Duplication Size Research Articles

Posttransplant Liver Mass

Question: A 55-year-old man who was 7 years post liver transplant for alcohol– and hepatitis C–induced cirrhosis with a 10-mm hepatocellular carcinoma (HCC) presented with right upper quadrant discomfort. The patient had a remote history of Epstein–Barr virus (EBV). Three months before presentation, his ultrasound (Figure A) and liver function tests (LFTs) were within normal limits. At presentation the LFTs were: Aspartate aminotransferase, 145 U/L; alanine aminotransferase, 52 U/L; bilirubin total, 24.1 mg/dL; alkaline phosphatase, 149 U/L; alpha fetoprotein, 6.2 ng/mL; and white blood count, 7.4. The liver appeared diffusely heterogeneous on ultrasound with a possible large mass in the right lobe of the liver (Figure B). Computed tomography (CT) was subsequently performed (only noncontrast images were obtained owing to patient's renal insufficiency: Creatinine, 4.64 mg/dL; estimated glomerular filtration rate, 13 mL/min). CT images showed a 15 × 11-cm mass in the right lobe of the liver (Figure C, arrows). The mass was mildly hyperdense compared with the surrounding liver parenchyma, and showed a central area of lower density (Figure C, asterisk). An ultrasound-guided core biopsy of the mass was obtained (Figure D; stain: hematoxylin and eosin). What is the diagnosis? See the Gastroenterology web site (www.gastrojournal.org) for more information on submitting your favorite image to Clinical Challenges and Images in GI. Posttransplant lymphoproliferative disease (PTLD) localized to the liver is a rare entity, with only 83 cases reported in the literature.1Izadi M. Fazel M. Saadat S.H. et al.Hepatic involvement by lymphoproliferative disorders post liver transplantation: PTLD.Survey Hepatol Int. 2011; 5: 759-766Crossref PubMed Scopus (15) Google Scholar The diagnosis is made on pathology by the characteristic cellular pattern: Liver parenchyma completely replaced by round, blue, pleomorphic cells with numerous apoptotic bodies, indicating a high turnover rate (Figure D, E; stain: hematoxylin and eosin), uniformly CD20 positive cells (Figure F), scattered cells expressing CD3 (Figure G), and nearly universal Ki-67 positivity (Figure H), confirming the high proliferative rate. The final pathology diagnosis was unclassified B-cell lymphoma, with features intermediate between diffuse large B-cell lymphoma and Burkitt's lymphoma. The diagnosis could have been suspected at imaging owing to the rapid growth of the mass in 3 months, which would have been very unusual for a HCC, even though HCC duplication size is faster among posttransplant patients.2Addley H.C. Griffin N. Shaw A.S. et al.Accuracy of hepatocellular carcinoma detection on multidetector CT in a transplant liver population with explant liver correlation.Clin Radiol. 2011; 66: 349-356Abstract Full Text Full Text PDF PubMed Scopus (33) Google Scholar PTLD has a high proliferative rate as demonstrated by pathology staining, and its incidence in post liver transplanted patients has been associated with HCV and EBV. Other reported reasons for PTLD include greater levels of immunosuppression and antibody induction therapy, including OKT3, antilymphoblast globulin, and antithymocyte globulin.3Kim R.D. Fujikawa T. Mizuno S. et al.Adult post-transplant lymphoproliferative disease in the liver graft in patients with recurrent hepatitis C.Eur J Gastroenterol Hepatol. 2011; 23: 559-565Crossref PubMed Scopus (4) Google Scholar The patient opted for palliative treatment only and died 1 month later.

The Behavioral Phenotype in MECP2 Duplication Syndrome: A Comparison With Idiopathic Autism

Alterations in the X-linked gene MECP2 encoding the methyl-CpG-binding protein 2 have been linked to autism spectrum disorders (ASDs). Most recently, data suggest that overexpression of MECP2 may be related to ASD. To better characterize the relevance of MECP2 overexpression to ASD-related behaviors, we compared the core symptoms of ASD in MECP2 duplication syndrome to nonverbal mental age-matched boys with idiopathic ASD. Within the MECP2 duplication group, we further delineated aspects of the behavioral phenotype and also examined how duplication size and gene content corresponded to clinical severity. We compared ten males with MECP2 duplication syndrome (ages 3-10) with a chronological and mental age-matched sample of nine nonverbal males with idiopathic ASD. Our results indicate that boys with MECP2 duplication syndrome share the core behavioral features of ASD (e.g. social affect, restricted/repetitive behaviors). Direct comparisons of ASD profiles revealed that a majority of boys with MECP2 duplication syndrome are similar to idiopathic ASD; they have impairments in social affect (albeit to a lesser degree than idiopathic ASD) and similar severity in restricted/repetitive behaviors. Nonverbal mental age did not correlate with severity of social impairment or repetitive behaviors. Within the MECP2 duplication group, breakpoint size does not predict differences in clinical severity. In addition to social withdrawal and stereotyped behaviors, we also found that hyposensitivity to pain/temperature are part of the behavioral phenotype of MECP2 duplication syndrome. Our results illustrate that overexpression/increased dosage of MECP2 is related to core features of ASD.

