35 results about "Prenatal diagnosis" patented technology

The invention relates to the field of noninvasive prenatal diagnosis, and particularly discloses a preeclampsia noninvasive screening method based on deep sequencing 8bp oligonucleotide double-fragment characteristics, which comprises the following steps: collecting preeclampsia and healthy pregnant woman peripheral blood samples, and extracting free DNA for high-throughput sequencing; the method comprises the following steps: extracting core 8-mer sequences' GTGCGCCC 'and' GATGGGGT 'in a long fragment of 150-200bp through bioinformatics analysis; an integrated support vector machine, K-nearest neighbor, extreme gradient lifting, a random forest and a multi-layer perceptron are combined with a logistic regression element classifier to construct a stacking model, the frequency of a core sequence is normalized, machine learning analysis is carried out, and the preeclampsia risk is predicted. According to the invention, two 8bp oligonucleotide characteristic fragments are specifically screened, and a deep learning architecture of multi-model fusion is combined, so that the limitations of low specificity and invasive detection of a traditional screening method are effectively broken through.

The invention provides a calculation method and system for accurately identifying heterozygosity deficiency in antenatal diagnosis, and is applied to the technical field of medical data processing. According to the method, the bam file and the variation information are obtained through whole-genome library building and sequencing analysis and data processing. SNP sites are screened, allele mutation frequency is calculated, and effective sites are screened. Dividing a genome window, calculating a homozygous rate HR value, and constructing a nonlinear weight reference based on a normal sample; and finally, an improved CBS algorithm is combined with weight reference to identify a significant AOH section, a table containing position and HR mean information is generated, heterozygosity deletion identification is completed, extra CMA detection is not needed, and the method is accurate and efficient.

The invention relates to the technical field of prenatal diagnosis, in particular to a biomarker for early prediction of preeclampsia based on body fluid free DNA and application of the biomarker, and particularly relates to a biomarker for prediction or diagnosis of pregnancy diseases, especially preeclampsia, identified through a machine learning model based on a sample set. The biomarker can be eclampsia specific motif and related motif variation trend, so that early prediction of preeclampsia with low cost, high efficiency and high accuracy is realized.

The invention provides methods for determining aneuploidy and / or fetal fraction in maternal samples comprising fetal and maternal ctDNA by massively parallel sequencing. The method comprises a novel protocol for preparing sequencing libraries that unexpectedly improves the quality of library DNA while expediting the process of analysis of samples for prenatal diagnoses.

The application belongs to the technical field of biology, and specifically discloses a truncated mutant of ANKRD11 and application thereof. The ANKRD11 gene mutant is any one of the following: a nucleic acid, wherein the nucleic acid has a target fragment, and the target fragment is compared with a wild-type ANKRD11 gene with a sequence of SEQ ID NO. 1, nucleotides from No. 1910 to No. 1913 are deleted; a polypeptide, wherein the polypeptide has a p.K637Tfs*15 mutation compared with a protein encoded by a wild-type ANKRD11 gene with a sequence of SEQ ID NO. 2. The application also relates to application of a reagent for detecting the aforementioned ANKRD11 gene mutant in screening of a KBG syndrome risk population. In the present disclosure, the pathogenic gene spectrum of the KBG syndrome is widened, the understanding of the disease is strengthened, experience is provided for clinical screening and diagnosis of the disease, and a basis is provided for prenatal diagnosis.

The application provides a calculation method and system for accurately identifying loss of heterozygosity in prenatal diagnosis, and is applied to the technical field of medical data processing. Bam files and variation information are obtained through whole genome library construction and sequencing analysis through data processing. SNP sites are screened, allele mutation frequency is calculated, and effective sites are screened. The genome window is divided, the homozygosity rate HR value is calculated, and the nonlinear weight reference is constructed based on normal samples. Finally, the improved CBS algorithm is used to identify significant AOH segments combined with the weight reference, generate a table containing position and HR average information, complete the identification of loss of heterozygosity, and do not need additional CMA detection, which is accurate and efficient.

The application belongs to the technical field of gene diagnosis, and specifically discloses a PHEX gene mutant and application thereof. The application mainly relates to the PHEX gene mutant and application thereof, and specifically relates to application of a PHEX c.112_113insA mutation in screening of a product of X-linked hypophosphatemic rickets resistant to vitamin D. The disclosure widens the pathogenic gene spectrum of X-linked hypophosphatemic rickets resistant to vitamin D, strengthens the understanding of the disease by clinical doctors, provides experience for screening and diagnosis of the disease in the clinic, and also provides a basis for prenatal diagnosis.

