum likelihood method; S105: judging the parent-child relationship between the pregnant woman's fetus and the pregnant woman according to the ratio of p2 to p1. The method can judge the parent-child relationship between a pregnant woman and a fetus by using the second-generation sequencing data of the pregnant woman's free DNA and the random paternal DNA, can utilize the advantage of the fast sequencing speed of the second-generation sequencing data, and the method has high accuracy.

Description

Technical Field

[0001] The present invention belongs to the technical field of paternity testing, and in particular relates to a method for judging the paternity relationship between a pregnant woman and a fetus by calculating the fetal concentration. Background Art

[0002] Paternity testing refers to the use of theories and techniques in biology, genetics and related disciplines to determine whether the alleged parents and children are in a biological relationship based on the inheritance laws of genetic traits between offspring and parents. In the paternity test of pregnant women and fetuses, the existing technology mainly determines whether the pregnant woman and the fetus have a parent-child relationship with a man. Usually, the pregnant woman and the fetus have a parent-child relationship, but the pregnant woman and the fetus may not have a parent-child relationship, such as pregnancy using stored eggs, pregnancy using other people's eggs, etc. That is, in some special circumstances, it is also necessary to determine the parent-child relationship between the pregnant woman and the fetus, but there is no public detection method in the existing technology. Summary of the invention

[0003] An embodiment of the present invention provides a method for determining the parent-child relationship between a pregnant woman and a fetus by calculating fetal concentration, the method comprising the following steps:

[0004] S101: Obtain DNA data S and F' of dimorphic sites of the pregnant woman's free DNA sample and the random paternal DNA sample;

[0005] S102: Obtain site sets X1 and X' in S that meet the following requirements,

[0006] X1={x i |0<na i (S) / n i (S)<0.2∪0<nA i (S) / n i (S)<0.2}

[0007] X'={x i |na i (S) / n i (S)≤0.2∩na i (F') / n i (F')≥0.9}∪{x i |nA i (S) / n i (S)≤0.2∩nA i (F') / n i (F')≥0.9}

[0008] Where nA and na represent the observed values ​​of dimorphic sites A and a, respectively, n = nA + na, k = na;

[0009] S103: Calculate the probability P of a certain site on the site sets X1 and X' respectively according to formula I,

[0010]

[0011] in, 0≤p≤0.5,0<Pm<0.2;

[0012] S104: using the point sets X1 and X', respectively, the fetal concentrations p1 and p2 are calculated using the maximum likelihood method;

[0013] S105: Determine the parent-child relationship between the fetus and the pregnant woman according to the ratio of p2 to p1.

[0014] Wherein, step S105 specifically includes:

[0015] S501: Calculate p2 / p1 to obtain B;

[0016] S502: Obtain judgment sets M(S1) and M(S2) respectively indicating that the pregnant woman and the fetus have a parent-child relationship and do not have a parent-child relationship;

[0017] S503: If B∈M(S1) and If And B∈M(S2), then the fetus in the sample to be tested has no parent-child relationship with the pregnant woman; if and The parent-child relationship between the pregnant woman and the fetus in the sample to be tested is yet to be determined;

[0018] Among them, M(S1) and M(S2) are both constant sets, or B is calculated according to steps S101-S104 using a simulated sample with a clear parent-child relationship between the pregnant woman and the fetus, and then B is fitted by quantile regression, or B is calculated according to steps S101-S104 using an actual measured sample with a clear parent-child relationship between the pregnant woman and the fetus, and then B is fitted by quantile regression.

[0019] Specifically, when M(S1) and M(S2) are both constant sets, M(S1)=[0.4554839, 0.5831579], M(S2)=[0.7031317, 0.827112].

[0020] Specifically, a sample set S1 of free DNA of pregnant women with parent-child relationship is obtained through simulated samples or actual measured samples, and then p1 and p2 are calculated according to steps S101-S104, and then p2 / p1 of each sample is calculated to obtain B, and B is fitted by quantile regression, with quantile Y, to obtain a judgment set M(S1);

[0021] A sample set S2 of free DNA of pregnant women with no parent-child relationship between the pregnant women and the fetus is obtained by simulating samples or measuring samples, and then p1 and p2 are calculated according to steps S101-S104, and then p2 / p1 of each sample is calculated to obtain B, and B is fitted by quantile regression, with the quantile being Y, to obtain a judgment set M(S2);

[0022] The Y is 90%-97.5%.

[0023] Preferably, the Y is 95%.

