Method for Determining Relatedness of Genomic Samples Using Partial Sequence Information

Abstract

Disclosed are methods for testing biological samples containing genomic nucleic acids obtained from an organism having a genome, such as a human genome. It is often desirable to analyze a DNA sample or more than one, different DNA samples, to determine whether the sample comes from one individual or two individuals. The present method requires very low amounts of DNA and can use partial sequences of DNA fragments. Partial sequences are analyzed for the presence of polymorphisms (e.g. SNP's) that can be mapped to a reference SNP map. The distance between similar SNPS, which are genetically linked, can be used to statistically determine a likelihood of identity of individuality in a sample.

1 . A method for genotyping uncharacterized genomic DNA, based on limited sequence information of the genomic DNA in a sample, comprising:
 (a) obtaining a plurality of independent DNA sequences from a genomic sample, wherein the sequences contain identified polymorphic sites;   (b) calculating a set of linkage disequilibrium (“LD”) scores for a set of two or more polymorphic sites obtained in step (a), resulting in a set of LD scores indicating likelihoods that polymorphic sites in a given set are linked on a chromosome and wherein LD scores are calculated in physical locations along a genome being genotyped; and   (c) preparing a compilation of scores from step (b).   
     
     
         2 . The method of  claim 1 , wherein said uncharacterized genomic DNA is from a sample that comprises one of human blood, hair, hair root, saliva, semen, or bone marrow. 
     
     
         3 . The method of  claim 1 , wherein the uncharacterized genomic DNA is from more than one sample. 
     
     
         4 . The method of  claim 1 , wherein said polymorphic sites are selected from the group consisting of variable number tandem repeats (VNTRs), simple-tandem repeats, short tandem repeats (STRs), single nucleotide polymorphisms (SNPs), and human mitochondrial DNA (mtDNA) first hypervariable region (HVI) and second hypervariable region (HVII). 
     
     
         5 . The method of  claim 4 , wherein the polymorphic sites are SNPs. 
     
     
         6 . The method of  claim 5 , wherein said SNPs are recorded in a publicly available archive containing chromosomal locations of SNPS within the archive. 
     
     
         7 . The method of  claim 5 , wherein said SNPs occur in unique subsequences within a genome. 
     
     
         8 . The method of  claim 5 , wherein the SNPs occurs in at least one percent of a population. 
     
     
         9 . The method of  claim 1 , wherein the step of obtaining a plurality of independent DNA sequences further comprises the step of massively parallel sequencing said genomic DNA in the sample. 
     
     
         10 . The method of  claim 1 , wherein said step of obtaining a plurality of independent DNA sequences further comprises massively paralleling sequencing in a platform generating read lengths between 50 bp and 350 bp. 
     
     
         11 . The method of  claim 10 , wherein said sequencing comprises a step of randomly fragmenting genomic DNA in a sample. 
     
     
         12 . The method of  claim 1 , wherein said limited sequence information is sequencing of between 1% and 10% of a genome or genome fragment being genotyped. 
     
     
         13 . The method of  claim 1 , wherein calculating a set of linkage disequilibrium (“LD”) comprises sliding windows of polymorphisms located in proximity on a chromosome. 
     
     
         14 .- 19 . (canceled) 
     
     
         20 . The method of  claim 1 , wherein the compilation indicates a likelihood that the plurality of sequences is from a single individual or are from more than one individual, based on compiled LD scores. 
     
     
         21 . The method of  claim 1 , wherein the compilation indicates a likelihood for a genotype, based on compiled LD scores. 
     
     
         22 . The method of  claim 1 , wherein the sequences in (a) are obtained by a massively parallel sequencing process performed at a coverage of 0.5% or greater of the genome of the genomic sample. 
     
     
         23 . The method of  claim 1 , wherein the sequences obtained in (a) contain thousands or more identified polymorphic sites. 
     
     
         24 . The method of  claim 23 , wherein the genomic sample comprises human genomic DNA. 
     
     
         25 . The method of  claim 1 , wherein the sequences obtained in (a) contain hundreds of thousands of identified polymorphic sites. 
     
     
         26 . The method of  claim 1 , wherein the sequences obtained in (a) contain millions of identified polymorphic sites.