Methods and systems for generating a virtual progeny genome

Abstract

Methods and systems for assessing the probabilities of the expression of one or more traits in progeny are described.

What is claimed is: 
     
         1 . A method for recommending a selection of a gamete donor from a plurality of gamete donors for a target individual, the gamete donors being either sperm donors or egg donors and the target individual being an individual of opposite sex to the gamete donors, the method comprising:
 (a) obtaining a first genome profile containing first genotypes in a sequence of genetic loci, the first genome profile generated by a first DNA sequencer scanning a biological sample from the target individual;   (b) generating a first haplopath from the first genome profile of the target individual, wherein the first haplopath represents a first sequence of haploid alleles corresponding to the sequence of genetic loci;   (c) selecting each allele in the first sequence of haploid alleles, wherein said selecting comprises:
 (i) retrieving a first linkage probability that is determined based on linkage disequilibrium within a first population to which the target individual belongs, and 
 (ii) selecting a first particular allele for the first sequence of haploid alleles at a first particular locus based on a first preceding allele selected for a first preceding locus along the sequence of genetic loci and the first linkage probability between the first preceding allele and the particular allele; 
   (d) selecting a subset of gamete donors from the plurality of gamete donors;   (e) for each potential gamete donor of the subset of gamete donors:
 (e1) obtaining a second genome profile containing second genotypes in the sequence of genetic loci, the second genome profile generated by a second DNA sequencer scanning a biological sample from the potential gamete donor; 
 (e2) generating a second haplopath from the second genome profile of the potential gamete donor, wherein the second haplopath represents a second sequence of haploid alleles correspond to the sequence of genetic loci; 
 (e3) selecting each allele in the second sequence of haploid alleles, wherein said selecting comprises:
 (i) retrieving a second linkage probability that is determined based on linkage disequilibrium within a second population to which the potential gamete donor belongs; and 
 (ii) selecting a second particular allele for the second sequence of haploid alleles at a second particular locus based on a second preceding allele selected for a second preceding locus along the sequence of genetic loci and the second linkage probability between the second preceding allele and the second particular allele; 
 
 (e4) forming a diploid genotype profile by matching the first sequence of haploid alleles and the second sequence of haploid alleles in accordance with the sequence of genetic loci, the diploid genotype profile corresponding to the sequence of genetic loci and having a diploid genotype at each locus of the sequence of genetic loci, each diploid genotype at each locus having a first haploid allele from the first sequence of haploid alleles and a second haploid allele from the second sequence of haploid alleles; 
 (e5) comparing one or more of the diploid genotypes of the diploid genotype profile to one or more databases of genotype-phenotype associations to determine a likelihood of expression of a set of phenotypes for the potential progeny having the diploid genotype profile; 
 (e6) repeating steps (b), (c), (e2), (e3), (e4), and (e5) to generate a plurality of diploid genotype profiles and associated likelihoods of expressing the set of phenotypes; and 
 (e7) based on results of step (e6), generating probabilities or probability distributions of progenies of the target individual and the potential gamete donor associating with expressing the set of phenotypes; 
   (f) selecting a gamete donor from the subset of gamete donors as a recommendation based on the generated probabilities of progenies of the target individual and the subset of gamete donors.   
     
     
         2 . The method of  claim 1 , wherein selecting the gamete donor from the subset of gamete donors as the recommendation further comprising:
 selecting one or more gamete donors including the gamete donor as recommendation from the subset of gamete donors by subtracting potential gamete donors that are not compatible with the target individual.   
     
     
         3 . The method of  claim 1 , further comprising:
 presenting, to the target individual, information for one or more gamete donors of the plurality of gamete donors, the information based on probability of exhibiting one or more traits.   
     
     
         4 . The method of  claim 3 , wherein the one or more traits are preselected by the target individual. 
     
     
         5 . The method of  claim 1 , wherein:
 the first genome profile of the target individual includes phased DNA sequences and the second genome profile includes phased DNA sequences;   generating the first haplopath includes simulating recombination between the phased DNA sequences from the first genome profile; and   generating the second haplopath includes simulating recombination between the phased DNA sequences from the second genome profile.   
     
     
         6 . The method of  claim 1 , wherein, prior to step (a):
 variants are identified, the variants comprising single base substitutions, insertion/deletions, copy number polymorphisms and combinations thereof at the sequence of genetic loci from DNA samples obtained from the target individual and each potential gamete donor of the subset of gamete donors.   
     
     
         7 . The method of  claim 6 , further comprising:
 for the target individual and for each potential gamete donor of the subset of gamete donors, comparing the identified variants to a plurality of predetermined genomic sequences of haplotypes to identify haplotypes present in the DNA samples obtained from the target individual and each potential gamete donor; and
 constructing the first and second genome profiles, wherein each of the genome profiles comprises the identified haplotypes present and association frequencies of consecutive haplotypes, respectively. 
   