Organelle Growth Control through Limiting Pools of Cytoplasmic Components

The critical importance of controlling the size and number of intracellular organelles has led to a variety of mechanisms for regulating the formation and growth of cellular structures. In this review, we explore a class of mechanisms for organelle growth control that rely primarily on the cytoplasm as a 'limiting pool' of available material. These mechanisms are based on the idea that, as organelles grow, they incorporate subunits from the cytoplasm. If this subunit pool is limited, organelle growth will lead to depletion of subunits from the cytoplasm. Free subunit concentration therefore provides a measure of the number of incorporated subunits and thus the current size of the organelle. Because organelle growth rates are typically a function of subunit concentration, cytoplasmic depletion links organelle size, free subunit concentration, and growth rates, ensuring that as the organelle grows, its rate of growth slows. Thus, a limiting cytoplasmic pool provides a powerful mechanism for size-dependent regulation of growth without recourse to active mechanisms to measure size or modulate growth rates. Variations of this general idea allow not only for size control, but also cell-size-dependent scaling of cellular structures, coordination of growth between similar structures within a cell, and the enforcement of singularity in structure formation, when only a single copy of a structure is desired. Here, we review several examples of such mechanisms in cellular processes as diverse as centriole duplication, centrosome and nuclear size control, cell polarity, and growth of flagella.

12p13 rearrangements: 6 Mb deletion responsible for ID/MCA and reciprocal duplication without clinical responsibility

Congenital balanced reciprocal translocations are one of the most frequent structural chromosomal aberrations in the population. We report a familial translocation t(12;22)(p13.3;pter) responsible for intellectual disabilities and congenital anomalies characterized by FISH and array CGH. Two patients carried a der(12)t(12;22)(p13.3;pter), resulting in a 6 Mb 12pter deletion. Patients presented with intellectual disabilities, pre- and post-natal growth retardation, ponderal development delay, global hypotonia, feeding problems and dysmorphic features. Two relatives presented with the reciprocal 12pter duplication, which had no clinical manifestations associated. For this translocation, we propose a mechanism based on a non-allelic recombination model, in which recombination of direct oriented segmental duplications between non-homologous chromatids leads to the reciprocal translocation. The characterization of this translocation has been critical for the family. Translocation carriers have a risk of 40% of having offspring carrying unbalanced products. 12p13.3 deletion carriers present with a recognizable syndrome and on the contrary, 12p13.3 duplication carriers present without clinical manifestations. Other published cases of 12p13.3 duplication show that this syndrome has a variable phenotype. It is advisable to delineate the duplication size and to discard other genetic aberrations, in order to give an accurate genetic counseling in patients carrying 12pter duplications.

A case of partial trisomy 3p syndrome with rare clinical manifestations

Partial trisomy 3p results from either unbalanced translocation or de novo duplication. Common clinical features consist of dysmorphic facial features, congenital heart defects, psychomotor and mental retardation, abnormal muscle tone, and hypoplastic genitalia. In this paper, we report a case of partial trisomy 3p with rare clinical manifestations. A full-term, female newborn was transferred to our clinic. She had cleft lip-plate, dysgenesis of the corpus callosum, patent ductus arteriosus, pulmonary hypertension, and severe right-sided hydronephrosis, associated with ureteropelvic junction obstruction. Cytogenetic investigation revealed partial trisomy 3p; 46,XX,der(4)t(3;4) (p21.1;p16). The karyotype of her father showed a balanced translocation, t(3;4)(p21.1;p16). Therefore, the size of duplication can be an important factor.

