Identification of genetic loci for basal cell nevus syndrome and inflammatory bowel disease in a single large pedigree

Basal Cell Nevus Syndrome (BCNS) is an autosomal dominant disease. PTCH1 gene mutations have been found responsible in many but not all pedigrees. Inflammatory Bowel Disease (IBD) is a complex genetic disorder, disproportionate in Ashkenazim, and characterized by chronic intestinal inflammation. We revisited a large Ashkenazim pedigree, first reported in 1968, with multiple diagnoses of BCNS and IBD, and with a common genetic cause for both disorders proposed. We expanded the pedigree to four generations and performed a genome-wide linkage study for BCNS and IBD traits. Twelve members with BCNS, seven with IBD, five with both diagnoses and eight unaffected were genotyped. Both non-parametric (GENEHUNTER 2.1) and parametric (FASTLINK) linkage analyses were performed and a validation through simulation was performed. BCNS linked to chromosome 9q22 (D9S1120) just proximal to the PTCH1 gene (NPL=3.26, P=0.003; parametric two-point LOD=2.4, parametric multipoint LOD=3.7). Novel IBD linkage evidence was observed at chromosome 1p13 (D1S420, NPL 3.92, P=0.0047; parametric two-point LOD=1.9). Linkage evidence was also observed to previously reported IBD loci on 4q, (D4S2623, NPL 3.02, P=0.012; parametric two-point LOD=2.15), 10q23 (D10S1225 near DLG5, NPL 3.33, P=0.0085; parametric two-point LOD=1.3), 12 overlapping the IBD2 locus (D12S313, NPL 2.6, P=0.018; parametric two-point LOD=1.52), and 7q (D7S510 and D7S3046, NPL 4.06, P=0.0035; parametric two-point LOD=2.18). In this pedigree affected by both BCNS and IBD, the two traits and their respective candidate genetic loci segregate independently; BCNS maps to the PTCH1 gene and IBD maps to several candidate regions, mostly overlapping previously observed IBD loci.Electronic Supplementary Material Supplementary material is available for this article at and is accessible for authorized users.Carolien I. Panhuysen and Amir Karban contributed equally to this work     

Induced defense in Nicotiana attenuata (Solanaceae) fruit and flowers

Plants protect themselves against herbivory using a continuum of strategies, ranging from constitutive defenses to intermittent induced responses. Induced defenses may not provide immediate and maximum protection, but could be advantageous when continuous defense is either energetically or ecologically costly. As such, induced defenses in flowers could help defend relatively valuable tissue while keeping reproductive structures accessible and attractive to pollinators. Thus far, no one has demonstrated the efficacy of induced defenses against floral herbivores (florivores) in the field. Here we show that mechanical leaf damage in wild tobacco, Nicotiana attenuata (Solanaceae), reduced both flower and fruit herbivory in the field and that exogenous application of methyl jasmonate, a potent elicitor of induced responses, reduced both leaf and floral damage in natural populations. This result is consistent with a survey of damage in the field, which showed a negative relationship between leaf damage and flower and fruit damage. Although optimal defense theory predicts that induced defenses should be rare in reproductive tissues, owing to their high fitness value, our results suggest otherwise. Induced defenses in leaves and reproductive tissues may allow plants to respond effectively to the concomitant pressures of defending against herbivory and attracting pollinators.     

Plant age, communication, and resistance to herbivores: young sagebrush plants are better emitters and receivers

Plants progress through a series of distinct stages during development, although the role of plant ontogeny in their defenses against herbivores is poorly understood. Recent work indicates that many plants activate systemic induced resistance after herbivore attack, although the relationship between resistance and ontogeny has not been a focus of this work. In addition, for sagebrush and a few other species, individuals near neighbors that experience simulated herbivory become more resistant to subsequent attack. Volatile, airborne cues are required for both systemic induced resistance among branches and for communication among individuals. We conducted experiments in stands of sagebrush of mixed ages to determine effects of plant age on volatile signaling between branches and individuals. Young and old control plants did not differ in levels of chewing damage that they experienced. Systemic induced resistance among branches was only observed for young plants. Young plants showed strong evidence of systemic resistance only if airflow was permitted among branches; plants with only vascular connections showed no systemic resistance. We also found evidence for volatile communication between individuals. For airborne communication, young plants were more effective emitters of cues as well as more responsive receivers of volatile cues.     

