84 results about "Aneuploidy" patented technology

The invention relates to the field of molecular cytogenetics and potato ploidy breeding, in particular to a potato ploidy identification method for marking and counting chromosome centromere based on a potato CENH3 antibody and a ploidy detection kit. According to the method, the chromosome centromere is marked by specifically recognizing the antibody of the potato centromere nucleosome core histone CENH3 and combining the immunofluorescence technology, so that the accurate counting of the chromosome centromere is realized at the single cell level, and the ploidy of potatoes is judged. The method comprises the following steps: preparing a leaf cell suspension, sequentially incubating a potato CENH3 antibody and a labeled secondary antibody after immobilization, and observing and counting by a microscope after redyeing. The method has the advantages of high species specificity, high throughput and low cost, is not limited by special material taking parts of root tips or shoot tips and cell division periods, can accurately identify the uploid and aneuploid of potatoes, and provides an efficient tool for potato germplasm resource evaluation and cross breeding.

The invention relates to a method and a device for detecting chromosome uploidy. The method comprises the following steps: acquiring nanopore sequencing data of a detection sample; obtaining window division information of the reference genome; for each detection sample, determining a standard comparison sequence number of the detection sample in each window based on the nanopore sequencing data of the detection sample and the window division information; for each negative sample, eliminating discrete values in the standard alignment sequence number of each negative sample in each window, and correcting the standard alignment sequence number of each negative sample in each window to obtain a standard alignment sequence number baseline value of each window; and according to the standard comparison sequence number of the to-be-analyzed sample in each window and the corresponding standard comparison sequence number baseline value of each window, evaluating the chromosome uploidy condition of the to-be-analyzed sample. According to the method, the third-generation sequencing data is creatively applied to chromosome aneuploidy analysis through a new baseline data construction mode.

The present invention addresses the problem of specifically clarifying the effects on a fertilized egg when 5-ALA is administered to a human female suffering from infertility, and constructing a more effective means for treating infertility through the suppression of chromosomal abnormalities. It has been confirmed that, when 5-ALA is ingested in combination with a drug therapy that is generally performed in the treatment of female infertility, the rate of chromosome aneuploidy in a fertilized egg or the like is significantly reduced, and the qualitative improvement of an embryo through improvement of the stability of the chromosomes is expected.

The invention provides methods for non-invasive prenatal testing that allow for detecting risk of chromosomal and subchromosomal abnormalities, including but not limited to aneuploidies, microdeletions and microduplications, insertions, translocations, inversions and small-size mutations including point mutations and mutational signatures. The methods of the invention utilize a pool of TArget Capture Sequences (TACS) to enrich for sequences of interest in a mixed sample containing both maternal and fetal DNA, followed by massive parallel sequencing and statistical analysis of the enriched population to thereby detect the risk of a genetic abnormality in the fetal DNA. Kits for carrying out the methods of the invention are also provided.

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 invention discloses a chromosome replacement method based on CRISPR / Cas9, MMCT and tetraploid complementation and application, and belongs to the technical field of molecular biology. According to the method, microcell-mediated chromosome transfer and CRISPR / Cas9 chromosome knockout are combined, endogenous homologous chromosomes are removed while exogenous chromosomes are transferred, the characteristics of cell uploidy are maintained, and the influence of aneuploidy is avoided; and chromosome replacement animal individuals are obtained at one time by using a tetraploid complementation technology, so that the experiment efficiency and success rate are improved. The method is accurate and efficient, has huge potential in the fields of regenerative medicine, synthetic biology and the like, successfully realizes mega-level length Y chromosome transfer and allosome and heterosome chromosome replacement, and shows the value of the method in large-fragment DNA operation and heterosome chromosome application research.

This document provides methods and materials for assessing and / or treating subjects (e.g., humans) suspected of having cancer. For example, this document provides methods and materials for a nucleic acid sequence analysis which can determine a sequence of B cell receptor. In some cases, determining a sequence of B cell receptor (and, optionally, identifying the presence of one or more mutations and / or identifying the presence of aneuploidy) in DNA (e.g., cell-free DNA (cfDNA)) in a fluid sample (e.g., a cerebrospinal fluid sample) obtained from a subject (e.g., a human subject such as a human suspected of having cancer) can be used to identify the subject as having cancer.

