Short Chromosome Research Articles

Double Helix Structure and Finite Persisting Sphere Genetic Algorithm in Designing Digital Circuit Structure

This paper proposes a new approach of chromosome representation in digital circuit design which is Double Helix Structure (DHS). The idea of DHS in chromosome representation is inspired from the nature of the DNA's structure that built up the formation of the chromosomes. DHS is an uncomplicated design method. It uses short chromosome string to represent the circuit structure. This new structure representation is flexible in size where it is not restricted by the conventional matrix structure representation. There are some advantages of the proposed method such as convenience to apply due to the simple formation and flexible structure, less requirement of memory allocation and faster processing time due to the short chromosomes representation. In this paper, DHS is combined with Finite Persisting Sphere Genetic Algorithm (FPSGA) to optimal the digital circuit structure design. The experimental results prove that DHS uses short chromosome string to produce the flexible digital circuit structure and FPSGA further optimal the number of gates used in the structure. The proposed method has better performance compared to other methods.

Genome downsizing and karyotype constancy in diploid and polyploid congeners: a model of genome size variation.

Evolutionary chromosome change involves significant variation in DNA amount in diploids and genome downsizing in polyploids. Genome size and karyotype parameters of Hippeastrum species with different ploidy level were analysed. In Hippeastrum, polyploid species show less DNA content per basic genome than diploid species. The rate of variation is lower at higher ploidy levels. All the species have a basic number x = 11 and bimodal karyotypes. The basic karyotypes consist of four short metacentric chromosomes and seven large chromosomes (submetacentric and subtelocentric). The bimodal karyotype is preserved maintaining the relative proportions of members of the haploid chromosome set, even in the presence of genome downsizing. The constancy of the karyotype is maintained because changes in DNA amount are proportional to the length of the whole-chromosome complement and vary independently in the long and short sets of chromosomes. This karyotype constancy in taxa of Hippeastrum with different genome size and ploidy level indicates that the distribution of extra DNA within the complement is not at random and suggests the presence of mechanisms selecting for constancy, or against changes, in karyotype morphology.

Haplotyping a single triploid individual based on genetic algorithm.

The minimum error correction model is an important combinatorial model for haplotyping a single individual. In this article, triploid individual haplotype reconstruction problem is studied by using the model. A genetic algorithm based method GTIHR is presented for reconstructing the triploid individual haplotype. A novel coding method and an effectual hill-climbing operator are introduced for the GTIHR algorithm. This relatively short chromosome code can lead to a smaller solution space, which plays a positive role in speeding up the convergence process. The hill-climbing operator ensures algorithm GTIHR converge at a good solution quickly, and prevents premature convergence simultaneously. The experimental results prove that algorithm GTIHR can be implemented efficiently, and can get higher reconstruction rate than previous algorithms.

Karyotypes in Ethiopian Aloe species (Xanthorrhoeaceae: Asphodeloideae)

A cytogenetic survey of 17 species in the succulent-leaved genus Aloe L. (Xanthorrhoeaceae subfamily Asphodeloideae) in Ethiopia was undertaken towards a more complete genetic characterisation of the genus throughout its distribution in Africa, Arabia and Madagascar. Somatic metaphase chromosomes of all species studied showed the same diploid chromosome number of 2n = 14, consisting of four pairs of long and three pairs of short chromosomes. Symmetry was characterised as Stebbins type 2B and the asymmetry indices AsK%, TF%, A1 and A2 revealed minor karyotypic variation common in closely related species. The metrics showed that A. benishangulana has a marginally higher degree of asymmetry than is typical, and the pubescent-flowered A. trichosantha has a more symmetrical karyotype than most other species. We suggest that the stable karyotype morphology in Aloe indicates that structural genome changes and ecological factors play a more prominent role in speciation in Aloe.

Karyology of endemicMatthiola anchoniifoliaHub. -Mor. (Brassicaceae) in Turkey

In this paper, the karyological properties of an endemic plant for Turkey, Matthiola anchoniifolia Hub.-Mor. grown in the Sivas Province in Turkey, are studied. Karyotype was made on somatic metaphases using an Image Analysis System. The somatic chromosome number is determined as 2n = 12. The karyotype formula of this species consists of five median chromosome pairs and one submedian chromosome pair. The shortest chromosome length is 4.89 μm, the longest is 9.18 μm, and haploid chromosome length is 38.66 μm. Photographs were taken using a BX51 Olympus microscope. An ideogram of the species was drawn using an Image Analysis System.

