Method and device for determining kinship based on non-invasive prenatal genetic testing data

Abstract

A method and device for determining kinship based on non-invasive prenatal genetic testing data, the method comprising: comparing the whole genome sequencing data of the child to be tested to the non-invasive prenatal genetic testing sequencing database of the mother; extracting the credible base sets of each potential mother and the child to be tested at the specified site set respectively; calculating the genetic similarity between the child to be tested and each potential mother based on the credible base set; calculating the kinship probability between the child to be tested and each potential mother according to the genetic similarity to form a kinship probability matrix; determining the exact kinship between the child to be tested and the potential mother according to the kinship probability matrix. By comparing the non-invasive prenatal genetic testing data set with the gene sequence obtained by the child's whole genome sequencing, the kinship information in the non-invasive prenatal genetic testing data is mined.

Description

Technical Field

[0001] The present invention relates to the technical field of paternity identification, and in particular to a method and device for determining kinship based on non-invasive prenatal genetic testing data. Background Art

[0002] At present, judicial parentage determination is mainly used in two scenarios: one is paternity testing, and the other is the recovery of lost children. The methods used in these two applications are the same, mainly through the short tandem repeat (STR) typing method to determine the parent-child relationship.

[0003] Specifically, the STR typing method first detects 13 or more specific autosomal STR loci. If necessary, it is necessary to continue to detect the loci of the Y chromosome, X chromosome, and mitochondrial DNA, and then calculate the cumulative paternity index (CPI) to finally obtain the test conclusion. Although STR is widely used in paternity testing, this method has defects in practical application. First, the high mutation rate of STR in the genetic process can easily lead to situations where the parent-child relationship cannot be determined or the parent-child relationship is misjudged. Secondly, for highly degraded samples, the STR test based on capillary electrophoresis may not be able to obtain complete typing results for all loci. Even if the miniSTR kit is used in conjunction, the sample DNA length is required to be more than 150bp. Finally, the STR typing method is often limited to the paternity testing of doublets or triplets, and is not suitable for finding corresponding paternity relationships in the population.

[0004] The determination of kinship among people is the most important aspect in finding lost children back to their families, but the number and scope of people included in the STR database of judicial authorities are currently limited. For families that have not yet entered STR data into judicial authorities, if a child is lost, even if he or she is eventually found by the public security authorities, the lack of data will make it impossible to find the child's family.

[0005] In addition to the short tandem repeat method, a new identification technology that uses the second-generation high-throughput sequencing technology (NGS) to detect single-base polymorphism (SNP) sites in samples and then compares them to derive parent-child relationships is also booming. Although this aspect is more comprehensive, due to the high cost of this method, it has not been widely promoted, so its original data accumulation is seriously insufficient and it is difficult to play a role in parent-child tracing.

[0006] At present, noninvasive prenatal testing (NIPT) is becoming more and more mature in clinical practice and is being promoted more and more widely in major cities and regions across the country. NIPT technology, also known as NIPS (noninvasive prenatal screening), is a method for detecting the possibility of a fetus suffering from a genetic disease. This technology extracts free DNA from the peripheral blood of pregnant women, uses high-throughput sequencing technology and combines bioinformatics analysis to detect whether the fetus has chromosomal aneuploidy. At present, more than nine million pregnant women in my country have undergone this test, covering a wide range of people and is still growing. This data contains DNA information of both the mother and a small amount of the fetus. In principle, it will be possible to assist judicial authorities in finding families for lost children based on such data. In addition, this data has two obvious advantages. First, the population is accurate. The people who undergo this test are pregnant mothers and families who are about to have children. Such data will play a greater role in finding lost children than other unrelated groups; second, the test data is still growing sustainably across the country, which will lay a continuous data foundation for its application in finding families for lost children. However, there is no clear method on how to apply this data in this regard.

[0007] Whole genome sequencing (WGS) is the use of a high-throughput sequencing platform to sequence all genes in the genome of an individual organism and determine the base sequence of its DNA. This technology can be used to detect multiple mutation information such as single nucleotide variation (SNV), insertion and deletion (InDel), copy number variation (CNV) and structural variation (SV) at the whole genome level. Summary of the invention

[0008] The purpose of the present invention is to provide a method and device for determining kinship based on non-invasive prenatal genetic testing (NIPT) data. By comparing the NIPT data set with the gene sequence obtained by the whole genome sequencing of the child, the kinship information in the NIPT data is fully mined to achieve the purpose of efficiently determining kinship in the NIPT test population.

