阅读说明：本技术 一种基于遗传疾病致病基因的分析系统及其应用 (Analysis system based on genetic disease pathogenic gene and application thereof ) 是由 吴皓 陈晓禾 李凤美 杨涛 郭宇 洪凯程 罗晓梅 于 2020-07-07 设计创作，主要内容包括：本发明提供一种基于遗传疾病致病基因的分析系统,至少包括以下模块：位点突变分类模块,用于将遗传疾病的致病基因内位点的突变结果进行分类,未发生突变的位点为0,杂合突变或异质突变的位点的为1,纯合突变或均质突变的位点的为2；突变值获得模块,用于获得致病基因的突变值；结果判断模块,用于根据致病基因的突变值判断该致病基因突变状态和/或致病性；报告单生成模块,用于根据致病基因突变状态和/或致病性,得到匹配的诊断结论,疾病风险评估与遗传咨询建议,并生成受检者的基因筛查分析报告单。本发明可以对正常表型的突变携带者本人进行风险评估,规避后天的损伤因素,同时评估其后代的致病风险,提供婚育指导和遗传咨询建议。(The invention provides an analysis system based on a genetic disease pathogenic gene, which at least comprises the following modules: the site mutation classification module is used for classifying the mutation results of internal sites of pathogenic genes of genetic diseases, wherein the sites which do not have mutation are 0, the sites which have heterozygous mutation or heterogeneous mutation are 1, and the sites which have homozygous mutation or homogeneous mutation are 2; a mutation value obtaining module for obtaining a mutation value of a pathogenic gene; the result judging module is used for judging the mutation state and/or pathogenicity of the pathogenic gene according to the mutation value of the pathogenic gene; and the report generation module is used for obtaining a matched diagnosis conclusion, a disease risk assessment and genetic counseling suggestion and generating a gene screening analysis report of the examined person according to the mutation state and/or pathogenicity of the pathogenic gene. The invention can carry out risk assessment on the normal phenotype mutation carriers, avoid the acquired damage factors, simultaneously assess the pathogenic risk of offspring, and provide marriage and childbirth guidance and genetic counseling suggestions.)

1. An analysis system based on a genetic disease causing gene, the system comprising at least the following modules:

the site mutation classification module is used for classifying the mutation results of internal sites of pathogenic genes of genetic diseases, wherein the sites which do not have mutation are 0, the sites which have heterozygous mutation or heterogeneous mutation are 1, and the sites which have homozygous mutation or homogeneous mutation are 2;

a mutation value obtaining module for obtaining a mutation value of a pathogenic gene;

and the result judging module is used for judging the mutation state and/or pathogenicity of the pathogenic gene according to the mutation value of the pathogenic gene: when the mutation value of the pathogenic gene is 0, the mutation type of the pathogenic gene is non-mutated, which indicates that the subject does not carry the gene mutation of the pathogenic gene or does not suffer from the related genetic disease, and when the mutation value of the pathogenic gene is greater than 0, the mutation type of the pathogenic gene is mutated, which indicates that the subject is a carrier of the gene mutation of the related genetic disease or a patient of the related genetic disease.

2. The genetic disease virulence gene-based analysis system of claim 1, further comprising one or more of the following characteristics:

1) the genetic disease is selected from one or more of hereditary deafness, hereditary hypothyroidism, alpha-thalassemia, beta-thalassemia or spinal muscular atrophy;

2) the system also comprises a data acquisition module, a site mutation classification module and a site mutation classification module, wherein the data acquisition module is used for reading the gene detection result of the detected person, extracting information of the gene detection result and uploading pathogenic gene data of the genetic disease of the detected person to the site mutation classification module, and the pathogenic gene data of the genetic disease of the detected person at least comprises the gene names and the site names of all positive mutations of the genetic disease of the detected person and mutation result data of sites in the pathogenic gene of the genetic disease;

3) the system also comprises a report generation module which is used for obtaining matched diagnosis conclusion, disease risk assessment and genetic consultation suggestion and generating a gene screening analysis report of the detected person according to the mutation state and/or pathogenicity of the pathogenic gene.

3. The genetic disease virulence gene-based analysis system of claim 2, further comprising one or more of the following characteristics:

1) the pathogenic gene of hereditary hearing loss is selected from GJB2 gene, SLC26A4 gene and mitochondrial 12S rRNA;

2) the causative gene of hereditary hypothyroidism is selected from autosomal recessive genes DUOX2, TG, TPO, TSHR, DUOXA1, DUOXA2 and DUOX1, and autosomal dominant genes PAX8, NKX 2.1;

3) the alpha-thalassemia-related gene is selected from HBA1 and HBA2 genes;

4) the gene related to the beta-thalassemia is an HBB gene;

5) the spinal muscular atrophy pathogenic gene is the SMN1 gene;

6) the site mutation classification module comprises a data conversion script, and the data conversion script converts pathogenic gene data of the genetic disease and a mutation result of a site in the pathogenic gene of the genetic disease into a numerical value to obtain a standardized gene data table.

4. The genetic disease virulence gene-based analysis system of claim 3, further comprising one or more of the following characteristics:

1) sites within the GJB2 gene are: c.35delG, c.176del16, c.235delC, c.299_300delAT, V37I, c.35insG, 512insAACG, 257C > G (p.T86R), 571T > C (p.F191L), 427C > T (p.R143W), V167M, W3X, R75Q, F115C, G4D, M195V, R75W, V63L; the sites within the SLC26a4 gene are: c.919-2A > G, p.H723R, p.M147V, p.R409H, c.916_917insG, c.1520delT, p.E682X, p.G197R, p.T410M, N392Y, L676Q, V659L, Q413R, S532I, A360V, D661E, T94I, 1686insA, S49R, IVS15+5G > A, S252P, 1179_1181delTCT, -2071_307+3801del7666, G497S, Q446X, S49 insC, 414delT, 600+2T > A, IVS13+9C > T, S610X, V650D, X781W;

sites within the mitochondrial 12S rRNA are: m.1494C > T, m.1555A > G and m.3243A > G.

2) Sites within the DUOX2 gene are: a1588T, G3329A, C4027T, G2048T, G2654T, 3693+1G > T, G2654A, G3632A, 3478_3480del, G2635A, G1232A, G2794A, G3616A, C1873T, 1871delG, C227T, a4567G, C4181T, G3566A, 3219_3234del, G2921A, G2335A, G2177A, G1868A, C1606T, C1428A, C109 1097T, T959C, C505T; the sites within the TG gene are: C4859T, a 7847T; the sites within the TPO gene are: 2268dupT, G1327C; the sites within the TSHR gene are: G1349A; sites within the DUOXA1 gene are: C503T, C166T, C787T; sites within the DUOXA2 gene are: 413dupA, T788C, C37T; sites within the DUOX1 gene are: T3435A, a1707T, C3236A, G3920A; the sites within the PAX8 gene are: C1037T; the sites within the NKX2.1 gene are: G1054A;

3) the internal sites of HBA1 are: (- -SEA /) deletion, (- -alpha 3.7/) deletion, (- -alpha 4.2/) deletion; the sites within the HBA2 gene are: (- -SEA /) deletion, (- - α 3.7/) deletion, (- - α 4.2/) deletion, c.369C > G (HbWS), c.427T > C (HbCS), c.377T > C (HbQS QS);

4) the sites within the HBB gene are: c.126_129delCTTT, c.52A > T, c.316-197C > T, c. -78A > G, c. -79A > G, c.79G > A, c.130G > T and c.216_217 insA;

5) the SMN1 gene is deleted at the No. 7 exon.

5. The genetic disease virulence gene-based analysis system of claim 4, further comprising one or more of the following characteristics:

(1) in the result judging module, the judgment standard for judging the mutation state and/or pathogenicity of the gene according to the mutation value of the genetic deafness pathogenic gene is as follows:

if the mutation value of the GJB2 gene is 0, the mutation type of the GJB2 gene is not mutated.

② if the mutation value of the GJB2 gene is 1, the mutation type of the GJB2 gene is single-site heterozygous mutation.

