Distal 7q11.23 Duplication, an Emerging Microduplication Syndrome: A Case Report and Further Characterisation.

PubMed

Faundes, Víctor; Santa María, Lorena; Morales, Paulina; Curotto, Bianca; Parraguez, María M

2016-10-01

Chromosome 7q11.23 duplication syndrome is a well-recognised syndrome which involves the duplication of the same genes located in the Williams-Beuren critical region. However, in 2010, 4 patients were reported with a microduplication only in the HIP1 and YWHAG genes. We refer to this as a distal 7q11.23 duplication (dup7q11.23D). Here, we report the fifth de novo patient with dup7q11.23D, whose symptoms may be explained by YWHAG overexpression as was demonstrated recently in mice and obese patients. Finally, further studies will be necessary to delineate this emerging microduplication syndrome.

Novel partial duplication of EYA1 causes branchiootic syndrome in a large Brazilian family.

PubMed

Dantas, Vitor G L; Freitas, Erika L; Della-Rosa, Valter A; Lezirovitz, Karina; de Moraes, Ana Maria S M; Ramos, Silvia B; Oiticica, Jeanne; Alves, Leandro U; Pearson, Peter L; Rosenberg, Carla; Mingroni-Netto, Regina C

2015-01-01

To identify novel genetic causes of syndromic hearing loss in Brazil. To map a candidate chromosomal region through linkage studies in an extensive Brazilian family and identify novel pathogenic variants using sequencing and array-CGH. Brazilian pedigree with individuals affected by BO syndrome characterized by deafness and malformations of outer, middle and inner ear, auricular and cervical fistulae, but no renal abnormalities. Whole genome microarray-SNP scanning on samples of 11 affected individuals detected a multipoint Lod score of 2.6 in the EYA1 gene region (chromosome 8). Sequencing of EYA1 in affected patients did not reveal pathogenic mutations. However, oligonucleotide-array-CGH detected a duplication of 71.8Kb involving exons 4 to 10 of EYA1 (heterozygous state). Real-time-PCR confirmed the duplication in fourteen of fifteen affected individuals and absence in 13 unaffected individuals. The exception involved a consanguineous parentage and was assumed to involve a different genetic mechanism. Our findings implicate this EYA1 partial duplication segregating with BO phenotype in a Brazilian pedigree and is the first description of a large duplication leading to the BOR/BO syndrome.

Surgical Management of Duplication of the Pituitary Gland-Plus Syndrome With Epignathus, Cleft Palate, Duplication of Mandible, and Lobulated Tongue.

PubMed

Noguchi, Tadahide; Sugiyama, Tomoko; Sasaguri, Ken-Ichi; Ono, Shigeru; Maeda, Kosaku; Nishino, Hiroshi; Jinbu, Yoshinori; Mori, Yoshiyuki

2017-03-01

A 1-day-old male infant was referred to our department for evaluation of multiple malformations in his oral cavity. He was diagnosed duplication of the pituitary gland-plus syndrome with epignathus, cleft palate, duplication of the mandible, and a lobulated tongue. A thumb-sized mass lesion was visible on the hard palate. The duplicated mandible and lower lip was fused at the midline. The alveolar ridge was protruding through a wide-cleft soft palate involving the uvula. Further examination showed a lobulated tongue, which was seen behind the duplicated part of the mandible. Five days after birth, tracheotomy and epignathus resection were performed. At 7 months of age, the excess tissue of the duplicated mandible was resected at the area of adhesion on the lingual side, and the duplicated tongue and lip were reconstructed. A palatoplasty was performed at 20 months of age. Thereafter, the patient's progress was uneventful, with no abnormality in swallowing. No recurrence of epignathus has been observed during 2 years of follow-up.

Congenital hyperinsulinism and Poland syndrome in association with 10p13-14 duplication.

PubMed

Giri, Dinesh; Patil, Prashant; Hart, Rachel; Didi, Mohammed; Senniappan, Senthil

2017-01-01

Poland syndrome (PS) is a rare congenital condition, affecting 1 in 30 000 live births worldwide, characterised by a unilateral absence of the sternal head of the pectoralis major and ipsilateral symbrachydactyly occasionally associated with abnormalities of musculoskeletal structures. A baby girl, born at 40 weeks' gestation with birth weight of 3.33 kg (-0.55 SDS) had typical phenotypical features of PS. She had recurrent hypoglycaemic episodes early in life requiring high concentration of glucose and glucagon infusion. The diagnosis of congenital hyperinsulinism (CHI) was biochemically confirmed by inappropriately high plasma concentrations of insulin and C-peptide and low plasma free fatty acids and β-hydroxyl butyrate concentrations during hypoglycaemia. Sequencing of ABCC8 , KCNJ11 and HNF4A did not show any pathogenic mutation. Microarray analysis revealed a novel duplication in the short arm of chromosome 10 at 10p13-14 region. This is the first reported case of CHI in association with PS and 10p duplication. We hypothesise that the HK1 located on the chromosome 10 encoding hexokinase-1 is possibly linked to the pathophysiology of CHI. Congenital hyperinsulinism (CHI) is known to be associated with various syndromes.This is the first reported association of CHI and Poland syndrome (PS) with duplication in 10p13-14.A potential underlying genetic link between 10p13-14 duplication, PS and CHI is a possibility.

Duplication of the pituitary gland associated with multiple blastogenesis defects: Duplication of the pituitary gland (DPG)-plus syndrome. Case report and review of literature.

PubMed

Manjila, Sunil; Miller, Erin A; Vadera, Sumeet; Goel, Rishi K; Khan, Fahd R; Crowe, Carol; Geertman, Robert T

2012-01-01

Duplication of the pituitary gland (DPG) is a rare craniofacial developmental anomaly occurring during blastogenesis with postulated etiology such as incomplete twinning, teratogens, median cleft face syndrome or splitting of the notochord. The complex craniocaudal spectrum of blastogenesis defects associated with DPG is examined with an illustrative case. We report for the first time in the medical literature some unique associations with DPG, such as a clival encephalocele, third cerebral peduncle, duplicate odontoid process and a double tongue with independent volitional control. This patient also has the previously reported common associations such as duplicated sella, cleft palate, hypertelorism, callosal agenesis, hypothalamic enlargement, nasopharyngeal teratoma, fenestrated basilar artery and supernumerary teeth. This study also reviews 37 cases of DPG identified through MEDLINE literature search from 1880 to 2011. It provides a detailed analysis of the current case through physical examination and imaging. The authors propose that the developmental deformities associated with duplication of pituitary gland (DPG) occur as part of a developmental continuum, not as chance associations. Considering the fact that DPG is uniquely and certainly present throughout the spectrum of these blastogenesis defects, we suggest the term DPG-plus syndrome.

Duplication of the pituitary gland associated with multiple blastogenesis defects: Duplication of the pituitary gland (DPG)-plus syndrome. Case report and review of literature

PubMed Central

Manjila, Sunil; Miller, Erin A.; Vadera, Sumeet; Goel, Rishi K.; Khan, Fahd R.; Crowe, Carol; Geertman, Robert T.

2012-01-01

Background: Duplication of the pituitary gland (DPG) is a rare craniofacial developmental anomaly occurring during blastogenesis with postulated etiology such as incomplete twinning, teratogens, median cleft face syndrome or splitting of the notochord. The complex craniocaudal spectrum of blastogenesis defects associated with DPG is examined with an illustrative case. Case Description: We report for the first time in the medical literature some unique associations with DPG, such as a clival encephalocele, third cerebral peduncle, duplicate odontoid process and a double tongue with independent volitional control. This patient also has the previously reported common associations such as duplicated sella, cleft palate, hypertelorism, callosal agenesis, hypothalamic enlargement, nasopharyngeal teratoma, fenestrated basilar artery and supernumerary teeth. This study also reviews 37 cases of DPG identified through MEDLINE literature search from 1880 to 2011. It provides a detailed analysis of the current case through physical examination and imaging. Conclusion: The authors propose that the developmental deformities associated with duplication of pituitary gland (DPG) occur as part of a developmental continuum, not as chance associations. Considering the fact that DPG is uniquely and certainly present throughout the spectrum of these blastogenesis defects, we suggest the term DPG-plus syndrome. PMID:22439114

Nutcracker syndrome and deep venous thrombosis in a patient with duplicated inferior vena cava.

PubMed

Yoshida, Ricardo de Alvarenga; Yoshida, Winston Bonetti; Costa, Renato Fanchiotti; Nacif, Marcelo Souto; Sobreira, Marcone Lima; Jaldin, Rodrigo Gibin

2016-04-01

Duplicated inferior vena cava is a rare anomaly, and thrombosis in one or both segments is even less frequent. We present a case of deep venous thrombosis of the left lower limb involving the popliteal, femoral, and iliac veins as well as the left segment of the duplicated vena cava and nutcracker syndrome. After catheter-directed thrombolysis complemented by mechanical thrombolysis, the compromised veins had complete revascularization; the nutcracker syndrome was treated with stent placement, followed by the use of anticoagulants. There was technical success and complete recovery of the patient. Copyright © 2016 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

Congenital hyperinsulinism and Poland syndrome in association with 10p13–14 duplication

PubMed Central

Giri, Dinesh; Patil, Prashant; Hart, Rachel; Didi, Mohammed

2017-01-01

Summary Poland syndrome (PS) is a rare congenital condition, affecting 1 in 30 000 live births worldwide, characterised by a unilateral absence of the sternal head of the pectoralis major and ipsilateral symbrachydactyly occasionally associated with abnormalities of musculoskeletal structures. A baby girl, born at 40 weeks’ gestation with birth weight of 3.33 kg (−0.55 SDS) had typical phenotypical features of PS. She had recurrent hypoglycaemic episodes early in life requiring high concentration of glucose and glucagon infusion. The diagnosis of congenital hyperinsulinism (CHI) was biochemically confirmed by inappropriately high plasma concentrations of insulin and C-peptide and low plasma free fatty acids and β-hydroxyl butyrate concentrations during hypoglycaemia. Sequencing of ABCC8, KCNJ11 and HNF4A did not show any pathogenic mutation. Microarray analysis revealed a novel duplication in the short arm of chromosome 10 at 10p13–14 region. This is the first reported case of CHI in association with PS and 10p duplication. We hypothesise that the HK1 located on the chromosome 10 encoding hexokinase-1 is possibly linked to the pathophysiology of CHI. Learning points: Congenital hyperinsulinism (CHI) is known to be associated with various syndromes. This is the first reported association of CHI and Poland syndrome (PS) with duplication in 10p13–14. A potential underlying genetic link between 10p13–14 duplication, PS and CHI is a possibility. PMID:28458900

Duplication 12q24----qter in an infant with Dandy-Walker syndrome.

PubMed

MacDonald, E A; Holden, J J

1985-04-01

A boy with the Dandy-Walker syndrome associated with multiple congenital abnormalities is described. Chromosomal analyses revealed an abnormal chromosome 21, inherited from his father who had a balanced translocation involving chromosomes 12 and 21: rcp(12;21)(q24.1;q22.1). The clinical features of this patient are compared with published descriptions for duplication 12q24----qter and a review of the literature pertaining to chromosomal anomalies found in other patients with the Dandy-Walker syndrome is presented.

A case of duplication of 13q32-->qter and deletion of 18p11.32-->pter with mild phenotype: Patau syndrome and duplications of 13q revisited.

PubMed Central

Helali, N; Iafolla, A K; Kahler, S G; Qumsiyeh, M B

1996-01-01

A mild clinical phenotype is described in a patient with duplication of 13q32-->qter and a small deletion of 18p11.32-->pter. The 8 year old white male presented with psychomotor retardation, tethered cord, soft, fleshy ears, and normal facial features except for thin lips. The karyotype was found to be 46, XY, der(18)t(13;18) (q32;p11.32) pat confirmed by fluorescence in situ hybridisation (FISH). A review of earlier studies showed that features of trisomy 13 are found in cases of duplication of bands 13q14 to qter. None of the cardinal features of trisomy 13 was seen in this patient. The absence of polydactyly, hernias, urogenital abnormalities, and haemangiomas contrast this condition with both trisomy 13 and duplication of 13q14-22-->qter. Possible explanations for lack of Patau syndrome in this patient could include restriction of the critical region for Patau syndrome to duplication 13q14-->13q32 with variable expression, gene interactions, or interchromosomal effects. Images PMID:8818949

A case of duplication of 13q32-->qter and deletion of 18p11.32-->pter with mild phenotype: Patau syndrome and duplications of 13q revisited.

PubMed

Helali, N; Iafolla, A K; Kahler, S G; Qumsiyeh, M B

1996-07-01

A mild clinical phenotype is described in a patient with duplication of 13q32-->qter and a small deletion of 18p11.32-->pter. The 8 year old white male presented with psychomotor retardation, tethered cord, soft, fleshy ears, and normal facial features except for thin lips. The karyotype was found to be 46, XY, der(18)t(13;18) (q32;p11.32) pat confirmed by fluorescence in situ hybridisation (FISH). A review of earlier studies showed that features of trisomy 13 are found in cases of duplication of bands 13q14 to qter. None of the cardinal features of trisomy 13 was seen in this patient. The absence of polydactyly, hernias, urogenital abnormalities, and haemangiomas contrast this condition with both trisomy 13 and duplication of 13q14-22-->qter. Possible explanations for lack of Patau syndrome in this patient could include restriction of the critical region for Patau syndrome to duplication 13q14-->13q32 with variable expression, gene interactions, or interchromosomal effects.

Neuroblastoma in a boy with MCA/MR syndrome, deletion 11q, and duplication 12q

DOE Office of Scientific and Technical Information (OSTI.GOV)

Koiffmann, C.P.; Vianna-Morgante, A.M.; Wajntal, A.

Deletion 11q23{r_arrow}qter and duplication 12q23{r_arrow}qter are described in a boy with neuroblastoma, multiple congenital anomalies, and mental retardation. The patient has clinical manifestations of 11q deletion and 12q duplication syndromes. The possible involvement of the segment 11q23{r_arrow}24 in the cause of the neuroblastoma is discussed. 18 refs., 2 figs., 1 tab.

Partial duplication of chromosome 19 associated with syndromic duane retraction syndrome.

PubMed

Abu-Amero, Khaled K; Kondkar, Altaf A; Al Otaibi, Abdullah; Alorainy, Ibrahim A; Khan, Arif O; Hellani, Ali M; Oystreck, Darren T; Bosley, Thomas M

2015-03-01

To evaluate possible monogenic and chromosomal anomalies in a patient with unilateral Duane retraction syndrome, modest dysmorphism, cerebral white matter abnormalities, and normal cognitive function. Performing high-resolution array comparative genomic hybridization (array CGH) and sequencing of HOXA1, KIF21A, SALL4, and CHN1 genes. The proband had unilateral Duane retraction syndrome (DRS) type III on the right with low-set ears, prominent forehead, clinodactyly, and a history of frequent infections during early childhood. Motor development and cognitive function were normal. Parents were not related, and no other family member was similarly affected. MRI revealed multiple small areas of high signal on T2 weighted images in cerebral white matter oriented along white matter tracts. Sequencing of HOXA1, KIF21A, SALL4, and CHN1 did not reveal any mutation(s). Array CGH showed a 95 Kb de novo duplication on chromosome 19q13.4 encompassing four killer cell immunoglobulin-like receptor (KIR) genes. Conclusions. KIR genes have not previously been linked to a developmental syndrome, although they are known to be expressed in the human brain and brainstem and to be associated with certain infections and autoimmune diseases, including some affecting the nervous system. DRS and brain neuroimaging abnormalities may imply a central and peripheral oligodendrocyte abnormality related in some fashion to an immunomodulatory disturbance.

Reciprocal duplication of the Williams-Beuren syndrome deletion on chromosome 7q11.23 is associated with schizophrenia.

PubMed

Mulle, Jennifer Gladys; Pulver, Ann E; McGrath, John A; Wolyniec, Paula S; Dodd, Anne F; Cutler, David J; Sebat, Jonathan; Malhotra, Dheeraj; Nestadt, Gerald; Conrad, Donald F; Hurles, Matthew; Barnes, Chris P; Ikeda, Masashi; Iwata, Nakao; Levinson, Douglas F; Gejman, Pablo V; Sanders, Alan R; Duan, Jubao; Mitchell, Adele A; Peter, Inga; Sklar, Pamela; O'Dushlaine, Colm T; Grozeva, Detelina; O'Donovan, Michael C; Owen, Michael J; Hultman, Christina M; Kähler, Anna K; Sullivan, Patrick F; Kirov, George; Warren, Stephen T

2014-03-01

Several copy number variants (CNVs) have been implicated as susceptibility factors for schizophrenia (SZ). Some of these same CNVs also increase risk for autism spectrum disorders, suggesting an etiologic overlap between these conditions. Recently, de novo duplications of a region on chromosome 7q11.23 were associated with autism spectrum disorders. The reciprocal deletion of this region causes Williams-Beuren syndrome. We assayed an Ashkenazi Jewish cohort of 554 SZ cases and 1014 controls for genome-wide CNV. An excess of large rare and de novo CNVs were observed, including a 1.4 Mb duplication on chromosome 7q11.23 identified in two unrelated patients. To test whether this 7q11.23 duplication is also associated with SZ, we obtained data for 14,387 SZ cases and 28,139 controls from seven additional studies with high-resolution genome-wide CNV detection. We performed a meta-analysis, correcting for study population of origin, to assess whether the duplication is associated with SZ. We found duplications at 7q11.23 in 11 of 14,387 SZ cases with only 1 in 28,139 control subjects (unadjusted odds ratio 21.52, 95% confidence interval: 3.13-922.6, p value 5.5 × 10(-5); adjusted odds ratio 10.8, 95% confidence interval: 1.46-79.62, p value .007). Of three SZ duplication carriers with detailed retrospective data, all showed social anxiety and language delay premorbid to SZ onset, consistent with both human studies and animal models of the 7q11.23 duplication. We have identified a new CNV associated with SZ. Reciprocal duplication of the Williams-Beuren syndrome deletion at chromosome 7q11.23 confers an approximately tenfold increase in risk for SZ. Copyright © 2014 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Distinguishing response to names in Rett and MECP2 Duplication syndrome: An ERP study of auditory social information processing.

PubMed

Peters, Sarika U; Katzenstein, Ashley; Jones, Dorita; Key, Alexandra P

2017-11-15

Despite significant advances at the level of basic research, the characterization of higher-level processes in Rett and MECP2 Duplication syndrome remains understudied. In this pilot study, we assessed social-emotional information processing by testing whether children (ages 4-12years) with Rett (n=9) and MECP2 Duplication syndrome (n=7) distinguished their own spoken name from other names. We hypothesized that own and familiar names would elicit more positive parietal P300 responses than unknown names, and that the groups would have different neural responses to these stimuli. The MECP2 Duplication group partially mirrored the parietal responses to own name observed in typically developing participants, and better name discrimination correlated with more adaptive behaviors. Conversely, participants with RTT did not resemble the typical group, and showed greater responses to close other names at frontal/central regions. These results may reflect the different consequences of too much (MECP2 Duplication) vs. too little (RTT) MeCP2 protein. Copyright © 2017 Elsevier B.V. All rights reserved.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Brown, A.; Phelan, M.C.; Rogers, R.C.

1996-05-17

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-Magenis 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/more » duplication event observed in Hereditary Neuropathy with Liability to Pressure Palsies (HNPP) and Charcot-Marie-Tooth Type 1A disease (CMT1A). 30 refs., 3 figs., 1 tab.« less

22q11.2q13 duplication including SOX10 causes sex-reversal and peripheral demyelinating neuropathy, central dysmyelinating leukodystrophy, Waardenburg syndrome, and Hirschsprung disease.

PubMed

Falah, Nadia; Posey, Jennifer E; Thorson, Willa; Benke, Paul; Tekin, Mustafa; Tarshish, Brocha; Lupski, James R; Harel, Tamar

2017-04-01

Diagnosis of genetic syndromes may be difficult when specific components of a disorder manifest at a later age. We present a follow up of a previous report [Seeherunvong et al., (2004); AJMGA 127: 149-151], of an individual with 22q duplication and sex-reversal syndrome. The subject's phenotype evolved to include peripheral and central demyelination, Waardenburg syndrome type IV, and Hirschsprung disease (PCWH; MIM 609136). DNA microarray analysis defined the duplication at 22q11.2q13, including SOX10. Sequencing of the coding region of SOX10 did not reveal any mutations. Our data suggest that SOX10 duplication can cause disorders of sex development and PCWH, supporting the hypothesis that SOX10 toxic gain of function rather than dominant negative activity underlies PCWH. © 2017 Wiley Periodicals, Inc.

22q11.2q13 Duplication Including SOX10 causes Sex-reversal and Peripheral Demyelinating Neuropathy, Central Dysmyelinating Leukodystrophy, Waardenburg Syndrome and Hirschsprung Disease

PubMed Central

Falah, Nadia; Posey, Jennifer E.; Thorson, Willa; Benke, Paul; Tekin, Mustafa; Tarshish, Brocha; Lupski, James R; Harel, Tamar

2017-01-01

Diagnosis of genetic syndromes may be difficult when specific components of a disorder manifest at a later age. We present a follow up of a previous report [Seeherunvong et al., 2004; Ajmga 127: 149–151], of an individual with 22q duplication and sex-reversal syndrome. The subject’s phenotype evolved to include peripheral and central demyelination, Waardenburg syndrome type IV, and Hirschsprung disease (PCWH; MIM 609136). DNA microarray analysis defined the duplication at 22q11.2q13, including SOX10. Sequencing of the coding region of SOX10 did not reveal any mutations. Our data suggest that SOX10 duplication can cause disorders of sex development and PCWH, supporting the hypothesis that SOX10 toxic gain-of-function rather than dominant negative activity underlies PCWH. PMID:28328136

Autopolyploidy genome duplication preserves other ancient genome duplications in Atlantic salmon (Salmo salar).

PubMed

Christensen, Kris A; Davidson, William S

2017-01-01

Salmonids (e.g. Atlantic salmon, Pacific salmon, and trouts) have a long legacy of genome duplication. In addition to three ancient genome duplications that all teleosts are thought to share, salmonids have had one additional genome duplication. We explored a methodology for untangling these duplications from each other to better understand them in Atlantic salmon. In this methodology, homeologous regions (paralogous/duplicated genomic regions originating from a whole genome duplication) from the most recent genome duplication were assumed to have duplicated genes at greater density and have greater sequence similarity. This assumption was used to differentiate duplicated gene pairs in Atlantic salmon that are either from the most recent genome duplication or from earlier duplications. From a comparison with multiple vertebrate species, it is clear that Atlantic salmon have retained more duplicated genes from ancient genome duplications than other vertebrates--often at higher density in the genome and containing fewer synonymous mutations. It may be that polysomic inheritance is the mechanism responsible for maintaining ancient gene duplicates in salmonids. Polysomic inheritance (when multiple chromosomes pair during meiosis) is thought to be relatively common in salmonids compared to other vertebrate species. These findings illuminate how genome duplications may not only increase the number of duplicated genes, but may also be involved in the maintenance of them from previous genome duplications as well.

Inherited Xq13.2-q21.31 duplication in a boy with recurrent seizures and pubertal gynecomastia: Clinical, chromosomal and aCGH characterization.

PubMed

Linhares, Natália D; Valadares, Eugênia R; da Costa, Silvia S; Arantes, Rodrigo R; de Oliveira, Luiz Roberto; Rosenberg, Carla; Vianna-Morgante, Angela M; Svartman, Marta

2016-09-01

We report on a 16-year-old boy with a maternally inherited ~ 18.3 Mb Xq13.2-q21.31 duplication delimited by aCGH. As previously described in patients with similar duplications, his clinical features included intellectual disability, developmental delay, speech delay, generalized hypotonia, infantile feeding difficulties, self-injurious behavior, short stature and endocrine problems. As additional findings, he presented recurrent seizures and pubertal gynecomastia. His mother was phenotypically normal and had completely skewed inactivation of the duplicated X chromosome, as most female carriers of such duplications. Five previously reported patients with partial Xq duplications presented duplication breakpoints similar to those of our patient. One of them, a fetus with multiple congenital abnormalities, had the same cytogenetic duplication breakpoint. Three of the reported patients shared many features with our proband but the other had some clinical features of the Prader-Willi syndrome. It was suggested that ATRX overexpression could be involved in the major clinical features of patients with partial Xq duplications. We propose that this gene could also be involved with the obesity of the patient with the Prader-Willi-like phenotype. Additionally, we suggest that the PCDH11X gene could be a candidate for our patient's recurrent seizures. In males, the Xq13-q21 duplication should be considered in the differential diagnosis of Prader-Willi syndrome, as previously suggested, and neuromuscular diseases, particularly mitochondriopathies.

A deletion and a duplication in distal 22q11.2 deletion syndrome region. Clinical implications and review

PubMed Central

Fernández, Luis; Nevado, Julián; Santos, Fernando; Heine-Suñer, Damià; Martinez-Glez, Victor; García-Miñaur, Sixto; Palomo, Rebeca; Delicado, Alicia; Pajares, Isidora López; Palomares, María; García-Guereta, Luis; Valverde, Eva; Hawkins, Federico; Lapunzina, Pablo

2009-01-01

Background Individuals affected with DiGeorge and Velocardiofacial syndromes present with both phenotypic diversity and variable expressivity. The most frequent clinical features include conotruncal congenital heart defects, velopharyngeal insufficiency, hypocalcemia and a characteristic craniofacial dysmorphism. The etiology in most patients is a 3 Mb recurrent deletion in region 22q11.2. However, cases of infrequent deletions and duplications with different sizes and locations have also been reported, generally with a milder, slightly different phenotype for duplications but with no clear genotype-phenotype correlation to date. Methods We present a 7 month-old male patient with surgically corrected ASD and multiple VSDs, and dysmorphic facial features not clearly suggestive of 22q11.2 deletion syndrome, and a newborn male infant with cleft lip and palate and upslanting palpebral fissures. Karyotype, FISH, MLPA, microsatellite markers segregation studies and SNP genotyping by array-CGH were performed in both patients and parents. Results Karyotype and FISH with probe N25 were normal for both patients. MLPA analysis detected a partial de novo 1.1 Mb deletion in one patient and a novel partial familial 0.4 Mb duplication in the other. Both of these alterations were located at a distal position within the commonly deleted region in 22q11.2. These rearrangements were confirmed and accurately characterized by microsatellite marker segregation studies and SNP array genotyping. Conclusion The phenotypic diversity found for deletions and duplications supports a lack of genotype-phenotype correlation in the vicinity of the LCRC-LCRD interval of the 22q11.2 chromosomal region, whereas the high presence of duplications in normal individuals supports their role as polymorphisms. We suggest that any hypothetical correlation between the clinical phenotype and the size and location of these alterations may be masked by other genetic and/or epigenetic modifying factors. PMID

4p terminal deletion and 11p subtelomeric duplication detected by genomic microarray in a patient with Wolf-Hirschhorn syndrome and an atypical phenotype.

PubMed

Stevenson, David A; Carey, John C; Cowley, Brett C; Bayrak-Toydemir, Pinar; Mao, Rong; Brothman, Arthur R

2004-12-01

We report a de novo cryptic 11p duplication found by genomic microarray with a cytogenetically detected 4p deletion. Terminal 4p deletions cause Wolf-Hirschhorn syndrome, but the phenotype probably was modified by the paternally derived 11p duplication. This emphasizes the clinical utility of genomic microarray.

Familial 4.3 Mb duplication of 21q22 sheds new light on the Down syndrome critical region

PubMed Central

Ronan, Anne; Fagan, Kerry; Christie, Louise; Conroy, Jeffrey; Nowak, Norma J; Turner, Gillian

2007-01-01

A 4.3 Mb duplication of chromosome 21 bands q22.13–q22.2 was diagnosed by interphase fluorescent in‐situ hybridisation (FISH) in a 31‐week gestational age baby with cystic hygroma and hydrops; the duplication was later found in the mother and in her 8‐year‐old daughter by the same method and confirmed by array comparative genomic hybridisation (aCGH). All had the facial gestalt of Down syndrome (DS). This is the smallest accurately defined duplication of chromosome 21 reported with a DS phenotype. The duplication encompasses the gene DYRK1 but not DSCR1 or DSCAM, all of which have previously been implicated in the causation of DS. Previous karyotype analysis and telomere screening of the mother, and karyotype analysis and metaphase FISH of a chorionic villus sample, had all failed to reveal the duplication. The findings in this family add to the identification and delineation of a “critical region” for the DS phenotype on chromosome 21. Cryptic chromosomal abnormalities can be missed on a routine karyotype for investigation of abnormal prenatal ultrasound findings, lending support to the use of aCGH analysis in this setting. PMID:17237124

Gene Duplication and the Evolution of Hemoglobin Isoform Differentiation in Birds*

PubMed Central

Grispo, Michael T.; Natarajan, Chandrasekhar; Projecto-Garcia, Joana; Moriyama, Hideaki; Weber, Roy E.; Storz, Jay F.

2012-01-01

The majority of bird species co-express two functionally distinct hemoglobin (Hb) isoforms in definitive erythrocytes as follows: HbA (the major adult Hb isoform, with α-chain subunits encoded by the αA-globin gene) and HbD (the minor adult Hb isoform, with α-chain subunits encoded by the αD-globin gene). The αD-globin gene originated via tandem duplication of an embryonic α-like globin gene in the stem lineage of tetrapod vertebrates, which suggests the possibility that functional differentiation between the HbA and HbD isoforms may be attributable to a retained ancestral character state in HbD that harkens back to a primordial, embryonic function. To investigate this possibility, we conducted a combined analysis of protein biochemistry and sequence evolution to characterize the structural and functional basis of Hb isoform differentiation in birds. Functional experiments involving purified HbA and HbD isoforms from 11 different bird species revealed that HbD is characterized by a consistently higher O2 affinity in the presence of allosteric effectors such as organic phosphates and Cl− ions. In the case of both HbA and HbD, analyses of oxygenation properties under the two-state Monod-Wyman-Changeux allosteric model revealed that the pH dependence of Hb-O2 affinity stems primarily from changes in the O2 association constant of deoxy (T-state)-Hb. Ancestral sequence reconstructions revealed that the amino acid substitutions that distinguish the adult-expressed Hb isoforms are not attributable to the retention of an ancestral (pre-duplication) character state in the αD-globin gene that is shared with the embryonic α-like globin gene. PMID:22962007

Gene duplication and the evolution of hemoglobin isoform differentiation in birds.

PubMed

Grispo, Michael T; Natarajan, Chandrasekhar; Projecto-Garcia, Joana; Moriyama, Hideaki; Weber, Roy E; Storz, Jay F

2012-11-02

The majority of bird species co-express two functionally distinct hemoglobin (Hb) isoforms in definitive erythrocytes as follows: HbA (the major adult Hb isoform, with α-chain subunits encoded by the α(A)-globin gene) and HbD (the minor adult Hb isoform, with α-chain subunits encoded by the α(D)-globin gene). The α(D)-globin gene originated via tandem duplication of an embryonic α-like globin gene in the stem lineage of tetrapod vertebrates, which suggests the possibility that functional differentiation between the HbA and HbD isoforms may be attributable to a retained ancestral character state in HbD that harkens back to a primordial, embryonic function. To investigate this possibility, we conducted a combined analysis of protein biochemistry and sequence evolution to characterize the structural and functional basis of Hb isoform differentiation in birds. Functional experiments involving purified HbA and HbD isoforms from 11 different bird species revealed that HbD is characterized by a consistently higher O(2) affinity in the presence of allosteric effectors such as organic phosphates and Cl(-) ions. In the case of both HbA and HbD, analyses of oxygenation properties under the two-state Monod-Wyman-Changeux allosteric model revealed that the pH dependence of Hb-O(2) affinity stems primarily from changes in the O(2) association constant of deoxy (T-state)-Hb. Ancestral sequence reconstructions revealed that the amino acid substitutions that distinguish the adult-expressed Hb isoforms are not attributable to the retention of an ancestral (pre-duplication) character state in the α(D)-globin gene that is shared with the embryonic α-like globin gene.

Multisite Semiautomated Clinical Data Repository for Duplication 15q Syndrome: Study Protocol and Early Uses.

PubMed

Ajayi, Oluwaseun Jessica; Smith, Ebony Jeannae; Viangteeravat, Teeradache; Huang, Eunice Y; Nagisetty, Naga Satya V Rao; Urraca, Nora; Lusk, Laina; Finucane, Brenda; Arkilo, Dimitrios; Young, Jennifer; Jeste, Shafali; Thibert, Ronald; Reiter, Lawrence T

2017-10-18

Chromosome 15q11.2-q13.1 duplication syndrome (Dup15q syndrome) is a rare disorder caused by duplications of chromosome 15q11.2-q13.1, resulting in a wide range of developmental disabilities in affected individuals. The Dup15q Alliance is an organization that provides family support and promotes research to improve the quality of life of patients living with Dup15q syndrome. Because of the low prevalence of this condition, the establishment of a single research repository would have been difficult and more time consuming without collaboration across multiple institutions. The goal of this project is to establish a national deidentified database with clinical and survey information on individuals diagnosed with Dup15q syndrome. The development of a multiclinic site repository for clinical and survey data on individuals with Dup15q syndrome was initiated and supported by the Dup15q Alliance. Using collaborative workflows, communication protocols, and stakeholder engagement tools, a comprehensive database of patient-centered information was built. We successfully established a self-report populating, centralized repository for Dup15q syndrome research. This repository also resulted in the development of standardized instruments that can be used for other studies relating to developmental disorders. By standardizing the data collection instruments, it allows us integrate our data with other national databases, such as the National Database for Autism Research. A substantial portion of the data collected from the questionnaires was facilitated through direct engagement of participants and their families. This allowed for a more complete set of information to be collected with a minimal turnaround time. We developed a repository that can efficiently be mined for shared clinical phenotypes observed at multiple clinic sites and used as a springboard for future clinical and basic research studies. ©Oluwaseun Jessica Ajayi, Ebony Jeannae Smith, Teeradache Viangteeravat

The Interstitial Duplication 15q11.2-q13 Syndrome Includes Autism, Mild Facial Anomalies and a Characteristic EEG Signature

PubMed Central

Urraca, Nora; Cleary, Julie; Brewer, Victoria; Pivnick, Eniko K; McVicar, Kathryn; Thibert, Ronald L; Schanen, N Carolyn; Esmer, Carmen; Lamport, Dustin; Reiter, Lawrence T

2013-01-01

Chromosomal copy number variants (CNV) are the most common genetic lesion found in autism. Many autism-associated CNVs are duplications of chromosome 15q. Although most cases of interstitial (int) dup(15) that present clinically are de novo and maternally derived or inherited, both pathogenic and unaffected paternal duplications of 15q have been identified. We performed a phenotype/genotype analysis of individuals with interstitial 15q duplications to broaden our understanding of the 15q syndrome and investigate the contribution of 15q duplication to increased autism risk. All subjects were recruited solely on the basis of interstitial duplication 15q11.2-q13 status. Comparative array genome hybridization was used to determine the duplication size and boundaries while the methylation status of the maternally methylated small nuclear ribonucleoprotein polypeptide N gene was used to determine the parent of origin of the duplication. We determined the duplication size and parental origin for 14 int dup(15) subjects: 10 maternal and 4 paternal cases. The majority of int dup(15) cases recruited were maternal in origin, most likely due to our finding that maternal duplication was coincident with autism spectrum disorder. The size of the duplication did not correlate with the severity of the phenotype as established by Autism Diagnostic Observation Scale calibrated severity score. We identified phenotypes not comprehensively described before in this cohort including mild facial dysmorphism, sleep problems and an unusual electroencephalogram variant. Our results are consistent with the hypothesis that the maternally expressed ubiquitin protein ligase E3A gene is primarily responsible for the autism phenotype in int dup(15) since all maternal cases tested presented on the autism spectrum. PMID:23495136

Brief Report: Functional MRI of a Patient with 7q11.23 Duplication Syndrome and Autism Spectrum Disorder

ERIC Educational Resources Information Center

Prontera, Paolo; Serino, Domenico; Caldini, Bernardo; Scarponi, Laura; Merla, Giuseppe; Testa, Giuseppe; Muti, Marco; Napolioni, Valerio; Mazzotta, Giovanni; Piccirilli, Massimo; Donti, Emilio

2014-01-01

The duplication of the Williams-Beuren syndrome (WBS) region (7q11.23) is a copy number variant associated with autism spectrum disorder (ASD). One of the most intriguing aspects is that the reciprocal microdeletion causes WBS, characterized by hypersociability, marked empathy, and a relative capacity in verbal short-term memory and language.…

Evaluation of a patient with classical Ehlers-Danlos syndrome due to a 9q34 duplication affecting COL5A1.

PubMed

Kuroda, Yukiko; Ohashi, Ikuko; Naruto, Takuya; Ida, Kazumi; Enomoto, Yumi; Saito, Toshiyuki; Nagai, Jun-Ichi; Kurosawa, Kenji

2018-03-09

Ehlers-Danlos syndrome classical type is a connective tissue disorder characterized by skin hyperextensibility, atrophic scarring, and joint hypermobility. The condition typically results from mutations in COL5A1 or COL5A2 leading to the functional haploinsufficiency. Here, we report of a 24-year-old male with mild intellectual disability, dysmorphic features, and a phenotype consistent with Ehlers-Danlos syndrome classical type. A copy number variant-calling algorithm from panel sequencing data identified the deletions exons 2-11 and duplications of exons 12-67 within COL5A1. Array comparative genomic hybridization confirmed a 94 kb deletion at 9q34.3 involving exons 2-11 of COL5A1, and a 3.4 Mb duplication at 9q34.3 involving exons 12-67 of COL5A1. © 2018 Japanese Teratology Society.

11p15 duplication and 13q34 deletion with Beckwith-Wiedemann syndrome and factor VII deficiency.

PubMed

Jurkiewicz, Dorota; Kugaudo, Monika; Tańska, Anna; Wawrzkiewicz-Witkowska, Angelika; Tomaszewska, Agnieszka; Kucharczyk, Marzena; Cieślikowska, Agata; Ciara, Elżbieta; Krajewska-Walasek, Małgorzata

2015-06-01

Here we report a patient with 11p15.4p15.5 duplication and 13q34 deletion presenting with Beckwith-Wiedemann syndrome (BWS) and moderate deficiency of factor VII (FVII). The duplication was initially diagnosed on methylation-sensitive multiplex ligation-dependent probe amplification. Array comparative genome hybridization confirmed its presence and indicated a 13q34 distal deletion. The patient's clinical symptoms, including developmental delay and facial dysmorphism, were typical of BWS with paternal 11p15 trisomy. Partial 13q monosomy in this patient is associated with moderate deficiency of FVII and may also overlap with a few symptoms of paternal 11p15 trisomy such as developmental delay and some facial features. To our knowledge this is the first report of 11p15.4p15.5 duplication associated with deletion of 13q34 and FVII deficiency. Moreover, this report emphasizes the importance of detailed clinical as well as molecular examinations in patients with BWS features and developmental delay. © 2015 Japan Pediatric Society.

Duplication 16p13.3 and the CREBBP gene: confirmation of the phenotype.

PubMed

Demeer, Bénédicte; Andrieux, Joris; Receveur, Aline; Morin, Gilles; Petit, Florence; Julia, Sophie; Plessis, Ghislaine; Martin-Coignard, Dominique; Delobel, Bruno; Firth, Helen V; Thuresson, Ann C; Lanco Dosen, Sandrine; Sjörs, Kerstin; Le Caignec, Cedric; Devriendt, Koenraad; Mathieu-Dramard, Michèle

2013-01-01

The introduction of molecular karyotyping technologies into the diagnostic work-up of patients with congenital disorders permitted the identification and delineation of novel microdeletion and microduplication syndromes. Interstitial 16p13.3 duplication, encompassing the CREBBP gene, which is mutated or deleted in the Rubinstein-Taybi syndrome, have been proposed to cause a recognisable syndrome with variable intellectual disability, normal growth, mild facial dysmorphism, mild anomalies of the extremities, and occasional findings such as developmental defects of the heart, genitalia, palate or the eyes. We here report the phenotypic and genotypic delineation of 9 patients carrying a submicroscopic 16p13.3 duplication, including the smallest 16p13.3 duplication reported so far. Careful clinical assessment confirms the distinctive clinical phenotype and also defines frequent associated features : marked speech problems, frequent ocular region involvement with upslanting of the eyes, narrow palpebral fissures, ptosis and strabismus, frequent proximal implantation of thumbs, cleft palate/bifid uvula and inguinal hernia. It also confirms that CREBBP is the critical gene involved in the duplication 16p13.3 syndrome. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

A method for determining haploid and triploid genotypes and their association with vascular phenotypes in Williams syndrome and 7q11.23 duplication syndrome.

PubMed

Gregory, Michael D; Kolachana, Bhaskar; Yao, Yin; Nash, Tiffany; Dickinson, Dwight; Eisenberg, Daniel P; Mervis, Carolyn B; Berman, Karen F

2018-04-04

Williams syndrome ([WS], 7q11.23 hemideletion) and 7q11.23 duplication syndrome (Dup7) show contrasting syndromic symptoms. However, within each group there is considerable interindividual variability in the degree to which these phenotypes are expressed. Though software exists to identify areas of copy number variation (CNV) from commonly-available SNP-chip data, this software does not provide non-diploid genotypes in CNV regions. Here, we describe a method for identifying haploid and triploid genotypes in CNV regions, and then, as a proof-of-concept for applying this information to explain clinical variability, we test for genotype-phenotype associations. Blood samples for 25 individuals with WS and 13 individuals with Dup7 were genotyped with Illumina-HumanOmni5M SNP-chips. PennCNV and in-house code were used to make genotype calls for each SNP in the 7q11.23 locus. We tested for association between the presence of aortic arteriopathy and genotypes of the remaining (haploid in WS) or duplicated (triploid in Dup7) alleles. Haploid calls in the 7q11.23 region were made for 99.0% of SNPs in the WS group, and triploid calls for 98.8% of SNPs in those with Dup7. The G allele of SNP rs2528795 in the ELN gene was associated with aortic stenosis in WS participants (p < 0.0049) while the A allele of the same SNP was associated with aortic dilation in Dup7. Commonly available SNP-chip information can be used to make haploid and triploid calls in individuals with CNVs and then to relate variability in specific genes to variability in syndromic phenotypes, as demonstrated here using aortic arteriopathy. This work sets the stage for similar genotype-phenotype analyses in CNVs where phenotypes may be more complex and/or where there is less information about genetic mechanisms.

Prader-Willi-like syndrome in a patient with an Xq23q25 duplication.

PubMed

Monaghan, K G; Van Dyke, D L; Feldman, G L

1998-11-16

We report on a 24-year old woman with an Xq duplication and findings suggestive of Prader-Willi syndrome (PWS). Her birth weight was at the 3rd centile and her birth length was less than the 3rd centile. She was hypotonic and had a weak cry as an infant. There were no feeding difficulties, although her mother reports that as an infant, she was "small for her age." Excessive weight gain began between 3 and 4 years. The patient's development was delayed and she received special education. She has a history of hiding food. She has a sleep disturbance disorder and inappropriate social behavior. At the age of 24 years her height was below the 5th centile and weight >95th centile. She has physical findings typical of PWS, skin picking, and speech articulation defects. Cytogenetic analysis showed a 46,X,dup(X)(q23q25) karyotype. Fluorescent in situ hybridization (FISH) studies using a chromosome X painting probe demonstrated that the rearrangement was intrachromosomal. The X-chromosome fold scoring technique was used to determine the X inactivation pattern and indicated that some cells expressed the abnormal X chromosome. Results of FISH studies using the SNRPN probe localized to 15q11q13 and DNA studies using the PW71B and SNRPN probes were normal. The duplicated X chromosome, random X inactivation pattern, and the negative molecular studies for PWS indicate that the abnormal X chromosome is the basis of this patient's phenotype. This patient emphasizes the importance of obtaining a karyotype even when a syndrome diagnosable by molecular methods is strongly suspected.

Gene duplication and the evolution of phenotypic diversity in insect societies.

PubMed

Chau, Linh M; Goodisman, Michael A D

2017-12-01

Gene duplication is an important evolutionary process thought to facilitate the evolution of phenotypic diversity. We investigated if gene duplication was associated with the evolution of phenotypic differences in a highly social insect, the honeybee Apis mellifera. We hypothesized that the genetic redundancy provided by gene duplication could promote the evolution of social and sexual phenotypes associated with advanced societies. We found a positive correlation between sociality and rate of gene duplications across the Apoidea, indicating that gene duplication may be associated with sociality. We also discovered that genes showing biased expression between A. mellifera alternative phenotypes tended to be found more frequently than expected among duplicated genes than singletons. Moreover, duplicated genes had higher levels of caste-, sex-, behavior-, and tissue-biased expression compared to singletons, as expected if gene duplication facilitated phenotypic differentiation. We also found that duplicated genes were maintained in the A. mellifera genome through the processes of conservation, neofunctionalization, and specialization, but not subfunctionalization. Overall, we conclude that gene duplication may have facilitated the evolution of social and sexual phenotypes, as well as tissue differentiation. Thus this study further supports the idea that gene duplication allows species to evolve an increased range of phenotypic diversity. © 2017 The Author(s). Evolution © 2017 The Society for the Study of Evolution.

Genetics Home Reference: MECP2 duplication syndrome

MedlinePlus

... of autism spectrum disorders that affect communication and social interaction. Females with a MECP2 gene duplication tend to ... Accessibility FOIA Viewers & Players U.S. Department of Health & Human Services National Institutes of Health National Library of ...

Dorsal dimelia in patau syndrome: a case report.

PubMed

Fattah, A; Pickford, M A

2007-10-01

We present a case of a child with Patau syndrome that exhibits features consistent with congenital palmar nail syndrome. The literature is reviewed and evidence presented to demonstrate that this is a defect in the dorso-ventral patterning of the limb and thus a form of dorsal dimelia. In order to differentiate this from other instances of ectopic nail tissue we suggest congenital palmar nail syndrome should be more specifically defined as duplicated nails, absent flexion creases, non-glabrous skin on the palmar surface, reduced movement at the interphalangeal joints and hypoplastic terminal phalanges.

5p13 microduplication syndrome: a new case and better clinical definition of the syndrome.

PubMed

Novara, Francesca; Alfei, Enrico; D'Arrigo, Stefano; Pantaleoni, Chiara; Beri, Silvana; Achille, Valentina; Sciacca, Francesca L; Giorda, Roberto; Zuffardi, Orsetta; Ciccone, Roberto

2013-01-01

Chromosome 5p13 duplication syndrome (OMIM #613174), a contiguous gene syndrome involving duplication of several genes on chromosome 5p13 including NIPBL (OMIM 608667), has been described in rare patients with developmental delay and learning disability, behavioral problems and peculiar facial dysmorphisms. 5p13 duplications described so far present with variable sizes, from 0.25 to 13.6 Mb, and contain a variable number of genes. Here we report another patient with 5p13 duplication syndrome including NIPBL gene only. Proband's phenotype overlapped that reported in patients with 5p13 microduplication syndrome and especially that of subjects with smaller duplications. Moreover, we better define genotype-phenotype relationship associated with this duplication and confirmed that NIPBL was likely the major dosage sensitive gene for the 5p13 microduplication phenotype. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

Differentiated thyroid cancer associated with intestinal polyposis syndromes: a review.

PubMed

Harb, William J; Sturgis, Erich M

2009-11-01

Intestinal polyposis syndromes, such as familial adenomatous polyposis (FAP) and Cowden's syndrome, are often associated with extraintestinal manifestations, and while many of these manifestations are benign, malignant extraintestinal manifestations, such as differentiated thyroid cancers, do occur. Although differentiated thyroid cancers (ie, papillary and follicular thyroid carcinomas) are associated with multiple syndromes, they are most commonly associated with intestinal polyposis syndromes. In the general population, the probability of developing thyroid cancer by age 65 years is only .5%. However, 1% to 2% of patients with FAP develop papillary thyroid carcinoma, the most common extraintestinal malignancy in patients with FAP. Also, up to 10% of patients with Cowden's syndrome will develop follicular thyroid carcinoma. The purpose of this review was to provide an overview of FAP, Cowden's syndrome, and Peutz-Jeghers syndrome, to discuss in detail the associations between intestinal polyposis syndromes and differentiated thyroid cancers, and to provide suggestions for screening and managing these diseases. (c) 2009 Wiley Periodicals, Inc. Head Neck, 2009.

Intrachromosomal 3p insertion as a cause of reciprocal pure interstitial deletion and duplication in two siblings: further delineation of the emerging proximal 3p deletion syndrome.

PubMed

Lloveras, Elisabet; Vendrell, Teresa; Fernández, Asunción; Castells, Neus; Cueto, Ana; del Campo, Miguel; Hernando, Cristina; Villa, Olaya; Plaja, Alberto

2014-01-01

Very few cases of constitutional interstitial deletions of the proximal short arm of chromosome 3 have been reported; however, the proximal 3p deletion is emerging as a clinically recognizable syndrome. We present an intrachromosomal insertion of 3p12.3p14.1 in a phenotypic normal man (46,XY,ins(3)(p25p12.3p14.1)) which is responsible for the unbalanced karyotype in 2 affected offspring, one with a 3p12.3p14.1 interstitial deletion and the other with a reciprocal duplication. The exceptionality of these 2 reciprocal recombinants contributes to a better definition of the proximal 3p deletion syndrome and its duplication counterpart.

Tandem duplication within a Neurofibromatosis type I (NFI) gene exon in a family with features of Watson syndrome and Noonan syndrome

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tassabehji, M.; Strachan, T.; Colley, A.

Type 1 neurofibromatosis (NF1), Watson syndrome (WS), and Noonan syndrome (NS) show some overlap in clinical manifestations. In addition, WS has been shown to be linked to markers flanking the NF1 locus and a deletion at the NF1 locus demonstrated in a WS patient. This suggests either that WS and NF1 are allelic or the phenotypes arise from mutations in very closely linked genes. Here the authors provide evidence for the former by demonstrating a mutation in the NF1 gene in a family with features of both WS and NS. The mutation is an almost perfect in-frame tandem duplication ofmore » 42 bases in exon 28 of the NF1 gene. Unlike the mutations previously described in classical NF1, which show a preponderance of null alleles, the mutation in this family would be expected to result in a mutant neurofibromin product. 31 refs., 2 figs.« less

Delusion of fetal duplication in a Capgras patient.

PubMed

Silva, J A; Leong, G B; Longhitano, M; Botello, T E

1991-02-01

A case of Capgras syndrome in a pregnant patient is described. In addition to perceiving living family members as impostors, she believed that there was a double or twin of her fetus. She conceptualized her "twins" differently than the way she viewed doubles of family members. Her fetus may represent the youngest "person" to have been duplicated. The relationship of Capgras syndrome to misidentification phenomena is discussed.

Differentiation of lepidoptera scale cells from epidermal stem cells followed by ecdysone-regulated DNA duplication and scale secreting.

PubMed

Yuan, Shenglei; Huang, Wuren; Geng, Lei; Beerntsen, Brenda T; Song, Hongsheng; Ling, Erjun

2017-01-01

Integuments are the first line to protect insects from physical damage and pathogenic infection. In lepidopteran insects, they undergo distinct morphology changes such as scale formation during metamorphosis. However, we know little about integument development and scale formation during this stage. Here, we use the silkworm, Bombyx mori, as a model and show that stem cells in the integument of each segment, but not intersegmental membrane, divide into two scale precursor cells during the spinning stage. In young pupae, the scale precursor cell divides again. One of the daughter cells becomes a mature scale-secreting cell that undergoes several rounds of DNA duplication and the other daughter cell undergoes apoptosis later on. This scale precursor cell division is crucial to the development and differentiation of scale-secreting cells because scale production can be blocked after treatment with the cell division inhibitor paclitaxel. Subsequently, the growth of scale-secreting cells is under the control of 20-hydroxyecdysone but not juvenile hormone since injection of 20-hydroxyecdysone inhibited scale formation. Further work demonstrated that 20-hydroxyecdysone injection inhibits DNA duplication in scale-secreting cells while the expression of scale-forming gene ASH1 was down-regulated by BR-C Z2. Therefore, this research demonstrates that the scale cells of the silkworm develops through stem cell division prior to pupation and then another wave of cell division differentiates these cells into scale secreting cells soon after entrance into the pupal stage. Additionally, DNA duplication and scale production in the scale-secreting cells were found to be under the regulation of 20-hydroxyecdysone.

Laparoscopic resection of adult colon duplication causing intussusception

PubMed Central

Kyo, Kennoki; Azuma, Masaki; Okamoto, Kazuya; Nishiyama, Motohiro; Shimamura, Takahiro; Maema, Atsushi; Shirakawa, Motoaki; Nakamura, Toshio; Koda, Kenji; Yokoyama, Hidetaro

2016-01-01

Gastrointestinal duplications are uncommon congenital malformations that can occur anywhere along the gastrointestinal tract. Most cases are recognized before the age of 2 years, and those encountered in adults are rare. We describe here a case of ascending colon duplication in a 20-year-old male that caused intussusception and was treated laparoscopically. Although computed tomography revealed a cystic mass filled with stool-like material, the preoperative diagnosis was a submucosal tumor of the ascending colon. We performed a laparoscopic right colectomy, and the postoperative pathological diagnosis was duplication of the ascending colon, both cystic and tubular components. We conclude that gastrointestinal duplications, although rare, should be considered in the differential diagnosis of all abdominal and submucosal cystic lesions and that laparoscopy is a preferred approach for the surgical treatment of gastrointestinal duplications. PMID:26900303

Genotype-phenotype characterization in 13 individuals with chromosome Xp11.22 duplications.

PubMed

Grams, Sarah E; Argiropoulos, Bob; Lines, Matthew; Chakraborty, Pranesh; Mcgowan-Jordan, Jean; Geraghty, Michael T; Tsang, Marilyn; Eswara, Marthand; Tezcan, Kamer; Adams, Kelly L; Linck, Leesa; Himes, Patricia; Kostiner, Dana; Zand, Dina J; Stalker, Heather; Driscoll, Daniel J; Huang, Taosheng; Rosenfeld, Jill A; Li, Xu; Chen, Emily

2016-04-01

We report 13 new individuals with duplications in Xp11.22-p11.23. The index family has one male and two female members in three generations with mild-severe intellectual disability (ID), speech delay, dysmorphic features, early puberty, constipation, and/or hand and foot abnormalities. Affected individuals were found to have two small duplications in Xp11.22 at nucleotide position (hg19) 50,112,063-50,456,458 bp (distal) and 53,160,114-53,713,154 bp (proximal). Collectively, these two regions include 14 RefSeq genes, prompting collection of a larger cohort of patients, in an attempt to delineate critical genes associated with the observed phenotype. In total, we have collected data on nine individuals with duplications overlapping the distal duplication region containing SHROOM4 and DGKK and eight individuals overlapping the proximal region including HUWE1. Duplications of HUWE1 have been previously associated with non-syndromic ID. Our data, with previously published reports, suggest that duplications involving SHROOM4 and DGKK may represent a new syndromic X-linked ID critical region associated with mild to severe ID, speech delay +/- dysarthria, attention deficit disorder, precocious puberty, constipation, and motor delay. We frequently observed foot abnormalities, 5th finger clinodactyly, tapering fingers, constipation, and exercise intolerance in patients with duplications of these two genes. Regarding duplications including the proximal region, our observations agree with previous studies, which have found associations with intellectual disability. In addition, expressive language delay, failure to thrive, motor delay, and 5th finger clinodactyly were also frequently observed in patients with the proximal duplication. © 2015 Wiley Periodicals, Inc.

