Cognitive decline in Huntington's disease expansion gene carriers

BACKGROUND: In Huntington's Disease (HD) cognitive decline can occur before unequivocal motor signs become apparent. As cognitive decline often starts early in the course of the disease and has a progressive nature over time, cognition can be regarded as a key target for symptomatic treatment. The specific progressive profile of cognitive decline over time is unknown. OBJECTIVE: The aim of this study is to quantify the progression of cognitive decline across all HD stages, from pre-motormanifest to advanced HD, and to investigate if CAG length mediates cognitive decline. METHODS: In the European REGISTRY study 2669 HD expansion gene carriers underwent annual cognitive assessment. General linear mixed models were used to model the cognitive decline for each cognitive task across all disease stages. Additionally, a model was developed to evaluate the cognitive decline based on CAG length and age rather than disease stage. RESULTS: There was significant cognitive decline on all administered tasks throughout pre-motormanifest (close to estimated disease onset) participants and the subsequent motormanifest participants from stage 1 to stage 4. Performance on the Stroop Word and Stroop Color tests additionally declined significantly across the two pre-motormanifest groups: far and close to estimated disease onset. The evaluation of cognition performance in relation to CAG length and age revealed a more rapid cognitive decline in participants with longer CAG length than participants with shorter CAG length over time. CONCLUSION: Cognitive performance already shows decline in pre-motormanifest HD gene expansion carriers and gradually worsens to late stage HD. HD gene expansion carriers with certain CAG length have their own cognitive profile, i.e., longer CAG length is associated with more rapid decline

The V471A polymorphism in autophagy-related gene ATG7 modifies age at onset specifically in Italian Huntington disease patients

The cause of Huntington disease (HD) is a polyglutamine repeat expansion of more than 36 units in the huntingtin protein, which is inversely correlated with the age at onset of the disease. However, additional genetic factors are believed to modify the course and the age at onset of HD. Recently, we identified the V471A polymorphism in the autophagy-related gene ATG7, a key component of the autophagy pathway that plays an important role in HD pathogenesis, to be associated with the age at onset in a large group of European Huntington disease patients. To confirm this association in a second independent patient cohort, we analysed the ATG7 V471A polymorphism in additional 1,464 European HD patients of the “REGISTRY” cohort from the European Huntington Disease Network (EHDN). In the entire REGISTRY cohort we could not confirm a modifying effect of the ATG7 V471A polymorphism. However, analysing a modifying effect of ATG7 in these REGISTRY patients and in patients of our previous HD cohort according to their ethnic origin, we identified a significant effect of the ATG7 V471A polymorphism on the HD age at onset only in the Italian population (327 patients). In these Italian patients, the polymorphism is associated with a 6-years earlier disease onset and thus seems to have an aggravating effect. We could specify the role of ATG7 as a genetic modifier for HD particularly in the Italian population. This result affirms the modifying influence of the autophagic pathway on the course of HD, but also suggests population-specific modifying mechanisms in HD pathogenesis

Using genetic methods to investigate dispersal in two badger (Meles meles) populations with different ecological characteristics

Understanding the dispersal behaviour of a species is important for understanding its ecology and evolution. Dispersal in the Eurasian badger (Meles meles) is believed to be very limited, with social groups forming primarily through the retention of offspring. However, most of our knowledge of dispersal in this species comes from studies of high-density populations in the United Kingdom, where badgers are atypical in their behaviour, physiology, ecology and prey specialization. In this study we use genetic methods to compare dispersal patterns in a British and a Swiss population that differ in their ecology and demography. We present well-supported evidence that badgers disperse much further in the low-density continental population, where dispersal may also be female biased. Limited dispersal thus seems not to be an intrinsic behavioural characteristic of the species. Rather, dispersal patterns seem to vary depending on population demography and, ultimately, habitat quality and characteristics. This could have important management consequences, as dispersal can affect the impact of local extinction, and host dispersal has a particularly important role in disease transmission. Even though concentrated studies of a species in a single location may not provide representative data for the species, there are few mammalian studies that compare demography and dispersal patterns across contrasting habitats. Our results provide an example of phenotypic plasticity and suggest that dispersal is determined by the interaction of individual, social and environmental factors that may differ between populations. Heredity (2010) 104, 493-501; doi:10.1038/hdy.2009.136; published online 7 October 200

The Taxonomic Status of Mazama bricenii and the Significance of the Táchira Depression for Mammalian Endemism in the Cordillera de Mérida, Venezuela.

We studied the taxonomy and biogeography of Mazama bricenii, a brocket deer classified as Vulnerable by the IUCN, drawing on qualitative and quantitative morphology and sequences of the mitochondrial cytochrome-b gene. We used Ecological Niche Modeling (ENM) to evaluate the hypothesis that M. bricenii of the Venezuelan Cordillera de Mérida (CM) might have become isolated from populations of its putative sister species, Mazama rufina, in the Colombian Cordillera Oriental (CO). This hypothesis assumes that warm, dry climatic conditions in the Táchira Depression were unsuitable for the species. Our analyses did not reveal morphological differences between specimens geographically attributable to M. bricenii and M. rufina, and phylogenetic analyses of molecular data recovered M. bricenii nested within the diversity of M. rufina. These results indicate that M. bricenii should be regarded as a junior synonym of M. rufina. ENM analyses revealed the existence of suitable climatic conditions for M. rufina in the Táchira Depression during the last glacial maximum and even at present, suggesting that gene flow between populations in the CO and CM may have occurred until at least the beginning of the current interglacial period and may continue today. Because this pattern might characterize other mammals currently considered endemic to the CM, we examined which of these species match two criteria that we propose herein to estimate if they can be regarded as endemic to the CM with confidence: (1) that morphological or molecular evidence exists indicating that the putative endemic taxon is distinctive from congeneric populations in the CO; and (2) that the putative endemic taxon is restricted to either cloud forest or páramo, or both. Only Aepeomys reigi, Cryptotis meridensis, and Nasuella meridensis matched both criteria; hence, additional research is necessary to assess the true taxonomic status and distribution of the remaining species thought to be CM endemics

Data from: Spatial genetic structure in American black bears (Ursus americanus): female philopatry is variable and related to population history

Previously, American black bears (Ursus americanus) were thought to follow the pattern of female philopatry and male-biased dispersal. However, recent studies have identified deviations from this pattern. Such flexibility in dispersal patterns can allow individuals greater ability to acclimate to changing environments. We explored dispersal and spatial genetic relatedness patterns across ten black bear populations—including long established (historic), with known reproduction >50 years ago, and newly established (recent) populations, with reproduction recorded <50 years ago—in the Interior Highlands and Southern Appalachian Mountains, United States. We used spatially-explicit, individual-based genetic simulations to model gene flow under scenarios with varying levels of population density, genetic diversity, and female philopatry. Using measures of genetic distance and spatial autocorrelation, we compared metrics between sexes, between population types (historic and recent), and among simulated scenarios which varied in density, genetic diversity, and sex-biased philopatry. In empirical populations, females in recent populations exhibited stronger patterns of isolation-by-distance (IBD) than females and males in historic populations. In simulated populations, low density populations had a stronger indication of IBD than medium to high density populations; however, this effect varied in empirical populations. Condition dependent dispersal strategies may permit species to cope with novel conditions and rapidly expand populations. Pattern-process modelling can provide qualitative and quantitative means to explore variable dispersal patterns, and could be employed in other species, particularly to anticipate range shifts in response to changing climate and habitat conditions