The invention belongs to the technical field of biological information detection, provides a genetic detection method, system, product and equipment before embryo implantation, and aims to solve the problems that a conventional genetic detection process before embryo implantation is complicated, depends on a complete family sample, is difficult to distinguish equilibrium translocation and unbalanced translocation, is low in linkage analysis efficiency, needs to independently detect items and the like. According to the method provided by the invention, parent haplotypes can be constructed on the basis of monomolecular length reading sequencing data of male parents, female parents and to-be-implanted embryo samples in families, sequence similarity is analyzed on the basis of the parent haplotypes, and the to-be-implanted embryo samples can be obtained by tracing genetic sources of the haplotypes of the to-be-implanted embryo samples. And determining whether the to-be-implanted embryo carries the single-gene genetic disease and / or chromosome structure rearrangement or not. According to the method, integrated detection of aneuploidy, monogenic hereditary diseases and chromosome structure rearrangement before embryo implantation can be completed on a single platform, and whether the embryo to be implanted has genetic defects or not can be quickly, simply, efficiently and accurately judged in a one-stop manner.

A method for detecting fetal CNVs through non-invasive prenatal testing, comprising steps: (a) collecting blood samples from pregnant women; (b) extracting cfDNA fragments from the blood samples, performing whole genome sequencing on extracted cfDNA fragments to obtain cfDNA sequencing data, and preprocessing cfDNA sequencing data by removing adapters, aligning and mapping reads to a referenced human genome; (c) performing quality control on obtained cfDNA sequencing data for being accepted for the prediction; (d) dividing referenced genome into a plurality of non-overlapping bins and filtering the bins based on a predetermined GC-content threshold for bins; (e) defining a CNV detection window, a bin size, a set of features for machine learning / deep learning models and fine-tune model for detecting fetal CNV for selecting a final model; and (f) applying the final model to predict fetal CNVs, including microdeletion syndromes, or microduplications, or aneuploidies, or the number of sex chromosomes.

An Artificial Intelligence (AI) based computational system is used to non-invasively estimate the presence of a range of aneuploidies and mosaicism in an image of embryo prior to implantation. Aneuploidies and mosaicism with similar risks of adverse outcomes are grouped and training images are labelled with their group. Separate AI models are trained for each group using the same training dataset and the separate models are then combined, such as by using an Ensemble or Distillation approach to develop a model that can identify a wide range of aneuploidy and mosaicism risks. The AI model for a group is generated by training multiple models including binary models, hierarchical layered models and a multi-class model. In particular the hierarchical layered models are generated by assigning quality labels to images. At each layer the training set is partitioned in the best quality images and other images. The model at that layer is trained on the best quality images, and the other images are passed down to the next layer and the process repeated (so the remaining images are separated into next best quality images and other images). The final model can then be used to non-invasively identify aneuploidy and mosaicism and associated risk of adverse outcomes from an image of an embryo prior to implantation.

Massively parallel sequencing of cell-free maternal plasma DNA has recently been demonstrated to be a safe and effective method for screening for fetal chromosomal aneuploidy. Here, we report an improved sequencing method that significantly increases throughput and reduces costs by replacing the laborious sequencing library preparation step with PCR using a single primer pair. Using this method, samples containing as little as 4% trisomy 21 DNA can be readily distinguished from euploid samples.

The present application belongs to the technical field of biological information detection, and provides a pre-implantation genetic diagnosis method, system, product and equipment. The present application is aimed at the problems of complex traditional pre-implantation genetic diagnosis process, dependence on complete family sample, difficulty in distinguishing balanced translocation and unbalanced translocation, low linkage analysis efficiency, and the need for independent detection, etc. The method provided by the present application can be based on single molecule long read sequencing data of the paternal sample, the maternal sample and the to-be-implanted embryo sample in the family, construct the parental haplotype, and analyze the sequence similarity based on the same. By tracing the genetic source of the haplotype of the to-be-implanted embryo sample, it is determined whether the to-be-implanted embryo carries a monogenic genetic disease and / or a chromosome structure rearrangement. The present application can complete the integrated detection of pre-implantation aneuploidy, monogenic genetic disease and chromosome structure rearrangement on a single platform, and quickly, simply, efficiently and accurately determine whether the to-be-implanted embryo has genetic defects.