Evolutionary crew scheduling with adaptive chromosomes

This paper presents an adaptive evolutionary approach incorporating a hybrid genetic algorithm (GA) for public transport crew scheduling problems, which are well-known to be NP-hard. To ensure the search efficiency, a suitable chromosome representation has to be determined first. Unlike a canonical GA for crew scheduling where the chromosome length is fixed, the chromosome length in the proposed approach may vary adaptively during the iterative process, and its initial value is elaborately designated as the lower bound of the number of shifts to be used in an unachievable optimal solution. Next, the hybrid GA with such a short chromosome length is employed to find a feasible schedule. During the GA process, the adaptation on chromosome lengths is achieved by genetic operations of crossover and mutation with removal and replenishment strategies aided by a simple greedy algorithm. If a feasible schedule cannot be found when the GA’s termination condition is met, the GA will restart with one more gene added. The above process is repeated until a feasible solution is found. Computational experiments based on 11 real-world crew scheduling problems in China show that, compared to a fuzzy GA known to be well performed for crew scheduling, better solutions are found for all the testing problems. Moreover, the algorithm works fast, has achieved results close to the lower bounds obtained by a standard linear programming solver in terms of the number of shifts, and has much potential for future developments.

English

  The Silene species are annual, biennial or perennial herbs mainly distributed in the northern hemisphere, Europe, Asia and northern Africa. The section, Inflatae Boiss., is the smallest section of the genus containing three species and four subspecies in Iran, out of which one subspecies is endemic with very restricted distribution in the western and northern regions. Studies on seed morphology with scanning electron microscope (SEM) have revealed taxonomically useful micro-characters. The present study was performed to study morphological and micromorphological features in seven Silene species and subspecies in the sect Auriculatae and Inflatae growing in Iran, to study their intraspecific variations and to find out if such data can be used in taxonomy of the genus. The grouping obtained by unweighted pair group method with arithmetic mean (UPGMA) dendrogram separated the species of the section Inflataefrom the species of the section Auriculatae. Siahbishe population of Silene vulgarisdiffered in morphological characters and was placed some distance from the other studied populations. It also had the highest values of total haploid chromosome length (50.51 µM), size of the longest chromosome, (5.42 µM), size of the shortest chromosome (2.88 µM) and the mean chromosome length (4.21 µM). Therefore morphological differences of this population may be related to its higher total chromosome length (genome size), compared to those of other populations studied. We also suggested that the Siahbishe population to be considered as a new variety ofS. vulgaris, based on both morphological and cytological grounds. The seed type in both section are symmetrical reniform, asymmetric reniform and rounded-reniform. In the sect. Auriculate, the length of seed ranged from 1.22 to 2.23 mm, while the size of seed width ranged from 0.86 to 1.38 mm. In the sect. Inflatae, the length of seed ranged from 1.30 to 1.86 mm and the seed width ranged from 0.80 to 1.42 mm. These two sections differed in some other seed characteristics which are discussed.   Key words: Morphometry, taxonomy, seed characteristics, Silene.

Homoeologous relationship of rye chromosome arms as detected with wheat PLUG markers

Based on the similarity in gene structure between rice and wheat, the polymerase chain reaction (PCR)-based landmark unique gene (PLUG) system enabled us to design primer sets that amplify wheat genic sequences including introns. From the previously reported wheat PLUG markers, we chose 144 markers that are distributed on different chromosomes and in known chromosomal regions (bins) to obtain rye-specific PCR-based markers. We conducted PCR with the 144 primer sets and the template of the Imperial rye genomic DNA and found that 131 (91.0%) primer sets successfully amplified PCR products. Of the 131 PLUG markers, 110 (76.4%) markers showed rye-specific PCR amplification with or without restriction enzyme digestion. We assigned 79 of the 110 markers to seven rye chromosomes (1R to 7R) using seven wheat-rye (cv. Imperial) chromosome addition and substitution lines: 12 to 1R, 8 to 2R, 11 to 3R, 8 to 4R, 16 to 5R, 12 to 6R, and 12 to 7R. Furthermore, we located their positions on the short or long (L) chromosome arm, using 13 Imperial rye telosomic lines of common wheat (except for 3RL). Referring to the chromosome bin locations of the 79 PLUG markers in wheat, we deduced the syntenic relationships between rye and wheat chromosomes. We also discussed chromosomal rearrangements in the rye genome with reference to the cytologically visible chromosomal gaps.

