A systems biology approach uncovers cell-specific gene regulatory effects of genetic associations in multiple sclerosis

Genome-wide association studies (GWAS) have identified more than 50,000 unique associations with common human traits. While this represents a substantial step forward, establishing the biology underlying these associations has proven extremely difficult. Even determining which cell types and which particular gene(s) are relevant continues to be a challenge. Here, we conduct a cell-specific pathway analysis of the latest GWAS in multiple sclerosis (MS), which had analyzed a total of 47,351 cases and 68,284 healthy controls and found more than 200 non-MHC genome-wide associations. Our analysis identifies pan immune cell as well as cell-specific susceptibility genes in T cells, B cells and monocytes. Finally, genotype-level data from 2,370 patients and 412 controls is used to compute intra-individual and cell-specific susceptibility pathways that offer a biological interpretation of the individual genetic risk to MS. This approach could be adopted in any other complex trait for which genome-wide data is available

A systems biology approach uncovers cell-specific gene regulatory effects of genetic associations in multiple sclerosis.

Genome-wide association studies (GWAS) have identified more than 50,000 unique associations with common human traits. While this represents a substantial step forward, establishing the biology underlying these associations has proven extremely difficult. Even determining which cell types and which particular gene(s) are relevant continues to be a challenge. Here, we conduct a cell-specific pathway analysis of the latest GWAS in multiple sclerosis (MS), which had analyzed a total of 47,351 cases and 68,284 healthy controls and found more than 200 non-MHC genome-wide associations. Our analysis identifies pan immune cell as well as cell-specific susceptibility genes in T cells, B cells and monocytes. Finally, genotype-level data from 2,370 patients and 412 controls is used to compute intra-individual and cell-specific susceptibility pathways that offer a biological interpretation of the individual genetic risk to MS. This approach could be adopted in any other complex trait for which genome-wide data is available

Social immunity in honeybees (Apis mellifera): transcriptome analysis of varroa-hygienic behaviour

Y. Le Conte, C. Alaux : contributed equallyInternational audienceHoneybees have evolved a social immunity consisting of the cooperation of individuals to decrease disease in the hive. We identified a set of genes involved in this social immunity by analysing the brain transcriptome of highly varroa-hygienic bees, who efficiently detect and remove brood infected with the Varroa destructor mite. The function of these candidate genes does not seem to support a higher olfactory sensitivity in hygienic bees, as previously hypothesized. However, comparing their genomic profile with those from other behaviours suggests a link with brood care and the highly varroa-hygienic Africanized honeybees. These results represent a first step toward the identification of genes involved in social immunity and thus provide first insights into the evolution of social immunit

Abundance and survival of a seed-infesting weevil, Pseudanthonomus hamamelidis (Coleoptera: Curculionidae), on its variable-fruiting host plant, witch-hazel ( Hamamelis virginiana )

1. The relative importance of seed abundance and of mortality factors in the population biology of Pseudanthonomus hamamelidis , a hostspecific predispersal seed predator on Hamamelis virginiana , is evaluated by analysis of weevil life tables and abundance estimates in three years with markedly different magnitudes of fruit production. 2. Fruit production of marked Hamamelis individuals averaged 336 m -2 in 1978, increased three- to four-fold in 1979, and declined again in 1980. More individuals fruited in 1979 than in the other two years. 3. The early larval stage of P.hamamelidis incurred the greatest mortality, with 42–58% dying from often undeterminable causes. Losses in the egg stage ranged from 22% to 31%. Three parasitoid species each accounted for minor mortality. Generation survival was similar in all three years, ranging from 21% to 28%. 4. The percentage of Hamamelis fruit crops infested by P.hamamelidis was high in 1978, averaging 76%, but was much lower in 1979, the year of abundant fruit. In 1980, when fruit were less abundant again, infestation was nearly complete. Egg densities on fruits were lower in 1979 than in the other two years. 5. The fluctuating fruit crops of Hamamelis are responsible for limitation of P.hamamelidis numbers during poor fruiting years. The occasional highly productive fruiting year results in satiation of weevil populations and concomitant seed escape by Hamamelis . Mortality factors appear less important in influencing weevil population dynamics.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/71454/1/j.1365-2311.1981.tb00629.x.pd