The evolution of duplicate gene expression in mammalian organs

PubMed Central

Guschanski, Katerina; Warnefors, Maria; Kaessmann, Henrik

2017-01-01

Gene duplications generate genomic raw material that allows the emergence of novel functions, likely facilitating adaptive evolutionary innovations. However, global assessments of the functional and evolutionary relevance of duplicate genes in mammals were until recently limited by the lack of appropriate comparative data. Here, we report a large-scale study of the expression evolution of DNA-based functional gene duplicates in three major mammalian lineages (placental mammals, marsupials, egg-laying monotremes) and birds, on the basis of RNA sequencing (RNA-seq) data from nine species and eight organs. We observe dynamic changes in tissue expression preference of paralogs with different duplication ages, suggesting differential contribution of paralogs to specific organ functions during vertebrate evolution. Specifically, we show that paralogs that emerged in the common ancestor of bony vertebrates are enriched for genes with brain-specific expression and provide evidence for differential forces underlying the preferential emergence of young testis- and liver-specific expressed genes. Further analyses uncovered that the overall spatial expression profiles of gene families tend to be conserved, with several exceptions of pronounced tissue specificity shifts among lineage-specific gene family expansions. Finally, we trace new lineage-specific genes that may have contributed to the specific biology of mammalian organs, including the little-studied placenta. Overall, our study provides novel and taxonomically broad evidence for the differential contribution of duplicate genes to tissue-specific transcriptomes and for their importance for the phenotypic evolution of vertebrates. PMID:28743766

Pathogenic role of mtDNA duplications in mitochondrial diseases associated with mtDNA deletions.

PubMed

Odoardi, Francesca; Rana, Michele; Broccolini, Aldobrando; Mirabella, Massimiliano; Modoni, Anna; D'Amico, Adele; Papacci, Manuela; Tonali, Pietro; Servidei, Serenella; Silvestri, Gabriella

2003-04-30

We estimated the frequency of multiple mtDNA rearrangements by Southern blot in 32 patients affected by mitochondrial disorders associated with single deletions in order to assess genotype-phenotype correlations and elucidate the pathogenic significance of mtDNA duplications. Muscle in situ hybridization studies were performed in patients showing mtDNA duplications at Southern blot. We found multiple rearrangements in 12/32 (37.5%) patients; in particular, mtDNA duplications were detected in 4/4 Kearns-Sayre syndrome (KSS), in 1 Pearson's syndrome, in 1/3 encephalomyopathies with progressive external ophthalmoplegia (PEO), and in 2/23 PEO. In situ studies documented an exclusive accumulation of deleted mtDNAs in cytochrome c oxidase negative fibers of patients with mtDNA duplications. The presence of mtDNA duplications significantly correlated with onset of symptoms before age 15 and occurrence of clinical multisystem involvement. Analysis of biochemical data documented a predominant reduction of complex III in patients without duplications compared to patients with mtDNA duplications. Our data indicate that multiple mtDNA rearrangements are detectable in a considerable proportion of patients with single deletions and that mtDNA duplications do not cause any oxidative impairment. They more likely play a pathogenic role in the determination of clinical expression of mitochondrial diseases associated with single mtDNA deletions, possibly generating deleted mtDNAs in embryonic tissues by homologous recombination. Copyright 2003 Wiley-Liss, Inc.

Prenatal detection of a de novo terminal inverted duplication 4p in a fetus with the Wolf-Hirschhorn syndrome phenotype.

PubMed

Beaujard, M-P; Jouannic, J-M; Bessières, B; Borie, C; Martin-Luis, I; Fallet-Bianco, C; Portnoï, M-F

2005-06-01

To present the prenatal diagnosis of a de novo terminal inversion duplication of the short arm of chromosome 4 and a review of the literature. An amniocentesis for chromosome analysis was performed at 33 weeks' gestation because ultrasound examination showed a female fetus with multiple abnormalities consisting of severe intrauterine growth retardation, microcephaly, a cleft lip and renal hypoplasia. Cytogenetic analysis and FISH studies of the cultured amniocytes revealed a de novo terminal inversion duplication of the short arm of chromosome 4 characterized by a duplication of 4p14-p16.1 chromosome region concomitant with a terminal deletion 4p16.1-pter. The karyotype was thus: 46,XX, inv dup del (4)(:p14-->p16.1::p16.1-->qter). The parents opted to terminate the pregnancy. Fetopathological examination showed dysmorphic features and abnormalities consistent with a Wolf-Hirschhorn syndrome (WHS) diagnosis, clinical manifestations of partial 4p trisomy being mild. Although relatively rare, inverted duplications have been reported repeatedly in an increasing number of chromosomes. Only two previous cases with de novo inv dup del (4p) and one with tandem dup 4p have been reported, all of them associated with a 4pter deletion. We report the first case diagnosed prenatally. Breakpoints are variable, resulting in different abnormal phenotype. In our case, clinical manifestations resulted in a WHS phenotype.

Experimental study of the embryogenesis of gastrointestinal duplication and enteric cyst.

PubMed

Emura, Takaki; Hashizume, Kohei; Asashima, Makoto

2003-05-01

The theory of gastrointestinal duplication and enteric cyst embryogenesis was verified by examining the developmental process of this experimentally induced anomaly. In Cynopus pyrrhogaster (amphibian) embryos (stage 18), the dorsal midline structures (including the neural plate and notochord) were split regionally to induce partial separation of the notochord and gut anlage endoderm herniation between the split elements of the notochord. Following this procedure, the embryonic development was traced morphologically and histologically. Control embryos were cultured without the procedure. Following the incubation and breeding period, gastrointestinal duplication and enteric cysts were observed with vertebral anomaly, spina bifida, split cord malformation and subcutaneous manifestations in the mature animals. The combination of anomalies that was observed in these experimental animals is consistent with that found in "split notochord syndrome." No abnormal morphology or histology was observed in the control group. The embryogenetic theory of gastrointestinal duplication and enteric cysts was thus verified by simulating the partial separation of the notochord, which induced split notochord syndrome in laboratory animals. The results indicate that gastrointestinal duplication and enteric cysts may arise through a process of herniation of the gut anlage endoderm between split elements of the notochord.

Differentiating fasciculoventricular pathway from Wolff-Parkinson-White syndrome by electrocardiography.

PubMed

Suzuki, Tsugutoshi; Nakamura, Yoshihide; Yoshida, Shuichiro; Yoshida, Yoko; Shintaku, Haruo

2014-04-01

In school-based cardiovascular screening programs in Japan, Wolff-Parkinson-White (WPW) syndrome is diagnosed based on the presence of an electrocardiographic (ECG) delta wave without differentiation from the fasciculoventricular pathway (FVP), although the risk of sudden death is associated only with the former. The purpose of this study was to differentiate FVP patients among children diagnosed with WPW syndrome by ECG. Children who were diagnosed with WPW syndrome through school screening between April 2006 and March 2008 and had QRS width ≤120 ms were included. Patients with asthma and/or coronary heart disease were excluded. FVP and WPW syndrome were differentiated based on ECG responses to adenosine triphosphate (ATP) injection. Age, PR interval, QRS width, and Rosenbaum classification were compared among patients. Thirty patients (median age 12.7 years, range 6.5-15.7 years) participated in the study. FVP was diagnosed in 23 patients (76.7%), and WPW syndrome in 7 (23.3%). In Rosenbaum type A patients, all six patients had WPW syndrome, whereas FVP was diagnosed in 23 of 24 and WPW syndrome was diagnosed in 1 of 24 of type B patients. Age, PR interval, and QRS width were not significantly different between the two conditions. ATP stress test was reliable in differentiating FVP from WPW syndrome. Although FVP is considered rare, the results of our study indicate that many WPW syndrome patients with QRS width ≤120 ms may actually have FVP. Patients categorized as type B are more likely to have FVP, whereas type A patients are most likely to have WPW syndrome. © 2013 Heart Rhythm Society Published by Heart Rhythm Society All rights reserved.

Restriction of the Patau syndrome to duplication of 13q22{yields}q.32 and possible role of interphase nuclear structure

DOE Office of Scientific and Technical Information (OSTI.GOV)

Helali, A.N.; Jafolla, A.K.; Oumsiych, M.B.

1994-09-01

A 10-year-old white male presented with mild microcephaly, slight growth and psychomotor retardation, soft fleshy ears, and normal facial features except for thin lips. No other significant anomalies were reported except for tethered cord discovered at age 8 years. The karyotype was found to be 46,XY,der(18)t(13;18)(q32;p11.32)pat. The mild phenotype appears to be primarily due to the duplication of 13q32{yields}qter. None of the cardinal features of trisomy 13 are found in cases of duplication of bands 13q22 to qter. This case shows that Patau syndrome phenotype does not originate by duplication of 13q32{yields}qter and may thus be restricted to 13q22 tomore » 13q32. The variability in phenotypes points to an alternative explanation to the classical one of additive and interactive gene effects. This model involves effects of changes in chromosome position in the interphase nucleus on gene expression.« less

B-acute lymphoblastic leukemia and cystinuria in a patient with duplication 22q11.21 detected by chromosomal microarray analysis.

PubMed

Chang, Vivian Y; Quintero-Rivera, Fabiola; Baldwin, Erin E; Woo, Kathy; Martinez-Agosto, Julian A; Fu, Cecilia; Gomperts, Brigitte N

2011-03-01

Duplication 22q11.2 syndrome is the result of a microduplication of the same chromosomal region that is deleted in DiGeorge and Velocardiofacial syndromes. We describe a patient with dysmorphic features who was diagnosed with pre-B acute lymphoblastic leukemia, and developed cystinuria and pancreatitis during treatment. Duplication 22q11.2 has not been previously described in association with hematologic abnormalities. Chromosomal microarray technology was used to diagnose duplication 22q11.2 syndrome. In this era of advanced genomics, this technology has become an important method for helping to determine the molecular basis of diseases, best treatments and ultimately patient outcomes. Copyright © 2010 Wiley-Liss, Inc.

Parental Origin of Interstitial Duplications at 15q11.2-q13.3 in Schizophrenia and Neurodevelopmental Disorders

PubMed Central

Isles, Anthony R.; Ingason, Andrés; Lowther, Chelsea; Gawlick, Micha; Stöber, Gerald; Potter, Harry; Georgieva, Lyudmila; Pizzo, Lucilla; Ozaki, Norio; Kushima, Itaru; Ikeda, Masashi; Iwata, Nakao; Levinson, Douglas F.; Gejman, Pablo V.; Shi, Jianxin; Sanders, Alan R.; Duan, Jubao; Sisodiya, Sanjay; Costain, Gregory; Degenhardt, Franziska; Giegling, Ina; Rujescu, Dan; Hreidarsson, Stefan J.; Saemundsen, Evald; Ahn, Joo Wook; Ogilvie, Caroline; Stefansson, Hreinn; Stefansson, Kari; O’Donovan, Michael C.; Owen, Michael J.; Bassett, Anne; Kirov, George

2016-01-01

Duplications at 15q11.2-q13.3 overlapping the Prader-Willi/Angelman syndrome (PWS/AS) region have been associated with developmental delay (DD), autism spectrum disorder (ASD) and schizophrenia (SZ). Due to presence of imprinted genes within the region, the parental origin of these duplications may be key to the pathogenicity. Duplications of maternal origin are associated with disease, whereas the pathogenicity of paternal ones is unclear. To clarify the role of maternal and paternal duplications, we conducted the largest and most detailed study to date of parental origin of 15q11.2-q13.3 interstitial duplications in DD, ASD and SZ cohorts. We show, for the first time, that paternal duplications lead to an increased risk of developing DD/ASD/multiple congenital anomalies (MCA), but do not appear to increase risk for SZ. The importance of the epigenetic status of 15q11.2-q13.3 duplications was further underlined by analysis of a number of families, in which the duplication was paternally derived in the mother, who was unaffected, whereas her offspring, who inherited a maternally derived duplication, suffered from psychotic illness. Interestingly, the most consistent clinical characteristics of SZ patients with 15q11.2-q13.3 duplications were learning or developmental problems, found in 76% of carriers. Despite their lower pathogenicity, paternal duplications are less frequent in the general population with a general population prevalence of 0.0033% compared to 0.0069% for maternal duplications. This may be due to lower fecundity of male carriers and differential survival of embryos, something echoed in the findings that both types of duplications are de novo in just over 50% of cases. Isodicentric chromosome 15 (idic15) or interstitial triplications were not observed in SZ patients or in controls. Overall, this study refines the distinct roles of maternal and paternal interstitial duplications at 15q11.2-q13.3, underlining the critical importance of maternally

Parental Origin of Interstitial Duplications at 15q11.2-q13.3 in Schizophrenia and Neurodevelopmental Disorders.

PubMed

Isles, Anthony R; Ingason, Andrés; Lowther, Chelsea; Walters, James; Gawlick, Micha; Stöber, Gerald; Rees, Elliott; Martin, Joanna; Little, Rosie B; Potter, Harry; Georgieva, Lyudmila; Pizzo, Lucilla; Ozaki, Norio; Aleksic, Branko; Kushima, Itaru; Ikeda, Masashi; Iwata, Nakao; Levinson, Douglas F; Gejman, Pablo V; Shi, Jianxin; Sanders, Alan R; Duan, Jubao; Willis, Joseph; Sisodiya, Sanjay; Costain, Gregory; Werge, Thomas M; Degenhardt, Franziska; Giegling, Ina; Rujescu, Dan; Hreidarsson, Stefan J; Saemundsen, Evald; Ahn, Joo Wook; Ogilvie, Caroline; Girirajan, Santhosh D; Stefansson, Hreinn; Stefansson, Kari; O'Donovan, Michael C; Owen, Michael J; Bassett, Anne; Kirov, George

2016-05-01

Duplications at 15q11.2-q13.3 overlapping the Prader-Willi/Angelman syndrome (PWS/AS) region have been associated with developmental delay (DD), autism spectrum disorder (ASD) and schizophrenia (SZ). Due to presence of imprinted genes within the region, the parental origin of these duplications may be key to the pathogenicity. Duplications of maternal origin are associated with disease, whereas the pathogenicity of paternal ones is unclear. To clarify the role of maternal and paternal duplications, we conducted the largest and most detailed study to date of parental origin of 15q11.2-q13.3 interstitial duplications in DD, ASD and SZ cohorts. We show, for the first time, that paternal duplications lead to an increased risk of developing DD/ASD/multiple congenital anomalies (MCA), but do not appear to increase risk for SZ. The importance of the epigenetic status of 15q11.2-q13.3 duplications was further underlined by analysis of a number of families, in which the duplication was paternally derived in the mother, who was unaffected, whereas her offspring, who inherited a maternally derived duplication, suffered from psychotic illness. Interestingly, the most consistent clinical characteristics of SZ patients with 15q11.2-q13.3 duplications were learning or developmental problems, found in 76% of carriers. Despite their lower pathogenicity, paternal duplications are less frequent in the general population with a general population prevalence of 0.0033% compared to 0.0069% for maternal duplications. This may be due to lower fecundity of male carriers and differential survival of embryos, something echoed in the findings that both types of duplications are de novo in just over 50% of cases. Isodicentric chromosome 15 (idic15) or interstitial triplications were not observed in SZ patients or in controls. Overall, this study refines the distinct roles of maternal and paternal interstitial duplications at 15q11.2-q13.3, underlining the critical importance of maternally

Dendritic Arborization and Spine Dynamics Are Abnormal in the Mouse Model of MECP2 Duplication Syndrome

PubMed Central

Jiang, Minghui; Ash, Ryan T.; Baker, Steven A.; Suter, Bernhard; Ferguson, Andrew; Park, Jiyoung; Rudy, Jessica; Torsky, Sergey P.; Chao, Hsiao-Tuan; Zoghbi, Huda Y.

2013-01-01

MECP2 duplication syndrome is a childhood neurological disorder characterized by intellectual disability, autism, motor abnormalities, and epilepsy. The disorder is caused by duplications spanning the gene encoding methyl-CpG-binding protein-2 (MeCP2), a protein involved in the modulation of chromatin and gene expression. MeCP2 is thought to play a role in maintaining the structural integrity of neuronal circuits. Loss of MeCP2 function causes Rett syndrome and results in abnormal dendritic spine morphology and decreased pyramidal dendritic arbor complexity and spine density. The consequences of MeCP2 overexpression on dendritic pathophysiology remain unclear. We used in vivo two-photon microscopy to characterize layer 5 pyramidal neuron spine turnover and dendritic arborization as a function of age in transgenic mice expressing the human MECP2 gene at twice the normal levels of MeCP2 (Tg1; Collins et al., 2004). We found that spine density in terminal dendritic branches is initially higher in young Tg1 mice but falls below control levels after postnatal week 12, approximately correlating with the onset of behavioral symptoms. Spontaneous spine turnover rates remain high in older Tg1 animals compared with controls, reflecting the persistence of an immature state. Both spine gain and loss rates are higher, with a net bias in favor of spine elimination. Apical dendritic arbors in both simple- and complex-tufted layer 5 Tg1 pyramidal neurons have more branches of higher order, indicating that MeCP2 overexpression induces dendritic overgrowth. P70S6K was hyperphosphorylated in Tg1 somatosensory cortex, suggesting that elevated mTOR signaling may underlie the observed increase in spine turnover and dendritic growth. PMID:24336718

Esophageal duplication and congenital esophageal stenosis.

PubMed

Trappey, A Francois; Hirose, Shinjiro

2017-04-01

Esophageal duplication and congenital esophageal stenosis (CES) may represent diseases with common embryologic etiologies, namely, faulty tracheoesophageal separation and differentiation. Here, we will re-enforce definitions for these diseases as well as review their embryology, diagnosis, and treatment. Copyright © 2017. Published by Elsevier Inc.

MLL duplication in a pediatric patient with B-cell lymphoblastic lymphoma.

PubMed

Mater, David Van; Goodman, Barbara K; Wang, Endi; Gaca, Ana M; Wechsler, Daniel S

2012-04-01

Lymphoblastic lymphoma is the second most common type of non-Hodgkin lymphoma seen in children. Approximately, 90% of lymphoblastic lymphomas arise from T cells, with the remaining 10% being B-cell-lineage derived. Although T-cell lymphoblastic lymphoma most frequently occurs in the anterior mediastinum (thymus), B-cell lymphoblastic lymphoma (B-LBL) predominates in extranodal sites such as skin and bone. Here, we describe a pediatric B-LBL patient who presented with extensive abdominal involvement and whose lymphoma cells displayed segmental duplication of the mixed lineage leukemia (MLL) gene. MLL duplication/amplification has been described primarily in acute myeloid leukemia and myelodysplastic syndrome with no published reports of discrete MLL duplication/amplification events in B-LBL. The MLL gene duplication noted in this case may represent a novel mechanism for tumorigenesis in B-LBL.

[Overview and prospect of syndrome differentiation of hypertension in traditional Chinese medicine].

PubMed

Yang, Xiao-Chen; Xiong, Xing-Jiang; Wang, Jie

2014-01-01

This article is to overview the literature of syndrome differentiation of traditional Chinese medicine on hypertension. According to the theory of disease in combination with syndrome, we concluded syndrome types of hypertension in four aspects, including national standards, industry standards, teaching standards and personal experience. Meanwhile, in order to provide new methods and approaches for normalized research, we integrated modern testing methods and statistical methods to analyze syndrome differentiation for the treatment of hypertension.

Hypergastrinemia and a duodenal ulcer caused by gastric duplication.

PubMed

Tanaka, Hideaki; Masumoto, Kouji; Sasaki, Takato; Sakamoto, Naoya; Gotoh, Chikashi; Urita, Yasuhisa; Shinkai, Toko; Takayasu, Hajime; Nakano, Noriyuki; Noguchi, Masayuki; Kudo, Toyoichiro

2016-12-01

Hypergastrinemia and the resultant peptic ulcer related to an enteric duplication has been quite rarely reported in the literature. We herein report the case of a 4-year-old girl who presented with hypergastrinemia and a duodenal ulcer at 2 years of age. She had been followed up with a proton pump inhibitor, which resulted in resolution of the ulcer; however, unexplained hypergastrinemia had continued. A cystic lesion at the antrum was discovered at 4 years of age, which we suspected to be a gastric duplication. After we resected the lesion, the hypergastrinemia resolved without recurrence of the duodenal ulcer. The histology was compatible with a gastric duplication, and the lumen was lined with antral mucosa that strongly stained positive for gastrin. We presumed that the antral mucosa inside the duplication in our case had no hydrogen ion feedback inhibition of gastrin release from gastrin cells and increased release of gastrin from the mucosa inside the duplication led to the duodenal ulcer. Only two cases have been reported in the literature that had hypergastrinemia related to enteric duplication. Gastric duplication should be included in the differential diagnosis of sustained hypergastrinemia in children.

Xq26.1-26.3 duplication including MOSPD1 and GPC3 identified in boy with short stature and double outlet right ventricle.

PubMed

Hirota, Yukiko; Minami, Takaomi; Sato, Tomoyuki; Yokomizo, Akiko; Matsumoto, Auimi; Goto, Masahide; Jinbo, Eriko; Yamamgata, Takanori

2017-09-01

Xq25q26 duplication syndrome has been reported in individuals with clinical features such as short stature, intellectual disability, syndromic facial appearance, small hands and feet, and genital abnormalities. The symptoms are related to critical chromosome regions including Xq26.1-26.3. In this particular syndrome, no patient with congenital heart disease was previously reported. Here, we report a 6-year-old boy with typical symptoms of Xq25q26 duplication syndrome and double outlet right ventricle (DORV) with pulmonary atresia (PA). He had the common duplicated region of Xq25q26 duplication syndrome extending to the distal region including the MOSPD1 locus. MOSPD1 regulates transforming growth factor beta (TGFβ) 2,3 and may be responsible for cardiac development including DORV. In the patient's lymphocytes, mRNA expression of TGFβ2 was lower than control, and might cause DORV as it does in TGFβ2-deficient mice. Therefore, MOSPD1 is a possible candidate gene for DORV, probably in combination with GPC3. Further studies of the combined functions of MOSPD1 and GPC3 are needed, and identification of additional patients with MOSPD1 and GPC3 duplication should be pursued. © 2017 Wiley Periodicals, Inc.

De novo direct duplication of chromosome segment 22q11.2-q13.1

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fujimoto, Atsuko; Lin, Ming S.

Lindsay et al. [1995] reported a case of de novo duplication of the segment 22q11-q12. Molecular cytogenetics studies showed that the segment includes the regions responsible for the {open_quotes}cat eye,{close_quotes} DiGeorge, and velo-cardio-facial syndrome, and extends distal to the breakpoint cluster region. The phenotype was milder than that of complete trisomy 22 and der(22)t(11;22) (q23;q11) syndrome and was similar in type and severity to that of {open_quotes}cat eye{close_quotes} syndrome (CES). They suggested that trisomy of gene(s) responsible for the CES might have a predominant phenotypic effect over other genes present in the region duplicated in their patient. 3 refs., 2more » figs.« less

Functional requirements driving the gene duplication in 12 Drosophila species.

PubMed

Zhong, Yan; Jia, Yanxiao; Gao, Yang; Tian, Dacheng; Yang, Sihai; Zhang, Xiaohui

2013-08-15

Gene duplication supplies the raw materials for novel gene functions and many gene families arisen from duplication experience adaptive evolution. Most studies of young duplicates have focused on mammals, especially humans, whereas reports describing their genome-wide evolutionary patterns across the closely related Drosophila species are rare. The sequenced 12 Drosophila genomes provide the opportunity to address this issue. In our study, 3,647 young duplicate gene families were identified across the 12 Drosophila species and three types of expansions, species-specific, lineage-specific and complex expansions, were detected in these gene families. Our data showed that the species-specific young duplicate genes predominated (86.6%) over the other two types. Interestingly, many independent species-specific expansions in the same gene family have been observed in many species, even including 11 or 12 Drosophila species. Our data also showed that the functional bias observed in these young duplicate genes was mainly related to responses to environmental stimuli and biotic stresses. This study reveals the evolutionary patterns of young duplicates across 12 Drosophila species on a genomic scale. Our results suggest that convergent evolution acts on young duplicate genes after the species differentiation and adaptive evolution may play an important role in duplicate genes for adaption to ecological factors and environmental changes in Drosophila.

Altered neuronal network and rescue in a human MECP2 duplication model

PubMed Central

Nageshappa, Savitha; Carromeu, Cassiano; Trujillo, Cleber A.; Mesci, Pinar; Espuny-Camacho, Ira; Pasciuto, Emanuela; Vanderhaeghen, Pierre; Verfaillie, Catherine; Raitano, Susanna; Kumar, Anujith; Carvalho, Claudia M.B.; Bagni, Claudia; Ramocki, Melissa B.; Araujo, Bruno H. S.; Torres, Laila B.; Lupski, James R.; Van Esch, Hilde; Muotri, Alysson R.

2015-01-01

Increased dosage of MeCP2 results in a dramatic neurodevelopmental phenotype with onset at birth. We generated induced pluripotent stem cells (iPSC) from patients with the MECP2 duplication syndrome (MECP2dup), carrying different duplication sizes, to study the impact of increased MeCP2 dosage in human neurons. We show that cortical neurons derived from these different MECP2dup iPSC lines have increase synaptogenesis and dendritic complexity. Additionally, using multi-electrodes arrays, we show that neuronal network synchronization was altered in MECP2dup-derived neurons. Given MeCP2 function at the epigenetic level, we tested if these alterations were reversible using a library of compounds with defined activity on epigenetic pathways. One histone deacetylase inhibitor, NCH-51, was validated as a potential clinical candidate. Interestingly, this compound has never been considered before as a therapeutic alternative for neurological disorders. Our model recapitulates early stages of the human MECP2 duplication syndrome and represents a promising cellular tool to facilitate therapeutic drug screening for severe neurodevelopmental disorders. PMID:26347316

Eagle's syndrome-A non-perceived differential diagnosis of temporomandibular disorder.

PubMed

Thoenissen, P; Bittermann, G; Schmelzeisen, R; Oshima, T; Fretwurst, T

2015-01-01

This article unveils a case of the classic styloid syndrome and states that panoramic imaging and ultrasound can be an alternative to computed tomography. In addition, the endoscope-assisted extraoral approach using CT-based navigation is useful. Eagle's Syndrome is an aggregate of symptoms described by Eagle in 1937. He described different forms: the classic styloid syndrome consisting of elongation of the styloid process which causes pain. Second, the stylo-carotid-artery syndrome which is responsible for transient ischemic attack or stroke. Using the example of a 66 years old male patient suffering from long term pain, we explain our diagnostic and surgical approach. After dissecting the styloid process of the right side using an extraoral approach, the pain ceased and the patient could be discharged without any recurrence of the pain up to this point. Eagle's syndrome, with its similar symptoms, is rather difficult to differentiate from temporomandibular joint disorders (TMD), but can be easily excluded from possible differential diagnoses of TMD using panoramic radiographs and ultrasound. Making use of low cost and easily accessible diagnostic workup techniques can reveal this particular cause for chronic pain restricting quality of life. Thereby differentiation from the TMD symptomatic complex is possible. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

A novel unstable duplication upstream of HAS2 predisposes to a breed-defining skin phenotype and a periodic fever syndrome in Chinese Shar-Pei dogs.

PubMed

Olsson, Mia; Meadows, Jennifer R S; Truvé, Katarina; Rosengren Pielberg, Gerli; Puppo, Francesca; Mauceli, Evan; Quilez, Javier; Tonomura, Noriko; Zanna, Giordana; Docampo, Maria José; Bassols, Anna; Avery, Anne C; Karlsson, Elinor K; Thomas, Anne; Kastner, Daniel L; Bongcam-Rudloff, Erik; Webster, Matthew T; Sanchez, Armand; Hedhammar, Ake; Remmers, Elaine F; Andersson, Leif; Ferrer, Lluis; Tintle, Linda; Lindblad-Toh, Kerstin

2011-03-01

Hereditary periodic fever syndromes are characterized by recurrent episodes of fever and inflammation with no known pathogenic or autoimmune cause. In humans, several genes have been implicated in this group of diseases, but the majority of cases remain unexplained. A similar periodic fever syndrome is relatively frequent in the Chinese Shar-Pei breed of dogs. In the western world, Shar-Pei have been strongly selected for a distinctive thick and heavily folded skin. In this study, a mutation affecting both these traits was identified. Using genome-wide SNP analysis of Shar-Pei and other breeds, the strongest signal of a breed-specific selective sweep was located on chromosome 13. The same region also harbored the strongest genome-wide association (GWA) signal for susceptibility to the periodic fever syndrome (p(raw) = 2.3 × 10⁻⁶, p(genome) = 0.01). Dense targeted resequencing revealed two partially overlapping duplications, 14.3 Kb and 16.1 Kb in size, unique to Shar-Pei and upstream of the Hyaluronic Acid Synthase 2 (HAS2) gene. HAS2 encodes the rate-limiting enzyme synthesizing hyaluronan (HA), a major component of the skin. HA is up-regulated and accumulates in the thickened skin of Shar-Pei. A high copy number of the 16.1 Kb duplication was associated with an increased expression of HAS2 as well as the periodic fever syndrome (p < 0.0001). When fragmented, HA can act as a trigger of the innate immune system and stimulate sterile fever and inflammation. The strong selection for the skin phenotype therefore appears to enrich for a pleiotropic mutation predisposing these dogs to a periodic fever syndrome. The identification of HA as a major risk factor for this canine disease raises the potential of this glycosaminoglycan as a risk factor for human periodic fevers and as an important driver of chronic inflammation.

A Novel Unstable Duplication Upstream of HAS2 Predisposes to a Breed-Defining Skin Phenotype and a Periodic Fever Syndrome in Chinese Shar-Pei Dogs

PubMed Central

Olsson, Mia; Mauceli, Evan; Quilez, Javier; Tonomura, Noriko; Zanna, Giordana; Docampo, Maria José; Bassols, Anna; Avery, Anne C.; Karlsson, Elinor K.; Thomas, Anne; Kastner, Daniel L.; Bongcam-Rudloff, Erik; Webster, Matthew T.; Sanchez, Armand; Hedhammar, Åke; Remmers, Elaine F.; Andersson, Leif; Ferrer, Lluis; Tintle, Linda; Lindblad-Toh, Kerstin

2011-01-01

Hereditary periodic fever syndromes are characterized by recurrent episodes of fever and inflammation with no known pathogenic or autoimmune cause. In humans, several genes have been implicated in this group of diseases, but the majority of cases remain unexplained. A similar periodic fever syndrome is relatively frequent in the Chinese Shar-Pei breed of dogs. In the western world, Shar-Pei have been strongly selected for a distinctive thick and heavily folded skin. In this study, a mutation affecting both these traits was identified. Using genome-wide SNP analysis of Shar-Pei and other breeds, the strongest signal of a breed-specific selective sweep was located on chromosome 13. The same region also harbored the strongest genome-wide association (GWA) signal for susceptibility to the periodic fever syndrome (praw = 2.3×10−6, pgenome = 0.01). Dense targeted resequencing revealed two partially overlapping duplications, 14.3 Kb and 16.1 Kb in size, unique to Shar-Pei and upstream of the Hyaluronic Acid Synthase 2 (HAS2) gene. HAS2 encodes the rate-limiting enzyme synthesizing hyaluronan (HA), a major component of the skin. HA is up-regulated and accumulates in the thickened skin of Shar-Pei. A high copy number of the 16.1 Kb duplication was associated with an increased expression of HAS2 as well as the periodic fever syndrome (p<0.0001). When fragmented, HA can act as a trigger of the innate immune system and stimulate sterile fever and inflammation. The strong selection for the skin phenotype therefore appears to enrich for a pleiotropic mutation predisposing these dogs to a periodic fever syndrome. The identification of HA as a major risk factor for this canine disease raises the potential of this glycosaminoglycan as a risk factor for human periodic fevers and as an important driver of chronic inflammation. PMID:21437276

[On establishing comparative reference system for syndrome classification study from the thinking characteristics of syndrome differentiation dependent therapy].

PubMed

Liu, Ping; Hu, Yi-yang; Ni, Li-qiang

2006-05-01

To create a comparative referential system for syndrome classification study by viewing from the thinking characteristics of TCM on syndrome differentiation dependent therapy (SDDT), through analyzing the thinking process of SDDT, and the basic features of disease, syndrome and prescription, combining the basic principles of modern evidence-based medicine and feasibility of establishing integrative disease-syndrome animal model. The practice of creating a comparative referential system based on clinical efficacy of prescription was discussed around syndrome pathogenesis and its relationship with disease and prescription, which was one of the important scientific problems in TCM syndrome study. The authors hold that, it may be one of the available approaches for the present study on integration of disease with syndrome by way of insisting on the thinking pathway of stressing the characteristics of TCM and intermerging with modern scientific design; on taking the efficacy of prescription as the comparative reference system to accumulate and improve unceasingly according to the TCM method of syndrome diagnosis inferred from effect of prescription with reverse thought (i.e., to differentiate syndrome from the effect of prescription), and thus build up the syndrome diagnostic standard on the solid clinical and scientific base.

Diagnosis of a terminal deletion of 4p with duplication of Xp22.31 in a patient with findings of Opitz G/BBB syndrome and Wolf-Hirschhorn syndrome.

PubMed

So, Joyce; Müller, Ines; Kunath, Melanie; Herrmann, Susanne; Ullmann, Reinhard; Schweiger, Susann

2008-01-01

Opitz G/BBB syndrome (OS) is a congenital midline malformation syndrome characterized by hypertelorism, hypospadias, cleft lip/palate, laryngotracheoesophageal abnormalities, imperforate anus, developmental delay and cardiac defects. The X-linked form is caused by mutations in the MID1 gene, while no gene has yet been identified for the autosomal dominant form. Here, we report on a 15-year-old boy who was referred for MID1 mutation analysis with findings typical of OS, including apparent hypertelorism, hypospadias, a history of feeding difficulties, dysphagia secondary to esophageal arteria lusoria, growth retardation and developmental delay. No MID1 mutation was found, but subsequent sub-megabase resolution array CGH unexpectedly documented a 2.34 Mb terminal 4p deletion, suggesting a diagnosis of WHS, and a duplication in Xp22.31. Wolf-Hirschhorn syndrome (WHS) is a contiguous gene deletion syndrome involving terminal chromosome 4p deletions, in particular 4p16.3. WHS is characterized by typical facial appearance ("Greek helmet facies"), mental retardation, congenital hypotonia, and growth retardation. While the severity of developmental delay in this patient supports the diagnosis of WHS rather than OS, this case illustrates the striking similarities of clinical findings in seemingly unrelated syndromes, suggesting common or interacting pathways at the molecular and pathogenetic level. This is the first report of arteria lusoria (esophageal vascular ring) in a patient with WHS. (c) 2007 Wiley-Liss, Inc.

Unique Theory of Mind Differentiation in Children with Autism and Asperger Syndrome

PubMed Central

Tine, Michele; Lucariello, Joan

2012-01-01

This study was designed to determine if ToM abilities of children with autism and Asperger syndrome differentiate into Intrapersonal ToM and Social ToM. A battery of Social and Intrapersonal ToM tasks was administered to 39 children with autism and 34 children with Asperger syndrome. For both groups of children, ToM differentiated and Intrapersonal ToM was stronger than Social ToM. This asymmetry was greater for children with autism, whose Social ToM was especially weak. These results support a differentiated, as opposed to integrated, ToM. Moreover, the findings provide a more thorough understanding of the cognitive abilities associated with autism and Asperger syndrome. PMID:22934174

Copy number variation at the 7q11.23 segmental duplications is a susceptibility factor for the Williams-Beuren syndrome deletion

PubMed Central

Cuscó, Ivon; Corominas, Roser; Bayés, Mònica; Flores, Raquel; Rivera-Brugués, Núria; Campuzano, Victoria; Pérez-Jurado, Luis A.

2008-01-01

Large copy number variants (CNVs) have been recently found as structural polymorphisms of the human genome of still unknown biological significance. CNVs are significantly enriched in regions with segmental duplications or low-copy repeats (LCRs). Williams-Beuren syndrome (WBS) is a neurodevelopmental disorder caused by a heterozygous deletion of contiguous genes at 7q11.23 mediated by nonallelic homologous recombination (NAHR) between large flanking LCRs and facilitated by a structural variant of the region, a ∼2-Mb paracentric inversion present in 20%–25% of WBS-transmitting progenitors. We now report that eight out of 180 (4.44%) WBS-transmitting progenitors are carriers of a CNV, displaying a chromosome with large deletion of LCRs. The prevalence of this CNV among control individuals and non-transmitting progenitors is much lower (1%, n = 600), thus indicating that it is a predisposing factor for the WBS deletion (odds ratio 4.6-fold, P = 0.002). LCR duplications were found in 2.22% of WBS-transmitting progenitors but also in 1.16% of controls, which implies a non–statistically significant increase in WBS-transmitting progenitors. We have characterized the organization and breakpoints of these CNVs, encompassing ∼100–300 kb of genomic DNA and containing several pseudogenes but no functional genes. Additional structural variants of the region have also been defined, all generated by NAHR between different blocks of segmental duplications. Our data further illustrate the highly dynamic structure of regions rich in segmental duplications, such as the WBS locus, and indicate that large CNVs can act as susceptibility alleles for disease-associated genomic rearrangements in the progeny. PMID:18292220

Case report of individual with cutaneous immunodeficiency and novel 1p36 duplication.

PubMed

Hatter, Alyn D; Soler, David C; Curtis, Christine; Cooper, Kevin D; McCormick, Thomas S

2016-01-01

Crusted or Norwegian scabies is an infectious skin dermatopathology usually associated with an underlying immunodeficiency condition. It is caused when the mite Sarcoptes scabiei infects the skin, and the immune system is unable to control its spread, leading to a massive hyperinfestation with a simultaneous inflammatory and hyperkeratotic reaction. This is the first report of a novel 1p36 duplication associated with a recurrent infection of crusted scabies. We describe a 34-year-old patient with a cutaneous immunodeficiency characterized by recurrent crusted scabies infestation, diffuse tinea, and recurrent staphylococcal cellulitis, who we suspected had an undiagnosed syndrome. The patient also suffered from mental retardation, renal failure, and premature senescence. A cytogenetic fluorescence in situ hybridization analysis revealed a 9.34 Mb duplication within the short (p) arm of chromosome 1, precisely from 1p36.11 to 1p36.21, with an adjacent 193 kb copy gain entirely within 1p36.11. In addition, chromosome 4 had a 906 kb gain in 4p16.1 and chromosome 9 had a 81 kb copy gain in 9p24.3. Over 100 genes localized within these duplicated regions. Gene expression array revealed 82 genes whose expression changed >1.5-fold compared to a healthy age-matched skin control, but among them only the lipolytic enzyme arylacetamide deacetylase-like 3 was found within the duplicated 1p36 region of chromosome 1. Although genetic duplications in the 1p36 region have been previously described, our report describes a novel duplicative variant within the 1p36 region. The patient did not have a past history of immunosuppression but was afflicted by a recurrent case of crusted scabies, raising the possibility that the recurrent infection was associated with the 1p36 genetic duplication. To our knowledge, the specific duplicated sequence between 1p36.11 and p36.21 found in our patient has never been previously reported. We reviewed and compared the clinical, genotyping, and gene

Case report of individual with cutaneous immunodeficiency and novel 1p36 duplication

PubMed Central

Hatter, Alyn D; Soler, David C; Curtis, Christine; Cooper, Kevin D; McCormick, Thomas S

2016-01-01

Introduction Crusted or Norwegian scabies is an infectious skin dermatopathology usually associated with an underlying immunodeficiency condition. It is caused when the mite Sarcoptes scabiei infects the skin, and the immune system is unable to control its spread, leading to a massive hyperinfestation with a simultaneous inflammatory and hyperkeratotic reaction. This is the first report of a novel 1p36 duplication associated with a recurrent infection of crusted scabies. Case report We describe a 34-year-old patient with a cutaneous immunodeficiency characterized by recurrent crusted scabies infestation, diffuse tinea, and recurrent staphylococcal cellulitis, who we suspected had an undiagnosed syndrome. The patient also suffered from mental retardation, renal failure, and premature senescence. A cytogenetic fluorescence in situ hybridization analysis revealed a 9.34 Mb duplication within the short (p) arm of chromosome 1, precisely from 1p36.11 to 1p36.21, with an adjacent 193 kb copy gain entirely within 1p36.11. In addition, chromosome 4 had a 906 kb gain in 4p16.1 and chromosome 9 had a 81 kb copy gain in 9p24.3. Over 100 genes localized within these duplicated regions. Gene expression array revealed 82 genes whose expression changed >1.5-fold compared to a healthy age-matched skin control, but among them only the lipolytic enzyme arylacetamide deacetylase-like 3 was found within the duplicated 1p36 region of chromosome 1. Discussion Although genetic duplications in the 1p36 region have been previously described, our report describes a novel duplicative variant within the 1p36 region. The patient did not have a past history of immunosuppression but was afflicted by a recurrent case of crusted scabies, raising the possibility that the recurrent infection was associated with the 1p36 genetic duplication. Conclusion To our knowledge, the specific duplicated sequence between 1p36.11 and p36.21 found in our patient has never been previously reported. We reviewed and

Cecum duplication in a 14-year-old female. Case report.

PubMed

Galván-Montaño, Alfonso; Guzmán-Martínez, Sonia; Lorenzana-Sandoval, Cuauhtémoc; Recinos-Carrera, Elio

2011-01-01

Duplications of the alimentary tract are a group of rare malformations occurring in about 1/5,000 live births. These may be either spherical or tubular and may communicate with the intestinal tract. Duplications of the cecum are very uncommon. A 14-year-old female was admitted to the emergency department with a 1-day history of abdominal pain, vomiting, constipation and abdominal distension. Abdominal examination revealed distension and tenderness around the umbilicus. Plain abdominal radiography showed dilated colon. The patient underwent surgical management with diagnosis of sigmoid volvulus. Laparotomy revealed spherical duplication from the cecum. Hemicolectomy was done and alimentary continuity was restored by end-to-end anastomosis. Pathological report was a spherical communicated duplication from the cecum (22 × 32 cm). Duplication of the cecum is extremely rare and is seen in 0.4% of duplications of the alimentary tract. The majority of cases (85%) are diagnosed before age 2 years. It is rare at 14 years of age. Diagnosis is difficult and volvulus, intussusception or appendicitis should be considered in the differential diagnosis. Ultrasonography and tomography are the imaging studies of choice. Plain abdominal x-ray is not specific. Resection of the duplication with restoration of alimentary continuity is the treatment of choice.

Genetics Home Reference: isodicentric chromosome 15 syndrome

MedlinePlus

... my area? Other Names for This Condition duplication/inversion 15q11 idic(15) inv dup(15) inverted duplication ... syndrome March of Dimes: Chromosomal Conditions Orphanet: Duplication/inversion 15q11 Unique Rare Chromosome Disorder Support Group: Idic( ...

De novo tandem duplication of chromosome segement 22q11-q12: Clinical, cytogenetic, and molecular characterization

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lindsay, E.A.; Shaffer, L.G.; Carrozzo, R.

We report on a case of duplication of the segment 22q11-q12 due to a de novo duplication. Molecular cytogenetics studies demonstrated this to be a tandem duplication, flanked proximally by the marker D22Z4, a centromeric alpha satellite DNA repeat, and distally by D22S260, an anonymous DNA marker proximal to the Ewing sarcoma breakpoint. The segment includes the regions responsible for the {open_quotes}cat-eye{close_quotes}, Di George, and velo-cardio-facial syndromes and extends distal to the breakpoint cluster region (BCR). The clinical picture is dominated by the cardiac defects and includes findings reminiscent of {open_quotes}cat-eye{close_quotes} syndrome. These findings reinforce the hypothesis that the proximalmore » 22q region contains dosage-sensitive genes involved in development. 20 refs., 3 figs.« less

Evolution of the duplicated intracellular lipid-binding protein genes of teleost fishes.

PubMed

Venkatachalam, Ananda B; Parmar, Manoj B; Wright, Jonathan M

2017-08-01

Increasing organismal complexity during the evolution of life has been attributed to the duplication of genes and entire genomes. More recently, theoretical models have been proposed that postulate the fate of duplicated genes, among them the duplication-degeneration-complementation (DDC) model. In the DDC model, the common fate of a duplicated gene is lost from the genome owing to nonfunctionalization. Duplicated genes are retained in the genome either by subfunctionalization, where the functions of the ancestral gene are sub-divided between the sister duplicate genes, or by neofunctionalization, where one of the duplicate genes acquires a new function. Both processes occur either by loss or gain of regulatory elements in the promoters of duplicated genes. Here, we review the genomic organization, evolution, and transcriptional regulation of the multigene family of intracellular lipid-binding protein (iLBP) genes from teleost fishes. Teleost fishes possess many copies of iLBP genes owing to a whole genome duplication (WGD) early in the teleost fish radiation. Moreover, the retention of duplicated iLBP genes is substantially higher than the retention of all other genes duplicated in the teleost genome. The fatty acid-binding protein genes, a subfamily of the iLBP multigene family in zebrafish, are differentially regulated by peroxisome proliferator-activated receptor (PPAR) isoforms, which may account for the retention of iLBP genes in the zebrafish genome by the process of subfunctionalization of cis-acting regulatory elements in iLBP gene promoters.

A Korean boy with 46,XX testicular disorder of sex development caused by SOX9 duplication.

PubMed

Lee, Gyung Min; Ko, Jung Min; Shin, Choong Ho; Yang, Sei Won

2014-06-01

The 46,XX testicular disorder of sex development (DSD), also known as 46,XX male syndrome, is a rare form of DSD and clinical phenotype shows complete sex reversal from female to male. The sex-determining region Y (SRY) gene can be identified in most 46,XX testicular DSD patients; however, approximately 20% of patients with 46,XX testicular DSD are SRY-negative. The SRY-box 9 (SOX9) gene has several important functions during testis development and differentiation in males, and overexpression of SOX9 leads to the male development of 46,XX gonads in the absence of SRY. In addition, SOX9 duplication has been found to be a rare cause of 46,XX testicular DSD in humans. Here, we report a 4.2-year-old SRY-negative 46,XX boy with complete sex reversal caused by SOX9 duplication for the first time in Korea. He showed normal external and internal male genitalia except for small testes. Fluorescence in situ hybridization and polymerase chain reaction (PCR) analyses failed to detect the presence of SRY, and SOX9 intragenic mutation was not identified by direct sequencing analysis. Therefore, we performed real-time PCR analyses with specific primer pairs, and duplication of the SOX9 gene was revealed. Although SRY-negative 46,XX testicular DSD is a rare condition, an effort to make an accurate diagnosis is important for the provision of proper genetic counseling and for guiding patients in their long-term management.

Differential diagnosis of food protein-induced enterocolitis syndrome

PubMed Central

Fiocchi, Alessandro; Claps, Alessia; Dahdah, Lamia; Brindisi, Giulia; Dionisi-Vici, Carlo; Martelli, Alberto

2014-01-01

Purpose of review To assess all the possible differential diagnosis of food protein-induced enterocolitis syndrome (FPIES), both in acute and chronic presentation, reviewing the data reported in published studies. Recent findings There is an increase of reported cases of FPIES in recent years. As the disease presents with nonspecific symptoms, it can be misunderstood in many ways. The differential diagnosis includes, in acute presentations, the following: sepsis, other infectious diseases, acute gastrointestinal episodes, surgical emergencies, food allergies. In its chronic forms, FPIES may mimic malabsorption syndromes, metabolic disorders, primary immunodeficiencies, neurological conditions, coagulation defects, and other types of non-IgE-mediated food allergy. Summary A thorough clinical evaluation, including symptoms, signs, and laboratory findings, is necessary to lead the clinicians toward the diagnosis of FPIES. The major reason for delayed diagnosis appears to be the lack of knowledge of the disease. PMID:24739227

A Rare de novo Interstitial Duplication at 4p15.2 in a Boy with Severe Congenital Heart Defects, Limb Anomalies, Hypogonadism, and Global Developmental Delay.

PubMed

Liang, Liyang; Xie, Yingjun; Shen, Yiping; Yin, Qibin; Yuan, Haiming

2016-01-01

Proximal 4p deletion syndrome is a relatively rare genetic condition characterized by dysmorphic facial features, limb anomalies, minor congenital heart defects, hypogonadism, cafe-au-lait spots, developmental delay, tall and thin habitus, and intellectual disability. At present, over 20 cases of this syndrome have been published. However, duplication of the same region in proximal 4p has never been reported. Here, we describe a 2-year-5-month-old boy with severe congenital heart defects, limb anomalies, hypogonadism, distinctive facial features, pre- and postnatal developmental delay, and mild cognitive impairments. A de novo 4.5-Mb interstitial duplication at 4p15.2p15.1 was detected by chromosomal microarray analysis. Next-generation sequencing was employed and confirmed the duplication, but revealed no additional pathogenic variants. Several candidate genes in this interval responsible for the complex clinical phenotype were identified, such as RBPJ, STIM2, CCKAR, and LGI2. The results suggest a novel contiguous gene duplication syndrome. © 2016 S. Karger AG, Basel.

Adaptations to High Salt in a Halophilic Protist: Differential Expression and Gene Acquisitions through Duplications and Gene Transfers

PubMed Central

Harding, Tommy; Roger, Andrew J.; Simpson, Alastair G. B.

2017-01-01

The capacity of halophiles to thrive in extreme hypersaline habitats derives partly from the tight regulation of ion homeostasis, the salt-dependent adjustment of plasma membrane fluidity, and the increased capability to manage oxidative stress. Halophilic bacteria, and archaea have been intensively studied, and substantial research has been conducted on halophilic fungi, and the green alga Dunaliella. By contrast, there have been very few investigations of halophiles that are phagotrophic protists, i.e., protozoa. To gather fundamental knowledge about salt adaptation in these organisms, we studied the transcriptome-level response of Halocafeteria seosinensis (Stramenopiles) grown under contrasting salinities. We provided further evolutionary context to our analysis by identifying genes that underwent recent duplications. Genes that were highly responsive to salinity variations were involved in stress response (e.g., chaperones), ion homeostasis (e.g., Na+/H+ transporter), metabolism and transport of lipids (e.g., sterol biosynthetic genes), carbohydrate metabolism (e.g., glycosidases), and signal transduction pathways (e.g., transcription factors). A significantly high proportion (43%) of duplicated genes were also differentially expressed, accentuating the importance of gene expansion in adaptation by H. seosinensis to high salt environments. Furthermore, we found two genes that were lateral acquisitions from bacteria, and were also highly up-regulated and highly expressed at high salt, suggesting that this evolutionary mechanism could also have facilitated adaptation to high salt. We propose that a transition toward high-salt adaptation in the ancestors of H. seosinensis required the acquisition of new genes via duplication, and some lateral gene transfers (LGTs), as well as the alteration of transcriptional programs, leading to increased stress resistance, proper establishment of ion gradients, and modification of cell structure properties like membrane

Lack of cilia and differentiation defects in the liver of human foetuses with the Meckel syndrome.

PubMed

Clotman, Frédéric; Libbrecht, Louis; Killingsworth, Murray C; Loo, Christine C K; Roskams, Tania; Lemaigre, Frédéric P

2008-03-01

Meckel syndrome is an autosomal-recessive disease characterized by a combination of renal cysts, anomalies of the central nervous system, polydactyly and ductal plate malformations (DPM), which are hepatic anomalies consisting of excessive and abnormal foetal biliary structures. Among the genomic loci associated with Meckel syndrome, mutations in four genes were recently identified. These genes code for proteins associated with primary cilia and are possibly involved in cell differentiation. The aim of the present work was to investigate the formation of the primary cilia and the differentiation of the hepatic cells in foetuses with Meckel syndrome. Sections of livers from human foetuses with Meckel syndrome were analysed by immunofluorescence, immunohistochemistry and electron microscopy. The primary cilia of the biliary cells were absent in some Meckel foetuses, but were present in others. In addition, defects in hepatic differentiation were observed in Meckel livers, as evidenced by the presence of hybrid cells co-expressing hepatocytic and biliary markers. Defects in cilia formation occur in some Meckel livers, and most cases show DPM associated with abnormal hepatic cell differentiation. Because differentiation precedes the formation of the cilia during liver development, we propose that defective differentiation may constitute the initial defect in the liver of Meckel syndrome foetuses.

A new case of Beckwith-Wiedemann syndrome with an 11p15 duplication of paternal origin [46,XY,-21,+der(21), t(11;21)(p15.2;q22.3)pat].

PubMed

Krajewska-Walasek, M; Gutkowska, A; Mospinek-Krasnopolska, M; Chrzanowska, K

1996-01-01

We present a new case of 11p15 duplication (trisomy 11p15) in a boy (46,XY,-21,+der(21), t(11;21)(p15.2;q22.3)] suffering from Beckwith-Wiedemann syndrome (BWS), whose phenotypically normal father carries a balanced translocation between chromosomes 11 and 21[46,XY, t(11;21)(p15.2;q22.3)]. The paternal grandmother has the same balanced translocation and is also clinically normal. BWS was suspected when the boy was 6 months old because of gigantism, macroglossia, visceromegaly, ear lobe creases and abdominal distention. Apart from the characteristic BWS phenotype, the boy has other features which are almost exclusively observed in 11p trisomy (high forehead with frontal upsweep of hair, wide central nose bridge, slightly beaked nose, chubby cheeks and severe mental retardation). So far, at least eight cases of 11p15 duplication have been described as patients with BWS. In six of these, the duplication was due to inheritance of a translocated or rearranged paternal chromosome. This was also the case in our patient. In the two other previously published cases, the 11p15 duplications were de novo, but in one of these, DNA analysis has subsequently shown that the duplication was of paternal origin. We discuss our observations in relation to the above-mentioned previous cases of 11p15 duplication and the possible role of genomic imprinting in the etiology of BWS.

Differential diagnosis of common tremor syndromes

PubMed Central

Bhidayasiri, R

2005-01-01

Tremor is one of the most common involuntary movement disorders seen in clinical practice. In addition to the detailed history, the differential diagnosis is mainly clinical based on the distinction at rest, postural and intention, activation condition, frequency, and topographical distribution. The causes of tremor are heterogeneous and it can present alone (for example, essential tremor) or as a part of a neurological syndrome (for example, multiple sclerosis). Essential tremor and the tremor of Parkinson's disease are the most common tremors encountered in clinical practice. This article focuses on a practical approach to these different forms of tremor and how to distinguish them clinically. Evidence supporting various strategies used in the differentiation is then presented, followed by a review of formal guidelines or recommendations when they exist. PMID:16344298

Further delineation of the 15q13 microdeletion and duplication syndromes: a clinical spectrum varying from non-pathogenic to a severe outcome.