[0024] Among them, the number of samples in the sample set S1 is greater than or equal to 60, and the number of sites in each sample is greater than or equal to 2500; the number of samples in the sample set S2 is greater than or equal to 60, and the number of sites in each sample is greater than or equal to 2500; more than 90% of the sites in the sample S are included in the sites of the sample set S1 or the sites of the sample set S2.

[0025] The number of sites of the sample S is greater than or equal to 1000.

[0026] More specifically, the judgment set M(S1) and the judgment set M(S2) obtained by simulating samples include:

[0027] S201: Generate paternal DNA sample F and maternal DNA sample M randomly through the frequency of Chinese population, generate offspring Z from F and M through Mendel's law of inheritance, mix the concentration of offspring Z from 0 to 0.2 at intervals of 0.01, mix offspring Z and maternal M to obtain simulated pregnant woman free DNA sample S1, generate 10 samples for each mixing ratio, the number of loci of each sample in sample set S1 is greater than 2500 and the dimorphic types include SNP and INDEL;

[0028] S202: Maternal M' and fetal Z' were randomly generated by the frequency of the Chinese population. The concentration of fetal Z' was mixed from 0 to 0.2 at intervals of 0.01. Maternal M' and fetal Z' were mixed to obtain simulated pregnant women's free DNA sample S2. Ten samples were generated for each ratio. The number of loci of each sample in sample set S2 was greater than 2500 and the dimorphic types included SNP and INDEL.

[0029] S203: Randomly generate paternal Fs using Chinese population frequency;

[0030] S204: Using sample set S1 and Fs according to steps S101-S104 to calculate p1 and p2, then calculate p2 / p1 to get B, fit B by quantile regression with a quantile of 95%, and obtain judgment set M(S1); Using sample set S2 and Fs according to steps S101-S104 to calculate p1 and p2, then calculate p2 / p1 to get B, fit B by quantile regression with a quantile of 95%, and obtain judgment set M(S2).

[0031] Wherein, the dimorphic site is a SNP site, the population frequency of the dimorphic site is 0.05-0.95, the A represents a wild-type site, and a represents a mutant site.

[0032] Step S104 includes: calculating the cumulative probability h of all sites on the site set X1 or X' according to formula II, p takes a value at every predetermined interval to calculate the cumulative probability h, and the value of p when h takes the maximum value is p max , the fetal concentration is 2p max ;

[0033]

[0034] This method can use the free DNA of the pregnant woman and the random paternal DNA through the second-generation sequencing data to determine the parent-child relationship between the pregnant woman and the fetus. It can take advantage of the fast sequencing speed of the second-generation sequencing data. This method has high accuracy and has the advantages of being simple, convenient and fast, and can be applied to different scenarios. BRIEF DESCRIPTION OF THE DRAWINGS

[0035] Figure 1 is a flow chart of a method for determining the parent-child relationship between a pregnant woman and a fetus by calculating fetal concentration provided by an embodiment of the present invention;

[0036] Figure 2 is a linear relationship diagram of p1-p2 concentration when the pregnant mother and the fetus are in a parent-child relationship in Example 3;

[0037] Figure 3 This is a linear relationship diagram of p1-p2 concentration when the pregnant mother and the fetus are not in a parent-child relationship in Example 3;

[0038] Figure 4 is a linear relationship diagram of p1-p2 concentration in Example 3;

[0039] Figure 5 This is a linear relationship diagram of p1-p2 concentration when the pregnant mother and the fetus are in a parent-child relationship in Example 4;

[0040] Figure 6 This is a linear relationship diagram of p1-p2 concentration when the pregnant mother and the fetus are not in a parent-child relationship in Example 4;

[0041] Figure 7 This is the linear relationship diagram of the p1-p2 concentration in Example 4. DETAILED DESCRIPTION

[0042] In order to make the objectives, technical solutions and advantages of the present invention more clear, the present invention will be further described in detail below with reference to the accompanying drawings.

[0043] Example 1

[0044] See also Figure 1 Embodiment 1 provides a method for determining the parent-child relationship between a pregnant woman and her fetus by calculating the fetal concentration, the method comprising the following steps:

[0045] S101: Obtain DNA data S and F' of dimorphic sites of free DNA samples of pregnant women and random paternal DNA samples; wherein, free DNA samples of pregnant women can be obtained by detecting peripheral blood of pregnant women, which contains both DNA of pregnant women and DNA of fetuses. Wherein, the DNA data S and F' in this embodiment are obtained by second-generation sequencing technology. Wherein, the dimorphic sites are selected from SNP sites, INDEL sites and / or STR sites, etc., and preferably, the dimorphic sites are SNP sites. Wherein, the population frequency of dimorphic sites is 0.05-0.95.

