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At least 1,423 records · Page 79Linked to original sources
PubMed1996

Frequent distribution of ultrarapid metabolizers of debrisoquine in an ethiopian population carrying duplicated and multiduplicated functional CYP2D6 alleles.

The debrisoquine hydroxylase (CYP2D6) catalyzes the oxidative metabolism of more than 40 different clinically important drugs. The CYP2D6 gene is highly polymorphic. Defect alleles, causing the poor metabolizer phenotype, and also alleles with duplicated or multiduplicated active genes, causing ultrarapid metabolism, have been described. In the current investigation, we have evaluated the CYP2D6 phenotype (n = 115) and genotype (n = 122) among healthy Ethiopians. Only two subjects (1.8%) exhibited metabolic reaction (MR) for debrisoquine > 12.6 and were classified as poor metabolizers. A mutation in exon 1 causing a 34Pro --> Ser amino acid exchange, typical of the Chinese CYP2D6*10B (Ch1) allele and yielding an unstable enzyme, was present among 16% of the population and the carriers exhibited a high MR (0.9-5.0). Increased MR was also found among 18% of the subjects with a 107Thr --> Ile mutation associated to the CYP2D6*17(Z) allele causing diminished activity of CYP2D6 in vivo. Interestingly, 29% of the population investigated carried alleles with duplicated or multiduplicated CYP2D6 genes, indicative of ultrarapid metabolism. Xbal and EcoRI RFLP analyses identified individuals having new alleles with four or five CYP2D6*2(L) genes. Subjects with duplicated or multiduplicated CYP2D6*2 genes exhibited the lowest MR. These results suggest that the Ethiopian population, in comparison to Caucasian, Oriental and other Black populations, is genetically different with respect to the constitution of the CYP2D locus. The results also show that subjects carrying duplicated or multiduplicated active CYP2D6 genes are very common in certain ethnic groups, implicating this issue of potential global importance.

Alleles↗
PubMedDate not supplied

The surface of investments poured against different duplicating media.

Two phosphate-bonded investments that were poured into molds of a duplicating gel and a poly(vinyl siloxane) duplicating medium were examined for surface hardness. Untreated surfaces were also examined by the confocal microscope and the scanning electron microscope. The Brinell hardness of samples poured in poly(vinyl siloxane) was greater than that of the same investment poured in duplicating gel. Investments were hardest as set and were significantly softened by drying. Cast hardeners achieved some rehardening of the dried investment samples. Microscopic examination of the investment surfaces revealed greater irregularity of samples poured in duplicating gel than in poly(vinyl siloxane), particularly in one investment.

Agar↗
PubMed1997

2q35qter duplication syndrome: phenotypic definition.

Two sibs with multiple congenital anomalies and severe mental retardation were found to have a 2q35qter duplication as a result of a balanced maternal translocation. The clinical features of our two cases are compared with those reported in literature as having either a 2q35qter duplication or a wider duplicated segment without the involvement of any other chromosome deletion or duplication. The typical phenotype is described considering the characteristic clinical features as: hypotonia, hypertelorism, short and beaked nose, flat nasal bridge, thin upper lip, micrognathia, low set and dysmorphic ears, clinodactyly finger V and cryptorchidism.

Abnormalities, Multiple↗
PubMed1998

Rapid detection of a recombinant hotspot associated with Charcot-Marie-Tooth disease type IA duplication by a PCR-based DNA test.

