# US 10,504,611 B2 · Ancestral human genomes

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- Number: US 10,504,611 B2
- Document ID: US10504611B2
- Status: Granted
- Kind: B2
- Application number: 15/519,105
- Filed: 2015-10-19
- Published: 2017-09-28
- Granted: 2019-12-10
- Earliest claimed: 2014-10-17
- Assignees: Ancestry.com DNA, LLC
- Applicants: Ancestry.com DNA, LLC
- Inventors: Julie M. Granka; Keith D. Noto
- Web page: https://patentgrep.com/patent/US10504611B2

## CPC

- G16B 20/20: Allele or variant detection, e.g. single nucleotide polymorphism [SNP] detection
- G06F 17/18: for evaluating statistical data {, e.g. average values, frequency distributions, probability functions, regression analysis (forecasting specially adapted for a specific administrative, business or logistic context G06Q10/04)}
- G16B 5/00: ICT specially adapted for modelling or simulations in systems biology, e.g. gene-regulatory networks, protein interaction networks or metabolic networks
- G16B 5/20: Probabilistic models
- G16B 20/00: ICT specially adapted for functional genomics or proteomics, e.g. genotype-phenotype associations
- G16B 40/00: ICT specially adapted for biostatistics; ICT specially adapted for bioinformatics-related machine learning or data mining, e.g. knowledge discovery or pattern finding
- G16B 40/20: Supervised data analysis
- G16B 40/30: Unsupervised data analysis
- G16B: BIOINFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR GENETIC OR PROTEIN-RELATED DATA PROCESSING IN COMPUTATIONAL MOLECULAR BIOLOGY
- G06F: ELECTRIC DIGITAL DATA PROCESSING (computer systems based on specific computational models G06N)

## Abstract

Described are computational methods to reconstruct the chromosomes (and genomes) of ancestors given genetic data, IBD information, and full or partial pedigree information of some number of their descendants.

## Claims

### Claim 1

A method for reconstructing at least one phased chromosomal haplotype of at least one genomic segment of an ancestral couple of interest, the method comprising
receiving, by a computer, genetic data for a plurality of individuals;
analyzing, by the computer, the genetic data to identify a genomic DNA segment that is identical by descent (IBD) among pairs of the individuals, the IBD genomic DNA segment identified by chromosome number and start and end coordinates, thereby identifying a set of pairs of individuals each pair sharing at least one IBD genomic DNA segment;
receiving, by the computer, pedigree data for the set;
analyzing, by the computer, the pedigree data to identify a most recent common ancestor (MRCA) of at least one of the pairs of individuals in the set, the MRCA belonging to the ancestral couple;
for one of the IBD genomic DNA segments shared by one of the pairs of individuals, comparing, by the computer, phased haplotypes of the pair of individuals to determine an inferred IBD haplotype;
generating a plurality of inferred IBD haplotypes based on other phased haplotypes of other pairs of individuals in the set; and
stitching together the inferred IBD haplotypes, by the computer, to generate stitched ancestral haplotypes reconstructing the at least one phased chromosomal haplotype of at least one genomic segment of the ancestral couple of interest.

### Claim 2 (depends on 1)

The method of claim 1, the stitching comprising:
ordering, by the computer, the inferred IBD haplotypes;
comparing, by the computer, each inferred IBD haplotype to a next inferred IBD haplotype to generate an identity score; and
creating, by the computer, a stitched ancestral haplotype by updating and extending if the identity score meets a threshold to generate a set of stitched ancestral haplotypes.

### Claim 3 (depends on 2)

The method of claim 2, the inferred IBD haplotypes prefiltered by IBD genomic DNA segment length, Family Network algorithm score, and/or number of common ancestors.

### Claim 4 (depends on 2)

The method of claim 2, the inferred IBD haplotypes ordered by chromosomal location, segment length, amount of overlap, and/or Family Network algorithm score.

### Claim 5 (depends on 2)

The method of claim 2, the identity score including amount of overlap and/or amount of identical sequences.

### Claim 6 (depends on 2)

The method of claim 2, further comprising ranking the stitched ancestral haplotype based on quantity of IBD genomic DNA segments involved in the stitched ancestral haplotype, total length of IBD genomic DNA segments involved in the stitched ancestral haplotypes, total Family Network algorithm score of IBD genomic DNA segments, total score based on recent common ancestor, total amount of overlap of stitched ancestral haplotypes and/or total amount of identity of stitched ancestral haplotypes.

