Methods of Selection, Reporting and Analysis of Genetic Markers Using Broad-Based Genetic Profiling Applications

Abstract

Disclosed is a method for determining whether an individual has an enhanced, diminished, or average probability of exhibiting one or more phenotypic attributes and related methods of selecting a set of genetic markers; for providing relevant genetic information to an individual; of evaluating the probability that progeny of two individuals of the opposite sex will exhibit one or more phenotypic attributes; and for determining the genomic ethnicity of an individual.

1 - 30 . (canceled) 
     
     
         31 . A computer-implemented method for providing an evaluation indicative of a probability that an individual will exhibit one or more phenotypic attributes, comprising:
 (a) evaluating markers of the individual that are preselected based on association or other studies to be linked with the one or more phenotypic attributes, wherein the markers map to at least 1,000 sites;   (b) evaluating a pattern of the markers to determine a genomic ethnicity of the individual;   (c) determining a probability that the individual will exhibit the one or more phenotypic attributes based at least in part on the pattern of the markers and the genomic ethnicity of the individual; and   (d) generating a report with an evaluation indicative of the probability that the individual will exhibit the one or more phenotypic attributes.   
     
     
         32 . The method according to  claim 31 , wherein the genomic ethnicity is determined with respect to haplotype blocks. 
     
     
         33 . The method according to  claim 32 , wherein the haplotype blocks are determined based on a presence of the markers. 
     
     
         34 . The method according to  claim 33 , further comprising evaluating common variants associated with complex diseases, wherein the common variants are present within the haplotype blocks identified by the markers. 
     
     
         35 . The method according to  claim 31 , further comprising determining a likely applicability of clinical research results based on the genomic ethnicity of the individual. 
     
     
         36 . The method according to  claim 31 , wherein the markers comprise a plurality of exon/intron junction sequences. 
     
     
         37 . The method according to  claim 36 , wherein at least about 20% of the markers in the preselected set are exon/intron junction sequences. 
     
     
         38 . The method according to  claim 31 , wherein the markers comprise a plurality of promoter sequences. 
     
     
         39 . The method according to  claim 38 , wherein at least about 20% of the markers are promoter sequences. 
     
     
         40 . The method according to  claim 31 , further comprising formatting the report according to an organizational matrix that determines a grouping and presentation of information on the report. 
     
     
         41 . The method according to  claim 40 , wherein the organizational matrix (i) groups together phenotypic attributes for which the individual has an enhanced probability, or (ii) groups together phenotypic attributes related to similar physiological systems. 
     
     
         42 . The method according to  claim 40 , wherein the organizational matrix (i) ranks phenotypic attributes as a function of potential impact on a lifestyle or quality of life of the individual, or (ii) ranks phenotypic attributes as a function of the genomic ethnicity of the individual. 
     
     
         43 . The method according to  claim 31 , wherein in the report, an identity of the individual is not associated with data corresponding to any genotypic characteristics or the probability that the individual will exhibit the one or more phenotypic attributes. 
     
     
         44 . The method according to  claim 31 , wherein the markers map to at least about 1,000 discrete loci. 
     
     
         45 . The method according to  claim 31 , further comprising placing associations between the one or more phenotypic attributes and the markers on a two-dimensional grid for display on the report. 
     
     
         46 . The method according to  claim 31 , further comprising performing a targeted assay to identify the markers, which assay includes nucleic acid amplification of a biological sample from the individual. 
     
     
         47 . The method according to  claim 31 , further comprising providing the report for display on a graphical user interface. 
     
     
         48 . The method according to  claim 31 , wherein in (a), the markers are preselected based on association or other studies to be linked with at least 10 phenotypic attributes, and wherein the markers map to at least 1,000 sites. 
     
     
         49 . The method according to  claim 31 , further comprising, subsequent to (b), obtaining a marker score by comparing the markers and the genomic ethnicity of the individual to a multivariate scoring matrix that relates patterns of markers and genomic ethnicity with probabilities of exhibiting phenotypic attributes, which phenotypic attributes include the one or more phenotypic attributes. 
     
     
         50 . The method according to  claim 49 , wherein the multivariate scoring matrix scores the markers at least with respect to three or more criteria selected from the group consisting of penetrance of a given marker in a population of interest, ontological classification, conservation of mutated sequence sites at conserved or less conserved sites, and biological significance. 
     
     
         51 . The method according to  claim 49 , wherein the multivariate scoring matrix comprises a combination of one or more scoring matrix vectors selected from the group consisting of a descriptor of family history, a descriptor of general medical physiological values, a descriptor of mRNA expression levels, a descriptor of methylation profiles, a descriptor of protein expression levels, a descriptor of enzyme activity, and a descriptor of antibody load. 
     
     
         52 . The method according to  claim 49 , further comprising using the marker score to determine the probability that the individual will exhibit the one or more phenotypic attributes.