③ if the mutation value of the GJB2 gene is 2 and the mutation result at the V371 site is 1 or 2, or if the mutation value of the GJB2 gene is 3 and the mutation result at the V371 site is 2; the mutation type of the GJB2 gene is a V37I homozygous mutation or a compound heterozygous mutation with any site of GJB2, namely V37I/V37I or V37I/XX;

if the mutation value of the GJB2 gene is 2 and the mutation result of the V371 site is 0; or, if the mutation value of the GJB2 gene is 3 and the mutation result of the V371 site is 0 or 1; the mutation type of the GJB2 gene is homozygous or compound heterozygous mutation;

if the mutation value of the SLC26A4 gene is 0, the SLC26A4 gene mutation type is not mutated;

sixthly, if the mutation value of the SLC26A4 gene is 1, the mutation type of the SLC26A4 gene is single-site heterozygous mutation;

seventhly, if the mutation value of the SLC26A4 gene is more than 1, the mutation type of the SLC26A4 gene is homozygous or compound heterozygous mutation;

if the mutation value of the 12S rRNA of the mitochondria is 0, the mutation type of the 12S rRNA of the mitochondria is not mutated;

ninthly, if the mutation value of the mitochondrial 12S rRNA is 1, carrying out homogeneous or heterogeneous mutation on the mutation type of the mitochondrial 12S rRNA;

obtaining the Cartesian product of the GJB2 gene mutation type, the SLC26A4 gene mutation type and the mitochondrial 12S rRNA mutation type to obtain the possible 24 mutation conditions of the examinee;

the mutation value is obtained by summing up the mutation results of all the sites in the same pathogenic gene;

(2) in the result judging module, the judgment standard for judging the mutation state and/or pathogenicity of the gene according to the mutation value of the hereditary hypothyroidism pathogenic gene is as follows:

when A is_max＝0，a_maxWhen the gene is 0, the mutation type of the autosomal dominant gene is non-mutated, and the mutation type of the autosomal recessive gene is non-mutated; indicating that the subject does not carry a genetic hypothyroidism gene mutation;

when A is_max＝0，a_maxWhen the result is 1, the mutation type of the autosomal dominant gene is not mutated, and the mutation type of the autosomal recessive gene is heterozygous mutation, which indicates that the detected person is a carrier of the hereditary hypothyroidism gene;

when A is_max＝0，a_maxWhen the mutation type of the autosomal dominant gene is not mutated when the mutation type is more than 1, the mutation type of the autosomal recessive gene is homozygous or compound heterozygous mutation, and the detected person is a hereditary hypothyroidism patient;

when A is_maxWhen the gene mutation is more than 0, the mutation type of the autosomal dominant gene is the occurrence of gene mutation, which indicates that the examined person is a hereditary hypothyroidism patient;

wherein A is_maxTaking the maximum value of the mutation value of an autosomal recessive gene, a_maxIs the maximum value of the mutation value in the autosomal dominant gene;

the mutation value is obtained by summing up the mutation results of all the sites in the same pathogenic gene;

(3) in the mutation value obtaining module, when obtaining the mutation value of α -thalassemia pathogenic gene, (-SEA /) mutation result is marked as H₁And the sum of the mutation results of the QS sites of Hb CS and Hb is recorded as H₂(- α 3.7.7 /) deletion, (- α 4.2.2 /) deletion and Hb WS site mutation junctionSum of fruits, marked as H₃；

In the result judging module, the judgment standard for judging the mutation state and/or pathogenicity of the alpha-thalassemia pathogenic gene according to the mutation value of the alpha-thalassemia pathogenic gene is as follows:

if H is₁＝0，H₂＝0，H₃0, indicating that the subject does not carry the α -thalassemia gene mutation;

if H is₁＝0，H₂＝0，H₃1, indicating that the subject is silent α -thalassemia;

if H is₁＝0，H₂＝0，H₃2; or, H₁＝0，H₂＝1，H₃1 is ═ 1; or, H₁＝1，H₂＝0，H₃0, indicating that the subject is mild α -thalassemia;

if H is₁＝0，H₂＝1，H₃0, indicating that the subject is silent α -thalassemia or light α -thalassemia;

if H is₁＝0，H₂2, indicating that the subject is thalassemia minor α or α -thalassemia intermediate;

if H is₁＝1，H₂＝0，H₃1 is ═ 1; or, H₁＝1，H₂1, indicating that the subject is intermediate α -thalassemia;

wherein H₁＝1，H₂＝0，H₃When the disease is 1, the subject is mild HbH disease; h₁＝1，H₂When the disease is 1, the subject is overweight HbH disease;

if H is₁2, indicating α -thalassemia major in the subject;

(4) in the result judging module, the judgment standard for judging the mutation state and/or pathogenicity of the gene according to the mutation value of the beta-thalassemia pathogenic gene is as follows:

if the gene mutation value of the HBB gene is 0, the mutation type of the HBB gene is not mutated, which indicates that the detected person does not carry the beta thalassemia gene or does not suffer from beta thalassemia;

if the mutation value of the HBB gene is 1, the mutation type of the HBB gene is heterozygous mutation at a single locus, which indicates that the examinee suffers from mild beta thalassemia;

when the mutation value of the HBB gene is 2, the mutation type of the HBB gene is homozygous mutation or compound heterozygous mutation, which indicates that the tested object suffers from the beta thalassemia mediterranean type;

the mutation value is obtained by summing up the mutation results of all the sites in the same pathogenic gene;

(5) in the result judgment module, the judgment standard for judging the mutation state and pathogenicity of the gene according to the mutation value of the spinal muscular atrophy pathogenic gene is as follows:

if the mutation value of the SMN1 gene is 0, the mutation type of the SMN1 gene is no mutation, indicating that the probability that the subject does not carry the spinal muscular atrophy gene or has spinal muscular atrophy is low, but not excluding the possibility that the subject is a carrier of type 2+0 or other rare mutation carriers or patients;

if the mutation value of the SMN1 gene is 1, the mutation type of the SMN1 gene is heterozygous mutation, which indicates that the examinee is a spinal muscular atrophy pathogenic gene carrier;

if the mutation value of the SMN1 gene is 2, the mutation type of the SMN1 gene is homozygous deletion mutation, and the detected person is a spinal muscular atrophy patient;

the mutation value is obtained by summing the mutation results of all the sites in the same pathogenic gene.

6. A computer-readable storage medium on which a computer program is stored, which program, when executed by a processor, implements a genetic disease-causing gene-based analysis method, the method comprising the steps of:

s1, classifying the mutation results of internal loci of pathogenic genes of genetic diseases, wherein the loci without mutation are 0, the loci with heterozygous mutation or heterogeneous mutation are 1, and the loci with homozygous mutation or homogeneous mutation are 2;

s2, obtaining a mutation value of the pathogenic gene;

s3, judging the mutation state and/or pathogenicity of the disease-causing gene according to the mutation value of the disease-causing gene: when the mutation value of the pathogenic gene is 0, the mutation type of the pathogenic gene is non-mutated, which indicates that the subject does not carry the gene mutation of the pathogenic gene or does not suffer from the related genetic disease, and when the mutation value of the pathogenic gene is greater than 0, the mutation type of the pathogenic gene is mutated, which indicates that the subject is a carrier of the gene mutation of the related genetic disease or a patient of the related genetic disease.

7. The computer-readable storage medium of claim 6, further comprising one or more of the following features:

1) the genetic disease is selected from one or more of hereditary deafness, hereditary hypothyroidism, alpha-thalassemia, beta-thalassemia or spinal muscular atrophy;

2) the method further comprises the steps of: s0, reading the gene detection result of the examinee, extracting information of the gene detection result, and uploading pathogenic gene data of the genetic disease of the examinee to a site mutation classification module, wherein the pathogenic gene data of the genetic disease of the examinee at least comprises gene names and site names of all positive mutations of the genetic disease of the examinee and mutation result data of sites in the pathogenic gene of the genetic disease;

3) the method further comprises the steps of: and S4, obtaining a matched diagnosis conclusion, disease risk assessment and genetic counseling suggestion according to the mutation state and/or pathogenicity of the pathogenic gene, and generating a gene screening analysis report sheet of the detected person.

8. The computer-readable storage medium of claim 7, further comprising one or more of the following features:

1) the pathogenic gene of hereditary hearing loss is selected from GJB2 gene, SLC26A4 gene and mitochondrial 12S rRNA;

2) the causative gene of hereditary hypothyroidism is selected from autosomal recessive genes DUOX2, TG, TPO, TSHR, DUOXA1, DUOXA2 and DUOX1, and autosomal dominant genes PAX8, NKX 2.1;

3) the alpha-thalassemia-related gene is selected from HBA1 and HBA2 genes;

4) the gene related to the beta-thalassemia is an HBB gene;

5) the spinal muscular atrophy pathogenic gene is the SMN1 gene;

6) in step S2, the pathogenic gene data of the genetic disease is converted by the data conversion script, and the mutation result of the internal site of the pathogenic gene of the genetic disease is converted into a numerical value, so as to obtain a standardized gene data table.

