Search

Seed development is an essential phenomenon for all sexual propagative plant species. The functional allele at SEED DEVELOPMENT 1 (SDVI) or SEED DEVELOPMENT2 (SDV2) loci is essential for seed development for Oryza sativa and Oryza meridionalis. In the present study, we performed fine mapping of SDV1, narrowing down the area of interest to 333kb on chromosome 6. Haplotype analysis around the SDV1 locus of O. meridionalis accessions indicated that they shared the DNA polymorphism, suggesting that they have a common abortive allele at the SDV1 locus. Linkage analysis of the candidate SDV2 gene showed that it was located on chromosome 4. The candidate SDV2 was confirmed using a population in which both the SDV1 and SDV2 genes were segregating. The chromosomal region covering the SDV1 gene was predicted to contain 30 protein-coding genes in O. sativa. Five of these genes have conserved DNA sequences in the chromosomal region of the SDV2 gene on chromosome 4, and not on chromosome 6, of O. meridionalis. These results suggest that these five genes could be candidates for SDVI, and that their orthologous genes located on chromosome 4 of O. meridionalis could be candidates for SDV2. [ABSTRACT FROM AUTHOR]

Physalis peruviana L. (physalis) has significant economic potential by virtue of the unique flavor of its fruit. However, the productivity of Brazilian plantations is low because of the limited number of varieties or cultivars available. The main obstacle in the selection of superior genotypes is the lack of information about genetic variability within- and between- populations and limited genetic basis that has likely resulted from evolutionary, domestication and selection processes of the natural or artificial populations. Physalis currently cultivated in Brazil is tetraploid, and such polyploidy may have led to the reproductive isolation of the species, preventing the occurrence of intraspecific hybridization. Moreover, cultivated populations derive from a common gene pool and have undergone a long process of domestication and selection carried out empirically by farmers. In Colombia and other Andean countries there are wild populations that exhibit genetic diversity which; although, fundamental for the conservation of the species, have low potential for the development of genotypes with superior agronomic traits. In order to create and expand the genetic variability of physalis, breeders have employed various strategies including induction of mutation, chromosome duplication, and interspecific and intraspecific hybridization. Furthermore, the production of double haploid lines from in vitro anther cultures has shown good results in the selection of hybrids. The mutant genotypes and/or hybrids obtained using these methods in association with those of wide genomic selection can generate cultivars with superior agronomic traits. [ABSTRACT FROM AUTHOR]

Copyright of Revista Caatinga is the property of Revista Caatinga and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: The occurrence of colorectal cancer (CRC) is increasing among young adults, but the etiology is still largely unknown. In addition to germline monogenetic variants also polygenic risk scores (PRS) have been proven to correctly estimate the risk of CRC., Case Description: We present a 24-year-old male with disseminated colon cancer who carried a germline duplication on chromosome 1 spanning 200 kb and covering CD101, TTF2, MIR942, TRIM45, and parts of PTGFRN and VTCN1 . The duplication was located in tandem. A similar duplication was previously reported in a family with CRC among two brothers aged 52 and 61 years old at diagnosis. Particularly, MIR942 was an interesting finding as it is involved in the regulation of the Wnt signaling pathway. Disruption of the Wnt pathway is known to cause CRC. However, in our case the duplication did not segregate with disease in the family. Calculation of a PRS in our patient found an average PRS for CRC., Conclusions: Our findings do not support that this duplication is a monogenetic cause of CRC, nor did a PRS point towards an increased risk in this 24-year-old male. Whether the duplication is a risk factor in combination with other genetic and non-genetic risk factors requires further studies., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jgo.amegroups.com/article/view/10.21037/jgo-24-148/coif). K.W. reports a speaking engagement at Seagen Denmark ApS for which she received payment. The other authors have no conflicts of interest to declare., (2024 AME Publishing Company. All rights reserved.)

