Sluggish dorsally-driven inhibition of return during orthographic processing in adults with dyslexia.

Dyslexia (D) is a neurodevelopmental reading disorder characterized by phonological and orthographic deficits. Before phonological decoding, reading requires a specialized orthographic system for parallel letter processing that assigns letter identities to different spatial locations. The magnocellular-dorsal (MD) stream rapidly process the spatial location of visual stimuli controlling visuo-spatial attention. To investigate the visuo-spatial attention efficiency during orthographic processing, inhibition of return (IOR) was measured in adults with and without D in a lexical decision task. IOR is the delay in responding to stimuli displayed in a cued location after a long cue-target interval. Only adults with D did not showed IOR effect during letter-string recognition, despite the typical left-hemisphere specialization for word identification. A specific deficit in coherent-dot-motion perception confirmed an MD-stream disorder in adults with D. Our results suggest that adults with D might develop an efficient visual word form area, but a dorsal-attentional dysfunction impairs their reading fluency.

Visual motion and rapid auditory processing are solid endophenotypes of developmental dyslexia.

Although a genetic component is known to have an important role in the etiology of developmental dyslexia (DD), we are far from understanding the molecular etiopathogenetic pathways. Reduced measures of neurobiological functioning related to reading (dis)ability, i.e. endophenotypes (EPs), are promising targets for gene finding and the elucidation of the underlying mechanisms. In a sample of 100 nuclear families with DD (229 offspring) and 83 unrelated typical readers, we tested whether a set of well-established, cognitive phenotypes related to DD [i.e. rapid auditory processing (RAP), rapid automatized naming (RAN), multisensory nonspatial attention and visual motion processing] fulfilled the criteria of the EP construct. Visual motion and RAP satisfied all testable criteria (i.e. they are heritable, associate with the disorder, co-segregate with the disorder within a family and represent reproducible measures) and are therefore solid EPs of DD. Multisensory nonspatial attention satisfied three of four criteria (i.e. it associates with the disorder, co-segregates with the disorder within a family and represents a reproducible measure) and is therefore a potential EP for DD. Rapid automatized naming is heritable but does not meet other criteria of the EP construct. We provide the first evidence of a methodologically and statistically sound approach for identifying EPs for DD to be exploited as a solid alternative basis to clinical phenotypes in neuroscience.

Neurogenetics of developmental dyslexia: from genes to behavior through brain neuroimaging and cognitive and sensorial mechanisms.

Developmental dyslexia (DD) is a complex neurodevelopmental deficit characterized by impaired reading acquisition, in spite of adequate neurological and sensorial conditions, educational opportunities and normal intelligence. Despite the successful characterization of DD-susceptibility genes, we are far from understanding the molecular etiological pathways underlying the development of reading (dis)ability. By focusing mainly on clinical phenotypes, the molecular genetics approach has yielded mixed results. More optimally reduced measures of functioning, that is, intermediate phenotypes (IPs), represent a target for researching disease-associated genetic variants and for elucidating the underlying mechanisms. Imaging data provide a viable IP for complex neurobehavioral disorders and have been extensively used to investigate both morphological, structural and functional brain abnormalities in DD. Performing joint genetic and neuroimaging studies in humans is an emerging strategy to link DD-candidate genes to the brain structure and function. A limited number of studies has already pursued the imaging-genetics integration in DD. However, the results are still not sufficient to unravel the complexity of the reading circuit due to heterogeneous study design and data processing. Here, we propose an interdisciplinary, multilevel, imaging-genetic approach to disentangle the pathways from genes to behavior. As the presence of putative functional genetic variants has been provided and as genetic associations with specific cognitive/sensorial mechanisms have been reported, new hypothesis-driven imaging-genetic studies must gain momentum. This approach would lead to the optimization of diagnostic criteria and to the early identification of 'biologically at-risk' children, supporting the definition of adequate and well-timed prevention strategies and the implementation of novel, specific remediation approach.