Flood relief solutions in metropolitan cities the Hong Kong experience theme: planning for sustainable water solutions oral presentation

In the older urban areas of Hong Kong, the stormwater drainage systems were built decades ago with older protection standards and became inadequate due to aging of the systems and expansion of the built-up urban areas. Although the Hong Kong Special Administrative Region Government (HKSARG) has been making improvements to the drainage systems to cater for the developments, some parts of the city are still susceptible to flooding during heavy rainstorms when coincided with high tide. To relieve the flooding problems in well–developed urban areas, HKSARG adopted floodwater reception approach to overcome the limitations of conventional approach like expansion or enhancement of existing drainage systems, through increasing the size of drains or duplications. This paper presents the background and planning of the floodwater reception schemes in the urban areas of Hong Kong and the challenges to deliver such an innovative, sustainable, efficient and integrated engineering solution for the city.

Agrobacterium-Mediated Virus-Induced Gene Silencing Assay In Cotton

Cotton (Gossypium hirsutum) is one of the most important crops worldwide. Considerable efforts have been made on molecular breeding of new varieties. The large-scale gene functional analysis in cotton has been lagged behind most of the modern plant species, likely due to its large size of genome, gene duplication and polyploidy, long growth cycle and recalcitrance to genetic transformation(1). To facilitate high throughput functional genetic/genomic study in cotton, we attempt to develop rapid and efficient transient assays to assess cotton gene functions. Virus-Induced Gene Silencing (VIGS) is a powerful technique that was developed based on the host Post-Transcriptional Gene Silencing (PTGS) to repress viral proliferation(2,3). Agrobacterium-mediated VIGS has been successfully applied in a wide range of dicots species such as Solanaceae, Arabidopsis and legume species, and monocots species including barley, wheat and maize, for various functional genomic studies(3,4). As this rapid and efficient approach avoids plant transformation and overcomes functional redundancy, it is particularly attractive and suitable for functional genomic study in crop species like cotton not amenable for transformation. In this study, we report the detailed protocol of Agrobacterium-mediated VIGS system in cotton. Among the several viral VIGS vectors, the tobacco rattle virus (TRV) invades a wide range of hosts and is able to spread vigorously throughout the entire plant yet produce mild symptoms on the hosts5. To monitor the silencing efficiency, GrCLA1, a homolog gene of Arabidopsis Cloroplastos alterados 1 gene (AtCLA1) in cotton, has been cloned and inserted into the VIGS binary vector pYL156. CLA1 gene is involved in chloroplast development(6), and previous studies have shown that loss-of-function of AtCLA1 resulted in an albino phenotype on true leaves(7), providing an excellent visual marker for silencing efficiency. At approximately two weeks post Agrobacterium infiltration, the albino phenotype started to appear on the true leaves, with 100% silencing efficiency in all replicated experiments. The silencing of endogenous gene expression was also confirmed by RT-PCR analysis. Significantly, silencing could potently occur in all the cultivars we tested, including various commercially grown varieties in Texas. This rapid and efficient Agrobacterium-mediated VIGS assay provides a very powerful tool for rapid large-scale analysis of gene functions at genome-wide level in cotton.

Evidence for disease penetrance relating to CNV size: Pelizaeus–Merzbacher disease and manifesting carriers with a familial 11 Mb duplication at Xq22

The potential causes for the incomplete penetrance of Pelizaeus-Merzbacher disease (PMD) in female carriers of PLP1 mutations are not well understood. We present a family with a boy having PMD in association with PLP1 duplication and three females who are apparent manifesting carriers. Custom high-resolution oligonucleotide array comparative genomic hybridization (aCGH) and breakpoint junction sequencing were performed and revealed a familial complex duplication consisting of a small duplicated genomic interval (∼56 kb) and a large segmental duplication (∼11 Mb) that resulted in a PLP1 copy number variation gain. Breakpoint junction analysis implicates a replication-based mechanism underlying the rearrangement formation. X-inactivation studies (XCI) showed a random to moderate advantageous skewing pattern in peripheral blood cells but a moderate to extremely skewed (≥90%) pattern in buccal cells. In conclusion, our data show that complex duplications involving PLP1 are not uncommon, can be detected at the level of genome resolution afforded by clinical aCGH and duplication and inversion can be produced in the same event. Furthermore, the observation of three manifesting carriers with a large genomic rearrangement supports the contention that duplication size along with genomic content can be an important factor for penetrance of the PMD phenotype in females.

