A Classifier for the SNP-Based Inference of Ancestry

Abstract

Ancestral inference from DNA could serve as an important adjunct for both standard and future human identity testing procedures. However, current STR methods for the inference of ancestral affiliation have inherent statistical and technical limitations. In an effort to identify biallelic markers that can be used to infer ancestral affiliation from DNA, we screened 211 SNPs in the human pigmentation and xenobiotic metabolism genes. Allele frequencies of 56 SNPs (most from pigmentation genes) were dramatically different between groups of unrelated individuals of Asian, African, and European descent, and both observed and simulated log likelihood ratios revealed that the markers were of exceptional value for ancestral inference. Log likelihood ratios of the multilocus estimates of biological ancestry (EAE/EBA) ranged from 7 to 10, which are on par with the best of the STR batteries yet described. A linear classification method was developed for incorporating these SNPs into a classifier model that was 99, 98, and 100% accurate for identifying individuals of European, African, and Asian descent, respectively. The methods and markers we describe are therefore an important first step for the development of a practical multiplex test for the inference of ancestry in a forensics setting.

Replicated Linkage for Eye Color on 15q Using Comparative Ratings of Sibling Pairs

“…When we adjusted the data for the locus on chromosome 15q and performed a new genomescan (data not shown), the next largest test statistics were LODs of 1.7 and 1.5, on chromosomes 12 and 11, respectively, which were slightly higher LOD scores than seen in the scan unadjusted for the 15q locus. Although these were not significant at the genome-wide level, the chromosome 11 peak is interesting as it is in a region that contains the tyrosinase gene (TYR, aka OCA1A on 11q14-11q21) which plays a role in melanine formation in the eye (Frudakis et al, 2003;Oetting and King, 1993). The same regions on 11 and 12 showed modest peaks in the analysis of Zhu et al, 2004. The regression method is robust and because it is extremely fast it lends itself to computer-intensive resampling methods such as permutation testing to obtain significance and for example bootstrapping to estimate the confidence region of the trait locus.…”

“…Frudakis et al (2003) used a hypothesis-driven SNP screen, focusing on pigmentation candidate genes. They identified 61 SNPs that were associated with iris pigmentation.…”

Bias in association studies of systemic lupus erythematosus susceptibility due to geographical variation in the frequency of a programmed cell death 1 polymorphism across Europe

“…The use of several collections of cases and controls with different origin, as performed here, will allow the identification of these situations. When the available population has an admixed origin the use of markers for inference of ancestry [35][36][37] could be useful as has been shown recently by the development of a panel of SNP markers that differentiate between Europeans from the South and from the North. 21 …”

Gender is a major factor explaining discrepancies in eye colour prediction based on HERC2/OCA2 genotype and the IrisPlex model

“…21 Human eye colour is a fully genetically determined trait with a 22 complex inheritance pattern, although most times it apparently 23 behaves as a simple Mendelian character. This is so because one 24 genetic region, HERC2/OCA2, accounts for the majority of the blue 25 and brown variation (the two most common colours) in human 26 eye colour [2,3]. 27 Although genetic association studies had already identified the 28 relationship between the OCA2 gene and eye colour [2,4], it was not 29 until 2008 when three independent studies found that HERC2, a 30 neighbouring gene, and specifically the SNP rs12913832, was the 31 key human eye colour regulator [5][6][7].…”

“…This is so because one 24 genetic region, HERC2/OCA2, accounts for the majority of the blue 25 and brown variation (the two most common colours) in human 26 eye colour [2,3]. 27 Although genetic association studies had already identified the 28 relationship between the OCA2 gene and eye colour [2,4], it was not 29 until 2008 when three independent studies found that HERC2, a 30 neighbouring gene, and specifically the SNP rs12913832, was the 31 key human eye colour regulator [5][6][7]. In addition, other genes 32 such as SLC24A4, SLC45A2, TYR, TYRP1, ASIP or IRF4 have also been 33 recognised to contribute to eye colour variation, although to a 34 much lesser extent [8][9][10].…”