Reply to Moura et al

Abstract

The authors appreciate the comments of Moura et al 1 in their letter and agree that when the markers are available, Amerindian genotypes probably better serve as a pseudoancestor group for the Brazilian population than the Chinese when this is the only comparison or consideration to be made. We further agree that in some, but not all instances, use of a Han Chinese data set in this way may result in inflation of 'Amerindian' ancestry relative to the Native American Microsatellite (NAM) panel of the HGDP-CEPH Diversity project or the AMI panel used in their analyses. However, there is no evidence that this would change any of the conclusions in the paper. We observe the following: (1) There was a comparison of ancestry estimates using pseudoancestors from the NAM panel with those from the CHB (Figure 2c and d). (2) Ancestry estimates are relative to the specific samples included and the markers used, so the influence of a pseudoancestor group will depend on the composition of the admixed sample being analyzed. (3) The degree of differentiation between groups in the paper by Pena et al cannot be taken as representative of these areas. (4) What degree of error is important depends on the magnitude of the error and on the question being asked.For our study, the markers used to genotype the Brazilian population were selected in [2004][2005][2006] for their relevance to a study on dengue along with~40 selected specifically as AIMs. Twice as many of the selected markers were present in the Hapmap CHB panel (237 SNPs) as the NAM set (108 SNPs). We did, however, directly compare the use of the CHB and NAM panels in our Figure 2. Visually the differences appear small and would not change any of the conclusions about association with self-identified ethnicity. We do find a 2-3-fold higher 'Amerindian' ancestry for Whites in Fortaleza when using the CHB population as pseudoancestors compared with the NAM. Because the accuracy of ancestry estimates improves with the number of markers used (informativeness for ancestry being equal 2 ), the larger number of markers available with the CHB panel improves the accuracy for comparison with the other source populations included in the analysis. Use of the NAM panel throughout would not have changed any of the conclusions in the paper.It should be kept in mind that all ancestry estimates are comparative and can be dialed up or down depending on which individuals are used in the comparison, the number of markers and the information content of the markers (when the number is small). There are no absolute ancestry proportions, except in simulation. We all pointedly use the term 'pseudoancestors' in recognition that we do not know what the genotypes of the original ancestors were. All estimates using current populations as source populations have an unknown degree of error relative to the true allelic composition. Further, Amerindians, unless from very isolated populations, tend to underestimate their degree of European Ancestry. That being said, most Amerindian populations clearly clust...

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