### Claim 7 (depends on 1)

The method of claim 1, wherein the genetic data comprises genotyping of at least 700,000 single nucleotide polymorphisms (SNPs).

### Claim 8 (depends on 1)

The method of claim 1, wherein the genetic data comprises single nucleotide polymorphisms (SNPs) data, partial sequence data, complete sequence data, exome data, restriction fragment length polymorphism (RFLP) data, copy number variant data, or indel data.

### Claim 9 (depends on 1)

The method of claim 1, wherein the plurality of individuals belongs to a Family Network.

### Claim 10 (depends on 1)

The method of claim 1, wherein the pedigree data does not include data for all individuals in the set.

### Claim 11 (depends on 1)

The method of claim 1, wherein analyzing the genetic data comprises a) phasing each individual's genotype; and b) inferring at least one genomic DNA segment that is identical by descent (IBD) among at least two individuals.

### Claim 12 (depends on 1)

The method of claim 1, wherein identifying the MRCA comprises using the pedigree data and Family Networks methods.

### Claim 13

A non-transitory computer-readable medium comprising computer-executable instructions for reconstructing at least one phase chromosomal haplotype of at least one genomic segment of an ancestral couple of interest, the instructions, when executed by one or more processors, cause the one or more processors to:
receive, by a computer, genetic data for a plurality of individuals;
analyzing, by the computer, the genetic data to identify a genomic DNA segment that is identical by descent (IBD) among pairs of the individuals, the IBD genomic DNA segment identified by chromosome number and start and end coordinates, thereby identifying a set of pairs of individuals each pair sharing at least one IBD genomic DNA segment;
receive, by the computer, pedigree data for the set;
analyze, by the computer, the pedigree data to identify a most recent common ancestor (MRCA) of at least one of the pairs of individuals in the set, the MRCA belonging to the ancestral couple;
for one of the IBD genomic DNA segments shared by one of the pairs of individuals, comparing, by the computer, phased haplotypes of the pair of individuals to determine an inferred IBD haplotype;
generate a plurality of inferred IBD haplotypes based on other phased haplotypes of other pairs of individuals in the set; and
stitch together the inferred IBD haplotypes, by the computer, to generate stitched ancestral haplotypes reconstructing the at least one phased chromosomal haplotype of at least one genomic segment of the ancestral couple of interest.

### Claim 14 (depends on 13)

The non-transitory, computer readable medium of claim 13, further comprising instructions to:
order, by the computer, the inferred IBD haplotypes;
compare, by the computer, each inferred IBD haplotype to a next inferred IBD haplotype to generate an identity score; and
create, by the computer, a stitched ancestral haplotype by updating and extending if the identity score meets a threshold to generate a set of stitched ancestral haplotypes.

### Claim 15 (depends on 14)

The non-transitory, computer readable medium of claim 14, wherein the identity score including amount of overlap and/or amount of identical sequences.

### Claim 16 (depends on 14)

The non-transitory, computer readable medium of claim 14, further comprising instructions to rank the stitched ancestral haplotype based on quantity of IBD genomic DNA segments involved in the stitched ancestral haplotype, total length of IBD genomic DNA segments involved in the stitched ancestral haplotypes, total Family Network algorithm score of IBD genomic DNA segments, total score based on recent common ancestor, total amount of overlap of stitched ancestral haplotypes and/or total amount of identity of stitched ancestral haplotypes.

### Claim 17 (depends on 13)

The non-transitory, computer readable medium of claim 13, wherein the genetic data comprises genotyping of at least 700,000 single nucleotide polymorphisms (SNPs).

### Claim 18 (depends on 13)

The non-transitory, computer readable medium of claim 13, wherein the genetic data comprises single nucleotide polymorphisms (SNPs) data, partial sequence data, complete sequence data, exome data, restriction fragment length polymorphism (RFLP) data, copy number variant data, or indel data.

### Claim 19 (depends on 13)

The non-transitory, computer readable medium of claim 13, further comprising instructions to analyze the genetic data using: a) phasing each individual's genotype;
and b) inferring at least one genomic DNA segment that is identical by descent (IBD) among at least two individuals.

### Claim 20 (depends on 13)

The non-transitory, computer readable medium of claim 13, wherein identifying the MRCA comprises using the pedigree data and Family Networks methods.