[0009] According to a first aspect of the present invention, the present invention provides a method for determining kinship based on non-invasive prenatal genetic testing data, comprising:

[0010] Compare the whole genome sequencing data of the child to be tested to the non-invasive prenatal genetic testing sequencing database of the mother, which contains the genetic sequencing data of multiple potential mothers;

[0011] Extract the reliable base sets at the specified site sets for each potential mother and child to be tested respectively;

[0012] Calculate the genetic similarity between the child to be tested and each potential mother based on the above-mentioned reliable base set;

[0013] The probability of kinship between the child to be tested and each potential mother is calculated based on the above genetic similarity to form a kinship probability matrix;

[0014] Based on the above-mentioned kinship probability matrix, the exact kinship relationship between the child to be examined and the potential mother is determined.

[0015] In a preferred embodiment, the sequencing depth of the above whole genome sequencing data is 3X.

[0016] In a preferred embodiment, the sequencing depth of the gene sequencing data of the mother is 0.08X.

[0017] In a preferred embodiment, the above-mentioned designated site set includes two-base polymorphic sites with base pair quality values ​​higher than a first preset value, base quality values ​​higher than a second preset value, and located in a gene polymorphism database.

[0018] In a preferred embodiment, the first preset value is 30, the second preset value is 20, and the gene polymorphism database is a gene polymorphism database of millions of Chinese people.

[0019] In a preferred embodiment, the above-mentioned reliable base set includes multiple reliable bases on a specified site set, and the above-mentioned reliable bases are bases with the longest sequencing read length covering the specified site.

[0020] In a preferred embodiment, the above genetic similarity is calculated by the following formula:

[0021]

[0022] Where n represents the total number of dibasic polymorphic sites, i represents the number of the child to be tested, j represents the number of the mother in the non-invasive prenatal genetic testing sequencing database, and d s Indicates the genetic distance of the site, PE s represents the exclusion probability when the mother and daughter bases are different at the dinucleotide polymorphic site s, p s Represents the frequency of one of the two genotypes of the dinucleotide polymorphism site s in the population.

[0023] In the above formula, "same" means that the bases of child i and the j-th mother at site s are the same, "different" means that the bases of child i and the j-th mother at site s are different, and "no coverage" means that no sequence information is measured at site s in the sequencing data of child i and the j-th mother.

[0024] In a preferred embodiment, the above kinship probability is calculated by the following formula:

[0025]

[0026] Among them, p represents the probability of the child being related to the mother, g mean is the mean of the genetic similarity between the child and all potential mothers, std is the standard deviation of the genetic similarity between the child and all potential mothers, N(0,1) refers to the standard normal distribution with a mean of 0 and a standard deviation of 1, and Z g Represents the value after genetic similarity standardization, N(0,1).cdf(Z g ) represents Z g Probability value obtained on the standard normal distribution.

[0027] In a preferred embodiment, the above method further comprises:

[0028] The mother samples with low mother-child relationship specificity in the above-mentioned kinship probability matrix are removed from the above-mentioned kinship probability matrix to obtain an adjusted kinship probability matrix, and then the adjusted kinship probability matrix is ​​used to determine the exact kinship relationship between the child to be tested and the potential mother, wherein the above-mentioned low mother-child relationship specificity means that the genetic similarity between the above-mentioned mother sample and all the children to be tested is higher than the similarity threshold.

[0029] In a preferred embodiment, the similarity threshold is greater than 0.9.

[0030] In a preferred embodiment, the above-mentioned determination of the exact kinship relationship between the child to be examined and the potential mother using the adjusted kinship probability matrix includes: determining the mother-child combination with a kinship probability greater than a kinship probability threshold as having a kinship relationship.

[0031] In a preferred embodiment, the above-mentioned kinship probability threshold is above 0.99.