[0046] S102: Obtain site sets X1 and X' in S that meet the following requirements,

[0047] X1={x i |0<na i (S) / n i (S)<0.2∪0<nA i (S) / n i (S)<0.2},

[0048] X'={x i |na i (S) / n i (S)≤0.2∩na i (F') / n i (F')≥0.9}∪{x i |nA i (S) / n i (S)≤0.2∩nA i (F') / n i (F') ≥ 0.9}

[0049] Wherein, nA and na represent the observed values ​​of dimorphic sites A and a respectively, n=nA+na, k=na, A represents the wild-type site, and a represents the mutant site; the value of F' represents that for data S, the same point on F' must meet the value requirements of X'.

[0050] S103: Calculate the probability P of a certain site on the site sets X1 and X' respectively according to formula I,

[0051]

[0052] in, 0≤p≤0.5, 0<Pm<0.2, specifically, p takes discrete values ​​at predetermined intervals starting from 0.

[0053] S104: Using the point sets X1 and X', the maximum likelihood method is used to calculate the fetal concentrations p1 and p2 respectively.

[0054] S105: Determine the parent-child relationship between the fetus and the pregnant woman according to the ratio of p2 to p1. The ratio of p2 to p1 can be p2 / p1 or p1 / p2. This embodiment is illustrated with p2 / p1 but is not intended to be a limitation of this patent.

[0055] Example 2

[0056] An embodiment of the present invention provides a method for determining the parent-child relationship between a pregnant woman and a fetus by calculating fetal concentration, the method comprising the following steps:

[0057] S101: Obtain DNA data S and F' of dimorphic sites of a pregnant woman's free DNA sample and a random paternal DNA sample.

[0058] S102: Obtain site sets X1 and X' in S that meet the following requirements,

[0059] X1={x i |0<na i (S) / n i (S)<0.2∪0<nA i (S) / n i (S)<0.2}

[0060] X'={x i |na i (S) / n i (S)≤0.2∩na i (F') / n i (F')≥0.9}∪{x i |nA i (S) / n i (S)≤0.2∩nA i (F') / n i (F')≥0.9}, where nA and na represent the observed values ​​of dimorphic sites A and a respectively, n=nA+na, k=na.

[0061] S103: Calculate the probability P of a certain site on the site sets X1 and X' respectively according to formula I,

[0062]

[0063] in, 0≤p≤0.5, 0<Pm<0.2.

[0064] S104: Calculate the cumulative probability h of all sites on the site set X1 or X' according to formula II. The cumulative probability h is calculated by taking values ​​at predetermined intervals. The value of p when h takes the maximum value is p max , the fetal concentration is 2p max ;

[0065]

[0066] S105: According to p2 (2p calculated by point set X' max ) and p1 (2p calculated from point set X1 max ) ratio to judge the parent-child relationship between the pregnant woman and the fetus, including:

[0067] S501: Calculate p2 / p1 to obtain B.

[0068] S502: Obtain judgment sets M(S1) and M(S2) respectively indicating that the pregnant woman and the fetus have a parent-child relationship and do not have a parent-child relationship.

[0069] S503: If B∈M(S1) and If And B∈M(S2), then the fetus in the sample to be tested has no parent-child relationship with the pregnant woman; if and The parent-child relationship between the pregnant woman and the fetus in the sample to be tested remains to be determined.

[0070] Among them, M(S1) and M(S2) are both constant sets, or B is calculated according to steps S101-S104 through simulated samples with clear parent-child relationship between pregnant women and fetuses (with parent-child relationship and without parent-child relationship), and then B is fitted by quantile regression, or B is calculated according to steps S101-S104 through measured samples with clear parent-child relationship between pregnant women and fetuses (with parent-child relationship and without parent-child relationship), and then B is fitted by quantile regression.

[0071] Specifically, when M(S1) and M(S2) are both constant sets, M(S1) = [0.4554839, 0.5831579], M(S2) = [0.7031317, 0.827112]. The constant set can be calculated by simulated samples or measured samples. When performing paternity testing, the constant set can be directly used without calculating M(S1) and M(S2) to improve the detection speed.