Array‐CGH study of partial trisomy 9p without mental retardation

Partial trisomy 9p is one of the most common detected autosomal structural anomalies, so the phenotype-genotype correlation of this rearrangement has been well described. Despite variation in size of the 9p duplications, trisomy 9p syndrome is characterized by typical dysmorphic features and a variable but constant psychomotor and mental retardation. Previously reported phenotype genotype correlation studies proposed that the critical region for phenotype is located in 9p22. We report here on a new patient with partial trisomy 9p13.3→9pter in an 8-year-old boy with typical trisomy 9p dysmorphic features but a normal mental development. Cytogenetics investigations showed that our patient karyotype was 47,XY,+ der(22)t(9;22)(p13.q11) inherited by a 3:1 disjunction of a maternal reciprocal translocation t(9;22)(p13.q11). FISH and array CGH analysis were used to better characterize duplicated chromosomal regions and showed a large duplication of chromosome 9p13.3→9pter associated to microduplication in 22q11.1. The size of the duplications in chromosomes 9p and 22q were estimated about 33.9 and 2.67 Mb, respectively. The comparison between this case and those reported in the literature allows us to support that all syndromes show variability and that not all partial trisomies 9p are associated with intellectual disability.

Further refinement of the critical minimal genetic region for the imprinting disorder 6q24 transient neonatal diabetes

Transient neonatal diabetes (TND) is associated with overexpression of genes within a critical region on 6q24. This study aims to refine the boundaries of this region to reduce the number of potential candidate genes for 6q24 TND. Fifteen patients with transient neonatal diabetes and submicroscopic chromosome 6 duplications were investigated. The duplications were confirmed by microsatellite analysis and subsequently mapped using tiled chromosome 6 array Comparative Genomic Hybridisation (aCGH) and MLPA. Duplication boundaries were compared to identify the minimal shared region of duplication. These data were then used with available clinical data to identify associations between size of 6q24 duplication and severity of TND phenotype. Alignment of the minimal region of duplication to the human genome reduced the minimal TND critical region, formerly estimated at 440kb, to 160-173kb, revealing PLAGL1 (pleiomorphic adenoma gene-like 1) and HYMAI (imprinted in hydatidiform mole) to be the only genes wholly included therein. Additionally, the complete paternal duplication of a region containing the theoretical protein FAM164B was associated with the severe growth restriction observed in 6q24 duplication patients. This study has significantly reduced the critical region associated with 6q24 TND. It has eliminated several previous TND candidate genes, leaving the overlapping imprinted genes PLAGL1 and HYMAI as the only remaining complete candidate genes for 6q24 TND. Moreover, these data provide the first evidence that an additional region, encompassing the theoretical protein FAM164B, may have a critical role in the growth restriction phenotype observed in many 6q24 TND patients.

Organ-specific enhancement of metastasis by spontaneous ploidy duplication and cell size enlargement

Aneuploidy is commonly observed in breast cancer and is associated with poor prognosis. One frequent type of aneuploidy, hypertetraploidy, may derive from ploidy duplication of hyperdiploid cells. However, the pathological consequences of ploidy duplication in breast cancer progression have not been characterized. Here, we present an experimental system demonstrating spontaneous appearance of hypertetraploid cells from organ-specific metastatic variants of the MDA-MB-231 breast cancer cell line through ploidy duplication in vitro and in vivo. The hypertetraploid progenies showed increased metastatic potential to lung and brain, but not to bone, which may be partially explained by the distinct capillary structures in these organs that confer differential lodging advantages to tumor cells with enlarged size. Our results suggest a potential mechanistic link between ploidy duplication and enhancement of metastatic potentials, as was observed in previous clinical studies of breast cancer.

Structures and molecular mechanisms for common 15q13.3 microduplications involving CHRNA7: benign or pathological?

We have investigated four approximately 1.6-Mb microduplications and 55 smaller 350-680-kb microduplications at 15q13.2-q13.3 involving the CHRNA7 gene that were detected by clinical microarray analysis. Applying high-resolution array-CGH, we mapped all 118 chromosomal breakpoints of these microduplications. We also sequenced 26 small microduplication breakpoints that were clustering at hotspots of nonallelic homologous recombination (NAHR). All four large microduplications likely arose by NAHR between BP4 and BP5 LCRs, and 54 small microduplications arose by NAHR between two CHRNA7-LCR copies. We identified two classes of approximately 1.6-Mb microduplications and five classes of small microduplications differing in duplication size, and show that they duplicate the entire CHRNA7. We propose that size differences among small microduplications result from preexisting heterogeneity of the common BP4-BP5 inversion. Clinical data and family histories of 11 patients with small microduplications involving CHRNA7 suggest that these microduplications might be associated with developmental delay/mental retardation, muscular hypotonia, and a variety of neuropsychiatric disorders. However, we conclude that these microduplications and their associated potential for increased dosage of the CHRNA7-encoded alpha 7 subunit of nicotinic acetylcholine receptors are of uncertain clinical significance at present. Nevertheless, if they prove to have a pathological effects, their high frequency could make them a common risk factor for many neurobehavioral disorders.