PubMed

van Bon, B W M; Mefford, H C; Menten, B; Koolen, D A; Sharp, A J; Nillesen, W M; Innis, J W; de Ravel, T J L; Mercer, C L; Fichera, M; Stewart, H; Connell, L E; Ounap, K; Lachlan, K; Castle, B; Van der Aa, N; van Ravenswaaij, C; Nobrega, M A; Serra-Juhé, C; Simonic, I; de Leeuw, N; Pfundt, R; Bongers, E M; Baker, C; Finnemore, P; Huang, S; Maloney, V K; Crolla, J A; van Kalmthout, M; Elia, M; Vandeweyer, G; Fryns, J P; Janssens, S; Foulds, N; Reitano, S; Smith, K; Parkel, S; Loeys, B; Woods, C G; Oostra, A; Speleman, F; Pereira, A C; Kurg, A; Willatt, L; Knight, S J L; Vermeesch, J R; Romano, C; Barber, J C; Mortier, G; Pérez-Jurado, L A; Kooy, F; Brunner, H G; Eichler, E E; Kleefstra, T; de Vries, B B A

2009-08-01

Recurrent 15q13.3 microdeletions were recently identified with identical proximal (BP4) and distal (BP5) breakpoints and associated with mild to moderate mental retardation and epilepsy. To assess further the clinical implications of this novel 15q13.3 microdeletion syndrome, 18 new probands with a deletion were molecularly and clinically characterised. In addition, we evaluated the characteristics of a family with a more proximal deletion between BP3 and BP4. Finally, four patients with a duplication in the BP3-BP4-BP5 region were included in this study to ascertain the clinical significance of duplications in this region. The 15q13.3 microdeletion in our series was associated with a highly variable intra- and inter-familial phenotype. At least 11 of the 18 deletions identified were inherited. Moreover, 7 of 10 siblings from four different families also had this deletion: one had a mild developmental delay, four had only learning problems during childhood, but functioned well in daily life as adults, whereas the other two had no learning problems at all. In contrast to previous findings, seizures were not a common feature in our series (only 2 of 17 living probands). Three patients with deletions had cardiac defects and deletion of the KLF13 gene, located in the critical region, may contribute to these abnormalities. The limited data from the single family with the more proximal BP3-BP4 deletion suggest this deletion may have little clinical significance. Patients with duplications of the BP3-BP4-BP5 region did not share a recognisable phenotype, but psychiatric disease was noted in 2 of 4 patients. Overall, our findings broaden the phenotypic spectrum associated with 15q13.3 deletions and suggest that, in some individuals, deletion of 15q13.3 is not sufficient to cause disease. The existence of microdeletion syndromes, associated with an unpredictable and variable phenotypic outcome, will pose the clinician with diagnostic difficulties and challenge the commonly

Pitt-Hopkins Syndrome: A Review of Current Literature, Clinical Approach, and 23-Patient Case Series.

PubMed

Goodspeed, Kimberly; Newsom, Cassandra; Morris, Mary Ann; Powell, Craig; Evans, Patricia; Golla, Sailaja

2018-03-01

Pitt-Hopkins syndrome (PTHS) is a rare, genetic disorder caused by a molecular variant of TCF4 which is involved in embryologic neuronal differentiation. PTHS is characterized by syndromic facies, psychomotor delay, and intellectual disability. Other associated features include early-onset myopia, seizures, constipation, and hyperventilation-apneic spells. Many also meet criteria for autism spectrum disorder. Here the authors present a series of 23 PTHS patients with molecularly confirmed TCF4 variants and describe 3 unique individuals. The first carries a small deletion but does not exhibit the typical facial features nor the typical pattern of developmental delay. The second exhibits typical facial features, but has attained more advanced motor and verbal skills than other reported cases to date. The third displays typical features of PTHS, however inherited a large chromosomal duplication involving TCF4 from his unaffected father with somatic mosaicism. To the authors' knowledge, this is the first chromosomal duplication case reported to date.

Hereditary mixed polyposis syndrome is caused by a 40-kb upstream duplication that leads to increased and ectopic expression of the BMP antagonist GREM1.

PubMed

Jaeger, Emma; Leedham, Simon; Lewis, Annabelle; Segditsas, Stefania; Becker, Martin; Cuadrado, Pedro Rodenas; Davis, Hayley; Kaur, Kulvinder; Heinimann, Karl; Howarth, Kimberley; East, James; Taylor, Jenny; Thomas, Huw; Tomlinson, Ian

2012-05-06

Hereditary mixed polyposis syndrome (HMPS) is characterized by apparent autosomal dominant inheritance of multiple types of colorectal polyp, with colorectal carcinoma occurring in a high proportion of affected individuals. Here, we use genetic mapping, copy-number analysis, exclusion of mutations by high-throughput sequencing, gene expression analysis and functional assays to show that HMPS is caused by a duplication spanning the 3' end of the SCG5 gene and a region upstream of the GREM1 locus. This unusual mutation is associated with increased allele-specific GREM1 expression. Whereas GREM1 is expressed in intestinal subepithelial myofibroblasts in controls, GREM1 is predominantly expressed in the epithelium of the large bowel in individuals with HMPS. The HMPS duplication contains predicted enhancer elements; some of these interact with the GREM1 promoter and can drive gene expression in vitro. Increased GREM1 expression is predicted to cause reduced bone morphogenetic protein (BMP) pathway activity, a mechanism that also underlies tumorigenesis in juvenile polyposis of the large bowel.

Duplicate origin of the posterior communicating artery diagnosed by magnetic resonance angiography.

PubMed

Uchino, Akira; Kamiya, Kouhei; Suzuki, Chihiro

2013-10-01

Extremely rarely, a posterior communicating artery (PCoA) of "duplicate origin" occurs when two branches of the PCoA arise separately from the supraclinoid segment of the internal carotid artery (ICA) and quickly fuse to form an arterial ring. Three such cases previously reported were described as "fenestration." We report the case of this rare variation diagnosed by magnetic resonance angiography and discuss the differentiation of PCoA of duplicate origin from PCoA fenestration, supraclinoid ICA fenestration, and hyperplastic anterior choroidal artery.

Retention of duplicated long-wavelength opsins in mosquito lineages by positive selection and differential expression.

PubMed

Giraldo-Calderón, Gloria I; Zanis, Michael J; Hill, Catherine A

2017-03-21

Opsins are light sensitive receptors associated with visual processes. Insects typically possess opsins that are stimulated by ultraviolet, short and long wavelength (LW) radiation. Six putative LW-sensitive opsins predicted in the yellow fever mosquito, Aedes aegypti and malaria mosquito, Anopheles gambiae, and eight in the southern house mosquito, Culex quinquefasciatus, suggest gene expansion in the Family Culicidae (mosquitoes) relative to other insects. Here we report the first detailed molecular and evolutionary analyses of LW opsins in three mosquito vectors, with a goal to understanding the molecular basis of opsin-mediated visual processes that could be exploited for mosquito control. Time of divergence estimates suggest that the mosquito LW opsins originated from 18 or 19 duplication events between 166.9/197.5 to 1.07/0.94 million years ago (MY) and that these likely occurred following the predicted divergence of the lineages Anophelinae and Culicinae 145-226 MY. Fitmodel analyses identified nine amino acid residues in the LW opsins that may be under positive selection. Of these, eight amino acids occur in the N and C termini and are shared among all three species, and one residue in TMIII was unique to culicine species. Alignment of 5' non-coding regions revealed potential Conserved Non-coding Sequences (CNS) and transcription factor binding sites (TFBS) in seven pairs of LW opsin paralogs. Our analyses suggest opsin gene duplication and residues possibly associated with spectral tuning of LW-sensitive photoreceptors. We explore two mechanisms - positive selection and differential expression mediated by regulatory units in CNS - that may have contributed to the retention of LW opsin genes in Culicinae and Anophelinae. We discuss the evolution of mosquito LW opsins in the context of major Earth events and possible adaptation of mosquitoes to LW-dominated photo environments, and implications for mosquito control strategies based on disrupting vision

[ZHANG Tangfa's characteristics of acupuncture academic ideology and clinical treatment of syndrome differentiation].

PubMed

Zhang, Hongxing

2015-10-01

Through collecting and sorting of works, literature and medical cases regarding professor ZHANG Tangfa, it is found that his acupuncture academic ideology and clinical treatment of syndrome differentiation can be summarized as: tracing the source and paying attention to basic theory, especially the meridian theory and conception vessel and governor vessel; focusing on acupuncture manipulation and emphasizing acupuncture basic skills; highly valuing treating spirit, acquiring and maintaining needling sensation; underlining "three differentiations" that is consisted of syndrome differentiation, disease differentiation and meridian differentiation to guide the clinical prescriptions of acupoints; exploring and ingenious use of scalp acupuncture; being concerned on research of difficult and complicated diseases; advocating comparative studies to optimize the clinical treatment plan; proposing the combination of Chinese and western medicine, including diagnosis, treatment and basic theory, to improve the clinical therapeutic effects of acupuncture.

Differentiating Familial Neuropathies from Guillain-Barré Syndrome.

PubMed

Bordini, Brett J; Monrad, Priya

2017-02-01

Differentiating Guillain-Barré syndrome (GBS) from inherited neuropathies and other acquired peripheral neuropathies requires understanding the atypical presentations of GBS and its variant forms, as well as historical and physical features suggestive of inherited neuropathies. GBS is typically characterized by the acute onset of ascending flaccid paralysis, areflexia, and dysesthesia secondary to peripheral nerve fiber demyelination. The disorder usually arises following a benign gastrointestinal or respiratory illness, is monophasic, reaches a nadir with several weeks, and responds to immunomodulatory therapy. Inherited neuropathies with onset before adulthood, whose presentation may mimic Guillain-Barré syndrome, are reviewed. Copyright © 2016 Elsevier Inc. All rights reserved.

Utility of Shear Wave Elastography for Differentiating Biliary Atresia From Infantile Hepatitis Syndrome.

PubMed

Wang, Xiaoman; Qian, Linxue; Jia, Liqun; Bellah, Richard; Wang, Ning; Xin, Yue; Liu, Qinglin

2016-07-01

The purpose of this study was to investigate the potential utility of shear wave elastography (SWE) for diagnosis of biliary atresia and for differentiating biliary atresia from infantile hepatitis syndrome by measuring liver stiffness. Thirty-eight patients with biliary atresia and 17 patients with infantile hepatitis syndrome were included, along with 31 healthy control infants. The 3 groups underwent SWE. The hepatic tissue of each patient with biliary atresia had been surgically biopsied. Statistical analyses for mean values of the 3 groups were performed. Optimum cutoff values using SWE for differentiation between the biliary atresia and control groups were calculated by a receiver operating characteristic (ROC) analysis. The mean SWE values ± SD for the 3 groups were as follows: biliary atresia group, 20.46 ± 10.19 kPa; infantile hepatitis syndrome group, 6.29 ± 0.99 kPa; and control group, 6.41 ± 1.08 kPa. The mean SWE value for the biliary atresia group was higher than the values for the control and infantile hepatitis syndrome groups (P < .01). The mean SWE values between the control and infantile hepatitis syndrome groups were not statistically different. The ROC analysis showed a cutoff value of 8.68 kPa for differentiation between the biliary atresia and control groups. The area under the ROC curve was 0.997, with sensitivity of 97.4%, specificity of 100%, a positive predictive value of 100%, and a negative predictive value of 96.9%. Correlation analysis suggested a positive correlation between SWE values and age for patients with biliary atresia, with a Pearson correlation coefficient of 0.463 (P < .05). The significant increase in liver SWE values in neonates and infants with biliary atresia supports their application for differentiating biliary atresia from infantile hepatitis syndrome.

Gene duplication, tissue-specific gene expression and sexual conflict in stalk-eyed flies (Diopsidae).

PubMed

Baker, Richard H; Narechania, Apurva; Johns, Philip M; Wilkinson, Gerald S

2012-08-19

Gene duplication provides an essential source of novel genetic material to facilitate rapid morphological evolution. Traits involved in reproduction and sexual dimorphism represent some of the fastest evolving traits in nature, and gene duplication is intricately involved in the origin and evolution of these traits. Here, we review genomic research on stalk-eyed flies (Diopsidae) that has been used to examine the extent of gene duplication and its role in the genetic architecture of sexual dimorphism. Stalk-eyed flies are remarkable because of the elongation of the head into long stalks, with the eyes and antenna laterally displaced at the ends of these stalks. Many species are strongly sexually dimorphic for eyespan, and these flies have become a model system for studying sexual selection. Using both expressed sequence tag and next-generation sequencing, we have established an extensive database of gene expression in the developing eye-antennal imaginal disc, the adult head and testes. Duplicated genes exhibit narrower expression patterns than non-duplicated genes, and the testes, in particular, provide an abundant source of gene duplication. Within somatic tissue, duplicated genes are more likely to be differentially expressed between the sexes, suggesting gene duplication may provide a mechanism for resolving sexual conflict.

Gene duplication, tissue-specific gene expression and sexual conflict in stalk-eyed flies (Diopsidae)

PubMed Central

Baker, Richard H.; Narechania, Apurva; Johns, Philip M.; Wilkinson, Gerald S.

2012-01-01

Gene duplication provides an essential source of novel genetic material to facilitate rapid morphological evolution. Traits involved in reproduction and sexual dimorphism represent some of the fastest evolving traits in nature, and gene duplication is intricately involved in the origin and evolution of these traits. Here, we review genomic research on stalk-eyed flies (Diopsidae) that has been used to examine the extent of gene duplication and its role in the genetic architecture of sexual dimorphism. Stalk-eyed flies are remarkable because of the elongation of the head into long stalks, with the eyes and antenna laterally displaced at the ends of these stalks. Many species are strongly sexually dimorphic for eyespan, and these flies have become a model system for studying sexual selection. Using both expressed sequence tag and next-generation sequencing, we have established an extensive database of gene expression in the developing eye-antennal imaginal disc, the adult head and testes. Duplicated genes exhibit narrower expression patterns than non-duplicated genes, and the testes, in particular, provide an abundant source of gene duplication. Within somatic tissue, duplicated genes are more likely to be differentially expressed between the sexes, suggesting gene duplication may provide a mechanism for resolving sexual conflict. PMID:22777023

Duplicate editorial on duplicate publication.

PubMed

Corson, Stephen L; Decherney, Alan H

2005-04-01

The authors define and discuss the various forms taken by duplicate publications, and provide suggested remedies to help authors, editors, reviewers, and readers avoid this form of internal plagiarism.

[Evaluation on methodological problems in reports concerning quantitative analysis of syndrome differentiation of diabetes mellitus].

PubMed

Chen, Bi-Cang; Wu, Qiu-Ying; Xiang, Cheng-Bin; Zhou, Yi; Guo, Ling-Xiang; Zhao, Neng-Jiang; Yang, Shu-Yu

2006-01-01

To evaluate the quality of reports published in recent 10 years in China about quantitative analysis of syndrome differentiation for diabetes mellitus (DM) in order to explore the methodological problems in these reports and find possible solutions. The main medical literature databases in China were searched. Thirty-one articles were included and evaluated by the principles of clinical epidemiology. There were many mistakes and deficiencies in these articles, such as clinical trial designs, diagnosis criteria for DM, standards of syndrome differentiation of DM, case inclusive and exclusive criteria, sample size and estimation, data comparability and statistical methods. It is necessary and important to improve the quality of reports concerning quantitative analysis of syndrome differentiation of DM in light of the principles of clinical epidemiology.

Prevalence and Spectrum of Large Deletions or Duplications in the Major Long QT Syndrome-Susceptibility Genes and Implications for Long QT Syndrome Genetic Testing

PubMed Central

Tester, David J.; Benton, Amber J.; Train, Laura; Deal, Barbara; Baudhuin, Linnea M.; Ackerman, Michael J.

2010-01-01

Long QT Syndrome (LQTS) is a cardiac channelopathy associated with syncope, seizures, and sudden death. Approximately 75% of LQTS is due to mutations in genes encoding for three cardiac ion channel alpha-subunits (LQT1-3). However, traditional mutational analyses have limited detection capabilities for atypical mutations such as large gene rearrangements. Here, we set out to determine the prevalence and spectrum of large deletions/duplications in the major LQTS-susceptibility genes among unrelated patients who were mutation-negative following point mutation analysis of LQT1-12-susceptibility genes. Forty-two unrelated clinically strong LQTS patients were analyzed using multiplex ligation-dependent probe amplification (MLPA), a quantitative fluorescent technique for detecting multiple exon deletions and duplications. The SALSA-MLPA LQTS Kit from MRC-Holland was used to analyze the three major LQTS-associated genes: KCNQ1, KCNH2, and SCN5A and the two minor genes: KCNE1 and KCNE2. Overall, 2 gene rearrangements were found in 2/42 (4.8%, CI, 1.7–11%) unrelated patients. A deletion of KCNQ1 exon 3 was identified in a 10 year-old Caucasian boy with a QTc of 660 milliseconds (ms), a personal history of exercise-induced syncope, and a family history of syncope. A deletion of KCNQ1 exon 7 was identified in a 17 year-old Caucasian girl with a QTc of 480 ms, a personal history of exercise-induced syncope, and a family history of sudden cardiac death. In conclusion, since nearly 5% of patients with genetically elusive LQTS had large genomic rearrangements involving the canonical LQTS-susceptibility genes, reflex genetic testing to investigate genomic rearrangements may be of clinical value. PMID:20920651

[Application of Bayes Probability Model in Differentiation of Yin and Yang Jaundice Syndromes in Neonates].

PubMed

Mu, Chun-sun; Zhang, Ping; Kong, Chun-yan; Li, Yang-ning

2015-09-01

To study the application of Bayes probability model in differentiating yin and yang jaundice syndromes in neonates. Totally 107 jaundice neonates who admitted to hospital within 10 days after birth were assigned to two groups according to syndrome differentiation, 68 in the yang jaundice syndrome group and 39 in the yin jaundice syndrome group. Data collected for neonates were factors related to jaundice before, during and after birth. Blood routines, liver and renal functions, and myocardial enzymes were tested on the admission day or the next day. Logistic regression model and Bayes discriminating analysis were used to screen factors important for yin and yang jaundice syndrome differentiation. Finally, Bayes probability model for yin and yang jaundice syndromes was established and assessed. Factors important for yin and yang jaundice syndrome differentiation screened by Logistic regression model and Bayes discriminating analysis included mothers' age, mother with gestational diabetes mellitus (GDM), gestational age, asphyxia, or ABO hemolytic diseases, red blood cell distribution width (RDW-SD), platelet-large cell ratio (P-LCR), serum direct bilirubin (DBIL), alkaline phosphatase (ALP), cholinesterase (CHE). Bayes discriminating analysis was performed by SPSS to obtain Bayes discriminant function coefficient. Bayes discriminant function was established according to discriminant function coefficients. Yang jaundice syndrome: y1= -21. 701 +2. 589 x mother's age + 1. 037 x GDM-17. 175 x asphyxia + 13. 876 x gestational age + 6. 303 x ABO hemolytic disease + 2.116 x RDW-SD + 0. 831 x DBIL + 0. 012 x ALP + 1. 697 x LCR + 0. 001 x CHE; Yin jaundice syndrome: y2= -33. 511 + 2.991 x mother's age + 3.960 x GDM-12. 877 x asphyxia + 11. 848 x gestational age + 1. 820 x ABO hemolytic disease +2. 231 x RDW-SD +0. 999 x DBIL +0. 023 x ALP +1. 916 x LCR +0. 002 x CHE. Bayes discriminant function was hypothesis tested and got Wilks' λ =0. 393 (P =0. 000). So Bayes

Evolution of Gene Duplication in Plants.

PubMed

Panchy, Nicholas; Lehti-Shiu, Melissa; Shiu, Shin-Han

2016-08-01

Ancient duplication events and a high rate of retention of extant pairs of duplicate genes have contributed to an abundance of duplicate genes in plant genomes. These duplicates have contributed to the evolution of novel functions, such as the production of floral structures, induction of disease resistance, and adaptation to stress. Additionally, recent whole-genome duplications that have occurred in the lineages of several domesticated crop species, including wheat (Triticum aestivum), cotton (Gossypium hirsutum), and soybean (Glycine max), have contributed to important agronomic traits, such as grain quality, fruit shape, and flowering time. Therefore, understanding the mechanisms and impacts of gene duplication will be important to future studies of plants in general and of agronomically important crops in particular. In this review, we survey the current knowledge about gene duplication, including gene duplication mechanisms, the potential fates of duplicate genes, models explaining duplicate gene retention, the properties that distinguish duplicate from singleton genes, and the evolutionary impact of gene duplication. © 2016 American Society of Plant Biologists. All Rights Reserved.

Duplication in DNA Sequences

NASA Astrophysics Data System (ADS)

Ito, Masami; Kari, Lila; Kincaid, Zachary; Seki, Shinnosuke

The duplication and repeat-deletion operations are the basis of a formal language theoretic model of errors that can occur during DNA replication. During DNA replication, subsequences of a strand of DNA may be copied several times (resulting in duplications) or skipped (resulting in repeat-deletions). As formal language operations, iterated duplication and repeat-deletion of words and languages have been well studied in the literature. However, little is known about single-step duplications and repeat-deletions. In this paper, we investigate several properties of these operations, including closure properties of language families in the Chomsky hierarchy and equations involving these operations. We also make progress toward a characterization of regular languages that are generated by duplicating a regular language.

[Analysis of syndrome discipline of generalized anxiety disorder using data mining techniques].

PubMed

Tang, Qi-sheng; Sun, Wen-jun; Qu, Miao; Guo, Dong-fang

2012-09-01

To study the use of data mining techniques in analyzing the syndrome discipline of generalized anxiety disorder (GAD). From August 1, 2009 to July 31, 2010, 705 patients with GAD in 10 hospitals of Beijing were investigated over one year. Data mining techniques, such as Bayes net and cluster analysis, were used to analyze the syndrome discipline of GAD. A total of 61 symptoms of GAD were screened out. By using Bayes net, nine syndromes of GAD were abstracted based on the symptoms. Eight syndromes were abstracted by cluster analysis. After screening for duplicate syndromes and combining the experts' experience and traditional Chinese medicine theory, six syndromes of GAD were defined. These included depressed liver qi transforming into fire, phlegm-heat harassing the heart, liver depression and spleen deficiency, heart-kidney non-interaction, dual deficiency of the heart and spleen, and kidney deficiency and liver yang hyperactivity. Based on the results, the draft of Syndrome Diagnostic Criteria for Generalized Anxiety Disorder was developed. Data mining techniques such as Bayes net and cluster analysis have certain future potential for establishing syndrome models and analyzing syndrome discipline, thus they are suitable for the research of syndrome differentiation.

Buffering of crucial functions by paleologous duplicated genes may contribute cyclicality to angiosperm genome duplication.

PubMed

Chapman, Brad A; Bowers, John E; Feltus, Frank A; Paterson, Andrew H

2006-02-21

Genome duplication followed by massive gene loss has permanently shaped the genomes of many higher eukaryotes, particularly angiosperms. It has long been believed that a primary advantage of genome duplication is the opportunity for the evolution of genes with new functions by modification of duplicated genes. If so, then patterns of genetic diversity among strains within taxa might reveal footprints of selection that are consistent with this advantage. Contrary to classical predictions that duplicated genes may be relatively free to acquire unique functionality, we find among both Arabidopsis ecotypes and Oryza subspecies that SNPs encode less radical amino acid changes in genes for which there exists a duplicated copy at a "paleologous" locus than in "singleton" genes. Preferential retention of duplicated genes encoding long complex proteins and their unexpectedly slow divergence (perhaps because of homogenization) suggest that a primary advantage of retaining duplicated paleologs may be the buffering of crucial functions. Functional buffering and functional divergence may represent extremes in the spectrum of duplicated gene fates. Functional buffering may be especially important during "genomic turmoil" immediately after genome duplication but continues to act approximately 60 million years later, and its gradual deterioration may contribute cyclicality to genome duplication in some lineages.

Buffering of crucial functions by paleologous duplicated genes may contribute cyclicality to angiosperm genome duplication

PubMed Central

Chapman, Brad A.; Bowers, John E.; Feltus, Frank A.; Paterson, Andrew H.

2006-01-01

Genome duplication followed by massive gene loss has permanently shaped the genomes of many higher eukaryotes, particularly angiosperms. It has long been believed that a primary advantage of genome duplication is the opportunity for the evolution of genes with new functions by modification of duplicated genes. If so, then patterns of genetic diversity among strains within taxa might reveal footprints of selection that are consistent with this advantage. Contrary to classical predictions that duplicated genes may be relatively free to acquire unique functionality, we find among both Arabidopsis ecotypes and Oryza subspecies that SNPs encode less radical amino acid changes in genes for which there exists a duplicated copy at a “paleologous” locus than in “singleton” genes. Preferential retention of duplicated genes encoding long complex proteins and their unexpectedly slow divergence (perhaps because of homogenization) suggest that a primary advantage of retaining duplicated paleologs may be the buffering of crucial functions. Functional buffering and functional divergence may represent extremes in the spectrum of duplicated gene fates. Functional buffering may be especially important during “genomic turmoil” immediately after genome duplication but continues to act ≈60 million years later, and its gradual deterioration may contribute cyclicality to genome duplication in some lineages. PMID:16467140

Case Report: Whole exome sequencing helps in accurate molecular diagnosis in siblings with a rare co-occurrence of paternally inherited 22q12 duplication and autosomal recessive non-syndromic ichthyosis.

PubMed Central

Gupta, Aayush; Sharma, Yugal; Deo, Kirti; Vellarikkal, Shamsudheen; Jayarajan, Rijith; Dixit, Vishal; Verma, Ankit; Scaria, Vinod; Sivasubbu, Sridhar

2015-01-01

Lamellar ichthyosis (LI), considered an autosomal recessive monogenic genodermatosis, has an incidence of approximately 1 in 250,000. Usually associated with mutations in the transglutaminase gene ( TGM1), mutations in six other genes have, less frequently, been shown to be causative. Two siblings, born in a collodion membrane, presented with fish like scales all over the body. Karyotyping revealed duplication of the chromosome arm on 22q12+ in the father and two siblings. Whole exome sequencing revealed a homozygous p.Gly218Ser variation in TGM1; a variation reported earlier in an isolated Finnish population in association with autosomal recessive non-syndromic ichthyosis. This concurrence of a potentially benign 22q12+ duplication and LI, both rare individually, is reported here likely for the first time. PMID:26594337

Clinical and molecular characterization of duplications encompassing the human SHOX gene reveal a variable effect on stature.

PubMed

Thomas, N Simon; Harvey, John F; Bunyan, David J; Rankin, Julia; Grigelioniene, Giedre; Bruno, Damien L; Tan, Tiong Y; Tomkins, Susan; Hastings, Robert

2009-07-01

Deletions of the SHOX gene are well documented and cause disproportionate short stature and variable skeletal abnormalities. In contrast interstitial SHOX duplications limited to PAR1 appear to be very rare and the clinical significance of the only case report in the literature is unclear. Mapping of this duplication has now shown that it includes the entire SHOX gene but little flanking sequence and so will not encompass any of the long-range enhancers required for SHOX transcription. We now describe the clinical and molecular characterization of three additional cases. The duplications all included the SHOX coding sequence but varied in the amount of flanking sequence involved. The probands were ascertained for a variety of reasons: hypotonia and features of Asperger syndrome, Leri-Weill dyschondrosteosis (LWD), and a family history of cleft palate. However, the presence of a duplication did not correlate with any of these features or with evidence of skeletal abnormality. Remarkably, the proband with LWD had inherited both a SHOX deletion and a duplication. The effect of the duplications on stature was variable: height appeared to be elevated in some carriers, particularly in those with the largest duplications, but was still within the normal range. SHOX duplications are likely to be under ascertained and more cases need to be identified and characterized in detail in order to accurately determine their phenotypic consequences.

Evolution of vertebrate central nervous system is accompanied by novel expression changes of duplicate genes.

PubMed

Chen, Yuan; Ding, Yun; Zhang, Zuming; Wang, Wen; Chen, Jun-Yuan; Ueno, Naoto; Mao, Bingyu

2011-12-20

The evolution of the central nervous system (CNS) is one of the most striking changes during the transition from invertebrates to vertebrates. As a major source of genetic novelties, gene duplication might play an important role in the functional innovation of vertebrate CNS. In this study, we focused on a group of CNS-biased genes that duplicated during early vertebrate evolution. We investigated the tempo-spatial expression patterns of 33 duplicate gene families and their orthologs during the embryonic development of the vertebrate Xenopus laevis and the cephalochordate Brachiostoma belcheri. Almost all the identified duplicate genes are differentially expressed in the CNS in Xenopus embryos, and more than 50% and 30% duplicate genes are expressed in the telencephalon and mid-hindbrain boundary, respectively, which are mostly considered as two innovations in the vertebrate CNS. Interestingly, more than 50% of the amphioxus orthologs do not show apparent expression in the CNS in amphioxus embryos as detected by in situ hybridization, indicating that some of the vertebrate CNS-biased duplicate genes might arise from non-CNS genes in invertebrates. Our data accentuate the functional contribution of gene duplication in the CNS evolution of vertebrate and uncover an invertebrate non-CNS history for some vertebrate CNS-biased duplicate genes. Copyright © 2011. Published by Elsevier Ltd.

Differential diagnosis and management of Behçet syndrome.

PubMed

Ambrose, Nicola L; Haskard, Dorian O

2013-02-01

Behçet syndrome (also known as Behçet disease) is a rare condition that is associated with considerable morbidity. Cases of Behçet syndrome have been reported worldwide, but the highest prevalence occurs in countries that border the ancient Silk Route, such as Turkey and Iran. Although oral ulceration, genital ulceration and eye disease are the classic triad of manifestations, the cardiovascular, gastrointestinal, musculoskeletal and central nervous systems can also be affected. The syndrome is chronic and relapsing with some patients having benign episodes whereas others have more serious complications, including blindness or the rupture of a pulmonary arterial aneurysm. Diagnosing Behçet syndrome, particularly outside of endemic regions, often incurs a considerable delay owing to the rarity of this condition. Furthermore, a paucity exists of data from randomized controlled trials on the optimal therapeutic approaches to use in patients, as well as a lack of informative laboratory surrogate markers to monitor disease progression. This Review discusses the issues surrounding the diagnosis and differential diagnosis of Behçet syndrome and presents the current approaches to managing patients with this complex group of disorders.

The fate of the duplicated androgen receptor in fishes: a late neofunctionalization event?

PubMed Central

2008-01-01

Background Based on the observation of an increased number of paralogous genes in teleost fishes compared with other vertebrates and on the conserved synteny between duplicated copies, it has been shown that a whole genome duplication (WGD) occurred during the evolution of Actinopterygian fish. Comparative phylogenetic dating of this duplication event suggests that it occurred early on, specifically in teleosts. It has been proposed that this event might have facilitated the evolutionary radiation and the phenotypic diversification of the teleost fish, notably by allowing the sub- or neo-functionalization of many duplicated genes. Results In this paper, we studied in a wide range of Actinopterygians the duplication and fate of the androgen receptor (AR, NR3C4), a nuclear receptor known to play a key role in sex-determination in vertebrates. The pattern of AR gene duplication is consistent with an early WGD event: it has been duplicated into two genes AR-A and AR-B after the split of the Acipenseriformes from the lineage leading to teleost fish but before the divergence of Osteoglossiformes. Genomic and syntenic analyses in addition to lack of PCR amplification show that one of the duplicated copies, AR-B, was lost in several basal Clupeocephala such as Cypriniformes (including the model species zebrafish), Siluriformes, Characiformes and Salmoniformes. Interestingly, we also found that, in basal teleost fish (Osteoglossiformes and Anguilliformes), the two copies remain very similar, whereas, specifically in Percomorphs, one of the copies, AR-B, has accumulated substitutions in both the ligand binding domain (LBD) and the DNA binding domain (DBD). Conclusion The comparison of the mutations present in these divergent AR-B with those known in human to be implicated in complete, partial or mild androgen insensitivity syndrome suggests that the existence of two distinct AR duplicates may be correlated to specific functional differences that may be connected to the well

Facial duplication: case, review, and embryogenesis.

PubMed

Barr, M

1982-04-01

The craniofacial anatomy of an infant with facial duplication is described. There were four eyes, two noses, two maxillae, and one mandible. Anterior to the single pituitary the brain was duplicated and there was bilateral arhinencephaly. Portions of the brain were extruded into a large frontal encephalocele. Cases of symmetrical facial duplication reported in the literature range from two complete faces on a single head (diprosopus) to simple nasal duplication. The variety of patterns of duplication suggests that the doubling of facial components arises in several different ways: Forking of the notochord, duplication of the prosencephalon, duplication of the olfactory placodes, and duplication of maxillary and/or mandibular growth centers around the margins of the stomatodeal plate. Among reported cases, the female:male ratio is 2:1.

Pyloric duplications: review and case study.

PubMed

Cooper, S; Abrams, R S; Carbaugh, R A

1995-12-01

Gastric duplications are unusual congenital anomalies that often require surgical treatment. Pyloric duplications are particularly rare; few are reported in the English literature. This article reviews the literature on pyloric duplications and describes a pyloric duplication associated with hypertrophic pyloric stenosis in a 5-week-old child and a duplication that recurred 7 years later.

Chromosome I duplications in Caenorhabditis elegans

DOE Office of Scientific and Technical Information (OSTI.GOV)

McKim, K.S.; Rose, A.M.

1990-01-01

We have isolated and characterized 76 duplications of chromosome I in the genome of Caenorhabditis elegans. The region studied is the 20 map unit left half of the chromosome. Sixty-two duplications were induced with gamma radiation and 14 arose spontaneously. The latter class was apparently the result of spontaneous breaks within the parental duplication. The majority of duplications behave as if they are free. Three duplications are attached to identifiable sequences from other chromosomes. The duplication breakpoints have been mapped by complementation analysis relative to genes on chromosome I. Nineteen duplication breakpoints and seven deficiency breakpoints divide the left halfmore » of the chromosome into 24 regions. We have studied the relationship between duplication size and segregational stability. While size is an important determinant of mitotic stability, it is not the only one. We observed clear exceptions to a size-stability correlation. In addition to size, duplication stability may be influenced by specific sequences or chromosome structure. The majority of the duplications were stable enough to be powerful tools for gene mapping. Therefore the duplications described here will be useful in the genetic characterization of chromosome I and the techniques we have developed can be adapted to other regions of the genome.« less

Prevalence and spectrum of large deletions or duplications in the major long QT syndrome-susceptibility genes and implications for long QT syndrome genetic testing.

PubMed

Tester, David J; Benton, Amber J; Train, Laura; Deal, Barbara; Baudhuin, Linnea M; Ackerman, Michael J

2010-10-15

Long QT syndrome (LQTS) is a cardiac channelopathy associated with syncope, seizures, and sudden death. Approximately 75% of LQTS is due to mutations in genes encoding for 3 cardiac ion channel α-subunits (LQT1 to LQT3). However, traditional mutational analyses have limited detection capabilities for atypical mutations such as large gene rearrangements. We set out to determine the prevalence and spectrum of large deletions/duplications in the major LQTS-susceptibility genes in unrelated patients who were mutation negative after point mutation analysis of LQT1- to LQT12-susceptibility genes. Forty-two unrelated, clinically strong LQTS patients were analyzed using multiplex ligation-dependent probe amplification, a quantitative fluorescent technique for detecting multiple exon deletions and duplications. The SALSA multiplex ligation-dependent probe amplification LQTS kit from MRC-Holland was used to analyze the 3 major LQTS-associated genes, KCNQ1, KCNH2, and SCN5A, and the 2 minor genes, KCNE1 and KCNE2. Overall, 2 gene rearrangements were found in 2 of 42 unrelated patients (4.8%, confidence interval 1.7 to 11). A deletion of KCNQ1 exon 3 was identified in a 10-year-old Caucasian boy with a corrected QT duration of 660 ms, a personal history of exercise-induced syncope, and a family history of syncope. A deletion of KCNQ1 exon 7 was identified in a 17-year-old Caucasian girl with a corrected QT duration of 480 ms, a personal history of exercise-induced syncope, and a family history of sudden cardiac death. In conclusion, because nearly 5% of patients with genetically elusive LQTS had large genomic rearrangements involving the canonical LQTS-susceptibility genes, reflex genetic testing to investigate genomic rearrangements may be of clinical value. Copyright © 2010 Elsevier Inc. All rights reserved.

Multidetector row computed tomography and ultrasound characteristics of caudal vena cava duplication in dogs.

PubMed

Bertolini, Giovanna; Diana, Alessia; Cipone, Mario; Drigo, Michele; Caldin, Marco

2014-01-01

Caudal vena cava duplication has been rarely reported in small animals. The purpose of this retrospective study was to describe characteristics of duplicated caudal vena cava in a large group of dogs. Computed tomography (CT) and ultrasound databases from two hospitals were searched for canine reports having the diagnosis "double caudal vena cava." One observer reviewed CT images for 71 dogs and two observers reviewed ultrasound images for 21 dogs. In all CT cases, the duplication comprised two vessels that were bilaterally symmetrical and approximately the same calibre (similar to Type I complete duplication in humans). In all ultrasound cases, the duplicated caudal vena cava appeared as a distinct vessel running on the left side of the abdominal segment of the descending aorta and extending from the left common iliac vein to the left renal vein. The prevalence of caudal vena cava duplication was 0.46% for canine ultrasound studies and 2.08% for canine CT studies performed at these hospitals. Median body weight for affected dogs was significantly lower than that of unaffected dogs (P < 0.0001). Breeds with increased risk for duplicated caudal vena cava were Yorkshire Terrier (odds ratio [OR] = 6.41), Poodle (OR = 7.46), West Highland White Terrier (OR = 6.33), and Maltese (OR = 3.87). Presence of a duplicated caudal vena cava was significantly associated with presence of extrahepatic portosystemic shunt(s) (P < 0.004). While uncommon in dogs, caudal vena cava duplication should be differentiated from other vascular anomalies when planning surgeries and for avoiding misdiagnoses. © 2014 American College of Veterinary Radiology.

Craniofacial duplication: a case report.

PubMed

Suryawanshi, Pradeep; Deshpande, Mandar; Verma, Nitin; Mahendrakar, Vivek; Mahendrakar, Sandhya

2013-09-01

A craniofacial duplication or diprosopus is an unusual variant of conjoined twinning. The reported incidence is one in 180,000-15 million births and 35 cases have been reported till date. The phenotype is wide, with the partial duplication of a few facial structures to complete dicephalus. A complete duplication is associated with a high incidence of anomalies in the central nervous system, cardiovascular system, gastrointestinal system and the respiratory system, whereas no major anomalies are found in the infants with a partial duplication. A term baby with the features of a craniofacial duplication has been described, with the proposed theories on embryogenesis and a brief review of the literature.

Delusional misidentifications and duplications: right brain lesions, left brain delusions.

PubMed

Devinsky, Orrin

2009-01-06

When the delusional misidentification syndromes reduplicative paramnesia and Capgras syndromes result from neurologic disease, lesions are usually bifrontal and/or right hemispheric. The related disorders of confabulation and anosognosis share overlapping mechanisms and anatomic pathology. A dual mechanism is postulated for the delusional misidentification syndromes: negative effects from right hemisphere and frontal lobe dysfunction as well as positive effects from release (i.e., overactivity) of preserved left hemisphere areas. Negative effects of right hemisphere injury impair self-monitoring, ego boundaries, and attaching emotional valence and familiarity to stimuli. The unchecked left hemisphere unleashes a creative narrator from the monitoring of self, memory, and reality by the frontal and right hemisphere areas, leading to excessive and false explanations. Further, the left hemisphere's cognitive style of categorization, often into dual categories, leads it to invent a duplicate or impostor to resolve conflicting information. Delusions result from right hemisphere lesions. But it is the left hemisphere that is deluded.

Saccharomyces cerevisiae ribosomal protein L37 is encoded by duplicate genes that are differentially expressed.

PubMed

Tornow, J; Santangelo, G M

1994-06-01

A duplicate copy of the RPL37A gene (encoding ribosomal protein L37) was cloned and sequenced. The coding region of RPL37B is very similar to that of RPL37A, with only one conservative amino-acid difference. However, the intron and flanking sequences of the two genes are extremely dissimilar. Disruption experiments indicate that the two loci are not functionally equivalent: disruption of RPL37B was insignificant, but disruption of RPL37A severely impaired the growth rate of the cell. When both RPL37 loci are disrupted, the cell is unable to grow at all, indicating that rpL37 is an essential protein. The functional disparity between the two RPL37 loci could be explained by differential gene expression. The results of two experiments support this idea: gene fusion of RPL37A to a reporter gene resulted in six-fold higher mRNA levels than was generated by the same reporter gene fused to RPL37B, and a modest increase in gene dosage of RPL37B overcame the lack of a functional RPL37A gene.

Craniofacial Duplication: A Case Report

PubMed Central

Suryawanshi, Pradeep; Deshpande, Mandar; Verma, Nitin; Mahendrakar, Vivek; Mahendrakar, Sandhya

2013-01-01

A craniofacial duplication or diprosopus is an unusual variant of conjoined twinning. The reported incidence is one in 180,000-15 million births and 35 cases have been reported till date. The phenotype is wide, with the partial duplication of a few facial structures to complete dicephalus. A complete duplication is associated with a high incidence of anomalies in the central nervous system, cardiovascular system, gastrointestinal system and the respiratory system, whereas no major anomalies are found in the infants with a partial duplication. A term baby with the features of a craniofacial duplication has been described, with the proposed theories on embryogenesis and a brief review of the literature. PMID:24179933

Ancient and Recent Duplications Support Functional Diversity of Daphnia Opsins.

PubMed

Brandon, Christopher S; Greenwold, Matthew J; Dudycha, Jeffry L

2017-01-01

Daphnia pulex has the largest known family of opsins, genes critical for photoreception and vision in animals. This diversity may be functionally redundant, arising from recent processes, or ancient duplications may have been preserved due to distinct functions and independent contributions to fitness. We analyzed opsins in D. pulex and its distant congener Daphnia magna. We identified 48 opsins in the D. pulex genome and 32 in D. magna. We inferred the complement of opsins in the last common ancestor of all Daphnia and evaluated the history of opsin duplication and loss. We further analyzed sequence variation to assess possible functional diversification among Daphnia opsins. Much of the opsin expansion occurred before the D. pulex-D. magna split more than 145 Mya, and both Daphnia lineages preserved most ancient opsins. More recent expansion occurred in pteropsins and long-wavelength visual opsins in both species, particularly D. pulex. Recent duplications were not random: the same ancestral genes duplicated independently in each modern species. Most ancient and some recent duplications involved differentiation at residues known to influence spectral tuning of visual opsins. Arthropsins show evidence of gene conversion between tandemly arrayed paralogs in functionally important domains. Intron-exon gene structure was generally conserved within clades inferred from sequences, although pteropsins showed substantial intron size variation. Overall, our analyses support the hypotheses that diverse opsins are maintained due to diverse functional roles in photoreception and vision, that functional diversification is both ancient and recent, and that multiple evolutionary processes have influenced different types of opsins.

Do Children Think that Duplicating the Body also Duplicates the Mind?

ERIC Educational Resources Information Center

Hood, Bruce; Gjersoe, Nathalia L.; Bloom, Paul

2012-01-01

Philosophers use hypothetical duplication scenarios to explore intuitions about personal identity. Here we examined 5- to 6-year-olds' intuitions about the physical properties and memories of a live hamster that is apparently duplicated by a machine. In Study 1, children thought that more of the original's physical properties than episodic…

Transducin Duplicates in the Zebrafish Retina and Pineal Complex: Differential Specialisation after the Teleost Tetraploidisation

PubMed Central

Lagman, David; Callado-Pérez, Amalia; Franzén, Ilkin E.

2015-01-01

Gene duplications provide raw materials that can be selected for functional adaptations by evolutionary mechanisms. We describe here the results of 350 million years of evolution of three functionally related gene families: the alpha, beta and gamma subunits of transducins, the G protein involved in vision. Early vertebrate tetraploidisations resulted in separate transducin heterotrimers: gnat1/gnb1/gngt1 for rods, and gnat2/gnb3/gngt2 for cones. The teleost-specific tetraploidisation generated additional duplicates for gnb1, gnb3 and gngt2. We report here that the duplicates have undergone several types of subfunctionalisation or neofunctionalisation in the zebrafish. We have found that gnb1a and gnb1b are co-expressed at different levels in rods; gnb3a and gnb3b have undergone compartmentalisation restricting gnb3b to the dorsal and medial retina, however, gnb3a expression was detected only at very low levels in both larvae and adult retina; gngt2b expression is restricted to the dorsal and medial retina, whereas gngt2a is expressed ventrally. This dorsoventral distinction could be an adaptation to protect the lower part of the retina from intense light damage. The ontogenetic analysis shows earlier onset of expression in the pineal complex than in the retina, in accordance with its earlier maturation. Additionally, gnb1a but not gnb1b is expressed in the pineal complex, and gnb3b and gngt2b are transiently expressed in the pineal during ontogeny, thus showing partial temporal subfunctionalisation. These retina-pineal distinctions presumably reflect their distinct functional roles in vision and circadian rhythmicity. In summary, this study describes several functional differences between transducin gene duplicates resulting from the teleost-specific tetraploidisation. PMID:25806532

The early stages of duplicate gene evolution

PubMed Central

Moore, Richard C.; Purugganan, Michael D.

2003-01-01

Gene duplications are one of the primary driving forces in the evolution of genomes and genetic systems. Gene duplicates account for 8–20% of the genes in eukaryotic genomes, and the rates of gene duplication are estimated at between 0.2% and 2% per gene per million years. Duplicate genes are believed to be a major mechanism for the establishment of new gene functions and the generation of evolutionary novelty, yet very little is known about the early stages of the evolution of duplicated gene pairs. It is unclear, for example, to what extent selection, rather than neutral genetic drift, drives the fixation and early evolution of duplicate loci. Analysis of recently duplicated genes in the Arabidopsis thaliana genome reveals significantly reduced species-wide levels of nucleotide polymorphisms in the progenitor and/or duplicate gene copies, suggesting that selective sweeps accompany the initial stages of the evolution of these duplicated gene pairs. Our results support recent theoretical work that indicates that fates of duplicate gene pairs may be determined in the initial phases of duplicate gene evolution and that positive selection plays a prominent role in the evolutionary dynamics of the very early histories of duplicate nuclear genes. PMID:14671323

Dose-sensitivity, conserved non-coding sequences, and duplicate gene retention through multiple tetraploidies in the grasses.

PubMed

Schnable, James C; Pedersen, Brent S; Subramaniam, Sabarinath; Freeling, Michael

2011-01-01

Whole genome duplications, or tetraploidies, are an important source of increased gene content. Following whole genome duplication, duplicate copies of many genes are lost from the genome. This loss of genes is biased both in the classes of genes deleted and the subgenome from which they are lost. Many or all classes are genes preferentially retained as duplicate copies are engaged in dose sensitive protein-protein interactions, such that deletion of any one duplicate upsets the status quo of subunit concentrations, and presumably lowers fitness as a result. Transcription factors are also preferentially retained following every whole genome duplications studied. This has been explained as a consequence of protein-protein interactions, just as for other highly retained classes of genes. We show that the quantity of conserved noncoding sequences (CNSs) associated with genes predicts the likelihood of their retention as duplicate pairs following whole genome duplication. As many CNSs likely represent binding sites for transcriptional regulators, we propose that the likelihood of gene retention following tetraploidy may also be influenced by dose-sensitive protein-DNA interactions between the regulatory regions of CNS-rich genes - nicknamed bigfoot genes - and the proteins that bind to them. Using grass genomes, we show that differential loss of CNSs from one member of a pair following the pre-grass tetraploidy reduces its chance of retention in the subsequent maize lineage tetraploidy.

Dose–Sensitivity, Conserved Non-Coding Sequences, and Duplicate Gene Retention Through Multiple Tetraploidies in the Grasses

PubMed Central

Schnable, James C.; Pedersen, Brent S.; Subramaniam, Sabarinath; Freeling, Michael

2011-01-01

Whole genome duplications, or tetraploidies, are an important source of increased gene content. Following whole genome duplication, duplicate copies of many genes are lost from the genome. This loss of genes is biased both in the classes of genes deleted and the subgenome from which they are lost. Many or all classes are genes preferentially retained as duplicate copies are engaged in dose sensitive protein–protein interactions, such that deletion of any one duplicate upsets the status quo of subunit concentrations, and presumably lowers fitness as a result. Transcription factors are also preferentially retained following every whole genome duplications studied. This has been explained as a consequence of protein–protein interactions, just as for other highly retained classes of genes. We show that the quantity of conserved noncoding sequences (CNSs) associated with genes predicts the likelihood of their retention as duplicate pairs following whole genome duplication. As many CNSs likely represent binding sites for transcriptional regulators, we propose that the likelihood of gene retention following tetraploidy may also be influenced by dose–sensitive protein–DNA interactions between the regulatory regions of CNS-rich genes – nicknamed bigfoot genes – and the proteins that bind to them. Using grass genomes, we show that differential loss of CNSs from one member of a pair following the pre-grass tetraploidy reduces its chance of retention in the subsequent maize lineage tetraploidy. PMID:22645525

Study on TCM Syndrome Differentiation of Primary Liver Cancer Based on the Analysis of Latent Structural Model.

PubMed

Gu, Zhan; Qi, Xiuzhong; Zhai, Xiaofeng; Lang, Qingbo; Lu, Jianying; Ma, Changping; Liu, Long; Yue, Xiaoqiang

2015-01-01

Primary liver cancer (PLC) is one of the most common malignant tumors because of its high incidence and high mortality. Traditional Chinese medicine (TCM) plays an active role in the treatment of PLC. As the most important part in the TCM system, syndrome differentiation based on the clinical manifestations from traditional four diagnostic methods has met great challenges and questions with the lack of statistical validation support. In this study, we provided evidences for TCM syndrome differentiation of PLC using the method of analysis of latent structural model from clinic data, thus providing basis for establishing TCM syndrome criteria. And also we obtain the common syndromes of PLC as well as their typical clinical manifestations, respectively.

Duplication of SOX9 associated with 46,XX ovotesticular disorder of sex development.

PubMed

López-Hernández, Berenice; Méndez, Juan Pablo; Coral-Vázquez, Ramón Mauricio; Benítez-Granados, Jesús; Zenteno, Juan Carlos; Villegas-Ruiz, Vanessa; Calzada-León, Raúl; Soderlund, Daniela; Canto, Patricia

2018-04-04

The purpose of the present study was to investigate whether ten unrelated SRY-negative individuals with this sex differentiation disorder presented a double dose of SOX9 as the cause of their disease. Ten unrelated SRY-negative 46,XX ovotesticular disorder of sexual development (DSD) subjects were molecularly studied. Multiplex-ligation dependent probe amplification (MLPA) and quantitative real-time PCR analysis (qRT-PCR) for SOX9 were performed. The MLPA analysis demonstrated that one patient presented a heterozygous duplication of the entire SOX9 coding region (above 1.3 value of peak ratio), as well as at least a ~ 483 kb upstream duplication. Moreover, no duplication of other SOX9 probes was observed corresponding to the region between -1007 and -1500 kb upstream. A qRT-PCR analysis showed a duplication of at least -581 kb upstream and ~1.63 kb of the coding region that encompasses exon 3. The limits of the duplication were mapped approximately from ~71539762 to 72122741 of Chr17. No molecular abnormalities were found in the remaining nine patients. This study is thought to be the first report regarding a duplication of SOX9 that is associated with the presence of 46,XX ovotesticular DSD, encompassing at least -581 kb upstream, and the almost entire coding region of the gene. Copyright © 2018 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

Gene Duplication and Evolutionary Innovations in Hemoglobin-Oxygen Transport

PubMed Central

2016-01-01

During vertebrate evolution, duplicated hemoglobin (Hb) genes diverged with respect to functional properties as well as the developmental timing of expression. For example, the subfamilies of genes that encode the different subunit chains of Hb are ontogenetically regulated such that functionally distinct Hb isoforms are expressed during different developmental stages. In some vertebrate taxa, functional differentiation between co-expressed Hb isoforms may also contribute to physiologically important divisions of labor. PMID:27053736

Recurrent acute pancreatitis secondary to a duodenal duplication cyst in an adult. A case report and literature review

PubMed Central

Salemis, Nikolaos S; Liatsos, Christos; Kolios, Michail; Gourgiotis, Stavros

2009-01-01

Duodenal duplication cysts are rare congenital abnormalities that are most commonly diagnosed in infancy and childhood. However, in rare cases, the lesion can remain asymptomatic until adulthood. An extremely rare case of a previously healthy adult patient with recurrent acute pancreatitis, who was diagnosed with a duodenal duplication cyst is presented. At laparotomy, a duplication cyst measuring 4.8 cm × 4 cm × 4 cm was found adjacent to the ampulla of Vater. A partial cyst excision and marsupialization into the duodenal lumen was performed. The patient is healthy and asymptomatic four years after surgery. The present case illustrates the necessity of considering a duodenal duplication cyst in the differential diagnosis of recurrent acute pancreatitis in previously healthy adults. PMID:19893770

Recurrent acute pancreatitis secondary to a duodenal duplication cyst in an adult. A case report and literature review.

PubMed

Salemis, Nikolaos S; Liatsos, Christos; Kolios, Michail; Gourgiotis, Stavros

2009-11-01

Duodenal duplication cysts are rare congenital abnormalities that are most commonly diagnosed in infancy and childhood. However, in rare cases, the lesion can remain asymptomatic until adulthood. An extremely rare case of a previously healthy adult patient with recurrent acute pancreatitis, who was diagnosed with a duodenal duplication cyst is presented. At laparotomy, a duplication cyst measuring 4.8 cm x 4 cm x 4 cm was found adjacent to the ampulla of Vater. A partial cyst excision and marsupialization into the duodenal lumen was performed. The patient is healthy and asymptomatic four years after surgery. The present case illustrates the necessity of considering a duodenal duplication cyst in the differential diagnosis of recurrent acute pancreatitis in previously healthy adults.

Analysis of LMNB1 Duplications in Autosomal Dominant Leukodystrophy Provides Insights into Duplication Mechanisms and Allele-Specific Expression

PubMed Central

Giorgio, Elisa; Rolyan, Harshvardhan; Kropp, Laura; Chakka, Anish Baswanth; Yatsenko, Svetlana; Gregorio, Eleonora Di; Lacerenza, Daniela; Vaula, Giovanna; Talarico, Flavia; Mandich, Paola; Toro, Camilo; Pierre, Eleonore Eymard; Labauge, Pierre; Capellari, Sabina; Cortelli, Pietro; Vairo, Filippo Pinto; Miguel, Diego; Stubbolo, Danielle; Marques, Lourenco Charles; Gahl, William; Boespflug-Tanguy, Odile; Melberg, Atle; Hassin-Baer, Sharon; Cohen, Oren S; Pjontek, Rastislav; Grau, Armin; Klopstock, Thomas; Fogel, Brent; Meijer, Inge; Rouleau, Guy; Bouchard, Jean-Pierre L; Ganapathiraju, Madhavi; Vanderver, Adeline; Dahl, Niklas; Hobson, Grace; Brusco, Alfredo; Brussino, Alessandro; Padiath, Quasar Saleem

2013-01-01

ABSTRACT Autosomal dominant leukodystrophy (ADLD) is an adult onset demyelinating disorder that is caused by duplications of the lamin B1 (LMNB1) gene. However, as only a few cases have been analyzed in detail, the mechanisms underlying LMNB1 duplications are unclear. We report the detailed molecular analysis of the largest collection of ADLD families studied, to date. We have identified the minimal duplicated region necessary for the disease, defined all the duplication junctions at the nucleotide level and identified the first inverted LMNB1 duplication. We have demonstrated that the duplications are not recurrent; patients with identical duplications share the same haplotype, likely inherited from a common founder and that the duplications originated from intrachromosomal events. The duplication junction sequences indicated that nonhomologous end joining or replication-based mechanisms such fork stalling and template switching or microhomology-mediated break induced repair are likely to be involved. LMNB1 expression was increased in patients’ fibroblasts both at mRNA and protein levels and the three LMNB1 alleles in ADLD patients show equal expression, suggesting that regulatory regions are maintained within the rearranged segment. These results have allowed us to elucidate duplication mechanisms and provide insights into allele-specific LMNB1 expression levels. PMID:23649844

Profiling of gene duplication patterns of sequenced teleost genomes: evidence for rapid lineage-specific genome expansion mediated by recent tandem duplications.

