Abstract: Provided herein are methods, processes and apparatuses for determining the fraction of fetal nucleic acid in a test sample derived from a pregnant female with improved accuracy and/or precision. Also, provided herein are methods, processes and apparatuses for determining the presence or absence of a genetic variation in a fetus with improved accuracy and/or precision. Certain methods include using fetal fraction measurements for the determination of a fetal genetic variation.
Type:
Grant
Filed:
March 14, 2013
Date of Patent:
February 5, 2019
Assignee:
Sequenom, Inc.
Inventors:
Cosmin Deciu, Zeljko Dzakula, John Allen Tynan, Grant Hogg
Abstract: Improved solid supports and methods for analyzing target nucleotide sequences are provided herein. Certain improvements are directed to efficiently preparing nucleic acids that comprise nucleotide sequences identical to or substantially identical to one or more target nucleotide sequences, or complement thereof. The prepared nucleic acids include a reference sequence that facilitates sequence analysis. The solid supports and methods provided herein minimize the number of steps required by published sequence analysis methodologies, and thereby offer improved sequence analysis efficiency.
Abstract: Systems, methods, and apparatus for determining at least a portion of fetal genome are provided. DNA fragments from a maternal sample (maternal and fetal DNA) can be analyzed to identify alleles at certain loci. The amounts of DNA fragments of the respective alleles at these loci can be analyzed together to determine relative amounts of the haplotypes for these loci and determine which haplotypes have been inherited from the parental genomes. Loci where the parents are a specific combination of homozygous and heterozygous can be analyzed to determine regions of the fetal genome. Reference haplotypes common in the population can be used along with the analysis of the DNA fragments of the maternal sample to determine the maternal and paternal genomes. Determination of mutations, a fractional fetal DNA concentration in a maternal sample, and a proportion of coverage of a sequencing of the maternal sample can also be provided.
Type:
Grant
Filed:
May 15, 2013
Date of Patent:
October 9, 2018
Assignees:
The Chinese University of Hong Kong, Sequenom Inc.
Inventors:
Yuk Ming Dennis Lo, Kwan Chee Chan, Wai Kwon Rossa Chiu, Charles Cantor
Abstract: Technology described herein pertains in part to diagnostic tests that make use of sequence reads generated by a sequencing process. In some embodiments, a component used to generate a chromosome representation can be based on counts of sequence reads not aligned to a reference genome.
Abstract: Provided herein are methods and compositions to extract and enrich by, physical separation or amplification, relatively short nucleic acids from a nucleic acid composition containing a high background of longer nucleic acids (e.g., host or maternal nucleic acids; genomic nucleic acid and the like).
Type:
Grant
Filed:
November 15, 2017
Date of Patent:
August 21, 2018
Assignee:
SEQUENOM, INC.
Inventors:
Michele Elizabeth Wisniewski, William Hang Kwong, Firouz Mohsenian, Jian-Hua Ding
Abstract: The present application relates to a nucleic acid molecule having a nucleotide sequence encoding a bifunctional polypeptide comprising the DNA-binding domain of a protein belonging to the family of Methyl-CpG binding proteins (MBDs) and the Fc portion of an antibody. In addition, vectors and host cells which comprise said nucleic acid molecule and polypeptides which are encoded by said nucleic acid molecule as well as processes for producing said polypeptide are disclosed. Moreover, the present application provides an antibody specifically binding said polypeptide and compositions, in particular diagnostic compositions comprising the nucleic acid molecule(s), vector(s), host cell(s), polypeptide(s) or antibodie(s) of the present application. Furthermore, methods and uses employing the polypeptides of the present invention for detecting methylated DNA, in particular in tumorous tissue or tumor cells are provided.
Abstract: Provided are methods for identifying the presence or absence of a chromosome abnormality by which a cell-free sample nucleic acid from a subject is analyzed. In certain embodiments, provided are methods for identifying the presence or absence of a fetal chromosome abnormality in a nucleic acid from cell-free maternal blood.
Type:
Grant
Filed:
December 20, 2010
Date of Patent:
March 27, 2018
Assignee:
SEQUENOM, INC.
Inventors:
Mathias Ehrich, Guy Del Mistro, Cosmin Deciu, Yong Qing Chen, Ron Michael McCullough, Roger Chan Tim
Abstract: The present application relates to a nucleic acid molecule having a nucleotide sequence encoding a bifunctional polypeptide comprising the DNA-binding domain of a protein belonging to the family of Methyl-CpG binding proteins (MBDs) and the Fc portion of an antibody. In addition, vectors and host cells which comprise said nucleic acid molecule and polypeptides which are encoded by said nucleic acid molecule as well as processes for producing said polypeptide are disclosed. Moreover, the present application provides an antibody specifically binding said polypeptide and compositions, in particular diagnostic compositions comprising the nucleic acid molecule(s), vector(s), host cell(s), polypeptide(s) or antibodie(s) of the present application. Furthermore, methods and uses employing the polypeptides of the present invention for detecting methylated DNA, in particular in tumorous tissue or tumor cells are provided.
