Inter-chromosomal variation in the pattern of human population genetic structure

The comprehensive identification and control of population genetic structure and dissection of polymorphism are important steps in genomic studies aimed at gene mapping through (either directly or indirectly) linkage disequilibrium (LD) [1-4]. Previous estimates of population structure have provided tremendous insight into population genetics and human evolution, and have increased our knowledge of the distribution of genetic variation and relationships among human populations [5-8]. Until recently, however, these studies have been based on limited numbers of loci/genes or small fractions of the genome and thus have provided only average estimates of quantities such as fixation index (FST) across whole genomes and populations [9].The study of a few genes with significant population differentiation can be extremely efficient -- for example, in screening for potential tumour markers or drug targets. Such analyses do not reach the full potential of genome-wide experiments to increase our understanding of whole biological processes, however. What is needed instead is a holistic approach to analysing the entire genome which shows major population differentiation and allows biologists to develop an integrated understanding of the functional networks/pathways driving population diversity [10]. P？？bo [11] suggested that, in variation studies, rather than 'populations', 'ethnicities' or 'races', a more efficient approach for studying within- and between-individual human chromosomal variation is to consider the genome of any particular individual as a mosaic of haplotype blocks.To date, analyses of the relationship between genetic variation and ancestral geographic origin have been limited to a few regions or genes because large-scale, genome-wide single nucleotide polymorphism (SNP) data from geographically diverse individuals have not been available. Given that levels of diversity/polymorphism are directly related to recombination (meiosis) and mutation rates that differ wi