Identity recognition and plant behavior

The ability to distinguish self from nonself allows organisms to protect themselves against attackers. Sagebrush plants use volatile cues emitted by clipped neighbors to adjust their defenses against herbivores. Recently, we reported that cues from genetically identical ‘self’ clones were more effective at reducing damage than were cues from ‘nonself’ clones. This indicates that plants can distinguish self from non-self through volatiles and respond differentially. Identity recognition may be an essential step in enabling plants to behave cooperatively. Emission of cues which enable other plant tissues (on the same or other individual) to respond appropriately to herbivore risk may have evolved if cues are aimed primarily at self tissue.Key words: communication, eavesdropping, herbivory, kin recognition, self/nonself, volatilesThe ability to recognize self from nonself is a fundamental property of individuals of all multicellular organisms. Distinguishing between molecules that are part of one''s own tissues and those of an invader provides a first step towards the evolution of a functioning immune system. An immune system responds differently towards self and nonself tissues, destroying the later. In addition to immune responses, many other sophisticated behaviors have been described for animals that differentiate self from non-self and even kin from strangers.¹ For example, social behaviors including altruism can be favored by natural selection when animals are able to first distinguish kin from non-kin and respond differently to individuals in these two categories.² Although plant behavior is far less well studied, plants too display many sophisticated and context-dependent behaviors.³Plant biologists have described various situations in which plants exhibit different behaviors based on identity. It has been known for some years that many angiosperms choose mates based on genetic identity.⁴ Numerous mechanisms have been described, primarily involving differential germination of pollen, growth of pollen tubes through stigmatic tissue, and production of competent zygotes. More recently, several workers have found that plants may differentiate self from non-self and alter their morphologies in response to cues from these two types of sources. Plants appeared to recognize their own roots and to grow fewer and shorter roots when they contacted self roots compared to non-self roots (reviewed in references ^5–7). A common feature of these experimental studies is that roots only showed self-recognition when they were physically attached. These experimental studies may be subject to alternate explanations.^8,9Recently we reported that sagebrush plants induced resistance more effectively against their herbivores in response to the volatile cues emitted by self clones compared to the cues of non-self clones.¹⁰ We had previously found that experimental clipping to branches caused systemic induced resistance within an individual against herbivores only when volatile cues were transmitted.¹¹ To evaluate self/non-self discrimination we first produced clones of 60 parent plants in the field by root crown division. These potted clones were propagated and then placed back in the field near either their genetically identical parent (self treatment) or a genetically different parent (nonself treatment). The potted clones were experimentally clipped in spring for both treatments and the damage that accumulated over the growing season was recorded for parents near self and non-self clones. We found that plants near clipped self clones received approximately 42% less damage by their herbivores than plants near clipped non-self clones (Fig. 1, One-way ANOVA, F_1,58 = 8.72, p = 0.005).Open in a separate windowFigure 1The mean number of leaves that were damaged by herbivores (grasshoppers, caterpillars and deer) on assay branches of sagebrush (±1 se). Cuttings were either genetically identical (self) or different (non-self) from the assay branch; assay branches were within 5 cm of potted cuttings but not in physical contact. Cuttings were experimentally clipped to simulate herbivory in May and herbivore damage accumulated on the assay branches until season''s end in September when damage was assayed.This result is novel in several ways. Past results showing self/nonself recognition between roots required that they be in physical contact for discrimination to occur; physical contact was not required in this case. In addition, this is the first identity study to measure responses in terms of damage by herbivores rather than plant morphology or reproduction. This result is more robust than the changes in root morphology because changes attributed to self or non-self volatiles cannot be explained by alternative hypotheses involving potentially confounding differences in resource availability or pot size.^8,9 The ability of plants to differentiate self from non-self is important because it may enable differential treatment towards ramets that share genes.Recent work has also suggested that plants may be able to discriminate between kin and strangers. Cakile edentula and Impatiens pallida changed their morphologies depending upon whether their roots contacted kin or strangers.^12,13 These altered morphologies were consistent with the notion that kin cooperated and non-kin competed. Examination of self/non-self recognition and kin/stranger recognition patterns in Arabidopsis thaliana indicated that these two forms of identity discrimination were affected differently by inhibitors and therefore suggested that they may involve different signaling mechanisms.¹⁴Plants that emit volatile cues that other individuals can use to adjust their defenses (eavesdropping) may be at a selective disadvantage.¹⁵ Why should a plant dispense information that allows its neighbors to fine tune their defenses against herbivory? One possible answer to this conundrum may be that plants emit volatile cues to coordinate their own defenses since volatile cues are active over relatively short distances. A second possible answer is that greater sensitivity to self volatiles reduces the cost of eaves-dropping. In designing our sagebrush experiment we cloned plants as a means of producing physically separate pairs of plants that were either genetically identical or different. Early genetic work indicated that populations of sagebrush were highly structured genetically.¹⁶ In other words, relatedness decreased as a function of the distance between individuals, also known as population viscosity. Recent genetic analyses of microsatellites indicate that vegetative reproduction by rhizomes also occurs in this species and some neighbors in nature are genetically identical (Ishizaki, et al. in review). Population viscosity has been considered to increase the likelihood of cooperation, in part because neighbors already share genes.^2,17 Applying similar logic, communication is facilitated by kin recognition if relatives are better able to communicate than non-kin. Communication may be favored if the tissue emitting cue is surrounded by primarily self tissue or if the exchange of cues is more effective and likely to occur between self tissues. In conclusion, plant communication using volatile cues may have evolved because individual plants were communicating primarily with themselves.     