Genetic Algorithm Tuned Fuzzy Logic Controller for Rotary Inverted Pendulum

In this study, a Genetic Algorithm (GA) is proposed to search for the optimal input membership functions of the fuzzy logic controller. With the optimal membership function, the fuzzy logic controller can efficiently control a rotary inverted pendulum. The advantage of the proposed method is tuning the parameters of membership functions automatically rather than tuning them manually. In genetic algorithm, these parameters are converted to a chromosome which is encoded into a binary string. Because the membership functions are symmetric to zero, the length of each chromosome could be reduced by half. The computation time will also be shorter with the shorter chromosomes. Moreover, the roulette wheel selection is chosen as reproduction operator and one-point crossover operator and random mutation operator are also used. After the genetic algorithm completes searching for optimal parameters, the optimal membership function will be introduced to the fuzzy logic controller. Finally, simulation results show that the proposed GA-tuned fuzzy logic controller is effective for the rotary inverted pendulum control system with robust stabilization capability.

Characterization of a 5HS-7DS.7DL wheat-barley translocation line and physical mapping of the 7D chromosome using SSR markers

A spontaneous wheat-barley translocation line was previously detected in the progenies of the Mv9kr1 × 'Igri' wheat-barley hybrid and the translocation was identified as 5HS-7DS.7DL. Multicolor genomic in situ hybridization (mcGISH) with D and H genomic DNA probes and three-color fluorescence in situ hybridization (FISH) with repetitive DNA probes (Afa-family, pSc119.2, and pTa71) were performed to characterize the rearranged chromosome. The effect of 5HS and the deleted 7DS fragment on the morphological traits (plant height, fertility, yield, and spike characteristics) of wheat was assessed. Despite the non-compensating nature of the translocation, the plants showed good viability. The aim of the study was to physically localize SSR markers to the telomeric and subtelomeric regions of the 7DS chromosome arm. Of the 45 microsatellite markers analyzed, ten (Xbarc0184, Xwmc0506, Xgdm0130, Xgwm0735, Xgwm1258, Xgwm1123, Xgwm1250, Xgwm1055, Xgwm1220, and Xgwm0635) failed to amplify any 7DS-specific fragments, signaling the elimination of a short chromosome segment in the telomeric region. The breakpoint of the 5HS-7DS.7DL translocation appeared to be more distal than that of reported deletion lines, which provides a new physical landmark for future deletion mapping studies.

Abstract 4857: Short overall telomere length and chromosome 17p-specific telomere length in peripheral blood leukocytes are associated with increased risk of esophageal adenocarcinoma.

Abstract Esophageal adenocarcinoma (EAC) is a deadly cancer. The incidence of EAC has increased dramatically in the United States in the past three decades. The biological mechanisms of EAC development are not fully understood. Telomeres are specialized chromatin structures essential for the maintenance of chromosomal integrity. Telomere shortening in somatic tissues has been shown as an early event during carcinogenesis. Previous studies also suggested that constitutive short telomeres in peripheral blood leukocytes (PBLs) are associated with increased risks of several cancers, including esophageal cancer. In this study, we measured overall telomere length in PBLs using real-time PCR in a large case control study of 805 EAC cases and 805 age and gender-matched controls. Furthermore, we developed a fluorescence in site hybridization (FISH) based method to evaluate several chromosome-specific telomere length with the risk of EAC in a subset of subjects. The mean overall telomere length in cases was significantly shorter than that in controls (p<0.001). Dichotomized at the median telomere length in controls, individuals with short PBL telomere length was associated with a 1.53-fold (95% CI, 1.26-1.87) increased risk of EAC. There was a significant dose-effect in quartile analysis: Individuals in quartile with the shortest telomeres showed a nearly 2-fold (95%CI: 1.47-2.57) elevated EAC risk compared to the reference group of the longest quartile of telomere length. In chromosome-specific telomere length analysis, we found that short chromosome 17p-specific telomere length (defined as the ratio of chromosome 17p-specific telomere length to overall telomere length), but not 2p- and 7q-specific telomere length, was associated with a significantly increased risk of EAC (OR=2.02, 95% CI, 1.00-4.08). This study validates that short overall telomere length in PBLs predisposes to EAC with a much larger sample size and supports the role of chromosome 17p aberrations in EAC development. Citation Format: Meng Chen, Jian Gu, Yilei Gong, Jaffer A. Ajani, Xifeng Wu. Short overall telomere length and chromosome 17p-specific telomere length in peripheral blood leukocytes are associated with increased risk of esophageal adenocarcinoma. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4857. doi:10.1158/1538-7445.AM2013-4857