The invention relates to the use of carbon monoxide for preserving gametes. Means and methods for preserving gametes are provided. The method of the invention comprises the steps of a) providing a gamete or a sample comprising said gamete in a container, and b) contacting said gamete in said container with carbon monoxide. The invention also provides the use of carbon monoxide in the treatment and / or prevention of diseases, such as diseases caused by or associated with elevated DNA cleavage, redox potential of gametes, and / or diseases of gametes caused by or associated with elevated ROS levels. Also provided are uses of carbon monoxide for the prevention of congenital abnormalities and / or aneuploidy, as well as for the treatment of diseases caused by and / or associated with elevated DNA cleavage and / or redox potential of gametes. The invention also relates to a method of treating congenital abnormalities or aneuploidy comprising contacting carbon monoxide gas with gametes of a patient in need thereof. Thus, the means, methods and uses of the present invention ensure that gametes are preserved in a functional / intact state, thereby ensuring maintained and / or improved gamete quality. Thus, such carbon monoxide treated / carbon monoxide exposed gametes are particularly useful in reproductive techniques, such as in vitro reproductive techniques, including in human assisted reproductive techniques and / or in animal (artificial) insemination techniques.

Methods of identifying genetic mutations and / or genetic alterations are provided.SOLUTION: Methods for classifying the presence or absence of genetic mosaicism for a copy number variation in one or more fetuses (e.g., predicting whether a fetus or more than one fetus is affected by a copy number variation) are provided. The sample nucleic acid is subjected to a sequencing process and the resulting sequence reads are analyzed to identify genetic copy number variation regions. Genetic mosaicism for a copy number variation region is classified for a fetus or more than one fetus based on (i) a mosaicism ratio of a fraction of nucleic acid having the copy number variation region to a fraction of fetal nucleic acid and (ii) a chromosome having the genetic copy number variation region (e.g., an identified type of aneuploidy) or (ii) a number of fetuses carried by a pregnant female.SELECTED DRAWING: None

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.

The application discloses a detection system, device and method for embryo chromosomal aneuploidy and parent contamination analysis. The system comprises a database module, an alignment module, an analysis and calculation module and a parent contamination detection module. The analysis and calculation module is used for performing the following steps: calculating the ratio of the number of effective sequences matched to each chromosome to the number of corresponding chromosome sequences in the reference database, performing statistical analysis, obtaining the number of target chromosomes of the sample to be detected, and obtaining the detection result of whether the frequency of alleles observed in the genetic linkage disequilibrium mode is abnormal. The parent contamination detection module comprises a contamination prediction model. The aneuploidy detection and parent contamination analysis of the embryo can be simultaneously realized by one detection.

A chromosomal aneuploidy analysis method and a use. The method comprises: using sequencing data of a sample to be tested and an alignment result thereof to calculate the fetal DNA concentration in said sample and the window depth of said sample within a set window; and calculating the average relative depth of all samples in a selected reference set within the set window as a correction baseline, using the correction baseline to correct the window depth of said sample, calculating a Z value of said sample on the basis of the corrected window depth, and on the basis of the Z value, determining whether an aneuploidy abnormality has occurred to a fetal chromosome of said sample. Using the selected reference set to calculate the correction baseline for correcting said sample enables more stable and accurate detection of the chromosomal aneuploidy abnormality in said sample under the condition that there are no samples in a same batch as references, thereby reducing inter-batch variability in testing.

Disclosed herein is a system and method for increasing the fidelity of measured genetic data, for making allele calls, and for determining the state of aneuploidy, in one or a small set of cells, or from fragmentary DNA, where a limited quantity of genetic data is available. Poorly or incorrectly measured base pairs, missing alleles and missing regions are reconstructed using expected similarities between the target genome and the genome of genetically related individuals. In accordance with one embodiment, incomplete genetic data from an embryonic cell are reconstructed at a plurality of loci using the more complete genetic data from a larger sample of diploid cells from one or both parents, with or without haploid genetic data from one or both parents. In another embodiment, the chromosome copy number can be determined from the measured genetic data, with or without genetic information from one or both parents.