Predicting novel herbivore–plant interactions

As human‐aided range expansions and climate change alter the distributions of plants and their herbivores, predicting and addressing novel species interactions will become increasingly pressing for community ecologists. In this context, a key, surprisingly understudied question is: when an exotic plant is introduced, which herbivores will adopt this new potential host? Whether the plant is a weed, an ornamental, or a crop, the development versus non‐development of a novel plant–insect interaction can have profound effects for both economic and conservation applications. In this paper, we sketch mechanistic and statistical frameworks for predicting these interactions, based on how plant and herbivore traits as well as shared evolutionary history can influence detection, recognition, and digestion of novel plants. By emphasizing mechanisms at each of these steps, we hope to clarify different aspects of novel interactions and why they may or may not occur. We also emphasize prediction and forecasting, as a major goal is to know in advance which interactions will develop from the many plant or insect introductions that occur in natural and man‐made systems.     

Small mammals cause non-trophic effects on habitat and associated snails in a native system

Legacy effects occur when particular species or their interactions with others have long-lasting impacts, and they are increasingly recognized as important determinants of ecological processes. However, when such legacy effects have been explicitly explored, they most often involve the long-term direct effects of species on systems, as opposed to the indirect effects. Here, we explore how a legacy of small mammal exclusion on the abundance of a shrub, bush lupine (Lupinus arboreus), influences the abundance of a native land snail (Helminthoglypta arrosa) in coastal prairie and dune habitats in central California. The factors that limit populations of land snails are very poorly known despite the threats to the persistence of this group of species. In grasslands, prior vole (Microtus californicus) exclusion created long-lasting gains in bush lupine abundance, mediated through the seedbank, and was associated with increased snail numbers (10×) compared to control plots where mammals were never excluded. Similar plots in dune habitat showed no difference in snail numbers due to previous mammal exclusion. We tested whether increased competition for food, increased predation, and/or lower desiccation explained the decline in snail numbers in plots with reduced lupine cover. Tethering experiments supported the hypothesis that voles can have long-lasting impacts as ecosystem engineers, reducing woody lupine habitat required for successful aestivation by snails. These results add to a growing list of studies that have found that non-trophic interactions can be limiting to invertebrate consumers.     