We describe a sporadic case of a pure, tandem, interstitial chromosome 4q duplication, arr[hg19] 4q28.1q32.3 (127,008,069-165,250,477) x3 in a boy born at 36 weeks of gestation. He presented with microcephaly (head circumference

We describe a sporadic case of a pure, tandem, interstitial chromosome 4q duplication, arr[hg19] 4q28.1q32.3 (127,008,069-165,250,477) x3 in a boy born at 36 weeks of gestation. He presented with microcephaly (head circumference <1st percentile), short stature (height <2nd percentile) and poor weight gain (weight <3rd percentile). Hypospadias and horseshoe shaped kidneys were also revealed following a urinary tract ultrasound. Biochemical analysis revealed normal growth hormone and thyroid hormone levels. While gross and fine motor skill development was in line with his age, speech delay was observed. This patient adds to a group of more than 30 cases of pure 4q tandem duplication with common and differing phenotypic presentations. Using a retrospective analysis of previous case studies alongside the current case and bioinformatics analysis of the duplicated region, we deduced the most likely dosage sensitive genes for some of the major phenotypes in the patient. The positive predictive value (PPV) was calculated for each gene and phenotype and was derived by comparing the previously reported patients who have gene duplications and an associated phenotype versus those who had the gene duplications but were unaffected. Thus, the growth retardation phenotype may be associated with NAA15 duplication, speech delay with GRIA2 and microcephaly with PLK4 duplication. Functional studies will help in confirming the observations and elucidating the mechanisms. However, our study highlights the importance of analysing case reports with pure duplications in defining phenotype-gene relationships and in improving our knowledge of the function of precise chromosomal regions. [ABSTRACT FROM AUTHOR]

Abstract In our previous study, a novel genome engineering technology, PCR-mediated chromosome duplication (PCDup), was developed in Saccharomyces cerevisiae that enabled the duplication of any desired chromosomal region, resulting in a segmental aneuploid. From one round of transformation, PCDup can duplicate a single chromosomal region efficiently. However, simultaneous duplication of multiple chromosomal regions is not possible using PCDup technology, which is a serious drawback. Sequential duplication is possible, but this approach requires significantly more time and effort. Because PCDup depends upon homologous recombination, we reasoned that it might be possible to simultaneously create duplications of multiple chromosomal regions if we could increase the frequency of these events. Double-strand breaks have been shown to increase the frequency of homologous recombination around the break point. Thus, we aimed to integrate the genome editing tool CRISPR/Cas9 system, which induces double-strand breaks, with our conventional PCDup. The new method, which we named CRISPR-PCDup increased the efficiency of a single duplication by up to 30 fold. CRISPR-PCDup enabled the simultaneous duplication of long chromosomal segments (160 kb and 200 kb regions). Moreover, we were also able to increase the length of the duplicated chromosome by up to at least 400 kb, whereas conventional PCDup can duplicate up to a maximum of 300 kb. Given the enhanced efficiency of chromosomal segmental duplication and the saving in both labor and time, we propose that CRISPR-PCDup will be an invaluable technology for generating novel yeast strains with desirable traits for specific industrial applications and for investigating genome function in segmental aneuploid.

Capsicum spp. is a horticultural crop of agronomic interest and is considered the fourth most important vegetable in the world. It is an important nutritional and medicinal source, and its production generates employment in the tropics. In this species, the genetic variability is wide and with great potential, which has been exploited to generate outstanding varieties. Breeding programs seek different alternatives to accelerate the production of improved varieties with desirable agronomic characteristics. These objectives can be achieved with the production of haploid and double haploid plants via androgenesis or gynogenesis, being androgenesis the approach most used for paprika cultures. The purpose of this review is to present the results of different researches in obtaining haploids and doubled haploids in cultivars of Capsicum spp. and its impact on the genetic improvement of this crop.

Prune belly syndrome (PBS) is a rare congenital disease that predominantly occurs in males and is identified by its classic triad of abdominal wall musculature deficiencies, cryptorchidism, and urinary tract abnormalities. However, numerous anomalies involving the kidneys, heart, lungs, and muscles have also been reported. A multitude of chromosomal abnormalities have been implicated in its pathogenesis. PBS can occur in association with trisomy 18 and 21. Gene duplications and deletions have also been reported; however, a definite cause of PBS is still unknown. We report the first PBS patient with a copy number variant in 16p11.2.