     
     
         8 . The method of  claim 1 , further comprising:
 repeating steps (b), (c), (e2), (e3), (e4), and (e5) a sufficient number of times to generate a stable estimate of the probabilities or probability distributions of progenies of the target individual and the potential gamete donor associating with expressing the set of phenotypes.   
     
     
         9 . A non-transitory computer readable medium for storing computer code comprising instructions for recommending a selection of a gamete donor from a plurality of gamete donors for a target individual, the gamete donors being either sperm donors or egg donors and the target individual being an individual of opposite sex to the gamete donors, the instructions, when executed by one or more computer processors, cause the one or more computer processors to perform steps comprising:
 (a) obtaining a first genome profile containing first genotypes in a sequence of genetic loci, the first genome profile generated by a first DNA sequencer scanning a biological sample from the target individual;   (b) generating a first haplopath from the first genome profile of the target individual, wherein the first haplopath represents a first sequence of haploid alleles corresponding to the sequence of genetic loci;   (c) selecting each allele in the first sequence of haploid alleles, wherein said selecting comprises:
 (i) retrieving a first linkage probability that is determined based on linkage disequilibrium within a first population to which the target individual belongs, and 
 (ii) selecting a first particular allele for the first sequence of haploid alleles at a first particular locus based on a first preceding allele selected for a first preceding locus along the sequence of genetic loci and the first linkage probability between the first preceding allele and the first particular allele; 
   (d) selecting a subset of gamete donors from the plurality of gamete donors;   (e) for each potential gamete donor of the subset of gamete donors:
 (e1) obtaining a second genome profile containing second genotypes in the sequence of genetic loci, the second genome profile generated by a second DNA sequencer scanning a biological sample from the potential gamete donor; 
 (e2) generating a second haplopath from the second genome profile of the potential gamete donor, wherein the second haplopath represents a second sequence of haploid alleles correspond to the sequence of genetic loci; 
 (e3) selecting each allele in the second sequence of haploid alleles, wherein said selecting comprises:
 (i) retrieving a second linkage probability that is determined based on linkage disequilibrium within a second population to which the potential gamete donor belongs; and 
 (ii) selecting a particular allele for the second sequence of haploid alleles at a second particular locus based on a second preceding allele selected for a second preceding locus along the sequence of genetic loci and the second linkage probability between the second preceding allele and the second particular allele; 
 
 (e4) forming a diploid genotype profile by matching the first sequence of haploid alleles and the second sequence of haploid alleles in accordance with the sequence of genetic loci, the diploid genotype profile corresponding to the sequence of genetic loci and having a diploid genotype at each locus of the sequence of genetic loci, each diploid genotype at each locus having a first haploid allele from the first sequence of haploid alleles and a second haploid allele from the second sequence of haploid alleles; 
 (e5) comparing one or more of the diploid genotypes of the diploid genotype profile to one or more databases of genotype-phenotype associations to determine a likelihood of expression of a set of phenotypes for the potential progeny having the diploid genotype profile; 
 (e6) repeating steps (b), (c), (e2), (e3), (e4), and (e5) to generate a plurality of diploid genotype profiles and associated likelihoods of expressing the set of phenotypes; and 
 (e7) based on results of repeating step (e6) generating probabilities or probability distributions of progenies of the target individual and the potential gamete donor associating with expressing the set of phenotypes; 
   (f) selecting a gamete donor from the subset of gamete donors as a recommendation based on the generated probabilities of progenies of the target individual and the subset of gamete donors.   
     
     
         10 . The computer readable medium of  claim 9 , wherein selecting the gamete donor from the subset of gamete donors as the recommendation further comprising:
 selecting one or more of gamete donors including the gamete donor as recommendation from the subset of gamete donors by subtracting potential gamete donors that are not compatible with the target individual.   
     
     
         11 . The computer readable medium of  claim 9 , further comprising:
 presenting, to the target individual, information for one or more gamete donors of the plurality of gamete donors, the information based on probability of exhibiting one or more traits.   
     
     
         12 . The computer readable medium of  claim 11 , wherein the one or more traits are preselected by the target individual. 
     
     
         13 . The computer readable medium of  claim 9 , wherein:
 the first genome profile of the target individual includes phased DNA sequences and the second genome profile includes phased DNA sequences;   generating the first haplopath includes simulating recombination between the phased DNA sequences from the first genome profile; and   generating the second haplopath includes simulating recombination between the phased DNA sequences from the second genome profile.   
     
     
         14 . The computer readable medium of  claim 9 , wherein, prior to step (a):
 variants are identified, the variants comprising single base substitutions, insertion/deletions, copy number polymorphisms and combinations thereof at the sequence of genetic loci from DNA samples obtained from the target individual and each potential gamete donor of the subset of gamete donors.   
     
