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Saturday, March 06, 2004 5:44:05 AM
http://www.tracegenetics.com/nativeamericandna.pdf
III. The autosomal (genome-wide) test
The autosomal test traces the ancestry of your genome (maternal and paternal) and provides percentage ancestry in broad geographic and linguistic groupings (not races), namely Sub-Saharan African, East Asian, European (namely, the Caucasoids, the diaspora of which correspond roughly to the distribution of individuals part of a language family that spreads from Western Europe to Northern India), and Native American. It should be noted that the current test offered has from 3-12% reported error rate (depending on the type of interbreeding, see Table 2 below), meaning that any ancestry in these groupings that is below 3-12% (depending on the groups) are not certain at the 95% confidence level (i.e. they could be inaccurately reported). Conversely, very low levels (<3%) of ancestry may not be detected. The test operates by screening approximately 180 genetic markers that show large frequency differences among the four population samples comprising the database. The inference of percentage ancestry is made from a statistical analysis of the 180 informative markers.
Table 2. Based on simulations, the minimum percentage ancestry required for accurate reporting in individuals of two ancestral backgrounds (unpublished data Frudakis and Shriver).
AFR EUR EAS NAM
Africans < 3.0% 7% 5% <3%
Europeans 3.50% < 3.0% 9% 10%
East Asians < 3.0% 8% < 3.0% 12.50%
Native American < 3.0% 7.50% 11.50% < 3.0%
The above table shows that greater than or equal to 10% Native American ancestry is required for an individual of polarized (i.e. mainly) European ancestry to conclude with 95% confidence that there is Native American ancestry. A greater than or equal to 12.5% Native American ancestry is needed for an individual of Native American and East Asian ancestry to conclude with accuracy that there is Native American ancestry. The values required to conclude Native American ancestry with 90% certainty are about 2/3rds those shown in Table 2.
Accuracy and Sampling Error
The individuals originally studied to determine Native American ancestry markers in this test are all from Southwest North America. Therefore, individuals with Native American ancestry from this region will likely be identified. However, Native American ancestry from other regions of North America may not be accurately identified. Unpublished research (Frudakis and Shriver) has shown that documented and relatively homogeneous American Indians from the United States reliably type with majority Native American ancestry using this test, and other research is ongoing to further define the sensitivity and accuracy limits in this subgroup of Native Americans.
The future of DNA testing to determine Native American Ancestry
Through haplotype analysis, DNA tests are already quite reliable in determining Native American ancestry along the direct maternal and paternal lines. Currently, the autosomal (genome-wide) test is fairly accurate at identifying individuals with a high percentage of Native American ancestry from Southwest North America, and unpublished data suggests that persons with Native American ancestry from outside of the Southwest also type as of mainly Native American ancestry using the Southwest group as a “calibration” group, but the sensitivity and accuracy in this group has yet to be established and could be lower for Native American groups distantly related to those in the Southwest. We can expect additional haplotypes that are informative about geographic and tribal ancestry within North America to be developed through advanced analyses that screen larger portions of the mitochondrial genome and the Y chromosome. For mtDNA only a small segment (approximately 2%) of the mitochondrial genome is sequenced to determine ancestry. Fortunately technological advances now allow for economical sequencing of the entire mitochondrial genome and researchers are already doing this for samples in the Americas (Bandelt et al. 2003). The number of informative markers available for analysis of ancestry based on the Y chromosome has increased substantially in the past few years (Zegura et al. 2003). With an appropriate sampling scheme, there is still a large potential for identifying Y chromosome markers that are informative about geographic and tribal ancestry within North America to be developed. Additional data for identifying autosomal markers that are informative about Native American ancestry have recently been published (Rosenberg et al. 2003, Collins-Schramm et al. 2003). With this data and an appropriate sampling scheme for the collection of samples, more accurate autosomal tests for determining and quantifying Native American ancestry will likely be available in the near future. The success of increasing the informativeness and accuracy of DNA based ancestry tests for Native Americans is highly dependent upon additional sampling of Native American individuals, which is contingent upon mutually beneficial relationships between private testing companies, universities, and Native American communities. Many Native American groups are understandably leery of the motives of private companies and government or university researchers. However a recent survey investigating the attitudes of Native American groups about genetic testing indicate that many Native American individuals do not oppose genetic research and believe they can benefit from it (Schroeder et al. 2004). To ensure that proper safeguards are in place to adequately protect Native American participants from the risks of genetic research, Native American communities would benefit from working with university researchers who are required to participate in human subjects protection protocols before proceeding with a project. Fortunately, the horizon looks bright for collaboration between Native American communities and university researchers on genetic research. Funding to initiate such collaborations is available through the National Human Genome Research Institute (NHGRI) and articles addressing issues of the best ways to proceed with such collaborations are becoming more frequent in the academic literature. Certain Native American communities are also taking a pro-active role in these collaborations and the direction and goals of research projects are being determined by Native American communities as well as researchers. Finally, it is up to the private DNA testing company to ensure that they are presenting the information about these diagnostic tests as accurately as possible. Due to the rapidly changing landscape of DNA based ancestry tests, private companies that are closely allied with university and academic research will likely be the companies with the best interpretation of the results from DNA based ancestry tests for Native Americans.
This is some of the recent research referred to above:
Collins-Schramm HE, Chima B, Morii T, Wah K, Figueroa Y, Criswell LA, Hanson RL, Knowler WC, Silva G, Belmont JW, Seldin MF. Mexican American ancestry-informative markers: examination of population structure and marker characteristics in European Americans, Mexican Americans, Amerindians and Asians. Hum Genet. 2004 Feb;114(3):263-71. Epub 2003 Nov 20.
Rowe Program in Human Genetics, Department of Biological Chemistry, University of California at Davis, One Shields Avenue, Davis, CA 95616-8669, USA.
Markers with large differences in allele frequencies between ethnicities provide ancestry information that can be applied to genetic studies. We identified over 100 biallelic ancestry informative markers (AIMs) with large allele frequency differences between European Americans (EA) and Pima Amerindians from laboratory and database screens. For 35 of these markers, Mayan, Yavapai and Quechuan Amerindians were genotyped and compared with EA and Pima allele frequencies. Markers with large allele frequency differences between EA and one Amerindian tribe showed only small differences between the Amerindian tribes. Examination of structure in individuals demonstrated a clear separation of subjects of European from those of Amerindian ancestry, and similarity between individuals from disparate Amerindian populations. The AIMs demonstrated the variation in ancestral composition of individual Mexican Americans, providing evidence of applicability in admixture mapping and in controlling for structure in association tests. In addition, a high percentage of single-nucleotide polymorphisms (SNPs) selected on the basis of large frequency differences between EA and Asian populations had large allele frequency differences between EA and Amerindians, suggesting an efficient method for greatly expanding AIMs for use in admixture mapping/structure analysis in Mexican Americans. Together, these data provide additional support for the practical application of admixture mapping in the Mexican American population.
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