Mapping the quantitative trait loci (QTL) for body shape and conformation measurements on BTA1 in Japanese Black cattle

The detection and mapping of segregating quantitative trait loci (QTL) that influence withers height, hip height, hip width, body length, chest width, chest depth, shoulder width, lumbar width, thurl width, pin bone width, rump length, cannon circumference, chest girth, abdominal width and abdominal girth at weaning was conducted on chromosomal regions of bovine chromosome one. The QTL analysis was performed by genotyping half-sib progeny of five Japanese Black sires using microsatellite DNA markers. Probability coefficients of inheriting allele 1 or 2 from the sire at specific chromosomal locations were computed. The phenotypic data of progeny were regressed on these probability coefficients in a within-common-parent regression analysis using a linear model that included fixed effects of sex, parity and season of birth, as well as age as a covariate. F-statistics were calculated every 1 cM on a linkage map. Permutation tests of 10 000 iterations were conducted to obtain chromosome-wide significance thresholds. A significant QTL for chest width was detected at 91 cM in family 3. The detection of this QTL boosts the prospects of implementing marker-assisted selection for body conformation traits in Japanese Black beef cattle

GWAS analysis implicates NF-κB-mediated induction of inflammatory T cells in multiple sclerosis

To identify genes and biologically relevant pathways associated with risk to develop multiple sclerosis (MS), the Genome-Wide Association Studies noise reduction method (GWAS-NR) was applied to MS genotyping data. Regions of association were defined based on the significance of linkage disequilibrium blocks. Candidate genes were cross-referenced based on a review of current literature, with attention to molecular function and directly interacting proteins. Supplementary annotations and pathway enrichment scores were generated using The Database for Annotation, Visualization and Integrated Discovery. The candidate set of 220 MS susceptibility genes prioritized by GWAS-NR was highly enriched with genes involved in biological pathways related to positive regulation of cell, lymphocyte and leukocyte activation (P=6.1E-15, 1.2E-14 and 5.0E-14, respectively). Novel gene candidates include key regulators of NF-κB signaling and CD4+ T helper type 1 (Th1) and T helper type 17 (Th17) lineages. A large subset of MS candidate genes prioritized by GWAS-NR were found to interact in a tractable pathway regulating the NF-κB-mediated induction and infiltration of pro-inflammatory Th1/Th17 T-cell lineages, and maintenance of immune tolerance by T-regulatory cells. This mechanism provides a biological context that potentially links clinical observations in MS to the underlying genetic landscape that may confer susceptibility