[0072] Specifically, a sample set S1 of free DNA of pregnant women with parent-child relationship is obtained by simulating samples or measuring samples, and then p1 and p2 are calculated according to steps S101-S104, and then p2 / p1 of each sample is calculated to obtain B, and B is fitted by quantile regression, and the quantile is Y, and the judgment set M(S1) is obtained. A sample set S2 of free DNA of pregnant women with no parent-child relationship is obtained by simulating samples or measuring samples, and then p1 and p2 are calculated according to steps S101-S104, and then p2 / p1 of each sample is calculated to obtain B, and B is fitted by quantile regression, and the quantile is Y, and the judgment set M(S2) is obtained. Among them, Y is 90%-97.5%, preferably 95%. Further, in calculating the judgment sets M(S1) and M(S2), it is best to obtain the judgment sets M(S1) and M(S2) respectively through simulated samples or measured samples.

[0073] Among them, the number of sites in sample set S1 and sample set S2 is as large as possible, and dimorphic sites related to paternity testing are included as much as possible. The number of samples in sample set S1 is greater than or equal to 60 (preferably 200), and the number of sites in each sample is greater than or equal to 2500. The number of samples in sample set S2 is greater than or equal to 60, and the number of sites in each sample is greater than or equal to 2500. More than 90% of the sites in sample S are included in the sites of sample set S1 or the sites of sample set S2.

[0074] The number of sites in sample S is greater than or equal to 1000.

[0075] More specifically, the judgment set M(S1) and the judgment set M(S2) obtained by simulating samples include:

[0076] S201: The paternal DNA sample F and the maternal DNA sample M are randomly generated according to the frequency of the Chinese population. The offspring Z is generated from F and M according to Mendel's law of inheritance. The concentration of offspring Z is mixed at intervals of 0.01 from 0 to 0.2. The offspring Z and the maternal M are mixed to obtain the simulated pregnant woman's free DNA sample S1. Ten samples are generated for each mixing ratio. The number of samples in sample set S1 is 200. The number of loci of each sample in sample set S1 is greater than 2500 and the dimorphic types include SNP and INDEL.

[0077] S202: Maternal M' and fetal Z' were randomly generated using the frequency of the Chinese population. The concentration of fetal Z' was mixed from 0 to 0.2 at intervals of 0.01. Maternal M' and fetal Z' were mixed to obtain simulated pregnant woman's free DNA sample S2. Ten samples were generated for each mixing ratio. The number of samples in sample set S2 was 200. The number of loci for each sample in sample set S2 was greater than 2500 and the dimorphic types included SNP and INDEL.

[0078] S203: Randomly generate the sire Fs according to the frequency of the Chinese population. The random sire used in the actual measurement and the calculation of the judgment set may be the same or different; in the actual calculation process, the random sire obtained in step S101 is different each time the calculation is performed.

[0079] S204: Using sample set S1 and Fs according to steps S101-S104 to calculate p1 and p2, then calculate p2 / p1 to get B, fit B by quantile regression with a quantile of 95%, and obtain judgment set M(S1); Using sample set S2 and Fs according to steps S101-S104 to calculate p1 and p2, then calculate p2 / p1 to get B, fit B by quantile regression with a quantile of 95%, and obtain judgment set M(S2).

[0080] Example 3 - Simulated sample mixing

[0081] Example 3 is to obtain the judgment sets M(S1) and M(S2) by simulating sample calculations, and the process is as follows:

[0082] 1. Generated the true father DNA sample F and the maternal DNA sample M randomly through the frequency of the Chinese population, and generated the offspring Z from F and M through Mendel's law of inheritance, and mixed the samples from 0-0.2 at intervals of 0.01. Mixed samples of offspring Z and maternal M can obtain simulated pregnant free DNA sample S1 (the fetus and pregnant woman have a parent-child relationship), and 10 samples were generated for each ratio, so the number of samples in the S sample set is 200. Each sample in the S sample set contains more than 1000 sites, and contains dimorphic types including SNP and INDEL.

[0083] 2. Generate random paternal F', maternal M' and fetal Z' using the same method as above. Mix samples at intervals of 0.01 from 0 to 0.2. Directly mix samples of fetal Z' and maternal M' to obtain simulated maternal free DNA sample S2 (the fetus and the pregnant woman have no parent-child relationship).

[0084] 3. A partial subset of polymorphic sites of the Chinese population is obtained as the detection site set X. This embodiment uses dimorphic SNP sites with a population frequency of 0.05-0.95.

[0085] 4. Obtain the polymorphism distribution of each site xi in the detection site set X of samples S1 and S2.