[0032] According to a second aspect of the present invention, the present invention provides a kinship determination device based on non-invasive prenatal genetic testing data, comprising:

[0033] A data acquisition unit, used to compare the whole genome sequencing data of the child to be tested to the non-invasive prenatal genetic testing sequencing database of the mother, wherein the above database contains the genetic sequencing data of multiple potential mothers;

[0034] A reliable base extraction unit, used for respectively extracting a reliable base set at a specified site set for each potential mother and child to be tested;

[0035] A genetic similarity calculation unit, used for calculating the genetic similarity between the child to be tested and each potential mother based on the above-mentioned reliable base set;

[0036] A kinship probability calculation unit is used to calculate the kinship probability between the child to be tested and each potential mother according to the above genetic similarity to form a kinship probability matrix;

[0037] The kinship determination unit is used to determine the exact kinship between the child to be tested and the potential mother according to the above kinship probability matrix.

[0038] According to a third aspect of the present invention, the present invention provides a computer-readable storage medium, which includes a program, and the program can be executed by a processor to implement the method as described in the first aspect.

[0039] The kinship determination method of the present invention fully mines the kinship information in the NIPT data by comparing the NIPT data set with the gene sequence obtained by the whole genome sequencing of the child, helps missing children find their relatives, and assists in solving the current problem that lost children cannot locate their families after being found by the public security organs. The present invention expands the value of NIPT data in the judicial field. BRIEF DESCRIPTION OF THE DRAWINGS

[0040] Figure 1 This is a flow chart of a method for determining kinship based on non-invasive prenatal genetic testing data in an embodiment of the present invention;

[0041] Figure 2 is an exemplary flow chart of a method for determining kinship based on non-invasive prenatal genetic testing data in an embodiment of the present invention;

[0042] Figure 3 This is a structural block diagram of a kinship determination device based on non-invasive prenatal genetic testing data in an embodiment of the present invention;

[0043] Figure 4 A result diagram of a kinship probability matrix calculated in one embodiment of the present invention;

[0044] Figure 5 A result diagram of a kinship probability matrix calculated in another embodiment of the present invention;

[0045] Figure 6 This is a diagram of the kinship probability matrix result obtained by adjustment in another embodiment of the present invention. DETAILED DESCRIPTION

[0046] The present invention is further described in detail below by specific embodiments in conjunction with the accompanying drawings. In the following embodiments, many details are described to enable the present invention to be better understood. However, those skilled in the art can easily recognize that some of the features can be omitted in different situations, or can be replaced by other materials or methods.

[0047] In addition, the features, operations or characteristics described in the specification can be combined in any appropriate manner to form various implementations. At the same time, the steps or actions in the method description can also be interchanged or adjusted in a manner that is obvious to those skilled in the art. Therefore, the various sequences in the specification and the drawings are only for the purpose of clearly describing a certain embodiment and are not meant to be a required sequence, unless otherwise specified that a certain sequence must be followed.

[0048] like Figure 1 As shown, the embodiment of the present invention provides a method for determining kinship based on non-invasive prenatal genetic testing data, comprising the following steps:

[0049] S110: The whole genome sequencing data of the child to be tested is compared to the mother's non-invasive prenatal genetic testing sequencing database, which contains the genetic sequencing data of multiple potential mothers.

[0050] The kinship determination method of the present invention utilizes non-invasive prenatal genetic testing (NIPT) data, with the help of the existing maternal NIPT database, and compares it with the gene sequence obtained by the child's whole genome sequencing (WGS), so as to fully mine the kinship information in the NIPT data and determine the kinship between the NIPT data and the lost child (i.e., the child to be tested), thereby narrowing the scope of kinship screening and assisting judicial authorities in helping lost children complete kinship search.

[0051] The kinship determination method of the present invention can utilize NIPT data with ultra-low sequencing depth (for example, the sequencing depth can be as low as 0.08X) and whole genome sequencing (WGS) data (sequencing depth can be as low as 3X) to perform kinship determination.

[0052] In the embodiment of the present invention, the non-invasive prenatal genetic testing sequencing database for mothers contains genetic sequencing data of multiple potential mothers. Potential mothers are women who have undergone non-invasive prenatal genetic testing during pregnancy and whose sequencing data are stored in the database.

[0053] like Figure 2 As shown, the child's 3X whole genome sequencing data can obtain a comparison file of the mother's NIPT data and the child's whole genome sequencing data through data quality control (for example, filtering using SOAPnuke software) and comparison (for example, comparison using BWA, Edico and other software).