Seasonality of herbivory and communication between individuals of sagebrush

Seasonal changes in herbivore numbers and in plant defenses are well known to influence plant–herbivore interactions. Some plant defenses are induced in response to herbivore attack or cues correlated with risk of attack although seasonal variation in these defenses is relatively poorly known. We previously reported that sagebrush becomes more resistant to its herbivores when neighboring plants have been experimentally clipped with scissors. In this study we asked whether herbivory to leaves of sagebrush varied seasonally and whether there was seasonal variation in natural levels of damage when neighbors were clipped. We found that sagebrush accumulated most chewing damage early in the season, soon after the spring flush of new leaves. This damage was caused by generalist grasshoppers, deer, specialist caterpillars, beetles, gall makers, and other less common herbivores. Sagebrush showed no evidence of preferentially abscising leaves that had been experimentally clipped. Experimental clipping by Trirhabda pilosa beetle larvae caused neighbors to accumulate less herbivore damage later that season, similar to results in which clipping was done with scissors. Induced resistance caused by experimentally clipping a neighbor was affected by season; plants with neighbors clipped in May accumulated less damage throughout the season relative to plants with unclipped neighbors or neighbors clipped later in the summer. We found a correlation between seasonal herbivore pressure, damage accumulated by plants, and induced responses to experimentally clipping neighbors. The causal mechanisms responsible for this correlation are unknown although a strong seasonal effect was clear.     

MDR1 Ala893 polymorphism is associated with inflammatory bowel disease

Crohn disease (CD) and ulcerative colitis (UC) are overlapping chronic inflammatory bowel diseases (IBDs). Suggestive evidence for linkage at chromosome 7q has been reported for both CD and UC. Contained within this region is the gene for MDR1 (multidrug resistance), a membrane transport protein for which human polymorphisms have been reported in Ala893Ser/Thr and C3435T that alter pharmacokinetic profiles for a variety of drugs. Because mdr1 knockout mice spontaneously develop colitis, exonic regions were resequenced and tested for IBD association in a large, multicenter North American cohort. Two missense mutations, Asn21Asp and Ala893Ser/Thr, as well as the expression-associated polymorphism C3435T, described elsewhere, were genotyped in the entire cohort. Significant association of Ala893 with IBD was observed by both case-control analysis (P=.002) and the pedigree disequilibrium test (PDT [P=.00020-.00030]) but not for the Asn21Asp or C3435T polymorphisms. Significant association by PDT was observed within the subset with CD (P=.0014-.00090), with similar, nonsignificant trends in a smaller subset with UC. The Ala893Ser/Thr variant is triallelic, and the associated, common allele is Ala893, with undertransmission of the 893Ser (common) and the 893Thr (rare) variants. The Ala893 variant has decreased activity compared with the 893Ser variant; therefore, the association with human IBD is consistent with the murine model of mdr1 deficiency. Taken together, these data support the association of the common Ala893 polymorphism with IBD specifically and, more broadly, provides additional support for its contribution to interindividual pharmacogenetic variation.     

Jasmonic acid induced resistance in grapevines to a root and leaf feeder

We investigated the effects of induced resistance to the folivore Pacific spider mite, Tetranychus pacificus McGregor (Acari: Tetranychidae), as well as the root-feeding grape phylloxera Daktulosphaira vitifoliae (Fitch) (Homoptera: Phylloxeridae) in grapevines using exogenous applications of the natural plant inducer, jasmonic acid. Foliar jasmonic acid application at concentrations that caused no phytotoxicity significantly reduced the performance of both herbivores. There were less than half as many eggs produced by spider mites feeding on the induced leaves compared with control grapevine leaves. Induction reduced the numbers of phylloxera eggs and nymphal instars by approximately threefold and twofold, respectively, on induced compared with control grapevine roots. The negative demographic effects of jasmonic acid application appeared to be caused by changes in fecundity for the Pacific spider mite, and possibly changes in development rate and fecundity for grape phylloxera.     

Effects of herbivory and plant conditioning on the population dynamics of spider mites

Plants vary in their resistance to tetranychid spider mites, and this can have profound effects on spider-mite population dynamics. Such variation can be attributable to many factors. In this review, however, we focus on how previous or concurrent feeding by phytophagous hervivores influences expression of plant resistance to spider mites.Induced resistance is a change in the host plant in response to extrinsic stimuli, resulting in reduced host suitability for the population growth of spider mites. We begin our review by summarizing the different ways in which spider mites and plants interact to produce induced resistance-like phenomena. We then discuss a number of hypotheses which address the mechanisms underlying induced resistance and end by suggesting agricultural applications. Although the potential use of induced resistance to manage spider mites is apparent, progress in this area will depend on a better understanding of the mechanisms involved and their associated costs and benefits to the plant.