PubMed

Lu, Jianguo; Peatman, Eric; Tang, Haibao; Lewis, Joshua; Liu, Zhanjiang

2012-06-15

Gene duplication has had a major impact on genome evolution. Localized (or tandem) duplication resulting from unequal crossing over and whole genome duplication are believed to be the two dominant mechanisms contributing to vertebrate genome evolution. While much scrutiny has been directed toward discerning patterns indicative of whole-genome duplication events in teleost species, less attention has been paid to the continuous nature of gene duplications and their impact on the size, gene content, functional diversity, and overall architecture of teleost genomes. Here, using a Markov clustering algorithm directed approach we catalogue and analyze patterns of gene duplication in the four model teleost species with chromosomal coordinates: zebrafish, medaka, stickleback, and Tetraodon. Our analyses based on set size, duplication type, synonymous substitution rate (Ks), and gene ontology emphasize shared and lineage-specific patterns of genome evolution via gene duplication. Most strikingly, our analyses highlight the extraordinary duplication and retention rate of recent duplicates in zebrafish and their likely role in the structural and functional expansion of the zebrafish genome. We find that the zebrafish genome is remarkable in its large number of duplicated genes, small duplicate set size, biased Ks distribution toward minimal mutational divergence, and proportion of tandem and intra-chromosomal duplicates when compared with the other teleost model genomes. The observed gene duplication patterns have played significant roles in shaping the architecture of teleost genomes and appear to have contributed to the recent functional diversification and divergence of important physiological processes in zebrafish. We have analyzed gene duplication patterns and duplication types among the available teleost genomes and found that a large number of genes were tandemly and intrachromosomally duplicated, suggesting their origin of independent and continuous duplication

Detecting long tandem duplications in genomic sequences.

PubMed

Audemard, Eric; Schiex, Thomas; Faraut, Thomas

2012-05-08

Detecting duplication segments within completely sequenced genomes provides valuable information to address genome evolution and in particular the important question of the emergence of novel functions. The usual approach to gene duplication detection, based on all-pairs protein gene comparisons, provides only a restricted view of duplication. In this paper, we introduce ReD Tandem, a software using a flow based chaining algorithm targeted at detecting tandem duplication arrays of moderate to longer length regions, with possibly locally weak similarities, directly at the DNA level. On the A. thaliana genome, using a reference set of tandem duplicated genes built using TAIR,(a) we show that ReD Tandem is able to predict a large fraction of recently duplicated genes (dS  <  1) and that it is also able to predict tandem duplications involving non coding elements such as pseudo-genes or RNA genes. ReD Tandem allows to identify large tandem duplications without any annotation, leading to agnostic identification of tandem duplications. This approach nicely complements the usual protein gene based which ignores duplications involving non coding regions. It is however inherently restricted to relatively recent duplications. By recovering otherwise ignored events, ReD Tandem gives a more comprehensive view of existing evolutionary processes and may also allow to improve existing annotations.

Evolution of Gene Duplication in Plants1[OPEN

PubMed Central

2016-01-01

Ancient duplication events and a high rate of retention of extant pairs of duplicate genes have contributed to an abundance of duplicate genes in plant genomes. These duplicates have contributed to the evolution of novel functions, such as the production of floral structures, induction of disease resistance, and adaptation to stress. Additionally, recent whole-genome duplications that have occurred in the lineages of several domesticated crop species, including wheat (Triticum aestivum), cotton (Gossypium hirsutum), and soybean (Glycine max), have contributed to important agronomic traits, such as grain quality, fruit shape, and flowering time. Therefore, understanding the mechanisms and impacts of gene duplication will be important to future studies of plants in general and of agronomically important crops in particular. In this review, we survey the current knowledge about gene duplication, including gene duplication mechanisms, the potential fates of duplicate genes, models explaining duplicate gene retention, the properties that distinguish duplicate from singleton genes, and the evolutionary impact of gene duplication. PMID:27288366

[Asperger Syndrome and/or Clinical High Risk of Psychosis? A Differential Diagnostic Challenge].

PubMed

Schmidt, Stefanie J; Behar, Ayla; Schultze-Lutter, Frauke

2018-03-01

Asperger Syndrome and/or Clinical High Risk of Psychosis? A Differential Diagnostic Challenge This case-study deals with the often difficult differential diagnosis of Asperger syndrome and a clinical high risk state of psychosis, in particular as indicated by attenuated psychotic symptoms, as well as with its therapeutic implications. The presented case is a 10-year old girl, who has not been diagnosed with an autism spectrum disorder before being referred to a specialized center for early detection of psychosis due to possible hallucinatory experiences and delusional ideas. We demonstrate how to perform a context-sensitive differential diagnosis to distinguish between specific interests as well as related behaviors and unusual thought content as well as perceptive abnormalities, between paranoid ideas and biased interpretations of the behaviors of others typical for autism, and between disorganized symptoms and autistic unusual communication and social behavior. The resulting dual diagnoses in our case-study formed the basis for a complex differential indication, which considered both the increased stress vulnerability associated with an increased risk for the development of psychosis as well as the rigid thinking style associated with autism. Our case-report shows that such a precise differential indication can lead to stabilization over the long-term, even in patients with dual diagnoses.

Meier-Gorlin syndrome mutations disrupt an Orc1 CDK inhibitory domain and cause centrosome reduplication.

PubMed

Hossain, Manzar; Stillman, Bruce

2012-08-15

Like DNA replication, centrosomes are licensed to duplicate once per cell division cycle to ensure genetic stability. In addition to regulating DNA replication, the Orc1 subunit of the human origin recognition complex controls centriole and centrosome copy number. Here we report that Orc1 harbors a PACT centrosome-targeting domain and a separate domain that differentially inhibits the protein kinase activities of Cyclin E-CDK2 and Cyclin A-CDK2. A cyclin-binding motif (Cy motif) is required for Orc1 to bind Cyclin A and inhibit Cyclin A-CDK2 kinase activity but has no effect on Cyclin E-CDK2 kinase activity. In contrast, Orc1 inhibition of Cyclin E-CDK2 kinase activity occurs by a different mechanism that is affected by Orc1 mutations identified in Meier-Gorlin syndrome patients. The cyclin/CDK2 kinase inhibitory domain of Orc1, when tethered to the PACT domain, localizes to centrosomes and blocks centrosome reduplication. Meier-Gorlin syndrome mutations that disrupt Cyclin E-CDK2 kinase inhibition also allow centrosome reduplication. Thus, Orc1 contains distinct domains that control centrosome copy number and DNA replication. We suggest that the Orc1 mutations present in some Meier-Gorlin syndrome patients contribute to the pronounced microcephaly and dwarfism observed in these individuals by altering centrosome duplication in addition to DNA replication defects.

Somatic mosaicism underlies X-linked acrogigantism syndrome in sporadic male subjects.

PubMed

Daly, Adrian F; Yuan, Bo; Fina, Frederic; Caberg, Jean-Hubert; Trivellin, Giampaolo; Rostomyan, Liliya; de Herder, Wouter W; Naves, Luciana A; Metzger, Daniel; Cuny, Thomas; Rabl, Wolfgang; Shah, Nalini; Jaffrain-Rea, Marie-Lise; Zatelli, Maria Chiara; Faucz, Fabio R; Castermans, Emilie; Nanni-Metellus, Isabelle; Lodish, Maya; Muhammad, Ammar; Palmeira, Leonor; Potorac, Iulia; Mantovani, Giovanna; Neggers, Sebastian J; Klein, Marc; Barlier, Anne; Liu, Pengfei; Ouafik, L'Houcine; Bours, Vincent; Lupski, James R; Stratakis, Constantine A; Beckers, Albert

2016-04-01

Somatic mosaicism has been implicated as a causative mechanism in a number of genetic and genomic disorders. X-linked acrogigantism (XLAG) syndrome is a recently characterized genomic form of pediatric gigantism due to aggressive pituitary tumors that is caused by submicroscopic chromosome Xq26.3 duplications that include GPR101 We studied XLAG syndrome patients (n= 18) to determine if somatic mosaicism contributed to the genomic pathophysiology. Eighteen subjects with XLAG syndrome caused by Xq26.3 duplications were identified using high-definition array comparative genomic hybridization (HD-aCGH). We noted that males with XLAG had a decreased log2ratio (LR) compared with expected values, suggesting potential mosaicism, whereas females showed no such decrease. Compared with familial male XLAG cases, sporadic males had more marked evidence for mosaicism, with levels of Xq26.3 duplication between 16.1 and 53.8%. These characteristics were replicated using a novel, personalized breakpoint junction-specific quantification droplet digital polymerase chain reaction (ddPCR) technique. Using a separate ddPCR technique, we studied the feasibility of identifying XLAG syndrome cases in a distinct patient population of 64 unrelated subjects with acromegaly/gigantism, and identified one female gigantism patient who had had increased copy number variation (CNV) threshold for GPR101 that was subsequently diagnosed as having XLAG syndrome on HD-aCGH. Employing a combination of HD-aCGH and novel ddPCR approaches, we have demonstrated, for the first time, that XLAG syndrome can be caused by variable degrees of somatic mosaicism for duplications at chromosome Xq26.3. Somatic mosaicism was shown to occur in sporadic males but not in females with XLAG syndrome, although the clinical characteristics of the disease were similarly severe in both sexes. © 2016 Society for Endocrinology.

Reciprocal Effects on Neurocognitive and Metabolic Phenotypes in Mouse Models of 16p11.2 Deletion and Duplication Syndromes.

PubMed

Arbogast, Thomas; Ouagazzal, Abdel-Mouttalib; Chevalier, Claire; Kopanitsa, Maksym; Afinowi, Nurudeen; Migliavacca, Eugenia; Cowling, Belinda S; Birling, Marie-Christine; Champy, Marie-France; Reymond, Alexandre; Herault, Yann

2016-02-01

The 16p11.2 600 kb BP4-BP5 deletion and duplication syndromes have been associated with developmental delay; autism spectrum disorders; and reciprocal effects on the body mass index, head circumference and brain volumes. Here, we explored these relationships using novel engineered mouse models carrying a deletion (Del/+) or a duplication (Dup/+) of the Sult1a1-Spn region homologous to the human 16p11.2 BP4-BP5 locus. On a C57BL/6N inbred genetic background, Del/+ mice exhibited reduced weight and impaired adipogenesis, hyperactivity, repetitive behaviors, and recognition memory deficits. In contrast, Dup/+ mice showed largely opposite phenotypes. On a F1 C57BL/6N × C3B hybrid genetic background, we also observed alterations in social interaction in the Del/+ and the Dup/+ animals, with other robust phenotypes affecting recognition memory and weight. To explore the dosage effect of the 16p11.2 genes on metabolism, Del/+ and Dup/+ models were challenged with high fat and high sugar diet, which revealed opposite energy imbalance. Transcriptomic analysis revealed that the majority of the genes located in the Sult1a1-Spn region were sensitive to dosage with a major effect on several pathways associated with neurocognitive and metabolic phenotypes. Whereas the behavioral consequence of the 16p11 region genetic dosage was similar in mice and humans with activity and memory alterations, the metabolic defects were opposite: adult Del/+ mice are lean in comparison to the human obese phenotype and the Dup/+ mice are overweight in comparison to the human underweight phenotype. Together, these data indicate that the dosage imbalance at the 16p11.2 locus perturbs the expression of modifiers outside the CNV that can modulate the penetrance, expressivity and direction of effects in both humans and mice.

Microduplications at 22q11.21 are associated with non-syndromic classic bladder exstrophy.

PubMed

Draaken, Markus; Reutter, Heiko; Schramm, Charlotte; Bartels, Enrika; Boemers, Thomas M; Ebert, Anne-Karoline; Rösch, Wolfgang; Schröder, Annette; Stein, Raimund; Moebus, Susanne; Stienen, Dietlinde; Hoffmann, Per; Nöthen, Markus M; Ludwig, Michael

2010-01-01

The exstrophy-epispadias complex (EEC) comprises a spectrum of urogenital anomalies in which part or all of the distal urinary tract fails to close. The present study aimed to identify microaberrations characterized by loss or gain of genomic material that contribute to the EEC at a genome-wide level. Molecular karyotyping, utilizing 549,839 single nucleotide polymorphisms (SNPs) with an average spacing of 5.7 kilobases, was performed to screen an initial cohort of 16 patients with non-syndromic EEC. A de novo microduplication involving chromosomal region 22q11.21 was identified in one patient with classic exstrophy of the bladder (CBE). Subsequent multiplex ligation-dependent probe amplification (MLPA) analysis was performed with an MLPA 22q11 kit in a further 50 non-syndromic EEC cases. We identified one CBE patient with an overlapping 22q11.21 duplication in whom the duplication had been transmitted from the unaffected mother. Chromosomal region 22q11 is well known for its susceptibility to genomic rearrangements, and these are associated with various syndromes including the velo-cardio-facial/DiGeorge syndrome (VCFS/DGS), the der(22) syndrome, and the cat-eye syndrome. Duplications in this region result in a wide and variable spectrum of clinical presentations that include features of the VCFS/DGS, while some carriers present with a completely normal phenotype. Our findings extend the phenotypic spectrum of the 22q11.2 duplication syndrome, and indicate that this aberration predisposes to CBE with incomplete penetrance. Copyright 2009 Elsevier Masson SAS. All rights reserved.

Metacarpophalangeal pattern profile analysis: useful diagnostic tool for differentiating between dyschondrosteosis, Turner syndrome, and hypochondroplasia.

PubMed

Laurencikas, E; Sävendahl, L; Jorulf, H

2006-06-01

To assess the value of the metacarpophalangeal pattern profile (MCPP) analysis as a diagnostic tool for differentiating between patients with dyschondrosteosis, Turner syndrome, and hypochondroplasia. Radiographic and clinical data from 135 patients between 1 and 51 years of age were collected and analyzed. The study included 25 patients with hypochondroplasia (HCP), 39 with dyschondrosteosis (LWD), and 71 with Turner syndrome (TS). Hand pattern profiles were calculated and compared with those of 110 normal individuals. Pearson correlation coefficient (r) and multivariate discriminant analysis were used for pattern profile analysis. Pattern variability index, a measure of dysmorphogenesis, was calculated for LWD, TS, HCP, and normal controls. Our results demonstrate that patients with LWD, TS, or HCP have distinct pattern profiles that are significantly different from each other and from those of normal controls. Discriminant analysis yielded correct classification of normal versus abnormal individuals in 84% of cases. Classification of the patients into LWD, TS, and HCP groups was successful in 75%. The correct classification rate was higher (85%) when differentiating two pathological groups at a time. Pattern variability index was not helpful for differential diagnosis of LWD, TS, and HCP. Patients with LWD, TS, or HCP have distinct MCPPs and can be successfully differentiated from each other using advanced MCPP analysis. Discriminant analysis is to be preferred over Pearson correlation coefficient because it is a more sensitive and specific technique. MCPP analysis is a helpful tool for differentiating between syndromes with similar clinical and radiological abnormalities.

Molecular mapping of the Edwards syndrome phenotype to two noncontiguous regions on chromosome 18

DOE Office of Scientific and Technical Information (OSTI.GOV)

Boghosian-Sell, L.; Mewar, R.; Harrison, W.

1994-09-01

In an effort to identify regions on chromosome 18 that may be critical in the appearance of the Edwards syndrome phenotype, the authors have analyzed six patients with partial duplication of chromosome 18. Four of the patients have duplications involving the distal half of 18q (18q21.1-qter) and are very mildly affected. The remaining two patients have most of 18q (18q12.1-qter) duplicated, are severely affected, and have been diagnosed with Edwards syndrome. The authors have employed FISH, using DNA probes from a chromosome 18-specific library, for the precise determination of the duplicated material in each of these patients. The clinical featuresmore » and the extent of the chromosomal duplication in these patients were compared with four previously reported partial trisomy 18 patients, to identify regions of chromosome 18 that may be responsible for certain clinical features of trisomy 18. The comparative analysis confirmed that there is no single region on 18q that is sufficient to produce the trisomy 18 phenotype and identified two regions on 18q that may work in conjunction to produce the Edwards syndrome phenotype. In addition, correlative analysis indicates that duplication of 18q12.3-q22.1 may be associated with more severe mental retardation in trisomy 18 individuals. 25 refs., 3 figs., 1 tab.« less

A duplicated PLP gene causing Pelizaeus-Merzbacher disease detected by comparative multiplex PCR

DOE Office of Scientific and Technical Information (OSTI.GOV)

Inoue, K.; Sugiyama, N.; Kawanishi, C.

1996-07-01

Pelizaeus-Merzbacher disease (PMD) is an X-linked dysmyelinating disorder caused by abnormalities in the proteolipid protein (PLP) gene, which is essential for oligodendrocyte differentiation and CNS myelin formation. Although linkage analysis has shown the homogeneity at the PLP locus in patients with PMD, exonic mutations in the PLP gene have been identified in only 10% - 25% of all cases, which suggests the presence of other genetic aberrations, including gene duplication. In this study, we examined five families with PMD not carrying exonic mutations in PLP gene, using comparative multiplex PCR (CM-PCR) as a semiquantitative assay of gene dosage. PLP genemore » duplications were identified in four families by CM-PCR and confirmed in three families by densitometric RFLP analysis. Because a homologous myelin protein gene, PMP22, is duplicated in the majority of patients with Charcot-Marie-Tooth 1A, PLP gene overdosage may be an important genetic abnormality in PMD and affect myelin formation. 38 ref., 5 figs., 2 tabs.« less

[DIFFERENTIATED TACTICS OF VIDEOTHORACOSCOPIC DIAGNOSIS OF THE PLEURAL EXUDATE SYNDROME].

PubMed

Ivashchenko, V E; Kalabukha, I A; Mayetnyi, E M

2016-04-01

Differentiated tactics of diagnostic videothoracoscopy (VTHS) in a pleural exudate syndrome, which ought to be treated with hydrothorax elimination and artificial pneumothorax creation, was proposed. Further roentgenological investigation permits to create a plan for the operation conduction and a certain anesthesia application. Criteria for the operation planning and the anesthesiological support choice were elaborated. Results of VTHS conduction in 261 patients in Department of Thoracic Surgery were analyzed. The differentiated tactics for the VTHS performance application have had saved the patients from the unnecessary endotracheal narcosis conduction, and reduced a pharmacological load on a patient, as well as a rate of contraindications for the operation usage and the stationary treatment duration.

Somatic Mosaicism Underlies X-linked Acrogigantism (XLAG) Syndrome in Sporadic Male Subjects

PubMed Central

Daly, Adrian F.; Yuan, Bo; Fina, Frederic; Caberg, Jean-Hubert; Trivellin, Giampaolo; Rostomyan, Liliya; de Herder, Wouter W.; Naves, Luciana A.; Metzger, Daniel; Cuny, Thomas; Rabl, Wolfgang; Shah, Nalini; Jaffrain-Rea, Marie-Lise; Zatelli, Maria Chiara; Faucz, Fabio R; Castermans, Emilie; Nanni-Metellus, Isabelle; Lodish, Maya; Muhammad, Ammar; Palmeira, Leonor; Potorac, Iulia; Mantovani, Giovanna; Neggers, Sebastian J.; Klein, Marc; Barlier, Anne; Liu, Pengfei; Ouafik, L'Houcine; Bours, Vincent; Lupski, James R.; Stratakis, Constantine A.; Beckers., Albert

2016-01-01

Somatic mosaicism has been implicated as a causative mechanism in a number of genetic and genomic disorders. X-linked acrogigantism (XLAG) syndrome is a recently characterized genomic form of pediatric gigantism due to aggressive pituitary tumors that is caused by submicroscopic chromosome Xq26.3 duplications that include GPR101. We studied XLAG syndrome patients (N=18) to determine if somatic mosaicism contributed to the genomic pathophysiology. Eighteen subjects with XLAG syndrome were identified with Xq26.3 duplications using high definition array comparative genome hybridization (HD-aCGH). We noted males with XLAG had a decreased log2 ratio compared with expected values, suggesting potential mosaicism, while females showed no such decrease. As compared with familial male XLAG cases, sporadic males had more marked evidence for mosaicism, with levels of Xq26.3 duplication between 16.1-53.8%. These characteristics were replicated using a novel, personalized breakpoint-junction specific quantification droplet digital PCR (ddPCR) technique. Using a separate ddPCR technique we studied the feasibility of identifying XLAG syndrome cases in a distinct patient population of 64 unrelated subjects with acromegaly/gigantism and identified one female gigantism patient that had increased copy number variation (CNV) threshold for GPR101 that was subsequently diagnosed as having XLAG syndrome on HD-aCGH. Employing a combination of HD-aCGH and novel ddPCR approaches, we have demonstrated, for the first time, that XLAG syndrome can be caused by variable degrees of somatic mosaicism for duplications at chromosome Xq26.3. Somatic mosaicism was shown to occur in sporadic males but not in females with XLAG syndrome, although the clinical characteristics of the disease were similarly severe in both sexes. PMID:26935837

Three neuropeptide Y receptor genes in the spiny dogfish, Squalus acanthias, support en bloc duplications in early vertebrate evolution.

PubMed

Salaneck, Erik; Ardell, David H; Larson, Earl T; Larhammar, Dan

2003-08-01

It has been debated whether the increase in gene number during early vertebrate evolution was due to multiple independent gene duplications or synchronous duplications of many genes. We describe here the cloning of three neuropeptide Y (NPY) receptor genes belonging to the Y1 subfamily in the spiny dogfish, Squalus acanthias, a cartilaginous fish. The three genes are orthologs of the mammalian subtypes Y1, Y4, and Y6, which are located in paralogous gene regions on different chromosomes in mammals. Thus, these genes arose by duplications of a chromosome region before the radiation of gnathostomes (jawed vertebrates). Estimates of duplication times from linearized trees together with evidence from other gene families supports two rounds of chromosome duplications or tetraploidizations early in vertebrate evolution. The anatomical distribution of mRNA was determined by reverse-transcriptase PCR and was found to differ from mammals, suggesting differential functional diversification of the new gene copies during the radiation of the vertebrate classes.

Duplicate document detection in DocBrowse

NASA Astrophysics Data System (ADS)

Chalana, Vikram; Bruce, Andrew G.; Nguyen, Thien

1998-04-01

Duplicate documents are frequently found in large databases of digital documents, such as those found in digital libraries or in the government declassification effort. Efficient duplicate document detection is important not only to allow querying for similar documents, but also to filter out redundant information in large document databases. We have designed three different algorithm to identify duplicate documents. The first algorithm is based on features extracted from the textual content of a document, the second algorithm is based on wavelet features extracted from the document image itself, and the third algorithm is a combination of the first two. These algorithms are integrated within the DocBrowse system for information retrieval from document images which is currently under development at MathSoft. DocBrowse supports duplicate document detection by allowing (1) automatic filtering to hide duplicate documents, and (2) ad hoc querying for similar or duplicate documents. We have tested the duplicate document detection algorithms on 171 documents and found that text-based method has an average 11-point precision of 97.7 percent while the image-based method has an average 11- point precision of 98.9 percent. However, in general, the text-based method performs better when the document contains enough high-quality machine printed text while the image- based method performs better when the document contains little or no quality machine readable text.

Differential accumulation of retroelements and diversification of NB-LRR disease resistance genes in duplicated regions following polyploidy in the ancestor of soybean.

PubMed

Innes, Roger W; Ameline-Torregrosa, Carine; Ashfield, Tom; Cannon, Ethalinda; Cannon, Steven B; Chacko, Ben; Chen, Nicolas W G; Couloux, Arnaud; Dalwani, Anita; Denny, Roxanne; Deshpande, Shweta; Egan, Ashley N; Glover, Natasha; Hans, Christian S; Howell, Stacy; Ilut, Dan; Jackson, Scott; Lai, Hongshing; Mammadov, Jafar; Del Campo, Sara Martin; Metcalf, Michelle; Nguyen, Ashley; O'Bleness, Majesta; Pfeil, Bernard E; Podicheti, Ram; Ratnaparkhe, Milind B; Samain, Sylvie; Sanders, Iryna; Ségurens, Béatrice; Sévignac, Mireille; Sherman-Broyles, Sue; Thareau, Vincent; Tucker, Dominic M; Walling, Jason; Wawrzynski, Adam; Yi, Jing; Doyle, Jeff J; Geffroy, Valérie; Roe, Bruce A; Maroof, M A Saghai; Young, Nevin D

2008-12-01

The genomes of most, if not all, flowering plants have undergone whole genome duplication events during their evolution. The impact of such polyploidy events is poorly understood, as is the fate of most duplicated genes. We sequenced an approximately 1 million-bp region in soybean (Glycine max) centered on the Rpg1-b disease resistance gene and compared this region with a region duplicated 10 to 14 million years ago. These two regions were also compared with homologous regions in several related legume species (a second soybean genotype, Glycine tomentella, Phaseolus vulgaris, and Medicago truncatula), which enabled us to determine how each of the duplicated regions (homoeologues) in soybean has changed following polyploidy. The biggest change was in retroelement content, with homoeologue 2 having expanded to 3-fold the size of homoeologue 1. Despite this accumulation of retroelements, over 77% of the duplicated low-copy genes have been retained in the same order and appear to be functional. This finding contrasts with recent analyses of the maize (Zea mays) genome, in which only about one-third of duplicated genes appear to have been retained over a similar time period. Fluorescent in situ hybridization revealed that the homoeologue 2 region is located very near a centromere. Thus, pericentromeric localization, per se, does not result in a high rate of gene inactivation, despite greatly accelerated retrotransposon accumulation. In contrast to low-copy genes, nucleotide-binding-leucine-rich repeat disease resistance gene clusters have undergone dramatic species/homoeologue-specific duplications and losses, with some evidence for partitioning of subfamilies between homoeologues.

The centriole duplication cycle

PubMed Central

Fırat-Karalar, Elif Nur; Stearns, Tim

2014-01-01

Centrosomes are the main microtubule-organizing centre of animal cells and are important for many critical cellular and developmental processes from cell polarization to cell division. At the core of the centrosome are centrioles, which recruit pericentriolar material to form the centrosome and act as basal bodies to nucleate formation of cilia and flagella. Defects in centriole structure, function and number are associated with a variety of human diseases, including cancer, brain diseases and ciliopathies. In this review, we discuss recent advances in our understanding of how new centrioles are assembled and how centriole number is controlled. We propose a general model for centriole duplication control in which cooperative binding of duplication factors defines a centriole ‘origin of duplication’ that initiates duplication, and passage through mitosis effects changes that license the centriole for a new round of duplication in the next cell cycle. We also focus on variations on the general theme in which many centrioles are created in a single cell cycle, including the specialized structures associated with these variations, the deuterosome in animal cells and the blepharoplast in lower plant cells. PMID:25047614

Brain evolution by brain pathway duplication

PubMed Central

Chakraborty, Mukta; Jarvis, Erich D.

2015-01-01

Understanding the mechanisms of evolution of brain pathways for complex behaviours is still in its infancy. Making further advances requires a deeper understanding of brain homologies, novelties and analogies. It also requires an understanding of how adaptive genetic modifications lead to restructuring of the brain. Recent advances in genomic and molecular biology techniques applied to brain research have provided exciting insights into how complex behaviours are shaped by selection of novel brain pathways and functions of the nervous system. Here, we review and further develop some insights to a new hypothesis on one mechanism that may contribute to nervous system evolution, in particular by brain pathway duplication. Like gene duplication, we propose that whole brain pathways can duplicate and the duplicated pathway diverge to take on new functions. We suggest that one mechanism of brain pathway duplication could be through gene duplication, although other mechanisms are possible. We focus on brain pathways for vocal learning and spoken language in song-learning birds and humans as example systems. This view presents a new framework for future research in our understanding of brain evolution and novel behavioural traits. PMID:26554045

[Differential diagnosis of Dandy-Walker syndrome different presentations].

PubMed

Tobías-González, Pablo; Gil Mira, Mar; Valero de Bernabé, Javier; Zapardiel, Ignacio

2012-08-01

Dandy-Walker syndrome is a set of abnormalities of the posterior fossa including three modalities: classic Dandy-Walker malformation, Dandy-Walker variant and mega-cisterna magna. Our objective is clarify the differential diagnosis among these entities. Descriptive and retrospective study of Dandy-Walker cases diagnosed at our Department during the last five years plus a review of the related Medical literature. Three cases of Dandy-Walker modalities are reported: one case of classic Dandy-Walker malformation, one case of Dandy-Walker variant, and one case of false Dandy-Walker. In the first two cases the patients underwent legal abortion, whereas in the last one a healthy male newborn was delivered in the week 38 of gestation. Malformations in the posterior fossa, including Dandy-Walker syndrome, are still a challenge in prenatal diagnosis. Technical developments in imaging, such as in three-dimensional sonography and magnetic resonance, allow higher resolution and multiplanar images for an easier diagnose. There is a high rate of false positive, particularly before the 18th week of gestation. It is advisable not to establish a final diagnose before that week.

Molecular evolution and patterns of duplication in the SEP/AGL6-like lineage of the Zingiberales: a proposed mechanism for floral diversification.

PubMed

Yockteng, Roxana; Almeida, Ana M R; Morioka, Kelsie; Alvarez-Buylla, Elena R; Specht, Chelsea D

2013-11-01

The diversity of floral forms in the plant order Zingiberales has evolved through alterations in floral organ morphology. One striking alteration is the shift from fertile, filamentous stamens to sterile, laminar (petaloid) organs in the stamen whorls, attributed to specific pollination syndromes. Here, we examine the role of the SEPALLATA (SEP) genes, known to be important in regulatory networks underlying floral development and organ identity, in the evolution of development of the diverse floral organs phenotypes in the Zingiberales. Phylogenetic analyses show that the SEP-like genes have undergone several duplication events giving rise to multiple copies. Selection tests on the SEP-like genes indicate that the two copies of SEP3 have mostly evolved under balancing selection, probably due to strong functional restrictions as a result of their critical role in floral organ specification. In contrast, the two LOFSEP copies have undergone differential positive selection, indicating neofunctionalization. Reverse transcriptase-polymerase chain reaction, gene expression from RNA-seq data, and in situ hybridization analyses show that the recovered genes have differential expression patterns across the various whorls and organ types found in the Zingiberales. Our data also suggest that AGL6, sister to the SEP-like genes, may play an important role in stamen morphology in the Zingiberales. Thus, the SEP-like genes are likely to be involved in some of the unique morphogenetic patterns of floral organ development found among this diverse order of tropical monocots. This work contributes to a growing body of knowledge focused on understanding the role of gene duplications and the evolution of entire gene networks in the evolution of flower development.

Identification of a Recurrent Microdeletion at 17q23.1q23.2 Flanked by Segmental Duplications Associated with Heart Defects and Limb Abnormalities

PubMed Central

Ballif, Blake C.; Theisen, Aaron; Rosenfeld, Jill A.; Traylor, Ryan N.; Gastier-Foster, Julie; Thrush, Devon Lamb; Astbury, Caroline; Bartholomew, Dennis; McBride, Kim L.; Pyatt, Robert E.; Shane, Kate; Smith, Wendy E.; Banks, Valerie; Gallentine, William B.; Brock, Pamela; Rudd, M. Katharine; Adam, Margaret P.; Keene, Julia A.; Phillips, John A.; Pfotenhauer, Jean P.; Gowans, Gordon C.; Stankiewicz, Pawel; Bejjani, Bassem A.; Shaffer, Lisa G.

2010-01-01

Segmental duplications, which comprise ∼5%–10% of the human genome, are known to mediate medically relevant deletions, duplications, and inversions through nonallelic homologous recombination (NAHR) and have been suggested to be hot spots in chromosome evolution and human genomic instability. We report seven individuals with microdeletions at 17q23.1q23.2, identified by microarray-based comparative genomic hybridization (aCGH). Six of the seven deletions are ∼2.2 Mb in size and flanked by large segmental duplications of >98% sequence identity and in the same orientation. One of the deletions is ∼2.8 Mb in size and is flanked on the distal side by a segmental duplication, whereas the proximal breakpoint falls between segmental duplications. These characteristics suggest that NAHR mediated six out of seven of these rearrangements. These individuals have common features, including mild to moderate developmental delay (particularly speech delay), microcephaly, postnatal growth retardation, heart defects, and hand, foot, and limb abnormalities. Although all individuals had at least mild dysmorphic facial features, there was no characteristic constellation of features that would elicit clinical suspicion of a specific disorder. The identification of common clinical features suggests that microdeletions at 17q23.1q23.2 constitute a novel syndrome. Furthermore, the inclusion in the minimal deletion region of TBX2 and TBX4, transcription factors belonging to a family of genes implicated in a variety of developmental pathways including those of heart and limb, suggests that these genes may play an important role in the phenotype of this emerging syndrome. PMID:20206336

De novo interstitial duplication of the 15q11.2-q14 PWS/AS region of maternal origin: Clinical description, array CGH analysis, and review of the literature.

PubMed

Kitsiou-Tzeli, Sophia; Tzetis, Maria; Sofocleous, Christalena; Vrettou, Christina; Xaidara, Athena; Giannikou, Krinio; Pampanos, Andreas; Mavrou, Ariadne; Kanavakis, E

2010-08-01

The 15q11-q13 PWS/AS critical region involves genes that are characterized by genomic imprinting. Multiple repeat elements within the region mediate rearrangements, including interstitial duplications, interstitial triplications, and supernumerary isodicentric marker chromosomes, as well as the deletions that cause Prader-Willi syndrome (PWS) and Angelman syndrome (AS). Recently, duplications of maternal origin concerning the same critical region have been implicated in autism spectrum disorders (ASD). We present a 6-month-old girl carrying a de novo duplication of maternal origin of the 15q11.2-q14 PWS/AS region (17.73 Mb in size) [46,XX,dup(15)(q11.2-q14)] detected with a high-resolution microarray-based comparative genomic hybridization (array-CGH). The patient is characterized by severe hypotonia, obesity, microstomia, long eyelashes, hirsutism, microretrognathia, short nose, severe psychomotor retardation, and multiple episodes of drug-resistant epileptic seizures, while her brain magnetic resonance imaging (MRI) documented partial corpus callosum dysplasia. In our patient the duplicated region is quite large extending beyond the Prader-Willi-Angelman critical region (PWACR), containing a number of genes that have been shown to be involved in ASD, exhibiting a severe phenotype, beyond the typical PWS/AS clinical manifestations. Reporting of similar well-characterized clinical cases with clearly delineated breakpoints of the duplicated region will clarify the contribution of specific genes to the phenotype.

The Use of Differentiated Mathematical Strategies with Secondary Students with Asperger's Syndrome

ERIC Educational Resources Information Center

Riera, Karla Rene

2013-01-01

Though the No Child Left Behind Act of 2001 requires secondary students with Asperger's syndrome (AS) to take high-stakes mathematical tests, many students with AS exhibit weaknesses in mathematical and executive functioning skills. The purpose of this mixed-methods case study was to explore the use of differentiated mathematical strategies with…

Deletion and duplication within the p11.2 region of chromosome 17

DOE Office of Scientific and Technical Information (OSTI.GOV)

McCorquodale, D.J.; McCorquodale, M.; Bereziouk, O.

1994-09-01

A 7 1/2-year-old male patient presented with mild mental retardation, speech delay, hyperactivity, behavioral problems, mild facial hypoplasia, short broad hands, digital anomalies, and self-injurious behavior. Chromosomes obtained from peripheral blood cells revealed a deletion of 17p11.2 in about 40% of the metaphases examined, suggesting that the patient had Smith-Magenis Syndrome. A similar pattern of mosaicism in peripheral blood cells, but not in fibroblasts in which all cells displayed the deletion, has been previously reported. Since some cases of Smith-Magenis Syndrome have a deletion that extends into the region associated with Charcot-Marie-Tooth (CMT) Syndrome, we examined interphase cells with amore » CMT1A-specific probe by the method of fluorescence in situ hybridization. The CMT1A region was not deleted, but about 40% of the cells gave signals indicating a duplication of the CMT1A region. The patient has not presented neuropathies associated with CMT at this time. Future tracking of the patient should be informative.« less

A candidate model for Angelman syndrome in the mouse.

PubMed

Cattanach, B M; Barr, J A; Beechey, C V; Martin, J; Noebels, J; Jones, J

1997-07-01

Prader-Willi syndrome (PWS) and Angelman syndrome (AS) are well-recognized examples of imprinting in humans. They occur most commonly with paternal and maternal 15q11-13 deletions, but also with maternal and paternal disomy. Both syndromes have also occurred more rarely in association with smaller deletions seemingly causing abnormal imprinting. A putative mouse model of PWS, occurring with maternal duplication (partial maternal disomy) for the homologous region, has been described in a previous paper but, although a second imprinting effect that could have provided a mouse model of AS was found, it appeared to be associated with a slightly different region of the chromosome. Here, we provide evidence that the same region is in fact involved and further demonstrate that animals with paternal duplication for the region exhibit characteristics of AS patients. A mouse model of AS is, therefore, strongly indicated.

The circadian clock of teleost fish: a comparative analysis reveals distinct fates for duplicated genes.

PubMed

Toloza-Villalobos, Jessica; Arroyo, José Ignacio; Opazo, Juan C

2015-01-01

The circadian clock is a central oscillator that coordinates endogenous rhythms. Members of six gene families underlie the metabolic machinery of this system. Although this machinery appears to correspond to a highly conserved genetic system in metazoans, it has been recognized that vertebrates possess a more diverse gene inventory than that of non-vertebrates. This difference could have originated in the two successive rounds of whole-genome duplications that took place in the common ancestor of the group. Teleost fish underwent an extra event of whole-genome duplication, which is thought to have provided an abundance of raw genetic material for the biological innovations that facilitated the radiation of the group. In this study, we assessed the relative contributions of whole-genome duplication and small-scale gene duplication to generate the repertoire of genes associated with the circadian clock of teleost fish. To achieve this goal, we annotated genes from six gene families associated with the circadian clock in eight teleost fish species, and we reconstructed their evolutionary history by inferring phylogenetic relationships. Our comparative analysis indicated that teleost species possess a variable repertoire of genes related to the circadian clock gene families and that the actual diversity of these genes has been shaped by a variety of phenomena, such as the complete deletion of ohnologs, the differential retention of genes, and lineage-specific gene duplications. From a functional perspective, the subfunctionalization of two ohnolog genes (PER1a and PER1b) in zebrafish highlights the power of whole-genome duplications to generate biological diversity.

Zoom‐in comparative genomic hybridisation arrays for the characterisation of variable breakpoint contiguous gene syndromes

PubMed Central

Johnston, Jennifer J; Walker, Robert L; Davis, Sean; Facio, Flavia; Turner, Joyce T; Bick, David P; Daentl, Donna L; Ellison, Jay W; Meltzer, Paul S; Biesecker, Leslie G

2007-01-01

Contiguous gene syndromes cause disorders via haploinsufficiency for adjacent genes. Some contiguous gene syndromes (CGS) have stereotypical breakpoints, but others have variable breakpoints. In CGS that have variable breakpoints, the extent of the deletions may be correlated with severity. The Greig cephalopolysyndactyly contiguous gene syndrome (GCPS‐CGS) is a multiple malformation syndrome caused by haploinsufficiency of GLI3 and adjacent genes. In addition, non‐CGS GCPS can be caused by deletions or duplications in GLI3. Although fluorescence in situ hybridisation (FISH) can identify large deletion mutations in patients with GCPS or GCPS‐CGS, it is not practical for identification of small intragenic deletions or insertions, and it is difficult to accurately characterise the extent of the large deletions using this technique. We have designed a custom comparative genomic hybridisation (CGH) array that allows identification of deletions and duplications at kilobase resolution in the vicinity of GLI3. The array averages one probe every 730 bp for a total of about 14 000 probes over 10 Mb. We have analysed 16 individuals with known or suspected deletions or duplications. In 15 of 16 individuals (14 deletions and 1 duplication), the array confirmed the prior results. In the remaining patient, the normal CGH array result was correct, and the prior assessment was a false positive quantitative polymerase chain reaction result. We conclude that high‐density CGH array analysis is more sensitive than FISH analysis for detecting deletions and provides clinically useful results on the extent of the deletion. We suggest that high‐density CGH array analysis should replace FISH analysis for assessment of deletions and duplications in patients with contiguous gene syndromes caused by variable deletions. PMID:17098889

Differential diagnostic of the burnout syndrome

PubMed Central

Korczak, Dieter; Huber, Beate; Kister, Christine

2010-01-01

it can have also negative effects on significant others (for example patients). There is no evidence for stigmatization of persons with burnout. Discussion The evidence of the majority of the studies is predominantly low. Most of the studies are descriptive and explorative. Self-assessment tools are mainly used, overall the Maslach Burnout Inventory (MBI). Objective data like medical parameters, health status, sick notes or judgements by third persons are extremely seldomly included in the studies. The sample construction is coincidental in the majority of cases, response rates are often low. Almost no longitudinal studies are available. There are insufficient results on the stability and the duration of related symptoms. The ambiguity of the burnout diagnosis is regularly neglected in the studies. Conclusions The authors conclude, that (1) further research, particularly high-quality studies are needed, to broaden the understanding of the burnout syndrome. Equally (2) a definition of the burnout syndrome has to be found which goes beyond the published understanding of burnout and is based on common scientific consent. Furthermore, there is a need (3) for finding a standardized, international accepted and valid procedure for the differentiated diagnostics of burnout and for (4) developing a third party assessment tool for the diagnosis of burnout. Finally, (5) the economic effects and implication of burnout diagnostics on the economy, the health insurances and the patients have to be analysed. PMID:21289882

Global analysis of human duplicated genes reveals the relative importance of whole-genome duplicates originated in the early vertebrate evolution.

PubMed

Acharya, Debarun; Ghosh, Tapash C

2016-01-22

Gene duplication is a genetic mutation that creates functionally redundant gene copies that are initially relieved from selective pressures and may adapt themselves to new functions with time. The levels of gene duplication may vary from small-scale duplication (SSD) to whole genome duplication (WGD). Studies with yeast revealed ample differences between these duplicates: Yeast WGD pairs were functionally more similar, less divergent in subcellular localization and contained a lesser proportion of essential genes. In this study, we explored the differences in evolutionary genomic properties of human SSD and WGD genes, with the identifiable human duplicates coming from the two rounds of whole genome duplication occurred early in vertebrate evolution. We observed that these two groups of duplicates were also dissimilar in terms of their evolutionary and genomic properties. But interestingly, this is not like the same observed in yeast. The human WGDs were found to be functionally less similar, diverge more in subcellular level and contain a higher proportion of essential genes than the SSDs, all of which are opposite from yeast. Additionally, we explored that human WGDs were more divergent in their gene expression profile, have higher multifunctionality and are more often associated with disease, and are evolutionarily more conserved than human SSDs. Our study suggests that human WGD duplicates are more divergent and entails the adaptation of WGDs to novel and important functions that consequently lead to their evolutionary conservation in the course of evolution.

A rare de novo interstitial duplication of 15q15.3q21.2 in a boy with severe short stature, hypogonadism, global developmental delay and intellectual disability.

PubMed

Yuan, Haiming; Meng, Zhe; Zhang, Lina; Luo, Xiangyang; Liu, Liping; Chen, Mengfan; Li, Xinwei; Zhao, Weiwei; Liang, Liyang

2016-01-01

Interstitial duplications distal to 15q13 are very rare. Here, we reported a 14-year-old boy with severe short stature, delayed bone age, hypogonadism, global developmental delay and intellectual disability. His had distinctive facial features including macrocephaly, broad forehead, deep-set and widely spaced eyes, broad nose bridge, shallow philtrum and thick lips. A de novo 6.4 Mb interstitial duplication of 15q15.3q21.2 was detected by chromosomal microarray analysis. We compared our patient's clinical phenotypes with those of several individuals with overlapping duplications and several candidate genes responsible for the phenotypes were identified as well. The results suggest a novel contiguous gene duplication syndrome characterized with shared features including short stature, hypogonadism, global developmental delay and other congenital anomalies.

Differential retention of metabolic genes following whole-genome duplication.

PubMed

Gout, Jean-François; Duret, Laurent; Kahn, Daniel

2009-05-01

Classical studies in Metabolic Control Theory have shown that metabolic fluxes usually exhibit little sensitivity to changes in individual enzyme activity, yet remain sensitive to global changes of all enzymes in a pathway. Therefore, little selective pressure is expected on the dosage or expression of individual metabolic genes, yet entire pathways should still be constrained. However, a direct estimate of this selective pressure had not been evaluated. Whole-genome duplications (WGDs) offer a good opportunity to address this question by analyzing the fates of metabolic genes during the massive gene losses that follow. Here, we take advantage of the successive rounds of WGD that occurred in the Paramecium lineage. We show that metabolic genes exhibit different gene retention patterns than nonmetabolic genes. Contrary to what was expected for individual genes, metabolic genes appeared more retained than other genes after the recent WGD, which was best explained by selection for gene expression operating on entire pathways. Metabolic genes also tend to be less retained when present at high copy number before WGD, contrary to other genes that show a positive correlation between gene retention and preduplication copy number. This is rationalized on the basis of the classical concave relationship relating metabolic fluxes with enzyme expression.

Evaluation of Immunophenotypic and Molecular Biomarkers for Sézary Syndrome Using Standard Operating Procedures: A Multicenter Study of 59 Patients.

PubMed

Boonk, Stephanie E; Zoutman, Willem H; Marie-Cardine, Anne; van der Fits, Leslie; Out-Luiting, Jacoba J; Mitchell, Tracey J; Tosi, Isabella; Morris, Stephen L; Moriarty, Blaithin; Booken, Nina; Felcht, Moritz; Quaglino, Pietro; Ponti, Renata; Barberio, Emanuela; Ram-Wolff, Caroline; Jäntti, Kirsi; Ranki, Annamari; Bernengo, Maria Grazia; Klemke, Claus-Detlev; Bensussan, Armand; Michel, Laurence; Whittaker, Sean; Bagot, Martine; Tensen, Cornelis P; Willemze, Rein; Vermeer, Maarten H

2016-07-01

Differentiation between Sézary syndrome and erythrodermic inflammatory dermatoses can be challenging, and a number of studies have attempted to identify characteristic immunophenotypic changes and molecular biomarkers in Sézary cells that could be useful as additional diagnostic criteria. In this European multicenter study, the sensitivity and specificity of these immunophenotypic and recently proposed but unconfirmed molecular biomarkers in Sézary syndrome were investigated. Peripheral blood CD4(+) T cells from 59 patients with Sézary syndrome and 19 patients with erythrodermic inflammatory dermatoses were analyzed for cell surface proteins by flow cytometry and for copy number alterations and differential gene expression using custom-made quantitative PCR plates. Experiments were performed in duplicate in two independent centers using standard operating procedures with almost identical results. Sézary cells showed MYC gain (40%) and MNT loss (66%); up-regulation of DNM3 (75%), TWIST1 (69%), EPHA4 (66%), and PLS3 (66%); and down-regulation of STAT4 (91%). Loss of CD26 (≥80% CD4(+) T cells) and/or CD7 (≥40% CD4(+) T cells) and combination of altered expression of STAT4, TWIST1, and DNM3 or PLS3 could distinguish, respectively, 83% and 98% of patients with Sézary syndrome from patients with erythrodermic inflammatory dermatoses with 100% specificity. These additional diagnostic panels will be useful adjuncts in the differential diagnosis of Sézary syndrome versus erythrodermic inflammatory dermatoses. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

ANSYS duplicate finite-element checker routine

NASA Technical Reports Server (NTRS)

Ortega, R.

1995-01-01

An ANSYS finite-element code routine to check for duplicated elements within the volume of a three-dimensional (3D) finite-element mesh was developed. The routine developed is used for checking floating elements within a mesh, identically duplicated elements, and intersecting elements with a common face. A space shuttle main engine alternate turbopump development high pressure oxidizer turbopump finite-element model check using the developed subroutine is discussed. Finally, recommendations are provided for duplicate element checking of 3D finite-element models.

De novo duplication of 17p13.1-p13.2 in a patient with intellectual disability and obesity.

PubMed

Kuroda, Yukiko; Ohashi, Ikuko; Tominaga, Makiko; Saito, Toshiyuki; Nagai, Jun-Ichi; Ida, Kazumi; Naruto, Takuya; Masuno, Mitsuo; Kurosawa, Kenji

2014-06-01

17p13.1 Deletion encompassing TP53 has been described as a syndrome characterized by intellectual disability and dysmorphic features. Only one case with a 17p13.1 duplication encompassing TP53 has been reported in a patient with intellectual disability, seizures, obesity, and diabetes mellitus. Here, we present a patient with a 17p13.1 duplication who exhibited obesity and intellectual disability, similar to the previous report. The 9-year-old proposita was referred for the evaluation of intellectual disability and obesity. She also exhibited insulin resistance and liver dysfunction. She had wide palpebral fissures, upturned nostrils, a long mandible, short and slender fingers, and skin hyperpigmentation. Array comparative genomic hybridization (array CGH) detected a 3.2 Mb duplication of 17p13.1-p13.2 encompassing TP53, FXR2, NLGN2, and SLC2A4, which encodes the insulin-responsive glucose transporter 4 (GLUT4) associated with insulin-stimulated glucose uptake in adipocytes and muscle. We suggest that 17p13.1 duplication may represent a clinically recognizable condition characterized partially by a characteristic facial phenotype, developmental delay, and obesity. © 2014 Wiley Periodicals, Inc.

Savant syndrome: realities, myths and misconceptions.

PubMed

Treffert, Darold A

2014-03-01

It was 126 years ago that Down first described savant syndrome as a specific condition and 70 years ago that Kanner first described Early Infantile Autism. While as many as one in ten autistic persons have savant abilities, such special skills occur in other CNS conditions as well such that approximately 50 % of cases of savant syndrome have autism as the underlying developmental disability and 50 % are associated with other disabilities. This paper sorts out realities from myths and misconceptions about both savant syndrome and autism spectrum disorders (ASD) that have developed through the years. The reality is that low IQ is not necessarily an accompaniment of savant syndrome; in some cases IQ can be superior. Also, savants can be creative, rather than just duplicative, and the skills increase over time on a continuum from duplication, to improvisation to creation, rather than diminishing or suddenly disappearing. Genius and prodigy exist separate from savant syndrome and not all such highly gifted persons have Asperger's Disorder. This paper also emphasizes the critical importance of separating 'autistic-like' symptoms from ASD especially in children when the savant ability presents as hyperlexia (children who read early) or as Einstein syndrome (children who speak late), or have impaired vision (Blindisms) because prognosis and outcome are very different when that careful distinction is made. In those cases the term 'outgrowing autism' might be mistakenly applied when in fact the child did not have ASD in the first place.

Duplication of 7p: Further delineation of the phenotype and restriction of the critical region to the distal part of the short arm

DOE Office of Scientific and Technical Information (OSTI.GOV)

Reish, O.; Berry, S.A.; King, R.A.

We report on a patient with duplication of 7p15{r_arrow}pter and review of the literature. Patients with partial duplication of the distal 7p, including only the distal segment 7p15{r_arrow}pter, have a syndrome comparable to that of patients with a larger or complete duplication of 7p. This suggests that the critical region for the dup(7p) phenotype is restricted to 7p15{r_arrow}pter. The complete clinical phenotype of dup (7)(p15{r_arrow}pter) includes mental retardation, skull anomalies, large anterior fontanel, cardiovascular defects, joint dislocation and contraction, and gastrointestinal and genital defects. Recognition of the clinical spectrum in patients with a smaller duplication 7p, and the assignment ofmore » this critical region, should prove valuable for accurate counseling, prediction of outcome, and further gene mapping. 33 refs., 3 figs., 2 tabs.« less

Clinical epidemiology survey of the traditional Chinese medicine etiology and syndrome differentiation of coronary artery disease: study protocol of a multicenter trial.

PubMed

Bi, Ying-fei; Mao, Jing-yuan; Wang, Xian-liang; Hou, Ya-zhu; Lu, Yi-zhu; Soh, Shan Bin; Zhang, Bo-li

2012-06-01

Coronary artery disease (CAD), a common disease with high incidence and mortality rate, has seriously threatened the health and life of the public. Traditional Chinese medicine (TCM) has an important role in the prevention and treatment of this disease. Through clinical epidemiological survey, a deeper understanding of TCM etiology and syndrome characteristics in CAD would further improve clinical efficacy in the treatment of this disease. The preliminary clinical questionnaire for TCM etiology and syndrome differentiation in CAD was designed after literature reviews and analysis. Through a series of clinical pre-surveys, expert consultation and demonstration, the formal TCM clinical epidemiology questionnaire on the etiology and syndrome differentiation in CAD was finalized, after which, the study protocol, inclusive and exclusive criteria and related quality control measures were prepared. The multiregional clinical epidemiological survey with more than 5000 participants with CAD will be carried out in 41 TCM hospitals of China for investigating the TCM etiology and syndrome differentiation of CAD. Multiregion large sample size clinical epidemiology survey on TCM etiology and syndrome differentiation in CAD will provide further evidence in preventing CAD and improving the standardization process of syndrome research. This study protocol was registered at the Chinese Clinical Trial Registry on November 27, 2011 in both Chinese and English editions and the registration number is ChiCTR-ECS-11001728.

Atlantic salmon populations reveal adaptive divergence of immune related genes - a duplicated genome under selection.

PubMed

Kjærner-Semb, Erik; Ayllon, Fernando; Furmanek, Tomasz; Wennevik, Vidar; Dahle, Geir; Niemelä, Eero; Ozerov, Mikhail; Vähä, Juha-Pekka; Glover, Kevin A; Rubin, Carl J; Wargelius, Anna; Edvardsen, Rolf B

2016-08-11

Populations of Atlantic salmon display highly significant genetic differences with unresolved molecular basis. These differences may result from separate postglacial colonization patterns, diversifying natural selection and adaptation, or a combination. Adaptation could be influenced or even facilitated by the recent whole genome duplication in the salmonid lineage which resulted in a partly tetraploid species with duplicated genes and regions. In order to elucidate the genes and genomic regions underlying the genetic differences, we conducted a genome wide association study using whole genome resequencing data from eight populations from Northern and Southern Norway. From a total of ~4.5 million sequencing-derived SNPs, more than 10 % showed significant differentiation between populations from these two regions and ten selective sweeps on chromosomes 5, 10, 11, 13-15, 21, 24 and 25 were identified. These comprised 59 genes, of which 15 had one or more differentiated missense mutation. Our analysis showed that most sweeps have paralogous regions in the partially tetraploid genome, each lacking the high number of significant SNPs found in the sweeps. The most significant sweep was found on Chr 25 and carried several missense mutations in the antiviral mx genes, suggesting that these populations have experienced differing viral pressures. Interestingly the second most significant sweep, found on Chr 5, contains two genes involved in the NF-KB pathway (nkap and nkrf), which is also a known pathogen target that controls a large number of processes in animals. Our results show that natural selection acting on immune related genes has contributed to genetic divergence between salmon populations in Norway. The differences between populations may have been facilitated by the plasticity of the salmon genome. The observed signatures of selection in duplicated genomic regions suggest that the recently duplicated genome has provided raw material for evolutionary adaptation.

Whole-genome sequencing in patients with ciliopathies uncovers a novel recurrent tandem duplication in IFT140.

