Digital karyotyping
First Claim
1. A method of karyotyping a genome of a test eukaryotic cell, comprising:
- sequencing a population of pieces of the genome of the test eukaryotic cell to provide nucleotide sequence of said pieces;
matching, in silico, pieces of the genome to genomic locations using the nucleotide sequence of said pieces;
counting the pieces within windows of a selected size throughout the genome to determine number of pieces as a function of genomic location, wherein each window comprises a plurality of genomically clustered pieces;
comparing the number of pieces enumerated within each window for the test eukaryotic cell to the average number of pieces in windows of the selected size throughout the genome to obtain piece densities per window, wherein the piece densities per window represent the karyotype of the genome of the test eukaryotic cell.
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Abstract
Alterations in the genetic content of a cell underlie many human diseases, including cancers. A method called Digital Karyotyping provides quantitative analysis of DNA copy number at high resolution. This approach involves the isolation and enumeration of short sequence tags from specific genomic loci. Analysis of human cancer cells using this method identified gross chromosomal changes as well as amplifications and deletions, including regions not previously known to be altered. Foreign DNA sequences not present in the normal human genome could also be readily identified. Digital Karyotyping provides a broadly applicable means for systematic detection of DNA copy number changes on a genomic scale.
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Citations
27 Claims
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1. A method of karyotyping a genome of a test eukaryotic cell, comprising:
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sequencing a population of pieces of the genome of the test eukaryotic cell to provide nucleotide sequence of said pieces; matching, in silico, pieces of the genome to genomic locations using the nucleotide sequence of said pieces; counting the pieces within windows of a selected size throughout the genome to determine number of pieces as a function of genomic location, wherein each window comprises a plurality of genomically clustered pieces; comparing the number of pieces enumerated within each window for the test eukaryotic cell to the average number of pieces in windows of the selected size throughout the genome to obtain piece densities per window, wherein the piece densities per window represent the karyotype of the genome of the test eukaryotic cell. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 21, 22, 23, 24, 25, 26, 27)
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9. A method of determining differences in copy number of portions of the genome of a test eukaryotic cell, comprising:
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sequencing a population of pieces of the genome of the test eukaryotic cell to provide nucleotide sequence of said pieces; matching, in silico, pieces of the genome to genomic locations using the nucleotide sequence of said pieces; dynamically counting the pieces within a moving window of a selected size to determine number of pieces as a function of genomic location, wherein the window comprises a plurality of genomically clustered pieces; comparing number of pieces enumerated within the window at a genomic location to an average number of pieces in windows of the selected size throughout the genome to obtain piece density per window, wherein a difference in piece density per window between windows reflects a difference in copy number between portions of the genome. - View Dependent Claims (10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20)
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Specification