[0054] S120: extracting the reliable base sets at the designated site sets for each potential mother and child to be tested respectively.

[0055] In an embodiment of the present invention, the designated site set includes a base pair quality value higher than a first preset value, a base quality value higher than a second preset value, and a di-base polymorphic site located in a gene polymorphism database. For example, in one embodiment of the present invention, the designated site set includes a base pair quality value higher than 30, a base quality value higher than 20, and a di-base polymorphic site located in a million Chinese gene polymorphism database (CMDB).

[0056] In an embodiment of the present invention, a set of designated sites is extracted according to the above-mentioned standards, and then highly reliable bases of each site are extracted to form a reliable base set (called Germbase). In one embodiment of the present invention, a reliable base set is extracted according to the number of sequencing reads covering the designated site. In detail, the number of sequencing reads covered by different bases at the designated site is sorted, and the base with the most sequencing reads is the most reliable. However, if the base covered by the sequencing reads has ALT (non-reference base, i.e., a base that is mutated and different from the reference sequence base), and the number of sequencing reads of the ALT is greater than 3, it is recorded as ALT. If there are multiple ALTs, the one with the most sequencing reads shall prevail.

[0057] like Figure 2 As shown, through this step, the credible base set of the child to be tested on the specified site set (child Germbase in the figure) and the credible base set of the mother in the NIPT database on the specified site set (mother Germbase database in the figure) are obtained respectively.

[0058] S130: Calculate the genetic similarity between the child to be tested and each potential mother based on the reliable base set.

[0059] In the method of the present invention, the mother-child genetic similarity and its calculation method are defined to quantitatively describe the genetic relationship between each potential mother and the child to be tested. The genetic similarity between the child and all mothers in the database is calculated and then converted into genetic probability, and finally the most likely genetic relationship is determined.

[0060] According to the laws of inheritance, any base site that differs between a mother and her child mainly comes from random mutations in the child's genome or non-kinship. According to the Hardy-Weinberg law, it can be inferred that for any two-base polymorphic site i, assuming there are two genotypes A and a, the frequencies of genotypes A and a in the population are p and q, respectively, where q = 1-p. If the mother and child bases at the two-base polymorphic site i are different, then the exclusion probability is:

[0061] In the calculation of genetic similarity, it is necessary to calculate the cumulative exclusion probability of all sites, so as to finally obtain the genetic similarity between the child and each mother in the database.

[0062] In one embodiment of the present invention, the genetic similarity is calculated by the following formula:

[0063]

[0064] Where n represents the total number of dibasic polymorphic sites, i represents the number of the child to be tested, j represents the number of the mother in the non-invasive prenatal genetic testing sequencing database, and d s Indicates the genetic distance of the site, PE s represents the exclusion probability when the mother and daughter bases are different at the dinucleotide polymorphic site s, p s Represents the frequency of one of the two genotypes of the dinucleotide polymorphism site s in the population.

[0065] S140: Calculate the probability of kinship between the child to be tested and each potential mother based on the genetic similarity to form a kinship probability matrix.

[0066] In one embodiment of the present invention, the kinship probability is calculated by the following formula:

[0067]

[0068] Among them, p represents the probability of the child being related to the mother, g mean is the mean of the genetic similarity between the child and all potential mothers, std is the standard deviation of the genetic similarity between the child and all potential mothers, N(0,1) refers to the standard normal distribution with a mean of 0 and a standard deviation of 1, and Z g Represents the value after genetic similarity standardization, N(0,1).cdf(Z g ) represents Z g The probability value obtained on the standard normal distribution is defined as the "kinship probability" in the present invention.

[0069] After calculation, each child will get a set of kinship probability data to describe the probability of the child coming from a certain mother. By calculating the kinship probabilities between multiple children to be tested and multiple potential mothers, a kinship probability matrix can be formed, which contains the kinship probability data of each child to be tested and each potential mother.

[0070] In some embodiments, there are mother samples with low specificity of mother-child relationship (MC) in the kinship probability matrix, and the genetic similarity of these samples with all the children to be tested is very close, for example, the genetic similarity with all the children to be tested is higher than the similarity threshold (for example, above 0.9). These samples have little effect on kinship judgment. Therefore, in one embodiment of the present invention, the method of the present invention also includes the following steps:

[0071] The mother samples with low specificity of mother-child relationship in the kinship probability matrix are removed from the kinship probability matrix to obtain an adjusted kinship probability matrix, and then the adjusted kinship probability matrix is ​​used to determine the exact kinship relationship between the child to be tested and the potential mother.