Gastrointestinal duplications: Experience in seven children and a review of the literature

Background/Aim:Enteric duplication (ED) is a rare congenital anomaly that can occur anywhere along the alimentary tract from the mouth, down to the anus and the nearby organs. This uncommon anomaly may be asymptomatic or presents with vague symptoms mimicking other common pathologies. We aim to present our experience, management challenges and patterns of ED with a review of the literature.Settings and Design:The study was carried out at a Nigerian Tertiary Hospital (2005–2008 inclusive).Materials and Methods:We retrospectively analyzed seven patients with ED managed in our hospital for sex, age, clinical presentations, duplication size and site, presence of ectopic tissue, complications, associated anomalies, radiological workups, and prognosis. Data was analyzed using SPSS 11.0 for window.Results:Seven children between the age range of 44 hours–10 years had ED, one sublingual and six intraabdominal duplications. Midgut volvulus with long segment bowel gangrene complicated two cases. The diagnosis was incidental in all. Three cases were diagnosed following conventional radiological contrast examination and the rest at surgery. Ultrasound was not helpful in making diagnosis in all the six intraabdominal duplications. Though surgery was recommended for all, one of the patients declined. Only one patient had unsuccessful surgery.Conclusions:ED requires high index of clinical suspicion and careful management. Many cases of nonspecific abdominal pains should be properly evaluated before patients suffer avoidable complications.

Autism and other neuropsychiatric symptoms are prevalent in individuals with MeCP2 duplication syndrome.

There have been no objective assessments to determine whether boys with MECP2 duplication have autism or whether female carriers manifest phenotypes. This study characterizes the clinical and neuropsychiatric phenotypes of affected boys and carrier females. Eight families (9 males and 9 females) with MECP2 duplication participated. A detailed history, physical examination, electroencephalogram, developmental evaluation, Autism Diagnostic Observation Schedule, and Autism Diagnostic Interview-Revised were performed for each boy. Carrier females completed the Symptom Checklist-90-R, Wechsler Abbreviated Scale of Intelligence, Broad Autism Phenotype Questionnaire, and detailed medical and mental health histories. Size and gene content of each duplication were determined by array comparative genome hybridization. X-chromosome inactivation patterns were analyzed using leukocyte DNA. MECP2 and IRAK1 RNA levels were quantified from lymphoblast cell lines, and western blots were performed to assess MeCP2 protein levels. All of the boys demonstrated mental retardation and autism. Poor expressive language, gaze avoidance, repetitive behaviors, anxiety, and atypical socialization were prevalent. Female carriers had psychiatric symptoms, including generalized anxiety, depression, and compulsions that preceded the birth of their children. The majority exhibited features of the broad autism phenotype and had higher nonverbal compared to verbal reasoning skills. Autism is a defining feature of the MECP2 duplication syndrome in boys. Females manifest phenotypes despite 100% skewing of X-inactivation and normal MECP2 RNA levels in peripheral blood. Analysis of the duplication size, MECP2 and IRAK1 RNA levels, and MeCP2 protein levels revealed that most of the traits in affected boys are likely due to the genomic region spanning of MECP2 and IRAK1. The phenotypes observed in carrier females may be secondary to tissue-specific dosage alterations and require further study. Ann Neurol 2009;66:771-782.

Inferring the Evolutionary History of Gene Clusters from Phylogenetic and Gene Order Data

Gene duplication is frequent within gene clusters and plays a fundamental role in evolution by providing a source of new genetic material upon which natural selection can act. Although classical phylogenetic inference methods provide some insight into the evolutionary history of a gene cluster, they are not sufficient alone to differentiate single- from multiple gene duplication events and to answer other questions regarding the nature and size of evolutionary events. In this paper, we present an algorithm allowing to infer a set of optimal evolutionary histories for a gene cluster in a single species, according to a general cost model involving variable length duplications (in tandem or inverted), deletions, and inversions. We applied our algorithm to the human olfactory receptor and protocadherin gene clusters, showing that the duplication size distribution differs significantly between the two gene families. The algorithm is available through a web interface at http://www-lbit.iro.umontreal.ca/DILTAG/.