9. The computer-readable storage medium of claim 8, further comprising one or more of the following features:

1) sites within the GJB2 gene are: c.35delG, c.176del16, c.235delC, c.299_300delAT, V37I, c.35insG, 512insAACG, 257C > G (p.T86R), 571T > C (p.F191L), 427C > T (p.R143W), V167M, W3X, R75Q, F115C, G4D, M195V, R75W, V63L; the sites within the SLC26a4 gene are: c.919-2A > G, p.H723R, p.M147V, p.R409H, c.916_917insG, c.1520delT, p.E682X, p.G197R, p.T410M, N392Y, L676Q, V659L, Q413R, S532I, A360V, D661E, T94I, 1686insA, S49R, IVS15+5G > A, S252P, 1179_1181delTCT, -2071_307+3801del7666, G497S, Q446X, S49 insC, 414delT, 600+2T > A, IVS13+9C > T, S610X, V650D, X781W;

sites within the mitochondrial 12S rRNA are: m.1494C > T, m.1555A > G and m.3243A > G.

2) Sites within the DUOX2 gene are: a1588T, G3329A, C4027T, G2048T, G2654T, 3693+1G > T, G2654A, G3632A, 3478_3480del, G2635A, G1232A, G2794A, G3616A, C1873T, 1871delG, C227T, a4567G, C4181T, G3566A, 3219_3234del, G2921A, G2335A, G2177A, G1868A, C1606T, C1428A, C109 1097T, T959C, C505T; the sites within the TG gene are: C4859T, a 7847T; the sites within the TPO gene are: 2268dupT, G1327C; the sites within the TSHR gene are: G1349A; sites within the DUOXA1 gene are: C503T, C166T, C787T; sites within the DUOXA2 gene are: 413dupA, T788C, C37T; sites within the DUOX1 gene are: T3435A, a1707T, C3236A, G3920A; the sites within the PAX8 gene are: C1037T; the sites within the NKX2.1 gene are: G1054A;

3) the internal sites of HBA1 are: (- -SEA /) deletion, (- -alpha 3.7/) deletion, (- -alpha 4.2/) deletion; the sites within the HBA2 gene are: (- -SEA /) deletion, (- - α 3.7/) deletion, (- - α 4.2/) deletion, c.369C > G (HbWS), c.427T > C (HbCS), c.377T > C (HbQS QS);

4) the sites within the HBB gene are: c.126_129delCTTT, c.52A > T, c.316-197C > T, c. -78A > G, c. -79A > G, c.79G > A, c.130G > T and c.216_217 insA;

5) the SMN1 gene is deleted at the No. 7 exon.

10. The computer-readable storage medium of claim 9, further comprising one or more of the following features:

(1) in step S3, the judgment criteria for judging the mutation status and/or pathogenicity of the gene according to the mutation value of the genetic deafness-causing gene are:

if the mutation value of the GJB2 gene is 0, the mutation type of the GJB2 gene is not mutated.

② if the mutation value of the GJB2 gene is 1, the mutation type of the GJB2 gene is single-site heterozygous mutation.

③ if the mutation value of the GJB2 gene is 2 and the mutation result at the V371 site is 1 or 2, or if the mutation value of the GJB2 gene is 3 and the mutation result at the V371 site is 2; the mutation type of the GJB2 gene is a V37I homozygous mutation or a compound heterozygous mutation with any site of GJB2, namely V37I/V37I or V37I/XX;

if the mutation value of the GJB2 gene is 2 and the mutation result of the V371 site is 0; or, if the mutation value of the GJB2 gene is 3 and the mutation result of the V371 site is 0 or 1; the mutation type of the GJB2 gene is homozygous or compound heterozygous mutation;

if the mutation value of the SLC26A4 gene is 0, the SLC26A4 gene mutation type is not mutated;

sixthly, if the mutation value of the SLC26A4 gene is 1, the mutation type of the SLC26A4 gene is single-site heterozygous mutation;

seventhly, if the mutation value of the SLC26A4 gene is more than 1, the mutation type of the SLC26A4 gene is homozygous or compound heterozygous mutation;

if the mutation value of the 12S rRNA of the mitochondria is 0, the mutation type of the 12S rRNA of the mitochondria is not mutated;

ninthly, if the mutation value of the mitochondrial 12S rRNA is 1, carrying out homogeneous or heterogeneous mutation on the mutation type of the mitochondrial 12S rRNA;

obtaining the Cartesian product of the GJB2 gene mutation type, the SLC26A4 gene mutation type and the mitochondrial 12S rRNA mutation type to obtain the possible 24 mutation conditions of the examinee;

the mutation value is obtained by summing up the mutation results of all the sites in the same pathogenic gene;

(2) in step S3, the judgment criteria for judging the mutation status and/or pathogenicity of the genetic methylotrophic pathogenicity-causing gene according to the mutation value of the gene are:

when A is_max＝0，a_maxWhen the gene is 0, the mutation type of the autosomal dominant gene is non-mutated, and the mutation type of the autosomal recessive gene is non-mutated; indicating that the subject does not carry a genetic hypothyroidism gene mutation;

when A is_max＝0，a_maxWhen the result is 1, the mutation type of the autosomal dominant gene is not mutated, and the mutation type of the autosomal recessive gene is heterozygous mutation, which indicates that the detected person is a carrier of the hereditary hypothyroidism gene;

when A is_max＝0，a_maxWhen the mutation type of the autosomal dominant gene is not mutated when the mutation type is more than 1, the mutation type of the autosomal recessive gene is homozygous or compound heterozygous mutation, and the detected person is a hereditary hypothyroidism patient;

when A is_maxWhen the gene mutation is more than 0, the mutation type of the autosomal dominant gene is the occurrence of gene mutation, which indicates that the examined person is a hereditary hypothyroidism patient;

wherein A is_maxTaking the maximum value of the mutation value of an autosomal recessive gene, a_maxIs the maximum value of the mutation value in the autosomal dominant gene;

the mutation value is obtained by summing up the mutation results of all the sites in the same pathogenic gene;

(3) in step S2, in obtaining α -groundThe mutation result of (-SEA /) deletion at the mutation value of the thalassemia-causing gene was recorded as H₁And the sum of the mutation results of the QS sites of Hb CS and Hb is recorded as H₂The sum of the results of (- α 3.7.7 /) deletion, (- α 4.2.2 /) deletion and Hb WS site mutation is marked as H₃；

In step S3, the judgment criteria for judging the mutation status and/or pathogenicity of the alpha-thalassemia causing gene according to the mutation value of the gene are:

if H is₁＝0，H₂＝0，H₃0, indicating that the subject does not carry the α -thalassemia gene mutation;

if H is₁＝0，H₂＝0，H₃1, indicating that the subject is silent α -thalassemia;

if H is₁＝0，H₂＝0，H₃2; or, H₁＝0，H₂＝1，H₃1 is ═ 1; or, H₁＝1，H₂＝0，H₃0, indicating that the subject is mild α -thalassemia;

if H is₁＝0，H₂＝1，H₃0, indicating that the subject is silent α -thalassemia or light α -thalassemia;

if H is₁＝0，H₂2, indicating that the subject is thalassemia minor α or α -thalassemia intermediate;

if H is₁＝1，H₂＝0，H₃1 is ═ 1; or, H₁＝1，H₂1, indicating that the subject is intermediate α -thalassemia;

wherein H₁＝1，H₂＝0，H₃When the disease is 1, the subject is mild HbH disease; h₁＝1，H₂When the disease is 1, the subject is overweight HbH disease;

if H is₁2, indicating α -thalassemia major in the subject;

(4) in step S3, the judgment criteria for judging the mutation status and/or pathogenicity of the gene according to the mutation value of the beta-thalassemia-causing gene are:

if the gene mutation value of the HBB gene is 0, the mutation type of the HBB gene is not mutated, which indicates that the detected person does not carry the beta thalassemia gene or does not suffer from beta thalassemia;

if the mutation value of the HBB gene is 1, the mutation type of the HBB gene is heterozygous mutation at a single locus, which indicates that the examinee suffers from mild beta thalassemia;

when the mutation value of the HBB gene is 2, the mutation type of the HBB gene is homozygous mutation or compound heterozygous mutation, which indicates that the tested object suffers from the beta thalassemia mediterranean type;

the mutation value is obtained by summing up the mutation results of all the sites in the same pathogenic gene;

(5) in step S3, the judgment criteria for judging the mutation status and pathogenicity of the spinal muscular atrophy pathogenic gene according to the mutation value of the gene are:

if the mutation value of the SMN1 gene is 0, the mutation type of the SMN1 gene is no mutation, indicating that the probability that the subject does not carry the spinal muscular atrophy gene or has spinal muscular atrophy is low, but not excluding the possibility that the subject is a carrier of type 2+0 or other rare mutation carriers or patients;

if the mutation value of the SMN1 gene is 1, the mutation type of the SMN1 gene is heterozygous mutation, which indicates that the examinee is a spinal muscular atrophy pathogenic gene carrier;

if the mutation value of the SMN1 gene is 2, the mutation type of the SMN1 gene is homozygous deletion mutation, and the detected person is a spinal muscular atrophy patient;

the mutation value is obtained by summing the mutation results of all the sites in the same pathogenic gene.

