We confirm a significant contribution of the Ala946Thr IFIH1 polymorphism to organ-specific autoimmune diseases, extending the range of conditions associated with this variant to include Graves' disease. This polymorphism may also contribute to several other autoimmune disorders.

Selenium (Se), a dietary trace metal essential for human health, is incorporated into *25 selenoproteins including selenoprotein S (SelS) and the 15-kDa selenoprotein (Sep15) both of which have functions in the endoplasmic reticulum protein unfolding response. The aim of this study was to investigate whether genetic variants in such selenoprotein genes are associated with altered risk of colorectal cancer (CRC). A Korean population of 827 patients with CRC and 733 healthy controls was genotyped for 7 SNPs in selenoprotein genes and one SNP in the gene encoding manganese superoxide dismutase using Sequenom technology. Multivariate logistic regression analysis showed that after adjustment for lifestyle factors three SNP variants were associated with altered disease risk. There was a mean odds ratio of 2.25 [95% CI 1.13,4.48] in females homozygous TT for rs34713741 in SELS with the T variant being associated with higher risk of rectal cancer, and odds ratios of 2.47 and 2.51, respectively, for rs5845 and rs5859 in SEP15 with the minor A and T alleles being associated with increased risk of male rectal cancer. The data indicate that the minor alleles for rs5845, rs5859 and rs34713741 are associated with increased rectal cancer risk and that the effects of the three SNPs are dependent on gender. The results highlight potential links between Se, the function of two selenoproteins involved in the protein unfolding response and CRC risk. Further studies are required to investigate whether the effects of the variants on CRC risk are also modulated by dietary Se intake.

By their paternal transmission, Y-chromosomal haplotypes are sensitive markers of population history and male-mediated introgression. Previous studies identified biallelic single-nucleotide variants in the SRY, ZFY and DDX3Y genes, which in domestic goats identified four major Y-chromosomal haplotypes, Y1A, Y1B, Y2A and Y2B, with a marked geographical partitioning. Here, we extracted goat Y-chromosomal variants from whole-genome sequences of 386 domestic goats (75 breeds) and seven wild goat species, which were generated by the VarGoats goat genome project. Phylogenetic analyses indicated domestic haplogroups corresponding to Y1B, Y2A and Y2B, respectively, whereas Y1A is split into Y1AA and Y1AB. All five haplogroups were detected in 26 ancient DNA samples from southeast Europe or Asia. Haplotypes from presentday bezoars are not shared with domestic goats and are attached to deep nodes of the trees and networks. Haplogroup distributions for 186 domestic breeds indicate ancient paternal population bottlenecks and expansions during migrations into northern Europe, eastern and southern Asia, and Africa south of the Sahara. In addition, sharing of haplogroups indicates male-mediated introgressions, most notably an early gene

49The male-specific part of the Y-chromosome is in mammalian and many other species the 50 longest haplotype that is inherited without recombination. By its paternal transmission it has a 51 small effective population size in species with dominant males. In several species, Y-52 chromosomal haplotypes are sensitive markers of population history and introgression. 53Previous studies have identified in domestic goats four major Y-chromosomal haplotypes 54 Y1A, Y1B, Y2A and Y2B with a marked geographic differentiation and several regional 55 variants. In this study we used published whole-genome sequences of 70 male goats from 16 56 modern breeds, 11 ancient-DNA samples and 29 samples from seven wild goat species. We 57 identified single-copy male-specific SNPs in four scaffolds, containing SRY, ZFY, DBY with 58 SSX3Y and UTY, and USP9Y with UMN2001, respectively. Phylogenetic analyses indicated 59 haplogroups corresponding to the haplotypes Y1B, Y2A and Y2B, respectively, but Y1A was 60 split into Y1AA and Y1AB. All haplogroups were detected in ancient DNA samples from 61 southeast Europe and, with the exception of Y1AB, in the bezoar goat, which is the wild 62 ancestor of the domestic goats. Combining these data with those of previous studies and with 63 genotypes obtained by Sanger sequencing or the KASP assay yielded haplogroup distributions 64 for 132 domestic breeds or populations. The phylogeographic differentiation indicated 65 paternal population bottlenecks on all three continents. This possibly occurred during the 66 Neolithic introductions of domestic goats to those continents with a particularly strong 67 influence in Europe along the Danubian route. This study illustrates the power of the Y-68 chromosomal haplotype for the reconstructing the history of mammalian species with a wide 69 geographic range. 70 71 223 2018-01-8708 "Application of NGS in assessment of genomic variability in ruminants" and 224 by the European Union (projects ECONOGENE QLK5-CT2001-02461. We are grateful to 225 Dr E. Cuppen (Utrecht Medical Centre) for access to the dideoxy sequencing facilities. 226 227Acknowldegements. 228This study has benefited from an interaction with Vargoats consortium 229