In this paper, we integrate the estimation of local ancestry in admixed individuals with targeted resequencing to obtain sequences directly inherited from the ancestral populations. Local ancestry can be inferred by estimating the number of copies inherited from each ancestral population at each location across the genome. Schematic showing a pair of chromosomes from an admixed individual with ancestry from different continental populations (shown in black and red). If the mixing between ancestral populations is recent (e.g., within the last 500 years), then the size of chromosomal вЂњchunksвЂќ inherited from one of the ancestral populations is still relatively large (e.g., several megabases long on average) and the methods tend to work reasonably well. Specifically, at each position in the genome, these methods estimate how many copies (0, 1, or 2) were inherited from prespecified ancestral populations (see fig. Recently, several methods have been developed to estimate local genetic ancestry in admixed individuals from dense genotype data (e.g., Falush et al. This heterogeneity is a problem both for evolutionary studies and for genetic association studies in Latinos unless genetic ancestry can be measured and accounted for. For example, the estimated proportion of European ancestry in a sample of 181 Mexican controls varied from в€ј0% to в€ј100% ( Choudhry et al. Latinos encompass a mix of European, Native American, and African ancestries, and the relative contributions of these three ancestral continental groups can vary substantially between self-identified Latino subgroups (e.g., between Mexican Americans and Puerto Ricans) and among individuals within the same subgroup (e.g., Salari et al. Latinos (also called Hispanics) are considered an ethnic group with a shared cultural heritage spread out over most of the Americas, without regard to race or ancestry. In this paper, we address this knowledge gap by collecting and analyzing genetic data from admixed вЂњLatinos,вЂќ who have partial Native American ancestry.

2007) studies have been performed with Native American samples, the amount of autosomal resequencing data generated (from Native American samples) is almost negligible (see, e.g., Hey 2005), and the insights gained from the analyses of Native American resequencing data have been limited. In fact, although large-scale SNP ( Jakobsson et al. Although Old World continental groups (i.e., Europeans, Asians, and Africans) are well sampled in these studies, populations indigenous to the Americas are generally not included. 2005 ENCODE Project Consortium 2007 Wall et al. With recent advances in molecular sequencing technology, we now have resequencing data from more than 1,000 genetic regions spanning more than 20 Mb of sequence (e.g., Reich et al. Resequencing studies, where all sampled individuals are fully sequenced across the target regions, are more informative than SNP or microsatellite-based studies because they provide an unbiased and complete snapshot of both rare and common variants in the study sample. 2006 International HapMap Consortium 2007), and resequencing data (e.g., Vigilant et al. 2002), single nucleotide polymorphism (SNP) data (e.g., Conrad et al. 1987), microsatellite data (e.g., Rosenberg et al. Using two different computational approaches, one novel, we estimate that this bottleneck occurred roughly 12.5 Kya when uncertainty in the estimation process is taken into account, our results are consistent with archeological estimates for the colonization of the Americas.Д®volutionary geneticists have long used genetic polymorphism data to make inferences about human demographic history, utilizing restriction site polymorphism surveys (e.g., Cann et al.

We observe low levels of diversity and high levels of linkage disequilibrium in the Native AmericanвЂ“derived sequences, consistent with a recent severe population bottleneck associated with the initial peopling of the Americas. We analyze roughly 6 Mb of resequencing data from 22 Mexican Americans to provide the first large-scale view of sequence level variation in Native Americans.

In this study, we introduce a new method for estimating local ancestry across the genomes of admixed individuals and show how this method, along with dense genotyping and targeted resequencing, can be used to assay genetic variation in ancestral Native American groups.

However, there are many resequencing studies involving Latinos, whose genomes contain segments inherited from their Native American ancestors. Analyses of genetic polymorphism data have the potential to be highly informative about the demographic history of Native American populations, but due to a combination of historical and political factors, there are essentially no autosomal sequence polymorphism data from any Native American group.

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