11. A computer processing device comprising a processor and the aforementioned computer readable storage medium, said processor executing a computer program on the computer readable storage medium of any of claims 6-10.

12. An electronic terminal, comprising: a processor, a memory, and a communicator; the memory is used for storing a computer program, the communicator is used for carrying out communication connection with an external device, and the processor is used for executing the computer program on the computer readable storage medium of any one of claims 6-10.

Technical Field

The invention relates to the field of gene detection, in particular to an analysis system based on a pathogenic gene of a genetic disease and application thereof.

Background

Some intelligent genetic disease diagnosis systems are already available in the market at present, but different from the scheme, most of the systems analyze second-generation gene sequencing data of examinees, and then find out disease-related pathogenic mutation from massive gene data, and the steps are as follows: 1) pathogenicity interpretation: classifying the variation according to ACMG criteria, removing benign or suspected benign variations, retaining pathogenic variations, 2) determining phenotypic correlations: inputting the normalized phenotype (clinical symptom) of the examined person, retrieving information in a gene disease phenotype database to obtain a corresponding disease and gene list, sorting according to the correlation degree of the disease and the phenotype of the patient, and finally determining which mutations are related to the disease. The system comprises a single-gene genetic disease auxiliary software-a plain-text system of Beijing precision science and technology, clinical symptoms of a patient are input into the system to obtain a related gene and disease list, and then the related gene and the disease list are compared with gene sequencing data of the patient to find pathogenic mutation; in addition, the system also comprises a marine cloud gene intelligent accurate diagnosis cooperative cloud system APCS, which can realize the automatic analysis and diagnosis based on phenotype (clinical symptoms), the analysis and diagnosis and report based on gene data, the retrieval of the interrelation among genes, phenotypes and diseases and the like. However, intelligent diagnostic systems for genetic screening data for genetic diseases remain open.

In addition, the current birth defect gene screening is generally single disease screening, and rarely comprises comprehensive screening of multiple birth defect diseases, most genetic disease gene reports only show gene detection results, but lack detailed explanation of mutant genes, descendant genetic risk assessment, genetic consultation suggestions and the like, and the profession of the reports makes most doctors difficult to interpret, so that an intelligent diagnosis system aiming at genetic disease gene screening data is particularly critical.

Disclosure of Invention

In view of the above-mentioned drawbacks of the prior art, it is an object of the present invention to provide an analysis system based on a genetic disease causing gene, the system comprising at least the following modules:

the site mutation classification module is used for classifying the mutation results of internal sites of pathogenic genes of genetic diseases, wherein the sites which do not have mutation are 0, the sites which have heterozygous mutation or heterogeneous mutation are 1, and the sites which have homozygous mutation or homogeneous mutation are 2;

a mutation value obtaining module for obtaining a mutation value of a pathogenic gene;

and the result judging module is used for judging the mutation state and/or pathogenicity of the pathogenic gene according to the mutation value of the pathogenic gene: when the mutation value of the pathogenic gene is 0, the mutation type of the pathogenic gene is non-mutated, which indicates that the subject does not carry the gene mutation of the pathogenic gene or does not suffer from the related genetic disease, and when the mutation value of the pathogenic gene is greater than 0, the mutation type of the pathogenic gene is mutated, which indicates that the subject is a carrier of the gene mutation of the related genetic disease or a patient of the related genetic disease.

The second aspect of the present invention provides a computer-readable storage medium having stored thereon a computer program which, when executed by a processor, implements a genetic disease-causing gene-based analysis method, the method comprising the steps of:

s1, classifying the mutation results of internal loci of pathogenic genes of genetic diseases, wherein the loci without mutation are 0, the loci with heterozygous mutation or heterogeneous mutation are 1, and the loci with homozygous mutation or homogeneous mutation are 2;

s2, obtaining a mutation value of the pathogenic gene;

s3, judging the mutation state and/or pathogenicity of the disease-causing gene according to the mutation value of the disease-causing gene: when the mutation value of the pathogenic gene is 0, the mutation type of the pathogenic gene is non-mutated, which indicates that the subject does not carry the gene mutation of the pathogenic gene or does not suffer from the related genetic disease, and when the mutation value of the pathogenic gene is greater than 0, the mutation type of the pathogenic gene is mutated, which indicates that the subject is a carrier of the gene mutation of the related genetic disease or a patient of the related genetic disease.

A third aspect of the invention provides a computer processing apparatus comprising a processor and the aforementioned computer-readable storage medium, the processor executing a computer program on the aforementioned computer-readable storage medium.

A fourth aspect of the present invention provides an electronic terminal, comprising: a processor, a memory, and a communicator; the memory is configured to store a computer program, the communicator is configured to communicatively couple with an external device, and the processor is configured to execute the computer program on the computer-readable storage medium of the preceding claims.

As described above, the analysis system based on the pathogenic gene of the genetic disease and the application thereof according to the present invention have the following advantageous effects:

1. besides being suitable for gene data analysis of sick people, the system can also carry out diagnosis and analysis on gene screening data of normal phenotype people, carry out risk assessment on mutation carriers of normal phenotypes, avoid acquired damage factors, simultaneously assess pathogenic risk of offspring of the mutation carriers, and provide effective marriage and education guidance and genetic counseling suggestion for the mutation carriers. The vacancy of the prior art is filled.

2. Different from the gene screening of single birth defect disease, the invention can realize the comprehensive screening and analysis diagnosis of various birth defect diseases at the same time. Directly provides diagnosis conclusion, genetic risk assessment and genetic counseling suggestion of five types of birth defect diseases according to the gene locus detection result.

3. Most of the existing prenatal screening reports of genetic diseases only present gene detection results, and the speciality of the existing prenatal screening reports makes interpretation of most of the patients difficult. The method carries out intelligent diagnosis based on birth defect gene data, gives a disease diagnosis conclusion, genetic risk assessment and genetic counseling suggestion, and generates a cloud platform diagnosis suggestion report sheet for the examinee, so that the examinee can interpret the gene data of the examinee by self and obtain reliable genetic counseling suggestion.

Drawings

FIG. 1 is a schematic diagram of an analysis system based on the pathogenic genes of a genetic disease according to an embodiment of the present invention.

FIG. 1-1 is a schematic diagram showing an analysis system based on a pathogenic gene of a genetic disease according to another embodiment of the present invention.

FIG. 2 shows the genetic deafness intelligent diagnosis map of the present invention.

FIG. 3 shows the genetic Intelligent diagnosis map of hypothyroidism in the invention.

FIG. 4 shows a map for intelligently diagnosing thalassemia according to the present invention.

Fig. 5 shows the intelligent diagnosis map of spinal muscular atrophy SMA in the invention.

Fig. 6 is a schematic diagram of an electronic terminal according to an embodiment of the invention.

Detailed Description

The embodiments of the present invention are described below with reference to specific embodiments, and other advantages and effects of the present invention will be easily understood by those skilled in the art from the disclosure of the present specification. The invention is capable of other and different embodiments and of being practiced or of being carried out in various ways, and its several details are capable of modification in various respects, all without departing from the spirit and scope of the present invention.

It should be noted that the drawings provided in the present embodiment are only for illustrating the basic idea of the present invention, and although the drawings only show the components related to the present invention and are not drawn according to the number, shape and size of the components in the actual implementation, the type, quantity and proportion of the components in the actual implementation may be changed arbitrarily, and the layout of the components may be more complicated. The embodiments of the present invention are described below with reference to specific embodiments, and other advantages and effects of the present invention will be easily understood by those skilled in the art from the disclosure of the present specification. The invention is capable of other and different embodiments and of being practiced or of being carried out in various ways, and its several details are capable of modification in various respects, all without departing from the spirit and scope of the present invention.

