Development of oviposition behavior of Brachymeria intermedia, a parasitoid of the gypsy moth, Lymantria dispar.

Brachymeria intermedia is an introduced endoparasitoid of the gypsy moth, Lymantria dispar. To gain understanding of the basic mechanisms by which B. intermedia influence population densities of the gypsy moth, the oviposition behavior of this parasitoid was studied. Both the physiological state and the informational state of the animal at a certain point in time may influence the development of the behavior. Factors of the physiological state here investigated are egg load and age of the female parasitoid. Factors of the informational state here investigated are the number of hosts previously encountered, the host species encountered and characteristics of the sites where pupae previously were encountered. Chapter 1 contains the introduction and outline of the study. Chapter 2 shows that experience is an important factor influencing the rate of acceptance of hosts by the parasitoid. The sequence of behaviors before ovipositor insertion does not change with experience. Chapter 3 shows that parasitoids, deprived of hosts from emergence, accumulate eggs up to a certain level, but have a low rate of acceptance. Early exposure to pupae increases the rate of acceptance. B. intermedia adjust their egg production to host availability. Chapter 4 shows that the rate of acceptance for an alternate host increased with age in parasitoids, deprived of hosts from emergence. Rearing the parasitoids on an alternate host and/or oviposition experience on an alternate host did not influence the rate of acceptance of the alternate host. After oviposition experience on the alternate host contaminated with kairomone, uncontaminated hosts were accepted at the same rate as gypsy moth. Chapter 4 shows that B. intermedia is able to use learned visual cues, thereby restricting their searching area to a microhabitat previously found to be profitable. Under laboratory conditions and under semi-natural conditions, parasitoids could be trained to search for pupae either on the ground or on a tree model. Subsequent training to the other microhabitat reversed this effect. The studies show that both the physiological state and the informational state of the parasitoid influence oviposition behavior. Questions are raised and discussed as to the extent of polyphagy of B. intermedia in North America

The genetic architecture of the human cerebral cortex

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder

Digenic inheritance of MSH6

We describe a family severely affected by colorectal cancer (CRC) where whole-exome sequencing identified the coinheritance of the germline variants encoding MSH6 p.Thr1100Met and MUTYH p.Tyr179Cys in, at least, three CRC patients diagnosed before 60 years of age. Digenic inheritance of monoallelic MSH6 variants of uncertain significance and MUTYH variants has been suggested to predispose to Lynch syndrome-associated cancers; however, cosegregation with disease in the familial setting has not yet been established. The identification of individuals carrying multiple potential cancer risk variants is expected to rise with the increased application of whole-genome sequencing and large multigene panel testing in clinical genetic counseling of familial cancer patients. Here we demonstrate the coinheritance of monoallelic variants in MSH6 and MUTYH consistent with cosegregation with CRC, further supporting a role for digenic inheritance in cancer predisposition.Hereditary cancer genetic

Comprehensive Mutation Analysis of PMS2 in a Large Cohort of Probands Suspected of Lynch Syndrome or Constitutional Mismatch Repair Deficiency Syndrome

Monoallelic PMS2 germline mutations cause 5%-15% of Lynch syndrome, a midlife cancer predisposition, whereas biallelic PMS2 mutations cause approximately 60% of constitutional mismatch repair deficiency (CMMRD), a rare childhood cancer syndrome. Recently improved DNA- and RNA-based strategies are applied to overcome problematic PMS2 mutation analysis due to the presence of pseudogenes and frequent gene conversion events. Here, we determined PMS2 mutation detection yield and mutation spectrum in a nationwide cohort of 396 probands. Furthermore, we studied concordance between tumor IHC/MSI (immunohistochemistry/microsatellite instability) profile and mutation carrier state. Overall, we found 52 different pathogenic PMS2 variants explaining 121 Lynch syndrome and nine CMMRD patients. In vitro mismatch repair assays suggested pathogenicity for three missense variants. Ninety-one PMS2 mutation carriers (70%) showed isolated loss of PMS2 in their tumors, for 31 (24%) no or inconclusive IHC was available, and eight carriers (6%) showed discordant IHC (presence of PMS2 or loss of both MLH1 and PMS2). Ten cases with isolated PMS2 loss (10%; 10/97) harbored MLH1 mutations. We confirmed that recently improved mutation analysis provides a high yield of PMS2 mutations in patients with isolated loss of PMS2 expression. Application of universal tumor prescreening methods will however miss some PMS2 germline mutation carriers

Comprehensive Mutation Analysis of PMS2 in a Large Cohort of Probands Suspected of Lynch Syndrome or Constitutional Mismatch Repair Deficiency (CMMRD) Syndrome

Monoallelic PMS2 germline mutations cause 5-15% of Lynch syndrome, a midlife cancer predisposition, whereas biallelic PMS2 mutations cause approximately 60% of constitutional MMR deficiency (CMMRD), a rare childhood cancer syndrome. Recently improved DNA and RNA-based strategies are applied to overcome problematic PMS2 mutation analysis due to the presence of pseudogenes and frequent gene conversion events. Here, we determined PMS2 mutation detection yield and mutation spectrum in a nationwide cohort of 396 probands. Furthermore, we studied concordance between tumor IHC/ MSI (immunohistochemistry/ microsatellite-instability) profile and mutation carrier state. Overall, we found 52 different pathogenic PMS2 variants explaining 121 Lynch syndrome and nine CMMRD patients. In vitro MMR assays suggested pathogenicity for three missense variants. Ninety-one PMS2 mutation carriers (70%) showed isolated loss of PMS2 in their tumors, for 31 (24%) no or inconclusive IHC was available, and eight carriers (6%) showed discordant IHC (presence of PMS2 or loss of both MLH1 and PMS2). Ten cases with isolated PMS2 loss (10%; 10/97) harbored MLH1 mutations. We confirmed that recently improved mutation analysis provides a high yield of PMS2 mutations in patients with isolated loss of PMS2 expression. Application of universal tumor pre-screening methods will however miss some PMS2 germline mutation carriers. This article is protected by copyright. All rights reserved