Monoamine oxidase A polymorphism moderates stability of attention problems and susceptibility to life stress during adolescence.

Attention problems affect a substantial number of children and adolescents and are predictive of academic underachievement and lower global adaptive functioning. Considerable variability has been observed with regard to the individual development of attention problems over time. In particular, the period of adolescence is characterized by substantial maturation of executive functioning including attentional processing, with the influence of genetic and environmental factors on individual trajectories not yet well understood. In the present investigation, we evaluated whether the monoamine oxidase A functional promoter polymorphism, MAOA-LPR, plays a role in determining continuity of parent-rated attention problems during adolescence. At the same time, a potential effect of severe life events (SLEs) was taken into account. A multi-group path analysis was used in a sample of 234 adolescents (149 males, 85 females) who took part in an epidemiological cohort study at the ages of 11 and 15 years. Attention problems during early adolescence were found to be a strong predictor of attention problems in middle adolescence. However, in carriers of the MAOA-LPR low-activity variant (MAOA-L), stability was found to be significantly higher than in carriers of the high-activity variant (MAOA-H). Additionally, only in MAOA-L carriers did SLEs during adolescence significantly impact on attention problems at the age of 15 years, implying a possible gene × environment interaction. To conclude, we found evidence that attention problems during adolescence in carriers of the MAOA-L allele are particularly stable and malleable to life stressors. The present results underline the usefulness of applying a more dynamic GxE perspective.

An assessment of gene-by-gene interactions as a tool to unfold missing heritability in dyslexia.

Even if substantial heritability has been reported and candidate genes have been identified extensively, all known marker associations explain only a small proportion of the phenotypic variance of developmental dyslexia (DD) and related quantitative phenotypes. Gene-by-gene interaction (also known as "epistasis"--G × G) triggers a non-additive effect of genes at different loci and should be taken into account in explaining part of the missing heritability of this complex trait. We assessed potential G × G interactions among five DD candidate genes, i.e., DYX1C1, DCDC2, KIAA0319, ROBO1, and GRIN2B, upon DD-related neuropsychological phenotypes in 493 nuclear families with DD, by implementing two complementary regression-based approaches: (1) a general linear model equation whereby the trait is predicted by the main effect of the number of rare alleles of the two genes and by the effect of the interaction between them, and (2) a family-based association test to detect G × G interactions between two unlinked markers by splitting up the association effect into a between- and a within-family genetic orthogonal components. After applying 500,000 permutations and correcting for multiple testing, both methods show that G × G effects between markers within the DYX1C1, KIAA0319/TTRAP, and GRIN2B genes lower the memory letters composite z-score of on average 0.55 standard deviation. We provided initial evidence that the effects of familial transmission of synergistic interactions between genetic risk variants can be exploited in the study of the etiology of DD, explain part of its missing heritability, and assist in designing customized charts of individualized neurocognitive impairments in complex disorders, such as DD.

A First Generation Heterobasidion Hybrid Discovered in Larix lyalli in Montana.

