The INSDC database entry for this submission can be accessed at. This use case exemplifies submission scenarios, where a single sequence and its CD are to be submitted to the INSDC databases. Single sequences can, for example, be marker genes or genomes that consist of a single sequence or contig. When considering the strength of the Abmole Sorafenib allele association in the analysis of the European consortium, the relationship arose quite clear; however regarding single countries, data are less clear-cut. As reported in Figure 3, a North-South gradient seems to be present in the distribution of the T1858 allele in both RA patients and controls, as previously remarked by Gregersen et al. in some European populations. Furthermore, it is also noteworthy that while in Germany, the frequency of the T1858 allele was significantly higher in RA patients compared to controls and the association was present irrespective of the presence or absence of anti-CCP and RF, in France the European Consortium Group provided evidence for an association of T1858 allele only with RF positive cases but not with RF negative RA patients. In Spain, there was no association with early RA but the association was significant with the anti-CCP positive RA. Genetic differences within European populations have been once more underlined by a recent work of Rodr? ��guez-Rodr? ��guez et al.. The authors described the association of another PTPN22 SNP, the R263Q, with RA in six different Caucasian populations. The 1858C.T SNP was also investigated using mostly previously published data. The T allele of the 1858C.T SNP showed an inhomogeneous distribution among the populations taken into account, with a prevalence of 10.5% in RA patients and 6.8% in controls in Spain, compared to 16.1% and 10.6% respectively in the other countries. Our data revealed a higher frequency of the T1858 allele in RA Italian patients compared to the controls cohort. On the other hand, the frequency in controls was lower than that observed in France or in Germany and similar to Turkish, Greek and Tunisian populations. Interestingly, Mediterranean populations are genetically linked by a common history of migrations, like the abiding one of Saracens and Moors. In fact a recent work, estimating the medieval North African contribution over Mediterranean countries through the analysis of the Y chromosome short tandem repeats, suggested a general correlation between historical and genetic data of Iberia, Sicily, Turkey and North Africa. No relationship arose between the C/T-T/T genotypes presence and auto-antibodies positivity. The demonstration of a gain-of-function conferred by the T1858 allele in suppressing TCR function in T cells and BCR function in B cells raises new hypotheses on the role of tyrosine phosphatases. The T1858 allele might increase the threshold for a persistent activation of both autoreactive T and B cells thus leading to a more defined autoimmune subset of RA. In our study, the trend for an association between the rs2476601 SNP and the positivity of anti-CCP seems to move towards this direction, though the only conclusion we can formulate with the data at hand is the geographical issue. In conclusion, the geographical distribution of SNPs in the world, linked to different population origins, should be taken into account in studies regarding genetic associations. Given that specific therapies directed toward Lyp will be available in the near future for various autoimmune diseases.