Abstract: Provided herein are methods and compositions to extract and enrich by, physical separation or amplification, relatively short nucleic acids from a nucleic acid composition containing a high background of longer nucleic acids (e.g., host or maternal nucleic acids; genomic nucleic acid and the like).
Type:
Grant
Filed:
January 18, 2017
Date of Patent:
December 26, 2017
Assignee:
SEQUENOM, INC.
Inventors:
Michele Elizabeth Wisniewski, William Hang Kwong, Firouz Mohsenian, Jian-Hua Ding
Abstract: Technology provided herein relates in part to methods, processes, machines and apparatuses for detecting genetic variations. In some embodiments, the technology is related to non-invasive assessment of aneuploidies.
Type:
Application
Filed:
May 26, 2017
Publication date:
November 30, 2017
Applicant:
Sequenom, Inc.
Inventors:
Taylor Jacob Jensen, Mathias Ehrich, Dirk van den Boom, John Allen Tynan, Sung Kyun Kim, Timothy S. Burcham, Christopher K. Ellison, Youting Sun
Abstract: Blood plasma of pregnant women contains fetal and (generally >90%) maternal circulatory extracellular DNA. Most of said fetal DNA contains ?500 base pairs, said maternal DNA having a greater size. Separation of circulatory extracellular DNA of <500 base pairs results in separation of fetal from maternal DNA. A fraction of a blood plasma or serum sample of a pregnant woman containing, due to size separation (e.g. by chromatography, density gradient centrifugation or nanotechnological methods), extracellular DNA substantially comprising ?500 base pairs is useful for non-invasive detection of fetal genetic traits (including the fetal RhD gene in pregnancies at risk for HDN; fetal Y chromosome-specific sequences in pregnancies at risk for X chromosome-linked disorders; chromosomal aberrations; hereditary Mendelian genetic disorders and corresponding genetic markers; and traits decisive for paternity determination) by e.g. PCR, ligand chain reaction or probe hybridization techniques, or nucleic acid arrays.
Type:
Grant
Filed:
February 1, 2013
Date of Patent:
August 22, 2017
Assignee:
SEQUENOM, INC.
Inventors:
Sinuhe Hahn, Wolfgang Holzgreve, Bernhard Zimmermann, Ying Li
Abstract: Provided herein are methods and compositions to extract and enrich by, physical separation or amplification, relatively short nucleic acids from a nucleic acid composition containing a high background of longer nucleic acids (e.g., host or maternal nucleic acids; genomic nucleic acid and the like).
Type:
Grant
Filed:
June 5, 2014
Date of Patent:
February 28, 2017
Assignee:
Sequenom, Inc.
Inventors:
Michele Elizabeth Wisniewski, William Hang Kwong, Firouz Mohsenian, Jian-Hua Ding
Abstract: Blood plasma of pregnant women contains fetal and (generally >90%) maternal circulatory extracellular DNA. Most of said fetal DNA contains ?500 base pairs, said maternal DNA having a greater size. Separation of circulatory extracellular DNA of <500 base pairs results in separation of fetal from maternal DNA. A fraction of a blood plasma or serum sample of a pregnant woman containing, due to size separation (e.g. by chromatography, density gradient centrifugation or nanotechnological methods), extracellular DNA substantially comprising ?500 base pairs is useful for non-invasive detection of fetal genetic traits (including the fetal RhD gene in pregnancies at risk for HDN; fetal Y chromosome-specific sequences in pregnancies at risk for X chromosome-linked disorders; chromosomal aberrations; hereditary Mendelian genetic disorders and corresponding genetic markers; and traits decisive for paternity determination) by e.g. PCR, ligand chain reaction or probe hybridization techniques, or nucleic acid arrays.
Type:
Grant
Filed:
February 17, 2011
Date of Patent:
February 28, 2017
Assignee:
SEQUENOM, INC.
Inventors:
Sinuhe Hahn, Wolfgang Holzgreve, Bernhard Zimmermann, Ying Li
Abstract: Systems, methods, and apparatus for determining at least a portion of fetal genome are provided. DNA fragments from a maternal sample (maternal and fetal DNA) can be analyzed to identify alleles at certain loci. The amounts of DNA fragments of the respective alleles at these loci can be analyzed together to determine relative amounts of the haplotypes for these loci and determine which haplotypes have been inherited from the parental genomes. Loci where the parents are a specific combination of homozygous and heterozygous can be analyzed to determine regions of the fetal genome. Reference haplotypes common in the population can be used along with the analysis of the DNA fragments of the maternal sample to determine the maternal and paternal genomes. Determination of mutations, a fractional fetal DNA concentration in a maternal sample, and a proportion of coverage of a sequencing of the maternal sample can also be provided.
Type:
Grant
Filed:
May 15, 2013
Date of Patent:
December 6, 2016
Assignees:
The Chinese University of Hong Kong, Sequenom Inc.
Inventors:
Yuk Ming Dennis Lo, Kwan Chee Chan, Wai Kwun Rossa Chiu, Charles Cantor