Common variants on 1p36 and 1q42 are associated with cutaneous basal cell carcinoma but not with melanoma or pigmentation traits

To search for new sequence variants that confer risk of cutaneous basal cell carcinoma (BCC), we conducted a genome-wide SNP association study of 930 Icelanders with BCC and 33,117 controls. After analyzing 304,083 SNPs, we observed signals from loci at 1p36 and 1q42, and replicated these associations in additional sample sets from Iceland and Eastern Europe. Overall, the most significant signals were from rs7538876 on 1p36 (OR = 1.28, P = 4.4 x 10(-12)) and rs801114 on 1q42 (OR = 1.28, P = 5.9 x 10(-12)). The 1p36 locus contains the candidate genes PADI4, PADI6, RCC2 and ARHGEF10L, and the gene nearest to the 1q42 locus is the ras-homolog RHOU. Neither locus was associated with fair pigmentation traits that are known risk factors for BCC, and no risk was observed for melanoma. Approximately 1.6% of individuals of European ancestry are homozygous for both variants, and their estimated risk of BCC is 2.68 times that of noncarriers.     

TRH analogue with C-terminal thioamide group. Synthesis, receptor binding, TSH-releasing activity and alpha-MSH-releasing activity

A new TRH analogue containing a C-terminal thioamide group was synthesized. This peptide was shown to have receptor-binding affinity, and TSH- as well as alpha-MSH-releasing activities very similar to native TRH.     

Synthesis of trypsin inhibitor CMTI III from squash seeds (Cucurbita maxima)

Summary Using the solid-phase procedure, a 29-peptide cross-linked by three disulphide bridges was synthesized. The synthetic product was shown to be identical with the trypsin inhibitor CMTI III from squash seeds (Cucurbita maxima).Acknowledgments. This work was supported by the Swedish Natural Science Research Council (K-GF 3020-107) and the Polish Academy of Sciences (Research grant No. MR I 12.1.6.1).     

Synthesis of three NH2-terminally extended arginine-vasopressins with prolonged biological activities

The synthesis of three novel AVP-analogues, extended by 1-3 amino acids at their NH2-2-termini in accordance with the sequence of the bovine arginine-vasopressin neurophysin II precursor, is reported. The compounds were assayed for their antidiuretic and vasopressor activities with particular attention to the duration of the effects. All compounds showed high potency, based on the intensity, and prolonged effects in both test systems compared with AVP.     

TRH analogue with C-terminal thioamide group. Synthesis,receptor binding,TSH-releasing activity and α-MSH-releasing activity

Summary A new TRH analogue containing a C-terminal thioamide group was synthesized. This peptide was shown to have receptor-binding affinity, and TSH- as well as -MSH-releasing activities very similar to native TRH.Acknowledgments. This work was supported by the Swedish Natural Science Research Council (K-KU 3020-112) and the Polish Academy of Sciences (Research Grant No. MR I 12.1.6.1).     

Two newly identified genetic determinants of pigmentation in Europeans

We present results from a genome-wide association study for variants associated with human pigmentation characteristics among 5,130 Icelanders, with follow-up analyses in 2,116 Icelanders and 1,214 Dutch individuals. Two coding variants in TPCN2 are associated with hair color, and a variant at the ASIP locus shows strong association with skin sensitivity to sun, freckling and red hair, phenotypic characteristics similar to those affected by well-known mutations in MC1R.     

Genetic determinants of hair, eye and skin pigmentation in Europeans

Hair, skin and eye colors are highly heritable and visible traits in humans. We carried out a genome-wide association scan for variants associated with hair and eye pigmentation, skin sensitivity to sun and freckling among 2,986 Icelanders. We then tested the most closely associated SNPs from six regions--four not previously implicated in the normal variation of human pigmentation--and replicated their association in a second sample of 2,718 Icelanders and a sample of 1,214 Dutch. The SNPs from all six regions met the criteria for genome-wide significance. A variant in SLC24A4 is associated with eye and hair color, a variant near KITLG is associated with hair color, two coding variants in TYR are associated with eye color and freckles, and a variant on 6p25.3 is associated with freckles. The fifth region provided refinements to a previously reported association in OCA2, and the sixth encompasses previously described variants in MC1R.