Short telomeres and chromosome instability prior to histologic malignant progression and cytogenetic aneuploidy in papillary urothelial neoplasms

PurposeEvaluation of the relationships existing among 3 histologic types of urothelial tumors, chromosomal instability, and telomere length. Patients and methodsWe examined 37 consecutive cases of papillary urothelial neoplasm, from which 26 (70.3%) were suitable for karyotype analysis, comprising 7 papillary urothelial neoplasms of low malignant potential (PUNLMPs), 10 low-grade papillary urothelial carcinomas (PUCs), and 9 high-grade PUCs. We performed karyotype and anaphase bridge analyses, and measured telomere lengths by quantitative fluorescence in situ hybridization. ResultsPUNLMPs were always diploid and had anaphase bridges. Low-grade PUCs showed diploidy (n = 2), hypoploidy (n = 4) and polyploidy (n = 4), and high-grade PUCs showed diploidy (n = 1) and polyploidy (n = 8); both had anaphase bridges. The incidence of anaphase bridges did not differ significantly between PUNLMPs and high-grade PUCs (P = 0.105). The telomere lengths of PUNLMP, low-grade PUC, and high-grade PUC, expressed as mean telomere fluorescence units (TFU)±SD, were 7906±3197, 4893±1567, and 3299±1406, respectively. The differences among the 3 groups were significant. However, 42.9% of the PUNLMPs had shorter telomeres than the mean value for low-grade PUCs, and 30.0% of the low-grade PUCs had shorter telomeres than those for high-grade PUCs. There was an inverse correlation between telomere length and the incidence of anaphase bridges. ConclusionsPUNLMP appears to progress to low-grade PUC and high-grade PUC in association with telomere shortening and chromosomal instability. Our data suggest that critically shortened telomeres cause chromosomal instability during progression of papillary urothelial neoplasms.

Chromosome Connections: Compelling Clues to Common Ancestry

Students compare banding patterns on hominid chromosomes and see striking evidence of their common ancestry. To test this, human chromosome no. 2 is matched with two shorter chimpanzee chromosomes, leading to the hypothesis that human chromosome 2 resulted from the fusion of the two shorter chromosomes. Students test that hypothesis by looking for (and finding) DNA evidence of telomere segments at the fusion site, thus reinforcing the likelihood of our common ancestry with chimps and showing that we all carry the molecular fossils of telomere fusion! Students see how multiple lines of evidence make a compelling case for common ancestry.

Visualization of the transmission of direct genomic values for paternal and maternal chromosomes for 15 traits in US Brown Swiss, Holstein, and Jersey cattle

Haplotypes are available for 220,671 Brown Swiss, Holstein, and Jersey bulls and cows that received genomic evaluations in August 2012. Differences in least squares means of direct genomic values (DGV) for paternal and maternal haplotypes of Bos taurus autosomes 1, 6, 14, and 18 for lifetime net merit were significant in all but one case. Those chromosomes were chosen to represent cases with and without known quantitative trait loci, and other chromosomes may differ as well. Paternal haplotypes had higher DGV than maternal haplotypes in most cases, and differences were larger when quantitative trait loci were present. Longer chromosomes generally accounted for more variance than shorter chromosomes, and differences among breeds were consistent with known mutations of large effect. For example, Bos taurus autosome 18 accounted for 2.5, 7, and 2.6% of the variance in lifetime net merit for Brown Swiss (BS), Holsteins, and Jerseys, respectively. Distributions of the number of positive DGV inherited from sires and dams were negatively skewed in all breeds, and modes were slightly higher for paternally than maternally derived haplotypes in Holsteins and BS (22 vs. 20 and 22 vs. 21, respectively) and slightly lower in BS (17 vs. 19). Graphical representations of DGV are available to all users through a query on the Animal Improvement Programs Laboratory (ARS, USDA, Beltsville, MD) web site. Query results were also used to illustrate several quantitative genetic principles using genotype information from real animals. For example, offspring DGV can be compared with parental DGV to demonstrate that a parent transmits the average value of its 2 chromosomes to its progeny. The frequency of DGV with positive and negative values in animals of different ages can be used to show how selection affects allele frequencies. The effect of selection for alleles with large effects versus those with small effects is demonstrated using an animal with undesirable alleles for a marker with a large effect but many desirable alleles for markers with small effects. Strategies for the use of those data in selection programs are being studied, and work is underway to add data on conformation traits to the system.

