Y-Chromosome Mismatch Distributions in Europe
Ancient demographic events can be inferred from the distribution of pairwise sequence differences (or mismatches) among individuals. We analyzed a database of 3,677 Y chromosomes typed for 11 biallelic markers in 48 human populations from Europe and the Mediterranean area. Contrary to what is observed in the analysis of mitochondrial polymorphisms, Tajima’s test was insignificant for most Y-chromosome samples, and in 47 populations the mismatch distributions had multiple peaks. Taken at face value, these results would suggest either (1) that the size of the male population stayed essentially constant over time, while the female population size increased, or (2) that different selective regimes have shaped mitochondrial and Y-chromosome diversity, leading to an excess of rare alleles only in the mitochondrial genome. An alternative explanation would be that the 11 variable sites of the Y chromosome do not provide sufficient statistical power, so a comparison with mitochondrial data (where more than 200 variable sites are studied in Europe) is impossible at present. To discriminate between these possibilities, we repeatedly analyzed a European mitochondrial database, each time considering only 11 variable sites, and we estimated mismatch distributions in stable and growing populations, generated by simulating coalescent processes. Along with theoretical considerations, these tests suggest that the difference between the mismatch distributions inferred from mitochondrial and Y-chromosome data are not a statistical artifact. Therefore, the observed mismatch distributions appear to reflect different underlying demographic histories and/or selective pressures for maternally and paternally transmitted loci.
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European Population Substructure: Clustering of Northern and Southern Populations
The development of methodologies for defining population genetic structure has provided the ability to identify the major ethnic contributions in individual subjects in diverse populations. Using a genome-wide SNP panel we observe population structure in a diverse group of Europeans and European Americans. Under a variety of conditions and tests there is a consistent and reproducible distinction between "northern" and "southern" European population groups: most individual subjects with southern European ancestry (Italian, Spanish, Portuguese, and Greek) have >85% membership in the "south" population; and most northern, western, eastern and central Europeans have >90% in the "north" population group. Ashkenazi Jewish as well as Sephardic Jewish origin also showed >85% membership in the "south" population consistent with a later Mediterranean origin of these ethnic groups. Based on this work, we have developed a core set of informative SNP markers that can control for this partition in European population structure in a variety of clinical and genetic studies.
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Measuring European Population Stratification with Microarray Genotype Data
A proper understanding of population genetic stratification - differences in individual ancestry within a population - is crucial in attempts to find genes for complex traits through association mapping. We report on genomewide typing of ~10,000 single-nucleotide polymorphisms in 297 individuals, to explore population structure in Europeans of known and unknown ancestry. The results reveal the presence of several significant axes of stratification, most prominently in a northern-southeastern trend, but also along an east-west axis. We also demonstrate the selection and application of EuroAIMs (European ancestry informative markers) for ancestry estimation and correction. The Coriell Caucasian and CEPH (Centre d'Étude du Polymorphisme Humain) Utah sample panels, often used as proxies for European populations, are found to reflect different subsets of the continent's ancestry.
PDF file
Ancient demographic events can be inferred from the distribution of pairwise sequence differences (or mismatches) among individuals. We analyzed a database of 3,677 Y chromosomes typed for 11 biallelic markers in 48 human populations from Europe and the Mediterranean area. Contrary to what is observed in the analysis of mitochondrial polymorphisms, Tajima’s test was insignificant for most Y-chromosome samples, and in 47 populations the mismatch distributions had multiple peaks. Taken at face value, these results would suggest either (1) that the size of the male population stayed essentially constant over time, while the female population size increased, or (2) that different selective regimes have shaped mitochondrial and Y-chromosome diversity, leading to an excess of rare alleles only in the mitochondrial genome. An alternative explanation would be that the 11 variable sites of the Y chromosome do not provide sufficient statistical power, so a comparison with mitochondrial data (where more than 200 variable sites are studied in Europe) is impossible at present. To discriminate between these possibilities, we repeatedly analyzed a European mitochondrial database, each time considering only 11 variable sites, and we estimated mismatch distributions in stable and growing populations, generated by simulating coalescent processes. Along with theoretical considerations, these tests suggest that the difference between the mismatch distributions inferred from mitochondrial and Y-chromosome data are not a statistical artifact. Therefore, the observed mismatch distributions appear to reflect different underlying demographic histories and/or selective pressures for maternally and paternally transmitted loci.
PDF file
European Population Substructure: Clustering of Northern and Southern Populations
The development of methodologies for defining population genetic structure has provided the ability to identify the major ethnic contributions in individual subjects in diverse populations. Using a genome-wide SNP panel we observe population structure in a diverse group of Europeans and European Americans. Under a variety of conditions and tests there is a consistent and reproducible distinction between "northern" and "southern" European population groups: most individual subjects with southern European ancestry (Italian, Spanish, Portuguese, and Greek) have >85% membership in the "south" population; and most northern, western, eastern and central Europeans have >90% in the "north" population group. Ashkenazi Jewish as well as Sephardic Jewish origin also showed >85% membership in the "south" population consistent with a later Mediterranean origin of these ethnic groups. Based on this work, we have developed a core set of informative SNP markers that can control for this partition in European population structure in a variety of clinical and genetic studies.
PDF file
Measuring European Population Stratification with Microarray Genotype Data
A proper understanding of population genetic stratification - differences in individual ancestry within a population - is crucial in attempts to find genes for complex traits through association mapping. We report on genomewide typing of ~10,000 single-nucleotide polymorphisms in 297 individuals, to explore population structure in Europeans of known and unknown ancestry. The results reveal the presence of several significant axes of stratification, most prominently in a northern-southeastern trend, but also along an east-west axis. We also demonstrate the selection and application of EuroAIMs (European ancestry informative markers) for ancestry estimation and correction. The Coriell Caucasian and CEPH (Centre d'Étude du Polymorphisme Humain) Utah sample panels, often used as proxies for European populations, are found to reflect different subsets of the continent's ancestry.
PDF file