PubMed

Geoffroy, Véronique; Stoetzel, Corinne; Scheidecker, Sophie; Schaefer, Elise; Perrault, Isabelle; Bär, Séverine; Kröll, Ariane; Delbarre, Marion; Antin, Manuela; Leuvrey, Anne-Sophie; Henry, Charline; Blanché, Hélène; Decker, Eva; Kloth, Katja; Klaus, Günter; Mache, Christoph; Martin-Coignard, Dominique; McGinn, Steven; Boland, Anne; Deleuze, Jean-François; Friant, Sylvie; Saunier, Sophie; Rozet, Jean-Michel; Bergmann, Carsten; Dollfus, Hélène; Muller, Jean

2018-04-24

Ciliopathies represent a wide spectrum of rare diseases with overlapping phenotypes and a high genetic heterogeneity. Among those, IFT140 is implicated in a variety of phenotypes ranging from isolated retinis pigmentosa to more syndromic cases. Using whole-genome sequencing in patients with uncharacterized ciliopathies, we identified a novel recurrent tandem duplication of exon 27-30 (6.7 kb) in IFT140, c.3454-488_4182+2588dup p.(Tyr1152_Thr1394dup), missed by whole-exome sequencing. Pathogenicity of the mutation was assessed on the patients' skin fibroblasts. Several hundreds of patients with a ciliopathy phenotype were screened and biallelic mutations were identified in 11 families representing 12 pathogenic variants of which seven are novel. Among those unrelated families especially with a Mainzer-Saldino syndrome, eight carried the same tandem duplication (two at the homozygous state and six at the heterozygous state). In conclusion, we demonstrated the implication of structural variations in IFT140-related diseases expanding its mutation spectrum. We also provide evidences for a unique genomic event mediated by an Alu-Alu recombination occurring on a shared haplotype. We confirm that whole-genome sequencing can be instrumental in the ability to detect structural variants for genomic disorders. © 2018 Wiley Periodicals, Inc.

Tubular duplication of the oesophagus presenting with dysphagia.

PubMed

Saha, A K; Kundu, A K

2014-06-01

Duplications of the alimentary tract are rare congenital malformations, with the ileum being the most commonly affected site, followed by the oesophagus. Among oesophageal duplications, cystic duplication is the most common and the tubular variety, the rarest. Herein, we report a rare case of tubular oesophageal duplication, complicated by adenosquamous carcinoma at the lower end of the oesophagus, in a 32-year-old man who presented with progressive dysphagia. Although proton pump inhibitors may relieve dysphagia, oesophagectomy and gastric interpositioning should be the first-line treatment for patients with tubular oesophageal duplication, in order to reduce the risk of malignant transformation at the lower end of the oesophagus.

Duplication and expression of CYC2-like genes in the origin and maintenance of corolla zygomorphy in Lamiales.

PubMed

Zhong, Jinshun; Kellogg, Elizabeth A

2015-01-01

Duplication, retention, and expression of CYCLOIDEA2 (CYC2)-like genes are thought to affect evolution of corolla symmetry. However, exactly what and how changes in CYC2-like genes correlate with the origin of corolla zygomorphy are poorly understood. We inferred and calibrated a densely sampled phylogeny of CYC2-like genes across the Lamiales and examined their expression in early diverging (EDL) and higher core clades (HCL). CYC2-like genes duplicated extensively in Lamiales, at least six times in core Lamiales (CL) around the Cretaceous-Paleogene (K-Pg) boundary, and seven more in EDL relatively more recently. Nested duplications and losses of CYC2-like paralogs are pervasive but may not correlate with transitions in corolla symmetry. We found evidence for dN/dS (ω) variation following gene duplications. CYC2-like paralogs in HCL show differential expression with higher expression in adaxial petals. Asymmetric expression but not recurrent duplication of CYC2-like genes correlates with the origin of corolla zygomorphy. Changes in both cis-regulatory and coding domains of CYC2-like genes are probably crucial for the evolution of corolla zygomorphy. Multiple selection regimes appear likely to play important roles in gene retention. The parallel duplications of CYC2-like genes are after the initial diversification of bumble bees and Euglossine bees. © 2014 The Authors. New Phytologist © 2014 New Phytologist Trust.

Genetics Home Reference: Koolen-de Vries syndrome

MedlinePlus

... of Koolen-de Vries syndrome , has undergone an inversion . An inversion involves two breaks in a chromosome; the resulting ... lineage have no health problems related to the inversion. However, genetic material can be lost or duplicated ...

Differential diagnosis of Bartter syndrome, Gitelman syndrome, and pseudo-Bartter/Gitelman syndrome based on clinical characteristics.

PubMed

Matsunoshita, Natsuki; Nozu, Kandai; Shono, Akemi; Nozu, Yoshimi; Fu, Xue Jun; Morisada, Naoya; Kamiyoshi, Naohiro; Ohtsubo, Hiromi; Ninchoji, Takeshi; Minamikawa, Shogo; Yamamura, Tomohiko; Nakanishi, Koichi; Yoshikawa, Norishige; Shima, Yuko; Kaito, Hiroshi; Iijima, Kazumoto

2016-02-01

Phenotypic overlap exists among type III Bartter syndrome (BS), Gitelman syndrome (GS), and pseudo-BS/GS (p-BS/GS), which are clinically difficult to distinguish. We aimed to clarify the differences between these diseases, allowing accurate diagnosis based on their clinical features. A total of 163 patients with genetically defined type III BS (n = 30), GS (n = 90), and p-BS/GS (n = 43) were included. Age at diagnosis, sex, body mass index, estimated glomerular filtration rate, and serum and urine electrolyte concentrations were determined. Patients with p-BS/GS were significantly older at diagnosis than those with type III BS and GS. Patients with p-BS/GS included a significantly higher percentage of women and had a lower body mass index and estimated glomerular filtration rate than did patients with GS. Although hypomagnesemia and hypocalciuria were predominant biochemical findings in patients with GS, 17 and 23% of patients with type III BS and p-BS/GS, respectively, also showed these abnormalities. Of patients with type III BS, GS, and p-BS/GS, 40, 12, and 63%, respectively, presented with chronic kidney disease. This study clarified the clinical differences between BS, GS, and p-BS/GS for the first time, which will help clinicians establish differential diagnoses for these three conditions.

Molecular analyses of unrelated Charcot-Marie-Tooth (CMT) disease patients suggest a high frequency of the CMT1A duplication

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wise, C.A.; Davis, S.N.; Heju, Z.

1993-10-01

Charcot-Marie-Tooth disease (CMT) is the most common inherited peripheral neuropathy. One form of CMT, CMT type 1A, is characterized by uniformly decreased nerve conduction velocities, usually shows autosomal dominant inheritance, and is associated with a large submicroscopic duplication of the p11.2-p12 region of chromosome 17. A cohort of 75 unrelated patients diagnosed clinically with CMT and evaluated by electrophysiological methods were analyzed molecularly for the presence of the CMT1A DNA duplication. Three methodologies were used to assess the duplication: Measurement of dosage differences between RFLP alleles, analysis of polymorphic (GT)[sub n] repeats, and detection of a junction fragment by pulsed-fieldmore » gel electrophoresis. The CMT1A duplication was found in 68% of the 63 unrelated CMT patients with electrophysiological studies consistent with CMT type 1 (CMT1). The CMT1A duplication was detected as a de novo event in two CMT1 families. Twelve CMT patients who did not have decreased nerve conduction velocities consistent with a diagnosis of CMT type 2 (CMT2) were found not to have the CMT1A duplication. The most informative molecular method was the detection of the CMT1A duplication-specific junction fragment. Given the high frequency of the CMT1A duplication in CMT patients and the high frequency of new mutations, the authors conclude that a molecular test for the CMT1A DNA duplication is very useful in the differential diagnosis of patients with peripheral neuropathies. 61 refs., 4 figs.« less

Startling Mosaicism of the Y-Chromosome and Tandem Duplication of the SRY and DAZ Genes in Patients with Turner Syndrome

PubMed Central

Premi, Sanjay; Srivastava, Jyoti; Panneer, Ganesan; Ali, Sher

2008-01-01

Presence of the human Y-chromosome in females with Turner Syndrome (TS) enhances the risk of development of gonadoblastoma besides causing several other phenotypic abnormalities. In the present study, we have analyzed the Y chromosome in 15 clinically diagnosed Turner Syndrome (TS) patients and detected high level of mosaicisms ranging from 45,XO:46,XY = 100:0% in 4; 45,XO:46,XY:46XX = 4:94:2 in 8; and 45,XO:46,XY:46XX = 50:30:20 cells in 3 TS patients, unlike previous reports showing 5–8% cells with Y- material. Also, no ring, marker or di-centric Y was observed in any of the cases. Of the two TS patients having intact Y chromosome in >85% cells, one was exceptionally tall. Both the patients were positive for SRY, DAZ, CDY1, DBY, UTY and AZFa, b and c specific STSs. Real Time PCR and FISH demonstrated tandem duplication/multiplication of the SRY and DAZ genes. At sequence level, the SRY was normal in 8 TS patients while the remaining 7 showed either absence of this gene or known and novel mutations within and outside of the HMG box. SNV/SFV analysis showed normal four copies of the DAZ genes in these 8 patients. All the TS patients showed aplastic uterus with no ovaries and no symptom of gonadoblastoma. Present study demonstrates new types of polymorphisms indicating that no two TS patients have identical genotype-phenotype. Thus, a comprehensive analysis of more number of samples is warranted to uncover consensus on the loci affected, to be able to use them as potential diagnostic markers. PMID:19030103

Association of an α-globin gene cluster duplication and heterozygous β-thalassemia in a patient with a severe thalassemia syndrome.

PubMed

Jiang, Hua; Liu, Sha; Zhang, Yong-Ling; Wan, Jun-Hui; Li, Ru; Li, Dong-Zhi

2015-01-01

We describe a new case of a β-thalassemia (β-thal) heterozygote with the mutation IVS-II-654 (C>T) presenting with a transfusion-dependent phenotype. Multiplex ligation-dependent probe amplification (MLPA) and array comparative genomic hybridization (CGH) analyses of the α-globin gene cluster revealed a full duplication of the α-globin genes including the upstream regulatory element. The duplicated allele and the normal allele in trans resulted in a total of six active α-globin genes. The severe clinical phenotype seemed to be related to the considerable excess of the α- and β-globin deficit caused by the presence of the β-thal. α-Globin cluster duplication should be considered in patients heterozygous for β-thal who show a more severe phenotype than β-thal trait.

Divergence of Gene Body DNA Methylation and Evolution of Plant Duplicate Genes

PubMed Central

Wang, Jun; Marowsky, Nicholas C.; Fan, Chuanzhu

2014-01-01

It has been shown that gene body DNA methylation is associated with gene expression. However, whether and how deviation of gene body DNA methylation between duplicate genes can influence their divergence remains largely unexplored. Here, we aim to elucidate the potential role of gene body DNA methylation in the fate of duplicate genes. We identified paralogous gene pairs from Arabidopsis and rice (Oryza sativa ssp. japonica) genomes and reprocessed their single-base resolution methylome data. We show that methylation in paralogous genes nonlinearly correlates with several gene properties including exon number/gene length, expression level and mutation rate. Further, we demonstrated that divergence of methylation level and pattern in paralogs indeed positively correlate with their sequence and expression divergences. This result held even after controlling for other confounding factors known to influence the divergence of paralogs. We observed that methylation level divergence might be more relevant to the expression divergence of paralogs than methylation pattern divergence. Finally, we explored the mechanisms that might give rise to the divergence of gene body methylation in paralogs. We found that exonic methylation divergence more closely correlates with expression divergence than intronic methylation divergence. We show that genomic environments (e.g., flanked by transposable elements and repetitive sequences) of paralogs generated by various duplication mechanisms are associated with the methylation divergence of paralogs. Overall, our results suggest that the changes in gene body DNA methylation could provide another avenue for duplicate genes to develop differential expression patterns and undergo different evolutionary fates in plant genomes. PMID:25310342

Diverse Cis-Regulatory Mechanisms Contribute to Expression Evolution of Tandem Gene Duplicates

PubMed Central

Baudouin-Gonzalez, Luís; Santos, Marília A; Tempesta, Camille; Sucena, Élio; Roch, Fernando; Tanaka, Kohtaro

2017-01-01

Abstract Pairs of duplicated genes generally display a combination of conserved expression patterns inherited from their unduplicated ancestor and newly acquired domains. However, how the cis-regulatory architecture of duplicated loci evolves to produce these expression patterns is poorly understood. We have directly examined the gene-regulatory evolution of two tandem duplicates, the Drosophila Ly6 genes CG9336 and CG9338, which arose at the base of the drosophilids between 40 and 60 Ma. Comparing the expression patterns of the two paralogs in four Drosophila species with that of the unduplicated ortholog in the tephritid Ceratitis capitata, we show that they diverged from each other as well as from the unduplicated ortholog. Moreover, the expression divergence appears to have occurred close to the duplication event and also more recently in a lineage-specific manner. The comparison of the tissue-specific cis-regulatory modules (CRMs) controlling the paralog expression in the four Drosophila species indicates that diverse cis-regulatory mechanisms, including the novel tissue-specific enhancers, differential inactivation, and enhancer sharing, contributed to the expression evolution. Our analysis also reveals a surprisingly variable cis-regulatory architecture, in which the CRMs driving conserved expression domains change in number, location, and specificity. Altogether, this study provides a detailed historical account that uncovers a highly dynamic picture of how the paralog expression patterns and their underlying cis-regulatory landscape evolve. We argue that our findings will encourage studying cis-regulatory evolution at the whole-locus level to understand how interactions between enhancers and other regulatory levels shape the evolution of gene expression. PMID:28961967

Duplication and concerted evolution in a master sex determiner under balancing selection.

PubMed

Privman, Eyal; Wurm, Yannick; Keller, Laurent

2013-05-07

The transformer (tra) gene is a key regulator in the signalling hierarchy controlling all aspects of somatic sexual differentiation in Drosophila and other insects. Here, we show that six of the seven sequenced ants have two copies of tra. Surprisingly, the two paralogues are always more similar within species than among species. Comparative sequence analyses indicate that this pattern is owing to the ongoing concerted evolution after an ancestral duplication rather than independent duplications in each of the six species. In particular, there was strong support for inter-locus recombination between the paralogues of the ant Atta cephalotes. In the five species where the location of paralogues is known, they are adjacent to each other in four cases and separated by only few genes in the fifth case. Because there have been extensive genomic rearrangements in these lineages, this suggests selection acting to conserve their synteny. In three species, we also find a signature of positive selection in one of the paralogues. In three bee species where information is available, the tra gene is also duplicated, the copies are adjacent and in at least one species there was recombination between paralogues. These results suggest that concerted evolution plays an adaptive role in the evolution of this gene family.

40 CFR 710.35 - Duplicative reporting.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Duplicative reporting. 710.35 Section 710.35 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC SUBSTANCES CONTROL ACT TSCA CHEMICAL INVENTORY REGULATIONS 2002 Inventory Update Reporting § 710.35 Duplicative reporting...

47 CFR 76.122 - Satellite network non-duplication.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 47 Telecommunication 4 2010-10-01 2010-10-01 false Satellite network non-duplication. 76.122... MULTICHANNEL VIDEO AND CABLE TELEVISION SERVICE Network Non-duplication Protection, Syndicated Exclusivity and Sports Blackout § 76.122 Satellite network non-duplication. (a) Upon receiving notification pursuant to...

47 CFR 76.122 - Satellite network non-duplication.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 47 Telecommunication 4 2011-10-01 2011-10-01 false Satellite network non-duplication. 76.122... MULTICHANNEL VIDEO AND CABLE TELEVISION SERVICE Network Non-duplication Protection, Syndicated Exclusivity and Sports Blackout § 76.122 Satellite network non-duplication. (a) Upon receiving notification pursuant to...

A study of the quality of duplicated radiographs.

PubMed

Erales, F A; Manson-Hing, L R

1979-01-01

The resolution, contrast, and clinical appearance of radiographs and duplicate radiographs made with two types of duplicating film were compared. Duplicating conditions evaluated were type and shape of light, light-film distance, type of exposure surface, and developer temperature. Major observations were as follows: both Kodak and DuPont films produced clinically acceptable duplicates; Kodak film was faster; DuPont film responded better in incandescent photoflood light than Kodak film; clear glass with appropriate light-film distance was the best exposure surface.

Partial USH2A deletions contribute to Usher syndrome in Denmark.

PubMed

Dad, Shzeena; Rendtorff, Nanna D; Kann, Erik; Albrechtsen, Anders; Mehrjouy, Mana M; Bak, Mads; Tommerup, Niels; Tranebjærg, Lisbeth; Rosenberg, Thomas; Jensen, Hanne; Møller, Lisbeth B

2015-12-01

Usher syndrome is an autosomal recessive disorder characterized by congenital hearing impairment, progressive visual loss owing to retinitis pigmentosa and in some cases vestibular dysfunction. Usher syndrome is divided into three subtypes, USH1, USH2 and USH3. Twelve loci and eleven genes have so far been identified. Duplications and deletions in PCDH15 and USH2A that lead to USH1 and USH2, respectively, have previously been identified in patients from United Kingdom, Spain and Italy. In this study, we investigate the proportion of exon deletions and duplications in PCDH15 and USH2A in 20 USH1 and 30 USH2 patients from Denmark using multiplex ligation-dependent probe amplification (MLPA). Two heterozygous deletions were identified in USH2A, but no deletions or duplications were identified in PCDH15. Next-generation mate-pair sequencing was used to identify the exact breakpoints of the two deletions identified in USH2A. Our results suggest that USH2 is caused by USH2A exon deletions in a small fraction of the patients, whereas deletions or duplications in PCDH15 might be rare in Danish Usher patients.

A conserved segmental duplication within ELA.

PubMed

Brinkmeyer-Langford, C L; Murphy, W J; Childers, C P; Skow, L C

2010-12-01

The assembled genomic sequence of the horse major histocompatibility complex (MHC) (equine lymphocyte antigen, ELA) is very similar to the homologous human HLA, with the notable exception of a large segmental duplication at the boundary of ELA class I and class III that is absent in HLA. The segmental duplication consists of a ∼ 710 kb region of at least 11 repeated blocks: 10 blocks each contain an MHC class I-like sequence and the helicase domain portion of a BAT1-like sequence, and the remaining unit contains the full-length BAT1 gene. Similar genomic features were found in other Perissodactyls, indicating an ancient origin, which is consistent with phylogenetic analyses. Reverse-transcriptase PCR (RT-PCR) of mRNA from peripheral white blood cells of healthy and chronically or acutely infected horses detected transcription from predicted open reading frames in several of the duplicated blocks. This duplication is not present in the sequenced MHCs of most other mammals, although a similar feature at the same relative position is present in the feline MHC (FLA). Striking sequence conservation throughout Perissodactyl evolution is consistent with a functional role for at least some of the genes included within this segmental duplication. © 2010 The Authors, Journal compilation © 2010 Stichting International Foundation for Animal Genetics.

A patient with de-novo partial deletion of Xp (p11.4-pter) and partial duplication of 22q (q11.2-qter).

PubMed

Armour, Christine M; McGowan-Jordan, Jean; Lawrence, Sarah E; Bouchard, Amélie; Basik, Mark; Allanson, Judith E

2008-01-01

We report on a girl with partial deletion of Xp and partial duplication of 22q. Family studies demonstrate that both the patient's mother and her nonidentical twin sister carry the corresponding balanced translocation; 46,X,t(X;22)(p11.4;q11.2). This girl has developmental delay, microcephaly, mild dysmorphisms and hearing loss but otherwise shows few of the features described in individuals with duplications of the long arm of chromosome 22. She does manifest characteristics, such as short stature and biochemical evidence of ovarian failure, which are seen in partial or complete Xp deletions and Turner's syndrome.

Reticulated acanthoma with sebaceous differentiation: another sebaceous neoplasm associated with Muir-Torre syndrome?

PubMed

Shon, Wonwoo; Wolz, Michael M; Newman, Catherine C; Bridges, Alina G

2014-11-01

Reticulated acanthoma with sebaceous differentiation (RASD) represents a rare benign cutaneous epithelial neoplasm with sebaceous differentiation. There has been much speculation about the relationship between RASD and Muir-Torre syndrome (MTS). We report a 53 year-old man who presented with RASD in addition to a prior history of sebaceous adenomas. Immunohistochemically, the tumour cells in the RASD and sebaceous adenomas showed a significantly reduced MSH6 protein expression, whereas there was no loss of MLH1, MSH2 and PMS2. This benign neoplasm, which can be mistaken for various other cutaneous lesions with sebaceous differentiation, deserves wider recognition for its possible association with MTS. © 2013 The Authors. Australasian Journal of Dermatology © 2013 The Australasian College of Dermatologists.

Embryonic duplications in sheep.

PubMed

Dennis, S M

1975-02-01

Twenty-seven embryonic duplications were examined during a 3-year investigation into the causes of perinatal lamb mortality. Twenty of the 27 were anomalous twins with 19 being conjoined (diplopagus 9 and heteropagus 10). The various duplications were: haloacardius acephalus 1, diprosopus 2, dicephalus 2, dipypus 3, diprosopus dipygus 1, syncephalus dipygus 1, pygopagus parasiticus 1, heteropagus dipygus 3, melodidymus 6, polyury 4, penile duplication 2, and bilateral otognathia 1. Four lambs were living and the time of death of the others was: parturient 8, and post-parturient 15. Average dry weight of the lambs was 3.35 kg (range 1.59 to 5.45 kg). Breed distribution was: Merino 77.8%, Crossbred 14.8%, Dorset Horn 3.7%, and Corriedale 3.7%. The caudal region was involved in 10 of the conjoined twins (52.6%), anterior region in 7 (36.9%), and both anterior and caudal regions in 2 (10.5%). Associated defects were present in 70.4% of the 27 lambs, the most common being atresia ani.

[Posterior reversible encephalopathy syndrome and cerebrovascular constriction syndrome in the differential diagnosis of post-partum headaches].

PubMed

Ruiz López, N; Cano Hernández, B; Balbás Álvarez, S

2016-02-01

Postpartum headache can be due to many causes. In a patient with previous epidural analgesia, the headache can be attributed to post-dural puncture headache, even if the symptoms are not typical of this clinical entity. We report a case of a post-partum with accidental dural tap during the insertion of an epidural catheter for labour analgesia, and who referred to headaches in the third post-partum day. Initially, a post-dural puncture headache was suspected, but the subsequent onset of seizures and visual impairment meant that the diagnosis had to be reconsidered. In this case report, the clinical and pathophysiological features of posterior reversible encephalopathy syndrome and reversible cerebral vasoconstriction syndrome, as well as the differential diagnosis of post-partum headaches are described. Copyright © 2014 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Publicado por Elsevier España, S.L.U. All rights reserved.

Mirror-symmetric duplicated chromosome 21q with minor proximal deletion, and with neocentromere in a child without the classical Down syndrome phenotype.

PubMed

Barbi, G; Kennerknecht, I; Wöhr, G; Avramopoulos, D; Karadima, G; Petersen, M B

2000-03-13

We report on a mentally retarded child with multiple minor anomalies and an unusually rearranged chromosome 21. This der(21) chromosome has a deletion of 21p and of proximal 21q, whereas the main portion of 21q is duplicated leading to a mirror-symmetric appearance with the mirror axis at the breakpoint. The centromere is only characterized by a secondary constriction (with a centromeric index of a G chromosome) at an unexpected distal position, but fluorescence in situ hybridization (FISH) with either chromosome specific or with all human centromeres alpha satellite DNA shows no cross hybridization. Thus, the marker chromosome represents a further example of an "analphoid marker with neocentromere." Molecular analysis using polymorphic markers on chromosome 21 verified a very small monosomic segment of the proximal long arm of chromosome 21, and additionally trisomy of the remaining distal segment. Although trisomic for almost the entire 21q arm, our patient shows no classical Down syndrome phenotype, but only a few minor anomalies found in trisomy 21 and in monosomy of proximal 21q, respectively. Copyright 2000 Wiley-Liss, Inc.

Insight into podocyte differentiation from the study of human genetic disease: nail-patella syndrome and transcriptional regulation in podocytes.

PubMed

Morello, Roy; Lee, Brendan

2002-05-01

In recent years, our understanding of the molecular basis of kidney development has benefited from the study of rare genetic diseases affecting renal function. This has especially been the case with the differentiation of the highly specialized podocyte in the pathogenesis of human disorders and mouse phenotypes affecting the renal filtration barrier. This filtration barrier represents the end product of a complex series of signaling events that produce a tripartite structure consisting of interdigitating podocyte foot processes with intervening slit diaphragms, the glomerular basement membrane, and the fenestrated endothelial cell. Dysregulation of unique cytoskeletal and extracellular matrix proteins in genetic forms of nephrotic syndrome has shown how specific structural proteins contribute to podocyte function and differentiation. However, much less is known about the transcriptional determinants that both specify and maintain this differentiated cell. Our studies of a skeletal malformation syndrome, nail-patella syndrome, have shown how the LIM homeodomain transcription factor, Lmx1b, contributes to transcriptional regulation of glomerular basement membrane collagen expression by podocytes. Moreover, they raise intriguing questions about more global transcriptional regulation of podocyte morphogenesis.

Targeted High Performance Liquid Chromatography Tandem Mass Spectrometry-based Metabolomics differentiates metabolic syndrome from obesity.

PubMed

Zhong, Fanyi; Xu, Mengyang; Bruno, Richard S; Ballard, Kevin D; Zhu, Jiangjiang

2017-04-01

Both obesity and the metabolic syndrome are risk factors for type 2 diabetes and cardiovascular disease. Identification of novel biomarkers are needed to distinguish metabolic syndrome from equally obese individuals in order to direct them to early interventions that reduce their risk of developing further health problems. We utilized mass spectrometry-based targeted metabolic profiling of 221 metabolites to evaluate the associations between metabolite profiles and established metabolic syndrome criteria (i.e. elevated waist circumference, hypertension, elevated fasting glucose, elevated triglycerides, and low high-density lipoprotein cholesterol) in plasma samples from obese men ( n = 29; BMI = 35.5 ± 5.2 kg/m 2 ) and women ( n = 40; 34.9 ± 6.7 kg/m 2 ), of which 26 met the criteria for metabolic syndrome (17 men and 9 women). Compared to obese individuals without metabolic syndrome, univariate statistical analysis and partial least squares discriminant analysis showed that a specific group of metabolites from multiple metabolic pathways (i.e. purine metabolism, valine, leucine and isoleucine degradation, and tryptophan metabolism) were associated with the presence of metabolic syndrome. Receiver operating characteristic curves generated based on the PLS-DA models showed excellent areas under the curve (0.85 and 0.96, for metabolites only model and enhanced metabolites model, respectively), high specificities (0.86 and 0.93), and good sensitivities (0.71 and 0.91). Moreover, principal component analysis revealed that metabolic profiles can be used to further differentiate metabolic syndrome with 3 versus 4-5 metabolic syndrome criteria. Collectively, these findings support targeted metabolomics approaches to distinguish metabolic syndrome from obesity alone, and to stratify metabolic syndrome status based on the number of criteria met. Impact statement We utilized mass spectrometry-based targeted metabolic profiling of 221 metabolites to

Quantifying the major mechanisms of recent gene duplications in the human and mouse genomes: a novel strategy to estimate gene duplication rates

PubMed Central

Pan, Deng; Zhang, Liqing

2007-01-01

Background The rate of gene duplication is an important parameter in the study of evolution, but the influence of gene conversion and technical problems have confounded previous attempts to provide a satisfying estimate. We propose a new strategy to estimate the rate that involves separate quantification of the rates of two different mechanisms of gene duplication and subsequent combination of the two rates, based on their respective contributions to the overall gene duplication rate. Results Previous estimates of gene duplication rates are based on small gene families. Therefore, to assess the applicability of this to families of all sizes, we looked at both two-copy gene families and the entire genome. We studied unequal crossover and retrotransposition, and found that these mechanisms of gene duplication are largely independent and account for a substantial amount of duplicated genes. Unequal crossover contributed more to duplications in the entire genome than retrotransposition did, but this contribution was significantly less in two-copy gene families, and duplicated genes arising from this mechanism are more likely to be retained. Combining rates of duplication using the two mechanisms, we estimated the overall rates to be from approximately 0.515 to 1.49 × 10-3 per gene per million years in human, and from approximately 1.23 to 4.23 × 10-3 in mouse. The rates estimated from two-copy gene families are always lower than those from the entire genome, and so it is not appropriate to use small families to estimate the rate for the entire genome. Conclusion We present a novel strategy for estimating gene duplication rates. Our results show that different mechanisms contribute differently to the evolution of small and large gene families. PMID:17683522

Duplicate Record Elimination in Large Data Files.

DTIC Science & Technology

1981-08-01

UNCLASSIFIJED CSTR -445 NL LmEE~hhE - I1.0 . 111112----5 1.~4 __112 ___IL25_ 1.4 111111.6 EI24 COMPUTER SCIENCES DEPARTMENT oUniversity of Wisconsin...we propose a combinatorial model for the use in the analysis of algorithms for duplicate elimination. We contend that this model can serve as a...duplicates in a multiset of records, knowing the size of the multiset and the number of distinct records in it. 3. Algorithms for Duplicate Elimination

FT Duplication Coordinates Reproductive and Vegetative Growth

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hsu, Chuan-Yu; Adams, Joshua P.; Kim, Hyejin

2011-01-01

Annual plants grow vegetatively at early developmental stages and then transition to the reproductive stage, followed by senescence in the same year. In contrast, after successive years of vegetative growth at early ages, woody perennial shoot meristems begin repeated transitions between vegetative and reproductive growth at sexual maturity. However, it is unknown how these repeated transitions occur without a developmental conflict between vegetative and reproductive growth. We report that functionally diverged paralogs FLOWERING LOCUS T1 (FT1) and FLOWERING LOCUS T2 (FT2), products of whole-genome duplication and homologs of Arabidopsis thaliana gene FLOWERING LOCUS T (FT), coordinate the repeated cycles ofmore » vegetative and reproductive growth in woody perennial poplar (Populus spp.). Our manipulative physiological and genetic experiments coupled with field studies, expression profiling, and network analysis reveal that reproductive onset is determined by FT1 in response to winter temperatures, whereas vegetative growth and inhibition of bud set are promoted by FT2 in response to warm temperatures and long days in the growing season. The basis for functional differentiation between FT1 and FT2 appears to be expression pattern shifts, changes in proteins, and divergence in gene regulatory networks. Thus, temporal separation of reproductive onset and vegetative growth into different seasons via FT1 and FT2 provides seasonality and demonstrates the evolution of a complex perennial adaptive trait after genome duplication.« less

Severe Expressive-Language Delay Related to Duplication of the Williams–Beuren Locus

PubMed Central

Somerville, Martin J.; Mervis, Carolyn B.; Young, Edwin J.; Seo, Eul-Ju; del Campo, Miguel; Bamforth, Stephen; Peregrine, Ella; Loo, Wayne; Lilley, Margaret; Pérez-Jurado, Luis A.; Morris, Colleen A.; Scherer, Stephen W.; Osborne, Lucy R.

2010-01-01

SUMMARY The Williams–Beuren syndrome (WBS) locus, at 7q11.23, is prone to recurrent chromosomal rearrangements, including the microdeletion that causes WBS, a multisystem condition with characteristic cardiovascular, cognitive, and behavioral features. It is hypothesized that reciprocal duplications of the WBS interval should also occur, and here we present such a case description. The most striking phenotype was a severe delay in expressive speech, in contrast to the normal articulation and fluent expressive language observed in persons with WBS. Our results suggest that specific genes at 7q11.23 are exquisitely sensitive to dosage alterations that can influence human language and visuospatial capabilities. PMID:16236740

Partial craniofacial duplication: a review of the literature and case report.

PubMed

Costa, Melinda A; Borzabadi-Farahani, Ali; Lara-Sanchez, Pedro A; Schweitzer, Daniela; Jacobson, Lia; Clarke, Noreen; Hammoudeh, Jeffery; Urata, Mark M; Magee, William P

2014-06-01

Diprosopus (Greek; di-, "two" + prosopon, "face"), or craniofacial duplication, is a rare craniofacial anomaly referring to the complete duplication of facial structures. Partial craniofacial duplication describes a broad spectrum of congenital anomalies, including duplications of the oral cavity. This paper describes a 15 month-old female with a duplicated oral cavity, mandible, and maxilla. A Tessier type 7 cleft, midline meningocele, and duplicated hypophysis were also present. The preoperative evaluation, surgical approach, postoperative results, and a review of the literature are presented. The surgical approach was designed to preserve facial nerve innervation to the reconstructed cheek and mouth. The duplicated mandible and maxilla were excised and the remaining left maxilla was bone grafted. Soft tissue repair included closure of the Tessier type VII cleft. Craniofacial duplication remains a rare entity that is more common in females. The pathophysiology remains incompletely characterized, but is postulated to be due to duplication of the notochord, as well as duplication of mandibular growth centres. While diprosopus is a severe deformity often associated with anencephaly, patients with partial duplication typically benefit from surgical treatment. Managing craniofacial duplication requires a detailed preoperative evaluation as well as a comprehensive, staged treatment plan. Long-term follow up is needed appropriately to address ongoing craniofacial deformity. Published by Elsevier Ltd.

Levels of duplicate gene expression in armoured catfishes.

PubMed

Dunham, R A; Philipp, D P; Whitt, G S

1980-01-01

Species of armoured catfishes differ significantly in their cellular DNA content and chromosome number. Starch gel electrophoresis of isozymes was used to determine whether each of 16 enzyme loci was expressed in a single or duplicate state. The percent of enzyme loci exhibiting duplicate locus expression in Corydoras aeneus, Corydoras julii, Corydoras melanistius, and Corydoras myersi was 37.5 percent, 18.75 percent, 12.5 percent, and 6.25 percent, respectively. The percentage of loci expressed in duplicate is higher in the species with higher haploid DNA contents, which are 4.4 pg, 3.0 pg, and 2.3 pg, respectively. These differences in DNA contents are also associated with differences in chromosome number. These data are consistent with the hypothesis that increases in DNA contents and enzyme loci occur both by tetraploidization and by regional gene duplication and that these increases are then followed by a partial loss of DNA and a reduction in the number of the duplicate isozyme loci expressed. Such analyses provide insight into the mechanisms of genome amplification and reduction as well as insights into the fats of duplicate genes.

Clinical Implications of Cardiac-MIBG SPECT in the Differentiation of Parkinsonian Syndromes

PubMed Central

Shin, Dong Hoon; Bang, Oh Young; Joo, In Soo; Huh, Kyoon

2006-01-01

Background and Purpose 123I cardiac meta-iodobenzylguanidine (MIBG), an analogue of norepinephrine, has been used to estimate myocardial sympathetic nerve function. We investigate whether cardiac-MIBG SPECT is clinically applicable in the differentiation of Parkinson's disease (PD) from parkinsonian syndromes. Methods Cardiac-MIBG scintigraphy was performed in 27 controls, in 40 patients with PD and in 52 patients with other parkinsonian syndromes comprising 23 with multiple system atrophy (MSA), 26 with drug-induced parkinsonism (DIP), and 3 with corticobasal degeneration (CBD). The heart to mediastinum (H/M) uptake ratio was calculated for each subjects. Patients who either had medical conditions that confused the MIBG SPECT results or who took medications that interfere with MIBG accumulation were excluded from the study. Results Both early and delayed H/M ratios were in patients with PD significantly lower than in controls (early, 1.34±0.15 vs 1.79±0.19; delayed, 1.29±0.15 vs 2.06±0.29, p<0.001). In patients with PD, both early and delayed H/M ratios were significantly lower than those in patients with MSA (early, 1.68±0.23; delayed, 1.80±0.34, p<0.001), DIP (early, 1.83±0.24; delayed, 2.07±0.4, p<0.001), or CBD (early, 1.85±0.01; delayed, 1.99±0.19, p<0.001). Two patients with DIP, who were within the range of patients with PD, showed clinically similar courses of PD. Conclusions This study demonstrates that cardiac-MIBG is a clinically powerful tools to differentiate PD from other parkinsonian syndromes. PMID:20396485

Children with High-Functioning Autism and Asperger's Syndrome: Can We Differentiate Their Cognitive Profiles?

ERIC Educational Resources Information Center

Planche, Pascale; Lemonnier, Eric

2012-01-01

The aim of this study was to investigate whether children with high-functioning autism (HFA) and Asperger's syndrome (AS) can be differentiated from each other and from typically developing children on their cognitive profiles. The present study included a total of 45 participants: children with autism (high-functioning autism or Asperger's…

Computerized analysis and duplication of mandibular motion.

PubMed

Knap, F J; Abler, J H; Richardson, B L

1975-05-01

A new digital system has been devised to analyze and duplicate jaw motion. The arrangement of the electronic system offers a range of versatility which includes graphic as well as numerical data analysis. The duplicator linkage is identical to the sensor linkage which, together with an accurate model transfer system, results in an encouraging level of accuracy in jaw-motion duplication. The data collected from normal subjects should offer some new knowledge in the normal motions of the mandible as well as establish a reference for comparison with abnormal masticatory function.

Expanding the mutational spectrum in Johanson-Blizzard syndrome: identification of whole exon deletions and duplications in the UBR1 gene by multiplex ligation-dependent probe amplification analysis.

PubMed

Sukalo, Maja; Schäflein, Eva; Schanze, Ina; Everman, David B; Rezaei, Nima; Argente, Jesús; Lorda-Sanchez, Isabel; Deshpande, Charu; Takahashi, Tsutomu; Kleger, Alexander; Zenker, Martin

2017-11-01

Johanson-Blizzard syndrome (JBS, MIM #243800) is a very rare autosomal recessive disorder characterized by exocrine pancreatic insufficiency, nasal wing hypoplasia, hypodontia, and other abnormalities. JBS is caused by mutations of the UBR1 gene (MIM *605981), encoding a ubiquitin ligase of the N-end rule pathway. Molecular findings in a total of 65 unrelated patients with a clinical diagnosis of JBS who were previously screened for UBR1 mutations by Sanger sequencing were reviewed and cases lacking a disease-causing UBR1 mutation on either one or both alleles were included in this study. In order to discover mutations that are not detectable by Sanger sequencing, we designed a probe set for multiplex ligation-dependent probe amplification (MLPA) analysis of the UBR1 gene and analyzed the copy number status of all 47 UBR1 exons. Our previous studies using Sanger sequencing could detect mutations in 93.1% of 130 disease-associated UBR1 alleles. Six patients with a highly suggestive clinical diagnosis of JBS and unsolved genotype were included in this study. MLPA analysis detected six alleles harboring exon deletions/duplications, thereby raising the mutation detection rate in the entire cohort to 97.7% (127/130 alleles). We conclude that single or multi-exon deletions or duplications account for a substantial proportion of JBS-associated UBR1 mutations. © 2017 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc.

Delimitation of duplicated segments and identification of their parental origin in two partial chromosome 3p duplications.

PubMed

Antonini, Sylvie; Kim, Chong A; Sugayama, Sofia M; Vianna-Morgante, Angela M

2002-11-22

Two chromosome 3 short arm duplications identified through G-banding were further investigated using fluorescence in situ hybridization (FISH) and polymerase chain reaction (PCR) of microsatellite markers, aiming at mapping breakpoints and disclosing mechanisms of origin of these chromosome aberrations. Patient 1 was found to be a mosaic: a 3p12 --> 3p21 duplication was observed in most of his cells, and a normal cell line occurred with a frequency of about 3% in blood. In situ hybridization of chromosome 3 short- and long-arm libraries confirmed the short-arm duplication. Using FISH of short-arm sequences, the YAC 961_h_3 was shown to contain the proximal breakpoint (3p12.1 or 3p12.2), and the distal breakpoint was located between the YACs 729_c_3 and 806_h_2, which are adjacent in the WC 3.10 contig (3p21.1). In Patient 2, G-banding indicated a 3p21 --> 3p24 duplication, without mosaicism. In situ hybridization of chromosome 3 short- and long-arm libraries confirmed the duplication of short-arm sequences. FISH of chromosome 3 sequences showed that the YAC 749_a_7 spanned the proximal breakpoint (3p21.33). The distal breakpoint mapped to the interval between YACs 932_b_6 (3p24.3) and 909_b_6 (3p25). In both cases, microsatellite genotyping pointed to a rearrangement between paternal sister chromatids. Copyright 2002 Wiley-Liss, Inc.

Somatic mosaicism of an intragenic FANCB duplication in both fibroblast and peripheral blood cells observed in a Fanconi anemia patient leads to milder phenotype.

PubMed

Asur, Rajalakshmi S; Kimble, Danielle C; Lach, Francis P; Jung, Moonjung; Donovan, Frank X; Kamat, Aparna; Noonan, Raymond J; Thomas, James W; Park, Morgan; Chines, Peter; Vlachos, Adrianna; Auerbach, Arleen D; Smogorzewska, Agata; Chandrasekharappa, Settara C

2018-01-01

Fanconi anemia (FA) is a rare disorder characterized by congenital malformations, progressive bone marrow failure, and predisposition to cancer. Patients harboring X-linked FANCB pathogenic variants usually present with severe congenital malformations resembling VACTERL syndrome with hydrocephalus. We employed the diepoxybutane (DEB) test for FA diagnosis, arrayCGH for detection of duplication, targeted capture and next-gen sequencing for defining the duplication breakpoint, PacBio sequencing of full-length FANCB aberrant transcript, FANCD2 ubiquitination and foci formation assays for the evaluation of FANCB protein function by viral transduction of FANCB-null cells with lentiviral FANCB WT and mutant expression constructs, and droplet digital PCR for quantitation of the duplication in the genomic DNA and cDNA. We describe here an FA-B patient with a mild phenotype. The DEB diagnostic test for FA revealed somatic mosaicism. We identified a 9154 bp intragenic duplication in FANCB, covering the first coding exon 3 and the flanking regions. A four bp homology (GTAG) present at both ends of the breakpoint is consistent with microhomology-mediated duplication mechanism. The duplicated allele gives rise to an aberrant transcript containing exon 3 duplication, predicted to introduce a stop codon in FANCB protein (p.A319*). Duplication levels in the peripheral blood DNA declined from 93% to 7.9% in the span of eleven years. Moreover, the patient fibroblasts have shown 8% of wild-type (WT) allele and his carrier mother showed higher than expected levels of WT allele (79% vs. 50%) in peripheral blood, suggesting that the duplication was highly unstable. Unlike sequence point variants, intragenic duplications are difficult to precisely define, accurately quantify, and may be very unstable, challenging the proper diagnosis. The reversion of genomic duplication to the WT allele results in somatic mosaicism and may explain the relatively milder phenotype displayed by the FA

[Intestinal volvulus due to yeyunal duplication].

PubMed

Rodríguez Iglesias, P; Carazo Palacios, M E; Lluna González, J; Ibáñez Pradas, V; Rodríguez Caraballo, L

2014-10-01

Duplications of the alimentary tract are congenital malformations. The ileum is the most commonly affected organ. A lot of duplications are incidentally diagnosed but most of patients present a combination of pain or complications such as obstructive symptoms, intestinal intussusception, perforation or volvulus. We report the case of a 6-years-old girl, with intermittent abdominal pain and vomits for two months long. Laboratory work was completely normal and in the radiology analysis (abdominal sonography and magnetic resonance) a cystic image with intestinal volvulus was observed. The patient underwent laparotomy, Ladd's procedure was done and the cyst was resected. In conclusion, if a patient is admitted with abdominal pain and obstructive symptoms, it is important to consider duplication of the alimentary tract as a possible diagnosis.

Performance of probabilistic method to detect duplicate individual case safety reports.

PubMed

Tregunno, Philip Michael; Fink, Dorthe Bech; Fernandez-Fernandez, Cristina; Lázaro-Bengoa, Edurne; Norén, G Niklas

2014-04-01

Individual case reports of suspected harm from medicines are fundamental for signal detection in postmarketing surveillance. Their effective analysis requires reliable data and one challenge is report duplication. These are multiple unlinked records describing the same suspected adverse drug reaction (ADR) in a particular patient. They distort statistical screening and can mislead clinical assessment. Many organisations rely on rule-based detection, but probabilistic record matching is an alternative. The aim of this study was to evaluate probabilistic record matching for duplicate detection, and to characterise the main sources of duplicate reports within each data set. vigiMatch™, a published probabilistic record matching algorithm, was applied to the WHO global individual case safety reports database, VigiBase(®), for reports submitted between 2000 and 2010. Reported drugs, ADRs, patient age, sex, country of origin, and date of onset were considered in the matching. Suspected duplicates for the UK, Denmark, and Spain were reviewed and classified by the respective national centre. This included evaluation to determine whether confirmed duplicates had already been identified by in-house, rule-based screening. Furthermore, each confirmed duplicate was classified with respect to the likely source of duplication. For each country, the proportions of suspected duplicates classified as confirmed duplicates, likely duplicates, otherwise related, and unrelated were obtained. The proportions of confirmed or likely duplicates that were not previously known by the national organisation were determined, and variations in the rates of suspected duplicates across subsets of reports were characterised. Overall, 2.5 % of the reports with sufficient information to be evaluated by vigiMatch were classified as suspected duplicates. The rates for the three countries considered in this study were 1.4 % (UK), 1.0 % (Denmark), and 0.7 % (Spain). Higher rates of suspected duplicates

Reliable Multi-Label Learning via Conformal Predictor and Random Forest for Syndrome Differentiation of Chronic Fatigue in Traditional Chinese Medicine

PubMed Central

Wang, Huazhen; Liu, Xin; Lv, Bing; Yang, Fan; Hong, Yanzhu

2014-01-01

Objective Chronic Fatigue (CF) still remains unclear about its etiology, pathophysiology, nomenclature and diagnostic criteria in the medical community. Traditional Chinese medicine (TCM) adopts a unique diagnostic method, namely ‘bian zheng lun zhi’ or syndrome differentiation, to diagnose the CF with a set of syndrome factors, which can be regarded as the Multi-Label Learning (MLL) problem in the machine learning literature. To obtain an effective and reliable diagnostic tool, we use Conformal Predictor (CP), Random Forest (RF) and Problem Transformation method (PT) for the syndrome differentiation of CF. Methods and Materials In this work, using PT method, CP-RF is extended to handle MLL problem. CP-RF applies RF to measure the confidence level (p-value) of each label being the true label, and then selects multiple labels whose p-values are larger than the pre-defined significance level as the region prediction. In this paper, we compare the proposed CP-RF with typical CP-NBC(Naïve Bayes Classifier), CP-KNN(K-Nearest Neighbors) and ML-KNN on CF dataset, which consists of 736 cases. Specifically, 95 symptoms are used to identify CF, and four syndrome factors are employed in the syndrome differentiation, including ‘spleen deficiency’, ‘heart deficiency’, ‘liver stagnation’ and ‘qi deficiency’. The Results CP-RF demonstrates an outstanding performance beyond CP-NBC, CP-KNN and ML-KNN under the general metrics of subset accuracy, hamming loss, one-error, coverage, ranking loss and average precision. Furthermore, the performance of CP-RF remains steady at the large scale of confidence levels from 80% to 100%, which indicates its robustness to the threshold determination. In addition, the confidence evaluation provided by CP is valid and well-calibrated. Conclusion CP-RF not only offers outstanding performance but also provides valid confidence evaluation for the CF syndrome differentiation. It would be well applicable to TCM practitioners and

Evaluation of Hematological Parameters in the Differentiation of Subarachnoid Hemorrhage and Other Headache Syndromes.

PubMed

Goktekin, Mehmet C; Yilmaz, Mustafa

2018-06-01

In this research, the aim was to compare hematological data for the differentiation of subarachnoid hemorrhage, migraine attack, and other headache syndromes during consultation in emergency service. In this research, which was designed as retrospective case control study, hematological parameters (WBC, HgB, HCT, PLT, lymphocyte and neutrophile counts and neutrophile/lymphocyte rates) of the patients consulting to emergency service with SAH and migraine and other consulting patients complaining mainly from headache and having normal cranial CT were analysed. Sixty migraine attack patients (F/M:47/13), 57 SAH patients (F/M:30/27), and 53 patients except migraine having normal brain CT (F/M:36/17) who were consulted to emergency service with headache complaint were included in our research. WBC, Hct, HgB, MCV, PLT, MPV, LY, Neu counts, and NY/LY rates were found to differentiate between SAH and migraine. WBC, PLT, MPV, LY, and Neu rates were found to differentiate between SAH and HS patients. Only Hct, HgB, MCV, and NY/LY rates were found to differ meaningfully between SAH and migraine patients but these rates were not found to have meaningful difference between SAH and HS patients. In addition, an increase in WBC counts and NY/LY rates and decrease in MPV counts in ROC analysis were found to be more specific for SAH. WBC, HgB, HCT, PLT, lymphocyte and Neu counts, and NY/LY rates can indicate distinguishing SAH and migraine. WBC, HgB, HCT, PLT, lymphocyte and Neu counts can indicate to the clinician a differentiation of SAH and other headache syndromes.

Targeted tandem duplication of a large chromosomal segment in Aspergillus oryzae.

PubMed

Takahashi, Tadashi; Sato, Atsushi; Ogawa, Masahiro; Hanya, Yoshiki; Oguma, Tetsuya

2014-08-01

We describe here the first successful construction of a targeted tandem duplication of a large chromosomal segment in Aspergillus oryzae. The targeted tandem chromosomal duplication was achieved by using strains that had a 5'-deleted pyrG upstream of the region targeted for tandem chromosomal duplication and a 3'-deleted pyrG downstream of the target region. Consequently,strains bearing a 210-kb targeted tandem chromosomal duplication near the centromeric region of chromosome 8 and strains bearing a targeted tandem chromosomal duplication of a 700-kb region of chromosome 2 were successfully constructed. The strains bearing the tandem chromosomal duplication were efficiently obtained from the regenerated protoplast of the parental strains. However, the generation of the chromosomal duplication did not depend on the introduction of double-stranded breaks(DSBs) by I-SceI. The chromosomal duplications of these strains were stably maintained after five generations of culture under nonselective conditions. The strains bearing the tandem chromosomal duplication in the 700-kb region of chromosome 2 showed highly increased protease activity in solid-state culture, indicating that the duplication of large chromosomal segments could be a useful new breeding technology and gene analysis method.

De Novo duplication in Charcot-Marie-Tooth Type 1A

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mandich, P.; Bellone, E.; Ajmar, F.

1996-09-01

We read with interest the paper on {open_quotes}Prevalence and Origin of De Novo Duplications in Charcot-Marie-Tooth Disease Type 1A: First Report of a De Novo Duplication with a Maternal Origin,{close_quotes}. They reported their experience with 10 sporadic cases of Charcot-Marie-Tooth type 1A (CMT1A) in which it was demonstrated that the disease had arisen as the result of a de novo duplication. They analyzed the de novo-duplication families by using microsatellite markers and identified the parental origin of the duplication in eight cases. In one family the duplication was of maternal origin, whereas in the remaining seven cases it was ofmore » paternal origin. The authors concluded that their report was the first evidence of a de novo duplication of maternal origin, suggesting that this is not a phenomenon associated solely with male meiosis. 7 refs.« less

29 CFR 1912.4 - Avoidance of duplication.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 29 Labor 7 2010-07-01 2010-07-01 false Avoidance of duplication. 1912.4 Section 1912.4 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR (CONTINUED) ADVISORY COMMITTEES ON STANDARDS Organizational Matters § 1912.4 Avoidance of duplication. No...

29 CFR 1912.4 - Avoidance of duplication.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 29 Labor 7 2011-07-01 2011-07-01 false Avoidance of duplication. 1912.4 Section 1912.4 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR (CONTINUED) ADVISORY COMMITTEES ON STANDARDS Organizational Matters § 1912.4 Avoidance of duplication. No...

Acute monocytic leukemia and multiple abnormalities in a child with duplication of 1q detected by GTG-banding and SKY.

PubMed

Scrideli, Carlos A; Baruffi, Marcelo R; Squire, Jeremy A; Ramos, Ester S; Karaskova, Jana; Heck, Benjamin; Tone, Luiz G

2005-12-01

Patients with 1q duplication have demonstrated a wide range of multiple congenital abnormalities. Alterations involving this chromosomal region have being described in hematopoietic malignancies and a series of candidate genes that may be associated with neoplasias have been mapped in this region. We describe a case of partial trisomy 1q "syndrome" and acute monocytic leukemia. Cytogenetic study of the bone marrow cells by GTG-banding and spectral karyotyping (SKY) showed dup(1)(q23q44) in all cells analyzed. The dismorphological features with the dup(1q) suggest a constitutional chromosome alteration and the first, in our knowledge, association of a trisomy 1q "syndrome" with AML.

Adaptations to Endosymbiosis in a Cnidarian-Dinoflagellate Association: Differential Gene Expression and Specific Gene Duplications

PubMed Central

Magnone, Virginie; Allemand, Denis; Furla, Paola; Sabourault, Cécile

2011-01-01

Trophic endosymbiosis between anthozoans and photosynthetic dinoflagellates forms the key foundation of reef ecosystems. Dysfunction and collapse of symbiosis lead to bleaching (symbiont expulsion), which is responsible for the severe worldwide decline of coral reefs. Molecular signals are central to the stability of this partnership and are therefore closely related to coral health. To decipher inter-partner signaling, we developed genomic resources (cDNA library and microarrays) from the symbiotic sea anemone Anemonia viridis. Here we describe differential expression between symbiotic (also called zooxanthellate anemones) or aposymbiotic (also called bleached) A. viridis specimens, using microarray hybridizations and qPCR experiments. We mapped, for the first time, transcript abundance separately in the epidermal cell layer and the gastrodermal cells that host photosynthetic symbionts. Transcriptomic profiles showed large inter-individual variability, indicating that aposymbiosis could be induced by different pathways. We defined a restricted subset of 39 common genes that are characteristic of the symbiotic or aposymbiotic states. We demonstrated that transcription of many genes belonging to this set is specifically enhanced in the symbiotic cells (gastroderm). A model is proposed where the aposymbiotic and therefore heterotrophic state triggers vesicular trafficking, whereas the symbiotic and therefore autotrophic state favors metabolic exchanges between host and symbiont. Several genetic pathways were investigated in more detail: i) a key vitamin K–dependant process involved in the dinoflagellate-cnidarian recognition; ii) two cnidarian tissue-specific carbonic anhydrases involved in the carbon transfer from the environment to the intracellular symbionts; iii) host collagen synthesis, mostly supported by the symbiotic tissue. Further, we identified specific gene duplications and showed that the cnidarian-specific isoform was also up-regulated both in the

Sorting by Cuts, Joins, and Whole Chromosome Duplications.

PubMed

Zeira, Ron; Shamir, Ron

2017-02-01

Genome rearrangement problems have been extensively studied due to their importance in biology. Most studied models assumed a single copy per gene. However, in reality, duplicated genes are common, most notably in cancer. In this study, we make a step toward handling duplicated genes by considering a model that allows the atomic operations of cut, join, and whole chromosome duplication. Given two linear genomes, [Formula: see text] with one copy per gene and [Formula: see text] with two copies per gene, we give a linear time algorithm for computing a shortest sequence of operations transforming [Formula: see text] into [Formula: see text] such that all intermediate genomes are linear. We also show that computing an optimal sequence with fewest duplications is NP-hard.

Use of ATC to describe duplicate medications in primary care prescriptions.

PubMed

Lim, Chiao Mei; Aryani Md Yusof, Faridah; Selvarajah, Sharmini; Lim, Teck Onn

2011-10-01

We aimed to demonstrate the suitability of the Anatomical Therapeutic Chemical Classification (ATC) to describe duplicate drugs and duplicate drug classes in prescription data and describe the pattern of duplicates from public and private primary care clinics of Kuala Lumpur, Malaysia. We analyzed prescription data year 2005 from all 14 public clinics in Kuala Lumpur with 12,157 prescriptions, and a sample of 188 private clinics with 25,612 prescriptions. As ATC Level 5 code represents the molecule and Level 4 represents the pharmacological subgroup, we used repetitions of codes in the same prescription to describe duplicate drugs or duplicate drug classes and compared them between the public and private clinics. At Level 4 ATC, prescriptions with duplicates drug classes were 1.46% of all prescriptions in private and 0.04% in public clinics. At Level 5 ATC, prescriptions with duplicate drugs were 1.81% for private and 0.95% for public clinics. In private clinics at Level 5, 73.3% of prescriptions with duplicates involved systemic combination drugs; at Level 4, 40.3% involved systemic combination drugs. In the public sector at Level 5, 95.7% of prescriptions with duplicates involved topical products. Repetitions of the same ATC codes were mostly useful to describe duplicate medications; however, we recommend avoid using ATC codes for tropical products for this purpose due to ambiguity. Combination products were often involved in duplicate prescribing; redesign of these products might improve prescribing quality. Duplicates occurred more often in private clinics than public clinics in Malaysia.

