Association of NTRK3 and its interaction with NGF suggest an altered cross-regulation of the neurotrophin signaling pathway in eating disorders

Eating disorders (EDs) are complex psychiatric diseases that include anorexia nervosa and bulimia nervosa, and have higher than 50% heritability. Previous studies have found association of BDNF and NTRK2 to ED, while animal models suggest that other neurotrophin genes might also be involved in eating behavior. We have performed a family-based association study with 151 TagSNPs covering 10 neurotrophin signaling genes: NGFB, BDNF, NTRK1, NGFR/p75, NTF4/5, NTRK2, NTF3, NTRK3, CNTF and CNTFR in 371 ED trios of Spanish, French and German origin. Besides several nominal associations, we found a strong significant association after correcting for multiple testing (P = 1.04 × 10−4) between ED and rs7180942, located in the NTRK3 gene, which followed an overdominant model of inheritance. Interestingly, HapMap unrelated individuals carrying the rs7180942 risk genotypes for ED showed higher levels of expression of NTRK3 in lymphoblastoid cell lines. Furthermore, higher expression of the orthologous murine Ntrk3 gene was also detected in the hypothalamus of the anx/anx mouse model of anorexia. Finally, variants in NGFB gene appear to modify the risk conferred by the NTRK3 rs7180942 risk genotypes (P = 4.0 × 10−5) showing a synergistic epistatic interaction. The reported data, in addition to the previous reported findings for BDNF and NTRK2, point neurotrophin signaling genes as key regulators of eating behavior and their altered cross-regulation as susceptibility factors for EDs.

Genetic characterization of the ABO blood group in Neandertals

Background: The high polymorphism rate in the human ABO blood group gene seems to be related to susceptibility to different pathogens. It has been estimated that all genetic variation underlying the human ABO alleles appeared along the human lineage, after the divergence from the chimpanzee lineage. A paleogenetic analysis of the ABO blood group gene in Neandertals allows us to directly test for the presence of the ABO alleles in these extinct humans. Results: We have analysed two male Neandertals that were retrieved under controlled conditions at the El Sidron site in Asturias (Spain) and that appeared to be almost free of modern human DNA contamination. We find a human specific diagnostic deletion for blood group O (O01 haplotype) in both Neandertal individuals. Conclusion: These results suggest that the genetic change responsible for the O blood group in humans predates the human and Neandertal divergence. A potential selective event associated with the emergence of the O allele may have therefore occurred after humans separated from their common ancestor with chimpanzees and before the human-Neandertal population divergence.

African signatures of recent positive selection in human FOXI1

Background: The human FOXI1 gene codes for a transcription factor involved in the physiology of the inner ear, testis, and kidney. Using three interspecies comparisons, it has been suggested that this may be a gene underhuman-specific selection. We sought to confirm this finding by using an extended set of orthologous sequences.Additionally, we explored for signals of natural selection within humans by sequencing the gene in 20 Europeans,20 East Asians and 20 Yorubas and by analysing SNP variation in a 2 Mb region centered on FOXI1 in 39worldwide human populations from the HGDP-CEPH diversity panel.Results: The genome sequences recently available from other primate and non-primate species showed that FOXI1divergence patterns are compatible with neutral evolution. Sequence-based neutrality tests were not significant inEuropeans, East Asians or Yorubas. However, the Long Range Haplotype (LRH) test, as well as the iHS and XP-Rsbstatistics revealed significantly extended tracks of homozygosity around FOXI1 in Africa, suggesting a recentepisode of positive selection acting on this gene. A functionally relevant SNP, as well as several SNPs either on theputatively selected core haplotypes or with significant iHS or XP-Rsb values, displayed allele frequencies stronglycorrelated with the absolute geographical latitude of the populations sampled.Conclusions: We present evidence for recent positive selection in the FOXI1 gene region in Africa. Climate mightbe related to this recent adaptive event in humans. Of the multiple functions of FOXI1, its role in kidney-mediatedwater-electrolyte homeostasis is the most obvious candidate for explaining a climate-related adaptation.

ΕΛΛΑΣ, seu Graecia universa / autore J. Laurenbergio

Échelle(s) : [1:2 135 000 environ] Milliaria Italica Communia 100 = [8,7 cm]

Hellas seu Graecia Universa / autore J. Laurenbergio

Échelle(s) : [1:2 110 000 ca] Milliaria Italica Communia 80 = [7 cm]

Graeciae Antiquae Tabula Nova in qua locorum situs tum ad distantias itinerarias tum ad Observationes Astronomicas exactus litorum flexurae et alia id genus ad accuratas recentiorum rationes accomodatae sunt. Graeciae Pars Meridionalis / Autore Guillelmo Delisle, ... ; J. Kondet sculp.

Échelle(s) : [1:1 275 000 environ], Milliaria Romana quorum 75 gradui respondent [= 8,6 cm]

Graeciae Antiquae Tabula Nova in qua locorum situs tum ad distantias itinerarias tum ad Observationes Astronomicas exactus litorum flexurae et alia id genus ad accuratas recentiorum rationes accomodatae sunt. Graeciae Pars Septentrionalis / Autore Guillelmo Delisle, ... ; J. Kondet sculp.

Échelle(s) : [1:1 275 000 environ], Milliaria Romana quorum 75 gradui respondent [= 8,6 cm]

Hellas seu Graecia Universa / autore J. Laurenbergio

Échelle(s) : [1:2 110 000 ca] Milliaria Italica Communia 80 = [7 cm]

Hellas seu Graecia Universa / autore J. Laurenbergio

Échelle(s) : [1:2 110 000 ca] Milliaria Italica Communia 80 = [7 cm]

Achaiae nova & accurata descriptio / autore I. Laurenbergio

Échelle(s) : [1:1 000 000 ca] Mil. Germ. 7 [= 4,8 cm], Mil. Gall. 9 [= 4,6 cm], Mil. Ital. 28 [= 4,8 cm], Stadia 250 [= 4,5 cm] (d'après échelles graphiques).

Peloponnesus, sive Morea / Auth. I. Laurenbergio

Échelle(s) : [1:1 000 000 ca] Mil. Germ. 8 [= 5,5 cm], Mil. Gall. 10 [= 5,2 cm], Mil. Ital. 30 [= 5,5 cm], Stadia 300 [= 5,5 cm] (d'après échelles graphiques)

Carte von der europaeischen Türkey : Nach vorzüglichen Hülfsmitteln in II. Blättern / entworfen und gezeichnet von J. v. Xylander

Échelle(s) : [1:1 914 000 environ], Geographische Meilen 15 auf 1° d. Breite [= 5,8 cm]