31 results about "Chromosomal rearrangement" patented technology

The present invention generally relates to spatial and structural genomic analysis compositions, which can be used for the mapping of chromosomes and structural analyses of chromosomal rearrangements, including the entire chromosome, as well as specific portions or regions of interest of the chromosomes. In some embodiments, multiple portions of the genome can be distinguished, for instance, using a first detection entity and a second detection entity different from the first detection entity. The detection entities may be immobilized relative to oligonucleotides, which may be selected to bind to different locations within the chromosome. For instance, the oligonucleotides may be at least substantially complementary to the chromosome, e.g., substantially complementary to a specific location of the chromosome.

The present invention generally relates to spatial and structural genomic analysis compositions, which can be used for the mapping of chromosomes and structural analyses of chromosomal rearrangements, including the entire chromosome, as well as specific portions or regions of interest of the chromosomes. In some embodiments, multiple portions of the genome can be distinguished, for instance, using a first detection entity and a second detection entity different from the first detection entity. The detection entities may be immobilized relative to oligonucleotides, which may be selected to bind to different locations within the chromosome. For instance, the oligonucleotides may be at least substantially complementary to the chromosome, e.g., substantially complementary to a specific location of the chromosome.

Provided are novel methods and compositions for the diagnosis, prognosis and treatment of tumor involving a chromosomal rearrangement, in particular a tumor or neoplasia of the thyroid gland. In addition, methods of identifying anti-tumor agents are described.

In some aspects, the present disclosure provides methods for enriching amplicons, or amplification products, comprising a concatemer of at least two or more copies of a target polynucleotide. In some embodiments, a method comprises sequencing the amplicons comprising at least two or more copies of a target polynucleotide. In some embodiments, the target polynucleotides comprise sequences resulting from chromosome rearrangement, including but not limited to point mutations, single nucleotide polymorphisms, insertions, deletions, and translocations including fusion genes. In some aspects, the present disclosure provides compositions and reaction mixtures useful in the described methods.

Multiplex (+ / -) stranded analyses, such as array comparative genomic hybridization (aCGH), are provided for detecting chromosomal rearrangements associated with cancer and other diseases. For example, an illustrative multiplex array for CGH includes discrete plus (+) strand and minus (-) strand DNA probes, complementary to each other but separable on the CGH array. The minus (-) strand DNA probes recover diagnostic information lost to conventional microarrays, since many genes transcribe from the minus (-) strand. In an illustrative system, patient and control DNA samples are prepared for CGH by amplification and labeling using comprehensive primers that generate both plus (+) strands and minus (-) strands of DNA in the samples. The breakpoints of a translocated chromosome may be detected on a multiplex microarray by DNA probes of one polarity, while DNA copy number changes associated with the translocation region may be detected by corresponding DNA probes of the complementary polarity. Related methods for identifying translocation partner genes are also provided.

Most clinically distinguishable malignant tumors are characterized by specific mutations, specific patterns of chromosomal rearrangements and a predominant mechanism of genetic instability. It has been suggested that the internal dynamics of genomic modifications as opposed to the external evolutionary forces have a significant and complex impact on Darwinian species evolution. A similar situation can be expected for somatic cancer evolution as the key mechanisms encountered in species evolution such as duplications, rearrangements or deletions of genes also constitute prevalent mutation mechanisms in cancers with chromosomal instability. The invention is an algorithm which is based on a systems concept describing the putative constraints of the cancer genome architecture on somatic cancer evolution. The algorithm allows the identification of therapeutic target genes in individual cancer patients which do not represent oncogenes or tumor suppressor genes but have become putative therapeutic targets due to constraints of the cancer genome architecture on individual somatic cancer evolution. Target genes or regulatory elements may be identified by their designation as essential genes or regulatory elements in cancer cells of the patient but not in normal tissue cells or they may be identified by their impact on the process of somatic cancer evolution in individual patients based on phylogenetic trees of somatic cancer evolution and on the constructed multilayered cancer genome maps. The algorithm can be used for delivering personalized cancer therapy as well as for the industrial identification of novel anti-cancer drugs. The algorithm is essential for designing software programs which allow the prediction of the natural history of cancer disease in individual patients.

