Computer systems and methods for associating genes with traits using cross species data

A computer program product for use in conjunction with a computer system, the computer program product comprising a computer readable storage medium and a computer program mechanism embedded therein, the computer program mechanism comprising:

• a clustering module for clustering quantitative trait locus data from a plurality of quantitative trait locus analyses to form a quantitative trait locus interaction map;
• wherein
• each quantitative trait locus analysis in said plurality of quantitative trait locus analyses is performed for a gene in a plurality of genes in the genome of a second species using a genetic marker map and a quantitative trait in order to produce said quantitative trait locus data, wherein, for each quantitative trait locus analysis, said quantitative trait comprises an expression statistic for the gene for which the quantitative trait locus analysis is performed, for each organism in a plurality of organisms of said second species;
• and wherein
• said genetic marker map is constructed from a set of genetic markers associated with said plurality of organisms of said second species;
• and
• an analysis module for analyzing said quantitative trait locus interaction map to identify a gene G′ in said second species that is associated with a clinical trait T exhibited by a first species and said second species, wherein said gene G′ is an ortholog of a gene G in said first species.

A computer system for identifying a quantitative trait locus for a complex trait in a first species, wherein the complex trait is exhibited by said first species and a second species, the computer system comprising:

• a central processing unit;
• a memory, coupled to the central processing unit, the memory storing a classification module and a genetic analysis module;
• wherein
• the classification module includes instructions for dividing a plurality of organisms of a second species into a plurality of subpopulations using a classification scheme that classifies each organism in said plurality of organisms of said second species into at least one subpopulation in said plurality of subpopulations, wherein said classification scheme uses a plurality of cellular constituent measurements from each said organism in said second species;
• and
• the genetic analysis module includes instructions that, for at least one subpopulation in said plurality of subpopulations, performs quantitative genetic analysis on said at least one subpopulation in order to identify said quantitative trait locus in said second species for said complex trait, wherein the quantitative trait locus in said second species is the ortholog of the quantitative trait locus in said first species.

A method of identifying a molecular target for a second trait in a second species, the method comprising:

• (a) identifying a first gene in a segregating population that is causal for a first trait exhibited by all or a portion of said segregating population, wherein each member of said segregating population is a member of a first species and wherein said second trait in said second species corresponds to said first trait in said first species;
• (b) mapping said first gene in said first species to a corresponding locus in the genome of the second species;
• and
• (c) determining whether a marker or a haplotype in said corresponding locus in the genome of the second species associates with said second trait, wherein, when said marker or said haplotype associates with said second trait in said second species, said locus is identified as said molecular target.

A method of identifying a molecular target for a second trait in a second species, the method comprising:

• (a) identifying a first gene in a segregating population that is causal for a first trait exhibited by all or a portion of said segregating population, wherein each member of said segregating population is a member of a first species and wherein said second trait in said second species corresponds to said first trait in said first species;
• (b) identifying a locus in the genome of the second species that is (1) linked to said second trait and (2) maps to the position in the genome of said first species where said first gene resides;
• and
• (c) determining whether a marker or a haplotype in said corresponding locus in the genome of the second species associates with said second trait, wherein, when said marker or said haplotype associates with said second trait in said second species, said locus is identified as said molecular target.

A method of identifying a molecular target for a second trait in a second species, the method comprising:

• (a) identifying a first gene in a segregating population that is causal for a first trait exhibited by all or a portion of said segregating population, wherein each member of said segregating population is a member of a first species and wherein said second trait in said second species corresponds to said first trait in said first species;
• and
• (b) identifying a second gene in the genome of the second species that is orthologous to said first gene and in which (i) the variation of the abundance of the second gene across biological samples taken from a plurality of members of said second species and (ii) the variation of the second trait across said plurality of members of said second species are associated, wherein
• said second gene is identified as said molecular target.

A computer system for identifying a molecular target for a second trait in a second species, the computer system comprising:

• a central processing unit;
• a memory, coupled to the central processing unit, the memory storing:
• instructions for identifying a first gene in a segregating population that is causal for a first trait exhibited by all or a portion of said segregating population, wherein each member of said segregating population is a member of a first species and wherein said second trait in said second species corresponds to said first trait in said first species;
• instructions for mapping said first gene in said first species to a corresponding locus in the genome of the second species;
• and
• instructions for determining whether a marker or a haplotype in said corresponding locus in the genome of the second species associates with said second trait.

A computer program product for use in conjunction with a computer system, the computer program product comprising a computer readable storage medium and a computer program mechanism embedded therein, the computer program mechanism comprising:

• instructions for identifying a first gene in a segregating population that is causal for a first trait exhibited by all or a portion of said segregating population, wherein each member of said segregating population is a member of a first species and wherein said second trait in said second species corresponds to said first trait in said first species;
• instructions for mapping said first gene in said first species to a corresponding locus in the genome of the second species;
• and
• instructions for determining whether a marker or a haplotype in said corresponding locus in the genome of the second species associates with said second trait.

A computer system for identifying a molecular target for a second trait in a second species, the computer system comprising:

• a central processing unit;
• a memory, coupled to the central processing unit, the memory storing:
• instructions for identifying a first gene in a segregating population that is causal for a first trait exhibited by all or a portion of said segregating population, wherein each member of said segregating population is a member of a first species and wherein said second trait in said second species corresponds to said first trait in said first species;
• instructions for identifying a locus in the genome of the second species that is (1) linked to said second trait and (2) maps to the position in the genome of said first species where said first gene resides;
• and
• instructions for determining whether a marker or a haplotype in said corresponding locus in the genome of the second species associates with said second trait.

A computer program product for use in conjunction with a computer system, the computer program product comprising a computer readable storage medium and a computer program mechanism embedded therein, the computer program mechanism comprising:

• instructions for identifying a first gene in a segregating population that is causal for a first trait exhibited by all or a portion of said segregating population, wherein each member of said segregating population is a member of a first species and wherein said second trait in said second species corresponds to said first trait in said first species;
• instructions for identifying a locus in the genome of the second species that is (1) linked to said second trait and (2) maps to the position in the genome of said first species where said first gene resides;
• and
• instructions for determining whether a marker or a haplotype in said corresponding locus in the genome of the second species associates with said second trait.

A computer system for identifying a molecular target for a second trait in a second species, the computer system comprising:

• a central processing unit;
• a memory, coupled to the central processing unit, the memory storing:
• instructions for identifying a first gene in a segregating population that is causal for a first trait exhibited by all or a portion of said segregating population, wherein each member of said segregating population is a member of a first species and wherein said second trait in said second species corresponds to said first trait in said first species;
• and
• instructions for identifying a second gene in the genome of the second species that is orthologous to said first gene and in which (i) the variation of the abundance of the second gene across biological samples taken from a plurality of members of said second species and (ii) the variation of the second trait across said plurality of members of said second species are associated.

A computer system for confirming the association of a query QTL or a query gene in the genome of a second species with a clinical trait T exhibited by said second species, the computer system comprising:

• a central processing unit;
• a memory, coupled to the central processing unit, the memory storing:
• instructions for mapping (i) a region of the genome of a first species that comprises a first abundance quantitative trait loci (eQTL) in said first species that is linked to a trait T′ exhibited by said first species to (ii) a region of said genome of said second species, wherein said trait T′ is indicative of the clinical trait T;
• and
• instructions for confirming the association of said query QTL or said query gene with said clinical trait T when said query QTL or said query gene is both (i) linked to said clinical trait T and (ii) is in said region of the genome of said second species.