Human STMN2 blocking peptide

The objective was to characterize the potential laying traits and underlying transcripts expressed in the hypothalamus and pituitary gland that were associated with egg production variability in five genetic stocks of chickens: two commercial lines, Red(n = 12) and Black-feather (n = 14) Taiwan country chickens (TCCs); two selected lines of TCCs, B (high body weight/comb size; n = 17) and L2 (high-egg production; n = 14); and a commercial single comb White Leghorn (WL; n = 17). Six laying traits, age at first egg, clutch length, pause length, oviposition lag within clutch, follicle rapid growth period, and rate of yolk accumulation were measured. The significance of differential values among five chicken stocks and correlation coefficients between laying traits and number of eggs to 50 weeks of age or laying rate after first egg, and the expression level of 33 transcripts were determined. Longer clutch length and shorter oviposition lag within clutch contributed to a higher number of eggs to 50 weeks of age or laying rate after first egg in L2 (P < 0.05) and WL strains (P < 0.05). However, their rate of yolk accumulation (P < 0.05) and follicle rapid growth period (P < 0.05) were different, indicating the accumulation of different alleles after long-term, independent selection. Across all five strains, numbers of eggs to 50 weeks of age were positive correlated with average clutch length (P < 0.05) as well as the rate of yolk accumulation (P < 0.05). Expressions of PLAGI, STMN2, PGDS, PARK7, ANP32A, PCDHA@, SCG2, BDH and SARIA transcripts contributed to number of eggs to 50 weeks of age (P < 0.05) or laying rate after first egg (P < 0.05). Analysis of correlation coefficients indicated that PLAGI additionally played roles in decreasing average pause length. Two transcripts, PRL and GARNL1, specifically contributed to number of eggs to 50 weeks of age or laying rate after first egg by reducing oviposition lag within clutch (P < 0.05) and/or increasing average clutch length (P < 0.05), respectively. Expression level of NCAM1, contributed to laying rate after first egg by association with a shorter oviposition lag within clutch (P < 0.05). The current study attributed egg production phenotype in five strains into several laying traits; correlations between these traits and expression levels of underlying transcripts expressed in the hypothalamus and pituitary gland were also established. (C) 2007 Published by Elsevier Inc.

Background Human and animal prion diseases are under genetic control, but apart from PRNP (the gene that encodes the prion protein), we understand little about human susceptibility to bovine spongiform encephalopathy (BSE) prions, the causal agent of variant Creutzfeldt-Jakob disease (vCJD). Methods We did a genome-wide association study of the risk of vCJD and tested for replication of our findings in samples from many categories of human prion disease (929 samples) and control samples from the UK and Papua New Guinea (4254 samples), including controls in the UK who were genotyped by the Wellcome Trust Case Control Consortium. We also did follow-up analyses of the genetic control of the clinical phenotype of prion disease and analysed candidate gene expression in a mouse cellular model of prion infection. Findings The PRNP locus was strongly associated with risk across several markers and all categories of prion disease (best single SNP [single nucleotide polymorphism] association in vCJD p=2.5X10(-17); best haplotypic association in vCJD p=1x10(-24)). Although the main contribution to disease risk was conferred by PRNP polymorphic codon 129, another nearby SNP conferred increased risk of vCJD. In addition to PRNP, one technically validated SNP association upstream of RARB (the gene that encodes retinoic acid receptor beta) had nominal genome-wide significance (p=1.9x10(-7)). A similar association was found in a small sample of patients with iatrogenic CJD (p=0.030) but not in patients with sporadic CJD (sCJD) or kuru. In cultured cells, retinoic acid regulates the expression of the prion protein. We found an association with acquired prion disease, including vCJD (p=5.640(-5)), kuru incubation time (p=0.017), and resistance to kuru (p=2.5x10(-4)), in a region upstream of STMN2 (the gene that encodes SCG10). The risk genotype was not associate with sCJD but conferred an earlier age of onset. Furthermore, expression of Stmn2 was reduced 30-fold post-infection in a mouse cellular model of prion disease. Interpretation The polymorphic codon 129 of PRNP was the main genetic risk factor for vCJD; however, additional candidate loci have been identified, which justifies functional analyses of these biological pathways in prion disease.