On September 25, 2010, a wood sample was collected from an entirely decayed root ball of an alpine larch (Larix lyallii Parl.), 10 cm in diameter at breast height, recently downed, but still green. No attempts were made to determine whether the decay progressed into the stem. The discovery occurred in a stand in the Bitterroot Mountains, south of Darby, Montana (elev. 2,530 m; 45.893528° N, 114.278322° W). Several adjacent alpine larches were either dead or displayed thin crowns, and an old Heterobasidion basidiocarp was found on the decayed root ball of a neighboring dead tree, suggesting the presence of a root disease pocket. The stand is mature and composed of alpine larch, whitebark pine (Pinus albicaulis Engelm.), and a few subalpine firs (Abies lasiocarpa (Hooker) Nuttall), but only larches were symptomatic. No stumps were visible, and the site is in a designated wilderness area characterized by minimal forest management. Wood chips displaying a white rot with bleached speckles were plated on 2% malt agar, and cultures displaying the typical Heterobasidion anamorph (Spiniger meineckellus) were visible after 7 days. DNA was extracted from two distinct cultures, and the sequences of three nuclear loci, namely the internal transcribed spacer, the elongation factor 1-alpha, and the glyceraldehyde 3-phosphate dehydrogenase, were analyzed. The sequence of the mitochondrial ATPase was also sequenced. All loci were amplified using the primers indicated in Linzer et al. (2). Sequences of all three nuclear loci (GenBank Accession Nos. KF811480 to 82) unequivocally indicated both isolates to be first generation hybrids between H. irregulare (Underw.) Garbel. & Otrosina and H. occidentale Otrosina & Garbel. Cumulatively, sequences were heterozygous at over 40 positions in all three loci, and for the presence of two indels (one in ITS, one in EF 1-alpha). Polymorphisms and indels indicated alleles from both species were present in these heterokaryotic (ploidy n+n) isolates. The mitochondrial ATPase (KF811483 to 84) indicated instead the cytoplasm belonged to H. occidentale, suggesting that species was the first to be established in the infected tree and was either dikaryotized by a basidiopsore of the other species, or subject to nuclear re-assortment through di-mon mating with a genotype of H. irregulare. This is the first report of a Heterobasidion sp. in L. lyalli, and it is the second report of a natural Heterobasidion hybrid in North America (1). This finding indicates Alpine larch may be a host for both Heterobasidion species, as described for pine stumps in California (1). Thus, this conifer may have provided a substrate for the hybridization and interspecific gene introgression documented to have occurred before stumps were generated in high frequency by modern forestry practices (2). References: (1) M. Garbelotto et al. Phytopathology 86:543, 1996. (2) R. Linzer et al. Mol. Phylogenet. Evol. 46:844, 2008.

Population genetic analyses provide insights on the introduction pathway and spread patterns of the North American forest pathogen Heterobasidion irregulare in Italy.

A population genetics approach is used to identify the most likely introduction site and introduction pathway for the North American forest pathogen Heterobasidion irregulare using 101 isolates from six sites in Italy and 34 isolates from five sites in North America. Diversity indices based on sequences from ten loci indicate the highest diversity in Italy is found in Castelfusano/Castelporziano and that diversity progressively decreases with increasing distance from that site. AMOVA, Bayesian clustering and principal coordinates analyses based on 12 SSR loci indicate high levels of gene flow among sites, high frequency of admixing, and fail to identify groups of genotypes exclusive to single locations. Cumulatively, these analyses suggest the current infestation is the result of multiple genotypes expanding their range from a single site. Based on two sequenced loci, a single source site in North America could provide enough variability to explain the variability observed in Italy. These results support the notion that H. irregulare was introduced originally in Castelporziano: because Castelporziano has been sealed off from the rest of the world for centuries except for a camp set up by the US military in 1944, we conclude the fungus may have been transported in infected wood used by the military. Finally, spatial autocorrelation analyses using SSR data indicate a significant under-dispersion of alleles up to 0.5-10 km, while a significant overdispersion of alleles was detected at distances over 80 km: these ranges can be used to make predictions on the likely dispersal potential of the invasive pathogen.

An assessment of gene-by-environment interactions in developmental dyslexia-related phenotypes.

While the genetic and environmental contributions to developmental dyslexia (DD) have been studied extensively, the effects of identified genetic risk susceptibility and of specified environmental hazardous factors have usually been investigated separately. We assessed potential gene-by-environment (GxE) interactions on DD-related reading, spelling and memory phenotypes. The presence of GxE effects were investigated for the DYX1C1, DCDC2, KIAA0319 and ROBO1 genes, and for seven specified environmental moderators in 165 nuclear families in which at least one member had DD, by implementing a general test for GxE interaction in sib-pair-based association analysis of quantitative traits. Our results support a diathesis-stress model for both reading and memory composites: GxE effects were found between some specified environmental moderators (i.e. maternal smoke during pregnancy, birth weight and socio-economic status) and the DYX1C1-1259C/G marker. We have provided initial evidence that the joint analysis of identified genetic risk susceptibility and measured putative risk factors can be exploited in the study of the etiology of DD and reading-related neuropsychological phenotypes, and may assist in identifying/preventing the occurrence of DD.