The invention belongs to the technical field of assisted reproduction, and particularly relates to a biological response type memristor for in-vitro embryo monitoring and application of the biological response type memristor. The memristor comprises a substrate, a bottom electrode, a dielectric layer and a top electrode which are sequentially arranged from bottom to top, the dielectric layer is a double-layer functional layer composed of an Nb2O5 thin film and a barium titanate thin film, the barium titanate thin film is located on the upper layer of the bottom electrode, and the Nb2O5 thin film is located on the upper layer of the barium titanate thin film. The memristor realizes response to biological information by monitoring metabolic byproducts and oxidative stress markers in an embryo in-vitro culture solution in real time, realizes operation by inducing redistribution of surface charges of an interface through ion adsorption, and shows a resistance state transformation characteristic. Besides, the system breaks through the limitation of traditional microscope visual evaluation, realizes direct, sensitive and quantitative electric signal reading of the embryo metabolism state and the oxidative stress level, and solves the problem of embryo development potential evaluation caused by the increase of aneuploid rate in old lying-in women and recurrent implantation failure groups.

The invention belongs to the field of genetics detection, and particularly relates to a genetics-integrated single-molecule sequencing detection kit and system before embryo implantation. Specifically, the kit and the system provided by the invention can realize synchronous detection of human pre-implantation embryo aneuploid, copy number variation, chromosome structure abnormality and monogenic diseases. According to the method, the parent sample and the embryo sample are subjected to single molecule length reading sequencing, family members except a certificate and parents are not needed, direct detection of aneuploidy, copy number variation, chromosome structure abnormality and the like and indirect detection based on haplotype inference are achieved, the detection result is accurate, sensitive and visual, and information is comprehensive. According to the kit and the system disclosed by the invention, only the same experimental system and the same single-molecule long-fragment sequencing platform are needed, so that PGT-A, PGT-M, PGT-SR and haplotype genetic condition detection can be completely supported, the process is simple and convenient, the application range is wide, and therefore, the kit and the system have a good practical application value.

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 the technical field of biological information processing, in particular to a cattle embryo pre-implantation genetic evaluation method and system based on whole genome sequencing, and the method comprises the following steps: obtaining whole genome sequencing data of a male parent and a female parent, embryo trophoblast live detection sequencing data and culture solution free desoxyribonucleic acid sequencing data; performing variation detection and haplotype phasing on male and female parent data to form haplotype data, and calculating a haplotype transmission posterior at an anchor point based on trophoblast data; performing genome segmentation based on reading depth observation and allele frequency observation of a trophoblast and a culture solution, and performing Bayesian inference by combining haplotype transfer posteriori as priori to obtain posteriori probabilities of aneuploid, copy number variation, chimera, pathogenic homozygosis and pollution events; and outputting a passing / rechecking / elimination conclusion, adding sequencing and updating the posteriori during rechecking until ending, and outputting a final conclusion and a genome breeding value, so that the evaluation reliability and the decision interpretability are improved.

Disclosed herein is a system and method for increasing the fidelity of measured genetic data, for making allele calls, and for determining the state of aneuploidy, in one or a small set of cells, or from fragmentary DNA, where a limited quantity of genetic data is available. Poorly or incorrectly measured base pairs, missing alleles and missing regions are reconstructed using expected similarities between the target genome and the genome of genetically related individuals. In accordance with one embodiment, incomplete genetic data from an embryonic cell are reconstructed at a plurality of loci using the more complete genetic data from a larger sample of diploid cells from one or both parents, with or without haploid genetic data from one or both parents. In another embodiment, the chromosome copy number can be determined from the measured genetic data, with or without genetic information from one or both parents.

The invention discloses an RIF whole course management method, which comprises the following steps: by adopting a next generation sequencing (NGS) technology, 24 chromosomes can be covered, whole chromosome aneuploidy can be screened, the detection resolution is below 1Mb, and microdeletion / microrepetition can be identified. Compared with a traditional array-CGH technology, the method has the advantages that the epiploid embryo screening precision is remarkably improved by 30%, high-quality embryos with normal chromosomes can be selected, the embryo implantation success rate is greatly improved, the abortion risk is reduced, bad pregnancy knots caused by chromosome abnormality are reduced, embryo development is dynamically recorded with the frequency of one frame every 10-20 minutes through a time-difference imaging system, and the screening accuracy of the epiploid embryos is improved. Key time nodes are analyzed through an AI algorithm, an embryo potential scoring model is constructed in combination with morphological parameters, and the prediction implantation probability accuracy rate reaches 75% or above. Scientific basis is provided for clinicians to select the embryo with the highest implantation potential, blind transplantation is avoided, and the success rate of test tube babies is increased.