It should be noted that the drawings provided in the present embodiment are only for illustrating the basic idea of the present invention, and although the drawings only show the components related to the present invention and are not drawn according to the number, shape and size of the components in the actual implementation, the type, quantity and proportion of the components in the actual implementation may be changed arbitrarily, and the layout of the components may be more complicated.

The genetic disease pathogenic gene-based analysis system can also be called a cloud platform intelligent diagnosis and genetic consultation system.

The genetic disease pathogenic gene-based analysis system of one embodiment of the present invention comprises at least the following modules:

the site mutation classification module is used for classifying the mutation results of internal sites of pathogenic genes of genetic diseases, wherein the sites which do not have mutation are 0, the sites which have heterozygous mutation or heterogeneous mutation are 1, and the sites which have homozygous mutation or homogeneous mutation are 2;

a mutation value obtaining module for obtaining a mutation value of a pathogenic gene;

and the result judging module is used for judging the mutation state and/or pathogenicity of the pathogenic gene according to the mutation value of the pathogenic gene: when the mutation value of the pathogenic gene is 0, the mutation type of the pathogenic gene is non-mutated, which indicates that the subject does not carry the gene mutation of the pathogenic gene or does not suffer from the related genetic disease, and when the mutation value of the pathogenic gene is greater than 0, the mutation type of the pathogenic gene is mutated, which indicates that the subject is a carrier of the gene mutation of the related genetic disease or a patient of the related genetic disease.

The invention can be implemented by Python coding.

Optionally, the site mutation classification module includes a data transformation script, and the data transformation script transforms pathogenic gene data of the genetic disease and transforms mutation results of sites in pathogenic genes of the genetic disease into numerical values to obtain a standardized gene data table.

In one embodiment, as shown in fig. 1-1, the system further comprises a data acquisition module for reading the gene detection result of the subject, extracting information of the gene detection result, and uploading pathogenic gene data of the genetic disease of the subject to the site mutation classification module, wherein the pathogenic gene data of the genetic disease of the subject at least comprises the gene names of all positive mutations of the genetic disease of the subject, the site names and mutation result data of sites in the pathogenic gene of the genetic disease.

Preferably, the system further comprises a report generation module for obtaining a matched diagnosis conclusion, a disease risk assessment and genetic counseling suggestion and generating a gene screening analysis report of the subject according to the mutation state and/or pathogenicity of the pathogenic gene.

The diagnosis conclusion, disease risk assessment and genetic counseling advice can be retrieved from a genetic risk assessment and genetic counseling advice database, wherein the database in the database is formed by summarizing clinical diagnosis prior knowledge collected from each disease unit.

The genetic disease is selected from one or more of hereditary deafness, hereditary hypothyroidism, alpha-thalassemia (Hbh disease), beta-thalassemia or Spinal Muscular Atrophy (SMA).

Wherein the pathogenic gene of hereditary hearing loss is selected from GJB2 gene, SLC26A4 gene and mitochondrial 12S rRNA. Further, the sites in the GJB2 gene are: c.35delG, c.176del16, c.235delC, c.299_300delAT, V37I, c.35insG, 512insAACG, 257C > G (p.T86R), 571T > C (p.F191L), 427C > T (p.R143W), V167M, W3X, R75Q, F115C, G4D, M195V, R75W, V63L;

the sites within the SLC26a4 gene are: c.919-2A > G, p.H723R, p.M147V, p.R409H, c.916_917insG, c.1520delT, p.E682X, p.G197R, p.T410M, N392Y, L676Q, V659L, Q413R, S532I, A360V, D661E, T94I, 1686insA, S49R, IVS15+5G > A, S252P, 1179_1181delTCT, -2071_307+3801del7666, G497S, Q446X, S49 insC, 414delT, 600+2T > A, IVS13+9C > T, S610X, V650D, X781W;

sites within the mitochondrial 12S rRNA are: m.1494C > T, m.1555A > G and m.3243A > G.

The specific information is shown in table 1.

TABLE 1 genetic deafness causing genes and site related information

Further, as shown in fig. 2, (1) in the result judgment module, the judgment criteria for judging the mutation status and/or pathogenicity of the gene according to the mutation value of the genetic deafness pathogenic gene are:

if the mutation value of the GJB2 gene is 0, the mutation type of the GJB2 gene is not mutated.

② if the mutation value of the GJB2 gene is 1, the mutation type of the GJB2 gene is single-site heterozygous mutation.

③ if the mutation value of the GJB2 gene is 2 and the mutation result at the V371 site is 1 or 2, or if the mutation value of the GJB2 gene is 3 and the mutation result at the V371 site is 2; the mutation type of the GJB2 gene is a V37I homozygous mutation or a compound heterozygous mutation with any site of GJB2, namely V37I/V37I or V37I/XX;

if the mutation value of the GJB2 gene is 2 and the mutation result of the V371 site is 0; or, if the mutation value of the GJB2 gene is 3 and the mutation result of the V371 site is 0 or 1; the mutation type of the GJB2 gene is homozygous or compound heterozygous mutation;

if the mutation value of the SLC26A4 gene is 0, the SLC26A4 gene mutation type is not mutated;

sixthly, if the mutation value of the SLC26A4 gene is 1, the mutation type of the SLC26A4 gene is single-site heterozygous mutation;

seventhly, if the mutation value of the SLC26A4 gene is more than 1, the mutation type of the SLC26A4 gene is homozygous or compound heterozygous mutation;

if the mutation value of the 12S rRNA of the mitochondria is 0, the mutation type of the 12S rRNA of the mitochondria is not mutated;

ninthly, if the mutation value of the mitochondrial 12S rRNA is 1, carrying out homogeneous or heterogeneous mutation on the mutation type of the mitochondrial 12S rRNA;

the mutation value is obtained by summing the mutation results of all the sites in the same pathogenic gene.

Further, the Cartesian product of the GJB2 gene mutation type, the SLC26A4 gene mutation type and the mitochondrial 12S rRNA mutation type is obtained to obtain the possible 24 mutation conditions of the subject. The diagnosis conclusion, the genetic risk assessment and the genetic consultation suggestion can be further matched in the report generation module, and the genetic risk assessment and the genetic consultation suggestion are derived from a genetic risk assessment and genetic consultation suggestion database, which is specifically shown in a table 1-1:

TABLE 1-124 pathogenicity and genetic counseling points of deafness gene mutation combination

The pathogenic gene of hereditary hypothyroidism is selected from DUOX2, TG, TPO, TSHR, DUOXA1, DUOXA2, DUOX1, PAX8, NKX 2.1.

Wherein, the autosomal recessive genes are DUOX2, TG, TPO, TSHR, DUOXA1, DUOXA2 and DUOX1, and the autosomal dominant genes are PAX8 and NKX 2.1.

Further, sites within the DUOX2 gene are: a1588T, G3329A, C4027T, G2048T, G2654T, 3693+1G > T, G2654A, G3632A, 3478_3480del, G2635A, G1232A, G2794A, G3616A, C1873T, 1871delG, C227T, a4567G, C4181T, G3566A, 3219_3234del, G2921A, G2335A, G2177A, G1868A, C1606T, C1428A, C109 1097T, T959C, C505T.

The sites within the TG gene are: C4859T, a 7847T.

The sites within the TPO gene are: 2268dupT, G1327C.

The sites within the TSHR gene are: G1349A.

Sites within the DUOXA1 gene are: C503T, C166T, C787T.

Sites within the DUOXA2 gene are: 413dupA, T788C, C37T.

Sites within the DUOX1 gene are: T3435A, a1707T, C3236A, G3920A.

The sites within the PAX8 gene are: C1037T.

The sites within the NKX2.1 gene are: G1054A.

The specific information is shown in Table 2.

TABLE 2 genetic onychomycosis virulence genes and site-related information

Further, as shown in fig. 3, (2) in the result judgment module, the judgment criteria for judging the mutation status and/or pathogenicity of the genetic nail reduction disease-causing gene according to the mutation value of the gene are:

when A is_max＝0，a_maxWhen the gene is 0, the mutation type of the autosomal dominant gene is non-mutated, and the mutation type of the autosomal recessive gene is non-mutated; indicating that the subject does not carry a genetic mutation in the hypothyroid gene.