Genetic epidemiology of the sudden oak death pathogen Phytophthora ramorum in California.

A total of 669 isolates of Phytophthora ramorum, the pathogen responsible for Sudden Oak Death, were collected from 34 Californian forests and from the ornamental plant-trade. Seven microsatellite markers revealed 82 multilocus genotypes (MGs) of which only three were abundant (>10%). Iteratively collapsing based upon minimum Phi(ST), yielded five meta-samples and five singleton populations. Populations in the same meta-sample were geographically contiguous, with one exception, possibly explained by the trade of infected plants from the same source into different locations. Multidimensional scaling corroborated this clustering and identified nursery populations as genetically most distant from the most recent outbreaks. A minimum-spanning network illustrated the evolutionary relationships among MGs, with common genotypes at the centre and singletons at the extremities; consistent with colonization by a few common genotypes followed by local evolution. Coalescent migration analyses used the original data set and a data set in which local genotypes were collapsed into common ancestral genotypes. Both analyses suggested that meta-samples 1 (Santa Cruz County) and 3 (Sonoma and Marin Counties), act as sources for most of the other forests. The untransformed data set best explains the first phases of the invasion, when the role of novel genotypes may have been minimal, whereas the second analysis best explains migration patterns in later phases of the invasion, when prevalence of novel genotypes was likely to have become more significant. Using this combined approach, we discuss possible migration routes based on our analyses, and compare them to historical and field observations from several case studies.

Reconstruction of the Sudden Oak Death epidemic in California through microsatellite analysis of the pathogen Phytophthora ramorum.

The genetic structure of the clonally reproducing Sudden Oak Death (SOD) pathogen in California was investigated using seven variable microsatellites. A total of 35 multilocus genotypes were identified among 292 samples representative of populations from 14 forest sites and of the nursery trade. amova indicated significant genetic variability both within (44.34%) and among populations (55.66%). Spatial autocorrelation analyses indicated that Moran's index of similarity reached a minimum of 0.1 at 350 m, increased to 0.4 at 1500 m and then decreased to zero at 10 km. These results suggest a bimodal pattern of spread, with medium range dispersal (1500-10,000 m) putatively attributed to the presence of strong winds. Lack of genetic structure was identified for three groups of populations. One group notably included the nurseries' population and two forest populations, both linked to early reports of the pathogen. A neighbour-joining analysis based on pairwise Phi(ST) values indicated that the clade inclusive of the nurseries' populations is basal to all California populations. A network analysis identified three common genotypes as the likely founders of the California infestation and proposes a stepwise model for local evolution of novel genotypes. This was supported by the identification in the same locations of novel genotypes and of their 1- or 2-step parents. We hypothesize that the few undifferentiated population groups indicate historical human spread of the pathogen, while the general presence of genetically structured populations indicates that new infestations are currently generated by rare medium or long-range natural movement of the pathogen, followed by local generation of new genotypes.

Haplotype analysis of the CD11 gene cluster in patients with chronic Helicobacter pylori infection and gastric ulcer disease.

