| Abstract |
Human population history has been described by analysing different genetic
markers. Much attention has focused on haploid markers (such as mtDNA and
Y chromosome), but this study addresses the X chromosome (haploid in
males, and with a female bias in its history) in order to describe genetic
diversity and to infer human population history in Western Europe.
HapMap Phase I/II data reveal haplotype blocks on the X chromosome, called
PHAXs (Phylogeographically informative Haplotypes on Autosomes and X
chromosome), in which recombination is historically absent and mutations
are likely to be the only source of genetic variation. Three such regions
were chosen to meet several criteria such that mutations in these loci are
putatively neutral. These loci have been deep sequenced in 240 samples
from Europe, the Middle East and Africa using the Ion Torrent PGM next-
generation sequencing (NGS) platform. Short-tandem repeats (STRs) were
also typed in order to provide: i) greater discrimination, and ii) a test
of different software tools able to call STRs from NGS data. This dataset
was validated against a standard STR typing procedure using capillary
electrophoresis. PHAXs were confirmed to be largely non-recombining across
European samples. All three loci show a remarkably homogeneous pattern
across Europe and high Fst values with the African sample. Overall, 30% of
singleton variants are European-specific, and this excess of rare alleles
is consistent with signals of expansion in Europe, with the Middle East
and Africa showing a weaker pattern. Additional samples from the Complete
Genomics dataset confirmed these patterns showing European-and Middle
Eastern-specific haplotypes. Bayesian skyline plots suggest a European-
specific expansion around 20 KYA with a more recent peak around 10 KYA.
This study demonstrates the value of the use of haplotype blocks, and the
accurate ascertainment of rare variants to infer human demographic history.
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