Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Duplication”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 793 records · Page 44Linked to original sources
PubMed2001

Polymorphic short tandem repeats for diagnosis of the Charcot-Marie-Tooth 1A duplication.

BACKGROUND: A 1.5-Mb microduplication containing the gene for peripheral myelin protein 22 (PMP22) on chromosome 17p11.2-12 is responsible for 75% of cases of the demyelinating form of Charcot-Marie-Tooth disease (CMT1A). Methods for molecular diagnosis of CMT1A use Southern blot and/or amplification by PCR of polymorphic poly(AC) repeats (microsatellites) located within the duplicated region, or the detection of junction fragments specific for the duplication. Difficulties with both strategies have led us to develop a new diagnostic strategy with highly polymorphic short tandem repeats (STRs) located inside the CMT1A duplicated region. METHODS: We tested 10 STRs located within the duplication for polymorphic behavior. Three STRs were selected and used to test a set of 130 unrelated CMT1A patients and were compared with nonduplicated controls. The study was then extended to a larger population of patients. Alleles of interest were sequenced. A manual protocol using polyacrylamide electrophoresis and silver staining and an automated capillary electrophoresis protocol to separate fluorescently labeled alleles were validated. RESULTS: We identified three new STRs covering 0.55 Mb in the center of the CMT1A duplication. One marker, 4A, is located inside the PMP22 gene. The two others, 9A and 9B, more telomerically positioned, have the highest observed heterozygosity reported to date for CMT1A markers: 0.80 for 9A, and 0.79 for 9B. Tetra- and pentanucleotide repeats offered clear amplification, accurate sizing, and easy quantification of intensities. CONCLUSIONS: Combined use of the three STRs allows robust diagnosis with almost complete informativeness. In our routine diagnosis for CMT1A, they have replaced the use of other polymorphic markers, either in a manual adaptation or combined with fluorescence labeling and allele sizing on a DNA sequencer.

Charcot-Marie-Tooth Disease↗
PubMed2001

[Homologous recombination and chromosomal rearrangements in Escherichia coli strains carrying a heterozygous tandem duplication].

Heterozygous tandem duplications formed in conjugational matings in Escherichia coli provides a convenient model system for studying the evolution of bacterial chromosome. Heterozygous duplications segregate various classes of haploid and diploid recombinants that appear as a result of unequal crossing over between sister chromosomes. In this work, an extended tandem duplication in the deo operon of E. coli carrying deoA deoB::Tn5/deoC deoD thr::Tn9 alleles was examined. Recombination between homologous DNA repeats in the duplication was studied in strains carrying different combinations of recBC, sbcBC, recB::Tn10, recQ::Tn3 mutations. The frequency of recombination between homologous DNA repeats was very high in all strains and did not decrease when the RecBCD and RecF recombinational pathways were simultaneously damaged in strains with the recB sbcBC recQ (or recF) genotype. It is assumed that unequal crossing over between direct DNA repeats in duplications may proceed through a particular pathway of "adaptive" recombination.

Alleles↗
PubMed2003

2R or not 2R: testing hypotheses of genome duplication in early vertebrates.

The widely popular hypothesis that there were two rounds of genome duplication by polyploidization early in vertebrate history (the 2R hypothesis) has been difficult to test until recently. Among the lines of evidence adduced in support of this hypothesis are relative genome size, relative gene number, and the existence of genomic regions putatively duplicated during polyploidization. The availability of sequence for a substantial portion of the human genome makes possible the first rigorous tests of this hypothesis. Comparison of gene family size in the human genome and in invertebrate genomes shows no evidence of a 4:1 ratio between vertebrates and invertebrates. Furthermore, explicit phylogenetic tests for the topology expected from two rounds of polyploidization have revealed alternative topologies in a substantial majority of human gene families. Likewise, phylogenetic analyses have shown that putatively duplicated genomic regions often include genes duplicated at widely different times over the evolution of life. The 2R hypothesis thus can be decisively rejected. Rather, current evidence favors a model of genome evolution in which tandem duplication, whether of genomic segments or of individual genes, predominates.