A 1.5-Mb duplication on chromosome 17p11.2-p12 (CMT1A duplication) caused by a misalignment of the CMT1A repeat sequences (CMT1A-REPs) is associated with Charcot-Marie-Tooth disease type 1A (CMT1A). A hotspot of crossover breakpoints located in a 3.2-kb region of the CMT1A-REPs accounts for three-quarters of the rearrangements in CMT1A patients. We developed a PCR-based diagnostic method to detect a recombination hotspot associated with the CMT1A duplication. Thirty-one CMT1A Chinese patients from different families and 50 healthy people over 65 years of age were studied. Twenty-seven of the 31 cases demonstrated the 3.2-kb hotspot crossover, of which there were two subgroups. The type 1 crossover breakpoint was located at the distal CMT1A-REP around the PmeI site, and accounted for 24 of the 27 cases with a 3.2-kb hotspot crossover in CMT1A duplication patients. The type 2 crossover breakpoint was located at the distal CMT1A-REP around the base 3625 region, accounting for 3 of the 27 cases. The results correlated very well with the results of Southern transfer analysis. This study has a potentially important role in the diagnosis of CMT1A disease.

Charcot-Marie-Tooth Disease↗
PubMed1998

Ipsilateral ureteroureterostomy for single ureteral reflux or obstruction in a duplicate system.

PURPOSE: The traditional treatment for obstruction or reflux involving a single ureter in a duplicated system has been common sheath reimplantation. More recently, ipsilateral ureteroureterostomy has been suggested as an alternative treatment. We reviewed cases with duplicate systems that were treated with ipsilateral ureteroureterostomy at our institution to determine the acceptability of this operation as an alternative to common sheath reimplantation. MATERIALS AND METHODS: A total of 22 patients with 24 duplicate systems underwent ipsilateral ureteroureterostomy between March 1986 and December 1996. Patient charts were reviewed and analyzed for patient age, sex, ureteral and renal anatomy, initial presentation, the clinical situation necessitating operation, and the occurrence of early and late complications. Patients were followed for a mean period of 41.4 months. RESULTS: Two adults and 20 children 10 years old or younger presented with urinary tract infection (13), hydronephrosis on maternal ultrasound (5), dribbling (2), ureteral calculus (1) and hydronephrosis on neonatal abdominal ultrasound (1). Mean hospital stay was 3 days. There was 1 early and 1 late complication. CONCLUSIONS: Ipsilateral ureteroureterostomy is an acceptable alternative to common sheath reimplantation in select patients with single ureteral disease in a duplicate system.

Adolescent↗
PubMed1998

Duplication cyst of the antrum: a case report.

Gastrointestinal duplication is a rare congenital anomaly. Although it usually presents within the first few years of life, it may appear much later as described in this report of a 19-year-old man who had symptoms of gastric outlet obstruction. He was found to have a noncommunicating antral duplication cyst. The cyst was managed by antrectomy with excision of the cyst and several centimetres of duodenum. Microscopically the duplication cyst contained a mucosa, submucosa and muscularis. There was no evidence of ulceration or malignant cells. His recovery was smooth. The etiology, presentation and management of antral duplication cysts causing gastric outlet obstruction are discussed.

Adult↗
PubMed1998

Analysis of two duplications of the LDL receptor gene affecting intracellular transport, catabolism, and surface binding of the LDL receptor.

Two novel mutations of the low density lipoprotein (LDL)-receptor gene were found in two Italian familial hypercholesterolemia (FH)-heterozygotes. The first mutation was an 18 nucleotide duplication in exon 8 which is preceded by an A-->T transversion. The translation product of the mutant allele was predicted to be a receptor with an in-frame insertion of 6 amino acids in repeat B of the epidermal growth factor precursor homology domain. Analysis of LDL-receptor activity in the proband's fibroblasts showed a 50% reduction of 125I-labeled LDL binding and pulse-chase studies suggested that little, if any, of the mutant protein was processed to the mature form. The second mutation was a 7 kb duplication (from intron 2 to intron 6) of exons 3 through 6, predicted to encode an elongated receptor with the duplication of repeats 2-7 of the ligand binding domain. The elongated receptor was processed slightly more slowly than the normal receptor, but was converted to a mature form of the expected size. This mature, mutant receptor was degraded more rapidly than the normal receptor. On ligand blotting the elongated receptor bound twice as much LDL or beta-very low density lipoprotein (betaVLDL) as the normal receptor. In contrast, maximum binding of LDL to proband's cells was decreased to approximately 70% of the normal cells with a significant increase in apparent affinity. Cell association at 37 degrees C, internalization, and degradation showed a similar reduced maximum. Thus these mutations demonstrate that duplications of amino acid sequences in the low density lipoprotein LDL-receptor may disrupt the LDL-receptor pathway at different levels.

