Artificial selection method and reagents

Abstract

The present invention provides methods for estimating the breeding value of individuals in populations such as those having small effective population size (Ne) e.g., to identify selection candidates having high breeding values, wherein the methods comprise inferring one or more genotypes for one or more markers at a locus or QTL to be the same as for an ancestor or founder or a subset of ancestors and/or founders from which a corresponding chromosome segment is derived and estimating the breeding value of the individual based on the inferred genotype(s).

1 . A method of artificial selection for a single gene or locus, said method comprising genotyping an individual in a current population for the presence or absence of one or more informative markers in a chromosome segment comprising a gene or locus of interest, inferring genotypes for the one or more markers at the locus or QTL to be the same as for an ancestor or founder from which the chromosome segment is derived, and estimating the breeding value of the individual based on the inferred genotype, wherein the ancestor or founder is an ancestor or founder providing a significant long term genetic contribution to the current population and wherein the genotype of the ancestor or founder for the one or more informative markers and for the locus or QTL is substantially known. 
     
     
         2 . A method of artificial selection for one or more loci or QTL said method comprising genotyping an individual in a current population for the presence or absence of one or more informative markers in one or more chromosome segments each containing one or more loci or QTL of interest, inferring genotypes at the one or more loci or QTL to be the same as for an ancestor or founder from which a chromosome segment is derived, and estimating the breeding value of the individual based on the inferred genotypes, wherein one or more ancestors and/or founders is an ancestor or founder providing a significant long term genetic contribution to the current population, and wherein the genotypes of the one or more ancestors and/or founders for the one or more informative markers and for the loci or QTL are substantially known. 
     
     
         3 . A method of artificial selection comprising genotyping an individual in a current population for the presence or absence of one or more informative markers in a plurality of chromosome segments, inferring genotypes of each chromosome segment to be the same as for one or more ancestors and/or founders from which the chromosome segments are derived, and estimating the breeding value of the individual based on the inferred genotypes, wherein each ancestor or founder is an ancestor or founder providing a significant long term genetic contribution to the current population and wherein the genotypes of the one or more ancestors and/or founders for one or more informative markers are substantially known. 
     
     
         4 . The method according to  claim 2 , wherein said method comprises:
 (i) optionally, determining a minimum set of ancestors and/or founders representative of the current population;   (ii) optionally, genotyping one or more ancestors and/or founders for known markers;   (iii) genotyping an individual in a current population for the presence or absence of one or more informative markers in one or a plurality of chromosome segments;   (iv) optionally, tracing the lineages of the one or plurality of chromosome segments back to one or more ancestors and/or founders from which they are derived;   (v) inferring genotypes of each chromosome segment to be the same as for one or more ancestors and/or founders from which the chromosome segments are derived; and   (vi) estimating the breeding value of the individual based on the inferred genotypes.   
     
     
         5 . The method according to  claim 2 , further comprising tracing the lineage of the one or more chromosome segment(s) back to one or more ancestors and/or founders from which they are derived. 
     
     
         6 . The method according to  claim 5 , comprising tracing individual chromosome segments in members of the current population back to the key ancestors and/or founders by a process comprising tracing chromosome segments in selection candidates of the current population to one or more immediate ancestors and/or founders using a small number of markers and tracing the chromosome segments in the immediate ancestors and/or founders to corresponding chromosome segments in one or more key ancestors and/or founders. 
     
     
         7 . The method of  claim 5 , comprising tracing the chromosome segments in the immediate ancestors and/or founders back to the chromosome segments in the key ancestors and/or founders using markers. 
     
     
         8 . The method according to  claim 2 , wherein said method comprises:
 (i) genotyping an individual in a current population for the presence or absence of one or more informative markers in one or a plurality of chromosome segments;   (ii) optionally, determining a minimum set of ancestors and/or founders representative of the current population;   (iii) tracing the lineages of the plurality of chromosome segments back to one or more ancestors and/or founders from which they are derived;   (iv) optionally, genotyping one or more ancestors and/or founders for known markers;   (v) inferring genotypes of each chromosome segment to be the same as for one or more ancestors and/or founders from which the chromosome segments are derived; and   (vi) estimating the breeding value of the individual based on the inferred genotypes.   
     
     
         9 . The method according to  claim 2 , wherein the population is a population of plants having a small effective population size. 
     
     
         10 . The method according to  claim 2 , wherein the population is a population of animals having a small effective population size. 
     
     
         11 . The method according to  claim 10 , wherein the population is a population of animals having a small effective population size being selected from cattle, sheep, pigs, poultry, fish and crustaceans. 
     
     
         12 . The method according to  claim 10 , wherein the population is a population of Holstein cattle. 
     
     
         13 . The method according to  claim 2 , wherein the markers within each chromosome segment are in linkage disequilibrium. 
     
     
         14 . The method according to  claim 2 , wherein the markers are selected from an allele, haplotype, haplogroup, locus, quantitative trait locus, polymorphism, STR and combinations thereof. 
     
     
         15 . The method according to  claim 14 , wherein the markers are single nuclear polymorphisms (SNPs). 
     
     
         16 . The method according to  claim 2 , to further comprising inferring the pedigree of the individual from markers that are used to trace chromosome segments. 
     
     
         17 . The method according to  claim 2 , wherein the pedigree of individual is known. 
     