Helicobacter pylori infection leads to a broad spectrum of disease manifestations such as gastritis, ulcer disease, and even gastric carcinoma. The genetically determined immune response and subsequent inflammation influence the degree of mucosal damage. Adhesion molecules of the CD11 cluster play an important role in adherence of neutrophils to endothelial cells in inflammation. We conducted a haplotype-based analysis of the CD11 cluster in a sample of 315 patients with H. pylori infection and investigated associations with gastric erosions and ulcer disease. Twelve single nucleotide polymorphisms (SNPs) covering the genes CD11a, CD11b, and CD11c were genotyped by Taqman technology. Linkage disequilibrium (LD) was assessed within the CD11 cluster and haplotype case-control analysis was conducted. Sliding window haplotype analysis identified a haplotype consisting of the markers CD11c exon 15 and intron 31 associated with gastric ulcer disease. Patients carrying the haplotype GA bear a 2.4-fold increased risk. No significant associations of single markers with disease outcome were found. High-density LD mapping and mutation detection of CD11c in larger samples will be necessary to confirm our findings and identify the causative variant. Thus, we conclude that genetic variants in the CD11 cluster may play a role in the development of gastric ulcer in chronic H. pylori infection presumably by influencing leukocyte adhesion. The biological effect of genetic variants of CD11c in gastric inflammation needs further clarification.

Genetic variants in the CCR gene cluster and spontaneous viral elimination in hepatitis C-infected patients.

Hepatitis C virus (HCV) infection results in chronic hepatitis in more than 80% of infected patients while 10-20% of patients recover spontaneously. Host genetic factors may influence the ability to clear the virus after infection. Six single nucleotide polymorphisms and a 32 bp deletion in the genes coding for CCR3, CCR2 and CCR5 (which are all located in a cluster on chromosome 3) were investigated in 465 consecutively recruited patients infected with HCV and 370 matched controls. Genetic variants were tested for association with spontaneous viral elimination and, in the chronically infected patients, stage of fibrosis and response to antiviral therapy. The G190A polymorphism (variant allele Ile64) in the first transmembrane domain of CCR2 was under-represented in the 29 patients who had cleared the hepatitis C virus spontaneously (P = 0.018). None of the other variants in the CCR gene cluster showed association with the natural course of the infection, stage of fibrosis or response to therapy.

Pharmacogenetic investigation of the TNF/TNF-receptor system in patients with chronic active Crohn's disease treated with infliximab.

Infliximab (anti-TNF-alpha monoclonal antibody) induces remission in 30-40% of Crohn's disease patients. Treatment response is a stable trait. Two cohorts from independent, prospective clinical trials of infliximab in Crohn's disease were studied. Hypotheses were generated in an exploratory cohort (n = 90) and then tested in a confirmatory cohort (n = 444), using a statistical design, which is stable against type 1 and type 2 errors. In the exploratory cohort, the mutant 196Arg allele of TNFR-II (exon 6 polymorphism) and a novel silent polymorphism in exon 2 of TNFR-II were associated with lack of response to infliximab (83.3% in homozygote mutant 196 Arg patients vs 36.9% in heterozygotes and wild-type homozygotes (P = 0.036) and 85.7% in homozygote mutant exon 2 patients vs 36.1% (P = 0.01), respectively). None of the homozygote mutant individuals (0/6) achieved clinical remission, whereas the remission rate was 35.7% (30/84) in wild-type homozygotes and heterozygotes. In the large second cohort, the observed genotype-phenotype associations were not replicated. Other polymorphisms (TNF-alpha promoter -238, -308, -376, -857, -1031, TNF-R-I -609, +36 (exon 1), TNF-R-II 1663, 1690 (3'-UTR)) were not associated with treatment response in both cohorts (P > 0.5). None of the polymorphisms was associated with refractory Crohn's disease itself when compared to healthy controls. In a two-cohort study, a series of polymorphisms in the TNF, the TNF-R-I and in the TNF-R-II genes could be thoroughly excluded as pharmacogenetic markers for a treatment response to infliximab and as etiologic factors for Crohn's disease, respectively. The discrepancy between the two cohorts observed for the TNF-R-II exon 6 and exon 2 polymorphism may point to a weak effect on treatment response but also serves to illustrate the need for a sequential exploratory/confirmatory design in pharmacogenetic studies.

Association between insertion mutation in NOD2 gene and Crohn's disease in German and British populations.