Complex Segmental Duplications Mediate a Recurrent dup(X)(p11.22-p11.23) Associated with Mental Retardation, Speech Delay, and EEG Anomalies in Males and Females

Submicroscopic copy-number variations make a considerable contribution to the genetic etiology of human disease. We have analyzed subjects with idiopathic mental retardation (MR) by using whole-genome oligonucleotide-based array comparative genomic hybridization (aCGH) and identified familial and de novo recurrent Xp11.22-p11.23 duplications in males and females with MR, speech delay, and a peculiar electroencephalographic (EEG) pattern in childhood. The size of the duplications ranges from 0.8-9.2 Mb. Most affected females show preferential activation of the duplicated X chromosome. Carriers of the smallest duplication show X-linked recessive inheritance. All other affected individuals present dominant expression and comparable clinical phenotypes irrespective of sex, duplication size, and X-inactivation pattern. The majority of the rearrangements are mediated by recombination between flanking complex segmental duplications. The identification of common clinical features, including the typical EEG pattern, predisposing genomic structure, and peculiar X-inactivation pattern, suggests that duplication of Xp11.22-p11.23 constitutes a previously undescribed syndrome.

Distal limb deficiencies, micrognathia syndrome, and syndromic forms of split hand foot malformation (SHFM) are caused by chromosome 10q genomic rearrangements

BackgroundThe 10q24 chromosomal region has previously been implicated in split hand foot malformation (SHFM). SHFM3 was mapped to a large interval on chromosome 10q. The corresponding dactylaplasia mouse model was...

Comprehensive genetic analyses of PLP1 in patients with Pelizaeus–Merzbacher disease applied by array-CGH and fiber-FISH analyses identified new mutations and variable sizes of duplications

Pelizaeus–Merzbacher disease (PMD; MIM#312080) is a rare X-linked recessive neurodegenerative disorder. The main cause of PMD is alterations in the proteolipid protein 1 gene ( PLP1) on chromosome Xq22.2. Duplications and point mutations of PLP1 have been found in 70% and 10–25% of all patients with PMD, respectively, with a wide clinical spectrum. Since the underlining genomic abnormalities are heterogeneous in patients with PMD, clarification of the genotype-phenotype correlation is the object of this study. Comprehensive genetic analyses using microarray-based comparative genomic hybridization (aCGH) analysis and genomic sequencing were applied to fifteen unrelated male patients with a clinical diagnosis of PMD. Duplicated regions were further analyzed by fiber-fluorescence in situ hybridization (FISH) analysis. Four novel and one known nucleotide alterations were identified in five patients. Five microduplications including PLP1 were identified by aCGH analysis with the sizes ranging from 374 to 951-kb. The directions of five PLP1 duplications were further investigated by fiber-FISH analysis, and all showed tandem duplications. The common manifestations of the disease in patients with PLP1 mutations or duplications in this study were nystagmus in early infancy, dysmyelination revealed by magnetic resonance imaging (MRI), and auditory brain response abnormalities. Although the grades of dysmyelination estimated by MRI findings were well correlated to the clinical phenotypes of the patients, there is no correlation between the size of the duplications and the phenotypic severity.

Optimization of the composition of crop collections for ex situ conservation

Many crop genetic resources collections have been established without a clearly defined conservation goal or mandate, which has resulted in collections of considerable size, unbalanced composition and high levels of duplication. Attempts to improve the composition of collections are hampered by the fact that conceptual views to optimize collection composition are very rare. An optimization strategy is proposed herein, which largely builds on the concepts of core collection and core selection. The proposed strategy relies on hierarchically structuring the crop gene pool and assigning a relative importance to each of its different components. Comparison of the resulting optimized distribution of the number of accessions with the actual distribution allows identification of under- and over-representation within a collection. Application of this strategy is illustrated by an example using potato. The proposed optimization strategy is applicable not only to individual genebanks, but also to consortia of cooperating genebanks, which makes it relevant for ongoing activities within projects that aim at sharing responsibilities among institutions on the basis of rational conservation, such as a European genebank integrated system and the global cacao genetic resources network CacaoNet.

Nucleophosmin ( NPM1) Mutations in Acute Myeloid Leukemia: An Ongoing (Cytoplasmic) Tale of Dueling Mutations and Duality of Molecular Genetic Testing Methodologies

This Commentary highlights two articles that focus on molecular techniques to identify mutations in nucleophosmin (NPM1), which is the most frequently mutated gene in cytogenetically normal acute myeloid leukemia (CN-AML)