[0072] S150: Determine the exact kinship relationship between the child to be examined and the potential mother based on the kinship probability matrix.

[0073] In the present invention, in the absence of a mother sample with low specificity of the mother-child relationship, the kinship probability matrix calculated in the previous step can be directly used to determine the exact kinship relationship between the child to be tested and the potential mother. In the presence of a mother sample with low specificity of the mother-child relationship, the adjusted kinship probability matrix is ​​used to determine the exact kinship relationship between the child to be tested and the potential mother. Specifically, in one embodiment of the present invention, a mother-child combination with a kinship probability greater than a kinship probability threshold (e.g., greater than 0.99) is determined to have a kinship relationship.

[0074] For example, in one embodiment of the present invention, the NIPT data with low MC specificity in the affinity probability matrix are moved to the candidate matrix, and then the MC combinations greater than 0.99 in the remaining affinity probability matrix are determined as combinations with affinity. If no valid affinity can be determined in these samples at this time, the NIPT sample data in the candidate matrix is ​​further used to retest the abnormal NIPT samples and rematch them.

[0075] The method for determining the relationship of the present invention is more conducive to regional scale promotion compared with the traditional method based on tandem repeat sequences (STR) and SNP method, and NIPT detection has gradually become a clinical pregnancy screening project, with a growing user base, and is also a deep application of NIPT data that was originally considered to have little secondary application value. In addition, the method for determining the relationship of the present invention does not require the mother to sample again, saving costs. The rapid expansion of the NIPT product market contributes to the accumulation of data volume, which is beneficial to the further promotion of this application, and with the accumulation of data volume, the utilization value of the method for determining the relationship of the present invention is more important.

[0076] Corresponding to the kinship determination method of the present invention, an embodiment of the present invention also provides a kinship determination device based on non-invasive prenatal genetic testing data, such as Figure 3 As shown, it includes: a data acquisition unit 310, which is used to compare the whole genome sequencing data of the child to be tested to the mother's non-invasive prenatal genetic testing sequencing database, and the database contains the genetic sequencing data of multiple potential mothers; a reliable base extraction unit 320, which is used to extract the reliable base sets of each potential mother and the child to be tested on the specified site set respectively; a genetic similarity calculation unit 330, which is used to calculate the genetic similarity between the child to be tested and each potential mother based on the reliable base set; a kinship probability calculation unit 340, which is used to calculate the kinship probability between the child to be tested and each potential mother according to the genetic similarity, and form a kinship probability matrix; a kinship determination unit 350, which is used to determine the exact kinship between the child to be tested and the potential mother according to the kinship probability matrix.

[0077] Those skilled in the art will appreciate that all or part of the functions of the various methods in the above-mentioned embodiments can be implemented by hardware or by computer programs. When all or part of the functions in the above-mentioned embodiments are implemented by computer programs, the program can be stored in a computer-readable storage medium, and the storage medium can include: read-only memory, random access memory, disk, optical disk, hard disk, etc., and the program is executed by a computer to implement the above-mentioned functions. For example, the program is stored in the memory of the device, and when the program in the memory is executed by the processor, all or part of the above-mentioned functions can be implemented. In addition, when all or part of the functions in the above-mentioned embodiments are implemented by computer programs, the program can also be stored in a storage medium such as a server, another computer, disk, optical disk, flash disk or mobile hard disk, and can be downloaded or copied and saved in the memory of the local device, or the system of the local device is updated, and when the program in the memory is executed by the processor, all or part of the functions in the above-mentioned embodiments can be implemented.

[0078] Therefore, in one embodiment of the present invention, a computer-readable storage medium is provided, including a program, which can be executed by a processor to implement the method of determining kinship based on non-invasive prenatal genetic testing data of the present invention.

[0079] The technical solutions and effects of the present invention are described in detail below through examples. It should be understood that the examples are merely illustrative and cannot be construed as limiting the present invention.

[0080] In the following examples, two rounds of testing were carried out on 15 families and 15 children - 1000 NIFTY data.