When A is_max＝0，a_maxWhen the mutation type of the autosomal dominant gene is no mutation, the mutation type of the autosomal recessive gene is heterozygous mutation, indicating that the subject is a carrier of the hereditary hypothyroidism gene.

When A is_max＝0，a_maxWhen the mutation type of the autosomal dominant gene is not mutated, the mutation type of the autosomal recessive gene is homozygous or compound heterozygous mutation, and the detected person is a hereditary hypothyroidism patient.

When A is_maxWhen the mutation type of the autosomal dominant gene is more than 0, the occurrence of gene mutation indicates that the detected person is a hereditary hypothyroidism patient.

Wherein A is_maxTaking the maximum value of the mutation value of an autosomal recessive gene, a_maxIs the maximum value of the mutation value in the autosomal dominant gene.

The mutation value is obtained by summing the mutation results of all the sites in the same pathogenic gene.

The alpha-thalassemia related gene is selected from HBA1 and HBA2 genes.

The internal sites of HBA1 are: (- -SEA /) deletion, (- -alpha 3.7/) deletion, (- -alpha 4.2/) deletion.

The sites within the HBA2 gene are: (- -SEA /) deletion, (- - α 3.7/) deletion, (- - α 4.2/) deletion, c.369C > G (Hb WS), c.427T > C (Hb CS), c.377T > C (Hb QS).

Human has four α globin genes, wherein the stationary α is poor at any α gene and the gene types comprise- α/αα and α^Tα/αα, the individuals are usually asymptomatic and have no positive hematological phenotype, but α^CSα/αα，α^QSα/αα may also exhibit a mild α thalassemia phenotype, a mild α thalassemia with 2 α gene abnormalities, including the genotypes- -SEA/αα, - - α/- α, - - α/α^Tα，α^Tα/α^Tα, clinically manifested as asymptomatic or mild anemia, with typical characteristic of hypochromic minicells, but α^QSα/α^QSα，α^QSα/α^CSα，α^CSα/α^CSα can also be manifested as HbH diseases, wherein the intermediate α has weak disease (HbH diseases) which is 3 α gene abnormalities, and is generally divided into a lighter HbH disease and a heavier HbH disease according to different clinical manifestations, wherein the lighter HbH diseases mainly comprise the following genotypes of-SEA/- α 3.7.7, -SEA/- α 4.2.2 and-SEA/α^WSα, SEA/α common to HbH overweight diseases^CSα，--SEA/α^QSα. HbH patients mostly show moderate hemolytic anemia, no clinical symptoms at birth, anemia, fatigue, weakness, hepatosplenomegaly, mild jaundice and the like gradually appear after infancy, α with severe anemia is 4 abnormal genes α, the genotype is-SEA/-SEA, Hb Bart's fetal edema syndrome is fatal hematopathy, and sick fetuses die at late pregnancy or soon after birth due to severe anemia and hypoxia (note that- α indicates- α 3.7.7 or- α 4.2.2, α^Tα denotes a numeral α^CSα、α^QSα or α^WSα)。

The specific information is shown in Table 3.

TABLE 3 alpha-thalassemia-causing genes and site-related information

Furthermore, in the mutation value obtaining module, when the mutation value of the alpha-thalassemia disease-causing gene is obtained, the mutation result of (-SEA /) deletion is recorded as H1, and the sum of the mutation results of Hb CS and Hb QS sites is recorded as H2; the sum of the results of (-alpha 3.7/) deletion, (-alpha 4.2/) deletion and Hb WS site mutation is marked as H3;

as shown in FIG. 4, in the result judgment module, the judgment criteria for judging the mutation status and/or pathogenicity of the alpha-thalassemia causing gene according to the mutation value of the gene are as follows:

if H is₁＝0，H₂＝0，H₃0, indicating that the subject does not carry the α -thalassemia gene mutation.

If H is₁＝0，H₂＝0，H ₃1, indicating that the subject is silent α -thalassemia.

If H is₁＝0，H₂＝0，H ₃2; or, H₁＝0，H₂＝1，H ₃1 is ═ 1; or, H₁＝1，H₂＝0，H₃0, indicating that the subject is mild α -thalassemia.

If H is₁＝0，H₂＝1，H₃0, indicating that the subject is silent α -thalassemia or light α -thalassemia.

If H is₁＝0，H ₂2, indicating that the subject is thalassemia minor α or α -thalassemia intermediate.

If H is₁＝1，H₂＝0，H ₃1 is ═ 1; or, H₁＝1，H ₂1, indicating that the subject is intermediate α -thalassemia (i.e. HbH disease),

wherein H₁＝1，H₂＝0，H₃When the disease is 1, the subject is mild HbH disease; h₁＝1，H₂When 1, the subject is overweight HbH.

If H is₁2, indicating that the subject is α -thalassemia major (i.e., Hb Bart's fetal edema syndrome).

The gene related to beta-thalassemia is the HBB gene.

Further, the sites within the HBB gene are: c.126_129delCTTT, c.52A > T, c.316-197C > T, c. -78A > G, c. -79A > G, c.79G > A, c.130G > T and c.216_217 insA.

The specific information is shown in Table 4.

TABLE 4 beta-thalassemia-causing genes and site-related information

Further, as shown in fig. 4, (1) in the result judgment module, the judgment criteria for judging the mutation status and/or pathogenicity of the gene according to the mutation value of the beta-thalassemia-causing gene are:

if the gene mutation value of the HBB gene is 0, the mutation type of the HBB gene is not mutated, which indicates that the tested person does not carry the beta thalassemia gene or does not suffer from beta thalassemia;

if the mutation value of the HBB gene is 1, the mutation type of the HBB gene is heterozygous mutation at a single locus, which indicates that the detected person suffers from light beta thalassemia;

when the mutation value of the HBB gene is 2, the mutation type of the HBB gene is the occurrence of a homozygous mutation or a compound heterozygous mutation, indicating that the subject has moderate-heavy beta-thalassemia;

the mutation value is obtained by summing up the mutation results of all the sites in the same pathogenic gene;

the spinal muscular atrophy pathogenic gene is SMN1 gene.

Furthermore, the site of SMN1 gene is exon 7 deletion.

The specific information is shown in Table 5.

TABLE 5 spinal muscular atrophy-causing genes and site-related information

Genetic diseases	Pathogenic gene	Site of the body	Chromosome	Position of
					SMA	SMN1	Exon 7 deletion	chr5	70247768-70247818

As shown in fig. 5, in the result judgment module, the judgment criteria for judging the mutation status and pathogenicity of the gene according to the mutation value of the spinal muscular atrophy pathogenic gene are as follows:

if the mutation value of the SMN1 gene is 0, the mutation type of the SMN1 gene is no mutation, indicating that the probability that the subject does not carry the spinal muscular atrophy gene or has spinal muscular atrophy is low, but not excluding the possibility that the subject is a carrier of type 2+0 or other rare mutation carriers or patients;

a "type 2+ 0" carrier means that the SMN1 gene has 2 copies on one chromosome and 0 copies on the other chromosome.

If the mutation value of the SMN1 gene is 1, the mutation type of the SMN1 gene is heterozygous mutation, which indicates that the examinee is a spinal muscular atrophy pathogenic gene carrier;

if the mutation value of the SMN1 gene is 2, the mutation type of the SMN1 gene is homozygous deletion mutation, and the detected object is a spinal muscular atrophy patient.

The mutation value is obtained by summing the mutation results of all the sites in the same pathogenic gene.

It should be noted that the division of the modules of the above system is only a logical division, and the actual implementation may be wholly or partially integrated into one physical entity, or may be physically separated. These modules may all be implemented in software invoked by a processing element; or may be implemented entirely in hardware; and part of the modules can be realized in the form of calling software by the processing element, and part of the modules can be realized in the form of hardware. For example, the obtaining module may be a processing element that is set up separately, or may be implemented by being integrated in a certain chip, or may be stored in a memory in the form of program code, and the certain processing element calls and executes the functions of the obtaining module. Other modules are implemented similarly. In addition, all or part of the modules can be integrated together or can be independently realized. The processing element described herein may be an integrated circuit having signal processing capabilities. In implementation, each step of the above method or each module above may be implemented by an integrated logic circuit of hardware in a processor element or an instruction in the form of software.