Animals↗
PubMed2003

Evolution of signal transduction by gene and genome duplication in fish.

Fishes possess more genes encoding receptor tyrosine kinases from the epidermal growth factor receptor (EGFR) family than other organisms. Three of the four genes present in higher vertebrates have been duplicated early during the evolution of the ray-finned fish lineage possibly as a consequence of an event of whole genome duplication. In the fish Xiphophorus, a much more recent local event of gene duplication of the egfr co-orthologue egfr-b generated a eighth gene, the Xmrk oncogene. This duplicate acquired within a short time a constitutive activity and a pigment cell-specific overexpression responsible for the induction of melanoma in certain interspecific hybrids. Despite its frequent loss during evolution of the genus Xiphophorus, the maintenance of Xmrk in numerous species and its evolution under purifying selection suggest a so far unknown function under certain natural conditions. One of the known functions of Xmrk in tumor cells is the suppression of differentiation of melanocytes induced by the microphthalmia-associated transcription factor MITF. While only one gene with alternative 5' exons and promoters is present in higher vertebrates, two mitf genes were identified in fish. Subfunctionalization of mitf paralogues by differential degeneration of alternative exons and regulatory sequences led particularly to the formation of a mitf gene specifically expressed in the melanocyte lineage. These observations validate fish as an outstanding model to study the mechanisms and biological consequences of gene and genome duplication but underline the complexity of the fish model and the caution necessary in transferring knowledge from fish to higher vertebrates and vice versa.

Amino Acid Sequence↗
PubMed2004

Hereditary motor and sensory neuropathy (HMSN) IA, developmental delay and autism related disorder in a boy with duplication (17)(p11.2p12).

We present a 6-year-old boy with moderate developmental delay, gait disturbance, autism related disorder and mild dysmorphic features. He was seen for evaluation of his retardation since the age of 2.8 years. At first sight, a cytogenetic analysis showed a normal 46,XY karyotype. Neurological examination at the age of 5.5 years revealed a motor and sensory polyneuropathy. A quantitative Southern blot with probes PMP22 and VAW409 specific for Charcot-Marie-Tooth type 1 (CMT1) disclosed a duplication which confirmed the diagnosis HMSN Ia. Subsequently, GTG banded metaphases were re-evaluated and a small duplication 17p was seen on retrospect. Additional FISH with probe LSISMS (Vysis) specific for the Smith-Magenis region at 17p11.2 again showed a duplication. Both parents had a normal karyotype and the duplication test for CMT1 showed normal results for both of them. The boy had a de novo 46,XY,dup(17)(p11.2p12) karyotype. The present observation confirms previous findings of mild psychomotor delay, neurobehavioural features and minor craniofacial anomalies as the major phenotypic features of dup(17)(p11.2) and dup(17)(p11.2p12); in cases of duplications comprising the PMP22 locus HMSN1 is associated. A recognizable facial phenotype emerges characterized by a broad forehead, hypertelorism, downslant of palpebral fissures, smooth philtrum, thin upper lip and ear anomalies.

Autistic Disorder↗
PubMed2003

AMID: autonomous modeler of intragenic duplication.

Intragenic duplication is an evolutionary process where segments of a gene become duplicated. While there has been much research into whole-gene or domain duplication, there have been very few studies of non-tandem intragenic duplication. The identification of intragenically replicated sequences may provide insight into the evolution of proteins, helping to link sequence data with structure and function. This paper describes a tool for autonomously modelling intragenic duplication. AMID provides: identification of modularly repetitive genes; an algorithm for identifying repeated modules; and a scoring system for evaluating the modules' similarity. An evaluation of the algorithms and use cases are presented.

Algorithms↗
PubMed2005

[Unequal crossing over is the principal pathway of homologous recombination in tandem duplications of Escherichia coli].