Painful ovulation in a 46,XX SRY -ve adult male with SOX9 duplication.

PubMed

Shankara Narayana, Nandini; Kean, Anne-Maree; Ewans, Lisa; Ohnesorg, Thomas; Ayers, Katie L; Watson, Geoff; Vasilaras, Arthur; Sinclair, Andrew H; Twigg, Stephen M; Handelsman, David J

2017-01-01

46,XX disorders of sexual development (DSDs) occur rarely and result from disruptions of the genetic pathways underlying gonadal development and differentiation. We present a case of a young phenotypic male with 46,XX SRY-negative ovotesticular DSD resulting from a duplication upstream of SOX9 presenting with a painful testicular mass resulting from ovulation into an ovotestis. We present a literature review of ovulation in phenotypic men and discuss the role of SRY and SOX9 in testicular development, including the role of SOX9 upstream enhancer region duplication in female-to-male sex reversal. In mammals, the early gonad is bipotent and can differentiate into either a testis or an ovary. SRY is the master switch in testis determination, responsible for differentiation of the bipotent gonad into testis.SRY activates SOX9 gene, SOX9 as a transcription factor is the second major gene involved in male sex determination. SOX9 drives the proliferation of Sertoli cells and activates AMH/MIS repressing the ovary. SOX9 is sufficient to induce testis formation and can substitute for SRY function.Assessing karyotype and then determination of the presence or absence of Mullerian structures are necessary serial investigations in any case of DSD, except for mixed gonadal dysgenesis identified by karyotype alone.Treatment is ideal in a multidisciplinary setting with considerations to genetic (implications to family and reproductive recurrence risk), psychological aspects (sensitive individualized counseling including patient gender identity and preference), endocrinological (hormone replacement), surgical (cosmetic, prophylactic gonadectomy) fertility preservation and reproductive opportunities and metabolic health (cardiovascular and bones).

Gene Duplicability of Core Genes Is Highly Consistent across All Angiosperms.

PubMed

Li, Zhen; Defoort, Jonas; Tasdighian, Setareh; Maere, Steven; Van de Peer, Yves; De Smet, Riet

2016-02-01

Gene duplication is an important mechanism for adding to genomic novelty. Hence, which genes undergo duplication and are preserved following duplication is an important question. It has been observed that gene duplicability, or the ability of genes to be retained following duplication, is a nonrandom process, with certain genes being more amenable to survive duplication events than others. Primarily, gene essentiality and the type of duplication (small-scale versus large-scale) have been shown in different species to influence the (long-term) survival of novel genes. However, an overarching view of "gene duplicability" is lacking, mainly due to the fact that previous studies usually focused on individual species and did not account for the influence of genomic context and the time of duplication. Here, we present a large-scale study in which we investigated duplicate retention for 9178 gene families shared between 37 flowering plant species, referred to as angiosperm core gene families. For most gene families, we observe a strikingly consistent pattern of gene duplicability across species, with gene families being either primarily single-copy or multicopy in all species. An intermediate class contains gene families that are often retained in duplicate for periods extending to tens of millions of years after whole-genome duplication, but ultimately appear to be largely restored to singleton status, suggesting that these genes may be dosage balance sensitive. The distinction between single-copy and multicopy gene families is reflected in their functional annotation, with single-copy genes being mainly involved in the maintenance of genome stability and organelle function and multicopy genes in signaling, transport, and metabolism. The intermediate class was overrepresented in regulatory genes, further suggesting that these represent putative dosage-balance-sensitive genes. © 2016 American Society of Plant Biologists. All rights reserved.

Craniofacial duplication (diprosopus).

PubMed

Turpin, I M; Furnas, D W; Amlie, R N

1981-02-01

No congenital malformation in infants is more profound than anterior craniofacial duplication. The precise term for this rare anomaly is diprosopus, referring to a fetus with a single trunk, normal limbs, and varying degrees of facial duplication. A search of the world literature produced only 16 cases of diprosopus since 1864. Despite the rarity of this anomaly, three such infants were born in the Southern California area during the past year, making this the largest reported series to date. The three infants were born with two distinctly formed faces. Each had four separate eyes, two mouths, two noses, and two ears with a primitive ear or sinus tract at the plane of fusion. In addition, multiple congenital aberrations existed which involved a variety of internal organs. The pathogenesis of diprosopus is not well understood, but environmental stress early in embryologic development has been suggested as a possible factor. The apparent mechanism is a slowing of pregastrulation oxidation with resultant focal developmental arrests.

Oculo-auriculo-vertebral spectrum, cat eye, and distal 22q11 microdeletion syndromes: a unique double rearrangement.

PubMed

Torti, Erin E; Braddock, Stephen R; Bernreuter, Kristen; Batanian, Jacqueline R

2013-08-01

An array-CGH on 19-year-old male showed a proximal 1.11 Mb duplication and a distal 1.7 Mb deletion of 22q11.2 regions flanking the Velocardiofacial/DiGeorge syndrome region that remained intact. FISH analyses revealed both abnormalities to be on the same homolog 22. This double rearrangement lead to the co-existence of two syndromes: Cat eye and distal 22q11.2 microdeletion syndromes with a rare associated phenotype of oculo-auriculo-vertebral spectrum (OAVS). A review of the literature indicates that this is the second report of a proximal duplication and the fifth report of a distal deletion and OAVS suggestive of a possible OAVS candidate gene in this region. Copyright © 2013 Wiley Periodicals, Inc.

Cushing syndrome: update on testing.

PubMed

Raff, Hershel

2015-03-01

Endogenous hypercortisolism (Cushing syndrome) is one of the most enigmatic diseases in clinical medicine. The diagnosis and differential diagnosis of Cushing syndrome depend on proper laboratory evaluation. In this review, an update is provided on selected critical issues in the diagnosis and differential diagnosis of Cushing syndrome: the use of late-night salivary cortisol in initial diagnosis and for postoperative surveillance, and the use of prolactin measurement to improve the performance of inferior petrosal sinus sampling to distinguish Cushing disease from ectopic adrenocorticotropic hormone (ACTH) syndrome during differential diagnosis of ACTH-dependent Cushing syndrome. Copyright © 2015 Elsevier Inc. All rights reserved.

SHOX gene and conserved noncoding element deletions/duplications in Colombian patients with idiopathic short stature.

PubMed

Sandoval, Gloria Tatiana Vinasco; Jaimes, Giovanna Carola; Barrios, Mauricio Coll; Cespedes, Camila; Velasco, Harvy Mauricio

2014-03-01

SHOX gene mutations or haploinsufficiency cause a wide range of phenotypes such as Leri Weill dyschondrosteosis (LWD), Turner syndrome, and disproportionate short stature (DSS). However, this gene has also been found to be mutated in cases of idiopathic short stature (ISS) with a 3-15% frequency. In this study, the multiplex ligation-dependent probe amplification (MLPA) technique was employed to determine the frequency of SHOX gene mutations and their conserved noncoding elements (CNE) in Colombian patients with ISS. Patients were referred from different centers around the county. From a sample of 62 patients, 8.1% deletions and insertions in the intragenic regions and in the CNE were found. This result is similar to others published in other countries. Moreover, an isolated case of CNE 9 duplication and a new intron 6b deletion in another patient, associated with ISS, are described. This is one of the first studies of a Latin American population in which deletions/duplications of the SHOX gene and its CNE are examined in patients with ISS.

SHOX gene and conserved noncoding element deletions/duplications in Colombian patients with idiopathic short stature

PubMed Central

Sandoval, Gloria Tatiana Vinasco; Jaimes, Giovanna Carola; Barrios, Mauricio Coll; Cespedes, Camila; Velasco, Harvy Mauricio

2014-01-01

SHOX gene mutations or haploinsufficiency cause a wide range of phenotypes such as Leri Weill dyschondrosteosis (LWD), Turner syndrome, and disproportionate short stature (DSS). However, this gene has also been found to be mutated in cases of idiopathic short stature (ISS) with a 3–15% frequency. In this study, the multiplex ligation-dependent probe amplification (MLPA) technique was employed to determine the frequency of SHOX gene mutations and their conserved noncoding elements (CNE) in Colombian patients with ISS. Patients were referred from different centers around the county. From a sample of 62 patients, 8.1% deletions and insertions in the intragenic regions and in the CNE were found. This result is similar to others published in other countries. Moreover, an isolated case of CNE 9 duplication and a new intron 6b deletion in another patient, associated with ISS, are described. This is one of the first studies of a Latin American population in which deletions/duplications of the SHOX gene and its CNE are examined in patients with ISS. PMID:24689071

[Clinical application of moving cupping therapy based on skin reaction observation and syndrome differentiation].

PubMed

Deng, Xiao-Lan; Chen, Bo; Chen, Ze-Lin

2014-12-01

The diagnostic evidence on clinical diseases and theoretic basis of moving cupping therapy were ex- plored in the paper. By the observation of the local reaction, such as skin appearance and color, the affected location, duration of sickness and nature of disease were judged. Different moving cupping methods were selected for different disorders. It was discovered that the property of syndromes should be recognized by the palpation on skin and muscle in the moving cupping therapy so that the pathogenesis and treating principle could be carefully determined. The moving cupping therapy is the important component of body surface therapy. Skin reaction observation and syndrome differentiation is the essential guidance of the moving cupping therapy.

[Elements of a clinical differential diagnosis between Asperger syndrome and the schizoid/paranoid personality].

PubMed

Mottron, Laurent; Soulières, Isabelle; Ménard, Edith

2007-01-01

Individuals with Asperger syndrome may, when exposed to hostility (e.g. bullying at school or at work), develop hostile ideas against their social environment, sometimes leading to aggression. These ideas and acts may be confounded with those arising from a persecutory state in schizoid or schizotypal personality, or even schizophrenia. These entities can be confounded with Asperger syndrome due to their permanent nature, and the presence of atypical social and emotional behaviours. This paper proposes cognitive (Wechsler profile), developmental (course of hostile behaviours), discursive (qualitative features of discourse reporting hostile thoughts), which may contribute to differential diagnosis in the presence of hostile thoughts and behaviours. Consequences for case management are also reported.

Soybean (Glycine max) expansin gene superfamily origins: segmental and tandem duplication events followed by divergent selection among subfamilies

PubMed Central

2014-01-01

Background Expansins are plant cell wall loosening proteins that are involved in cell enlargement and a variety of other developmental processes. The expansin superfamily contains four subfamilies; namely, α-expansin (EXPA), β-expansin (EXPB), expansin-like A (EXLA), and expansin-like B (EXLB). Although the genome sequencing of soybeans is complete, our knowledge about the pattern of expansion and evolutionary history of soybean expansin genes remains limited. Results A total of 75 expansin genes were identified in the soybean genome, and grouped into four subfamilies based on their phylogenetic relationships. Structural analysis revealed that the expansin genes are conserved in each subfamily, but are divergent among subfamilies. Furthermore, in soybean and Arabidopsis, the expansin gene family has been mainly expanded through tandem and segmental duplications; however, in rice, segmental duplication appears to be the dominant process that generates this superfamily. The transcriptome atlas revealed notable differential expression in either transcript abundance or expression patterns under normal growth conditions. This finding was consistent with the differential distribution of the cis-elements in the promoter region, and indicated wide functional divergence in this superfamily. Moreover, some critical amino acids that contribute to functional divergence and positive selection were detected. Finally, site model and branch-site model analysis of positive selection indicated that the soybean expansin gene superfamily is under strong positive selection, and that divergent selection constraints might have influenced the evolution of the four subfamilies. Conclusion This study demonstrated that the soybean expansin gene superfamily has expanded through tandem and segmental duplication. Differential expression indicated wide functional divergence in this superfamily. Furthermore, positive selection analysis revealed that divergent selection constraints might have

Gallbladder Duplication: Evaluation, Treatment, and Classification

DTIC Science & Technology

2010-02-01

2009; revised 16 December 2009; accepted 16 December 2009h o th 0 d Key words: Duplicate gallbladder; Hepatobiliary embryology ; Multiple gallbladders...anatomic variations [5]. These three types vary depending upon the embryologic development and occur in the same manner as duplicated gallbladders. Given... embryology and adds a third group that occurs when there is a combination of types 1 and 2 anatomy. The triple combined group occurs from a split in

The short arm deletion syndrome of chromosome 4 (4p- syndrome).

PubMed

Zellweger, H; Bardach, J; Bordwell, J; Williams, K

1975-01-01

Partial deletion of the short arm of chromosome 4 (4p-) represents another (rare) cause of cleft lip and cleft palate. Further characteristic manifestations of the syndrome (also called Wolf or Wolf-Hirschhorn syndrome) are growth failure, microcephaly, prominent glabella, hypertelorism, beaked nose, poorly differentiated and low set ears, cardiac and renal malformation and hypospadias. Life expectancy is often shortened. The 4p- syndrome has many features in common with another deletion syndrome, the cri-du-chat syndrome, and also with the Smith-Lemli-Opitz syndrome. The latter is a hereditary condition with normal karyotype. The cri-du-chat syndrome is characterized by a peculiar high-pitched, mewing cry and can be differentiated from the Wolf syndrome by the different staining characteristics (banding) of chromosomes 4 and 5.

Duplicates, redundancies and inconsistencies in the primary nucleotide databases: a descriptive study

PubMed Central

Chen, Qingyu; Zobel, Justin; Verspoor, Karin

2017-01-01

GenBank, the EMBL European Nucleotide Archive and the DNA DataBank of Japan, known collectively as the International Nucleotide Sequence Database Collaboration or INSDC, are the three most significant nucleotide sequence databases. Their records are derived from laboratory work undertaken by different individuals, by different teams, with a range of technologies and assumptions and over a period of decades. As a consequence, they contain a great many duplicates, redundancies and inconsistencies, but neither the prevalence nor the characteristics of various types of duplicates have been rigorously assessed. Existing duplicate detection methods in bioinformatics only address specific duplicate types, with inconsistent assumptions; and the impact of duplicates in bioinformatics databases has not been carefully assessed, making it difficult to judge the value of such methods. Our goal is to assess the scale, kinds and impact of duplicates in bioinformatics databases, through a retrospective analysis of merged groups in INSDC databases. Our outcomes are threefold: (1) We analyse a benchmark dataset consisting of duplicates manually identified in INSDC—a dataset of 67 888 merged groups with 111 823 duplicate pairs across 21 organisms from INSDC databases – in terms of the prevalence, types and impacts of duplicates. (2) We categorize duplicates at both sequence and annotation level, with supporting quantitative statistics, showing that different organisms have different prevalence of distinct kinds of duplicate. (3) We show that the presence of duplicates has practical impact via a simple case study on duplicates, in terms of GC content and melting temperature. We demonstrate that duplicates not only introduce redundancy, but can lead to inconsistent results for certain tasks. Our findings lead to a better understanding of the problem of duplication in biological databases. Database URL: the merged records are available at https

Typewriting: Toward Duplicating Success

ERIC Educational Resources Information Center

Orsborn, Karen J.

1977-01-01

A description of two projects (secretarial handbook and memo pad and personalized stationery) for use in teaching the duplication process that will capture the interests of students in an advanced typewriting class. (HD)

Identification of approximately duplicate material records in ERP systems

NASA Astrophysics Data System (ADS)

Zong, Wei; Wu, Feng; Chu, Lap-Keung; Sculli, Domenic

2017-03-01

The quality of master data is crucial for the accurate functioning of the various modules of an enterprise resource planning (ERP) system. This study addresses specific data problems arising from the generation of approximately duplicate material records in ERP databases. Such problems are mainly due to the firm's lack of unique and global identifiers for the material records, and to the arbitrary assignment of alternative names for the same material by various users. Traditional duplicate detection methods are ineffective in identifying such approximately duplicate material records because these methods typically rely on string comparisons of each field. To address this problem, a machine learning-based framework is developed to recognise semantic similarity between strings and to further identify and reunify approximately duplicate material records - a process referred to as de-duplication in this article. First, the keywords of the material records are extracted to form vectors of discriminating words. Second, a machine learning method using a probabilistic neural network is applied to determine the semantic similarity between these material records. The approach was evaluated using data from a real case study. The test results indicate that the proposed method outperforms traditional algorithms in identifying approximately duplicate material records.

Identification of three duplicated Spin genes in medaka (Oryzias latipes).

PubMed

Wang, Xiao-Lei; Mei, Jie; Sun, Min; Hong, Yun-Han; Gui, Jian-Fang

2005-05-09

Gene and genomic duplications are very important and frequent events in fish evolution, and the divergence of duplicated genes in sequences and functions is a focus of research on gene evolution. Here, we report the identification and characterization of three duplicated Spindlin (Spin) genes from medaka (Oryzias latipes): OlSpinA, OlSpinB, and OlSpinC. Molecular cloning, genomic DNA Blast analysis and phylogenetic relationship analysis demonstrated that the three duplicated OlSpin genes should belong to gene duplication. Furthermore, Western blot analysis revealed significant expression differences of the three OlSpins among different tissues and during embryogenesis in medaka, and suggested that sequence and functional divergence might have occurred in evolution among them.

Duplication of 17(p11.2p11.2) in a male child with autism and severe language delay.

PubMed

Nakamine, Alisa; Ouchanov, Leonid; Jiménez, Patricia; Manghi, Elina R; Esquivel, Marcela; Monge, Silvia; Fallas, Marietha; Burton, Barbara K; Szomju, Barbara; Elsea, Sarah H; Marshall, Christian R; Scherer, Stephen W; McInnes, L Alison

2008-03-01

Duplications of 17(p11.2p11.2) have been associated with various behavioral manifestations including attention deficits, obsessive-compulsive symptoms, autistic traits, and language delay. We are conducting a genetic study of autism and are screening all cases for submicroscopic chromosomal abnormalities, in addition to standard karyotyping, and fragile X testing. Using array-based comparative genomic hybridization analysis of data from the Affymetrix GeneChip(R) Human Mapping Array set, we detected a duplication of approximately 3.3 Mb on chromosome 17p11.2 in a male child with autism and severe expressive language delay. The duplication was confirmed by measuring the copy number of genomic DNA using quantitative polymerase chain reaction. Gene expression analyses revealed increased expression of three candidate genes for the Smith-Magenis neurobehavioral phenotype, RAI1, DRG2, and RASD1, in transformed lymphocytes from Case 81A, suggesting gene dosage effects. Our results add to a growing body of evidence suggesting that duplications of 17(p11.2p11.2) result in language delay as well as autism and related phenotypes. As Smith-Magenis syndrome is also associated with language delay, a gene involved in acquisition of language may lie within this interval. Whether a parent of origin effect, gender of the case, the presence of allelic variation, or changes in expression of genes outside the breakpoints influence the resultant phenotype remains to be determined. (c) 2007 Wiley-Liss, Inc.

Duplicated genes evolve independently in allopolyploid cotton.

Treesearch

Richard C. Cronn; Randall L. Small; Jonathan F. Wendel

1999-01-01

Of the many processes that generate gene duplications, polyploidy is unique in that entire genomes are duplicated. This process has been important in the evolution of many eukaryotic groups, and it occurs with high frequency in plants. Recent evidence suggests that polyploidization may be accompanied by rapid genomic changes, but the evolutionary fate of discrete loci...

Tempo and Mode of Gene Duplication in Mammalian Ribosomal Protein Evolution

PubMed Central

Gajdosik, Matthew D.; Simon, Amanda; Nelson, Craig E.

2014-01-01

Gene duplication has been widely recognized as a major driver of evolutionary change and organismal complexity through the generation of multi-gene families. Therefore, understanding the forces that govern the evolution of gene families through the retention or loss of duplicated genes is fundamentally important in our efforts to study genome evolution. Previous work from our lab has shown that ribosomal protein (RP) genes constitute one of the largest classes of conserved duplicated genes in mammals. This result was surprising due to the fact that ribosomal protein genes evolve slowly and transcript levels are very tightly regulated. In our present study, we identified and characterized all RP duplicates in eight mammalian genomes in order to investigate the tempo and mode of ribosomal protein family evolution. We show that a sizable number of duplicates are transcriptionally active and are very highly conserved. Furthermore, we conclude that existing gene duplication models do not readily account for the preservation of a very large number of intact retroduplicated ribosomal protein (RT-RP) genes observed in mammalian genomes. We suggest that selection against dominant-negative mutations may underlie the unexpected retention and conservation of duplicated RP genes, and may shape the fate of newly duplicated genes, regardless of duplication mechanism. PMID:25369106

Partial duplication of head--a rare congenital anomaly.

PubMed

Hemachandran, Manikkapurath; Radotra, Bishan Dass

2004-10-01

Duplication of notochord results in rare congenital anomalies like double headed monsters, with or without trunk/limb duplication, depending upon the extent of notochordal abnormality. Here we describe the morphological abnormalities in a case of partial duplication of cranial structures with fusion of the two. Autopsy findings suggest that the bifurcation of the neural tube took place around 4th to 6th week of gestation. There are only few reports in English literature describing the autopsy findings of such an anomaly, which is termed as Diprosopus triophthalmus in the modern literature.

Diagnostic Accuracy of Copeptin in the Differential Diagnosis of the Polyuria-polydipsia Syndrome: A Prospective Multicenter Study.

PubMed

Timper, Katharina; Fenske, Wiebke; Kühn, Felix; Frech, Nica; Arici, Birsen; Rutishauser, Jonas; Kopp, Peter; Allolio, Bruno; Stettler, Christoph; Müller, Beat; Katan, Mira; Christ-Crain, Mirjam

2015-06-01

The polyuria-polydipsia syndrome comprises primary polydipsia (PP) and central and nephrogenic diabetes insipidus (DI). Correctly discriminating these entities is mandatory, given that inadequate treatment causes serious complications. The diagnostic "gold standard" is the water deprivation test with assessment of arginine vasopressin (AVP) activity. However, test interpretation and AVP measurement are challenging. The objective was to evaluate the accuracy of copeptin, a stable peptide stoichiometrically cosecreted with AVP, in the differential diagnosis of polyuria-polydipsia syndrome. This was a prospective multicenter observational cohort study from four Swiss or German tertiary referral centers of adults >18 years old with the history of polyuria and polydipsia. A standardized combined water deprivation/3% saline infusion test was performed and terminated when serum sodium exceeded 147 mmol/L. Circulating copeptin and AVP levels were measured regularly throughout the test. Final diagnosis was based on the water deprivation/saline infusion test results, clinical information, and the treatment response. Fifty-five patients were enrolled (11 with complete central DI, 16 with partial central DI, 18 with PP, and 10 with nephrogenic DI). Without prior thirsting, a single baseline copeptin level >21.4 pmol/L differentiated nephrogenic DI from other etiologies with a 100% sensitivity and specificity, rendering a water deprivation testing unnecessary in such cases. A stimulated copeptin >4.9 pmol/L (at sodium levels >147 mmol/L) differentiated between patients with PP and patients with partial central DI with a 94.0% specificity and a 94.4% sensitivity. A stimulated AVP >1.8 pg/mL differentiated between the same categories with a 93.0% specificity and a 83.0% sensitivity. This study was limited by incorporation bias from including AVP levels as a diagnostic criterion. Copeptin is a promising new tool in the differential diagnosis of the polyuria-polydipsia syndrome

Unusual X-chromosome inactivation pattern in patients with Xp11.23-p11.22 duplication: Report and review.

PubMed

Di-Battista, Adriana; Meloni, Vera Ayres; da Silva, Magnus Dias; Moysés-Oliveira, Mariana; Melaragno, Maria Isabel

2016-12-01

In females carrying structural rearrangements of an X-chromosome, cells with the best dosage balance are preferentially selected, frequently resulting in a skewed inactivation pattern and amelioration of the phenotype. The Xp11.23-p11.22 region is involved in a recently described microduplication syndrome associated with severe clinical consequences in males and females, causing intellectual disability, behavior problems, epilepsy with electroencephalogram anomalies, minor facial anomalies, and early onset of puberty. Female carriers usually present an unusual X-chromosome inactivation pattern in favor of the aberrant chromosome, resulting in functional disomy of the duplicated segment. Here, we describe a girl carrying a de novo ∼9.7 Mb Xp11.3-p11.22 duplication of paternal origin and skewed X-chromosome inactivation pattern of the normal X-chromosome. We reviewed other cases previously reported and determined the minimal critical region possibly responsible for this unusual inactivation pattern. The critical region encompasses 36 RefSeq genes, including at least 10 oncogenes and/or genes related to the cell cycle control. We discuss the molecular mechanisms that underlie the positive selection of the cells with the active duplicated chromosome. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Chromosomal duplications in bacteria, fruit flies, and humans

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lupski, J.R.; Weinstock, G.M.; Roth, J.R.

1996-01-01

Tandem duplication of chromosomal segments has been recognized as a frequent mutational mechanism in several genetic model systems. In bacteria, fruit flies, and humans, duplications form by similar molecular mechanisms and appear to be important in genome evolution. 80 refs.

Adrenal GIPR expression and chromosome 19q13 microduplications in GIP-dependent Cushing's syndrome.

PubMed

Lecoq, Anne-Lise; Stratakis, Constantine A; Viengchareun, Say; Chaligné, Ronan; Tosca, Lucie; Deméocq, Vianney; Hage, Mirella; Berthon, Annabel; Faucz, Fabio R; Hanna, Patrick; Boyer, Hadrien-Gaël; Servant, Nicolas; Salenave, Sylvie; Tachdjian, Gérard; Adam, Clovis; Benhamo, Vanessa; Clauser, Eric; Guiochon-Mantel, Anne; Young, Jacques; Lombès, Marc; Bourdeau, Isabelle; Maiter, Dominique; Tabarin, Antoine; Bertherat, Jérôme; Lefebvre, Hervé; de Herder, Wouter; Louiset, Estelle; Lacroix, André; Chanson, Philippe; Bouligand, Jérôme; Kamenický, Peter

2017-09-21

GIP-dependent Cushing's syndrome is caused by ectopic expression of glucose-dependent insulinotropic polypeptide receptor (GIPR) in cortisol-producing adrenal adenomas or in bilateral macronodular adrenal hyperplasias. Molecular mechanisms leading to ectopic GIPR expression in adrenal tissue are not known. Here we performed molecular analyses on adrenocortical adenomas and bilateral macronodular adrenal hyperplasias obtained from 14 patients with GIP-dependent adrenal Cushing's syndrome and one patient with GIP-dependent aldosteronism. GIPR expression in all adenoma and hyperplasia samples occurred through transcriptional activation of a single allele of the GIPR gene. While no abnormality was detected in proximal GIPR promoter methylation, we identified somatic duplications in chromosome region 19q13.32 containing the GIPR locus in the adrenocortical lesions derived from 3 patients. In 2 adenoma samples, the duplicated 19q13.32 region was rearranged with other chromosome regions, whereas a single tissue sample with hyperplasia had a 19q duplication only. We demonstrated that juxtaposition with cis-acting regulatory sequences such as glucocorticoid response elements in the newly identified genomic environment drives abnormal expression of the translocated GIPR allele in adenoma cells. Altogether, our results provide insight into the molecular pathogenesis of GIP-dependent Cushing's syndrome, occurring through monoallelic transcriptional activation of GIPR driven in some adrenal lesions by structural variations.

β2-microglobulin gene duplication in cetartiodactyla remains intact only in pigs and possibly confers selective advantage to the species.

PubMed

Le, Thong Minh; Le, Quy Van Chanh; Truong, Dung Minh; Lee, Hye-Jeong; Choi, Min-Kyeung; Cho, Hyesun; Chung, Hak-Jae; Kim, Jin-Hoi; Do, Jeong-Tae; Song, Hyuk; Park, Chankyu

2017-01-01

Several β2-microglobulin (B2M) -bound protein complexes undertake key roles in various immune system pathways, including the neonatal Fc receptor (FcRn), cluster of differentiation 1 (CD1) protein, non-classical major histocompatibility complex (MHC), and well-known MHC class I molecules. Therefore, the duplication of B2M may lead to an increase in the biological competence of organisms to the environment. Based on the pig genome assembly SSC10.2, a segmental duplication of ~45.5 kb, encoding the entire B2M protein, was identified in pig chromosome 1. Through experimental validation, we confirmed the functional duplication of the B2M gene with a completely identical coding sequence between two copies in pigs. Considering the importance of B2M in the immune system, we performed the phylogenetic analysis of B2M duplication in ten mammalian species, confirming the presence of B2M duplication in cetartioldactyls, like cattle, sheep, goats, pigs and whales, but non-cetartiodactyl species, like mice, cats, dogs, horses, and humans. The density of long interspersed nuclear element (LINE) at the edges of duplicated blocks (39 to 66%) was found to be 2 to 3-fold higher than the average (20.12%) of the pig genome, suggesting its role in the duplication event. The B2M mRNA expression level in pigs was 12.71 and 7.57 times (2-ΔΔCt values) higher than humans and mice, respectively. However, we were unable to experimentally demonstrate the difference in the level of B2M protein because species specific anti-B2M antibodies are not available. We reported, for the first time, the functional duplication of the B2M gene in animals. The identification of partially remaining duplicated B2M sequences in the genomes of only cetartiodactyls indicates that the event was lineage specific. B2M duplication could be beneficial to the immune system of pigs by increasing the availability of MHC class I light chain protein, B2M, to complex with the proteins encoded by the relatively large

Prevention of data duplication for high throughput sequencing repositories

PubMed Central

Gabdank, Idan; Chan, Esther T; Davidson, Jean M; Hilton, Jason A; Davis, Carrie A; Baymuradov, Ulugbek K; Narayanan, Aditi; Onate, Kathrina C; Graham, Keenan; Miyasato, Stuart R; Dreszer, Timothy R; Strattan, J Seth; Jolanki, Otto; Tanaka, Forrest Y; Hitz, Benjamin C

2018-01-01

Abstract Prevention of unintended duplication is one of the ongoing challenges many databases have to address. Working with high-throughput sequencing data, the complexity of that challenge increases with the complexity of the definition of a duplicate. In a computational data model, a data object represents a real entity like a reagent or a biosample. This representation is similar to how a card represents a book in a paper library catalog. Duplicated data objects not only waste storage, they can mislead users into assuming the model represents more than the single entity. Even if it is clear that two objects represent a single entity, data duplication opens the door to potential inconsistencies between the objects since the content of the duplicated objects can be updated independently, allowing divergence of the metadata associated with the objects. Analogously to a situation in which a catalog in a paper library would contain by mistake two cards for a single copy of a book. If these cards are listing simultaneously two different individuals as current book borrowers, it would be difficult to determine which borrower (out of the two listed) actually has the book. Unfortunately, in a large database with multiple submitters, unintended duplication is to be expected. In this article, we present three principal guidelines the Encyclopedia of DNA Elements (ENCODE) Portal follows in order to prevent unintended duplication of both actual files and data objects: definition of identifiable data objects (I), object uniqueness validation (II) and de-duplication mechanism (III). In addition to explaining our modus operandi, we elaborate on the methods used for identification of sequencing data files. Comparison of the approach taken by the ENCODE Portal vs other widely used biological data repositories is provided. Database URL: https://www.encodeproject.org/ PMID:29688363

Duplication of 20qter and deletion of 20pter due to paternal pericentric inversion: patient report and review of 20qter duplications.

PubMed

Starr, Lois J; Truemper, Edward J; Pickering, Diane L; Sanger, Warren G; Olney, Ann Haskins

2014-08-01

Duplications of the terminal long arm of chromosome 20 are rare chromosomal anomalies. We report a male infant found on array comparative genomic hybridization analysis to have a 19.5 Mb duplication of chromosome 20q13.12-13.33, as well as an 886 kb deletion of 20p13 at 18,580-904,299 bp. This anomaly occurred as the recombinant product of a paternal pericentric inversion. There have been 23 reported clinical cases involving 20qter duplications; however, to our knowledge this is only the second reported patient with a paternal pericentric inversion resulting in 46,XY,rec(20)dup(20q). This patient shares many characteristics with previously described patients with 20qter duplications, including microphthalmia, anteverted nares, long ears, cleft palate, small chin, dimpled chin, cardiac malformations, and normal intrauterine growth. While there is variable morbidity in patients with terminal duplications of 20q, a review of previously reported patients and comparison to our patient's findings shows significant phenotypic similarity. © 2014 Wiley Periodicals, Inc.

Duplicates, redundancies and inconsistencies in the primary nucleotide databases: a descriptive study.

PubMed

Chen, Qingyu; Zobel, Justin; Verspoor, Karin

2017-01-01

GenBank, the EMBL European Nucleotide Archive and the DNA DataBank of Japan, known collectively as the International Nucleotide Sequence Database Collaboration or INSDC, are the three most significant nucleotide sequence databases. Their records are derived from laboratory work undertaken by different individuals, by different teams, with a range of technologies and assumptions and over a period of decades. As a consequence, they contain a great many duplicates, redundancies and inconsistencies, but neither the prevalence nor the characteristics of various types of duplicates have been rigorously assessed. Existing duplicate detection methods in bioinformatics only address specific duplicate types, with inconsistent assumptions; and the impact of duplicates in bioinformatics databases has not been carefully assessed, making it difficult to judge the value of such methods. Our goal is to assess the scale, kinds and impact of duplicates in bioinformatics databases, through a retrospective analysis of merged groups in INSDC databases. Our outcomes are threefold: (1) We analyse a benchmark dataset consisting of duplicates manually identified in INSDC-a dataset of 67 888 merged groups with 111 823 duplicate pairs across 21 organisms from INSDC databases - in terms of the prevalence, types and impacts of duplicates. (2) We categorize duplicates at both sequence and annotation level, with supporting quantitative statistics, showing that different organisms have different prevalence of distinct kinds of duplicate. (3) We show that the presence of duplicates has practical impact via a simple case study on duplicates, in terms of GC content and melting temperature. We demonstrate that duplicates not only introduce redundancy, but can lead to inconsistent results for certain tasks. Our findings lead to a better understanding of the problem of duplication in biological databases.Database URL: the merged records are available at https

A limited role for gene duplications in the evolution of platypus venom.

PubMed

Wong, Emily S W; Papenfuss, Anthony T; Whittington, Camilla M; Warren, Wesley C; Belov, Katherine

2012-01-01

Gene duplication followed by adaptive selection is believed to be the primary driver of venom evolution. However, to date, no studies have evaluated the importance of gene duplications for venom evolution using a genomic approach. The availability of a sequenced genome and a venom gland transcriptome for the enigmatic platypus provides a unique opportunity to explore the role that gene duplication plays in venom evolution. Here, we identify gene duplication events and correlate them with expressed transcripts in an in-season venom gland. Gene duplicates (1,508) were identified. These duplicated pairs (421), including genes that have undergone multiple rounds of gene duplications, were expressed in the venom gland. The majority of these genes are involved in metabolism and protein synthesis not toxin functions. Twelve secretory genes including serine proteases, metalloproteinases, and protease inhibitors likely to produce symptoms of envenomation such as vasodilation and pain were detected. Only 16 of 107 platypus genes with high similarity to known toxins evolved through gene duplication. Platypus venom C-type natriuretic peptides and nerve growth factor do not possess lineage-specific gene duplicates. Extensive duplications, believed to increase the potency of toxic content and promote toxin diversification, were not found. This is the first study to take a genome-wide approach in order to examine the impact of gene duplication on venom evolution. Our findings support the idea that adaptive selection acts on gene duplicates to drive the independent evolution and functional diversification of similar venom genes in venomous species. However, gene duplications alone do not explain the "venome" of the platypus. Other mechanisms, such as alternative splicing and mutation, may be important in venom innovation.

A Limited Role for Gene Duplications in the Evolution of Platypus Venom

PubMed Central

Wong, Emily S. W.; Papenfuss, Anthony T.; Whittington, Camilla M.; Warren, Wesley C.; Belov, Katherine

2012-01-01

Gene duplication followed by adaptive selection is believed to be the primary driver of venom evolution. However, to date, no studies have evaluated the importance of gene duplications for venom evolution using a genomic approach. The availability of a sequenced genome and a venom gland transcriptome for the enigmatic platypus provides a unique opportunity to explore the role that gene duplication plays in venom evolution. Here, we identify gene duplication events and correlate them with expressed transcripts in an in-season venom gland. Gene duplicates (1,508) were identified. These duplicated pairs (421), including genes that have undergone multiple rounds of gene duplications, were expressed in the venom gland. The majority of these genes are involved in metabolism and protein synthesis not toxin functions. Twelve secretory genes including serine proteases, metalloproteinases, and protease inhibitors likely to produce symptoms of envenomation such as vasodilation and pain were detected. Only 16 of 107 platypus genes with high similarity to known toxins evolved through gene duplication. Platypus venom C-type natriuretic peptides and nerve growth factor do not possess lineage-specific gene duplicates. Extensive duplications, believed to increase the potency of toxic content and promote toxin diversification, were not found. This is the first study to take a genome-wide approach in order to examine the impact of gene duplication on venom evolution. Our findings support the idea that adaptive selection acts on gene duplicates to drive the independent evolution and functional diversification of similar venom genes in venomous species. However, gene duplications alone do not explain the “venome” of the platypus. Other mechanisms, such as alternative splicing and mutation, may be important in venom innovation. PMID:21816864

Duplication Is Ubiquitous

ERIC Educational Resources Information Center

Tenopir, Carol

2005-01-01

This article discusses how Phil Davis, Life Sciences Bibliographer at Cornell University, found duplicate articles in Emerald/MCB University Press journals. According to Davis, he has found hundreds of examples of the same article published in more than one journal in at least 73 Emerald/MCB journals over 30 years. This article gives the details…

Painful ovulation in a 46,XX SRY −ve adult male with SOX9 duplication

PubMed Central

Kean, Anne-Maree; Ewans, Lisa; Ohnesorg, Thomas; Ayers, Katie L; Watson, Geoff; Vasilaras, Arthur; Sinclair, Andrew H; Twigg, Stephen M; Handelsman, David J

2017-01-01

46,XX disorders of sexual development (DSDs) occur rarely and result from disruptions of the genetic pathways underlying gonadal development and differentiation. We present a case of a young phenotypic male with 46,XX SRY-negative ovotesticular DSD resulting from a duplication upstream of SOX9 presenting with a painful testicular mass resulting from ovulation into an ovotestis. We present a literature review of ovulation in phenotypic men and discuss the role of SRY and SOX9 in testicular development, including the role of SOX9 upstream enhancer region duplication in female-to-male sex reversal. Learning points: In mammals, the early gonad is bipotent and can differentiate into either a testis or an ovary. SRY is the master switch in testis determination, responsible for differentiation of the bipotent gonad into testis. SRY activates SOX9 gene, SOX9 as a transcription factor is the second major gene involved in male sex determination. SOX9 drives the proliferation of Sertoli cells and activates AMH/MIS repressing the ovary. SOX9 is sufficient to induce testis formation and can substitute for SRY function. Assessing karyotype and then determination of the presence or absence of Mullerian structures are necessary serial investigations in any case of DSD, except for mixed gonadal dysgenesis identified by karyotype alone. Treatment is ideal in a multidisciplinary setting with considerations to genetic (implications to family and reproductive recurrence risk), psychological aspects (sensitive individualized counseling including patient gender identity and preference), endocrinological (hormone replacement), surgical (cosmetic, prophylactic gonadectomy) fertility preservation and reproductive opportunities and metabolic health (cardiovascular and bones). PMID:28620497

Genotype-phenotype analysis of recombinant chromosome 4 syndrome: an array-CGH study and literature review

PubMed Central

2013-01-01

Background Recombinant chromosome 4, a rare constitutional rearrangement arising from pericentric inversion, comprises a duplicated segment of 4p13~p15→4pter and a deleted segment of 4q35→4qter. To date, 10 cases of recombinant chromosome 4 have been reported. Result We describe the second case in which array-CGH was used to characterize recombinant chromosome 4 syndrome. The patient was a one-year old boy with consistent clinical features. Conventional cytogenetics and FISH documented a recombinant chromosome 4, derived from a paternal pericentric inversion, leading to partial trisomy 4p and partial monosomy of 4q. Array-CGH, performed to further characterize the rearranged chromosome 4 and delineate the breakpoints, documented a small (4.36 Mb) 4q35.1 terminal deletion and a large (23.81 Mb) 4p15.1 terminal duplication. Genotype-phenotype analysis of 10 previously reported cases and the present case indicated relatively consistent clinical features and breakpoints. This consistency was more evident in our case and another characterized by array-CGH, where both showed the common breakpoints of p15.1 and q35.1. A genotype-phenotype correlation study between rec(4), dup(4p), and del(4q) syndromes revealed that urogenital and cardiac defects are probably due to the deletion of 4q whereas the other clinical features are likely due to 4p duplication. Conclusion Our findings support that the clinical features of patients with rec(4) are relatively consistent and specific to the regions of duplication or deletion. Recombinant chromosome 4 syndrome thus appears to be a discrete entity that can be suspected on the basis of clinical features or specific deleted and duplicated chromosomal regions. PMID:23639048

Genotype-phenotype analysis of recombinant chromosome 4 syndrome: an array-CGH study and literature review.

PubMed

Hemmat, Morteza; Hemmat, Omid; Anguiano, Arturo; Boyar, Fatih Z; El Naggar, Mohammed; Wang, Jia-Chi; Wang, Borris T; Sahoo, Trilochan; Owen, Renius; Haddadin, Mary

2013-05-02

Recombinant chromosome 4, a rare constitutional rearrangement arising from pericentric inversion, comprises a duplicated segment of 4p13~p15→4pter and a deleted segment of 4q35→4qter. To date, 10 cases of recombinant chromosome 4 have been reported. We describe the second case in which array-CGH was used to characterize recombinant chromosome 4 syndrome. The patient was a one-year old boy with consistent clinical features. Conventional cytogenetics and FISH documented a recombinant chromosome 4, derived from a paternal pericentric inversion, leading to partial trisomy 4p and partial monosomy of 4q. Array-CGH, performed to further characterize the rearranged chromosome 4 and delineate the breakpoints, documented a small (4.36 Mb) 4q35.1 terminal deletion and a large (23.81 Mb) 4p15.1 terminal duplication. Genotype-phenotype analysis of 10 previously reported cases and the present case indicated relatively consistent clinical features and breakpoints. This consistency was more evident in our case and another characterized by array-CGH, where both showed the common breakpoints of p15.1 and q35.1. A genotype-phenotype correlation study between rec(4), dup(4p), and del(4q) syndromes revealed that urogenital and cardiac defects are probably due to the deletion of 4q whereas the other clinical features are likely due to 4p duplication. Our findings support that the clinical features of patients with rec(4) are relatively consistent and specific to the regions of duplication or deletion. Recombinant chromosome 4 syndrome thus appears to be a discrete entity that can be suspected on the basis of clinical features or specific deleted and duplicated chromosomal regions.

7 CFR 27.23 - Duplicate sets of samples of cotton.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 7 Agriculture 2 2011-01-01 2011-01-01 false Duplicate sets of samples of cotton. 27.23 Section 27... REGULATIONS COTTON CLASSIFICATION UNDER COTTON FUTURES LEGISLATION Regulations Inspection and Samples § 27.23 Duplicate sets of samples of cotton. The duplicate sets of samples shall be inclosed in wrappers or...

7 CFR 27.23 - Duplicate sets of samples of cotton.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 2 2010-01-01 2010-01-01 false Duplicate sets of samples of cotton. 27.23 Section 27... REGULATIONS COTTON CLASSIFICATION UNDER COTTON FUTURES LEGISLATION Regulations Inspection and Samples § 27.23 Duplicate sets of samples of cotton. The duplicate sets of samples shall be inclosed in wrappers or...

7 CFR 27.23 - Duplicate sets of samples of cotton.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 7 Agriculture 2 2014-01-01 2014-01-01 false Duplicate sets of samples of cotton. 27.23 Section 27... REGULATIONS COTTON CLASSIFICATION UNDER COTTON FUTURES LEGISLATION Regulations Inspection and Samples § 27.23 Duplicate sets of samples of cotton. The duplicate sets of samples shall be inclosed in wrappers or...

7 CFR 27.23 - Duplicate sets of samples of cotton.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 7 Agriculture 2 2013-01-01 2013-01-01 false Duplicate sets of samples of cotton. 27.23 Section 27... REGULATIONS COTTON CLASSIFICATION UNDER COTTON FUTURES LEGISLATION Regulations Inspection and Samples § 27.23 Duplicate sets of samples of cotton. The duplicate sets of samples shall be inclosed in wrappers or...

7 CFR 27.23 - Duplicate sets of samples of cotton.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 7 Agriculture 2 2012-01-01 2012-01-01 false Duplicate sets of samples of cotton. 27.23 Section 27... REGULATIONS COTTON CLASSIFICATION UNDER COTTON FUTURES LEGISLATION Regulations Inspection and Samples § 27.23 Duplicate sets of samples of cotton. The duplicate sets of samples shall be inclosed in wrappers or...

Supervised Learning for Detection of Duplicates in Genomic Sequence Databases.

PubMed

Chen, Qingyu; Zobel, Justin; Zhang, Xiuzhen; Verspoor, Karin

2016-01-01

First identified as an issue in 1996, duplication in biological databases introduces redundancy and even leads to inconsistency when contradictory information appears. The amount of data makes purely manual de-duplication impractical, and existing automatic systems cannot detect duplicates as precisely as can experts. Supervised learning has the potential to address such problems by building automatic systems that learn from expert curation to detect duplicates precisely and efficiently. While machine learning is a mature approach in other duplicate detection contexts, it has seen only preliminary application in genomic sequence databases. We developed and evaluated a supervised duplicate detection method based on an expert curated dataset of duplicates, containing over one million pairs across five organisms derived from genomic sequence databases. We selected 22 features to represent distinct attributes of the database records, and developed a binary model and a multi-class model. Both models achieve promising performance; under cross-validation, the binary model had over 90% accuracy in each of the five organisms, while the multi-class model maintains high accuracy and is more robust in generalisation. We performed an ablation study to quantify the impact of different sequence record features, finding that features derived from meta-data, sequence identity, and alignment quality impact performance most strongly. The study demonstrates machine learning can be an effective additional tool for de-duplication of genomic sequence databases. All Data are available as described in the supplementary material.

Germline or somatic GPR101 duplication leads to X-linked acrogigantism: a clinico-pathological and genetic study.

PubMed

Iacovazzo, Donato; Caswell, Richard; Bunce, Benjamin; Jose, Sian; Yuan, Bo; Hernández-Ramírez, Laura C; Kapur, Sonal; Caimari, Francisca; Evanson, Jane; Ferraù, Francesco; Dang, Mary N; Gabrovska, Plamena; Larkin, Sarah J; Ansorge, Olaf; Rodd, Celia; Vance, Mary L; Ramírez-Renteria, Claudia; Mercado, Moisés; Goldstone, Anthony P; Buchfelder, Michael; Burren, Christine P; Gurlek, Alper; Dutta, Pinaki; Choong, Catherine S; Cheetham, Timothy; Trivellin, Giampaolo; Stratakis, Constantine A; Lopes, Maria-Beatriz; Grossman, Ashley B; Trouillas, Jacqueline; Lupski, James R; Ellard, Sian; Sampson, Julian R; Roncaroli, Federico; Korbonits, Márta

2016-06-01

Non-syndromic pituitary gigantism can result from AIP mutations or the recently identified Xq26.3 microduplication causing X-linked acrogigantism (XLAG). Within Xq26.3, GPR101 is believed to be the causative gene, and the c.924G > C (p.E308D) variant in this orphan G protein-coupled receptor has been suggested to play a role in the pathogenesis of acromegaly.We studied 153 patients (58 females and 95 males) with pituitary gigantism. AIP mutation-negative cases were screened for GPR101 duplication through copy number variation droplet digital PCR and high-density aCGH. The genetic, clinical and histopathological features of XLAG patients were studied in detail. 395 peripheral blood and 193 pituitary tumor DNA samples from acromegaly patients were tested for GPR101 variants.We identified 12 patients (10 females and 2 males; 7.8 %) with XLAG. In one subject, the duplicated region only contained GPR101, but not the other three genes in found to be duplicated in the previously reported patients, defining a new smallest region of overlap of duplications. While females presented with germline mutations, the two male patients harbored the mutation in a mosaic state. Nine patients had pituitary adenomas, while three had hyperplasia. The comparison of the features of XLAG, AIP-positive and GPR101&AIP-negative patients revealed significant differences in sex distribution, age at onset, height, prolactin co-secretion and histological features. The pathological features of XLAG-related adenomas were remarkably similar. These tumors had a sinusoidal and lobular architecture. Sparsely and densely granulated somatotrophs were admixed with lactotrophs; follicle-like structures and calcifications were commonly observed. Patients with sporadic of familial acromegaly did not have an increased prevalence of the c.924G > C (p.E308D) GPR101 variant compared to public databases.In conclusion, XLAG can result from germline or somatic duplication of GPR101. Duplication of GPR101

Identification of a duplication of Xq28 associated with bilateral periventricular nodular heterotopia.

PubMed Central

Fink, J M; Dobyns, W B; Guerrini, R; Hirsch, B A

1997-01-01

Bilateral periventricular nodular heterotopia (BPNH) is a malformation of neuronal migration and is characterized by nodules of heterotopic gray matter lining the lateral ventricles of the brain. The majority of BPNH patients are female and have epilepsy as a sole clinical manifestation of their disease. Familial BPNH has been mapped to Xq28 by linkage analysis. A multiple congenital anomaly-mental retardation syndrome (BPNH/MR) was recently delineated in three unrelated boys with BPNH, cerebellar hypoplasia, severe mental retardation, epilepsy, and syndactyly. High-resolution chromosome analysis revealed a subtle abnormality of Xq28 in one of the boys with BPNH/MR syndrome. FISH with cosmids and YACs from Xq28 further characterized this abnormality as a 2.25-3.25-Mb inverted duplication. No abnormality of Xq28 was detected by G-banding or FISH in the other two boys. These data support the linkage assignment of BPNH to band Xq28 and narrow the critical region to the distal 2.25-3.25 Mb of Xq28. Images Figure 1 Figure 3 Figure 4 Figure 5 PMID:9311743

Regulatory divergence of homeologous Atlantic salmon elovl5 genes following the salmonid-specific whole-genome duplication.

PubMed

Carmona-Antoñanzas, Greta; Zheng, Xiaozhong; Tocher, Douglas R; Leaver, Michael J

2016-10-10

Fatty acyl elongase 5 (elovl5) is a critical enzyme in the vertebrate biosynthetic pathway which produces the physiologically essential long-chain polyunsaturated fatty acids (LC-PUFA), docosahexenoic acid (DHA), and eicosapentenoic acid (EPA) from 18 carbon fatty acids precursors. In contrast to most other vertebrates, Atlantic salmon possess two copies of elovl5 (elovl5a and elovl5b) as a result of a whole-genome duplication (WGD) which occurred at the base of the salmonid lineage. WGDs have had a major influence on vertebrate evolution, providing extra genetic material, enabling neofunctionalization to accelerate adaptation and speciation. However, little is known about the mechanisms by which such duplicated homeologous genes diverge. Here we show that homeologous Atlantic salmon elovl5a and elovl5b genes have been asymmetrically colonised by transposon-like elements. Identical locations and identities of insertions are also present in the rainbow trout duplicate elovl5 genes, but not in the nearest extant representative preduplicated teleost, the northern pike. Both elovl5 salmon duplicates possessed conserved regulatory elements that promoted Srebp1- and Srebp2-dependent transcription, and differences in the magnitude of Srebp response between promoters could be attributed to a tandem duplication of SRE and NF-Y cofactor binding sites in elovl5b. Furthermore, an insertion in the promoter region of elovl5a confers responsiveness to Lxr/Rxr transcriptional activation. Our results indicate that most, but not all, transposon mobilisation into elovl5 genes occurred after the split from the common ancestor of pike and salmon, but before more recent salmonid speciations, and that divergence of elovl5 regulatory regions have enabled neofuntionalization by promoting differential expression of these homeologous genes. Copyright © 2016 Elsevier B.V. All rights reserved.

Comparative inference of duplicated genes produced by polyploidization in soybean genome.

PubMed

Yang, Yanmei; Wang, Jinpeng; Di, Jianyong

2013-01-01

Soybean (Glycine max) is one of the most important crop plants for providing protein and oil. It is important to investigate soybean genome for its economic and scientific value. Polyploidy is a widespread and recursive phenomenon during plant evolution, and it could generate massive duplicated genes which is an important resource for genetic innovation. Improved sequence alignment criteria and statistical analysis are used to identify and characterize duplicated genes produced by polyploidization in soybean. Based on the collinearity method, duplicated genes by whole genome duplication account for 70.3% in soybean. From the statistical analysis of the molecular distances between duplicated genes, our study indicates that the whole genome duplication event occurred more than once in the genome evolution of soybean, which is often distributed near the ends of chromosomes.

Segmental Duplications and Copy-Number Variation in the Human Genome

PubMed Central

Sharp, Andrew J. ; Locke, Devin P. ; McGrath, Sean D. ; Cheng, Ze ; Bailey, Jeffrey A. ; Vallente, Rhea U. ; Pertz, Lisa M. ; Clark, Royden A. ; Schwartz, Stuart ; Segraves, Rick ; Oseroff, Vanessa V. ; Albertson, Donna G. ; Pinkel, Daniel ; Eichler, Evan E. 

2005-01-01

The human genome contains numerous blocks of highly homologous duplicated sequence. This higher-order architecture provides a substrate for recombination and recurrent chromosomal rearrangement associated with genomic disease. However, an assessment of the role of segmental duplications in normal variation has not yet been made. On the basis of the duplication architecture of the human genome, we defined a set of 130 potential rearrangement hotspots and constructed a targeted bacterial artificial chromosome (BAC) microarray (with 2,194 BACs) to assess copy-number variation in these regions by array comparative genomic hybridization. Using our segmental duplication BAC microarray, we screened a panel of 47 normal individuals, who represented populations from four continents, and we identified 119 regions of copy-number polymorphism (CNP), 73 of which were previously unreported. We observed an equal frequency of duplications and deletions, as well as a 4-fold enrichment of CNPs within hotspot regions, compared with control BACs (P < .000001), which suggests that segmental duplications are a major catalyst of large-scale variation in the human genome. Importantly, segmental duplications themselves were also significantly enriched >4-fold within regions of CNP. Almost without exception, CNPs were not confined to a single population, suggesting that these either are recurrent events, having occurred independently in multiple founders, or were present in early human populations. Our study demonstrates that segmental duplications define hotspots of chromosomal rearrangement, likely acting as mediators of normal variation as well as genomic disease, and it suggests that the consideration of genomic architecture can significantly improve the ascertainment of large-scale rearrangements. Our specialized segmental duplication BAC microarray and associated database of structural polymorphisms will provide an important resource for the future characterization of human genomic

A yeast gene essential for regulation of spindle pole duplication.