Copy number variants (CNVs) are an important source of normal and pathogenic genome variations. Unbalanced chromosome abnormalities are either gains or losses of large genomic regions that do not or only minimally clinically affect the individual. Noninvasive prenatal testing (NIPT) is widely used in the screening of common fetal chromosome aneuploidy. One example is the duplication of 10q11.21q11.23, which includes the 10q11.2 region. This region contains a complex set of low-copy repeats that may lead to various genomic alterations through non-allelic homologous recombination. In this report, we present a case of a de novo 10q11.21q11.23 duplication with a normal phenotype. This case may be helpful for prenatal diagnosis and genetic counseling. A combination of NIPT, prenatal ultrasound, karyotype analysis, copy number variation sequencing, and genetic counseling is helpful for the prenatal diagnosis of CNVs., Competing Interests: Declaration of conflicting interestThe authors declare that there is no conflict of interest.

Interpretation of the significance of maternally inherited X chromosome variants in males with neurocognitive phenotypes continues to present a challenge to clinical geneticists and diagnostic laboratories. Here we report 14 males from 9 families with duplications at the Xq13.2-q13.3 locus with a common facial phenotype, intellectual disability (ID), distinctive behavioral features, and a seizure disorder in two cases. All tested carrier mothers had normal intelligence. The duplication arose de novo in three mothers where grandparental testing was possible. In one family the duplication segregated with ID across three generations. RLIM is the only gene common to our duplications. However, flanking genes duplicated in some but not all the affected individuals included the brain-expressed genes NEXMIF , SLC16A2 , and the long non-coding RNA gene FTX. The contribution of the RLIM -flanking genes to the phenotypes of individuals with different size duplications has not been fully resolved. Missense variants in RLIM have recently been identified to cause X-linked ID in males, with heterozygous females typically having normal intelligence and highly skewed X chromosome inactivation. We detected consistent and significant increase of RLIM mRNA and protein levels in cells derived from seven affected males from five families with the duplication. Subsequent analysis of MDM2, one of the targets of the RLIM E3 ligase activity, showed consistent downregulation in cells from the affected males. All the carrier mothers displayed normal RLIM mRNA levels and had highly skewed X chromosome inactivation. We propose that duplications at Xq13.2-13.3 including RLIM cause a recognizable but mild neurocognitive phenotype in hemizygous males. [ABSTRACT FROM AUTHOR]

In our previous study, a novel genome engineering technology, PCR-mediated chromosome duplication (PCDup), was developed in Saccharomyces cerevisiae that enabled the duplication of any desired chromosomal region, resulting in a segmental aneuploid. From one round of transformation, PCDup can duplicate a single chromosomal region efficiently. However, simultaneous duplication of multiple chromosomal regions is not possible using PCDup technology, which is a serious drawback. Sequential duplication is possible, but this approach requires significantly more time and effort. Because PCDup depends upon homologous recombination, we reasoned that it might be possible to simultaneously create duplications of multiple chromosomal regions if we could increase the frequency of these events. Double-strand breaks have been shown to increase the frequency of homologous recombination around the break point. Thus, we aimed to integrate the genome editing tool CRISPR/Cas9 system, which induces double-strand breaks, with our conventional PCDup. The new method, which we named CRISPR-PCDup increased the efficiency of a single duplication by up to 30 fold. CRISPR-PCDup enabled the simultaneous duplication of long chromosomal segments (160 kb and 200 kb regions). Moreover, we were also able to increase the length of the duplicated chromosome by up to at least 400 kb, whereas conventional PCDup can duplicate up to a maximum of 300 kb. Given the enhanced efficiency of chromosomal segmental duplication and the saving in both labor and time, we propose that CRISPR-PCDup will be an invaluable technology for generating novel yeast strains with desirable traits for specific industrial applications and for investigating genome function in segmental aneuploid. [ABSTRACT FROM AUTHOR]

