IP Library › Granted Patent US 12,571,047
Granted Patent B2
US 12,571,047 · App. 17/503,182 · Granted Mar 10, 2026

System and method for cleaning noisy genetic data and determining chromosome copy number

Inventors: Matthew Rabinowitz (San Francisco, CA); Milena Banjevic (Los Altos Hills, CA); Zachary Demko (San Francisco, CA); David Johnson (San Francisco, CA); Dusan Kijacic (Los Altos Hills, CA); Dimitri Petrov (Stanford, CA); Joshua Sweetkind-Singer (San Jose, CA); Jing Xu (Jersey City, NJ)
Assignee: Natera, Inc.
C12Q1/6883C12Q1/6806C12Q1/6827C12Q1/6855C12Q1/6869C12Q1/6876C12Q1/6886G16B20/00G16B25/00G16B30/00G16B40/00C12Q2537/149C12Q2545/114C12Q2600/118C12Q2600/156C12Q2600/158
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Quick Facts
Patent No.
US 12,571,047
App. No.
17/503,182
Granted
Mar 10, 2026
Kind
B2
Abstract

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.

Claims (19)

1 . A method for preparing a non-naturally occurring composition of amplified DNA derived from one or more embryonic or fetal cells of an embryo or unborn fetus useful for reconstructing at least a portion of the genome of the embryo or fetus, comprising:

(a) extracting genomic DNA from the one or more embryonic or fetal cells;

(b) preparing a non-naturally occurring composition of amplified DNA by amplification of a plurality of target loci from the genomic DNA extracted in (a) to obtain amplified DNA;

(c) analyzing the non-naturally occurring composition of amplified DNA obtained in (b) by sequencing-by-synthesis to obtain genetic data of the embryo or fetus for the plurality of target loci, and reconstructing at least a portion of the genome of the embryonic or fetal cells using the genetic data of the embryo or fetus and genetic data of at least one biological parent of the embryo or fetus.

2 . The method of claim 1 , wherein the extracting comprises extracting genomic DNA from one or more embryonic cells.

3 . The method of claim 1 , wherein the extracting comprises extracting genomic DNA from a single embryonic cell.

4 . The method of claim 1 , wherein the extracting comprises extracting genomic DNA from one or more fetal cells.

5 . The method of claim 1 , wherein the extracting comprises extracting genomic DNA from one or more fetal cells isolated from a maternal blood sample or a fraction thereof.

6 . The method of claim 1 , wherein the target loci comprise SNP loci.

7 . The method of claim 1 , wherein the amplification comprises targeted amplification of the target loci.

8 . The method of claim 1 , wherein the amplification comprises ligation of adaptors to the genomic DNA extracted in (a) followed by universal amplification.

9 . The method of claim 1 , wherein the sequencing-by-synthesis comprises clonal amplification and measurement of sequences of the clonally amplified DNA.

10 . The method of claim 1 , wherein the reconstructing comprises reconstructing at least a portion of the genome of the embryo or fetus using the genetic data of the embryo or fetus and genetic data of both biological parents of the embryo or fetus.

11 . The method of claim 1 , wherein the method further comprises determining haplotypic genetic data of the at least one biological parent of the embryo or fetus.

12 . The method of claim 10 , wherein the method further comprises determining haplotypic genetic data of both biological parents of the embryo or fetus.

13 . A method for preparing a non-naturally occurring composition of amplified DNA derived from one or more embryonic or fetal cells of an embryo or unborn fetus useful for reconstructing at least a portion of the genome of the embryo or fetus, comprising:

(a) extracting genomic DNA from the one or more embryonic or fetal cells;

(b) preparing a non-naturally occurring composition of amplified DNA by amplification of a plurality of SNP loci from the genomic DNA extracted in (a) to obtain amplified DNA;

(c) analyzing the non-naturally occurring composition of amplified DNA obtained in (b) by sequencing-by-synthesis to obtain genetic data of the embryo or fetus for the plurality of SNP loci, and reconstructing at least a portion of the genome of the embryonic or fetal cells using the genetic data of the embryo or fetus and genetic data of both biological parents of the embryo or fetus.

Assignments (2)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Oct 15, 2021
From: RABINOWITZ, MATTHEW; BANJEVIC, MILENA; DEMKO, ZACHARY PAUL; JOHNSON, DAVID SCOTT; KIJACIK, DUSAN; PETROV, DMITRI; SWEETKIND-SINGER, JOSHUA; XU, JING
To: GENE SECURITY NETWORK, INC.
Reel/Frame 057810/0095 →
CHANGE OF NAME Recorded Oct 15, 2021
From: GENE SECURITY NETWORK INC.
To: NATERA, INC.
Reel/Frame 058180/0443 →
Continuity (34)
Continuation 17164599 · Feb 1, 2021
Continuation 16823127 · Mar 18, 2020
Continuation In Part 16411507 · May 14, 2019
Continuation In Part 16399911 · Apr 30, 2019
Continuation 16288690 · Feb 28, 2019
Continuation 15887746 · Feb 2, 2018
Continuation 15446778 · Mar 1, 2017
Continuation 15187555 · Jun 20, 2016
Continuation 14092457 · Nov 27, 2013
Continuation 13949212 · Jul 23, 2013
Continuation 13793186 · Mar 11, 2013
Continuation 13793133 · Mar 11, 2013
Continuation 12076348 · Mar 17, 2008
Continuation In Part 11634550 · Dec 6, 2006
Continuation 11603406 · Nov 22, 2006
Continuation In Part 11603406 · Nov 22, 2006
Continuation In Part 11603406 · Nov 22, 2006
Continuation In Part 11496982 · Jul 31, 2006
Continuation In Part 11496982 · Jul 31, 2006
Provisional Application 61008637 · Dec 21, 2007
Provisional Application 61003101 · Nov 13, 2007
Provisional Application 60934440 · Jun 13, 2007
Provisional Application 60932456 · May 31, 2007
Provisional Application 60926198 · Apr 25, 2007
Provisional Application 60918292 · Mar 16, 2007
Provisional Application 60846610 · Sep 22, 2006
Provisional Application 60817741 · Jun 30, 2006
Provisional Application 60789506 · Apr 4, 2006
Provisional Application 60774976 · Feb 21, 2006
Provisional Application 60754396 · Dec 29, 2005
Provisional Application 60742305 · Dec 6, 2005
Provisional Application 60739882 · Nov 26, 2005
Provisional Application 60703415 · Jul 29, 2005
Related Publication 20220033908A1 · Feb 3, 2022
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