A method for detecting chromosome aneuploidy of a fetus on the basis of synthetic data, and a computer-readable medium for recording a program applied to perform the method are provided. According to exemplary embodiments, non-invasive prenatal diagnosis of chromosome aneuploidy in a fetus can be performed with excellent sensitivity and specificity.

This invention belongs to the field of biotechnology, specifically disclosing novel mutations of ANKRD11 and their applications. The ANKRD11 gene mutation can be any of the following: a nucleic acid having a target fragment, wherein the target fragment has a G repeat at position 4708 compared to the wild-type ANKRD11 gene with sequence SEQ ID NO.1; or a polypeptide having the p.E1570Gfs*71 mutation compared to the wild-type protein encoded by the ANKRD11 gene with sequence SEQ ID NO.2. The invention also relates to the application of reagents for detecting the aforementioned ANKRD11 gene mutation in screening individuals at risk for KBG syndrome. This disclosure broadens the pathogenic gene spectrum of KBG syndrome, enhances the understanding of the disease, provides experience for clinical screening and diagnosis of the disease, and also provides a basis for prenatal diagnosis.

The application relates to circular RNA diagnostic markers for placenta implantation lineage diagnosis and application thereof. The circular RNA diagnostic markers comprise one or two of circPHACTR4 and circZMYM4, and the cDNA sequences of the circPHACTR4 and the circZMYM4 are respectively shown as SEQ ID NO: 1 and SEQ ID NO: 2. The two circular RNA diagnostic markers are significantly up-regulated in PAS peripheral blood, and can be used as PAS diagnostic markers alone or in combination to realize high-sensitivity, specificity and objective detection of placenta implantation lineage. The sensitivity of circPHACTR4 alone is 74%, the sensitivity of circZMYM4 alone is 68.4%, the two circRNAs are combined to have a good prediction effect on PAS, and the sensitivity and specificity can reach 82% and 88.9% in combination with the diagnosis results of clinical indexes and B ultrasonic waves, so that the precision of the prenatal diagnosis of PAS is greatly improved.

The invention belongs to the technical field of gene diagnosis, and discloses an SLC16A2 gene mutant and application of the SLC16A2 gene mutant in AHDS disease risk analysis. The specifically disclosed SLC16A2 gene mutant is any one of nucleic acid, a target fragment exists in the nucleic acid, and compared with a wild type SLC16A2 gene with the sequence of SEQ ID NO.1, the target fragment has c.963964delinsAA mutation, and the target fragment has c.963964delinsAA mutation. Compared with a protein coded by a wild type SLC16A2 gene with a sequence of SEQ ID NO.2, the polypeptide has p.Y321 * mutation. Meanwhile, the invention discloses application of a reagent for detecting the SLC16A2 gene mutant in preparation of a product for screening AHDS. According to the invention, the pathogenic gene spectrum of the AHDS is expanded, the cognition of a clinician on the disease is improved, experience is accumulated for clinical screening and diagnosis of the disease, and a basis is provided for prenatal diagnosis.

The invention discloses a rapid free DNA enrichment method based on a paramagnetic particle method, which comprises the following steps: (1) taking plasma, adding a protease K solution, fully and uniformly mixing, and incubating; (2) adding the magnetic beads and the binding liquid, oscillating, instantaneously centrifuging and standing until the magnetic beads are completely adhered to the wall; (3) absorbing and abandoning all supernatant; (4) adding an eluent, oscillating, instantaneously centrifuging, continuously placing on the magnetic frame, and standing for 5 minutes until the magnetic beads are completely adhered to the wall; and (5) taking the supernatant, and transferring the supernatant into a sample storage tube for enrichment. According to the method, the DNA purity is high, a QSep result shows that no impurity peak interference exists, the feasibility of the method is proved, and the corresponding magnetic beads carrying positive charges can be used for extraction of the method, so that the method has relatively high practicability. A high-quality template can be provided for downstream molecule detection and analysis (including NGS sequencing, digital PCR and the like), and particularly, important values are shown in clinical application scenes such as liquid biopsy and antenatal diagnosis.

