Evolution of sex-specific pace-of-life syndromes: genetic architecture and physiological mechanisms

Sex differences in life history, physiology, and behavior are nearly ubiquitous across taxa, owing to sex-specific selection that arises from different reproductive strategies of the sexes. The pace-of-life syndrome (POLS) hypothesis predicts that most variation in such traits among individuals, populations, and species falls along a slow-fast pace-of-life continuum. As a result of their different reproductive roles and environment, the sexes also commonly differ in pace-of-life, with important consequences for the evolution of POLS. Here, we outline mechanisms for how males and females can evolve differences in POLS traits and in how such traits can covary differently despite constraints resulting from a shared genome. We review the current knowledge of the genetic basis of POLS traits and suggest candidate genes and pathways for future studies. Pleiotropic effects may govern many of the genetic correlations, but little is still known about the mechanisms involved in trade-offs between current and future reproduction and their integration with behavioral variation. We highlight the importance of metabolic and hormonal pathways in mediating sex differences in POLS traits; however, there is still a shortage of studies that test for sex specificity in molecular effects and their evolutionary causes. Considering whether and how sexual dimorphism evolves in POLS traits provides a more holistic framework to understand how behavioral variation is integrated with life histories and physiology, and we call for studies that focus on examining the sex-specific genetic architecture of this integration

Impact on parents of HLA-DQ2/DQ8 genotyping in healthy children from coeliac families

Due to the association of coeliac disease and HLA-specificities DQ2 and DQ8, HLA-typing can be used for risk determination of the disease. This study was designed to evaluate the knowledge of parents from coeliac families regarding HLA-typing and the impact of HLA-typing on the perception of the health of their children. A structured questionnaire was sent to the Dutch, Spanish and German parents participating with their child in the European PreventCD study on disease prevention in high-risk families, addressing parents' understanding of and attitude towards HLA-typing, distress related to HLA-typing and perceived health and health-related quality of life of their children. Sixty-eight percent of parents of 515 children returned the questionnaires, with 85% of children being DQ2/DQ8 positive. The majority of all parents answered the questions on knowledge correctly. Forty-eight percent of parents of DQ2/DQ8-negative children thought their child could develop coeliac disease. More distress was reported by parents of DQ2/DQ8-positive children (

Immunogenetics of Celiac Disease

Celiac disease (CD) is a model for common complex disorders with a high degree of heritability. The human leukocyte antigen (HLA) DQ genotype, specifically HLA-DQ2 and HLA-DQ8, is the strongest genetic risk factor. Genome-wide association studies (GWAS) have identified 57 single nucleotide polymorphisms (SNPs) located in the associated 39 non-HLA regions with mainly immunological functions. Together with HLA, these regions explain approximately 54 % of the disease’s heritability. Molecular functional analyses are necessary to delineate the true causal genetic variants and the pathways involved. Since CD shares many of its genetic susceptibility regions and implicated pathways with other immune-related diseases, a combined analysis may discover more common genetic variants with smaller effect sizes. HLA-DQ genotyping can already be used to exclude a diagnosis of CD, for example, as a test in the screening of individuals from high-risk groups, such as patients with type 1 diabetes or autoimmune thyroiditis, and first-degree relatives of CD patients. Discovering more genetic susceptibility variants and the pathways involved may ultimately contribute to risk stratification for follow-up and treatment, and lead to new therapeutic targets