US 12,718,953 B2Granted

Polygenic risk score for in vitro fertilization

AssigneeMyome, Inc.

InventorsAkash Kumar, Kate M. Im, Elan Bechor, Luisa Galhardo, Abhiram Rao, Pauline Ng, Matthew Rabinowitz

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Abstract

Provided are methods for determining a disease risk associated with an embryo that comprise constructing the genome of the embryo based on (i) one or more genetic variants in the embryo, (ii) a paternal haplotype, (iii) a maternal haplotype (iv) a transmission probability of the paternal haplotype, and (v) a transmission probability of the maternal haplotype; assigning a polygenic risk score to the embryo based on the constructed genome of the embryo; determining the disease risk associated with the embryo based on the polygenic risk score; and determining transmission of disease causing genetic variants and/or haplotypes from the paternal genome and/or maternal genome to the embryo. Also provided are methods of determining a range of disease risk for potential children for a mother and a potential sperm donor. Also provided are methods of determining disease risk in an individual.

Claims17

Dependent claims

A method for determining a disease risk associated with an embryo, the method comprising:

(a) performing whole genome sequencing on a biological sample obtained from a paternal subject to identify a genome associated with the paternal subject;
(b) performing whole genome sequencing on a biological sample obtained from a maternal subject to identify a genome associated with the maternal subject;
(c) phasing the genome associated with the paternal subject to identify a paternal haplotype;
(d) phasing the genome associated with the maternal subject to identify a maternal haplotype;
(e) performing sparse genotyping on the embryo to identify one or more genetic variants in the embryo;
(f) constructing the genome of the embryo based on (i) the one or more genetic variants in the embryo, (ii) the paternal haplotype, (iii) the maternal haplotype, (iv) a transmission probability of the paternal haplotype, and (v) a transmission probability of the maternal haplotype;
(g) assigning a polygenic risk score to the embryo based on the constructed genome of the embryo;
(h) determining the disease risk associated with the embryo based on the polygenic risk score;
(i) determining transmission of monogenic disease causing genetic variants and/or haplotypes from the paternal genome and/or maternal genome to the embryo;
and
(j) determining a combined disease risk associated with the embryo based on the polygenic disease risk and the transmission of monogenic disease causing genetic variants and/or haplotypes from the paternal genome and/or maternal genome to the embryo.

8 more elements

A method for determining a range of disease risk for potential children for (i) a prospective mother and one or more potential sperm donor(s) or (ii) a prospective father and one or more potential egg donor(s), the method comprising:

(a) performing whole genome sequencing on (i) the prospective mother and the one or more potential sperm donor(s) to obtain a maternal genotype and one or more sperm donor genotype(s) or (ii) the prospective father and the one or more potential egg donor(s) to obtain a paternal genotype and one or more egg donor genotype(s);
(b) estimating possible genotypes for one or more potential children using (i) the maternal genotype and the potential sperm donor genotype(s) or (ii) the prospective father genotype and the potential egg donor genotype(s);
(c) phasing (i) the maternal genotype to identify a maternal haplotype or (ii) the paternal genotype to identify a paternal haplotype;
(d) phasing (i) the one or more sperm donor(s) genotype to identify a sperm donor haplotype or (ii) the one or more egg donor genotype(s) to identify an egg donor haplotype;
(e) performing sparse genotyping on the one or more potential children to identify one or more genetic variants in the one or more potential children;
(f) constructing the genome of the one or more potential children based on (i) the one or more genetic variants in the one or more potential children, (ii) the maternal haplotype or the paternal haplotype, (iii) the sperm donor haplotype or the egg donor haplotype, (iv) a transmission probability of the maternal haplotype or the paternal haplotype, and (v) a transmission probability of the sperm donor haplotype or the egg donor haplotype;
(g) estimating a lowest possible polygenic risk score of a potential child using the constructed genome of the one or more potential children;
and
(h) estimating a highest possible polygenic risk score of a potential child using the constructed genome of the one or more potential children.

6 more elements

Dependencies are inferred from the claim text.

Facts

Application: 17/765,073Filed 30 Sep 2020 · us provisional application
Priority: 30 Sep 2019
Published: US 2022/0367063 A117 Nov 2022
Granted: 25 Aug 2026
Term ends: Not estimatedThe source records don’t support an estimate.

Classification10 codes

G16B 20/00
Ict specially adapted for functional genomics or proteomics
G16H 50/30
ICT specially adapted for medical diagnosis, medical simulation or medical data mining; ICT specially adapted for detecting, monitoring or…: for…
G16B 20/40
ICT specially adapted for functional genomics or proteomics, e.g. genotype-phenotype associations: population genetics; Linkage disequilibrium
G16B 30/00
Ict specially adapted for sequence analysis involving nucleotides or amino acids