The invention provides methods for determining aneuploidy and / or fetal fraction in maternal samples comprising fetal and maternal cfDNA by massively parallel sequencing. The method comprises a novel protocol for preparing sequencing libraries that unexpectedly improves the quality of library DNA while expediting the process of analysis of samples for prenatal diagnoses.

The invention relates to a Z value correction method for NIPT inspection. The method comprises the following steps: acquiring an NIPT test sample set, a normal diploid reference sample set and an interventional prenatal diagnosis data set of the NIPT test sample set; establishing an NIPT test misdiagnosis sample set based on the NIPT test sample set and the interventional antenatal diagnosis data set; obtaining free DNA sequencing data of the NIPT test misdiagnosis sample set and the normal diploid reference sample set; identifying a DNA sequence vigilance Z value region and a DNA sequence effective Z value contribution region based on free DNA sequencing data of the NIPT test misdiagnosis sample set and the normal diploid reference sample set; and performing Z value correction based on the data feature information of the free DNA sequencing data of the DNA sequence vigilance Z value region of the NIPT test misdiagnosis sample set and the normal diploid reference sample set, and generating Z value correction result information. By adopting the method, the accuracy and reliability of NIPT detection can be effectively improved, and the positive predicted value of NIPT detection is improved.

The invention relates to a method and a kit for generating nucleic acid for target capture. The method involves binding of a circ-olio sequence to at least one target oligonucleotide to generate a single stranded circular DNA. The single stranded circular DNA is bidirectionally amplified with the sense and antisense oligonucleotides, followed by biotinylation to obtain for a double-stranded concatemer of linear sequence. The double-stranded concatemer of linear sequence with the restriction endonucleases produces a target capture nucleic acid. The method offers a scalable targeted capture of pr eselected genomic regions, and is cost effective. The method of generating nucleic acid for target capture has application in the field of oncology hematology, inherited malignancies, germline disorders, microbiology and prenatal diagnosis. The invention generates baits over high GC-rich regions of the genome.

The application belongs to the technical field of gene detection and molecular diagnosis, and particularly relates to a kit for detecting a pathogenic gene of phenylketonuria and application thereof. The kit comprises a primer pair for amplifying specific exons and splicing regions of a phenylalanine hydroxylase gene, and specific probes for detecting hot spot mutations and deletion / repetition variations of the gene. The application can detect genetic variations related to phenylketonuria in one time, quickly and accurately by combining optimized multiplex polymerase chain reaction with high-throughput sequencing or gene chip technology, and covers various known hot spot mutations and copy number variations including c.1222C>T, c.1068-11G>A, c.728G>A and c.1162G>A. The kit has high detection sensitivity and strong specificity, and is suitable for positive recall diagnosis of neonatal phenylketonuria screening, genetic diagnosis of suspected patients, carrier screening and prenatal diagnosis, and provides an efficient tool for precise prevention and control of phenylketonuria.

Prenatal genetic testing allows early detection of genetic disease in a fetus. Described herein are methods of detecting the presence or absence of a genetic variant in a region of interest in the genome of a fetus in a pregnant woman. The methods are noninvasive, and can use cell-free DNA (cfDNA) present in the plasma of the pregnant woman. A DNA library is constructed from the cfDNA, and DNA molecules comprising the region of interest or portions thereof are enriched and analyzed, for example by sequencing. The methods described herein can also rely on constructing a maternal haplotype to provide even higher resolution fetal genetic variant determination.

The application belongs to the technical field of gene diagnosis, and discloses a new pathogenic gene CYLC1 of sperm head deformity and a mutation detection reagent thereof; the new pathogenic gene CYLC1 of sperm head deformity is used as a candidate gene diagnosis object of sperm head deformity, and four homozygous missense mutations thereof are c.1157A>C / p.N386T, c.1377G>T / p.K459N, c.1402T>G / p.S468A and c.1834T>A / p.C612S. The application can use the detection reagent to perform simple, fast and accurate gene diagnosis on sperm head deformity patients, and is also helpful for understanding pathogenesis, genetic counseling, prenatal diagnosis and gene therapy. The application can also use the established Cylc1 gene knockout mouse model to reveal the role and mechanism of Calicin-1 protein on sperm acrosome anchoring and head development of mammals.