Chromosome Bandings and Signal Pattern of FISH Using rDNAs in <i>Bellevalia romana</i>

The karyotype of Bellevalia romana L., which is composed of two long metacentric chromosomes (chromosome 1), two short subtelocentric chromosomes (chromosome 2), and four short submetacentric chromosomes (chromosomes 3 and 4), were analyzed by several techniques. C-bands, CMA3 bands, Ag-staining bands, and FISH signals of 18S rDNA appeared at the same sites on the end of an arm of chromosomes 1 and 3. A large FISH signal with 5S rDNA was localized at the end of the long arm of chromosome 2, and a small signal appeared at the interstitial region of the long arm of chromosome 1. When compared with a previous report, there were differences in the CMA3 band on chromosome 2 and a small 5S rDNA signal on chromosome 1.

Genes & cell: Telomeres linked to birds' life span: Short chromosome caps tied to mortality in warblers

Science NewsVolume 182, Issue 13 p. 13-13 In the News Genes & cell: Telomeres linked to birds' life span: Short chromosome caps tied to mortality in warblers Tina Hesman Saey, Tina Hesman SaeySearch for more papers by this author Tina Hesman Saey, Tina Hesman SaeySearch for more papers by this author First published: 21 December 2012 https://doi.org/10.1002/scin.5591821314Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume182, Issue1329 December 2012Pages 13-13 RelatedInformation

Cytogenetic characterization of Taphronota thaelephora Stal. 1873. (Orthoptera: Pyrgomorphidae) from Cameroon. II. Description of mitotic chromosomes

Taphronota thaelephora Stal. 1873 is generating a lot of interest for biological and cytogenetic studies because it has demonstrated the potential for a future veritable pest in Cameroon. The lack of previouslyestablished karyotype for the species has necessitated this study. Testes from five adult individuals collected from Balepa - Mbouda in the West Region of Cameroon and treated with 1% colchicine were analyzed usingthe Lactic-Propionic Orcein squash technique. Mitotic metaphase chromosomes were measured directly from the microscope and pictures taken with the help of the Lietz photomicroscope. Pictures were processed with the Microsoft Office Picture Manager. The species revealed the standard Pyrgomorphidae karyotype of 2n‰= 19 acrocentric chromosomes. Mean length of the chromosomes ranged from 8.10}1.7 to 3.75}0.0 ƒÊm. Analysis of Relative Chromosome Lengths (RCL) revealed three distinct size groups of long, medium and short. The karyotype of T. thaelephora was made up of 2 pairs of long chromosomes (2LL) and the X-chromosome, 6 pairs of medium chromosomes (6MM) and 1 pair of short chromosomes (1SS). The mean lengths of the long, medium and short sized chromosomes were 7.2 ƒÊm, 4.8 ƒÊm and 3.51 ƒÊm respectively. The X-chromosome was the shortest of the large chromosomes with a mean length of 6.75 ƒÊm.

Population diversity and analysis of cytogenetic affinities between different Silybum marianum L. populations from Iran

Cytogenetic diversity on ten different Silybum marianum populations was evaluated in this study by using karyotype decomposition technique. The obtained results from karyologic studies of root tip samples showed that the base number of chromosomes was x = 17 in all the considered populations and the number of chromosomes were 2n = 2x = 34. Regarding the ploidy level, all the populations were diploid. According to Stebbin’s classification of karytype symmetry, all the populations were placed in “2B” category, indicating the similar evolutionary situations of the populations. The obtained results from the variance analysis of the resulted data from measuring the characteristics showed that there is a significant difference; as for the probability of 0.1, between the populations, regarding the total chromosome lengths (TL), sum of long arms (Sla), coefficient of variability of centromic index (CVci) and the asymmetric index (AI) and there is a significant difference (p < 0.05) regarding the longest and shortest chromosomes (LC, SC), sum of short arms (SSa), difference in relative lengths (DRL) and the ratio of long to short arms (AR). This indicated the diversity in the size and symmetry of chromosomes among the considered populations. Factor analysis provided three factors that justified nearly 96 % of the total variations between the populations, such that in the first factor, the difference in the relative length and the total chromosome length had the greatest role in creating variations in the populations by having the highest specific vector coefficients. For the 2nd factor, the asymmetric index and variation coefficient of centromic index had a great importance for the variance between the populations. For the 3rd factor, the relative length difference had the most important role in establishing this factor. Cluster analysis with dendrogram sectioning at the distance of 10.59 categorized populations in 4 groups. The least Euclidean distance was observed between the populations in Ahvaz and Sari and the most Euclidean distance was between the populations of Ahvaz and Rasht. The results from cluster variances analyses showed that all the characteristics, apart from DRL had significant diversity between the groups. Regarding the characteristics related to genome length, the populations of Ahvaz, Sari and Esfahan had the highest amounts and Kurdestan population in the 4th group had the highest value regarding AI, CVci and AR characteristics.