Copyright of Revista Facultad Nacional de Agronomía Medellín is the property of Universidad Nacional de Colombia and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: Precocious and early puberty are reported findings in children with pre-existing medical conditions including certain syndromes. Series pertaining to such situations are limited.Methods: A retrospective, single-center study was conducted on children with central precocious puberty (onset before the age of 8 years in girls and 9 years in boys) or early puberty (onset between 8 and 9 years in girls and between 9 and 10.5 years in boys) diagnosed on the background of a known pre-existing chronic significant medical condition. Patients with a CNS tumor and those exposed to cranial irradiation were excluded.Results: Precocious puberty was diagnosed in 13 patients and early puberty in 12. Mean age at onset of puberty was 6.65 ± 2.3 years in girls (n = 15) and 9.4 ± 0.84 years in boys (n = 10). The most common disorders were psychomotor delay (n = 12), psychiatric disorders (n = 7) and/or epilepsy (n = 5). Precocious or early puberty was among the symptoms experienced by patients with a variety of syndromes including lipofuscinosis (2 siblings), Dravet syndrome and Silver-Russel syndrome. Pituitary stalk interruption with agenesis of olfactory bulbs and optic nerve atrophy was found on imaging in one patient who presented with blindness, epilepsy, and autism spectrum disorder. The other diseases associated with precocious or early puberty are adrenocorticotropic deficiency, dyspraxia and bone abnormalities, glomerulopathy with complete renal failure, and repeated intra-fetal deaths in the mother. Karyotype analysis revealed chromosomal duplication (chromosome 15 in 2 cases; chromosomes 17 and 11 in one case each) in 4 of 8 patients evaluated.Conclusions: Data from patients with complex disease who experience precocious or early puberty may provide clues regarding the genetic determinants of pubertal development.

Background: Chromosomal duplications involving 17p13.3 have recently been defined as a new distinctive syndrome with several diagnosed patients. Some variation is known to occur in the breakpoints of the duplicated region and, consequently, in the phenotype as well. Aims: We report on a patient, the fifth to our knowledge, a 4-year-old girl with a pure de novo subtelomeric 17p13.2-pter duplication. She presents all of the facial features described so far for this duplication and in addition, a unilateral palmar transversal crease and oculocutaneous albinism which has not been reported previously. Methods: A detailed molecular description of the reported aberration and correlation with the observed phenotypical features based on a literature review. We discuss the possible molecular etiology of albinism in regard to the mode of inheritance. Conclusion: The new data provided here may be useful for further genotype correlations in syndromes with oculocutaneous albinism, especially of autosomal dominant inheritance.

The selection of yeast with good fermentation characteristics is critical for producing beer with desirable qualities. A yeast population was selected with an enhanced fermentation rate, referred to as high‐fermentation yeast (HFY), which was derived from the wild‐type Sacchromyces pastorianus yeast population (WTY). To identify genes that contribute to the fermentation performance, we compared the genetic profiles of the WTY and HFY populations by next‐generation sequencing. Several chromosomal regions were found to exhibit markedly different sequence coverage, suggesting chromosomal duplications and deletions, which might have occurred during selection of the HFY population. Among the genes with altered coverage, the copy number of the Saccharomyces eubayanus‐type YCK1 (SeYCK1) gene was almost two times higher in the HFY population than in the WTY population. The gene which is involved in glucose sensing in Saccharomyces cerevisiae was at a higher level in the HFY population throughout fermentation. These findings suggest that the chromosomal duplication of a region including the SeYCK1 gene locus of the HFY population is at least partially responsible for the differences in the fermentation properties between the WTY and HFY populations. © 2018 The Institute of Brewing & Distilling [ABSTRACT FROM AUTHOR]

Recent experiments established that a culture of Saccharomyces cerevisiae (baker’s yeast) survives sudden high temperatures by specifically duplicating the entire chromosome III and two chromosomal fragments (from IV and XII). Heat shock proteins (HSPs) are not significantly over-abundant in the duplication. In contrast, we suggest a simple algorithm to “ postdict ” the experimental results: Find a small enough chromosome with minimal protein disorder and duplicate this region. This algorithm largely explains all observed duplications. In particular, all regions duplicated in the experiment reduced the overall content of protein disorder. The differential analysis of the functional makeup of the duplication remained inconclusive. Gene Ontology (GO) enrichment suggested over-representation in processes related to reproduction and nutrient uptake. Analyzing the protein-protein interaction network (PPI) revealed that few network-central proteins were duplicated. The predictive hypothesis hinges upon the concept of reducing proteins with long regions of disorder in order to become less sensitive to heat shock attack.