     
         18 . The method according to  claim 2 , further comprising characterizing the ancestors and/or founders by genotyping one or more ancestors and/or founders for known markers. 
     
     
         19 . The method according to  claim 2 , further comprising identifying the ancestors and/or founders. 
     
     
         20 . The method according to  claim 19 , wherein the ancestors and/or founders are determined by determining a minimum set of ancestors and/or founders representative of the current population. 
     
     
         21 . The method according to  claim 2 , wherein the genome sequences of the key ancestors and/or founders are known and wherein said method comprises inferring genome sequences of individuals in the current population. 
     
     
         22 . A computer-readable medium for use in artificial selection said computer-readable medium comprising a database of estimated breeding values for one or more individuals of a population having a small effective population size and optionally comprising data selected from the group consisting of: data on ancestors and/or founders of individuals in the current population; data on individuals in the current population; data on chromosome segments for individuals in the current population; data on chromosome segments for ancestors and/or founders of individuals in the current population; data on marker genotype(s) in chromosome segment(s) for individuals in the current population; data on marker genotype(s) in chromosome segment(s) for ancestors and/or founders; data on lineages between the marker genotype(s) and/or chromosome segment(s); and combinations thereof, wherein the estimated breeding values are obtained by performing the method according to  claim 2 . 
     
     
         23 . The computer-readable medium of  claim 22 , wherein the marker genotype(s) of one or more ancestors are arrayed in linkage groups. 
     
     
         24 . A computer system for use in artificial selection comprising:
 (i) a database of estimated breeding values for one or more individuals of a population having a small effective population size and optionally comprising data selected from the group consisting of: data on ancestors and/or founders for individuals; data on chromosome segments for individuals in the current population; data on chromosome segments for ancestors and/or founders of individuals in the current population; data on marker genotype(s) in chromosome segment(s) for individuals in the current population; data on marker genotype(s) in chromosome segment(s) for ancestors and/or founders; data on lineages between the marker genotype(s) and/or chromosome segment(s); and combinations thereof, wherein the estimated breeding values are obtained by performing the method according to  claim 2 ; and   (ii) a user interface allowing a user to input data pertaining to an individual and/or query the database and/or display results of a database query.   
     
     
         25 . The computer system according to  claim 24 , wherein the marker genotype(s) of one or more ancestors and/or founders are arrayed in linkage groups. 
     
     
         26 . The computer system according to  claim 24 , wherein the data pertaining to an individual are selected from data on chromosome segment, genetic marker, haplotype, haplogroup, nucleotide sequence, nucleotide occurrences for the individual and combinations thereof. 
     
     
         27 . (canceled) 
     
     
         28 . A process for producing genetic gain in a population comprising performing the method according to  claim 2  and selecting an individual having a high estimated breeding value from a population. 
     
     
         29 . The process of  claim 28 , comprising obtaining reproductive or regenerative material from the selected individual. 
     
     
         30 . Reproductive or regenerative material obtained by performing the process of  claim 29 . 
     
     
         31 - 35 . (canceled) 
     
     
         36 . A process for producing genetic gain in a population comprising:
 (i) performing the method according to  claim 2  to thereby estimate the breeding value of one or more individuals in a population;   (ii) selecting an individual from (i) having a high estimated breeding value;   (iii) obtaining reproductive or regenerative material from the selected individual; and   (iv) producing one or more individuals or one or more generations of individuals from the reproductive or regenerative material.   
     
     
         37 . A non-human produced by performing the method of  claim 36 . 
     
     
         38 . A method for determining a set of ancestors and/or founders that is representative of a current population having a small effective population size, said method comprising determining the long term contributions of ancestors and/or founders to the population with reference to pedigrees of individuals of the current population and selecting those individuals providing the largest long term contributions to the current population such that the smallest number of ancestors and/or founders is selected to substantially describe the variance in the current population. 
     
     
         39 . A computer-readable medium for use in artificial selection said computer-readable medium comprising a database of one or more sets of ancestors and/or founders that are representative of one or more current populations having a small effective population size produced by performing the method according to  claim 38 , and optionally comprising additional data selected from the group consisting of: data on actual or estimated breeding values for one or more ancestors and/or founders; data on chromosome segments for ancestors of individuals in the current population; data on one or more markers contained within one or more chromosome segments for ancestors and/or founders of individuals in the current population; and combinations thereof. 
     
     
         40 . A computer system for use in artificial selection comprising:
 (i) a database of one or more sets of ancestors and/or founders that are representative of one or more current populations having a small effective population size produced by performing the method according to  claim 38 , and optionally comprising additional data selected from the group consisting of: data on actual or estimated breeding values for one or more ancestors and/or founders; data on chromosome segments for ancestors and/or founders of individuals in the current population; data on one or more markers contained within one or more chromosome segments for ancestors and/or founders of individuals in the current population and combinations thereof; and   (ii) a user interface allowing a user to input data pertaining to an individual and/or query the database and/or display results of a database query.   
     
     
         41 . The computer system according to  claim 40 , wherein marker genotype(s) of one or more ancestors and/or founders are arrayed in linkage groups. 
     
     
         42 . The computer system according to  claim 40 , wherein the data pertaining to an individual are selected from data on chromosome segment, genetic marker, haplotype, haplogroup, nucleotide sequence, nucleotide occurrences for the individual and combinations thereof.