[0086] 5. Calculate the ratio of p2 / p1 and the corresponding judgment set M(S) according to steps S101-S104 of Example 1. With the calculated p1 as the X-axis and p2 as the Y-axis, a p1-p2 linear graph can be obtained. When the pregnant woman and the fetus have a parent-child relationship, p2 = 0.490384*p1, R 2 =0.9964, such as Figure 2 As shown in the figure (the other line in the figure is p2 = 0.5*p1). When the pregnant woman and the fetus have no parent-child relationship, we can get p2 = 0.75392*p1, R 2 =0.9981, such as Figure 3 As shown (the other line in the figure is p2=0.75*p1). Figure 4 Linear schematic diagrams of the two.

[0087] The p1 and p2 values ​​are fitted using quantile regression. When the fetal concentration is less than 0.2 and Y is 95%, the calculation results are as follows:

[0088] M(S1)=[0.4554839,0.5831579]; M(S2)=[0.7031317,0.827112].

[0089] Among them, the calculation process of the other line (theoretical value) p2=0.5*p1 and p2=0.75*p1 is as follows:

[0090] Conditions: Assume that the concentration of fetuses in pregnant women is p and the population frequency is 0.5, that is, A:a=1:1, AA:Aa:aa=1:2:1; the maternal genotype is AA.

[0091] Parent-child relationship:

[0092]

[0093]

[0094]

[0095] Non-parent-child relationship:

[0096]

[0097]

[0098]

[0099] Example 4 - Actual Sample Mixing

[0100] Example 4 is to calculate the judgment sets M(S1) and M(S2) based on a large number of measured samples, and the process is as follows:

[0101] 1. The polymorphic sites of maternal DNA sample M, random maternal DNA sample M', random paternal DNA sample F' and offspring DNA sample Z were obtained through experimental sequencing analysis.

[0102] 2. Mixing Z and M samples at the known ratio p in Example 3 can obtain a simulated pregnant woman's free DNA sample S (parent-child relationship); mixing Z and M' samples can obtain a pregnant woman's free DNA sample S' (non-parent-child relationship).

[0103] 3. Obtain the polymorphism distribution of each site xi in the detection site set X of samples S and S'.

[0104] 4. Calculate the ratio of p2 / p1 according to steps S101-S104 of Example 1.

[0105] 5. With the calculated p1 as the X-axis and p2 as the Y-axis, a p1-p2 linear graph can be obtained. When the mother and the fetus are in a parent-child relationship, p2 = 0.527636*p1, R 2 =0.9961, such as Figure 5 As shown in the figure (the other line in the figure is p2 = 0.5*p1). When the mother and the fetus are not parent-child relationship, p2 = 0.756347*p1, R 2 =0.9982, such as Figure 6 As shown (the other line in the figure is p2=0.75*p1). Figure 7 Linear schematic diagrams of the two.

[0106] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc. made within the spirit and principle of the present invention should be included in the protection scope of the present invention.

Claims

1. The method of judging the parent-child relationship between pregnant women and fetuses by calculating fetal concentration. It is characterized in that The method comprises the following steps: S101: obtaining DNA data S and F' of dimorphic sites of the pregnant woman's free DNA sample and the random paternal DNA sample; S102: Obtain site sets X1 and X' in S that meet the following requirements, X1={x i |0<na i (S) / n i (S)<0.2∪0<nA i (S) / n i (S)<0.2} X'={x i |na i (S) / n i (S)≤0.2∩na i (F') / n i (F')≥0.9}∪{x i |nA i (S) / n i (S)≤0.2∩nA i (F') / n i (F')≥0.9} Where nA and na represent the observed values ​​of dimorphic sites A and a, respectively, n = nA + na, k = na; S103: Calculate the probability P of a certain site on the site sets X1 and X' respectively according to formula I, in, S104: using the point sets X1 and X', respectively, the fetal concentrations p1 and p2 are calculated using the maximum likelihood method; S105: judging the parent-child relationship between the fetus and the pregnant woman according to the ratio of p2 to p1; Step S105 specifically includes: S501: Calculate p2 / p1 to obtain B; S502: Obtain judgment sets M(S1) and M(S2) respectively indicating that the pregnant woman and the fetus have a parent-child relationship and do not have a parent-child relationship; S503: If B∈M(S1) and If And B∈M(S2), then the fetus in the sample to be tested has no parent-child relationship with the pregnant woman; if and The parent-child relationship between the pregnant woman and the fetus in the sample to be tested is yet to be determined; Among them, M(S1) and M(S2) are both constant sets, or B is calculated according to steps S101-S104 using a simulated sample with a clear parent-child relationship between the pregnant woman and the fetus, and then B is fitted by quantile regression, or B is calculated according to steps S101-S104 using an actual measured sample with a clear parent-child relationship between the pregnant woman and the fetus, and then B is fitted by quantile regression.