Chromosome doubling of Italian ryegrass genotypes (Lolium multiflorum Lam.) adapted to the brazilian edaphoclimatic conditions is an important strategy used by breeders and aims to obtain more vigorous genotypes with better forage quality and disease resistance. The effectiveness of chromosome doubling can be measured by genetic stability and fertility rates of plants over generations. However, a common problem in the polyploidization process is the regeneration of mixoploid plants that have impaired fertility and genetic stability. The objective of this study was to verify if progenies of recently tetraploidized plants remain stable regarding DNA content and chromosome number, over two generations. Progenies of L. multiflorum plants artificially tetraploidized with colchicine treatment were evaluated. Chromosome counting and estimates of the DNA content were used to evaluate the genetic stability. The percentage of tetraploid plants (4X) increased over generations (18%, 34% and 91% in cycle 0, 1 and 2, respectively). All progenies identified as tetraploid by flow citometry showed variation in chromosome number (mixoploidy), but produced viable seeds. Results showed that stabilization in chromosome number and DNA content in tetraploidized plant progenies requires time and that the success of this procedure depends on a continuous and accurate screening and selection. [ABSTRACT FROM AUTHOR]

Backgound: Evolution of cancer cells is characterized by large scale and rapid changes in the chromosomal landscape. The fluorescence in situ hybridization (FISH) technique provides a way to measure the copy numbers of preselected genes in a group of cells and has been found to be a reliable source of data to model the evolution of tumor cells. Chowdhury et al. (Bioinformatics 29(13):189-98, 23; PLoS Comput Biol 10(7):1003740, 24) recently develop a computational model for tumor progression driven by gains and losses in cell count patterns obtained by FISH probes. Their model aims to find the rectilinear Steiner minimum tree (RSMT) (Chowdhury et al. in Bioinformatics 29(13):189-98, 23) and the duplication Steiner minimum tree (DSMT) (Chowdhury et al. in PLoS Comput Biol 10(7):1003740, 24) that describe the progression of FISH cell count patterns over its branches in a parsimonious manner. Both the RSMT and DSMT problems are NP-hard and heuristics are required to solve the problems efficiently. Methods: In this paper we propose two approaches to solve the RSMT problem, one inspired by iterative methods to address the "small phylogeny" problem (Sankoff et al. in J Mol Evol 7(2):133-49, 27; Blanchette et al. in Genome Inform 8:25-34, 28), and the other based on maximum parsimony phylogeny inference. We further show how to extend these heuristics to obtain solutions to the DSMT problem, that models large scale duplication events. Results: Experimental results from both simulated and real tumor data show that our methods outperform previous heuristics (Chowdhury et al. in Bioinformatics 29(13):189-98, 23; Chowdhury et al. in PLoS Comput Biol 10(7):1003740, 24) in obtaining solutions to both RSMT and DSMT problems. Conclusion: The methods introduced here are able to provide more parsimony phylogenies compared to earlier ones which are consider better choices. [ABSTRACT FROM AUTHOR]

HEY2 is a basic helix-loop-helix (bHLH) transcription factor that plays an important role in the developing mammalian heart and brain. In humans, nonsynonymous mutations in HEY2 have been described in patients with atrial ventricular septal defects, and a subset of individuals with chromosomal deletions involving HEY2 have cardiac defects and cognitive impairment. Less is known about the potential effects of HEY2 overexpression. Here, we describe a female child with tetralogy of Fallot who developed severe right ventricular outflow tract obstruction due to a combination of infundibular and valvular pulmonary stenosis. She was also noted to have hypotonia, lower extremity weakness, fine motor delay and speech delay. A copy number variation (CNV) detection analysis followed by real-time quantitative PCR analysis revealed a single gene duplication of HEY2. This is the only duplication involving HEY2 identified in our database of over 70,000 individuals referred for CNV analysis. In the developing heart, overexpression of HEY2 is predicted to cause decreased expression of the cardiac transcription factor GATA4 which, in turn, has been shown to cause tetralogy of Fallot. In mice, misexpression of Hey2 in the developing brain leads to inhibition of neurogenesis and promotion of gliogenesis. Hence, duplication of HEY2 may be a contributing factor to both the congenital heart defects and the neurodevelopmental problems evident in our patient. These results suggest that individuals with HEY2 duplications should be screened for congenital heart defects and monitored closely for evidence of developmental delay and/or cognitive impairment. © 2015 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Background. Chromosomal duplications involving 17p13.3 have recently been defined as a new distinctive syndrome with several diagnosed patients. Some variation is known to occur in the breakpoints of the duplicated region and, consequently, in the phenotype as well. Aims. We report on a patient, the fifth to our knowledge, a 4-year-old girl with a pure de novo subtelomeric 17p13.2- pter duplication. She presents all of the facial features described so far for this duplication and in addition, a unilateral palmar transversal crease and oculocutaneous albinism which has not been reported previously. Methods. A detailed molecular description of the reported aberration and correlation with the observed phenotypical features based on a literature review. We discuss the possible molecular etiology of albinism in regard to the mode of inheritance. Conclusion. The new data provided here may be useful for further genotype correlations in syndromes with oculocutaneous albinism, especially of autosomal dominant inheritance. [ABSTRACT FROM AUTHOR]