For example, the above modules may be one or more integrated circuits configured to implement the above methods, such as: one or more Application Specific Integrated Circuits (ASICs), or one or more microprocessors (DSPs), or one or more Field Programmable Gate Arrays (FPGAs), among others. For another example, when one of the above modules is implemented in the form of a Processing element scheduler code, the Processing element may be a general-purpose processor, such as a Central Processing Unit (CPU) or other processor capable of calling program code. For another example, these modules may be integrated together and implemented in the form of a system-on-a-chip (SOC).

In some embodiments of the present invention, there is also provided a computer-readable storage medium on which a computer program is stored, which when executed by a processor, implements a genetic disease causing gene based analysis method, the method comprising the steps of:

s1, classifying the mutation results of internal loci of pathogenic genes of genetic diseases, wherein the loci without mutation are 0, the loci with heterozygous mutation or heterogeneous mutation are 1, and the loci with homozygous mutation or homogeneous mutation are 2;

s2, obtaining a mutation value of the pathogenic gene;

s3, judging the mutation state and/or pathogenicity of the disease-causing gene according to the mutation value of the disease-causing gene: when the mutation value of the pathogenic gene is 0, the mutation type of the pathogenic gene is non-mutated, which indicates that the subject does not carry the gene mutation of the pathogenic gene or does not suffer from the related genetic disease, and when the mutation value of the pathogenic gene is greater than 0, the mutation type of the pathogenic gene is mutated, which indicates that the subject is a carrier of the gene mutation of the related genetic disease or a patient of the related genetic disease.

Optionally, the genetic disease is selected from one or more of genetic deafness, genetic hypothyroidism, alpha-thalassemia, beta-thalassemia or spinal muscular atrophy.

Optionally, the method further comprises the following steps: s0, reading the gene detection result of the examinee, extracting the information of the gene detection result, and uploading the pathogenic gene data of the genetic disease of the examinee to the site mutation classification module, wherein the pathogenic gene data of the genetic disease of the examinee at least comprises the gene names and the site names of all positive mutations of the genetic disease of the examinee and the mutation result data of the internal sites of the pathogenic genes of the genetic disease.

In one embodiment, in step S2, a normalized gene data table is obtained by converting the data transformation script into pathogenic gene data of the genetic disease and transforming the mutation result of the site in the pathogenic gene of the genetic disease into a numerical value.

Preferably, the method further comprises the steps of: and S4, obtaining a matched diagnosis conclusion, disease risk assessment and genetic counseling suggestion according to the mutation state and/or pathogenicity of the pathogenic gene, and generating a gene screening analysis report sheet of the detected person.

In one embodiment, the causative gene of genetic deafness is selected from the group consisting of the GJB2 gene, the SLC26A4 gene, and the mitochondrial 12S rRNA;

in one embodiment, the causative gene of the genetic hypothyroidism is selected from the group consisting of autosomal recessive genes DUOX2, TG, TPO, TSHR, DUOXA1, DUOXA2, and DUOX1, and autosomal dominant genes PAX8, NKX 2.1;

in one embodiment, the α -thalassemia-associated gene is selected from the group consisting of the HBA1 and HBA2 genes;

in one embodiment, the beta-thalassemia-associated gene is the HBB gene;

in one embodiment, the spinal muscular atrophy causing gene is the SMN1 gene.

Further, the sites in the GJB2 gene are: c.35delG, c.176del16, c.235delC, c.299_300delAT, V37I, c.35insG, 512insAACG, 257C > G (p.T86R), 571T > C (p.F191L), 427C > T (p.R143W), V167M, W3X, R75Q, F115C, G4D, M195V, R75W, V63L;

the sites within the SLC26a4 gene are: c.919-2A > G, p.H723R, p.M147V, p.R409H, c.916_917insG, c.1520delT, p.E682X, p.G197R, p.T410M, N392Y, L676Q, V659L, Q413R, S532I, A360V, D661E, T94I, 1686insA, S49R, IVS15+5G > A, S252P, 1179_1181delTCT, -2071_307+3801del7666, G497S, Q446X, S49 insC, 414delT, 600+2T > A, IVS13+9C > T, S610X, V650D, X781W;

sites within the mitochondrial 12S rRNA are: m.1494C > T, m.1555A > G and m.3243A > G.

Further, sites within the DUOX2 gene are: a1588T, G3329A, C4027T, G2048T, G2654T, 3693+1G > T, G2654A, G3632A, 3478_3480del, G2635A, G1232A, G2794A, G3616A, C1873T, 1871delG, C227T, a4567G, C4181T, G3566A, 3219_3234del, G2921A, G2335A, G2177A, G1868A, C1606T, C1428A, C109 1097T, T959C, C505T; the sites within the TG gene are: C4859T, a 7847T; the sites within the TPO gene are: 2268dupT, G1327C; the sites within the TSHR gene are: G1349A; sites within the DUOXA1 gene are: C503T, C166T, C787T; sites within the DUOXA2 gene are: 413dupA, T788C, C37T; sites within the DUOX1 gene are: T3435A, a1707T, C3236A, G3920A; the sites within the PAX8 gene are: C1037T; the sites within the NKX2.1 gene are: G1054A;

further, the internal sites of HBA1 are: (- -SEA /) deletion, (- -alpha 3.7/) deletion, (- -alpha 4.2/) deletion;

the sites within the HBA2 gene are: (- -SEA /) deletion, (- -alpha 3.7/) deletion, (- -alpha 4.2/) deletion,

c.369C>G(Hb WS)，c.427T>C(Hb CS)，c.377T>C(Hb QS)；

further, the sites within the HBB gene are: c.126_129delCTTT, c.52A > T, c.316-197C > T, c. -78A > G, c. -79A > G, c.79G > A, c.130G > T and c.216_217 insA;

furthermore, the site of SMN1 gene is exon 7 deletion.

Further, in step S3, the judgment criteria for judging the mutation status and/or pathogenicity of the gene according to the mutation value of the genetic deafness-causing gene are:

if the mutation value of the GJB2 gene is 0, the mutation type of the GJB2 gene is not mutated.

② if the mutation value of the GJB2 gene is 1, the mutation type of the GJB2 gene is single-site heterozygous mutation.

③ if the mutation value of the GJB2 gene is 2 and the mutation result at the V371 site is 1 or 2, or if the mutation value of the GJB2 gene is 3 and the mutation result at the V371 site is 2; the mutation type of the GJB2 gene is a V37I homozygous mutation or a compound heterozygous mutation with any site of GJB2, namely V37I/V37I or V37I/XX;

if the mutation value of the GJB2 gene is 2 and the mutation result of the V371 site is 0; or, if the mutation value of the GJB2 gene is 3 and the mutation result of the V371 site is 0 or 1; the mutation type of the GJB2 gene is homozygous or compound heterozygous mutation;

if the mutation value of the SLC26A4 gene is 0, the SLC26A4 gene mutation type is not mutated;

sixthly, if the mutation value of the SLC26A4 gene is 1, the mutation type of the SLC26A4 gene is single-site heterozygous mutation;

seventhly, if the mutation value of the SLC26A4 gene is more than 1, the mutation type of the SLC26A4 gene is homozygous or compound heterozygous mutation;

if the mutation value of the 12S rRNA of the mitochondria is 0, the mutation type of the 12S rRNA of the mitochondria is not mutated;

ninthly, if the mutation value of the mitochondrial 12S rRNA is 1, carrying out homogeneous or heterogeneous mutation on the mutation type of the mitochondrial 12S rRNA;

obtaining the Cartesian product of the GJB2 gene mutation type, the SLC26A4 gene mutation type and the mitochondrial 12S rRNA mutation type to obtain the possible 24 mutation conditions of the examinee;

the mutation value is obtained by summing up the mutation results of all the sites in the same pathogenic gene;

further, in step S3, the judgment criteria for judging the mutation status and/or pathogenicity of the genetic methylotrophic norrhea gene according to the mutation value of the gene are:

when A is_max＝0，a_maxWhen the gene is 0, the mutation type of the autosomal dominant gene is non-mutated, and the mutation type of the autosomal recessive gene is non-mutated; indicating that the subject does not carry a genetic hypothyroidism gene mutation;

when A is_max＝0，a_maxWhen the result is 1, the mutation type of the autosomal dominant gene is not mutated, and the mutation type of the autosomal recessive gene is heterozygous mutation, which indicates that the detected person is a carrier of the hereditary hypothyroidism gene;

when A is_max＝0，a_maxWhen the mutation type of the autosomal dominant gene is not mutated when the mutation type is more than 1, the mutation type of the autosomal recessive gene is homozygous or compound heterozygous mutation, and the detected person is a hereditary hypothyroidism patient;

when A is_maxWhen the gene mutation is more than 0, the mutation type of the autosomal dominant gene is the occurrence of gene mutation, which indicates that the examined person is a hereditary hypothyroidism patient;

wherein A is_maxTaking the maximum value of the mutation value of an autosomal recessive gene, a_maxIs the maximum value of the mutation value in the autosomal dominant gene;

the mutation value is obtained by summing up the mutation results of all the sites in the same pathogenic gene;

further, in step S2, when the mutation value of α -thalassemia causing gene was obtained, the result of (-SEA /) deletion mutation was marked as H₁And the sum of the mutation results of the QS sites of Hb CS and Hb is recorded as H₂；(-α 3.7.7 /) deletion, (- α 4.2.2 /) deletion and Hb WS site mutation result, and is recorded as H₃；

