Abstract: The present invention concerns the analysis of cell-free nucleic acids to determine the contribution of cell-free nucleic acids from specific tissues. In addition, the invention provides methods for diagnosing diseases based on cell-free nucleic acid analysis. The methods of the invention are also useful to detect quality defects in samples containing cell-free nucleic acids.

Abstract: The present invention provides a method for analysis of target nucleic acids which are present in low amounts. In particular, the method comprises the following steps: i. providing a sample wherein target nucleic acids are present in a low amount, ii. generating a reduced representation library of said target nucleic acids by a method comprising: fragmenting said target nucleic acids; ligating adaptors to said fragments; and selecting a subset of said adaptor-ligated fragments, iii. massively parallel sequencing said reduced representation library, and iv. identifying variants in said target nucleic acids by analyzing results obtained by said sequencing.

Abstract: We developed a generic approach to type genome-wide single nucleotide polymorphisms in single human cells and to reconstruct for the first time genome-wide haplotypes of single- or dual-cell derived genotypes. Proof-of-principle is delivered for EBV-transformed lymphoblastoid cells as well as human blastomeres. To this end, multiple displacement amplified DNA samples of single cells were hybridized to Affymetrix 250K SNP-arrays. Different algorithmic designs were subsequently developed to assess from the single-cell derived SNP-probe intensities the sequence of syntenic alleles and to pinpoint accurately the majority of parental homologous recombination sites across the entire genome using a linkage-based approach. This included the development of algorithms that rectify a large part of the discrepant allelic assignments in raw single or dual-cell derived haplotypes. This method to infer genome-wide haplotypes from the analysis of only one or two cells has tremendous applicative value.

Abstract: The present invention provides a method for analysis of target nucleic acids which are present in low amounts. In particular, the method comprises the following steps: i. providing a sample wherein target nucleic acids are present in a low amount, ii. generating a reduced representation library of said target nucleic acids by a method comprising: —fragmenting said target nucleic acids; ligating adaptors to said fragments; and selecting a subset of said adaptor-ligated fragments, iii. massively parallel sequencing said reduced representation library, and iv. identifying variants in said target nucleic acids by analyzing results obtained by said sequencing.

Abstract: The present invention concerns the analysis of cell-free nucleic acids to determine the contribution of cell-free nucleic acids from specific tissues. In addition, the invention provides methods for diagnosing diseases based on cell-free nucleic acid analysis. The methods of the invention are also useful to detect quality defects in samples containing cell-free nucleic acids.

Abstract: The present invention provides a method for the analysis of genetic material of a subject, said method comprising: —obtaining continuous polymorphic variant allele frequency (PVAF) values of genetic material of a subject; —obtaining genotype information of a first and second parent; —categorizing the continuous PVAF values in a category corresponding to the first parent based on the genotype information of the first parent and second parent; —segmenting said categorized PVAF values; and —providing the segmented PVAF values to indicate a genetic anomaly in the genetic material of the subject and/or inheritance of the genetic material of the subject.

Abstract: The present invention provides a method for analysis of target nucleic acids which are present in low amounts. In particular, the method comprises the following steps: i. providing a sample wherein target nucleic acids are present in a low amount, ii. generating a reduced representation library of said target nucleic acids by a method comprising: fragmenting said target nucleic acids; ligating adaptors to said fragments; and selecting a subset of said adaptor-ligated fragments, iii. massively parallel sequencing said reduced representation library, and iv. identifying variants in said target nucleic acids by analyzing results obtained by said sequencing.

Abstract: We developed a generic approach to type genome-wide single nucleotide polymorphisms in single human cells and to reconstruct for the first time genome-wide haplotypes of single- or dual-cell derived genotypes. Proof-of-principle is delivered for EBV-transformed lymphoblastoid cells as well as human blastomeres. To this end, multiple displacement amplified DNA samples of single cells were hybridized to Affymetrix 250K SNP-arrays. Different algorithmic designs were subsequently developed to assess from the single-cell derived SNP-probe intensities the sequence of syntenic alleles and to pinpoint accurately the majority of parental homologous recombination sites across the entire genome using a linkage-based approach. This included the development of algorithms that rectify a large part of the discrepant allelic assignments in raw single or dual-cell derived haplotypes. This method to infer genome-wide haplotypes from the analysis of only one or two cells has tremendous applicative value.

Abstract: Novel chromosomal vectors, particularly human artificial chromosomes, which are efficiently transmitted through the male and female germ line in each generation. The vectors are also transmitted through mitosis in substantially all dividing cells and provide a position independent expression of an exogenous DNA sequence. These vectors can be used in gene therapy and are useful for the production of transgenic animals and plants and products thereof.