Karyotype of potato tuber moth, Phthorimaea operculella (Zeller) – first report from India

In the present study, the karyotype of potato tuber moth, Phthorimaea operculella (Zeller) was studied from Himachal Pradesh, India. The diploid chromosome number (2n) in this moth species was found to be 58. The chromosomes at diplotene stage showed variation in size but at metaphase stage, these appeared almost of similar size. The total bivalent complement length was 63.37 μm ± 0.93 S.E. The longest chromosome was 4.69 μm ± 0.09 S.E. in the length while the shortest chromosome was 1.12 μm ± 0.03 S.E. The percentage relative length of chromosome ranged from 1.77 ± 0.05 S.E. in the shortest chromosome to 7.40 ± 0.19 S.E. in the longest chromosome. This is the first report on the karyotype of this species from India. Meiotic divisions were found clearly in testis preparation. In diplotene stage, 29 bivalents were clearly visible showing high degree of condensation and during metaphase I of male meiosis, these 29 bivalents were maximally condensed. In early anaphase I, the homologues started separating from each other. Two types of spermatozoa, apyrene and eupyene were also observed.

Mechanisms of Telomere Maintenance Dysfunction in B-Chronic Lymphocytic Leukemia Through CpG Island Methylation

AbstractAbstract 3489Telomeres are a repetitive DNA sequences associated with a protein complex named shelterin that protect chromosome ends. Two types of mechanisms maintain telomere in cancer cells. The first involves telomerase an enzyme able to copy the telomeric motif that consists of three principal subunits, including the telomerase reverse transcriptase hTERT. The second, named ALT (Alternative Lengthening of Telomere), corresponds to the recombination between telomeres that involves notably a complex formed by the topoisomerase III alpha (hTopoIIIa), BLM, RMI1 and RMI2. Little is known about the involvement of the ALT mechanism in B-chronic lymphocytic leukemia (B-CLL). In fact this leukemic disease shows low telomerase activity, shelterin defect and telomeric dysfunction.In an effort to characterize ALT cells from 31 B-CLL patients, we analyzed their telomere length and telomerase activity. B-CLL patients showed almost no hTERT transcript (detected in three cases), low telomerase activity (detected in 7 cases) and a telomere average size ranging from 3 to 10 kb. Moreover, a strong deregulation of genes encoding three shelterin proteins, TRF1, TRF2, Pot1, and an at least two fold downregulation of hTopoIIIa gene expression in 21 cases were observed, suggesting the presence of a telomere maintenance dysfunction affecting both mechanisms, telomerase dependent and ALT. CpG island methylation has been mapped for both promoters and if hTERT shows a disseminated methylation profile in 22 patients, for hTopoIIIα we identified nine CpG upstream the minimal promoter, being methylated in 19 of our 31 analyzed patients. We then performed luciferase experiments and we showed that methylation in this 9 CpG induced a strong inhibition of hTopoIIIa transcription. Finally we correlated telomere length and hTopoIIIa methylation status as we observed that 25.4% of the hTopoIIIa promoters were methylated in patients with shorter chromosomes and only 11.1 % were methylated in patients with longer telomeres (p<0.0025).As nearly no telomerase activity have been detected in our patients and as downregulation of hTopoIIIa could increase recombination rate between sister chromatid, methylation of hTERT and hTopoIIIa promoter CpG islands may lead to telomere dysfunction and increased genetic instability in B-CLL. Disclosures:No relevant conflicts of interest to declare.