Adult↗
PubMed1998

[Analysis of results after primary heminephrectomy in surgical treatment of duplicated pyelo-caliceal system].

AIM: Determination of the effective diagnostics and therapeutic procedures in duplicated pyelo-calyceal system with upper pole dysfunction. METHOD: Retrospective review of operative procedures and follow-up. MATERIAL: In Department of Pediatric Surgery University of Medical Sciences in Poznań (Poland), 383 children with duplicated pyelo-calyceal system were treated between 1976 and 1997. The diagnosis was based on: IVP, MCU, scintigraphy, cystoscopy, and since 1984 on US. Conservative treatment was performed in 103 (26%) children with low VOR. The most frequent surgical procedure was Politano-Leadbetter ureteroneocystostomy carried out in 167 (44%) children. Primary heminephrectomy was performed in 79 (21%) patients with complete deterioration of the upper pole of the kidney. In order to attain upper pole parenchyma protection in 34 (9%) children the following primary procedures were performed: extirpation of the ureterocele with ureteroneocystostomy of both ureters, cutaneous uretral stoma or uretero-pyeloanastomosis. RESULTS: Among 79 children with primary heminephrectomy of the duplicated system with ureterocele, secondary operation was required only in 18 patients. From 34 children with kidney parenchyma protecting procedures in 18 patients secondary heminephrectomy or nephrectomy was performed. CONCLUSIONS: 1. Primary heminephrectomy with ureterectomy with partial ureterectomy is a method of choice in the treatment of seriously deteriorated upper pole of the duplicated pyelo-calyceal system. 2. Secondary surgical procedures were required only in 25% of children in whom primary heminephrectomy was performed. 3. Primary heminephrectomy is a save procedure with a low complication rate.

Adolescent↗
PubMed1998

Genomic organization and partial duplication of the human alpha7 neuronal nicotinic acetylcholine receptor gene (CHRNA7).

The human alpha7 neuronal nicotinic acetylcholine receptor gene (HGMW-approved symbol CHRNA7) has been characterized from genomic clones. The gene is similar in structure to the chick alpha7 gene with 10 exons and conserved splice junction positions. The size of the human gene is estimated to be larger than 75 kb. A putative promoter 5' of the translation start in exon 1 has been cloned and sequenced. The promoter region lacks a TATA box and has a high GC content (77%). Consensus Sp1, AP-2, Egr-1, and CREB transcription factor binding sites appear to be conserved between bovine and human genes. The alpha7 nAChR gene was found to be partially duplicated, with both loci mapping to the chromosome 15q13 region. A yeast artificial chromosome contig was constructed over a genetic distance of 5 cM that includes both alpha7 loci and the region between them. Four novel exons are described, located in genomic clones containing the partially duplicated gene. The duplicated sequences, including the novel exons, are expressed in human brain.

Base Sequence↗
PubMed2002

Evolution of duplicated reggie genes in zebrafish and goldfish.

Invertebrates, tetrapod vertebrates, and fish might be expected to differ in their number of gene copies, possibly due the occurrence of genome duplication events during animal evolution. Reggie (flotillin) genes code for membrane-associated proteins involved in growth signaling in developing and regenerating axons. Until now, there appeared to be only two reggie genes in fruitflies, mammals, and fish. The aim of this research was to search for additional copies of reggie genes in fishes, since a genome duplication might have increased the gene copy number in this group. We report the presence of up to four distinct reggie genes (two reggie-1 and two reggie-2 genes) in the genomes of zebrafish and goldfish. Phylogenetic analyses show that the zebrafish and goldfish sequence pairs are orthologous, and that the additional copies could have arisen through a genome duplication in a common ancestor of bony fish. The presence of novel reggie mRNAs in fish embryos indicates that the newly discovered gene copies are transcribed and possibly expressed in the developing and regenerating nervous system. The intron/exon boundaries of the new fish genes characterized here correspond with those of human genes, both in location and phase. An evolutionary scenario for the evolution of reggie intron-exon structure, where loss of introns appears to be a distinctive trait in invertebrate reggie genes, is presented.