[0081] Embodiment 1:

[0082] The samples of this family were randomly selected from the NIFTY (non-invasive prenatal genetic testing for fetal chromosomal abnormalities) data of the normal mother and the WGS sequencing data of the child after birth.

[0083] (1) First, the comparison file of each mother's NIFTY data was truncated to a depth of about 0.08X, and the child's WGS data was truncated to a depth of about 3X to simulate the usage scenario.

[0084] (2)Germbase extraction

[0085] First, extract high-quality sites. Select those sites with alignment quality values ​​higher than 30, base quality values ​​higher than 20, and base information located at CMDB dinucleotide polymorphic sites.

[0086] Then, extract the highly reliable base set for each site of the sample, i.e., the Germbase file, and determine the most reliable base for the site based on the bases corresponding to the sequencing reads at each site.

[0087] (3) Mother-child (MC) matching: Calculate the genetic similarity between mother and child at the CMDB dimorphic loci, and then further calculate the kinship probability matrix based on the genetic similarity matrix formed by the genetic similarity of the Germbase files between MCs.

[0088] (4) Determine the kinship relationship based on the kinship probability matrix. Figure 4 As shown in the figure, m1-m15 represents the mother's NIPT data, c1-c15 represents the child's WGS data, and the pedigrees correspond to the numerical numbers one by one. The test results show that the kinship determination of the 15 pedigrees is all correct, which is in line with expectations.

[0089] Example 2

[0090] This example expands the sample range, and the samples are randomly selected from the NIFTY data of 1000 normal mothers and the WGS data of the mothers and children of the 15 families in Example 1.

[0091] (1) First, the comparison file of each mother's NIFTY data was truncated to a depth of about 0.08X, and the child's WGS data was truncated to 3X to suit the usage scenario.

[0092] (2)Germbase extraction

[0093] First, extract high-quality sites. Select those sites with alignment quality values ​​higher than 30, base quality values ​​higher than 20, and base information located at CMDB dinucleotide polymorphic sites.

[0094] Then, extract the highly reliable base set for each site of the sample, i.e., the Germbase file, and determine the most reliable base for the site based on the bases corresponding to the sequencing reads at each site.

[0095] (3) Mother-child (MC) matching: Calculate the genetic similarity between mother and child at the CMDB dimorphic loci, and then further calculate the kinship probability matrix based on the genetic similarity matrix formed by the genetic similarity of the Germbase files between MCs.

[0096] (4) Determine the kinship relationship based on the kinship probability matrix. Figure 5 As shown in the figure, the preliminary kinship probability matrix shows that the probability of kinship determination of 15 families is obviously the highest, and all the determinations are correct. However, some samples among the 1,000 people have low specificity, such as sample 810, whose genetic similarity with all children's samples is higher than 0.9. After removing such samples from the alternative database, the one-to-one correspondence between m1-15 and c1-c15 can still be correctly determined using the remaining database. Figure 6 Some representative results are shown.

[0097] The above specific examples are used to illustrate the present invention, which is only used to help understand the present invention and is not intended to limit the present invention. For those skilled in the art, according to the concept of the present invention, some simple deductions, modifications or substitutions can be made.

