ANCESTRAL-SPECIFIC REFERENCE GENOMES AND USES IN IDENTIFYING A CANDIDATE FOR A CLINICAL TRIAL

摘要

Ancestry has a significant impact on the major and minor alleles found in each nucleotide position within the genome. Due to mechanisms of inheritance, ancestral-specific information contained within the genome is conserved within members of an ancestry. For this reason, individuals within a specific ancestry are more likely to share alleles in their genomes with other members of the same ancestry. Functionally, the combination of alleles at all positions within a group of individuals defines that group as having a common ancestry. Moreover, the aggregation of differences between alleles at all positions distinguishes one ancestry from another. The genomic similarities and differences between ancestries provides a mechanism to generate reference genomes that are specific for each ancestry. Reference genomes that are specific to an ancestry can be used to increase the accuracy of whole genome sequencing, DNA-based diagnostics and therapeutic marker discovery and in a variety of real-world DNA-based applications. Provided herein is a method for identifying a candidate individual for participation in a clinical trial, comprising the step of comparing a DNA sequence of the whole genome of a patient with any one or more of the ancestral-specific reference genomes of an ancestral-specific reference genome database described herein, wherein the presence or absence of a clinically relevant genetic marker indicates that the individual is candidate for participation in the clinical trial.

主权项

1. A method for identifying a candidate individual for participation in a clinical trial using an ancestral-specific reference genome constructed by steps comprising:
a) obtaining a familial genome data set comprising DNA sequences from members of the candidate individual's family; b) comparing the DNA sequences within the familial genome data set to obtain a corrected familial genome data set; c) preparing a first composite familial genome data set from the corrected familial genome data set; d) repeating steps a-c for a second, third or more families to obtain a second, third or more composite familial genome data sets; e) evaluating the first, second, third or more composite familial genome data sets for single nucleotide polymorphisms (SNPs) and/or haplotypes and assigning statistical significance to the SNPs and/or haplotypes; f) grouping the first, second, third or more composite familial genome data sets based on single nucleotide polymorphisms (SNPs) and/or haplotypes that are statistically significant; g) preparing the ancestral-specific reference genome by compiling the SNPs and/or haplotypes shared by a group of composite familial genome data sets with the same ancestry; and h) comparing a DNA sequence of the candidate individual's genome with the ancestral-specific reference genome, wherein the presence or absence of a clinically relevant genetic marker indicates that the individual is or is not a candidate for participation in the clinical trial.