The invention relates to the technical field of seedling cultivation, in particular to an abdomen protection device for antenatal diagnos.The abdomen protection device comprises a positioning sliding base, movable sliding blocks are slidably installed at the left end and the right end of the front side of the positioning sliding base respectively, a swing clamping block is rotatably installed at the front end of each movable sliding block, and an adjusting sliding plate is installed on each swing clamping block; an inserting buckle is installed at the front end of each adjusting sliding plate, a protection band is installed between the two inserting buckles, an adjusting box is installed on the protection band, and a fetal heart monitor is detachably installed in the adjusting box. The fetal heart monitor monitors the heartbeat frequency of a fetus, helps to evaluate the health condition of the fetus in the uterus and can also reflect whether the fetus is hypoxia or not and whether intrauterine distress exists or not, and due to the fact that the protective cotton cloth is arranged on the outer side face of the protective band, the pressure on the abdomen can be relieved, and the protection effect on the abdomen is achieved.

The invention relates to the field of molecular biology, in particular to Down's syndrome induced pluripotent stem cells as well as a construction method and application thereof. Four transcription factor reprogramming methods of KLF4, OCT4, c-MYC and SOX2 are utilized to construct Down's syndrome induced pluripotent stem cells, an expression profile of non-coding RNA in derived exosomes of the Down's syndrome induced pluripotent stem cells is systematically analyzed, differentially expressed non-coding RNA is screened, an RT-ddPCR technology is further adopted to analyze the expression condition of the differentially expressed non-coding RNA in maternal peripheral blood, and the DDown's syndrome induced pluripotent stem cells are obtained. And new information is provided for screening of novel markers for antenatal diagnosis of Down's syndrome and establishment of a detection method.

The invention relates to a triploid and / or copy number neutral heterozygosity deletion detection method and device and application, and belongs to the technical field of biological information. The method comprises the following steps: 1) acquiring genome sequencing comparison data of a sample to be detected; 2) performing bin division processing on the genome sequencing comparison data, determining SNP (Single Nucleotide Polymorphism) feature information in each bin, and performing bin filtering based on the feature information; 3) constructing a reference baseline by using a normal sample; and 4) based on the steps 1)-3), performing triploid and / or copy number neutral heterozygosity deletion detection on the to-be-detected sample. According to the method, detection can be completed based on low-depth genome sequencing data, the detection cost is effectively reduced, and the detection accuracy and sensitivity are improved through bin division and SNP feature information filtering. A reference baseline constructed by a normal sample is used for constructing a dynamic threshold value, so that the reliability of a detection result is enhanced, and the method is suitable for various scenes such as prenatal diagnosis, genetic diseases and hematologic tumors.

Prenatal genetic testing allows early detection of genetic disease in a fetus. Described herein are methods of detecting the presence or absence of a genetic variant in a region of interest in the genome of a fetus in a pregnant woman. The methods are noninvasive, and can use cell-free DNA (cfDNA) present in the plasma of the pregnant woman. A DNA library is constructed from the cfDNA, and DNA molecules comprising the region of interest or portions thereof are enriched and analyzed, for example by sequencing. The methods described herein can also rely on constructing a maternal haplotype to provide even higher resolution fetal genetic variant determination.

The invention provides a cfDNA extraction kit and an extraction method. The cfDNA extraction kit provided by the invention comprises the first binding solution, the second binding solution and the magnetic microspheres, and by limiting the components and contents of the first binding solution and the second binding solution, the cfDNA extraction kit can be promoted to generate a good matching effect with the magnetic microspheres, so that the bottleneck of a traditional single-step paramagnetic particle method is broken through by regulating and controlling the binding environment of the magnetic microspheres in stages, and the detection sensitivity of the cfDNA extraction kit is improved. The extraction efficiency and the extraction purity of the cfDNA are effectively improved, and the method has the advantages of simplicity and convenience in operation and high repeatability. Reliable technical support is provided for liquid biopsy, and the method is suitable for application scenes such as tumor liquid biopsy and noninvasive prenatal diagnosis.

The application belongs to the technical field of biology, and specifically discloses a new mutation of ANKRD11 related to KBG syndrome and application thereof. The ANKRD11 gene mutation is any one of the following: a nucleic acid, the nucleic acid has a target fragment, and the target fragment is compared with a wild-type ANKRD11 gene with a sequence of SEQ ID NO. 1, nucleotides from No. 6281 to No. 6282 are deleted; a polypeptide, compared with a protein encoded by a wild-type ANKRD11 gene with a sequence of SEQ ID NO. 2, has a p.L2095Gfs*6 mutation. The application also relates to application of a reagent for detecting the aforementioned ANKRD11 gene mutation in screening of a KBG syndrome risk population. In the disclosure, the pathogenic gene spectrum of KBG syndrome is widened, the understanding of the disease is strengthened, experience is provided for clinical screening and diagnosis of the disease, and a basis is provided for prenatal diagnosis.