PubMed Central

Baum, P; Yip, C; Goetsch, L; Byers, B

1988-01-01

In eucaryotic cells, duplication of spindle poles must be coordinated with other cell cycle functions. We report here the identification in Saccharomyces cerevisiae of a temperature-sensitive lethal mutation, esp1, that deregulates spindle pole duplication. Mutant cells transferred to the nonpermissive temperature became unable to continue DNA synthesis and cell division but displayed repeated duplication of their spindle pole bodies. Although entry into this state after transient challenge by the nonpermissive temperature was largely lethal, rare survivors were recovered and found to have become increased in ploidy. If the mutant cells were held in G0 or G1 during exposure to the elevated temperature, they remained viable and maintained normal numbers of spindle poles. These results suggest dual regulation of spindle pole duplication, including a mechanism that promotes duplication as cells enter the division cycle and a negative regulatory mechanism, controlled by ESP1, that limits duplication to a single occurrence in each cell division cycle. Tetrad analysis has revealed that ESP1 resides at a previously undescribed locus on the right arm of chromosome VII. Images PMID:3072479

Activity-Dependent Dysfunction in Visual and Olfactory Sensory Systems in Mouse Models of Down Syndrome

PubMed Central

Saqran, Lubna; Herrick, Scott P.; Frosch, Matthew P.; Hyman, Bradley T.

2017-01-01

Activity-dependent synaptic plasticity plays a critical role in the refinement of circuitry during postnatal development and may be disrupted in conditions that cause intellectual disability, such as Down syndrome (DS). To test this hypothesis, visual cortical plasticity was assessed in Ts65Dn mice that harbor a chromosomal duplication syntenic to human chromosome 21q. We find that Ts65Dn mice demonstrate a defect in ocular dominance plasticity (ODP) following monocular deprivation. This phenotype is similar to that of transgenic mice that express amyloid precursor protein (APP), which is duplicated in DS and in Ts65DN mice; however, normalizing APP gene copy number in Ts65Dn mice fails to rescue plasticity. Ts1Rhr mice harbor a duplication of the telomeric third of the Ts65Dn-duplicated sequence and demonstrate the same ODP defect, suggesting a gene or genes sufficient to drive the phenotype are located in that smaller duplication. In addition, we find that Ts65Dn mice demonstrate an abnormality in olfactory system connectivity, a defect in the refinement of connections to second-order neurons in the olfactory bulb. Ts1Rhr mice do not demonstrate a defect in glomerular refinement, suggesting that distinct genes or sets of genes underlie visual and olfactory system phenotypes. Importantly, these data suggest that developmental plasticity and connectivity are impaired in sensory systems in DS model mice, that such defects may contribute to functional impairment in DS, and that these phenotypes, present in male and female mice, provide novel means for examining the genetic and molecular bases for neurodevelopmental impairment in model mice in vivo. SIGNIFICANCE STATEMENT Our understanding of the basis for intellectual impairment in Down syndrome is hindered by the large number of genes duplicated in Trisomy 21 and a lack of understanding of the effect of disease pathology on the function of neural circuits in vivo. This work describes early postnatal developmental

TECHNIQUES OF TAPE PREPARATION AND DUPLICATION, WITH SUGGESTIONS FOR A LANGUAGE LABORATORY.

ERIC Educational Resources Information Center

Kansas State Dept. of Public Instruction, Topeka.

PART ONE OF THIS BULLETIN PROVIDES HELP IN THE TWO CRITICAL AREAS OF MASTER TAPE PREPARATION AND DUPLICATION. SUPPLEMENTED BY NUMEROUS PHOTOGRAPHS AND DIAGRAMS OF EQUIPMENT AND DUPLICATION TECHNIQUES, THE BULLETIN DESCRIBES MASTER PROGRAM DUPLICATION USING LANGUAGE LABORATORY EQUIPMENT, A PROFESSIONAL MASS DUPLICATOR, A TAPE RECORDER, A RECORD…

Differential diagnosis and diagnostic flow chart of joint hypermobility syndrome/ehlers-danlos syndrome hypermobility type compared to other heritable connective tissue disorders.

PubMed

Colombi, Marina; Dordoni, Chiara; Chiarelli, Nicola; Ritelli, Marco

2015-03-01

Joint hypermobility syndrome/Ehlers-Danlos syndrome hypermobility type (JHS/EDS-HT) is an evolving and protean disorder mostly recognized by generalized joint hypermobility and without a defined molecular basis. JHS/EDS-HT also presents with other connective tissue features affecting a variety of structures and organs, such as skin, eye, bone, and internal organs. However, most of these signs are present in variable combinations and severity in many other heritable connective tissue disorders. Accordingly, JHS/EDS-HT is an "exclusion" diagnosis which needs the absence of any consistent feature indicative of other partially overlapping connective tissue disorders. While both Villefranche and Brighton criteria include such an exclusion as a mandatory item, a systematic approach for reaching a stringent clinical diagnosis of JHS/EDS-HT is still lacking. The absence of a consensus on the diagnostic approach to JHS/EDS-HT concerning its clinical boundaries with similar conditions contribute to limit our actual understanding of the pathologic and molecular bases of this disorder. In this review, we revise the differential diagnosis of JHS/EDS-HT with those heritable connective tissue disorders which show a significant overlap with the former and mostly include EDS classic, vascular and kyphoscoliotic types, osteogenesis imperfecta, Marfan syndrome, Loeys-Dietz syndrome, arterial tortuosity syndrome, and lateral meningocele syndrome. A diagnostic flow chart is also offered with the attempt to support the less experienced clinician in stringently recognizing JHS/EDS-HT and stimulate the debate in the scientific community for both management and research purposes. © 2015 Wiley Periodicals, Inc.

Characterization of various promoter regions of the human DNA helicase-encoding genes and identification of duplicated ets (GGAA) motifs as an essential transcription regulatory element.

PubMed

Uchiumi, Fumiaki; Watanabe, Takeshi; Tanuma, Sei-ichi

2010-05-15

DNA helicases are important in the regulation of DNA transaction and thereby various cellular functions. In this study, we developed a cost-effective multiple DNA transfection assay with DEAE-dextran reagent and analyzed the promoter activities of the human DNA helicases. The 5'-flanking regions of the human DNA helicase-encoding genes were isolated and subcloned into luciferase (Luc) expression plasmids. They were coated onto 96-well plate and used for co-transfection with a renilla-Luc expression vector into various cells, and dual-Luc assays were performed. The profiles of promoter activities were dependent on cell lines used. Among these human DNA helicase genes, XPB, RecQL5, and RTEL promoters were activated during TPA-induced HL-60 cell differentiation. Interestingly, duplicated ets (GGAA) elements are commonly located around the transcription start sites of these genes. The duplicated GGAA motifs are also found in the promoters of DNA replication/repair synthesis factor genes including PARG, ATR, TERC, and Rb1. Mutation analyses suggested that the duplicated GGAA-motifs are necessary for the basal promoter activity in various cells and some of them positively respond to TPA in HL-60 cells. TPA-induced response of 44-bp in the RTEL promoter was attenuated by co-transfection of the PU.1 expression vector. These findings suggest that the duplicated ets motifs regulate DNA-repair associated gene expressions during macrophage-like differentiation of HL-60 cells. Copyright 2010 Elsevier Inc. All rights reserved.

Prevalence and origin of De Novo duplications in Charcot-Marie-Tooth disease type 1A: First report of a De Novo duplication with a maternal origin

DOE Office of Scientific and Technical Information (OSTI.GOV)

Blair, I.P.; Nash, J.; Gordon, M.J.

1996-03-01

Charcot-Marie-Tooth disease (CMT) is the most common inherited peripheral neuropathy. Sporadic cases of CMT have been described since the earliest reports of the disease. The most frequent form of the disorder, CMT1A, is associated with a 1.5-Mb DNA duplication on chromosome 17p11.2, which segregates with the disease. In order to investigate the prevalence of de novo CMT1A duplications, this study examined 118 duplication-positive CMT1A families. In 10 of these families it was demonstrated that the disease had arisen as the result of a de novo mutation. By taking into account the ascertainment of families, it can be estimated that {>=}10%more » of autosomal dominant CMT1 families are due to de novo duplications. The CMT1A duplication is thought to be the product of unequal crossing over between parental chromosome 17 homologues during meiosis. Polymorphic markers from within the duplicated region were used to determine the parental origin of these de novo duplications in eight informative families. Seven were of paternal and one of maternal origin. This study represents the first report of a de novo duplication with a maternal origin and indicates that it is not a phenomenon associated solely with male meioses. Recombination fractions for the region duplicated in CMT1A are larger in females than in males. That suggests that oogenesis may be afforded greater protection from misalignment during synapsis, and/or that there may be lower activity of those factors or mechanisms that lead to unequal crossing over at the CMT1A locus. 41 refs., 2 figs.« less

47 CFR 76.93 - Parties entitled to network non-duplication protection.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 47 Telecommunication 4 2010-10-01 2010-10-01 false Parties entitled to network non-duplication... RADIO SERVICES MULTICHANNEL VIDEO AND CABLE TELEVISION SERVICE Network Non-duplication Protection, Syndicated Exclusivity and Sports Blackout § 76.93 Parties entitled to network non-duplication protection...

47 CFR 76.93 - Parties entitled to network non-duplication protection.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 47 Telecommunication 4 2011-10-01 2011-10-01 false Parties entitled to network non-duplication... RADIO SERVICES MULTICHANNEL VIDEO AND CABLE TELEVISION SERVICE Network Non-duplication Protection, Syndicated Exclusivity and Sports Blackout § 76.93 Parties entitled to network non-duplication protection...

Gene Duplicability of Core Genes Is Highly Consistent across All Angiosperms[OPEN

PubMed Central

Li, Zhen; Van de Peer, Yves; De Smet, Riet

2016-01-01

Gene duplication is an important mechanism for adding to genomic novelty. Hence, which genes undergo duplication and are preserved following duplication is an important question. It has been observed that gene duplicability, or the ability of genes to be retained following duplication, is a nonrandom process, with certain genes being more amenable to survive duplication events than others. Primarily, gene essentiality and the type of duplication (small-scale versus large-scale) have been shown in different species to influence the (long-term) survival of novel genes. However, an overarching view of “gene duplicability” is lacking, mainly due to the fact that previous studies usually focused on individual species and did not account for the influence of genomic context and the time of duplication. Here, we present a large-scale study in which we investigated duplicate retention for 9178 gene families shared between 37 flowering plant species, referred to as angiosperm core gene families. For most gene families, we observe a strikingly consistent pattern of gene duplicability across species, with gene families being either primarily single-copy or multicopy in all species. An intermediate class contains gene families that are often retained in duplicate for periods extending to tens of millions of years after whole-genome duplication, but ultimately appear to be largely restored to singleton status, suggesting that these genes may be dosage balance sensitive. The distinction between single-copy and multicopy gene families is reflected in their functional annotation, with single-copy genes being mainly involved in the maintenance of genome stability and organelle function and multicopy genes in signaling, transport, and metabolism. The intermediate class was overrepresented in regulatory genes, further suggesting that these represent putative dosage-balance-sensitive genes. PMID:26744215

Screening for duplications, deletions and a common intronic mutation detects 35% of second mutations in patients with USH2A monoallelic mutations on Sanger sequencing.

PubMed

Steele-Stallard, Heather B; Le Quesne Stabej, Polona; Lenassi, Eva; Luxon, Linda M; Claustres, Mireille; Roux, Anne-Francoise; Webster, Andrew R; Bitner-Glindzicz, Maria

2013-08-08

Usher Syndrome is the leading cause of inherited deaf-blindness. It is divided into three subtypes, of which the most common is Usher type 2, and the USH2A gene accounts for 75-80% of cases. Despite recent sequencing strategies, in our cohort a significant proportion of individuals with Usher type 2 have just one heterozygous disease-causing mutation in USH2A, or no convincing disease-causing mutations across nine Usher genes. The purpose of this study was to improve the molecular diagnosis in these families by screening USH2A for duplications, heterozygous deletions and a common pathogenic deep intronic variant USH2A: c.7595-2144A>G. Forty-nine Usher type 2 or atypical Usher families who had missing mutations (mono-allelic USH2A or no mutations following Sanger sequencing of nine Usher genes) were screened for duplications/deletions using the USH2A SALSA MLPA reagent kit (MRC-Holland). Identification of USH2A: c.7595-2144A>G was achieved by Sanger sequencing. Mutations were confirmed by a combination of reverse transcription PCR using RNA extracted from nasal epithelial cells or fibroblasts, and by array comparative genomic hybridisation with sequencing across the genomic breakpoints. Eight mutations were identified in 23 Usher type 2 families (35%) with one previously identified heterozygous disease-causing mutation in USH2A. These consisted of five heterozygous deletions, one duplication, and two heterozygous instances of the pathogenic variant USH2A: c.7595-2144A>G. No variants were found in the 15 Usher type 2 families with no previously identified disease-causing mutations. In 11 atypical families, none of whom had any previously identified convincing disease-causing mutations, the mutation USH2A: c.7595-2144A>G was identified in a heterozygous state in one family. All five deletions and the heterozygous duplication we report here are novel. This is the first time that a duplication in USH2A has been reported as a cause of Usher syndrome. We found that 8 of

Duplicate retention in signalling proteins and constraints from network dynamics.

PubMed

Soyer, O S; Creevey, C J

2010-11-01

Duplications are a major driving force behind evolution. Most duplicates are believed to fix through genetic drift, but it is not clear whether this process affects all duplications equally or whether there are certain gene families that are expected to show neutral expansions under certain circumstances. Here, we analyse the neutrality of duplications in different functional classes of signalling proteins based on their effects on response dynamics. We find that duplications involving intermediary proteins in a signalling network are neutral more often than those involving receptors. Although the fraction of neutral duplications in all functional classes increase with decreasing population size and selective pressure on dynamics, this effect is most pronounced for receptors, indicating a possible expansion of receptors in species with small population size. In line with such an expectation, we found a statistically significant increase in the number of receptors as a fraction of genome size in eukaryotes compared with prokaryotes. Although not confirmative, these results indicate that neutral processes can be a significant factor in shaping signalling networks and affect proteins from different functional classes differently. © 2010 The Authors. Journal Compilation © 2010 European Society For Evolutionary Biology.

47 CFR 76.92 - Cable network non-duplication; extent of protection.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 47 Telecommunication 4 2011-10-01 2011-10-01 false Cable network non-duplication; extent of... RADIO SERVICES MULTICHANNEL VIDEO AND CABLE TELEVISION SERVICE Network Non-duplication Protection, Syndicated Exclusivity and Sports Blackout § 76.92 Cable network non-duplication; extent of protection. (a...

47 CFR 76.92 - Cable network non-duplication; extent of protection.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 47 Telecommunication 4 2010-10-01 2010-10-01 false Cable network non-duplication; extent of... RADIO SERVICES MULTICHANNEL VIDEO AND CABLE TELEVISION SERVICE Network Non-duplication Protection, Syndicated Exclusivity and Sports Blackout § 76.92 Cable network non-duplication; extent of protection. (a...

PTGBase: an integrated database to study tandem duplicated genes in plants.

PubMed

Yu, Jingyin; Ke, Tao; Tehrim, Sadia; Sun, Fengming; Liao, Boshou; Hua, Wei

2015-01-01

Tandem duplication is a wide-spread phenomenon in plant genomes and plays significant roles in evolution and adaptation to changing environments. Tandem duplicated genes related to certain functions will lead to the expansion of gene families and bring increase of gene dosage in the form of gene cluster arrays. Many tandem duplication events have been studied in plant genomes; yet, there is a surprising shortage of efforts to systematically present the integration of large amounts of information about publicly deposited tandem duplicated gene data across the plant kingdom. To address this shortcoming, we developed the first plant tandem duplicated genes database, PTGBase. It delivers the most comprehensive resource available to date, spanning 39 plant genomes, including model species and newly sequenced species alike. Across these genomes, 54 130 tandem duplicated gene clusters (129 652 genes) are presented in the database. Each tandem array, as well as its member genes, is characterized in complete detail. Tandem duplicated genes in PTGBase can be explored through browsing or searching by identifiers or keywords of functional annotation and sequence similarity. Users can download tandem duplicated gene arrays easily to any scale, up to the complete annotation data set for an entire plant genome. PTGBase will be updated regularly with newly sequenced plant species as they become available. © The Author(s) 2015. Published by Oxford University Press.

Xq28 duplication overlapping the int22h-1/int22h-2 region and including RAB39B and CLIC2 in a family with intellectual and developmental disability.

PubMed

Andersen, Erica F; Baldwin, Erin E; Ellingwood, Sara; Smith, Rosemarie; Lamb, Allen N

2014-07-01

Duplications involving terminal Xq28 are a known cause of intellectual disability (ID) in males and in females with unfavorable X-inactivation patterns. Within Xq28, functional disomy of MECP2 causes a severe ID syndrome, however the dosage sensitivity of other Xq28 duplicated genes is less certain. Duplications involving the int22h-1/int22h-2 LCR-flanked region in distal Xq28 have recently been linked to a novel ID-associated phenotype. While evidence for the dosage sensitivity of this region is emerging, the phenotypic contribution of individual genes within the int22h-1/int22h-2-flanked region has yet to be determined. We report a familial case of a novel 774 kb Xq28-qter duplication, detected by cytogenomic microarray analysis, that partially overlaps the int22h-1/int22h-2-flanked region. This duplication and a 570 kb Xpter-p22.33 loss within the pseudoautosomal region were identified in three siblings, one female and two males, who presented with developmental delays/intellectual disability, mild dysmorphic features and short stature. Although unconfirmed, these results are suggestive of maternal inheritance of a recombinant X. We compare our clinical findings to patients with int22h-1/int22h-2-mediated duplications and discuss the potential pathogenicity of genes within the duplicated region, including those within the shared region of overlap, RAB39B and CLIC2. © 2014 Wiley Periodicals, Inc.

Genome Mutational and Transcriptional Hotspots Are Traps for Duplicated Genes and Sources of Adaptations.

PubMed

Fares, Mario A; Sabater-Muñoz, Beatriz; Toft, Christina

2017-05-01

Gene duplication generates new genetic material, which has been shown to lead to major innovations in unicellular and multicellular organisms. A whole-genome duplication occurred in the ancestor of Saccharomyces yeast species but 92% of duplicates returned to single-copy genes shortly after duplication. The persisting duplicated genes in Saccharomyces led to the origin of major metabolic innovations, which have been the source of the unique biotechnological capabilities in the Baker's yeast Saccharomyces cerevisiae. What factors have determined the fate of duplicated genes remains unknown. Here, we report the first demonstration that the local genome mutation and transcription rates determine the fate of duplicates. We show, for the first time, a preferential location of duplicated genes in the mutational and transcriptional hotspots of S. cerevisiae genome. The mechanism of duplication matters, with whole-genome duplicates exhibiting different preservation trends compared to small-scale duplicates. Genome mutational and transcriptional hotspots are rich in duplicates with large repetitive promoter elements. Saccharomyces cerevisiae shows more tolerance to deleterious mutations in duplicates with repetitive promoter elements, which in turn exhibit higher transcriptional plasticity against environmental perturbations. Our data demonstrate that the genome traps duplicates through the accelerated regulatory and functional divergence of their gene copies providing a source of novel adaptations in yeast. © The Author 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

A Rare Variant of Wallenberg’s Syndrome: Opalski syndrome

PubMed Central

KK, Parathan; P, Chitrambalam; Aiyappan, Senthil Kumar; N, Deepthi

2014-01-01

Lateral Medullary Syndrome (LMS) is a well-documented vascular syndrome of the posterior circulation territory. This syndrome is easily localised because of characteristic presentation, unique territory of blood supply and very small area of involvement. We present a case of Wallenberg’s syndrome which did not have all the classical components of the syndrome, like Horner’s syndrome. Opalski syndrome is a rare variant of Wallenberg syndrome, where lateral medullary syndrome is associated with ipsilateral hemiparesis. This case report highlights how differential involvement of the lateral part of medulla can result in varied presentation. PMID:25177595

Maintenance and Loss of Duplicated Genes by Dosage Subfunctionalization.

PubMed

Gout, Jean-Francois; Lynch, Michael

2015-08-01

Whole-genome duplications (WGDs) have contributed to gene-repertoire enrichment in many eukaryotic lineages. However, most duplicated genes are eventually lost and it is still unclear why some duplicated genes are evolutionary successful whereas others quickly turn to pseudogenes. Here, we show that dosage constraints are major factors opposing post-WGD gene loss in several Paramecium species that share a common ancestral WGD. We propose a model where a majority of WGD-derived duplicates preserve their ancestral function and are retained to produce enough of the proteins performing this same ancestral function. Under this model, the expression level of individual duplicated genes can evolve neutrally as long as they maintain a roughly constant summed expression, and this allows random genetic drift toward uneven contributions of the two copies to total expression. Our analysis suggests that once a high level of imbalance is reached, which can require substantial lengths of time, the copy with the lowest expression level contributes a small enough fraction of the total expression that selection no longer opposes its loss. Extension of our analysis to yeast species sharing a common ancestral WGD yields similar results, suggesting that duplicated-gene retention for dosage constraints followed by divergence in expression level and eventual deterministic gene loss might be a universal feature of post-WGD evolution. © The Author 2015. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Drosophila Ana2 is a conserved centriole duplication factor

PubMed Central

Stevens, Naomi R.; Dobbelaere, Jeroen; Brunk, Kathrin; Franz, Anna

2010-01-01

In Caenorhabditis elegans, five proteins are required for centriole duplication: SPD-2, ZYG-1, SAS-5, SAS-6, and SAS-4. Functional orthologues of all but SAS-5 have been found in other species. In Drosophila melanogaster and humans, Sak/Plk4, DSas-6/hSas-6, and DSas-4/CPAP—orthologues of ZYG-1, SAS-6, and SAS-4, respectively—are required for centriole duplication. Strikingly, all three fly proteins can induce the de novo formation of centriole-like structures when overexpressed in unfertilized eggs. Here, we find that of eight candidate duplication factors identified in cultured fly cells, only two, Ana2 and Asterless (Asl), share this ability. Asl is now known to be essential for centriole duplication in flies, but no equivalent protein has been found in worms. We show that Ana2 is the likely functional orthologue of SAS-5 and that it is also related to the vertebrate STIL/SIL protein family that has been linked to microcephaly in humans. We propose that members of the SAS-5/Ana2/STIL family of proteins are key conserved components of the centriole duplication machinery. PMID:20123993

Characterization of distinct classes of differential gene expression in osteoblast cultures from non-syndromic craniosynostosis bone.

PubMed

Rojas-Peña, Monica L; Olivares-Navarrete, Rene; Hyzy, Sharon; Arafat, Dalia; Schwartz, Zvi; Boyan, Barbara D; Williams, Joseph; Gibson, Greg

2014-01-01

Craniosynostosis, the premature fusion of one or more skull sutures, occurs in approximately 1 in 2500 infants, with the majority of cases non-syndromic and of unknown etiology. Two common reasons proposed for premature suture fusion are abnormal compression forces on the skull and rare genetic abnormalities. Our goal was to evaluate whether different sub-classes of disease can be identified based on total gene expression profiles. RNA-Seq data were obtained from 31 human osteoblast cultures derived from bone biopsy samples collected between 2009 and 2011, representing 23 craniosynostosis fusions and 8 normal cranial bones or long bones. No differentiation between regions of the skull was detected, but variance component analysis of gene expression patterns nevertheless supports transcriptome-based classification of craniosynostosis. Cluster analysis showed 4 distinct groups of samples; 1 predominantly normal and 3 craniosynostosis subtypes. Similar constellations of sub-types were also observed upon re-analysis of a similar dataset of 199 calvarial osteoblast cultures. Annotation of gene function of differentially expressed transcripts strongly implicates physiological differences with respect to cell cycle and cell death, stromal cell differentiation, extracellular matrix (ECM) components, and ribosomal activity. Based on these results, we propose non-syndromic craniosynostosis cases can be classified by differences in their gene expression patterns and that these may provide targets for future clinical intervention.

Characterization of Distinct Classes of Differential Gene Expression in Osteoblast Cultures from Non-Syndromic Craniosynostosis Bone

PubMed Central

Rojas-Peña, Monica L.; Olivares-Navarrete, Rene; Hyzy, Sharon; Arafat, Dalia; Schwartz, Zvi; Boyan, Barbara D.; Williams, Joseph; Gibson, Greg

2014-01-01

Craniosynostosis, the premature fusion of one or more skull sutures, occurs in approximately 1 in 2500 infants, with the majority of cases non-syndromic and of unknown etiology. Two common reasons proposed for premature suture fusion are abnormal compression forces on the skull and rare genetic abnormalities. Our goal was to evaluate whether different sub-classes of disease can be identified based on total gene expression profiles. RNA-Seq data were obtained from 31 human osteoblast cultures derived from bone biopsy samples collected between 2009 and 2011, representing 23 craniosynostosis fusions and 8 normal cranial bones or long bones. No differentiation between regions of the skull was detected, but variance component analysis of gene expression patterns nevertheless supports transcriptome-based classification of craniosynostosis. Cluster analysis showed 4 distinct groups of samples; 1 predominantly normal and 3 craniosynostosis subtypes. Similar constellations of sub-types were also observed upon re-analysis of a similar dataset of 199 calvarial osteoblast cultures. Annotation of gene function of differentially expressed transcripts strongly implicates physiological differences with respect to cell cycle and cell death, stromal cell differentiation, extracellular matrix (ECM) components, and ribosomal activity. Based on these results, we propose non-syndromic craniosynostosis cases can be classified by differences in their gene expression patterns and that these may provide targets for future clinical intervention. PMID:25184005

The origins and impact of primate segmental duplications.

PubMed

Marques-Bonet, Tomas; Girirajan, Santhosh; Eichler, Evan E

2009-10-01

Duplicated sequences are substrates for the emergence of new genes and are an important source of genetic instability associated with rare and common diseases. Analyses of primate genomes have shown an increase in the proportion of interspersed segmental duplications (SDs) within the genomes of humans and great apes. This contrasts with other mammalian genomes that seem to have their recently duplicated sequences organized in a tandem configuration. In this review, we focus on the mechanistic origin and impact of this difference with respect to evolution, genetic diversity and primate phenotype. Although many genomes will be sequenced in the future, resolution of this aspect of genomic architecture still requires high quality sequences and detailed analyses.

Centrioles: duplicating precariously.

PubMed

Pelletier, Laurence

2007-09-04

To assemble a mitotic spindle and accurately segregate chromosomes to progeny, a cell needs to precisely regulate its centrosome number, a feat largely accomplished through the tight control of centriole duplication. Recent work showing that the overexpression of centriolar proteins can lead to the formation of multiple centrioles in the absence of pre-existing centrioles challenges the idea that it is a self-replicating organelle.

Quantitative fluorescence-polymerase chain reaction assay for the detection of the duplication of the Charcot Marie Tooth disease type 1A critical region.

PubMed

De Toffol, Simona; Bellone, Emilia; Dulcetti, Francesca; Ruggeri, Anna Maria; Maggio, Pietro Paolo; Pulimeno, Maria Rosaria; Mandich, Paola; Maggi, Federico; Simoni, Giuseppe; Grati, Francesca Romana

2010-04-01

Charcot Marie Tooth (CMT) syndrome is the most common hereditary peripheral neuropathy, with an incidence of about 1 in 2500. The subtype 1A (CMT1A) is caused by a tandem duplication of a 1.5-Mb region encompassing the PMP22 gene. Conventional short tandem repeat (STR) analysis can reveal this imbalance if a triallelic pattern, defining with certainty the presence of duplication, is present. In case of duplication with a biallelic pattern, it can only indicate a semiquantitative dosage of the fluorescence intensity ratio of the two fragments. In this study we developed a quantitative fluorescence-PCR using seven highly informative STRs within the CMT1A critical region that successfully disclosed or excluded the presence of the pathogenic imbalance in a cohort of 60 samples including 40 DNAs from samples with the CMT1A duplication previously characterized with two different molecular approaches, and 20 diagnostic samples from 10 members of a five-generation pedigree segregating CMT1A, 8 unrelated cases and 2 prenatal samples. The application of the quantitative fluorescence-PCR using STRs located in the critical region could be a reliable method to evaluate the presence of the PMP22 duplication for the diagnosis and classification of hereditary neuropathies in asymptomatic subjects with a family history of inherited neuropathy, in prenatal samples in cases with one affected parent, and in unrelated patients with a sporadic demyelinating neuropathy with clinical features resembling CMT (i.e., pes cavus with hammer toes) or with conduction velocities in the range of CMT1A.

Functional characterization of duplicated Suppressor of Overexpression of Constans 1-like genes in petunia.

PubMed

Preston, Jill C; Jorgensen, Stacy A; Jha, Suryatapa G

2014-01-01

Flowering time is strictly controlled by a combination of internal and external signals that match seed set with favorable environmental conditions. In the model plant species Arabidopsis thaliana (Brassicaceae), many of the genes underlying development and evolution of flowering have been discovered. However, much remains unknown about how conserved the flowering gene networks are in plants with different growth habits, gene duplication histories, and distributions. Here we functionally characterize three homologs of the flowering gene Suppressor Of Overexpression of Constans 1 (SOC1) in the short-lived perennial Petunia hybrida (petunia, Solanaceae). Similar to A. thaliana soc1 mutants, co-silencing of duplicated petunia SOC1-like genes results in late flowering. This phenotype is most severe when all three SOC1-like genes are silenced. Furthermore, expression levels of the SOC1-like genes Unshaven (UNS) and Floral Binding Protein 21 (FBP21), but not FBP28, are positively correlated with developmental age. In contrast to A. thaliana, petunia SOC1-like gene expression did not increase with longer photoperiods, and FBP28 transcripts were actually more abundant under short days. Despite evidence of functional redundancy, differential spatio-temporal expression data suggest that SOC1-like genes might fine-tune petunia flowering in response to photoperiod and developmental stage. This likely resulted from modification of SOC1-like gene regulatory elements following recent duplication, and is a possible mechanism to ensure flowering under both inductive and non-inductive photoperiods.

Functional Characterization of Duplicated SUPPRESSOR OF OVEREXPRESSION OF CONSTANS 1-Like Genes in Petunia

PubMed Central

Preston, Jill C.; Jorgensen, Stacy A.; Jha, Suryatapa G.

2014-01-01

Flowering time is strictly controlled by a combination of internal and external signals that match seed set with favorable environmental conditions. In the model plant species Arabidopsis thaliana (Brassicaceae), many of the genes underlying development and evolution of flowering have been discovered. However, much remains unknown about how conserved the flowering gene networks are in plants with different growth habits, gene duplication histories, and distributions. Here we functionally characterize three homologs of the flowering gene SUPPRESSOR OF OVEREXPRESSION OF CONSTANS 1 (SOC1) in the short-lived perennial Petunia hybrida (petunia, Solanaceae). Similar to A. thaliana soc1 mutants, co-silencing of duplicated petunia SOC1-like genes results in late flowering. This phenotype is most severe when all three SOC1-like genes are silenced. Furthermore, expression levels of the SOC1-like genes UNSHAVEN (UNS) and FLORAL BINDING PROTEIN 21 (FBP21), but not FBP28, are positively correlated with developmental age. In contrast to A. thaliana, petunia SOC1-like gene expression did not increase with longer photoperiods, and FBP28 transcripts were actually more abundant under short days. Despite evidence of functional redundancy, differential spatio-temporal expression data suggest that SOC1-like genes might fine-tune petunia flowering in response to photoperiod and developmental stage. This likely resulted from modification of SOC1-like gene regulatory elements following recent duplication, and is a possible mechanism to ensure flowering under both inductive and non-inductive photoperiods. PMID:24787903

Sox9 duplications are a relevant cause of Sry-negative XX sex reversal dogs.

PubMed

Rossi, Elena; Radi, Orietta; De Lorenzi, Lisa; Vetro, Annalisa; Groppetti, Debora; Bigliardi, Enrico; Luvoni, Gaia Cecilia; Rota, Ada; Camerino, Giovanna; Zuffardi, Orsetta; Parma, Pietro

2014-01-01

Sexual development in mammals is based on a complicated and delicate network of genes and hormones that have to collaborate in a precise manner. The dark side of this pathway is represented by pathological conditions, wherein sexual development does not occur properly either in the XX and the XY background. Among them a conundrum is represented by the XX individuals with at least a partial testis differentiation even in absence of SRY. This particular condition is present in various mammals including the dog. Seven dogs characterized by XX karyotype, absence of SRY gene, and testicular tissue development were analysed by Array-CGH. In two cases the array-CGH analysis detected an interstitial heterozygous duplication of chromosome 9. The duplication contained the SOX9 coding region. In this work we provide for the first time a causative mutation for the XXSR condition in the dog. Moreover this report supports the idea that the dog represents a good animal model for the study of XXSR condition caused by abnormalities in the SOX9 locus.

NASA printing, duplicating, and copying management handbook

NASA Technical Reports Server (NTRS)

1993-01-01

This handbook provides information and procedures for the implementation of NASA policy and applicable laws and regulations relating to printing, duplicating, and copying. The topics addressed include a description of relevant laws and regulations, authorizations required, and responsible entities for NASA printing, duplicating, and copying. The policy of NASA is to ensure understanding and application of authority and responsibility on printing matters. Where necessary, the handbook clarifies the intent of basic laws and regulations applicable to NASA.

47 CFR 76.1609 - Non-duplication and syndicated exclusivity.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 47 Telecommunication 4 2010-10-01 2010-10-01 false Non-duplication and syndicated exclusivity. 76.1609 Section 76.1609 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) BROADCAST RADIO SERVICES MULTICHANNEL VIDEO AND CABLE TELEVISION SERVICE Notices § 76.1609 Non-duplication and syndicated...

47 CFR 76.1609 - Non-duplication and syndicated exclusivity.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 47 Telecommunication 4 2012-10-01 2012-10-01 false Non-duplication and syndicated exclusivity. 76.1609 Section 76.1609 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) BROADCAST RADIO SERVICES MULTICHANNEL VIDEO AND CABLE TELEVISION SERVICE Notices § 76.1609 Non-duplication and syndicated...

47 CFR 76.1609 - Non-duplication and syndicated exclusivity.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 47 Telecommunication 4 2014-10-01 2014-10-01 false Non-duplication and syndicated exclusivity. 76.1609 Section 76.1609 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) BROADCAST RADIO SERVICES MULTICHANNEL VIDEO AND CABLE TELEVISION SERVICE Notices § 76.1609 Non-duplication and syndicated...

47 CFR 76.1609 - Non-duplication and syndicated exclusivity.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 47 Telecommunication 4 2013-10-01 2013-10-01 false Non-duplication and syndicated exclusivity. 76.1609 Section 76.1609 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) BROADCAST RADIO SERVICES MULTICHANNEL VIDEO AND CABLE TELEVISION SERVICE Notices § 76.1609 Non-duplication and syndicated...

47 CFR 76.1609 - Non-duplication and syndicated exclusivity.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 47 Telecommunication 4 2011-10-01 2011-10-01 false Non-duplication and syndicated exclusivity. 76.1609 Section 76.1609 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) BROADCAST RADIO SERVICES MULTICHANNEL VIDEO AND CABLE TELEVISION SERVICE Notices § 76.1609 Non-duplication and syndicated...

Use of Diagnostic Imaging in the Evaluation of Gastrointestinal Tract Duplications

PubMed Central

Laskowska, Katarzyna; Gałązka, Przemysław; Daniluk-Matraś, Irena; Leszczyński, Waldemar; Serafin, Zbigniew

2014-01-01

Summary Background Gastrointestinal tract duplication is a rare malformation associated with the presence of additional segment of the fetal gut. The aim of this study was to retrospectively review clinical features and imaging findings in intraoperatively confirmed cases of gastrointestinal tract duplication in children. Material/Methods The analysis included own material from the years 2002–2012. The analyzed group included 14 children, among them 8 boys and 6 girls. The youngest patient was diagnosed at the age of three weeks, and the oldest at 12 years of age. Results The duplication cysts were identified in the esophagus (n=2), stomach (n=5), duodenum (n=1), terminal ileum (n=5), and rectum (n=1). In four cases, the duplication coexisted with other anomalies, such as patent urachus, Meckel’s diverticulum, mesenteric cyst, and accessory pancreas. Clinical manifestation of gastrointestinal duplication cysts was variable, and some of them were detected accidently. Thin- or thick-walled cystic structures adjacent to the wall of neighboring gastrointestinal segment were documented on diagnostic imaging. Conclusions Ultrasound and computed tomography are the methods of choice in the evaluation of gastrointestinal duplication cysts. Apart from the diagnosis of the duplication cyst, an important issue is the detection of concomitant developmental pathologies, including pancreatic heterotopy. PMID:25114725

Usher syndrome clinical types I and II: could ocular symptoms and signs differentiate between the two types?

PubMed

Tsilou, Ekaterini T; Rubin, Benjamin I; Caruso, Rafael C; Reed, George F; Pikus, Anita; Hejtmancik, James F; Iwata, Fumino; Redman, Joy B; Kaiser-Kupfer, Muriel I

2002-04-01

Usher syndrome types I and II are clinical syndromes with substantial genetic and clinical heterogeneity. We undertook the current study in order to identify ocular symptoms and signs that could differentiate between the two types. Sixty-seven patients with Usher syndrome were evaluated. Based on audiologic and vestibular findings, patients were classified as either Usher type I or II. The severity of the ocular signs and symptoms present in each type were compared. Visual acuity, visual field area, electroretinographic amplitude, incidence of cataract and macular lesions were not significantly different between Usher types I and II. However, the ages when night blindness was perceived and retinitis pigmentosa was diagnosed differed significantly between the two types. There seems to be some overlap between types I and II of Usher syndrome in regard to the ophthalmologic findings. However, night blindness appears earlier in Usher type I (although the difference in age of appearance appears to be less dramatic than previously assumed). Molecular elucidation of Usher syndrome may serve as a key to understanding these differences and, perhaps, provide a better tool for use in clinical diagnosis, prognosis and genetic counseling.

The large soybean (Glycine max) WRKY TF family expanded by segmental duplication events and subsequent divergent selection among subgroups

PubMed Central

2013-01-01

Background WRKY genes encode one of the most abundant groups of transcription factors in higher plants, and its members regulate important biological process such as growth, development, and responses to biotic and abiotic stresses. Although the soybean genome sequence has been published, functional studies on soybean genes still lag behind those of other species. Results We identified a total of 133 WRKY members in the soybean genome. According to structural features of their encoded proteins and to the phylogenetic tree, the soybean WRKY family could be classified into three groups (groups I, II, and III). A majority of WRKY genes (76.7%; 102 of 133) were segmentally duplicated and 13.5% (18 of 133) of the genes were tandemly duplicated. This pattern was not apparent in Arabidopsis or rice. The transcriptome atlas revealed notable differential expression in either transcript abundance or in expression patterns under normal growth conditions, which indicated wide functional divergence in this family. Furthermore, some critical amino acids were detected using DIVERGE v2.0 in specific comparisons, suggesting that these sites have contributed to functional divergence among groups or subgroups. In addition, site model and branch-site model analyses of positive Darwinian selection (PDS) showed that different selection regimes could have affected the evolution of these groups. Sites with high probabilities of having been under PDS were found in groups I, II c, II e, and III. Together, these results contribute to a detailed understanding of the molecular evolution of the WRKY gene family in soybean. Conclusions In this work, all the WRKY genes, which were generated mainly through segmental duplication, were identified in the soybean genome. Moreover, differential expression and functional divergence of the duplicated WRKY genes were two major features of this family throughout their evolutionary history. Positive selection analysis revealed that the different groups have

The large soybean (Glycine max) WRKY TF family expanded by segmental duplication events and subsequent divergent selection among subgroups.

PubMed

Yin, Guangjun; Xu, Hongliang; Xiao, Shuyang; Qin, Yajuan; Li, Yaxuan; Yan, Yueming; Hu, Yingkao

2013-10-03

WRKY genes encode one of the most abundant groups of transcription factors in higher plants, and its members regulate important biological process such as growth, development, and responses to biotic and abiotic stresses. Although the soybean genome sequence has been published, functional studies on soybean genes still lag behind those of other species. We identified a total of 133 WRKY members in the soybean genome. According to structural features of their encoded proteins and to the phylogenetic tree, the soybean WRKY family could be classified into three groups (groups I, II, and III). A majority of WRKY genes (76.7%; 102 of 133) were segmentally duplicated and 13.5% (18 of 133) of the genes were tandemly duplicated. This pattern was not apparent in Arabidopsis or rice. The transcriptome atlas revealed notable differential expression in either transcript abundance or in expression patterns under normal growth conditions, which indicated wide functional divergence in this family. Furthermore, some critical amino acids were detected using DIVERGE v2.0 in specific comparisons, suggesting that these sites have contributed to functional divergence among groups or subgroups. In addition, site model and branch-site model analyses of positive Darwinian selection (PDS) showed that different selection regimes could have affected the evolution of these groups. Sites with high probabilities of having been under PDS were found in groups I, II c, II e, and III. Together, these results contribute to a detailed understanding of the molecular evolution of the WRKY gene family in soybean. In this work, all the WRKY genes, which were generated mainly through segmental duplication, were identified in the soybean genome. Moreover, differential expression and functional divergence of the duplicated WRKY genes were two major features of this family throughout their evolutionary history. Positive selection analysis revealed that the different groups have different evolutionary rates

Detection of Turner syndrome using X-chromosome inactivation specific differentially methylated CpG sites: A pilot study.

PubMed

Zhang, Qiang; Guo, Xiaohong; Tian, Tian; Wang, Teng; Li, Qiaoli; Wang, Lei; Liu, Yun; Xing, Qinghe; He, Lin; Zhao, Xinzhi

2017-05-01

Early diagnosis of Turner syndrome (TS) may improve preventive measures and treatment. X-chromosome inactivation specific differentially methylated CpG sites (XIDMSs) that are high methylated in inactive X chromosomes (Xi) and unmethylated in active X chromosomes (Xa) may be potential makers for TS detection. The candidate XIDMSs were screened from 9 male and 12 female DNA samples with normal karyotypes using the Illumina 450k array and validated by bisulfite sequencing PCR and pyrosequencing assay. X chromosome dosage was calculated according to the methylation level of multiple XIDMSs. Overall, 108 candidate XIDMSs were screened by the 450k array. Validations indicated that XIDMSs gathered and formed the X-chromosome inactivation specific differentially methylated regions (XIDMRs). Using 3 XIDMRs at SAT1, UXT and UTP14A loci, 36 TS, 22 normal female and 6 male samples were analyzed. Methylation levels of the 20 XIDMSs in the XIDMRs could distinguish between TS and normal female DNA samples, the X chromosome dosage was consistent with karyotyping data. Analyzing samples of 2 triple X syndrome and 3 Klinefelter syndrome patients suggested that this method could be used to detect X chromosome aneuploids other than TS. XIDMSs are widely spread along the X chromosome and might be effective markers for detection of TS and other X chromosome aneuploids. Copyright © 2017 Elsevier B.V. All rights reserved.

Yeast Interspecies Comparative Proteomics Reveals Divergence in Expression Profiles and Provides Insights into Proteome Resource Allocation and Evolutionary Roles of Gene Duplication*

PubMed Central

Kito, Keiji; Ito, Haruka; Nohara, Takehiro; Ohnishi, Mihoko; Ishibashi, Yuko; Takeda, Daisuke

2016-01-01

Omics analysis is a versatile approach for understanding the conservation and diversity of molecular systems across multiple taxa. In this study, we compared the proteome expression profiles of four yeast species (Saccharomyces cerevisiae, Saccharomyces mikatae, Kluyveromyces waltii, and Kluyveromyces lactis) grown on glucose- or glycerol-containing media. Conserved expression changes across all species were observed only for a small proportion of all proteins differentially expressed between the two growth conditions. Two Kluyveromyces species, both of which exhibited a high growth rate on glycerol, a nonfermentative carbon source, showed distinct species-specific expression profiles. In K. waltii grown on glycerol, proteins involved in the glyoxylate cycle and gluconeogenesis were expressed in high abundance. In K. lactis grown on glycerol, the expression of glycolytic and ethanol metabolic enzymes was unexpectedly low, whereas proteins involved in cytoplasmic translation, including ribosomal proteins and elongation factors, were highly expressed. These marked differences in the types of predominantly expressed proteins suggest that K. lactis optimizes the balance of proteome resource allocation between metabolism and protein synthesis giving priority to cellular growth. In S. cerevisiae, about 450 duplicate gene pairs were retained after whole-genome duplication. Intriguingly, we found that in the case of duplicates with conserved sequences, the total abundance of proteins encoded by a duplicate pair in S. cerevisiae was similar to that of protein encoded by nonduplicated ortholog in Kluyveromyces yeast. Given the frequency of haploinsufficiency, this observation suggests that conserved duplicate genes, even though minor cases of retained duplicates, do not exhibit a dosage effect in yeast, except for ribosomal proteins. Thus, comparative proteomic analyses across multiple species may reveal not only species-specific characteristics of metabolic processes under

Human-Specific Duplication and Mosaic Transcripts: The Recent Paralogous Structure of Chromosome 22

PubMed Central

Bailey, Jeffrey A. ; Yavor, Amy M. ; Viggiano, Luigi ; Misceo, Doriana ; Horvath, Juliann E. ; Archidiacono, Nicoletta ; Schwartz, Stuart ; Rocchi, Mariano ; Eichler, Evan E. 

2002-01-01

In recent decades, comparative chromosomal banding, chromosome painting, and gene-order studies have shown strong conservation of gross chromosome structure and gene order in mammals. However, findings from the human genome sequence suggest an unprecedented degree of recent (<35 million years ago) segmental duplication. This dynamism of segmental duplications has important implications in disease and evolution. Here we present a chromosome-wide view of the structure and evolution of the most highly homologous duplications (⩾1 kb and ⩾90%) on chromosome 22. Overall, 10.8% (3.7/33.8 Mb) of chromosome 22 is duplicated, with an average sequence identity of 95.4%. To organize the duplications into tractable units, intron-exon structure and well-defined duplication boundaries were used to define 78 duplicated modules (minimally shared evolutionary segments) with 157 copies on chromosome 22. Analysis of these modules provides evidence for the creation or modification of 11 novel transcripts. Comparative FISH analyses of human, chimpanzee, gorilla, orangutan, and macaque reveal qualitative and quantitative differences in the distribution of these duplications—consistent with their recent origin. Several duplications appear to be human specific, including a ∼400-kb duplication (99.4%–99.8% sequence identity) that transposed from chromosome 14 to the most proximal pericentromeric region of chromosome 22. Experimental and in silico data further support a pericentromeric gradient of duplications where the most recent duplications transpose adjacent to the centromere. Taken together, these data suggest that segmental duplications have been an ongoing process of primate genome evolution, contributing to recent gene innovation and the dynamic transformation of genome architecture within and among closely related species. PMID:11731936

Testing of duplicate rinse aliquots for presence of Salmonella

USDA-ARS?s Scientific Manuscript database

Testing of chicken carcass rinses for Salmonella prevalence is often performed in duplicate because of the potential importance of the results, but anecdotal reports indicate that duplicate samples often disagree. This might be due to normal variation in microbiological methods or to the testing of...

Methods, apparatus and system for selective duplication of subtasks

DOEpatents

Andrade Costa, Carlos H.; Cher, Chen-Yong; Park, Yoonho; Rosenburg, Bryan S.; Ryu, Kyung D.

2016-03-29

A method for selective duplication of subtasks in a high-performance computing system includes: monitoring a health status of one or more nodes in a high-performance computing system, where one or more subtasks of a parallel task execute on the one or more nodes; identifying one or more nodes as having a likelihood of failure which exceeds a first prescribed threshold; selectively duplicating the one or more subtasks that execute on the one or more nodes having a likelihood of failure which exceeds the first prescribed threshold; and notifying a messaging library that one or more subtasks were duplicated.

Persons with Quebec platelet disorder have a tandem duplication of PLAU, the urokinase plasminogen activator gene.

PubMed

Paterson, Andrew D; Rommens, Johanna M; Bharaj, Bhupinder; Blavignac, Jessica; Wong, Isidro; Diamandis, Maria; Waye, John S; Rivard, Georges E; Hayward, Catherine P M

2010-02-11

Quebec platelet disorder (QPD) is an autosomal dominant bleeding disorder linked to a region on chromosome 10 that includes PLAU, the urokinase plasminogen activator gene. QPD increases urokinase plasminogen activator mRNA levels, particularly during megakaryocyte differentiation, without altering expression of flanking genes. Because PLAU sequence changes were excluded as the cause of this bleeding disorder, we investigated whether the QPD mutation involved PLAU copy number variation. All 38 subjects with QPD had a direct tandem duplication of a 78-kb genomic segment that includes PLAU. This mutation was specific to QPD as it was not present in any unaffected family members (n = 114), unrelated French Canadians (n = 221), or other persons tested (n = 90). This new information on the genetic mutation will facilitate diagnostic testing for QPD and studies of its pathogenesis and prevalence. QPD is the first bleeding disorder to be associated with a gene duplication event and a PLAU mutation.

Models for loosely linked gene duplicates suggest lengthy persistence of both copies.

PubMed

O'Hely, Martin; Wockner, Leesa

2007-06-21

Consider the appearance of a duplicate copy of a gene at a locus linked loosely, if at all, to the locus at which the gene is usually found. If all copies of the gene are subject to non-functionalizing mutations, then two fates are possible: loss of functional copies at the duplicate locus (loss of duplicate expression), or loss of functional copies at the original locus (map change). This paper proposes a simple model to address the probability of map change, the time taken for a map change and/or loss of duplicate expression, and considers where in the spectrum between loss of duplicate expression and map change such a duplicate complex is likely to be found. The findings are: the probability of map change is always half the reciprocal of the population size N, the time for a map change to occur is order NlogN generations, and that there is a marked tendency for duplicates to remain near equi-frequency with the gene at the original locus for a large portion of that time. This is in excellent agreement with simulations.

Adrenal GIPR expression and chromosome 19q13 microduplications in GIP-dependent Cushing’s syndrome

PubMed Central

Lecoq, Anne-Lise; Stratakis, Constantine A.; Viengchareun, Say; Chaligné, Ronan; Tosca, Lucie; Hage, Mirella; Berthon, Annabel; Faucz, Fabio R.; Hanna, Patrick; Boyer, Hadrien-Gaël; Servant, Nicolas; Salenave, Sylvie; Tachdjian, Gérard; Adam, Clovis; Benhamo, Vanessa; Clauser, Eric; Guiochon-Mantel, Anne; Young, Jacques; Lombès, Marc; Bourdeau, Isabelle; Maiter, Dominique; Tabarin, Antoine; Bertherat, Jérôme; Lefebvre, Hervé; Louiset, Estelle; Lacroix, André; Bouligand, Jérôme; Kamenický, Peter

2017-01-01

GIP-dependent Cushing’s syndrome is caused by ectopic expression of glucose-dependent insulinotropic polypeptide receptor (GIPR) in cortisol-producing adrenal adenomas or in bilateral macronodular adrenal hyperplasias. Molecular mechanisms leading to ectopic GIPR expression in adrenal tissue are not known. Here we performed molecular analyses on adrenocortical adenomas and bilateral macronodular adrenal hyperplasias obtained from 14 patients with GIP-dependent adrenal Cushing’s syndrome and one patient with GIP-dependent aldosteronism. GIPR expression in all adenoma and hyperplasia samples occurred through transcriptional activation of a single allele of the GIPR gene. While no abnormality was detected in proximal GIPR promoter methylation, we identified somatic duplications in chromosome region 19q13.32 containing the GIPR locus in the adrenocortical lesions derived from 3 patients. In 2 adenoma samples, the duplicated 19q13.32 region was rearranged with other chromosome regions, whereas a single tissue sample with hyperplasia had a 19q duplication only. We demonstrated that juxtaposition with cis-acting regulatory sequences such as glucocorticoid response elements in the newly identified genomic environment drives abnormal expression of the translocated GIPR allele in adenoma cells. Altogether, our results provide insight into the molecular pathogenesis of GIP-dependent Cushing’s syndrome, occurring through monoallelic transcriptional activation of GIPR driven in some adrenal lesions by structural variations. PMID:28931750

Both mechanism and age of duplications contribute to biased gene retention patterns in plants.

PubMed

Rody, Hugo V S; Baute, Gregory J; Rieseberg, Loren H; Oliveira, Luiz O

2017-01-06

All extant seed plants are successful paleopolyploids, whose genomes carry duplicate genes that have survived repeated episodes of diploidization. However, the survival of gene duplicates is biased with respect to gene function and mechanism of duplication. Transcription factors, in particular, are reported to be preferentially retained following whole-genome duplications (WGDs), but disproportionately lost when duplicated by tandem events. An explanation for this pattern is provided by the Gene Balance Hypothesis (GBH), which posits that duplicates of highly connected genes are retained following WGDs to maintain optimal stoichiometry among gene products; but such connected gene duplicates are disfavored following tandem duplications. We used genomic data from 25 taxonomically diverse plant species to investigate the roles of duplication mechanism, gene function, and age of duplication in the retention of duplicate genes. Enrichment analyses were conducted to identify Gene Ontology (GO) functional categories that were overrepresented in either WGD or tandem duplications, or across ranges of divergence times. Tandem paralogs were much younger, on average, than WGD paralogs and the most frequently overrepresented GO categories were not shared between tandem and WGD paralogs. Transcription factors were overrepresented among ancient paralogs regardless of mechanism of origin or presence of a WGD. Also, in many cases, there was no bias toward transcription factor retention following recent WGDs. Both the fixation and the retention of duplicated genes in plant genomes are context-dependent events. The strong bias toward ancient transcription factor duplicates can be reconciled with the GBH if selection for optimal stoichiometry among gene products is strongest following the earliest polyploidization events and becomes increasingly relaxed as gene families expand.

An increased duplication of ZRS region that caused more than one supernumerary digits preaxial polydactyly in a large Chinese family.

PubMed

Wang, Bin; Diao, Yutao; Liu, Qiji; An, Hongqiang; Ma, Ruiping; Jiang, Guosheng; Lai, Nannan; Li, Ziwei; Zhu, Xiaoxiao; Zhao, Lin; Guo, Qiang; Zhang, Zhen; Sun, Rong; Li, Xia

2016-12-06

Preaxial polydactyly (PPD) is inherited in an autosomal dominant fashion and characterized by the presence of one or more supernumerary digits on the thumb side. It had been identified that point mutation or genomic duplications of the long-range limb-specific cis-regulator - zone of polarizing activity regulatory sequence (ZRS) cause PPD or other limb deformities such as syndactyly type IV (SD4) and Triphalangeal thumb-polysyndactyly syndrome (TPTPS). Most previously reported cases involved with no more than one extra finger; however, the role of the point mutation or genomic duplications of ZRS in the case of more than one redundant finger polydactyly remains unclear. In this article, we reported a family case of more than one redundant finger polydactyly on the thumb side for bilateral hands with a pedigree chart of the family. Results of quantitative PCR (qPCR) and sequence analysis suggested that the relative copy number (RCN) of ZRS but not point mutation (including insertion and deletion) was involved in all affected individuals.