Methods for detecting and mapping chromosomal rearrangements associated with various diseases using comparative genomic hybridization are disclosed. Included are methods to identify translocation partners of known genomic loci and to determine translocation breakpoints. These methods may be used in the prognosis, diagnosis, and determination of predisposition to diseases that involve chromosomal rearrangements.

The present disclosure relates to methods for the early detection of ERG over-expression, gene rearrangements, and diagnosis and / or prognosis of prostate cancer using a combined ERG IHC-FISH assay.

Most clinically distinguishable malignant tumors are characterized by specific mutations, specific patterns of chromosomal rearrangements and a predominant mechanism of genetic instability. It has been suggested that the internal dynamics of genomic modifications as opposed to the external evolutionary forces have a significant and complex impact on Darwinian species evolution. A similar situation can be expected for somatic cancer evolution as the key mechanisms encountered in species evolution such as duplications, rearrangements or deletions of genes also constitute prevalent mutation mechanisms in cancers with chromosomal instability. The invention is an algorithm which is based on a systems concept describing the putative constraints of the cancer genome architecture on somatic cancer evolution. The algorithm allows the identification of therapeutic target genes in individual cancer patients which do not represent oncogenes or tumor suppressor genes but have become putative therapeutic targets due to constraints of the cancer genome architecture on individual somatic cancer evolution. Target genes or regulatory elements may be identified by their designation as essential genes or regulatory elements in cancer cells of the patient but not in normal tissue cells or they may be identified by their impact on the process of somatic cancer evolution in individual patients based on phylogenetic trees of somatic cancer evolution and on the constructed multilayered cancer genome maps. The algorithm can be used for delivering personalized cancer therapy as well as for the industrial identification of novel anti-cancer drugs. The algorithm is essential for designing software programs which allow the prediction of the natural history of cancer disease in individual patients.

Disclosed herein are systems and methods for performing secondary analyses of nucleotide sequencing data in a time-efficient manner. Some embodiments include performing a secondary analysis iteratively while sequence reads are generated by a sequencing system. Secondary analyses can encompass both alignment of sequence reads to a reference sequence (e.g., the human reference genome sequence) and utilization of this alignment to detect differences between a sample and the reference. Secondary analysis can enable detection of genetic differences, variant detection and genotyping, identification of single nucleotide polymorphisms (SNPs), small insertions and deletion (indels) and structural changes in the DNA, such as copy number variants (CNVs) and chromosomal rearrangements.

The present disclosure provides novel compositions and methods suitable for specifically eliminating target cells (e.g., cancer cells) without affecting non-target cells (e.g., non-cancer cells). For example, CRISPR system and the compositions of the present disclosure can be employed to specifically introduce a suicidal gene into a cancer cell in the loci of a cancer-specific target sequence, which as a result of chromosomal re-arrangement or translocation in a cancer cell presents a cancer specific sequence for a guide RNA and CAS to be recognized and such sequence is absent in a non-cancer cell. Consequently, the specific introduction of the composition(s) to cancer-specific site(s) and integration of suicide gene in the target genome, which is inapplicable to normal cells for lack of the site(s), leads to selective elimination of cancer cells but not non-cancer cells, and therefore render novel therapeutic methods and compositions for cancer treatment.

Provided in the present invention are a method and kit for detecting chromosome rearrangement. Specifically, the method for detecting chromosomal rearrangement of the present invention comprises: obtaining sample DNA from a sample of a subject; performing long-distance PCR (LD-PCR) and quantitative PCR (qPCR) on the sample DNA; comparing a detection result with a result of a normal control sample; and from the result of the comparison, inferring whether a chromosomal rearrangement is present in the sample DNA. The LD-PCR and qPCR may be performed in succession or in the same reaction container. Further provided in the present invention are a kit for performing the method, as well as primers and probes.