Homologous recombination between direct DNA repeats in tandem duplications usually leads to their dissociation. An even number of crossovers between two copies of a duplication should lead to the formation of diploid segregants, i.e., to the preservation of the duplication. However, in studies of the genotype of diploid segregants in heterozygous tandem duplications of Escherichia coli, it was shown that they arise by unequal exchanges between sister chromosomes rather than by intrachromosomal exchanges. Generally, these exchanges lead to the establishment of the homozygous state of (heterozygous) duplications. Since the available data suggest that the exchange between sister chromosomes may be coupled with DNA replication, it is supposed that unequal exchanges between direct DNA repeats occur in the process of DNA replication.

Chromosomes, Bacterial↗
PubMed2005

[Detection of duplications or deletions of the PMP22 gene using real-time quantitative PCR].

OBJECTIVE: To detect the duplication or deletion of peripheral myelin protein 22(PMP22) gene in Chinese patients with Charcot-Marie-Tooth disease(CMT) or hereditary neuropathy with liability to pressure palsies(HNPP) using real-time quantitative polymerase chain reaction. METHODS: Duplications or deletions of PMP22 gene were detected in 113 CMT cases, 4 HNPP cases and 50 normal controls by using real-time quantitative PCR. RESULTS: Thirty-six of 113 CMT cases had the PMP22 duplication, 4 HNPP cases had the PMP22 deletion. No duplication or deletion was found in 50 normal controls. CONCLUSION: The PMP22 duplication rate in Chinese patients with CMT is 31.9%(36/113). PMP22 deletion is the common cause of HNPP.

Adult↗
PubMed2005

Relationship between segmental duplications and repeat sequences in human chromosome 7.

Various types of repeat sequences are abundant in genomic sequences, and they are associated with the biological phenomena at distinct levels. In particular, comparative analyses of whole-genome-sized sequence data have revealed that repeat sequences cause segmental duplications, which are a type of chromosomal structural arrangement. In this study, we analyzed the relationships between segmental duplications and repeat sequences in human chromosome 7. For this purpose, three methods for detecting repeat sequences were applied to the genomic sequences of human chromosome 7: RepeatMasker for the dispersed repeats, TRF for the tandem repeats, and STEPSTONE for the inter-spread repeats. By plotting the detected repeat sequences against the locations on the chromosome, all three types of repeats were found to be concentrated around the regions of segmental duplications, as a macroscopic feature of their distributions. Furthermore, the latter two repeat sequences were classified in terms of their periods, and the distribution bias of the detected repeat sequences was statistically tested between the segmental duplication regions and the other regions. As a result, the periods of two repeats were biased, with less than a 5% level of significance probability by the chi(2) test, and the repeats with long periods, about 130bp and more than 400bp, were attributed to a bias with a 5% level of significance probability by the normalized residual test. The mechanism of segmental duplications is discussed based on the present results.

Base Composition↗
PubMed2001

Congenital foregut duplication cysts of the anterior tongue.

OBJECTIVE: To review our experience with foregut duplication cysts of the anterior tongue, an unusual and rarely encountered mass in this location. DESIGN: A retrospective review of patients with anterior tongue foregut duplication cysts identified between 1990 and 2000. SETTING: Academic, tertiary care children's medical center. PATIENTS: Six pediatric patients (5 boys and 1 girl) ranging in age from birth to 8 months at diagnosis. INTERVENTION: Three patients underwent preoperative magnetic resonance imaging (MRI). All 6 patients underwent excisional biopsy. MAIN OUTCOME MEASURES: Clinical description of foregut duplication cysts, ability to make the diagnosis preoperatively, and recurrence rates. RESULTS: No patient presented with respiratory compromise, despite the large size of the anterior tongue masses (range, 1.5-2.4 cm). An MRI study was performed in 3 patients, all given a presumptive diagnosis of dermoid cyst based on the radiographic findings. No patient was diagnosed correctly prior to surgical excision. All patients underwent surgical excision, and the average time from birth to surgical excision was 11 months (range, 3 days to 3.7 years). Surgical pathologic findings were reported as a foregut duplication cyst (enterocystoma) in all patients, with 3 specimens containing foci of gastric mucosa. No recurrence has occurred at 1-month follow-up. CONCLUSIONS: Foregut duplication cysts rarely present in the anterior tongue and are easily misdiagnosed preoperatively. An MRI study is helpful in preoperative planning, although all lesions were radiologically indistinguishable from dermoid cysts. These masses may be an underappreciated entity in the differential diagnosis of congenital anterior tongue masses.