Comparative genomic hybridization (CGH) arrays have significantly changed the approach to identifying genetic alterations causing intellectual disability and congenital anomalies. Several studies have described the microduplication of Xp22.31, involving the STS gene. In such reports characteristic features and pathogenicity of Xp22.31 duplications remains a subject of debate. Here we present a series of nine previously unreported individuals with Xp22.31 duplications, found through microarray analysis in the course of genetic workup for developmental delay, associated with a combination of talipes anomalies, seizures and/or feeding difficulties. The size of the Xp22.31 duplications ranged from 294 kb to 1.6 Mb. We show a comparison of the breakpoints, inheritance and clinical phenotype, and a review of the literature. This clinically detailed series of Xp22.31 duplication patients provides evidence that the Xp22.31 duplication contributes to a common phenotype. © 2014 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Background Genomic structure variation (GSV) is widely distributed in various organisms and is an important contributor to human diversity and disease susceptibility. Efficient approaches to induce targeted genomic structure variation are crucial for both analytic and therapeutic studies of GSV. Here, we presented an efficient strategy to induce targeted GSV including chromosomal deletions, duplications and inversions in a precise manner. Results Utilizing Transcription Activator-Like Effector Nucleases (TALEN) designed to target two distinct sites, we demonstrated targeted deletions, duplications and inversions of an 8.9 Mb chromosomal segment, which is about one third of the entire chromosome. We developed a novel method by combining TALEN-induced GSV and single stranded oligodeoxynucleotide (ssODN) mediated gene modifications to reduce unwanted mutations occurring during the targeted GSV using TALEN or Zinc finger nuclease (ZFN). Furthermore, we showed that cointroduction of TALEN and ssODN generated unwanted complex structure variation other than the expected chromosomal deletion. Conclusions We demonstrated the ability of TALEN to induce targeted GSV and provided an efficient strategy to perform GSV precisely. Furthermore, it is the first time to show that cointroduction of TALEN and ssODN generated unwanted complex structure variation. It is plausible to believe that the strategies developed in this study can be applied to other organisms, and will help understand the biological roles of GSV and therapeutic applications of TALEN and ssODN. [ABSTRACT FROM AUTHOR]

Terminal deletions of chromosome 3p26.3 confined to the CHL1 gene have previously been described in children with intellectual disability and epilepsy. Here, we report for the first time, a 3p26.3 duplication including only the CHL1 gene in an intellectually disabled girl with epilepsy. The penetrance of both deletions and duplications in 3p26.3 is reduced because all chromosomal imbalances were inherited from healthy parents. Further studies are needed to specify the pathogenic mechanism of 3p26.3 imbalances and to estimate recurrence risks in genetic counseling. However, the description of both deletions and duplications of chromosome 3p26.3 in nonsyndromic intellectual disability suggests that CHL1 is a dosage-sensitive gene with an important role for normal cognitive development. [ABSTRACT FROM AUTHOR]

In 1979 a 'new' syndrome characterized by X-linked inheritance, hypogonadism, gynecomastia, intellectual disability, obesity, and short stature was described. The now-36-year-old propositus was recently referred to the genetics clinic for profound intellectual disability. Fragile X testing initially demonstrated a duplication of the FMR1 region, and upon further testing we identified an Xq27.3-q28 8.05 Mb-long duplication responsible for a syndrome. Our report describes the molecular and clinical aspects of the X-linked syndrome. Our results suggest that male patients with intellectual disability, hypogonadism, short stature, and gynecomastia should be further investigated for rearrangements in the Xq27.3-q28 region. In the future, when more cases of the duplication are identified, it may become possible to more accurately determine the specific genes affected by overexpression and responsible for the phenotype. © 2013 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

