Pathogenic Huntingtin Repeat Expansions in Patients with Frontotemporal Dementia and Amyotrophic Lateral Sclerosis.

We examined the role of repeat expansions in the pathogenesis of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) by analyzing whole-genome sequence data from 2,442 FTD/ALS patients, 2,599 Lewy body dementia (LBD) patients, and 3,158 neurologically healthy subjects. Pathogenic expansions (range, 40-64 CAG repeats) in the huntingtin (HTT) gene were found in three (0.12%) patients diagnosed with pure FTD/ALS syndromes but were not present in the LBD or healthy cohorts. We replicated our findings in an independent collection of 3,674 FTD/ALS patients. Postmortem evaluations of two patients revealed the classical TDP-43 pathology of FTD/ALS, as well as huntingtin-positive, ubiquitin-positive aggregates in the frontal cortex. The neostriatal atrophy that pathologically defines Huntington's disease was absent in both cases. Our findings reveal an etiological relationship between HTT repeat expansions and FTD/ALS syndromes and indicate that genetic screening of FTD/ALS patients for HTT repeat expansions should be considered

DNA Sequence Analyses Reveal Abundant Diversity, Endemism and Evidence for Asian Origin of the Porcini Mushrooms

<div><p>The wild gourmet mushroom <em>Boletus edulis</em> and its close allies are of significant ecological and economic importance. They are found throughout the Northern Hemisphere, but despite their ubiquity there are still many unresolved issues with regard to the taxonomy, systematics and biogeography of this group of mushrooms. Most phylogenetic studies of <em>Boletus</em> so far have characterized samples from North America and Europe and little information is available on samples from other areas, including the ecologically and geographically diverse regions of China. Here we analyzed DNA sequence variation in three gene markers from samples of these mushrooms from across China and compared our findings with those from other representative regions. Our results revealed fifteen novel phylogenetic species (about one-third of the known species) and a newly identified lineage represented by <em>Boletus</em> sp. HKAS71346 from tropical Asia. The phylogenetic analyses support eastern Asia as the center of diversity for the porcini sensu stricto clade. Within this clade, <em>B. edulis</em> is the only known holarctic species. The majority of the other phylogenetic species are geographically restricted in their distributions. Furthermore, molecular dating and geological evidence suggest that this group of mushrooms originated during the Eocene in eastern Asia, followed by dispersal to and subsequent speciation in other parts of Asia, Europe, and the Americas from the middle Miocene through the early Pliocene. In contrast to the ancient dispersal of porcini in the strict sense in the Northern Hemisphere, the occurrence of <em>B. reticulatus</em> and <em>B. edulis</em> sensu lato in the Southern Hemisphere was probably due to recent human-mediated introductions.</p> </div

Divergence time estimation and ancestral area reconstruction of porcini s.s. using the ITS data.

<p>The Chronogram is obtained from molecular clock analysis using BEAST. Pie chart in each node indicates the possible ancestral distributions inferred from Baysian Binary MCMC analysis (BBM) implemented in RASP, while characters above and beneath each clade identify the possible ancestral distribution estimated by maximum likelihood-based program LAGRANGE. Red circles around pie charts indicate possible dispersal and vicariance events as suggested by BBM analysis, while green circles show only dispersal events. Red branches identify dispersal events inferred by LAGRANGE. Characters beyond species names show current distribution area of each species.</p

Phylogenetic tree inferred from the Maximum Likelihood (ML) analysis based on the RPB1-nrLSU data.

<p>Bootstrap values (ML)/posterior possibilities (from Bayesian Inference) are shown above or beneath individual branches. The positions of five lineages are marked with bold lines, where 1, 2, 3 represent our newly identified lineage (<i>Boletus</i> sp. HKAS71346), “<i>Inferiboletus</i>”, and “<i>Obtextiporus</i>”, respectively. All names in the porcini s.s. lineage were the same as those from ITS analysis (see Fig. 2).</p

Chronogram and estimated divergence times of porcini s.l. generated from molecular clock analysis using the RPB1-nrLSU data.

<p>Chronogram obtained using the Ascomycota – Basidiomycota divergence time of 582 Mya as the calibration point is shown in panel A. The calibration point and objects of this study are marked in the chronogram. The geological time scale is in millions of years ago (Mya). Estimated divergence times of main nodes are summarized in panel B, with divergence times of lineages in the porcini s.l. highlighted in blue color.</p

Average evolutionary divergence over ITS sequence pairs within and between groups (provincially adopted phylogenetic species) calculated by MEGA 5 using the Maximum Composite Likelihood model.

<p>Average evolutionary divergence over ITS sequence pairs within and between groups (provincially adopted phylogenetic species) calculated by MEGA 5 using the Maximum Composite Likelihood model.</p

Phylogenetic tree and distribution patterns of the species within the porcini s.s. lineage.

<p>Panel A shows the topology inferred from ML analysis using the ITS data. The two values at each node represent the percentage of bootstrap supports (ML)/posterior probabilities (BI). Provisionally adopted names (based on tree topology) and finally accepted names (based on our proposed criterion for phylogenetic species identification) for all taxa are listed. Newly identified phylogenetic species are highlighted by adding asterisks after their names. Three major clades are separately marked with bold lines, and the fourth one is not marked due to its low statistical support values. Panel B lists the distribution patterns of the porcini s.s. as a pie chart. Colors in both panels represent different distribution ranges.</p