Choristoma↗
PubMed1987

Duplication of the appendix mimicking adenocarcinoma of the colon.

Duplication of the appendix is a rare anomaly that has been reported fewer than 60 times. Three anatomic types of appendiceal duplications have been described--each the result of a different embryologic occurrence. A unique case of appendiceal duplication is presented, in which the duplication caused a constricting lesion of the colon and mimicked carcinoma. The anomalous appendix in this patient was not compatible with any of the previously described types of appendiceal duplications.

Adenocarcinoma↗
PubMed1996

Two patients with duplication of 17p11.2: the reciprocal of the Smith-Magenis syndrome deletion?

J.M. and H.G. are two unrelated male patients with developmental delay. Cytogenetic analysis detected a duplication of 17p11.2 in both patients. The extent of the duplicated region was determined using single copy DNA probes: cen-D17S58-D17S29-D17S258-D17S71-D17S445-+ ++D17S122-tel. Four of the six markers, D17S29, D17S258, D17S71, and D17S445, were duplicated by dosage analysis. Fluorescent in situ hybridization (FISH) analysis of H.G., using cosmids for locus D17S29, confirmed the duplication in 17p11.2. Because the deletion that causes the Smith-Magnesis syndrome involves the same region of 17p11.2 as the duplication in these patients, the mechanism may be similar to that proposed for the reciprocal deletion/duplication event observed in Hereditary Neuropathy with Liability to Pressure Palsies (HNPP) and Charcot-Marie-Tooth Type 1A disease (CMT1A).

Abnormalities, Multiple↗
PubMed1999

Tandem duplication polymorphism upstream of the dopamine D4 receptor gene (DRD4).

The dopamine D4 receptor (DRD4) is a member of the D2-like dopamine receptor family. Polymorphisms at the DRD4 gene have been examined for association with a wide range of neuropsychiatric disorders and normal behavioral variation. The DRD4 gene is unusual in its high amount of expressed polymorphism in humans. Here we study the identification of a polymorphic tandem duplication of 120 bp located 1.2 kb upstream of the initiation codon. The duplicated region contains consensus sequences of binding sites for several known transcription factors, suggesting that different alleles may differ in their transcriptional activity. Because chimpanzees, gorillas, and orangutans lack the duplication, the duplicated allele is inferred to be derived. The frequency of this derived duplication allele ranges from 0.40-0.81 in the 11 populations from around the world typed for this polymorphism. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 88:705-709, 1999.

Alleles↗
PubMed1995

Interstitial duplication of proximal 22q: phenotypic overlap with cat eye syndrome.

We describe a child with downslanting palpebral fissures, preauricular malfunctions, congenital heart defect (total anomalous pulmonary venous return), unilateral absence of a kidney, and developmental delay with an apparent interstitial duplication of proximal 22q. Fluorescent in situ hybridization (FISH) analysis showed duplication of the IGLC locus, and C-banding of the duplicated region was negative. The duplication appears to involve 22q11.2-q12. Although the child has neither colobomas nor microphthalmia, he shows phenotypic overlap with the cat eye syndrome, which is caused by a supernumerary bisatellited chromosome arising from inverted duplication of the short arm and proximal long arm of chromosome 22. Further molecular studies of this patient should help to define the regions responsible for the manifestations of cat eye syndrome.

Abnormalities, Multiple↗
PubMed1995

Mirror image duplication of the hands and feet: report of a sporadic case with multiple congenital anomalies.

