Location and structure of palindrome P6, showing positions of PSVs analysed.

<p>a) Idiogram of Y chromosome, showing positions of the 8 palindromes, with structure and coordinates (in GRCh37) of P6 below. b) Position and nature of the differences between the arms of P6, indicating the 10 SN-PSVs analysed, and the positions of PCR primers used in arm-specific amplifications. STSs marking the arm boundaries are also shown (with ‘sY’ prefixes). Asterisks indicate the two SN-PSVs identified from a haplogroup O3a chromosome.</p

Patterns of P6 nucleotide replacements in the human and chimpanzee lineages.

a<p>2×2 contingency table, Chi-square test with Yates correction.</p>*<p>p-value<0.05.</p>**<p>p-value<0.01.</p

Recognition of gene conversion, co-conversion and inversion events.

<p>a) Existence of three genotypes at a hypothetical PSV indicates that gene conversion has taken place, if recurrent mutation is neglected. Genotyping the PSV in a phylogenetic context, and applying the principle of maximum parsimony, allows the recognition of: b) Haplogroup descending from an ancestor in which the PSV mutation has not yet arisen (G/G), and is therefore uninformative; c) Haplogroup descending from an ancestor in which the PSV mutation has arisen (G/A), but shows no variation, and therefore no evidence for gene conversion; d) Haplogroup descending from an ancestor in which the PSV mutation has arisen, and shows evidence of at least two bidirectional conversion events (G/G and A/A); e) Recognition of co-conversion of more than one PSV requires ‘phase’ information, as does (f) recognition of inversions.</p

Inter-specific sequence divergence in arms and spacers of palindrome P6.

a<p>2×2 contingency table, Chi-square test with Yates correction.</p

Schematic representation of the inversions identified within three haplogroups.

<p>The approximate position of each inversion is indicated by a red cross.</p

Signatures of human European Paleolithic expansion shown by resequencing of nonrecombining X-chromosome segments

Human genetic diversity in Europe has been extensively studied using uniparentally-inherited sequences (mitochondrial DNA [mtDNA] and the Y chromosome), which reveal very different patterns indicating sex-specific demographic histories. The X chromosome, haploid in males and inherited twice as often from mothers as from fathers, could provide insights into past female behaviours, but has not been extensively investigated. Here, we use HapMap SNP data to identify genomewide segments of the X chromosome in which recombination is historically absent and mutations are likely to be the only source of genetic variation, referring to these as Phylogeographically informative Haplotypes on Autosomes and X chromosome (PHAXs). Three such sequences on the X chromosome spanning a total of ~49 kb were resequenced in 240 males from Europe, the Middle East and Africa at an average coverage of 181 ×. These PHAXs were confirmed to be essentially non-recombining across European samples. All three loci show highly homogeneous patterns across Europe and are highly differentiated from the African sample. Star-like structures of European-specific haplotypes in median-joining networks indicate past population expansions. Bayesian skyline plots and time-to-most-recent-common-ancestor estimates suggest expansions pre-dating the Neolithic transition, a finding that is more compatible with data on mtDNA than the Y chromosome, and with the female bias of Xchromosomal inheritance. This study demonstrates the potential of the use of Xchromosomal haplotype blocks, and the utility of the accurate ascertainment of rare variants for inferring human demographic history

Mean topological overlap for proteins associated to asthma, eczema and rhinitis.

<p>(A) Blue dots indicate the observed mean topological overlap (TO) for proteins common to asthma and eczema, asthma and rhinitis, eczema and rhinitis, and common to all three. Orange scatter boxplots indicate random expectation. (B) Blue dots indicate the observed mean TO for proteins common to the combinations of diseases shown in the previous figure. Orange scatter boxplots indicate observed TO values for pairs/trios of immune system diseases. (C) Blue dots indicate the observed mean TO between proteins unique to asthma and unique to eczema, unique to asthma and unique to rhinitis, unique to eczema and unique to rhinitis, and unique to each disease. Orange scatter boxplots indicate random expectation. (D) Blue dots indicate the observed mean TO for proteins unique to the combinations of diseases shown in the previous figure. Orange scatter boxplots indicate observed TO values for pairs/trios of immune system diseases. One asterisk: observed results are significantly larger than random expectation (<i>P</i> < 0.05). Two asterisks: observed results are significantly larger than random expectation (<i>P</i> < 0.01).</p

Potential disease-associated proteins predicted for asthma, eczema and rhinitis.

<p>NetZcore prediction scores are shown as <i>z</i>-scores. Proteins are ranked according to their average <i>z</i>-score for all diseases. Empty cell: the protein was not predicted to be associated with the disease with <i>z</i>-score > 2.31 (corresponding to <i>P</i> < 0.01). <i>Exp</i>: the protein is experimentally known to be associated to the disease. This table only shows the 30 top-scoring proteins that were found to be associated to more than one disease. The complete list is available in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0179125#pone.0179125.s023" target="_blank">S12 Table</a>.</p

Functional Interaction Networks of asthma, eczema and rhinitis.

<p>Fraction of the Functional Interaction Networks comprising the proteins associated to asthma, eczema, rhinitis and all proteins connected to them (i.e. their direct neighbors in the network). A node represents a protein. A link between two nodes represents a functional connection between them. Isolated nodes represent proteins not directly connected neither to any other disease-associated protein nor to any of its direct neighbors. (A) Large red nodes represent asthma-associated proteins. Red links represent functional connections of these proteins. (B) Large yellow nodes represent eczema-associated proteins. Yellow links represent functional connections of these proteins. (C) Large blue nodes represent rhinitis-associated proteins. Blue links represent functional connections of these proteins.</p

Functional similarity between asthma, eczema and rhinitis.

<p>Numerical values show how similar is the use of a cellular pathway by pairs of trios of diseases. Similarity = 1 means that the diseases affect the pathway in exactly the same way. Similarity = 0 is represented by blank cells. Two asterisks: similarity is significantly larger than random expectation (<i>z</i>-test; <i>P</i> < 0.01). One asterisk: similarity is significantly larger than random expectation (<i>z</i>-test; <i>P</i> < 0.05). All significant similarities were also significantly larger than observed for pairs and trios of immune system diseases (empirical distribution test; <i>P</i> < 0.01).</p