AβPP locus duplications have been recently identified in early-onset Alzheimer's disease. We describe a patient who initiated memory problems and behavioral disturbances at 57 years, with a progressive cognitive decline, who died at the age of 68 years with dementia. Neuropathological examination revealed a temporobasal hemorrhage, extensive Alzheimer-type pathology, and severe cerebral amyloid angiopathy. We observed a chromosomal 21 region duplication spanning 0.59 Mb, which comprised JAM2, ATP5J, GABPA, and AβPP genes. We propose a replication based mutational mechanism (single Fork-Stalling and Template-Switching) or a recombination based one (non-homologous end-joining repair) for the AβPP locus duplication in this case. [ABSTRACT FROM AUTHOR]

Mycobacterium tuberculosis isolates with identical IS 6110 restriction fragment length polymorphism (RFLP) patterns are considered to be clonally related. The presence of IS 6110 in the dnaA–dnaN intergenic region, one preferential locus for the integration of IS 6110, was evaluated in 125 M. tuberculosis isolates. Five isolates had IS 6110 inserted in this region, and two consisted of a mix of isogenic strains that putatively have evolved during a single infection. Strains from the same isolate had identical spoligo and mycobacterial interspersed repetitive unit–variable-number tandem repeat profiles, but had slight variations in IS 6110 RFLP patterns, due to the presence of IS 6110 in the dnaA–dnaN intergenic region. Duplication of the dnaA–dnaN intergenic region was found in one isogenic strain. [ABSTRACT FROM AUTHOR]

Abstract: We report triallelic patterns in several short tandem repeat (STR) loci revealed by routine paternity testing using the commercial AMPFlSTR®Profiler™ and AMPFlSTR®SGMplus™ kits. One case where the TPOX-locus (2p25.3) produced three peaks from the blood sample of a child was analysed further. Quantitative polymerase chain reaction (QPCR) and STR typing of the DNAs of the family trio revealed a large (>1.59Mb) duplication flanking the TPOX-locus in chromosome 2 in both the mother and child. The implications of such genetic anomalies for paternity testing are discussed. [Copyright &y& Elsevier]

Summary: The genome of Mycobacterium smegmatis mc2155 contains a 56kb duplicated region. We isolated a mutant of mc2155 lacking this duplication (ΔDRKIN). This mutation did not affect the growth rate, surface properties or transformation efficiency of the organism, confirming the potential utility of ΔDRKIN for the study of genes contained within the duplicated region. [Copyright &y& Elsevier]

Investigation of the co-occurrence of panic and phobic disorders with joint laxity led to the identification of interstitial duplications involving human chromosome 15q24-26 (named ‘DUP25’) in a Spanish population. DUP25 was observed in 97% of patients and in 7% of control individuals. In the present study, we used two different methods to detect DUP25: high-throughput molecular gene dosage analysis and fluorescence in situ hybridization (FISH). We evaluated 56 lymphoblastoid cell lines derived from 26 unrelated patients with panic disorder obtained from several European and American populations and 30 normal controls. We could not find any cell line showing a result consistent with DUP25. These data do not support any association of DUP25 with panic disorder.European Journal of Human Genetics (2004) 12, 505-508. doi:10.1038/sj.ejhg.5201181 Published online 31 March 2004 [ABSTRACT FROM AUTHOR]

Prader-Willi syndrome (PWS) is a rare neurodevelopmental disorder resulting from chromosomal duplications, deletions, or imprinting within the 15q11-q13 region. In most cases, patients with PWS inherit a de novo paternally inherited deletion, and the remaining result from maternal disomy 15 and imprinting. Currently, DNA methylation analysis remains the gold standard for diagnosing PWS. However, this diagnostic test provides no information concerning the molecular class of PWS. As a result, clinicians remain unable to accurately determine diagnostic and prognostic information for patients with PWS. Further research is needed toward establishing standardized, accurate, and cost-effective testing methods for diagnosis and treatment of patients with PWS. [ABSTRACT FROM AUTHOR]