In this case, in step S3, the judgment criteria for judging the mutation status and/or pathogenicity of the alpha-thalassemia causing gene based on the mutation value of the gene are:

if H is₁＝0，H₂＝0，H₃0, indicating that the subject does not carry the α -thalassemia gene mutation;

if H is₁＝0，H₂＝0，H ₃1, indicating that the subject is silent α -thalassemia;

if H is₁＝0，H₂＝0，H ₃2; or, H₁＝0，H₂＝1，H ₃1 is ═ 1; or, H₁＝1，H₂＝0，H₃0, indicating that the subject is mild α -thalassemia;

if H is₁＝0，H₂＝1，H₃0, indicating that the subject is silent α -thalassemia or light α -thalassemia;

if H is₁＝0，H ₂2, indicating that the subject is thalassemia minor α or α -thalassemia intermediate;

if H is₁＝1，H₂＝0，H ₃1 is ═ 1; or, H₁＝1，H ₂1, indicating that the subject is intermediate α -thalassemia;

wherein H₁＝1，H₂＝0，H₃When the disease is 1, the subject is mild HbH disease; h₁＝1，H₂When the disease is 1, the subject is overweight HbH disease;

if H is₁2, indicating α -thalassemia major in the subject;

further, in step S3, the judgment criteria for judging the mutation status and/or pathogenicity of the gene according to the mutation value of the beta-thalassemia-causing gene are:

if the gene mutation value of the HBB gene is 0, the mutation type of the HBB gene is not mutated, which indicates that the detected person does not carry the beta thalassemia gene or does not suffer from beta thalassemia;

if the mutation value of the HBB gene is 1, the mutation type of the HBB gene is heterozygous mutation at a single locus, which indicates that the examinee suffers from mild beta thalassemia;

when the mutation value of the HBB gene is 2, the mutation type of the HBB gene is homozygous mutation or compound heterozygous mutation, which indicates that the tested object suffers from the beta thalassemia mediterranean type;

the mutation value is obtained by summing up the mutation results of all the sites in the same pathogenic gene;

further, in step S3, the judgment criteria for judging the mutation status and pathogenicity of the spinal muscular atrophy pathogenic gene according to the mutation value of the gene are:

if the mutation value of the SMN1 gene is 0, the mutation type of the SMN1 gene is no mutation, indicating that the probability that the subject does not carry the spinal muscular atrophy gene or has spinal muscular atrophy is low, but not excluding the possibility that the subject is a carrier of type 2+0 or other rare mutation carriers or patients;

if the mutation value of the SMN1 gene is 1, the mutation type of the SMN1 gene is heterozygous mutation, which indicates that the examinee is a spinal muscular atrophy pathogenic gene carrier;

if the mutation value of the SMN1 gene is 2, the mutation type of the SMN1 gene is homozygous deletion mutation, and the detected person is a spinal muscular atrophy patient;

the mutation value is obtained by summing the mutation results of all the sites in the same pathogenic gene.

In some embodiments of the present invention, there is also provided a computer processing apparatus comprising a processor and the aforementioned computer-readable storage medium, the processor executing the computer program on the aforementioned computer-readable storage medium.

In some embodiments of the present invention, there is also provided an electronic terminal, including: a processor, a memory, and a communicator; the memory is used for storing computer programs, the communicator is used for carrying out communication connection with external equipment, and the processor is used for executing the computer programs on the computer readable storage medium.

As shown in fig. 6, a schematic diagram of an electronic terminal provided by the present invention is shown. The electronic terminal comprises a processor 31, a memory 32, a communicator 33, a communication interface 34 and a system bus 35; the memory 32 and the communication interface 34 are connected with the processor 31 and the communicator 33 through a system bus 35 and are used for achieving mutual communication, the memory 32 is used for storing computer programs, the communicator 34 and the communication interface 34 are used for communicating with other devices, and the processor 31 and the communicator 33 are used for operating the computer programs so that the electronic terminal can execute the steps of the image analysis method.

The above-mentioned system bus may be a Peripheral Component Interconnect (PCI) bus, an Extended Industry Standard Architecture (EISA) bus, or the like. The system bus may be divided into an address bus, a data bus, a control bus, and the like. For ease of illustration, only one thick line is shown, but this does not mean that there is only one bus or one type of bus. The communication interface is used for realizing communication between the database access device and other equipment (such as a client, a read-write library and a read-only library). The memory may include a Random Access Memory (RAM), and may further include a non-volatile memory (non-volatile memory), such as at least one disk memory.

The processor may be a general-purpose processor, and includes a Central Processing Unit (CPU), a Network Processor (NP), and the like; the integrated circuit may also be a Digital Signal Processor (DSP), an Application Specific Integrated Circuit (ASIC), a Field Programmable Gate Array (FPGA) or other programmable logic device, discrete gate or transistor logic device, or discrete hardware components.

Those of ordinary skill in the art will understand that: all or part of the steps for implementing the above method embodiments may be performed by hardware associated with a computer program. The aforementioned computer program may be stored in a computer readable storage medium. When executed, the program performs steps comprising the method embodiments described above; the computer-readable storage medium may include, but is not limited to, floppy diskettes, optical disks, CD-ROMs (compact disc-read only memories), magneto-optical disks, ROMs (read-only memories), RAMs (random access memories), EPROMs (erasable programmable read only memories), EEPROMs (electrically erasable programmable read only memories), magnetic or optical cards, flash memory, or other type of media/machine-readable medium suitable for storing machine-executable instructions. The computer readable storage medium may be a product that is not accessed by the computer device or may be a component that is used by an accessed computer device.

In particular implementations, the computer programs are routines, programs, objects, components, data structures, etc. that perform particular tasks or implement particular abstract data types.

The invention can be used for carrying out intelligent diagnosis and genetic counseling suggestion on the gene detection results of a large number of women of childbearing age and pregnant women. Through testing, accurate diagnosis suggestions can be output for various gene mutation results, a cloud platform diagnosis suggestion report sheet is generated, and the content accords with clinical medical common knowledge. The simulated examinee is screened by the five birth defect diseases of hereditary deafness, hereditary hypothyroidism, alpha-thalassemia, beta-thalassemia and spinal muscular atrophy related hot spot sites, and the examinee is detected to carry 235delC heterozygous mutation and V37I heterozygous mutation in the GJB2 gene; a1588T heterozygous mutation within the DUOX2 gene; (- -SEA /) deletion heterozygous mutation within the alphaglobin gene. The detection result is uploaded to a cloud platform intelligent diagnosis and genetic consultation system, the cloud platform intelligent diagnosis and genetic consultation system automatically generates a cloud platform diagnosis suggestion report sheet of a detected person through program discrimination based on a knowledge map, and the report sheet comprises the case information (name, sex, age, nationality, native place, contact telephone, identity card number, medical record number) of the detected person, sample information (sample number, sample type, sampling time and reporting time), gene detection information (sent to a doctor, clinical diagnosis items, detection methods, detection content and gene detection results), and detailed diagnosis conclusion, descendant genetic risk assessment and genetic consultation suggestion are listed aiming at each genetic disease. The contents of the generated report for this subject are shown in table 6:

TABLE 6 cloud platform diagnosis suggestion report

The foregoing embodiments are merely illustrative of the principles and utilities of the present invention and are not intended to limit the invention. Any person skilled in the art can modify or change the above-mentioned embodiments without departing from the spirit and scope of the present invention. Accordingly, it is intended that all equivalent modifications or changes which can be made by those skilled in the art without departing from the spirit and technical spirit of the present invention be covered by the claims of the present invention.