     
         15 . The computer readable medium of  claim 14 , further comprising:
 for the target individual and for each potential gamete donor of the subset of gamete donors, comparing the identified variants to a plurality of predetermined genomic sequences of haplotypes to identify haplotypes present in the DNA samples obtained from the target individual and each potential gamete donor; and
 using the processors, constructing the first and second genome profiles, wherein each of the genome profiles comprises the identified haplotypes present and association frequencies of consecutive haplotypes, respectively. 
   
     
     
         16 . The computer readable medium of  claim 9 , further comprising:
 repeating steps (b), (c), (e2), (e3), (e4), and (e5) a sufficient number of times to generate a stable estimate of the probabilities or probability distributions of progenies of the target individual and the potential gamete donor associating with expressing the set of phenotypes.   
     
     
         17 . A system comprising:
 one or more computer processors; and   memory for storing computer code comprising instructions for performing genetic screening for recommending a selection of a gamete donor from a plurality of gamete donors for a target individual, the gamete donors being either sperm donors or egg donors and the target individual being an individual of opposite sex to the gamete donors, the instructions, when executed by the one or more computer processors, cause the one or more computer processors to perform steps comprising:
 (a) obtaining a first genome profile containing first genotypes in a sequence of genetic loci, the first genome profile generated by a first DNA sequencer scanning a biological sample from the target individual; 
 (b) generating a first haplopath from the first genome profile of the target individual, wherein the first haplopath represents a first sequence of haploid alleles corresponding to the sequence of genetic loci; 
 (c) selecting each allele in the first sequence of haploid alleles, wherein said selecting comprises:
 (i) retrieving a first linkage probability that is determined based on linkage disequilibrium within a first population to which the target individual belongs, and 
 (ii) selecting a first particular allele for the first sequence of haploid alleles at a particular locus based on a first preceding allele selected for a first preceding locus along the sequence of genetic loci and the first linkage probability between the first preceding allele and the first particular allele; 
 
 (d) selecting a subset of gamete donors from the plurality of gamete donors; 
 (e) for each potential gamete donor of the subset of gamete donors:
 (e1) obtaining a second genome profile containing second genotypes in the sequence of genetic loci, the second genome profile generated by a second DNA sequencer scanning a biological sample from the potential gamete donor; 
 (e2) generating a second haplopath from the second genome profile of the potential gamete donor, wherein the second haplopath represents a second sequence of haploid alleles correspond to the sequence of genetic loci; 
 (e3) selecting each allele in the second sequence of haploid alleles, wherein said selecting comprises:
 (i) retrieving a second linkage probability that is determined based on linkage disequilibrium within a second population to which the potential gamete donor belongs; and 
 (ii) selecting a second particular allele for the second sequence of haploid alleles at a second particular locus based on a second preceding allele selected for a second preceding locus along the sequence of genetic loci and the second linkage probability between the second preceding allele and the second particular allele; 
 
 (e4) forming a diploid genotype profile by matching the first sequence of haploid alleles and the second sequence of haploid alleles in accordance with the sequence of genetic loci, the diploid genotype profile corresponding to the sequence of genetic loci and having a diploid genotype at each locus of the sequence of genetic loci, each diploid genotype at each locus having a first haploid allele from the first sequence of haploid alleles and a second haploid allele from the second sequence of haploid alleles; 
 (e5) comparing one of more of the diploid genotypes of the diploid genotype profile to one or more databases of genotype-phenotype associations to determine a likelihood of expression of a set of phenotypes for the potential progeny having the diploid genotype profile; 
 (e6) repeating steps (b), (c), (e2), (e3), (e4), and (e5) to generate a plurality of diploid genotype profiles and associated likelihoods of expressing the set of phenotypes; and 
 (e7) based on results of repeating step (e6), generating probabilities or probability distributions of progenies of the female individual and the potential gamete donor associating with expressing the set of phenotypes; 
 
 (f) selecting a gamete donor from the subset of gamete donors as a recommendation based on the generated probabilities of progenies of the target individual and the subset of gamete donors. 
   
     
     
         18 . The system of  claim 17 , wherein selecting the gamete donor from the subset of gamete donors as a recommendation further comprises:
 selecting one or more of gamete donors including the gamete donor as the recommendation from the subset of gamete donors by subtracting potential gamete donors that are not compatible with the target individual.   
     
     
         19 . The system of  claim 17 , wherein the steps further comprising:
 presenting, to the target individual, information for one or more gamete donors of the plurality of gamete donors, the information based on probability of exhibiting one or more traits.   
     
     
         20 . The system of  claim 17 , wherein:
 the first genome profile of the target individual includes phased DNA sequences and the second genome profile includes phased DNA sequences; and, wherein the steps further comprising:
 generating the first haplopath includes simulating recombination between the phased DNA sequences from the first genome profile; and 
 generating the second haplopath includes simulating recombination between the phased DNA sequences from the second genome profile.