Mirror image duplication of the hands and feet is a rare entity. Based on 3 previous reports, findings include nasal abnormalities, dimelia of ulna and fibula, tibial hypoplasia and mirror image duplication of hands and feet. We report on a sporadic case in which mirror image duplication was associated with multiple congenital anomalies. Although these cases may represent variable expression of the same dominantly transmitted complex polysyndactyly syndrome, it is possible that mirror image duplication of the hands and feet is a manifestation common to a number of distinct clinical entities. During limb bud development, duplication and aberrant positioning of the zone of polarizing activity in relation to the apical ectodermal ridge may account for the anatomic abnormalities of the hands and feet in these patients.

Abnormalities, Multiple↗
PubMed2003

Newborn with malformations and a combined duplication of 9pter-q22 and 16q22-qter resulting from unbalanced segregation of a complex maternal translocation.

We report a patient with duplication of 9pter-q22 combined with duplication of 16q22-qter. The chromosome anomaly was the result of a 3:1 segregation of a maternal translocation (46,XX,t[9;16;21]). This newborn had intrauterine growth retardation and microcephaly, the characteristic recognizable pattern of trisomy 9p, cerebellar hypoplasia, a porencephalic cyst in the parieto-occipital region, and rocker-bottom feet. We compare the clinical features with another previously described case of duplication of an identical 9p segment combined with distal 16q duplication of a similar, but not identical segment, as well as with cases with duplication of either one of the two segments.

Abnormalities, Multiple↗
PubMed2005

An Xq22.3 duplication detected by comparative genomic hybridization microarray (Array-CGH) defines a new locus (FGS5) for FG syndrome.

FG syndrome is an X-linked multiple congenital anomalies (MCA) syndrome. It has been mapped to four distinct loci FGS1-4, through linkage analysis (Xq13, Xp22.3, and Xp11.4-p11.3) and based on the breakpoints of an X chromosome inversion (Xq11:Xq28), but so far no gene has been identified. We describe a boy with FG syndrome who has an inherited duplication at band Xq22.3 detected by comparative genomic hybridization microarray (Array-CGH). These duplication maps outside all four loci described so far for FG syndrome, representing therefore a new locus, which we propose to be called FGS5. MID2, a gene closely related to MID1, which is known to be mutated in Opitz G/BBB syndrome, maps within the duplicated segment of our patient. Since FG and Opitz G/BBB syndromes share many manifestations we considered MID2 a candidate gene for FG syndrome. We also discuss the involvement of other potential genes within the duplicated segment and its relationship with clinical symptoms of our patient, as well as the laboratory abnormalities found in his mother, a carrier of the duplication.

Abnormalities, Multiple↗
PubMed2001

Evidence of a common pathogenesis for foregut duplications and esophageal atresia with tracheo-esophageal fistula.

The pathogenesis of the alimentary tract duplications, including foregut duplications (FgD) remains speculative. The accidental finding of FgD in fetal rats with esophageal atresia and tracheoesophageal fistula (EA-TEF) induced by Adriamycin provided an animal model to investigate a possible relationship between these two entities. Timed-pregnant rats were intraperitoneally injected with Adriamycin (1.75 mg/kg) on gestational Days 6 to 9. Their embryos were harvested by Caesarean section from gestational Days 14 to 21. Forty-six of embryos were processed and serially sectioned in the transverse or sagittal planes. EA-TEF occurred in 43/46 (93%) embryos of which 11 (24%) were found to have an associated FgD located at the level where the esophagus was absent. Six FgDs communicated with the foregut or the trachea. Five noncommunicating FgDs were located between the foregut and the vertebral column. In the control embryo, the notochord was located in the centre of the vertebral column from Day 11 of the gestation. In Day 14, 15 and 16, however, embryos exposed to Adriamycin, an abnormal notochord or branch frequently was located within the mesenchyme of the maldeveloped foregut or attached to the duplication cyst. In some, it appeared that the notochord was drawing the cyst-like structure away from the foregut. The present study confirms that duplications adjacent to the esophagus arise from the foregut and that failure of the foregut to detach from the notochord at the normal time may contribute to the development of foregut duplications.

Abnormalities, Drug-Induced↗