Disclosed herein is a system and method for increasing the fidelity of measured genetic data, for making allele calls, and for determining the state of aneuploidy, in one or a small set of cells, or from fragmentary DNA, where a limited quantity of genetic data is available. Poorly or incorrectly measured base pairs, missing alleles and missing regions are reconstructed using expected similarities between the target genome and the genome of genetically related individuals. In accordance with one embodiment, incomplete genetic data from an embryonic cell are reconstructed at a plurality of loci using the more complete genetic data from a larger sample of diploid cells from one or both parents, with or without haploid genetic data from one or both parents. In another embodiment, the chromosome copy number can be determined from the measured genetic data, with or without genetic information from one or both parents.

To provide a method for identifying the presence of aneuploidy in the genome of a mammal.SOLUTION: Amplifying a plurality of chromosomal sequences in a cell-free DNA sample with a single primer pair complementary to the chromosomal sequences, wherein the primer pair amplifies a unique amplicon comprising short interspersed repeat sequences, determining at least a portion of the nucleic acid sequence of the plurality of amplicons to produce amplicon sequences, mapping the amplicon sequences to a reference genome, dividing the amplicon sequences into a plurality of genomic intervals, quantifying the number of reads for amplicon sequences mapped to the genomic intervals, and comparing the number of reads of amplicon sequences within a first genomic interval to: Comparing the number of reads of amplicon sequences in the one or more different genomic intervals, thereby identifying the presence of an aneuploidy in the genome of the mammal.SELECTED DRAWING: None

Provided herein are methods and materials for detecting and / or treating a subject (e.g., a human) having cancer. In some embodiments, methods and materials are provided for identifying a subject has cancer (e.g., local cancer) in which the presence of one or more members of two or more categories of biomarkers is detected. In some embodiments, methods and materials are provided for identifying a subject has cancer (e.g., local cancer) in which the presence of one or more members of at least one category of biomarkers and the presence of aneuploidy are detected. In some embodiments, the methods described herein provide for increased sensitivity and / or specificity in detecting cancer in a subject (e.g., a human).

The present invention discloses a kit for detecting aneuploidy changes in the AZF region of the Y chromosome based on a multiplex PCR method, and relates to the field of gene detection technology. The present invention provides a method and a kit for detecting sperm disomy rate and minor copy number changes of Y chromosome aneuploidy using multiplex PCR, with a detection sensitivity of about 1% and a detection lower limit of 5%, which is higher than the current industry sensitivity level of 20% to 30%. The method and kit disclosed in this patent can predict the clinical outcomes of subsequent auxiliary diagnosis by detecting minor changes in sperm aneuploidy, and avoid fertility risks in advance. The technology disclosed in the present invention achieves the detection purpose that cannot be achieved by current conventional technologies, and the disclosed technical parameters exceed the technical indicators of current conventional technologies by 4-30 times, which is extremely innovative.

This application discloses a method, apparatus, and storage medium for detecting fetal chromosomal aneuploidy. The method for detecting fetal chromosomal aneuploidy includes calculating a new Z-value for the sample based on the fetal DNA concentration, Z-value, and chimerism of the cell-free DNA in the pregnant woman's blood; the new Z-value is used to determine whether fetal chromosomal aneuploidy has occurred. Chimerism is the ratio of abnormal fetal cells to all fetal cells. This application is the first to incorporate chimerism into the detection of fetal chromosomal aneuploidy, comprehensively considering three variables—fetal DNA concentration, chimerism, and Z-value—to calculate a new Z-value, which improves the accuracy of NIPT detection, provides excellent differentiation between true positive and false positive samples, and reduces false positives. The new Z-value conforms to a normal distribution, meeting current regulatory and clinical requirements, reducing data distribution volatility, thereby reducing the gray area rate, reducing the retest rate, and improving the stability of the test results.

The application provides a non-invasive prenatal fetal chromosome detection device, which enriches fetal free DNA in the plasma of a pregnant woman to be detected through a magnetic bead purification method, obtains a free DNA sample to be detected, improves the fetal free DNA concentration proportion in the sample to be detected, can realize automatic detection of the free DNA sample to be detected, reduces the occurrence of detection failure or false negative results, performs chromosome detection based on a negative Z value and a positive Z value corresponding to the chromosome to be detected, can effectively improve the accuracy and comprehensiveness of fetal chromosome detection, covers non-euploid abnormality detection of 23 pairs of chromosomes, improves the sensitivity and specificity of chromosome detection, provides stronger technical support for prenatal screening, and can be widely applied to the technical field of chromosome detection.