Claims

1. A method for determining kinship based on non-invasive prenatal genetic testing data, characterized in that: The method comprises: Comparing the whole genome sequencing data of the child to be tested to the non-invasive prenatal genetic testing sequencing database of the mother, wherein the database contains the genetic sequencing data of multiple potential mothers; Extract the credible base sets of each potential mother and child to be tested at the designated site set respectively; the designated site set includes two-base polymorphic sites with base pair quality values ​​higher than 30, base quality values ​​higher than 20, and located in the million Chinese genetic polymorphism database; The genetic similarity between the child to be tested and each potential mother is calculated based on the credible base set; the credible base set includes multiple credible bases on a specified site set, and the credible base is the base with the longest sequencing read length covering the specified site; the genetic similarity is calculated by the following formula: in, n represents the total number of dinucleotide polymorphic sites, i Indicates the number of the child to be examined, j represents the mother's number in the non-invasive prenatal genetic testing sequencing database, d s represents the genetic distance of the locus, PE s Denotes a dinucleotide polymorphic site s The exclusion probability when the mother and daughter bases are different, p s Denotes a dinucleotide polymorphic site s The frequency of one of the two genotypes in the population, in the above formula, " d s =1" means children i and j Mothers at the site s The bases on the d s =1- PE s " means children i and j Mothers at the site s The bases on the d s = ━" means children i and j There is no locus in the sequencing data of the mother s No sequence information was detected; The probability of kinship between the child to be tested and each potential mother is calculated based on the genetic similarity to form a kinship probability matrix; the kinship probability is calculated using the following formula: in, p represents the probability of the child being related to the mother, g mean is the mean genetic similarity of the child to all potential mothers, std is the standard deviation of the genetic similarity between the child and all potential mothers, N(0,1) refers to the standard normal distribution with mean 0 and standard deviation 1, Z g represents the value after genetic similarity is standardized. express Z g Probability values ​​obtained on the standard normal distribution; According to the kinship probability matrix, the exact kinship relationship between the child to be tested and the potential mother is determined; the mother sample with low mother-child relationship specificity in the kinship probability matrix is ​​removed from the kinship probability matrix to obtain an adjusted kinship probability matrix, wherein the low mother-child relationship specificity means that the genetic similarity between the mother sample and all the children to be tested is higher than 0.9; and the adjusted kinship probability matrix is ​​used to determine the exact kinship relationship between the child to be tested and the potential mother, and the mother-child combination with a kinship probability greater than 0.99 is determined to have a kinship relationship.

2. The method for determining kinship according to claim 1, characterized in that: The sequencing depth of the whole genome sequencing data is 3X.

3. The method for determining kinship according to claim 1, characterized in that: The sequencing depth of the mother's gene sequencing data is 0.08X.

4. A kinship determination device based on non-invasive prenatal genetic testing data, characterized in that: The device comprises: A data acquisition unit, used to compare the whole genome sequencing data of the child to be tested to the non-invasive prenatal genetic testing sequencing database of the mother, wherein the database contains the genetic sequencing data of multiple potential mothers; A credible base extraction unit, used to extract credible base sets of each potential mother and child to be tested at a designated site set; the designated site set includes two-base polymorphic sites with a base pair quality value higher than 30, a base quality value higher than 20, and located in the million Chinese gene polymorphism database; A genetic similarity calculation unit is used to calculate the genetic similarity between the child to be tested and each potential mother based on the credible base set; the credible base set includes multiple credible bases on a specified site set, and the credible base is the base with the longest sequencing read length covering the specified site; the genetic similarity is calculated by the following formula: in, n represents the total number of dinucleotide polymorphic sites, i Indicates the number of the child to be examined, j represents the mother's number in the non-invasive prenatal genetic testing sequencing database, d s represents the genetic distance of the locus, PE s Denotes a dinucleotide polymorphic site s The exclusion probability when the mother and daughter bases are different, p s Denotes a dinucleotide polymorphic site s The frequency of one of the two genotypes in the population, in the above formula, " d s =1" means children i and j Mothers at the site s The bases on the d s =1- PE s " means children i and j Mothers at the site s The bases on the d s = ━" means children i and j There is no locus in the sequencing data of the mother s No sequence information was detected; A kinship probability calculation unit is used to calculate the kinship probability between the child to be tested and each potential mother according to the genetic similarity to form a kinship probability matrix; the kinship probability is calculated by the following formula: in, p represents the probability of the child being related to the mother, g mean is the mean genetic similarity of the child to all potential mothers, std is the standard deviation of the genetic similarity between the child and all potential mothers, N(0,1) refers to the standard normal distribution with mean 0 and standard deviation 1, Z g represents the value after genetic similarity is standardized. express Z g Probability values ​​obtained on the standard normal distribution; A kinship determination unit is used to determine the exact kinship relationship between the child to be tested and the potential mother according to the kinship probability matrix, which includes removing the mother sample with low mother-child relationship specificity in the kinship probability matrix from the kinship probability matrix to obtain an adjusted kinship probability matrix, wherein the low mother-child relationship specificity means that the genetic similarity between the mother sample and all the children to be tested is higher than 0.9; and then using the adjusted kinship probability matrix to determine the exact kinship relationship between the child to be tested and the potential mother, and determining the mother-child combination with a kinship probability greater than 0.99 as having a kinship relationship.

5. A computer-readable storage medium comprising a program, wherein the program can be executed by a processor to implement the method according to any one of claims 1 to 3.

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