In some aspects, the present disclosure provides methods for enriching amplicons, or amplification products, comprising a concatemer of at least two or more copies of a target polynucleotide. In some embodiments, a method comprises sequencing the amplicons comprising at least two or more copies of a target polynucleotide. In some embodiments, the target polynucleotides comprise sequences resulting from chromosome rearrangement, including but not limited to point mutations, single nucleotide polymorphisms, insertions, deletions, and translocations including fusion genes. In some aspects, the present disclosure provides compositions and reaction mixtures useful in the described methods.

The present specification discloses methods for detecting and localizing chromosomal rearrangements associated with various diseases using comparative genomic hybridization. Methods include identifying translocation partners at known loci and determining translocation breakpoints. These methods can be used for the prognosis, diagnosis, and determination of susceptibility to diseases involving chromosomal rearrangements.

The invention discloses an optimization method for efficiently and quickly building an ophiopogon japonicus saturation high resistance homogeneous mutant library. Ethylmethane sulfonate (EMS) and <60> Co-gamma ray are physical and chemical mutagenic agents which are most widely used, efficient and stable. The EMS can generate a plurality of point mutations on one genome, the generated mutations can be randomly distributed on the whole genome, the distribution is even, the density is high, the cost is low, and the obtaining of allelic mutants is facilitated, especially, a saturated mutant library can be obtained by a smaller mutant population; Gamma ray mutagenesis mainly causes the loss of DNA fragments and chromosomal rearrangement and is specially suitable for the building of a mutant library of which multiple family gene functions are lost; therefore, by using the two method simultaneously to make their respective advantages complementary to each other, the capacity of the mutant library is increased, the demands of the saturated mutant library are satisfied, the content of the saturated mutant library is enriched, and moreover, the obtained mutants do not involve a GM event, so the safety is high and the application is convenient.

The invention especially relates to a generation method for the variation of the chromosome number of Saccharomyces cerevisiae, belonging to the field of synthetic biology. According to the invention,in virtue of the characteristics of genome rearrangement of Saccharomyces cerevisiae and through genome rearrangement of the ring chromosomes of Saccharomyces cerevisiae, an aneuploid Saccharomyces cerevisiae strain with chromosome number variation is obtained, the continuous variation of the circular chromosome copy number of Saccharomyces cerevisiae is realized, a Saccharomyces cerevisiae strain with continuously evolved phenotypes is obtained, and correlation between structural variation and phenotype enhancement is revealed. According to the invention, the variation of the chromosome number, the copy number and the structure of Saccharomyces cerevisiae is realized and the structural variation is revealed by using a chromosome rearrangement method, and a novel research means is provided for obtaining aneuploid Saccharomyces cerevisiae strains and studying the relationship between chromosome structure variation and functions.

The present disclosure provides novel compositions and methods suitable for specifically eliminating target cells (e.g., cancer cells) without affecting non-target cells (e.g., non-cancer cells). For example, CR-ISPR system and the compositions of the present disclosure can be employed to specifically introduce a suicidal gene into a cancer cell in the loci of a cancer-specific target sequence, which as a result of chromosomal re-arrangement or translocation in a cancer cell presents a cancer specific sequence for a guide RNA and CAS to be recognized and such sequence is absent in a non-cancer cell. Consequently, the specific introduction of the composition(s) to cancer-specific site(s) and integration of suicide gene in the target genome, which is inapplicable to normal cells for lack of the site(s), leads to selective elimination of cancer cells but not non-cancer cells, and therefore render novel therapeutic methods and compositions for cancer treatment.

The invention relates to a method for generating a non-human animal model of a chromosomal rearrangement, comprising creating a transgenic non-human mammal expressing a site-specific recombinase under the control of a cell type specific promoter, and having sites recognized by the recombinase present in its genome such that a chromosomal rearrangement is catalysed by the recombinase.