Background: Currently, chromosomal microarray analysis is considered the first-tier test in pediatric care and prenatal diagnosis. However, the diagnostic yield of chromosomal microarray analysis for prenatal diagnosis of congenital heart disease has not been evaluated based on a large cohort.Objective: Our aim was to evaluate the clinical utility of chromosomal microarray as the first-tier test for chromosomal abnormalities in fetuses with congenital heart disease.Study Design: In this prospective study, 602 prenatal cases of congenital heart disease were investigated using single nucleotide polymorphism array over a 5-year period.Results: Overall, pathogenic chromosomal abnormalities were identified in 125 (20.8%) of 602 prenatal cases of congenital heart disease, with 52.0% of them being numerical chromosomal abnormalities. The detection rates of likely pathogenic copy number variations and variants of uncertain significance were 1.3% and 6.0%, respectively. The detection rate of pathogenic chromosomal abnormalities in congenital heart disease plus additional structural anomalies (48.9% vs 14.3%, P < .0001) or intrauterine growth retardation group (50.0% vs 14.3%, P = .044) was significantly higher than that in isolated congenital heart disease group. Additionally, the detection rate in congenital heart disease with additional structural anomalies group was significantly higher than that in congenital heart disease with soft markers group (48.9% vs 19.8%, P < .0001). No significant difference was observed in the detection rates between congenital heart disease with additional structural anomalies and congenital heart disease with intrauterine growth retardation groups (48.9% vs 50.0%), congenital heart disease with soft markers and congenital heart disease with intrauterine growth retardation groups (19.8% vs 50.0%), or congenital heart disease with soft markers and isolated congenital heart disease groups (19.8% vs 14.3%). The detection rate in fetuses with congenital heart disease plus mild ventriculomegaly was significantly higher than in those with other types of soft markers (50.0% vs 15.6%, P < .05).Conclusion: Our study suggests chromosomal microarray analysis is a reliable and high-resolution technology and should be used as the first-tier test for prenatal diagnosis of congenital heart disease in clinical practice. [ABSTRACT FROM AUTHOR]

Prader-Willi syndrome (PWS) is a rare neurodevelopmental disorder resulting from chromosomal duplications, deletions, or imprinting within the 15q11-q13 region. In most cases, patients with PWS inherit a de novo paternally inherited deletion, and the remaining result from maternal disomy 15 and imprinting. Currently, DNA methylation analysis remains the gold standard for diagnosing PWS. However, this diagnostic test provides no information concerning the molecular class of PWS. As a result, clinicians remain unable to accurately determine diagnostic and prognostic information for patients with PWS. Further research is needed toward establishing standardized, accurate, and cost-effective testing methods for diagnosis and treatment of patients with PWS.

Purpose: Duplications encompassing the MECP2 gene on the Xq28 region have been described in male patients with moderate to severe mental retardation, absent speech, neonatal hypotonia, progressive spasticity and/or ataxia, recurrent severe respiratory infections, gastrointestinal problems, mild facial dysmorphisms (midface hypoplasia, depressed nasal bridge, large ears) and epilepsy. Epilepsy can occur in >50% of cases, but the types of seizures and the electroclinical findings in affected male individuals have been poorly investigated up to the present. Herein we describe eight patients with MECP2 duplication syndrome and a specific clinical and electroencephalographic pattern. Methods: Array CGH of genomic DNA from the probands was performed, and an Xq28 duplication ranging from 209 kb to 6.36 Mb was found in each patient. Electroencephalography studies and clinical and seizure features of all the patients were analyzed. Key findings: We found that epilepsy tended to occur between late childhood and adolescence. Episodes of loss of tone of the head and/or the trunk were the most represented seizure types. Generalized tonic-clonic seizures were rarely observed. The typical interictal EEG pattern showed abnormal background activity, with generalized slow spike and wave asynchronous discharge with frontotemporal predominance. Sleep electroencephalography studies also demonstrated abnormal background activity; spindles and K complex were often abnormal in morphology and amplitude. Response to therapy was generally poor and drug resistance was a significant feature. Significance: Although these cases and a review of the literature indicate that epilepsy associated with MECP2 duplication syndrome cannot be considered a useful marker for early diagnosis, epilepsy is present in >90% of adolescent patients and shows a peculiar electroclinical pattern. Consequently, it should be considered a significant sign of the syndrome, and an EEG follow-up of these patients should be encouraged from early childhood. Moreover, the definition of a more specific epileptic phenotype could be useful in order to suspect MECP2 duplication syndrome in older undiagnosed patients. [ABSTRACT FROM AUTHOR]