2. The method for determining the parent-child relationship between a pregnant woman and her fetus by calculating the fetal concentration according to claim 1, It is characterized in that When M(S1) and M(S2) are both constant sets, M(S1)=[0.4554839, 0.5831579], M(S2)=[0.7031317, 0.827112].

3. The method for determining the parent-child relationship between a pregnant woman and her fetus by calculating the fetal concentration according to claim 1, It is characterized in that A sample set S1 of free DNA of pregnant women with parent-child relationship between the pregnant women and the fetus is obtained by simulating samples or measuring samples, and then p1 and p2 are calculated according to steps S101-S104, and then p2 / p1 of each sample is calculated to obtain B, and B is fitted by quantile regression, with quantile Y, to obtain a judgment set M(S1); A sample set S2 of free DNA of pregnant women with no parent-child relationship between the pregnant women and the fetus is obtained by simulating samples or measuring samples, and then p1 and p2 are calculated according to steps S101-S104, and then p2 / p1 of each sample is calculated to obtain B, and B is fitted by quantile regression, with the quantile being Y, to obtain a judgment set M(S2); The Y is 90%-97.5%.

4. The method for determining the parent-child relationship between a pregnant woman and her fetus by calculating the fetal concentration according to claim 3, It is characterized in that The Y is 95%.

5. The method for determining the parent-child relationship between a pregnant woman and her fetus by calculating the fetal concentration according to claim 3, It is characterized in that The number of samples in the sample set S1 is greater than or equal to 60, and the number of sites in each sample is greater than or equal to 2500; the number of samples in the sample set S2 is greater than or equal to 60, and the number of sites in each sample is greater than or equal to 2500; more than 90% of the sites in sample S are included in the sites of sample set S1 or the sites of sample set S2.

6. The method for determining the parent-child relationship between a pregnant woman and her fetus by calculating the fetal concentration according to claim 5, It is characterized in that The number of sites of the sample S is greater than or equal to 1000.

7. The method for determining the parent-child relationship between a pregnant woman and her fetus by calculating the fetal concentration according to claim 3, It is characterized in that The judgment set M(S1) and judgment set M(S2) obtained by simulating samples include: S201: Generate paternal DNA sample F and maternal DNA sample M randomly through the frequency of Chinese population, generate offspring Z from F and M through Mendel's law of inheritance, mix the concentration of offspring Z from 0 to 0.2 at intervals of 0.01, mix offspring Z and maternal M to obtain simulated pregnant woman free DNA sample S1, generate 10 samples for each mixing ratio, the number of loci of each sample in sample set S1 is greater than 2500 and the dimorphic types include SNP and INDEL; S202: Maternal M' and fetal Z' were randomly generated by the frequency of the Chinese population. The concentration of fetal Z' was mixed from 0 to 0.2 at intervals of 0.

01. Maternal M' and fetal Z' were mixed to obtain simulated pregnant women's free DNA sample S2. Ten samples were generated for each ratio. The number of loci of each sample in sample set S2 was greater than 2500 and the dimorphic types included SNP and INDEL. S203: Randomly generate paternal Fs using Chinese population frequency; S204: Using sample set S1 and Fs according to steps S101-S104 to calculate p1 and p2, then calculate p2 / p1 to get B, fit B by quantile regression with a quantile of 95%, and obtain judgment set M(S1); Using sample set S2 and Fs according to steps S101-S104 to calculate p1 and p2, then calculate p2 / p1 to get B, fit B by quantile regression with a quantile of 95%, and obtain judgment set M(S2).

8. The method for determining the parent-child relationship between a pregnant woman and her fetus by calculating the fetal concentration according to claim 1, It is characterized in that The dimorphic site is a SNP site, the population frequency of the dimorphic site is 0.05-0.95, the A represents a wild-type site, and a represents a mutant site.

9. The method for determining the parent-child relationship between a pregnant woman and her fetus by calculating the fetal concentration according to claim 1, It is characterized in that Step S104 includes: calculating the cumulative probability h of all sites on locus set X1 or X' according to Formula II, taking values of p at a predetermined interval to calculate the cumulative probability h, and the p value when h takes the maximum value is p max , and the fetal concentration is 2p max ;

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