Background Genetic predisposition to inflammatory bowel disease (IBD) has been shown by epidemiological and linkage studies. Genetic linkage of IBD to chromosome 16 has been previously observed and replicated in independent populations. The recently identified NOD2 gene is a good positional and functional candidate gene since it is located in the region of linkage on chromosome 16q12, and activates nuclear factor (NF) kappaB in response to bacterial lipopolysaccharides. Methods We sequenced the coding region of the NOD2 gene and genotyped an insertion polymorphism affecting the leucine-rich region of the protein product in 512 individuals with IBD from 309 German or British families, 369 German trios (ie, German patients with sporadic IBD and their unaffected parents), and 272 normal controls. We then tested for association with Crohn's disease and ulcerative colitis. Findings Family-based association analyses were consistently positive in 95 British and 99 German affected sibling pairs with Crohn's disease (combined p<0.0001); the association was confirmed in the 304 German trios with Crohn's disease. No association was seen in the 115 sibling pairs and 65 trios with ulcerative colitis. The genotype-specific disease risks conferred by heterozygous and homozygous mutant genotypes were 2.6 (95% CI 1.5-4.5) and 42.1 (4.3-infinity), respectively. Interpretation The insertion mutation in the NOD2 gene confers a substantially increased susceptibility to Crohn's disease but not to ulcerative colitis.

Multiple nuclear pseudogenes of mitochondrial cytochrome b in Ctenomys (Caviomorpha, rodentia) with either great similarity to or high divergence from the true mitochondrial sequence.

A fragment of the mitochondrial cytochrome b gene was studied in 13 species of the South American fossorial rodent Ctenomys using PCR with 'universal' primers and DNA sequencing after cloning. Five different groups of sequences were found, one of which corresponds to the functional mitochondrial gene (mt). The other four groups (A, B, C and D) were believed to be nuclear pseudogenes. Sequences A-C were highly divergent from the mt sequences and included substitutions, deletions and insertions such that they could not possibly have coded a functional protein. They all shared a common insertion between positions 15055 and 15056 suggestive of a common origin, although the A, B and C sequences otherwise differed greatly from each other. The D sequences also could not have been functional on the basis of nucleotide sequence, but the differences with the mt sequences were far more subtle and in a more limited study the D sequences could easily have been classified as a true mtDNA sequence. It is suggested that there were two transfers of the cytochrome b gene from the mitochondrion to the nucleus; the first leading to sequences A-C and the second to the D sequence. Subsequent to transfer, a sequence of duplications within the nucleus appears to have generated the full range of pseudogenes that are observed. This study adds to other recent observations suggesting the frequent transfer of mtDNA sequences to the nucleus and reinforces the necessity of great care in interpreting PCR-generated sequences, particularly those produced with universal primers. There are now data from several species of mammals and birds relating to PCR-generated nuclear copies of cytochrome b, which we review.

Linkage of inflammatory bowel disease to human chromosome 6p.

Inflammatory bowel disease (IBD) is characterized by a chronic relapsing intestinal inflammation. IBD is subdivided into Crohn disease and ulcerative colitis phenotypes. Given the immunologic dysregulation in IBD, the human-leukocyte-antigen region on chromosome 6p is of significant interest. Previous association and linkage analysis has provided conflicting evidence as to the existence of an IBD-susceptibility locus in this region. Here we report on a two-stage linkage and association analysis of both a basic population of 353 affected sibling pairs (ASPs) and an extension of this population to 428 white ASPs of northern European extraction. Twenty-eight microsatellite markers on chromosome 6 were genotyped. A peak multipoint LOD score of 4.2 was observed, at D6S461, for the IBD phenotype. A transmission/disequilibrium test (TDT) result of P=.006 was detected for D6S426 in the basic population and was confirmed in the extended cohort (P=.004; 97 vs. 56 transmissions). The subphenotypes of Crohn disease, ulcerative colitis, and mixed IBD contributed equally to this linkage, suggesting a general role for the chromosome 6 locus in IBD. Analysis of five single-nucleotide polymorphisms in the TNFA and LTA genes did not reveal evidence for association of these important candidate genes with IBD. In summary, we provide firm linkage evidence for an IBD-susceptibility locus on chromosome 6p and demonstrate that TNFA and LTA are unlikely to be susceptibility loci for IBD.