Amino Acid Sequence↗
PubMed2026

A duplicated female pathway gene figla-like evolves as the male sex-determining gene in tilapia.

As the largest group of vertebrates, fish exhibit frequent turnover of sex-determining (SD) genes. Here, we assemble a chromosome-level YY red tilapia genome and identify figla-like (figlal) as the SD gene on tilapia linkage group (LG) 1. Integrative phylogenetic and genomic evidence suggests that figlal originated from a tilapia-specific duplication and transposition of the ancestral bHLH family gene figla from LG12 to LG1. Fluorescence in situ hybridization reveals expression divergence between figla and figlal, with figla expressed in female oocytes and figlal expressed in male gonadal somatic cells during early gonadal differentiation. The shift in expression after duplication might be driven by the insertion of cis-regulatory elements mediated by transposable elements. Knockout of figlal in XY fish results in male-to-female sex reversal as indicated by ovarian morphology, down-regulation of the male pathway gene dmrt1, and up-regulation of the female pathway gene cyp19a1a in the gonads. In contrast, overexpression of figlal in XX fish induces female-to-male sex reversal. These findings implicate figlal as an SD gene on tilapia LG1 and reveal the history of a unique evolutionary innovation in which a female oocyte gene evolved into a male SD gene via duplication, transposition, and cis-regulatory rewiring.

Animals↗
PubMed2006

An anthropoid-specific segmental duplication on human chromosome 1q22.

Segmental duplications (SDs) play a key role in genome evolution by providing material for gene diversification and creation of variant or novel functions. They also mediate recombinations, resulting in microdeletions, which have occasionally been associated with human genetic diseases. Here, we present a detailed analysis of a large genomic region (about 240 kb), located on human chromosome 1q22, that contains a tandem SD, SD1q22. This duplication occurred about 37 million years ago in a lineage leading to anthropoid primates, after their separation from prosimians but before the Old and New World monkey split. We reconstructed the hypothetical unduplicated ancestral locus and compared it with the extant SD1q22 region. Our data demonstrate that, as a consequence of the duplication, new anthropoid-specific genetic material has evolved in the resulting paralogous segments. We describe the emergence of two new genes, whose new functions could contribute to the speciation of anthropoid primates. Moreover, we provide detailed information regarding structure and evolution of the SD1q22 region that is a prerequisite for future studies of its anthropoid-specific functions and possible linkage to human genetic disorders.

Animals↗
PubMed2001

Gene and genome duplication.

Genomic sequencing projects have revealed the productivity of processes duplicating genes or entire chromosome segments. Substantial proportions of the yeast, Arabidopsis and human gene complements are made up of duplicates. This has prompted much interest in the processes of duplication, functional divergence and loss of genes, has renewed the debate on whether an early vertebrate genome was tetraploid, and has inspired mathematical models and algorithms in computational biology.

Algorithms↗
PubMed2004

Duplication-degeneration as a mechanism of gene fission and the origin of new genes in Drosophila species.