The invention discloses an antenatal diagnosis and examination device, and relates to the technical field of antenatal diagnosis. Under the action of the puncture component, the puncture needle is driven to move and puncture into an amniotic cavity of a pregnant woman; through the operation of the driving mechanism, the hemisphere I and the hemisphere II are driven to synchronously and reversely rotate under the action of the two transmission mechanisms; under the action of the switching part, the two transmission mechanisms are driven to move relatively, so that the hemisphere I and the hemisphere II shake continuously; and along with the continuous operation of the switching part, the hemisphere I and the hemisphere II synchronously rotate in the same direction. According to the device, a mechanical puncture mode is achieved, amniotic fluid and non-liquid substances in the amniotic fluid can be collected, the situation that a puncture needle is blocked can be avoided, the purpose of scattering and conveying the non-liquid substances can be achieved through switching and matching of multiple movement modes, and the excellent intelligent effect is achieved.

The present application relates to the field of noninvasive prenatal diagnosis, and specifically discloses a preeclampsia noninvasive screening method based on deep sequencing of 8bp oligonucleotide double-fragment features, comprising: collecting peripheral blood samples of preeclampsia and healthy pregnant women, extracting free DNA for high-throughput sequencing; extracting core 8-mer sequences 'GTGCGCCC' and 'GATGGGGT' in 150-200bp long fragments through bioinformatics analysis; using integrated support vector machines, K-nearest neighbors, extreme gradient boosting, random forests and multilayer perceptron combined with logistic regression meta-classifier to construct a stacking model, normalizing the frequency of core sequences, performing machine learning analysis, and predicting the risk of preeclampsia. The present application effectively breaks through the limitations of traditional screening methods with low specificity and invasive detection by specifically screening two 8bp oligonucleotide feature fragments and combining a deep learning architecture with multi-model fusion.

The invention relates to the technical field of noninvasive prenatal diagnosis, and particularly discloses a preeclampsia noninvasive screening method based on deep sequencing 4-mer terminal motif spectrum characteristics, which comprises the following steps: collecting preeclampsia and healthy pregnant woman peripheral blood samples, and extracting free DNA for high-throughput sequencing; 12 key terminal 4-mer motifs are extracted and screened out through bioinformatics; and a multi-layer perceptron (MLP) model is adopted to carry out machine learning analysis, and the preeclampsia risk is predicted. According to the method, 12 terminal 4-mer motif spectrums are specifically screened, and the MLP model is combined, so that the limitation that a traditional screening method is low in specificity and invasive in detection is effectively broken through.

The invention provides a nevus basal cell carcinoma syndrome gene mutation site and application thereof, the gene mutation site is a frame-shift mutation c.724725delCA of a No. 5 exon of a PTCH1 gene, and the mutation causes the change of a subsequent codon reading frame and causes the frame-shift mutation p.Q242Vfs * 9 of PTCH1 protein. According to the c.724725delCA mutation site disclosed by the invention, the pathogenic gene spectrum of the NBCCS is expanded. The PTCH1 gene c.724725delCA mutation provided by the invention can be applied to NBCCS diagnosis, and can also be used for preparing a kit containing a mutation detection primer or probe, and a genetic counseling and prenatal diagnosis method based on the mutation.

The present application belongs to the technical field of non-invasive prenatal testing, and particularly relates to a preparation method of a pregnant woman simulated plasma standard product capable of fetal concentration enrichment through fragment size. The present application provides a preparation method of a pregnant woman plasma free DNA simulation sample. The method combines specific DNA fragmentation processing technology to prepare a simulation sample with high fidelity and stability and capable of accurately simulating the fetal free DNA and pregnant woman free DNA distribution proportion in real pregnant woman plasma, for quality control and evaluation of non-invasive prenatal diagnosis technology. The method can accurately prepare the pregnant woman simulated plasma DNA with the corresponding fetal concentration according to the requirement, and the prepared pregnant woman simulated plasma can meet the requirement of the application of fetal concentration enrichment test, and at the same time, the cfDNA fragment distribution in the pregnant woman plasma is restored in the maximum range.