Mediterranean Europe as an area of endemism for small mammals rather than a source for northwards postglacial colonization.

There is a general perception that central and northern Europe were colonized by range expansion from Mediterranean refugia at the end of the last glaciation. Data from various species support this scenario, but we question its universality. Our mitochondrial DNA studies on three widespread species of small mammal suggest that colonization may have occurred from glacial refugia in central Europe-western Asia. The haplotypes on the Mediterranean peninsulae are distinctive from those found elsewhere. Rather than contributing to the postglacial colonization of Europe, Mediterranean populations of widespread small mammals may represent long-term isolates undergoing allopatric speciation. This could explain the high endemism of small mammals associated with the Mediterranean peninsulae.

Genome composition in Venezuelan spiny-rats of the genus Proechimys(Rodentia, Echimyidae). I. Genome size, C-heterochromatin and repetitive DNAs in situ hybridization patterns.

The genome sizes of the Venezuelan spiny-rats Proechimys guairae guairae (2n = 48) and P. trinitatis (2n = 62) were evaluated and proved to be 12.5 +/- 0.5 pg and 12.6 +/- 0.3 pg respectively, the highest so far recorded among mammals; also the C-heterochromatin (32.7%, Coefficient of Variation [CV] 3.8 and 35.8%, CV 4.4) and GC (44.2%, CV 2.7 and 43.6%, CV 2.9) contents are very high. Highly repetitive (rep) DNAs were isolated from restriction enzyme digested genomic DNAs of both species. The intra- and inter-specific chromosomal allocations of these rep DNAs were analyzed by direct and cross-hybridizations. Results show that the two genomes harbour several rep DNA families which show both species-specificity and interspecific relatedness in their in situ hybridization patterns. The rep DNA families show an equilocal distribution at both the pericentromeric areas of all chromosomes and in the whole arms of two pairs of the uniarmed group, suggesting co-evolution of the rep DNAs. P. g. guairae BamHI digested DNA, when cloned and sequenced, proved to consist of a long "composite" unit (1,239 bp) containing two copies of each of 75-bp and 110-bp internal subrepeats. Karyotype restructuring between P. g. guairae and P. trinitatis, mainly due to Robertsonian changes, was accompanied by slight intra- and intergenomic movements of the putative satellite DNA families within stable genome sizes and C-heterochromatin contents. We discuss the findings obtained in Proechimys in the light of those regarding the kangaroo rat, the pocket gopher and the house mouse; they support the idea that karyotype restructuring could be the expression of molecular driven events of rep DNA amplification and homogenisation through non-homologous chromosomes.

Non-telomeric chromosome localization of (TTAGGG)n repeats in the genus Eulemur.

The chromosomal distribution of the (TTAGGG)n telomeric repetitive sequences was studied in the Malagasy species Eulemur fulvus fulvus (2n = 60), Eulemur rubriventer (2n = 50), Eulemur coronatus (2n = 46) and Eulemur macaco (2n = 44). These sequences hybridize to the telomeres of all chromosomes of the four species and also to the pericentromeres of all chromosomes of E. fulvus, E. coronatus and E. macaco, with the exception of the pericentromeres of E. coronatus and E. macaco chromosomes 9, the homeologous E. fulvus chromosomes 2 and E. macaco chromosomes 1. In E. rubriventer only a very weak signal was detected at the pericentromeres of a few chromosomes. In E. fulvus, E. coronatus and E. macaco, non-telomeric (TTAGGG)n sequences collocalize with constitutive heterochromatin. The interspecific differences of the hybridization pattern of (TTAGGG)n sequences at the pericentromeres suggest that E. rubriventer branched off the common trunk before amplification of endogenous (TTAGGG)n sequences occurred in pericentromeric regions.