Gene fission and fusion, the processes by which a single gene is split into two separate genes and two adjacent genes are fused into a single gene, respectively, are among the primary processes that generate new genes. Despite their seeming reversibility, nothing is known about the mechanism of gene fission. Because the nucleotide sequences of fission genes record little about their origination process, conventional analysis of duplicate genes may not be powerful enough to unravel the underlying mechanism. In a survey for young genes in species of the Drosophila melanogaster subgroup using fluorescence in situ hybridization, we identified a young gene family, monkey king, whose genesis sheds light on the evolutionary process of gene fission. Its members originated 1-2 million years ago as retroposed duplicates and evolved into fission genes that separately encode protein domains from a multidomain ancestor. The mechanism underlying this process is gene duplication with subsequent partial degeneration.

Animals↗
PubMed2005

Identification of large ancient duplications associated with human gene deserts.

We identified 15 regions of >1 Mb in the human genome composed of large ancient local duplications corresponding to gene deserts. We detected these intrachromosomal duplications in mouse and dog but not in chicken; they present as patches of similarity as low as 60%. These findings suggest that some human gene deserts originated from duplications of segments lacking genes in a mammalian common ancestor.

Animals↗
PubMed2004

Dblox: a genome-wide test for ancient segmental duplication.

UNLABELLED: Dblox and RDblox provide a simple statistical test for duplicated genomic structure; the same programs can also be used to identify putatively duplicated regions. The method focuses on ancient duplication events involving protein-coding genes. AVAILABILITY: http://www.biol.sc.edu/~austin/

Algorithms↗
PubMed2004

Excess of amino acid substitutions relative to polymorphism between X-linked duplications in Drosophila melanogaster.

We have obtained sequence polymorphism data from 13 genes belonging to 5 gene families in Drosophila melanogaster where the K(a)/K(s) between copies is greater than 1. Twelve of these 13 loci are X-linked. In general, there is evidence of purifying selection in all families, as inferred both from levels of silent and replacement variation and insertion/deletion variation, suggesting that the loci are likely functional. Shared polymorphisms indicative of gene conversion between paralogs are rare among the X-linked families, in contrast to available data from autosomal duplicates. McDonald-Kreitman tests between duplicates reveal an excess of amino-acid fixations between copies in the X-linked families, suggesting that the divergence between these loci was driven by positive selection. In contrast, available data from autosomal duplicates show a deficit of fixations, consistent with gene conversion being a strong homogenizing force.

Amino Acid Substitution↗
PubMed2025

Comprehensive identification and analysis of clusters of tandemly duplicated genes reveal their contributions to adaptive evolution of green plants.

Tandem gene duplication occurred more frequently compared with the episodic whole-genome duplication (WGD), providing a continuous supply of genetic material for evolutionary innovation and adaptation to changing environments. The rising roles of clusters of tandemly duplicated genes (CTDGs) in the evolution of phenotypic diversity have been unraveled in mammals. However, the content and biological roles of CTDGs remain largely unknown in plants. Here, we comprehensively identified CTDGs in 220 published plant genomes representing major lineages of green plants. The number of CTDGs showed great variation across taxa, ranging from 0 to 6028. The size of CTDGs varied from 2 to 47 genes, with small clusters containing two members predominating. Interestingly, significant expansion of CTDGs was found in early-diverging land plants and is closely associated with the evolution of key traits (e.g., ABA response, plant cuticle, UV-B resistance) required for plants to conquer terrestrial environments. Functional enrichment analysis revealed conserved and specialized functional profiles among different sizes of CTDGs in both Arabidopsis thaliana and the bryophyte Physcomitrium patens. Small CTDGs were enriched in fundamental stress responses, including protein modification, signal transduction, and responses to diverse stress stimuli, while large CTDGs were enriched in more sophisticated processes such as plant hormone biosynthesis and signaling, plant-microbe interactions, and reproductive processes. Expression pattern analyses of CTDGs under different stress conditions in A. thaliana and P. patens revealed that the highest number of CTDGs showed differential expression under drought stress, suggesting important roles of CTDGs in the evolution of desiccation tolerance in early land plants. The results of this study provide new additions to our knowledge about the abundance of CTDGs across green plants and reveal their important contributions to enable plants to overcome stressful environments on land.

Gene Duplication↗