Asymmetric histone modifications between the original and derived loci of human segmental duplications

PubMed Central

Zheng, Deyou

2008-01-01

Background Sequencing and annotation of several mammalian genomes have revealed that segmental duplications are a common architectural feature of primate genomes; in fact, about 5% of the human genome is composed of large blocks of interspersed segmental duplications. These segmental duplications have been implicated in genomic copy-number variation, gene novelty, and various genomic disorders. However, the molecular processes involved in the evolution and regulation of duplicated sequences remain largely unexplored. Results In this study, the profile of about 20 histone modifications within human segmental duplications was characterized using high-resolution, genome-wide data derived from a ChIP-Seq study. The analysis demonstrates that derivative loci of segmental duplications often differ significantly from the original with respect to many histone methylations. Further investigation showed that genes are present three times more frequently in the original than in the derivative, whereas pseudogenes exhibit the opposite trend. These asymmetries tend to increase with the age of segmental duplications. The uneven distribution of genes and pseudogenes does not, however, fully account for the asymmetry in the profile of histone modifications. Conclusion The first systematic analysis of histone modifications between segmental duplications demonstrates that two seemingly 'identical' genomic copies are distinct in their epigenomic properties. Results here suggest that local chromatin environments may be implicated in the discrimination of derived copies of segmental duplications from their originals, leading to a biased pseudogenization of the new duplicates. The data also indicate that further exploration of the interactions between histone modification and sequence degeneration is necessary in order to understand the divergence of duplicated sequences. PMID:18598352

Two Rounds of Whole Genome Duplication in the Ancestral Vertebrate

PubMed Central

Dehal, Paramvir; Boore, Jeffrey L

2005-01-01

The hypothesis that the relatively large and complex vertebrate genome was created by two ancient, whole genome duplications has been hotly debated, but remains unresolved. We reconstructed the evolutionary relationships of all gene families from the complete gene sets of a tunicate, fish, mouse, and human, and then determined when each gene duplicated relative to the evolutionary tree of the organisms. We confirmed the results of earlier studies that there remains little signal of these events in numbers of duplicated genes, gene tree topology, or the number of genes per multigene family. However, when we plotted the genomic map positions of only the subset of paralogous genes that were duplicated prior to the fish–tetrapod split, their global physical organization provides unmistakable evidence of two distinct genome duplication events early in vertebrate evolution indicated by clear patterns of four-way paralogous regions covering a large part of the human genome. Our results highlight the potential for these large-scale genomic events to have driven the evolutionary success of the vertebrate lineage. PMID:16128622

A Duplicate Construction Experiment.

ERIC Educational Resources Information Center

Bridgeman, Brent

This experiment was designed to assess the ability of item writers to construct truly parallel tests based on a "duplicate-construction experiment" in which Cronbach argues that if the universe description and sampling are ideally refined, the two independently constructed tests will be entirely equivalent, and that within the limits of item…

10 CFR 7.21 - Cost of duplication of documents.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 10 Energy 1 2014-01-01 2014-01-01 false Cost of duplication of documents. 7.21 Section 7.21 Energy NUCLEAR REGULATORY COMMISSION ADVISORY COMMITTEES § 7.21 Cost of duplication of documents. Copies of the records, reports, transcripts, minutes, appendices, working papers, drafts, studies, agenda, or other...

10 CFR 7.21 - Cost of duplication of documents.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 10 Energy 1 2013-01-01 2013-01-01 false Cost of duplication of documents. 7.21 Section 7.21 Energy NUCLEAR REGULATORY COMMISSION ADVISORY COMMITTEES § 7.21 Cost of duplication of documents. Copies of the records, reports, transcripts, minutes, appendices, working papers, drafts, studies, agenda, or other...

10 CFR 7.21 - Cost of duplication of documents.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 10 Energy 1 2012-01-01 2012-01-01 false Cost of duplication of documents. 7.21 Section 7.21 Energy NUCLEAR REGULATORY COMMISSION ADVISORY COMMITTEES § 7.21 Cost of duplication of documents. Copies of the records, reports, transcripts, minutes, appendices, working papers, drafts, studies, agenda, or other...

10 CFR 7.21 - Cost of duplication of documents.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 10 Energy 1 2010-01-01 2010-01-01 false Cost of duplication of documents. 7.21 Section 7.21 Energy NUCLEAR REGULATORY COMMISSION ADVISORY COMMITTEES § 7.21 Cost of duplication of documents. Copies of the records, reports, transcripts, minutes, appendices, working papers, drafts, studies, agenda, or other...

10 CFR 7.21 - Cost of duplication of documents.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 10 Energy 1 2011-01-01 2011-01-01 false Cost of duplication of documents. 7.21 Section 7.21 Energy NUCLEAR REGULATORY COMMISSION ADVISORY COMMITTEES § 7.21 Cost of duplication of documents. Copies of the records, reports, transcripts, minutes, appendices, working papers, drafts, studies, agenda, or other...

Coexistence of 9p Deletion Syndrome and Autism Spectrum Disorder

ERIC Educational Resources Information Center

Günes, Serkan; Ekinci, Özalp; Ekinci, Nuran; Toros, Fevziye

2017-01-01

Deletion or duplication of the short arm of chromosome 9 may lead to a variety of clinical conditions including craniofacial and limb abnormalities, skeletal malformations, mental retardation, and autism spectrum disorder. Here, we present a case report of 5-year-old boy with 9p deletion syndrome and autism spectrum disorder.

Duplicate laboratory test reduction using a clinical decision support tool.

PubMed

Procop, Gary W; Yerian, Lisa M; Wyllie, Robert; Harrison, A Marc; Kottke-Marchant, Kandice

2014-05-01

Duplicate laboratory tests that are unwarranted increase unnecessary phlebotomy, which contributes to iatrogenic anemia, decreased patient satisfaction, and increased health care costs. We employed a clinical decision support tool (CDST) to block unnecessary duplicate test orders during the computerized physician order entry (CPOE) process. We assessed laboratory cost savings after 2 years and searched for untoward patient events associated with this intervention. This CDST blocked 11,790 unnecessary duplicate test orders in these 2 years, which resulted in a cost savings of $183,586. There were no untoward effects reported associated with this intervention. The movement to CPOE affords real-time interaction between the laboratory and the physician through CDSTs that signal duplicate orders. These interactions save health care dollars and should also increase patient satisfaction and well-being.

A Y-Encoded Suppressor of Feminization Arose via Lineage-Specific Duplication of a Cytokinin Response Regulator in Kiwifruit[OPEN

PubMed Central

Ohtani, Haruka; Morimoto, Takuya; Beppu, Kenji; Kataoka, Ikuo

2018-01-01

Dioecy, the presence of male and female flowers on distinct individuals, has evolved independently in multiple plant lineages, and the genes involved in this differential development are just starting to be uncovered in a few species. Here, we used genomic approaches to investigate this pathway in kiwifruits (genus Actinidia). Genome-wide cataloging of male-specific subsequences, combined with transcriptome analysis, led to the identification of a type-C cytokinin response regulator as a potential sex determinant gene in this genus. Functional transgenic analyses in two model systems, Arabidopsis thaliana and Nicotiana tabacum, indicated that this gene acts as a dominant suppressor of carpel development, prompting us to name it Shy Girl (SyGI). Evolutionary analyses in a panel of Actinidia species revealed that SyGI is located in the Y-specific region of the genome and probably arose from a lineage-specific gene duplication. Comparisons with the duplicated autosomal counterpart, and with orthologs from other angiosperms, suggest that the SyGI-specific duplication and subsequent evolution of cis-elements may have played a key role in the acquisition of separate sexes in this species. PMID:29626069

A computational method for estimating the PCR duplication rate in DNA and RNA-seq experiments.

PubMed

Bansal, Vikas

2017-03-14

PCR amplification is an important step in the preparation of DNA sequencing libraries prior to high-throughput sequencing. PCR amplification introduces redundant reads in the sequence data and estimating the PCR duplication rate is important to assess the frequency of such reads. Existing computational methods do not distinguish PCR duplicates from "natural" read duplicates that represent independent DNA fragments and therefore, over-estimate the PCR duplication rate for DNA-seq and RNA-seq experiments. In this paper, we present a computational method to estimate the average PCR duplication rate of high-throughput sequence datasets that accounts for natural read duplicates by leveraging heterozygous variants in an individual genome. Analysis of simulated data and exome sequence data from the 1000 Genomes project demonstrated that our method can accurately estimate the PCR duplication rate on paired-end as well as single-end read datasets which contain a high proportion of natural read duplicates. Further, analysis of exome datasets prepared using the Nextera library preparation method indicated that 45-50% of read duplicates correspond to natural read duplicates likely due to fragmentation bias. Finally, analysis of RNA-seq datasets from individuals in the 1000 Genomes project demonstrated that 70-95% of read duplicates observed in such datasets correspond to natural duplicates sampled from genes with high expression and identified outlier samples with a 2-fold greater PCR duplication rate than other samples. The method described here is a useful tool for estimating the PCR duplication rate of high-throughput sequence datasets and for assessing the fraction of read duplicates that correspond to natural read duplicates. An implementation of the method is available at https://github.com/vibansal/PCRduplicates .

MECP2 duplications in six patients with complex sex chromosome rearrangements

PubMed Central

Breman, Amy M; Ramocki, Melissa B; Kang, Sung-Hae L; Williams, Misti; Freedenberg, Debra; Patel, Ankita; Bader, Patricia I; Cheung, Sau Wai

2011-01-01

Duplications of the Xq28 chromosome region resulting in functional disomy are associated with a distinct clinical phenotype characterized by infantile hypotonia, severe developmental delay, progressive neurological impairment, absent speech, and proneness to infections. Increased expression of the dosage-sensitive MECP2 gene is considered responsible for the severe neurological impairments observed in affected individuals. Although cytogenetically visible duplications of Xq28 are well documented in the published literature, recent advances using array comparative genomic hybridization (CGH) led to the detection of an increasing number of microduplications spanning MECP2. In rare cases, duplication results from intrachromosomal rearrangement between the X and Y chromosomes. We report six cases with sex chromosome rearrangements involving duplication of MECP2. Cases 1–4 are unbalanced rearrangements between X and Y, resulting in MECP2 duplication. The additional Xq material was translocated to Yp in three cases (cases 1–3), and to the heterochromatic region of Yq12 in one case (case 4). Cases 5 and 6 were identified by array CGH to have a loss in copy number at Xp and a gain in copy number at Xq28 involving the MECP2 gene. In both cases, fluorescent in situ hybridization (FISH) analysis revealed a recombinant X chromosome containing the duplicated material from Xq28 on Xp, resulting from a maternal pericentric inversion. These cases add to a growing number of MECP2 duplications that have been detected by array CGH, while demonstrating the value of confirmatory chromosome and FISH studies for the localization of the duplicated material and the identification of complex rearrangements. PMID:21119712

Perspectives on Program Duplication

ERIC Educational Resources Information Center

Morrison, Gail M.

2010-01-01

Concerns about program duplication in higher education are often reminiscent of Supreme Court Justice Potter Stewart's now famous remark about pornography: "I know it when I see it." The problem with that reaction is that, at least on its surface, this response seems intuitive and emotional, to say nothing of subjective and personal. The…

Consensus properties and their large-scale applications for the gene duplication problem.

PubMed

Moon, Jucheol; Lin, Harris T; Eulenstein, Oliver

2016-06-01

Solving the gene duplication problem is a classical approach for species tree inference from gene trees that are confounded by gene duplications. This problem takes a collection of gene trees and seeks a species tree that implies the minimum number of gene duplications. Wilkinson et al. posed the conjecture that the gene duplication problem satisfies the desirable Pareto property for clusters. That is, for every instance of the problem, all clusters that are commonly present in the input gene trees of this instance, called strict consensus, will also be found in every solution to this instance. We prove that this conjecture does not generally hold. Despite this negative result we show that the gene duplication problem satisfies a weaker version of the Pareto property where the strict consensus is found in at least one solution (rather than all solutions). This weaker property contributes to our design of an efficient scalable algorithm for the gene duplication problem. We demonstrate the performance of our algorithm in analyzing large-scale empirical datasets. Finally, we utilize the algorithm to evaluate the accuracy of standard heuristics for the gene duplication problem using simulated datasets.

Evolution of a Novel Antiviral Immune-Signaling Interaction by Partial-Gene Duplication

PubMed Central

Korithoski, Bryan; Kolaczkowski, Oralia; Mukherjee, Krishanu; Kola, Reema; Earl, Chandra; Kolaczkowski, Bryan

2015-01-01

The RIG-like receptors (RLRs) are related proteins that identify viral RNA in the cytoplasm and activate cellular immune responses, primarily through direct protein-protein interactions with the signal transducer, IPS1. Although it has been well established that the RLRs, RIG-I and MDA5, activate IPS1 through binding between the twin caspase activation and recruitment domains (CARDs) on the RLR and a homologous CARD on IPS1, it is less clear which specific RLR CARD(s) are required for this interaction, and almost nothing is known about how the RLR-IPS1 interaction evolved. In contrast to what has been observed in the presence of immune-modulating K63-linked polyubiquitin, here we show that—in the absence of ubiquitin—it is the first CARD domain of human RIG-I and MDA5 (CARD1) that binds directly to IPS1 CARD, and not the second (CARD2). Although the RLRs originated in the earliest animals, both the IPS1 gene and the twin-CARD domain architecture of RIG-I and MDA5 arose much later in the deuterostome lineage, probably through a series of tandem partial-gene duplication events facilitated by tight clustering of RLRs and IPS1 in the ancestral deuterostome genome. Functional differentiation of RIG-I CARD1 and CARD2 appears to have occurred early during this proliferation of RLR and related CARDs, potentially driven by adaptive coevolution between RIG-I CARD domains and IPS1 CARD. However, functional differentiation of MDA5 CARD1 and CARD2 occurred later. These results fit a general model in which duplications of protein-protein interaction domains into novel gene contexts could facilitate the expansion of signaling networks and suggest a potentially important role for functionally-linked gene clusters in generating novel immune-signaling pathways. PMID:26356745

Kindler syndrome.

PubMed

Kaviarasan, P K; Prasad, P V S; Shradda; Viswanathan, P

2005-01-01

Kindler syndrome is a rare autosomal recessive disorder associated with skin fragility. It is characterized by blistering in infancy, photosensitivity and progressive poikiloderma. The syndrome involves the skin and mucous membrane with radiological changes. The genetic defect has been identified on the short arm of chromosome 20. This report describes an 18-year-old patient with classical features like blistering and photosensitivity in childhood and the subsequent development of poikiloderma. The differential diagnosis of Kindler syndrome includes diseases like Bloom syndrome, Cockayne syndrome, dyskeratosis congenita, epidermolysis bullosa, Rothmund-Thomson syndrome and xeroderma pigmentosum. Our patient had classical cutaneous features of Kindler syndrome with phimosis as a complication.

TGM5 mutations impact epidermal differentiation in acral peeling skin syndrome.

PubMed

Pigors, Manuela; Kiritsi, Dimitra; Cobzaru, Cristina; Schwieger-Briel, Agnes; Suárez, Jose; Faletra, Flavio; Aho, Heikki; Mäkelä, Leeni; Kern, Johannes S; Bruckner-Tuderman, Leena; Has, Cristina

2012-10-01

Acral peeling skin syndrome (APSS) is an autosomal recessive skin disorder characterized by acral blistering and peeling of the outermost layers of the epidermis. It is caused by mutations in the gene for transglutaminase 5, TGM5. Here, we report on clinical and molecular findings in 11 patients and extend the TGM5 mutation database by four, to our knowledge, previously unreported mutations: p.M1T, p.L41P, p.L214CfsX15, and p.S604IfsX9. The recurrent mutation p.G113C was found in 9 patients, but also in 3 of 100 control individuals in a heterozygous state, indicating that APSS might be more widespread than hitherto expected. Using quantitative real-time PCR, immunoblotting, and immunofluorescence analysis, we demonstrate that expression and distribution of several epidermal differentiation markers and corneodesmosin (CDSN) is altered in APSS keratinocytes and skin. Although the expression of transglutaminases 1 and 3 was not changed, we found an upregulation of keratin 1, keratin 10, involucrin, loricrin, and CDSN, probably as compensatory mechanisms for stabilization of the epidermal barrier. Our results give insights into the consequences of TGM5 mutations on terminal epidermal differentiation.

[Anterior rectal duplication in adult patient: a case report].

PubMed

Rodríguez-Cabrera, J; Villanueva-Sáenz, E; Bolaños-Badillo, L E

2009-01-01

To report a case of rectal duplication in the adult and make a literature review. The intestinal duplications are injuries of congenital origin that can exist from the base of the tongue to the anal verge, being the most frequent site at level of terminal ileum (22%) and at the rectal level in 5% To date approximately exist 80 reports in world-wide Literature generally in the pediatric population being little frequent in the adult age. Its presentation could be tubular or cystic. The recommended treatment is the surgical resection generally in block with coloanal anastomosis. A case review of rectal duplication in the adult and the conducted treatment. The case of a patient appears with diagnose of rectal duplication with tubular type,whose main symptom was constipation and fecal impactation. In the exploration was detect double rectal lumen (anterior and posterior) that it above initiates by of the anorectal ring with fibrous ulcer of fibrinoid aspect of 3 approx cm of length x 1 cm wide, at level of the septum that separates both rectal lumina. The rectal duplication is a rare pathology in the adult nevertheless is due to suspect before the existence of alterations in the mechanics of the defecation, rectal prolapse and rectal bleeding,the election treatment is a protectomy with colonic pouch in "J" and coloanal anastomosis.

Genome duplication and the evolution of conspecific pollen precedence.

PubMed

Baldwin, Sarah J; Husband, Brian C

2011-07-07

Conspecific pollen precedence can be a strong reproductive barrier between polyploid and diploid species, but the role of genome multiplication in the evolution of this barrier has not been investigated. Here, we examine the direct effect of genome duplication on the evolution of pollen siring success in tetraploid Chamerion angustifolium. To separate the effects of genome duplication from selection after duplication, we compared pollen siring success of synthesized tetraploids (neotetraploids) with that of naturally occurring tetraploids by applying 2x, 4x (neo or established) or 2x + 4x pollen to diploid and tetraploid flowers. Seed set increased in diploids and decreased in both types of tetraploids as the proportion of pollen from diploid plants increased. Based on offspring ploidy from mixed-ploidy pollinations, pollen of the maternal ploidy always sired the majority of offspring but was strongest in established tetraploids and weakest in neotetraploids. Pollen from established tetraploids had significantly higher siring rates than neotetraploids when deposited on diploid (4x(est) = 47.2%, 4x(neo) = 27.1%) and on tetraploid recipients (4x(est) = 91.9%, 4x(neo) = 56.0%). Siring success of established tetraploids exceeded that of neotetraploids despite having similar pollen production per anther and pollen diameter. Our results suggest that, while pollen precedence can arise in association with the duplication event, the strength of polyploid siring success evolves after the duplication event.

Spotting and validation of a genome wide oligonucleotide chip with duplicate measurement of each gene

DOE Office of Scientific and Technical Information (OSTI.GOV)

Thomassen, Mads; Skov, Vibe; Eiriksdottir, Freyja

2006-06-16

The quality of DNA microarray based gene expression data relies on the reproducibility of several steps in a microarray experiment. We have developed a spotted genome wide microarray chip with oligonucleotides printed in duplicate in order to minimise undesirable biases, thereby optimising detection of true differential expression. The validation study design consisted of an assessment of the microarray chip performance using the MessageAmp and FairPlay labelling kits. Intraclass correlation coefficient (ICC) was used to demonstrate that MessageAmp was significantly more reproducible than FairPlay. Further examinations with MessageAmp revealed the applicability of the system. The linear range of the chips wasmore » three orders of magnitude, the precision was high, as 95% of measurements deviated less than 1.24-fold from the expected value, and the coefficient of variation for relative expression was 13.6%. Relative quantitation was more reproducible than absolute quantitation and substantial reduction of variance was attained with duplicate spotting. An analysis of variance (ANOVA) demonstrated no significant day-to-day variation.« less

Ideal photon number amplifier and duplicator

NASA Technical Reports Server (NTRS)

Dariano, G. M.

1992-01-01

The photon number-amplification and number-duplication mechanism are analyzed in the ideal case. The search for unitary evolutions leads to consider also a number-deamplification mechanism, the symmetry between amplification and deamplification being broken by the integer-value nature of the number operator. Both transformations, amplification and duplication, need an auxiliary field which, in the case of amplification, turns out to be amplified in the inverse way. Input-output energy conservation is accounted for using a classical pump or through frequency-conversion of the fields. Ignoring one of the fields is equivalent to considering the amplifier as an open system involving entropy production. The Hamiltonians of the ideal devices are given and compared with those of realistic systems.

41 CFR 302-2.20 - What is a duplicate reimbursement disclosure statement?

Code of Federal Regulations, 2012 CFR

2012-07-01

... 41 Public Contracts and Property Management 4 2012-07-01 2012-07-01 false What is a duplicate reimbursement disclosure statement? 302-2.20 Section 302-2.20 Public Contracts and Property Management Federal... knowledge, no third party has accepted duplicate reimbursement for your relocation expenses. The duplicate...

41 CFR 302-2.20 - What is a duplicate reimbursement disclosure statement?

Code of Federal Regulations, 2014 CFR

2014-07-01

... 41 Public Contracts and Property Management 4 2014-07-01 2014-07-01 false What is a duplicate reimbursement disclosure statement? 302-2.20 Section 302-2.20 Public Contracts and Property Management Federal... knowledge, no third party has accepted duplicate reimbursement for your relocation expenses. The duplicate...

41 CFR 302-2.20 - What is a duplicate reimbursement disclosure statement?

Code of Federal Regulations, 2013 CFR

2013-07-01

... 41 Public Contracts and Property Management 4 2013-07-01 2012-07-01 true What is a duplicate reimbursement disclosure statement? 302-2.20 Section 302-2.20 Public Contracts and Property Management Federal... knowledge, no third party has accepted duplicate reimbursement for your relocation expenses. The duplicate...

The inv dup (15) or idic (15) syndrome (Tetrasomy 15q).

PubMed

Battaglia, Agatino

2008-11-19

The inv dup(15) or idic(15) syndrome displays distinctive clinical findings represented by early central hypotonia, developmental delay and intellectual disability, epilepsy, and autistic behaviour. Incidence at birth is estimated at 1 in 30,000 with a sex ratio of almost 1:1. Developmental delay and intellectual disability affect all individuals with inv dup(15) and are usually moderate to profound. Expressive language is absent or very poor and often echolalic. Comprehension is very limited and contextual. Intention to communicate is absent or very limited. The distinct behavioral disorder shown by children and adolescents has been widely described as autistic or autistic-like. Epilepsy with a wide variety of seizure types can occur in these individuals, with onset between 6 months and 9 years. Various EEG abnormalities have been described. Muscle hypotonia is observed in almost all individuals, associated, in most of them, with joint hyperextensibility and drooling. Facial dysmorphic features are absent or subtle, and major malformations are rare. Feeding difficulties are reported in the newborn period.Chromosome region 15q11q13, known for its instability, is highly susceptible to clinically relevant genomic rearrangements, such as supernumerary marker chromosomes formed by the inverted duplication of proximal chromosome 15. Inv dup(15) results in tetrasomy 15p and partial tetrasomy 15q. The large rearrangements, containing the Prader-Willi/Angelman syndrome critical region (PWS/ASCR), are responsible for the inv dup(15) or idic(15) syndrome. Diagnosis is achieved by standard cytogenetics and FISH analysis, using probes both from proximal chromosome 15 and from the PWS/ASCR. Microsatellite analysis on parental DNA or methylation analysis on the proband DNA, are also needed to detect the parent-of-origin of the inv dup(15) chromosome. Array CGH has been shown to provide a powerful approach for identifying and detecting the extent of the duplication. The possible

Complexity of Gene Expression Evolution after Duplication: Protein Dosage Rebalancing

PubMed Central

Rogozin, Igor B.

2014-01-01

Ongoing debates about functional importance of gene duplications have been recently intensified by a heated discussion of the “ortholog conjecture” (OC). Under the OC, which is central to functional annotation of genomes, orthologous genes are functionally more similar than paralogous genes at the same level of sequence divergence. However, a recent study challenged the OC by reporting a greater functional similarity, in terms of gene ontology (GO) annotations and expression profiles, among within-species paralogs compared to orthologs. These findings were taken to indicate that functional similarity of homologous genes is primarily determined by the cellular context of the genes, rather than evolutionary history. Subsequent studies suggested that the OC appears to be generally valid when applied to mammalian evolution but the complete picture of evolution of gene expression also has to incorporate lineage-specific aspects of paralogy. The observed complexity of gene expression evolution after duplication can be explained through selection for gene dosage effect combined with the duplication-degeneration-complementation model. This paper discusses expression divergence of recent duplications occurring before functional divergence of proteins encoded by duplicate genes. PMID:25197576

PGDD: a database of gene and genome duplication in plants

PubMed Central

Lee, Tae-Ho; Tang, Haibao; Wang, Xiyin; Paterson, Andrew H.

2013-01-01

Genome duplication (GD) has permanently shaped the architecture and function of many higher eukaryotic genomes. The angiosperms (flowering plants) are outstanding models in which to elucidate consequences of GD for higher eukaryotes, owing to their propensity for chromosomal duplication or even triplication in a few cases. Duplicated genome structures often require both intra- and inter-genome alignments to unravel their evolutionary history, also providing the means to deduce both obvious and otherwise-cryptic orthology, paralogy and other relationships among genes. The burgeoning sets of angiosperm genome sequences provide the foundation for a host of investigations into the functional and evolutionary consequences of gene and GD. To provide genome alignments from a single resource based on uniform standards that have been validated by empirical studies, we built the Plant Genome Duplication Database (PGDD; freely available at http://chibba.agtec.uga.edu/duplication/), a web service providing synteny information in terms of colinearity between chromosomes. At present, PGDD contains data for 26 plants including bryophytes and chlorophyta, as well as angiosperms with draft genome sequences. In addition to the inclusion of new genomes as they become available, we are preparing new functions to enhance PGDD. PMID:23180799

Extensive Local Gene Duplication and Functional Divergence among Paralogs in Atlantic Salmon

PubMed Central

Warren, Ian A.; Ciborowski, Kate L.; Casadei, Elisa; Hazlerigg, David G.; Martin, Sam; Jordan, William C.; Sumner, Seirian

2014-01-01

Many organisms can generate alternative phenotypes from the same genome, enabling individuals to exploit diverse and variable environments. A prevailing hypothesis is that such adaptation has been favored by gene duplication events, which generate redundant genomic material that may evolve divergent functions. Vertebrate examples of recent whole-genome duplications are sparse although one example is the salmonids, which have undergone a whole-genome duplication event within the last 100 Myr. The life-cycle of the Atlantic salmon, Salmo salar, depends on the ability to produce alternating phenotypes from the same genome, to facilitate migration and maintain its anadromous life history. Here, we investigate the hypothesis that genome-wide and local gene duplication events have contributed to the salmonid adaptation. We used high-throughput sequencing to characterize the transcriptomes of three key organs involved in regulating migration in S. salar: Brain, pituitary, and olfactory epithelium. We identified over 10,000 undescribed S. salar sequences and designed an analytic workflow to distinguish between paralogs originating from local gene duplication events or from whole-genome duplication events. These data reveal that substantial local gene duplications took place shortly after the whole-genome duplication event. Many of the identified paralog pairs have either diverged in function or become noncoding. Future functional genomics studies will reveal to what extent this rich source of divergence in genetic sequence is likely to have facilitated the evolution of extreme phenotypic plasticity required for an anadromous life-cycle. PMID:24951567

Proteomic Profiling for Identification of Novel Biomarkers Differentially Expressed in Human Ovaries from Polycystic Ovary Syndrome Patients

PubMed Central

Li, Li; Zhang, Jiangyu; Deng, Qingshan; Li, Jieming; Li, Zhengfen; Xiao, Yao; Hu, Shuiwang; Li, Tiantian; Tan, Qiuxiao; Li, Xiaofang; Luo, Bingshu; Mo, Hui

2016-01-01

Objectives To identify differential protein expression pattern associated with polycystic ovary syndrome (PCOS). Methods Twenty women were recruited for the study, ten with PCOS as a test group and ten without PCOS as a control group. Differential in-gel electrophoresis (DIGE) analysis and mass spectroscopy were employed to identify proteins that were differentially expressed between the PCOS and normal ovaries. The differentially expressed proteins were further validated by western blot (WB) and immunohistochemistry (IHC). Results DIGE analysis revealed eighteen differentially expressed proteins in the PCOS ovaries of which thirteen were upregulated, and five downregulated. WB and IHC confirmed the differential expression of membrane-associated progesterone receptor component 1 (PGRMC1), retinol-binding protein 1 (RBP1), heat shock protein 90B1, calmodulin 1, annexin A6, and tropomyosin 2. Also, WB analysis revealed significantly (P<0.05) higher expression of PGRMC1 and RBP1 in PCOS ovaries as compared to the normal ovaries. The differential expression of the proteins was also validated by IHC. Conclusions The present study identified novel differentially expressed proteins in the ovarian tissues of women with PCOS that can serve as potential biomarkers for the diagnosis and development of novel therapeutics for the treatment of PCOS using molecular interventions. PMID:27846214

Proteomic Profiling for Identification of Novel Biomarkers Differentially Expressed in Human Ovaries from Polycystic Ovary Syndrome Patients.

PubMed

Li, Li; Zhang, Jiangyu; Deng, Qingshan; Li, Jieming; Li, Zhengfen; Xiao, Yao; Hu, Shuiwang; Li, Tiantian; Tan, Qiuxiao; Li, Xiaofang; Luo, Bingshu; Mo, Hui

2016-01-01

To identify differential protein expression pattern associated with polycystic ovary syndrome (PCOS). Twenty women were recruited for the study, ten with PCOS as a test group and ten without PCOS as a control group. Differential in-gel electrophoresis (DIGE) analysis and mass spectroscopy were employed to identify proteins that were differentially expressed between the PCOS and normal ovaries. The differentially expressed proteins were further validated by western blot (WB) and immunohistochemistry (IHC). DIGE analysis revealed eighteen differentially expressed proteins in the PCOS ovaries of which thirteen were upregulated, and five downregulated. WB and IHC confirmed the differential expression of membrane-associated progesterone receptor component 1 (PGRMC1), retinol-binding protein 1 (RBP1), heat shock protein 90B1, calmodulin 1, annexin A6, and tropomyosin 2. Also, WB analysis revealed significantly (P<0.05) higher expression of PGRMC1 and RBP1 in PCOS ovaries as compared to the normal ovaries. The differential expression of the proteins was also validated by IHC. The present study identified novel differentially expressed proteins in the ovarian tissues of women with PCOS that can serve as potential biomarkers for the diagnosis and development of novel therapeutics for the treatment of PCOS using molecular interventions.

Rapid diversification of FoxP2 in teleosts through gene duplication in the teleost-specific whole genome duplication event.

PubMed

Song, Xiaowei; Wang, Yajun; Tang, Yezhong

2013-01-01

As one of the most conserved genes in vertebrates, FoxP2 is widely involved in a number of important physiological and developmental processes. We systematically studied the evolutionary history and functional adaptations of FoxP2 in teleosts. The duplicated FoxP2 genes (FoxP2a and FoxP2b), which were identified in teleosts using synteny and paralogon analysis on genome databases of eight organisms, were probably generated in the teleost-specific whole genome duplication event. A credible classification with FoxP2, FoxP2a and FoxP2b in phylogenetic reconstructions confirmed the teleost-specific FoxP2 duplication. The unavailability of FoxP2b in Danio rerio suggests that the gene was deleted through nonfunctionalization of the redundant copy after the Otocephala-Euteleostei split. Heterogeneity in evolutionary rates among clusters consisting of FoxP2 in Sarcopterygii (Cluster 1), FoxP2a in Teleostei (Cluster 2) and FoxP2b in Teleostei (Cluster 3), particularly between Clusters 2 and 3, reveals asymmetric functional divergence after the gene duplication. Hierarchical cluster analyses of hydrophobicity profiles demonstrated significant structural divergence among the three clusters with verification of subsequent stepwise discriminant analysis, in which FoxP2 of Leucoraja erinacea and Lepisosteus oculatus were classified into Cluster 1, whereas FoxP2b of Salmo salar was grouped into Cluster 2 rather than Cluster 3. The simulated thermodynamic stability variations of the forkhead box domain (monomer and homodimer) showed remarkable divergence in FoxP2, FoxP2a and FoxP2b clusters. Relaxed purifying selection and positive Darwinian selection probably were complementary driving forces for the accelerated evolution of FoxP2 in ray-finned fishes, especially for the adaptive evolution of FoxP2a and FoxP2b in teleosts subsequent to the teleost-specific gene duplication.

Rapid Diversification of FoxP2 in Teleosts through Gene Duplication in the Teleost-Specific Whole Genome Duplication Event

PubMed Central

Song, Xiaowei; Wang, Yajun; Tang, Yezhong

2013-01-01

As one of the most conserved genes in vertebrates, FoxP2 is widely involved in a number of important physiological and developmental processes. We systematically studied the evolutionary history and functional adaptations of FoxP2 in teleosts. The duplicated FoxP2 genes (FoxP2a and FoxP2b), which were identified in teleosts using synteny and paralogon analysis on genome databases of eight organisms, were probably generated in the teleost-specific whole genome duplication event. A credible classification with FoxP2, FoxP2a and FoxP2b in phylogenetic reconstructions confirmed the teleost-specific FoxP2 duplication. The unavailability of FoxP2b in Danio rerio suggests that the gene was deleted through nonfunctionalization of the redundant copy after the Otocephala-Euteleostei split. Heterogeneity in evolutionary rates among clusters consisting of FoxP2 in Sarcopterygii (Cluster 1), FoxP2a in Teleostei (Cluster 2) and FoxP2b in Teleostei (Cluster 3), particularly between Clusters 2 and 3, reveals asymmetric functional divergence after the gene duplication. Hierarchical cluster analyses of hydrophobicity profiles demonstrated significant structural divergence among the three clusters with verification of subsequent stepwise discriminant analysis, in which FoxP2 of Leucoraja erinacea and Lepisosteus oculatus were classified into Cluster 1, whereas FoxP2b of Salmo salar was grouped into Cluster 2 rather than Cluster 3. The simulated thermodynamic stability variations of the forkhead box domain (monomer and homodimer) showed remarkable divergence in FoxP2, FoxP2a and FoxP2b clusters. Relaxed purifying selection and positive Darwinian selection probably were complementary driving forces for the accelerated evolution of FoxP2 in ray-finned fishes, especially for the adaptive evolution of FoxP2a and FoxP2b in teleosts subsequent to the teleost-specific gene duplication. PMID:24349554

Neutral and Non-Neutral Evolution of Duplicated Genes with Gene Conversion

PubMed Central

Fawcett, Jeffrey A.; Innan, Hideki

2011-01-01

Gene conversion is one of the major mutational mechanisms involved in the DNA sequence evolution of duplicated genes. It contributes to create unique patters of DNA polymorphism within species and divergence between species. A typical pattern is so-called concerted evolution, in which the divergence between duplicates is maintained low for a long time because of frequent exchanges of DNA fragments. In addition, gene conversion affects the DNA evolution of duplicates in various ways especially when selection operates. Here, we review theoretical models to understand the evolution of duplicates in both neutral and non-neutral cases. We also explain how these theories contribute to interpreting real polymorphism and divergence data by using some intriguing examples. PMID:24710144

ALTERNATIVES TO DUPLICATE DIET METHODOLOGY

EPA Science Inventory

Duplicate Diet (DD) methodology has been used to collect information about the dietary exposure component in the context of total exposure studies. DD methods have been used to characterize the dietary exposure component in the NHEXAS pilot studies. NERL desired to evaluate it...

Hypospadiac Duplication of Anterior Urethra-a Rare Congenital Anomaly.

PubMed

Goyal, Bhawana; Gupta, Suresh; Goyal, Parag

2017-02-01

Duplication of the urethra is a complex and rarely seen congenital anomaly with three anatomic variants: epispadiac (dorsal), hypospadiac (ventral), and Y-type. We report here a case of hypospadiac duplication of anterior urethra with dorsal blind ending urethra in a 9-year-old boy who presented with complaint of passing urine from the ventral aspect of penis.

Ongoing resolution of duplicate gene functions shapes the diversification of a metabolic network

PubMed Central

Kuang, Meihua Christina; Hutchins, Paul D; Russell, Jason D; Coon, Joshua J; Hittinger, Chris Todd

2016-01-01

The evolutionary mechanisms leading to duplicate gene retention are well understood, but the long-term impacts of paralog differentiation on the regulation of metabolism remain underappreciated. Here we experimentally dissect the functions of two pairs of ancient paralogs of the GALactose sugar utilization network in two yeast species. We show that the Saccharomyces uvarum network is more active, even as over-induction is prevented by a second co-repressor that the model yeast Saccharomyces cerevisiae lacks. Surprisingly, removal of this repression system leads to a strong growth arrest, likely due to overly rapid galactose catabolism and metabolic overload. Alternative sugars, such as fructose, circumvent metabolic control systems and exacerbate this phenotype. We further show that S. cerevisiae experiences homologous metabolic constraints that are subtler due to how the paralogs have diversified. These results show how the functional differentiation of paralogs continues to shape regulatory network architectures and metabolic strategies long after initial preservation. DOI: http://dx.doi.org/10.7554/eLife.19027.001 PMID:27690225

Ongoing resolution of duplicate gene functions shapes the diversification of a metabolic network

DOE PAGES

Kuang, Meihua Christina; Hutchins, Paul D.; Russell, Jason D.; ...

2016-09-30

The evolutionary mechanisms leading to duplicate gene retention are well understood, but the long-term impacts of paralog differentiation on the regulation of metabolism remain underappreciated. Here we experimentally dissect the functions of two pairs of ancient paralogs of theGALactose sugar utilization network in two yeast species. Here, we show that theSaccharomyces uvarumnetwork is more active, even as over-induction is prevented by a second co-repressor that the model yeastSaccharomyces cerevisiaelacks. Surprisingly, removal of this repression system leads to a strong growth arrest, likely due to overly rapid galactose catabolism and metabolic overload. Alternative sugars, such as fructose, circumvent metabolic control systemsmore » and exacerbate this phenotype. Furthermore, we show thatS. cerevisiaeexperiences homologous metabolic constraints that are subtler due to how the paralogs have diversified. Our results show how the functional differentiation of paralogs continues to shape regulatory network architectures and metabolic strategies long after initial preservation.« less

Comparing genomes with rearrangements and segmental duplications.

PubMed

Shao, Mingfu; Moret, Bernard M E

2015-06-15

Large-scale evolutionary events such as genomic rearrange.ments and segmental duplications form an important part of the evolution of genomes and are widely studied from both biological and computational perspectives. A basic computational problem is to infer these events in the evolutionary history for given modern genomes, a task for which many algorithms have been proposed under various constraints. Algorithms that can handle both rearrangements and content-modifying events such as duplications and losses remain few and limited in their applicability. We study the comparison of two genomes under a model including general rearrangements (through double-cut-and-join) and segmental duplications. We formulate the comparison as an optimization problem and describe an exact algorithm to solve it by using an integer linear program. We also devise a sufficient condition and an efficient algorithm to identify optimal substructures, which can simplify the problem while preserving optimality. Using the optimal substructures with the integer linear program (ILP) formulation yields a practical and exact algorithm to solve the problem. We then apply our algorithm to assign in-paralogs and orthologs (a necessary step in handling duplications) and compare its performance with that of the state-of-the-art method MSOAR, using both simulations and real data. On simulated datasets, our method outperforms MSOAR by a significant margin, and on five well-annotated species, MSOAR achieves high accuracy, yet our method performs slightly better on each of the 10 pairwise comparisons. http://lcbb.epfl.ch/softwares/coser. © The Author 2015. Published by Oxford University Press.

Generation of Tandem Direct Duplications by Reversed-Ends Transposition of Maize Ac Elements

PubMed Central

Peterson, Thomas

2013-01-01

Tandem direct duplications are a common feature of the genomes of eukaryotes ranging from yeast to human, where they comprise a significant fraction of copy number variations. The prevailing model for the formation of tandem direct duplications is non-allelic homologous recombination (NAHR). Here we report the isolation of a series of duplications and reciprocal deletions isolated de novo from a maize allele containing two Class II Ac/Ds transposons. The duplication/deletion structures suggest that they were generated by alternative transposition reactions involving the termini of two nearby transposable elements. The deletion/duplication breakpoint junctions contain 8 bp target site duplications characteristic of Ac/Ds transposition events, confirming their formation directly by an alternative transposition mechanism. Tandem direct duplications and reciprocal deletions were generated at a relatively high frequency (∼0.5 to 1%) in the materials examined here in which transposons are positioned nearby each other in appropriate orientation; frequencies would likely be much lower in other genotypes. To test whether this mechanism may have contributed to maize genome evolution, we analyzed sequences flanking Ac/Ds and other hAT family transposons and identified three small tandem direct duplications with the structural features predicted by the alternative transposition mechanism. Together these results show that some class II transposons are capable of directly inducing tandem sequence duplications, and that this activity has contributed to the evolution of the maize genome. PMID:23966872

Duplicate publications and related problems in published papers on oral and maxillofacial surgery.

PubMed

Le, A; Moran, C M P; Bezuhly, M; Hong, P

2015-07-01

As duplicate publication is unethical, our aim was to find out how common it is among published papers on oral and maxillofacial surgery. We used PubMed to identify index articles published in 2010 in the Journal of Oral and Maxillofacial Surgery, the British Journal of Oral and Maxillofacial Surgery, and the European Journal of Cranio-Maxillo-Facial Surgery, and searched for possible duplicate publications from 2008 to 2012 using the first or second and last authors' names. Suspected duplicates were categorised into "non-duplicate" (no overlap), "duplicate" (identical results and conclusions), or "salami-sliced" publications (part of the index article repeated or continued). Of the 589 index articles, 17 (3%) had some form of duplication, but specifically, we found 3 duplicate, and 15 salami-sliced publications. Most redundant articles originated from China (n=4), followed by Italy, Japan, and Germany (3 from each) and the United States and Denmark (2 each). Of the 18 redundant publications, 9 did not reference the related index article. Duplicate material is still being published, and salami-slicing is relatively common among publications on oral and maxillofacial surgery. Further research is required into the extent and impact of this finding. Copyright © 2015 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

True duplication of the vas deferens: a case report and review of literature.

PubMed

Liang, Mike K; Subramanian, Anuradha; Weedin, John; Griffith, Donald P; Awad, Samir S

2012-04-01

Duplication of the vas deferens is the identification of a second vas deferens within the spermatic cord; it is a rarely reported congenital anomaly. Duplicate vas deferens should not be confused with double vas deferens that describes ipsilateral renal agenesis with a blind ureter ending in the ejaculatory system. We present a case of duplicated vas deferens, and a PubMed Medline (National Library of Medicine) search was performed using the terms "[duplicated OR double]" and "vas deferens". Nineteen papers for a total of twenty-two cases (including ours) were identified. Duplication of vas deferens is a rare finding; it is likely under-reported and underrecognized. Failure to recognize this variation can result in injury to the vas deferens or an ineffective vasectomy. Following identification of a suspected duplicated vas deferens, the structure should be tracked from the internal ring down to the epididymis and intra-operative Doppler should be performed. Post-operatively, renal and bladder imaging can be considered though there have been no reported cases of non-testicular genito-urinary anomalies associated with duplicated vas deferens.

Lynch syndrome and Lynch syndrome mimics: The growing complex landscape of hereditary colon cancer

PubMed Central

Carethers, John M; Stoffel, Elena M

2015-01-01

Hereditary non-polyposis colorectal cancer (HNPCC) was previously synonymous with Lynch syndrome; however, identification of the role of germline mutations in the DNA mismatch repair (MMR) genes has made it possible to differentiate Lynch syndrome from other conditions associated with familial colorectal cancer (CRC). Broadly, HNPCC may be dichotomized into conditions that demonstrate defective DNA MMR and microsatellite instability (MSI) vs those conditions that demonstrate intact DNA MMR. Conditions characterized by MMR deficient CRCs include Lynch syndrome (germline MMR mutation), Lynch-like syndrome (biallelic somatic MMR mutations), constitutional MMR deficiency syndrome (biallelic germline MMR mutations), and sporadic MSI CRC (somatic biallelic methylation of MLH1). HNPCC conditions with intact DNA MMR associated with familial CRC include polymerase proofreading associated polyposis and familial colorectal cancer type X. Although next generation sequencing technologies have elucidated the genetic cause for some HNPCC conditions, others remain genetically undefined. Differentiating between Lynch syndrome and the other HNPCC disorders has profound implications for cancer risk assessment and surveillance of affected patients and their at-risk relatives. Clinical suspicion coupled with molecular tumor analysis and testing for germline mutations can help differentiate the clinical mimicry within HNPCC and facilitate diagnosis and management. PMID:26309352

Lynch syndrome and Lynch syndrome mimics: The growing complex landscape of hereditary colon cancer.

PubMed

Carethers, John M; Stoffel, Elena M

2015-08-21

Hereditary non-polyposis colorectal cancer (HNPCC) was previously synonymous with Lynch syndrome; however, identification of the role of germline mutations in the DNA mismatch repair (MMR) genes has made it possible to differentiate Lynch syndrome from other conditions associated with familial colorectal cancer (CRC). Broadly, HNPCC may be dichotomized into conditions that demonstrate defective DNA MMR and microsatellite instability (MSI) vs those conditions that demonstrate intact DNA MMR. Conditions characterized by MMR deficient CRCs include Lynch syndrome (germline MMR mutation), Lynch-like syndrome (biallelic somatic MMR mutations), constitutional MMR deficiency syndrome (biallelic germline MMR mutations), and sporadic MSI CRC (somatic biallelic methylation of MLH1). HNPCC conditions with intact DNA MMR associated with familial CRC include polymerase proofreading associated polyposis and familial colorectal cancer type X. Although next generation sequencing technologies have elucidated the genetic cause for some HNPCC conditions, others remain genetically undefined. Differentiating between Lynch syndrome and the other HNPCC disorders has profound implications for cancer risk assessment and surveillance of affected patients and their at-risk relatives. Clinical suspicion coupled with molecular tumor analysis and testing for germline mutations can help differentiate the clinical mimicry within HNPCC and facilitate diagnosis and management.

Duplication methods for replacement of broken orthoses.

PubMed

Bradbury, R L; Gastwirth, B W; O'Connor, K J; Bloom, J

1988-04-01

The methods presented for replacement of broken orthoses have proved very effective (Fig. 9). In more than 5 years of employing such duplication techniques, we have found patient satisfaction in the product to be commensurate with that for their originally prescribed devices. The techniques presented are not the only methods by which orthoses can be duplicated. We recognize that the clinician should refabricate the same orthosis only when the cause of breakage has been determined to be material fatigue or stress. Should the patient's weight, foot structure, or activities have changed, new orthoses should be fabricated with those factors in mind.

Therapeutic Duplicates in a Cohort of Hospitalized Elderly Patients: Results from the REPOSI Study.

PubMed

Pasina, Luca; Astuto, Sarah; Cortesi, Laura; Tettamanti, Mauro; Franchi, Carlotta; Marengoni, Alessandra; Mannucci, Pier Mannuccio; Nobili, Alessandro

2016-09-01

Explicit criteria for potentially inappropriate prescriptions in the elderly are recommended to avoid prescriptions of duplicate drug classes and to optimize monotherapy within a single drug class before a new agent is considered. Duplicate drug class prescription (or therapeutic duplicates) puts the patient at increased risk of adverse drug reactions with no additional therapeutic benefits. To our knowledge, the prevalence of elderly inpatients receiving therapeutic duplicates has never been studied. Our objective was to assess the prevalence of therapeutic duplicates at admission, discharge, and 3-month follow-up of hospitalized elderly patients. This cross-sectional prospective study was conducted in 97 Italian internal medicine and geriatric wards. Therapeutic duplicates were defined as at least two drugs of the same therapeutic class prescribed simultaneously to a patient. A patient's drug therapy at admission relates to prescriptions from general practitioners, whereas prescriptions at discharge are those from hospital internists or geriatricians. The study sample comprised 5821 admitted and 4983 discharged patients. In all, 143 therapeutic duplicates were found at admission and 170 at discharge. The prevalence of patients exposed to at least one therapeutic duplicate rose significantly from hospital admission (2.5 %) to discharge (3.4 %; p = 0.0032). Psychotropic drugs and drugs for peptic ulcer or gastroesophageal reflux disease were the most frequently involved. A total of 86.8 % of patients discharged with at least one therapeutic duplicate were still receiving them at 3-month follow-up. Hospitalization and drugs prescribed by internists and geriatricians are both factors associated with a small but definite increase in overall therapeutic duplicates in elderly patients admitted to internal medicine and geriatric wards. More attention should be paid to the indications for each drug prescribed, because therapeutic duplicates are not supported by evidence

Xq28 duplication presenting with intestinal and bladder dysfunction and a distinctive facial appearance

PubMed Central

Clayton-Smith, Jill; Walters, Sarah; Hobson, Emma; Burkitt-Wright, Emma; Smith, Rupert; Toutain, Annick; Amiel, Jeanne; Lyonnet, Stanislas; Mansour, Sahar; Fitzpatrick, David; Ciccone, Roberto; Ricca, Ivana; Zuffardi, Orsetta; Donnai, Dian

2009-01-01

Xq28 duplications encompassing MECP2 have been described in male patients with a severe neurodevelopmental disorder associated with hypotonia and spasticity, severe learning disability and recurrent pneumonia. We identified an Xq28 duplication in three families where several male patients had presented with intestinal pseudo-obstruction or bladder distension. The affected boys had similar dysmorphic facial appearances. Subsequently, we ascertained seven further families where the proband presented with similar features. We demonstrated duplications of the Xq28 region in five of these additional families. In addition to MECP2, these duplications encompassed several other genes already known to be associated with diseases including SLC6A8, L1CAM and Filamin A (FLNA). The two remaining families were shown to have intragenic duplications of FLNA only. We discuss which elements of the Xq28 duplication phenotype may be associated with the various genes in the duplication. We propose that duplication of FLNA may contribute to the bowel and bladder phenotype seen in these seven families. PMID:18854860

Genomic profiling of Sézary Syndrome identifies alterations of key T-cell signaling and differentiation genes

PubMed Central

Wang, Linghua; Ni, Xiao; Covington, Kyle R.; Yang, Betty Y.; Shiu, Jessica; Zhang, Xiang; Xi, Liu; Meng, Qingchang; Langridge, Timothy; Drummond, Jennifer; Donehower, Lawrence A.; Doddapaneni, Harshavardhan; Muzny, Donna M.; Gibbs, Richard A.; Wheeler, David A.; Duvic, Madeleine

2016-01-01

Sézary Syndrome is a rare leukemic form of cutaneous T-cell lymphoma defined as erythroderma, adenopathy, and circulating atypical T-lymphocytes. It is rarely curable with poor prognosis. Here we present a multi-platform genomic analysis of 37 Sézary Syndrome patients that implicates dysregulation of the cell cycle checkpoint and T-cell signaling. Frequent somatic alterations were identified in TP53, CARD11, CCR4, PLCG1, CDKN2A, ARID1A, RPS6KA1, and ZEB1. Activating CCR4 and CARD11 mutations were detected in nearly a third of patients. ZEB1, a transcription repressor essential for T-cell differentiation, was deleted in over half of patients. IL32 and IL2RG were over-expressed in nearly all cases. Analysis of T-cell receptor Vβ and Vα expression revealed ongoing rearrangement of the receptors after the expansion of a malignant clone in one third of subjects. Our results demonstrate profound disruption of key signaling pathways in Sézary Syndrome and suggest potential targets for novel therapies. PMID:26551670

Co-expression network analysis of duplicate genes in maize (Zea mays L.) reveals no subgenome bias.

PubMed

Li, Lin; Briskine, Roman; Schaefer, Robert; Schnable, Patrick S; Myers, Chad L; Flagel, Lex E; Springer, Nathan M; Muehlbauer, Gary J

2016-11-04

Gene duplication is prevalent in many species and can result in coding and regulatory divergence. Gene duplications can be classified as whole genome duplication (WGD), tandem and inserted (non-syntenic). In maize, WGD resulted in the subgenomes maize1 and maize2, of which maize1 is considered the dominant subgenome. However, the landscape of co-expression network divergence of duplicate genes in maize is still largely uncharacterized. To address the consequence of gene duplication on co-expression network divergence, we developed a gene co-expression network from RNA-seq data derived from 64 different tissues/stages of the maize reference inbred-B73. WGD, tandem and inserted gene duplications exhibited distinct regulatory divergence. Inserted duplicate genes were more likely to be singletons in the co-expression networks, while WGD duplicate genes were likely to be co-expressed with other genes. Tandem duplicate genes were enriched in the co-expression pattern where co-expressed genes were nearly identical for the duplicates in the network. Older gene duplications exhibit more extensive co-expression variation than younger duplications. Overall, non-syntenic genes primarily from inserted duplications show more co-expression divergence. Also, such enlarged co-expression divergence is significantly related to duplication age. Moreover, subgenome dominance was not observed in the co-expression networks - maize1 and maize2 exhibit similar levels of intra subgenome correlations. Intriguingly, the level of inter subgenome co-expression was similar to the level of intra subgenome correlations, and genes from specific subgenomes were not likely to be the enriched in co-expression network modules and the hub genes were not predominantly from any specific subgenomes in maize. Our work provides a comprehensive analysis of maize co-expression network divergence for three different types of gene duplications and identifies potential relationships between duplication types

Neonatal intestinal obstruction secondary to a small bowel duplication cyst

PubMed Central

Puralingegowda, Anil Kumar; Mohanty, Pankaj Kumar; Razak, Abdul; Nagesh N, Karthik; Chandrayya, Ramachandra

2014-01-01

A 3-week-old neonate developed abdominal distension and vomiting which subsided after conservative management. However, there was a recurrence of symptoms for which a lower gastrointestinal tract contrast study was performed. The infant had a filling defect in the area of the transverse colon. A CT scan was performed, showing a duplication cyst arising from the small bowel and indenting the transverse colon. Resection of the duplication cyst and end-to-end anastomosis of the bowel was performed. The duplication cyst was of tubular type, and a sealed perforation was noted in the cyst wall. PMID:25006055

SATB2-associated syndrome: Mechanisms, phenotype, and practical recommendations.

PubMed

Zarate, Yuri A; Fish, Jennifer L

2017-02-01

The SATB2-associated syndrome is a recently described syndrome characterized by developmental delay/intellectual disability with absent or limited speech development, craniofacial abnormalities, behavioral problems, dysmorphic features, and palatal and dental abnormalities. Alterations of the SATB2 gene can result from a variety of different mechanisms that include contiguous deletions, intragenic deletions and duplications, translocations with secondary gene disruption, and point mutations. The multisystemic nature of this syndrome demands a multisystemic approach and we propose evaluation and management guidelines. The SATB2-associated syndrome registry has now been started and that will allow gathering further clinical information and refining the provided surveillance recommendations. © 2016 The Authors. American Journal of Medical Genetics Part A Published by Wiley Periodicals, Inc. © 2016 The Authors. American Journal of Medical Genetics Part A Published by Wiley Periodicals, Inc.

Yeast Interspecies Comparative Proteomics Reveals Divergence in Expression Profiles and Provides Insights into Proteome Resource Allocation and Evolutionary Roles of Gene Duplication.

PubMed

Kito, Keiji; Ito, Haruka; Nohara, Takehiro; Ohnishi, Mihoko; Ishibashi, Yuko; Takeda, Daisuke

2016-01-01

Omics analysis is a versatile approach for understanding the conservation and diversity of molecular systems across multiple taxa. In this study, we compared the proteome expression profiles of four yeast species (Saccharomyces cerevisiae, Saccharomyces mikatae, Kluyveromyces waltii, and Kluyveromyces lactis) grown on glucose- or glycerol-containing media. Conserved expression changes across all species were observed only for a small proportion of all proteins differentially expressed between the two growth conditions. Two Kluyveromyces species, both of which exhibited a high growth rate on glycerol, a nonfermentative carbon source, showed distinct species-specific expression profiles. In K. waltii grown on glycerol, proteins involved in the glyoxylate cycle and gluconeogenesis were expressed in high abundance. In K. lactis grown on glycerol, the expression of glycolytic and ethanol metabolic enzymes was unexpectedly low, whereas proteins involved in cytoplasmic translation, including ribosomal proteins and elongation factors, were highly expressed. These marked differences in the types of predominantly expressed proteins suggest that K. lactis optimizes the balance of proteome resource allocation between metabolism and protein synthesis giving priority to cellular growth. In S. cerevisiae, about 450 duplicate gene pairs were retained after whole-genome duplication. Intriguingly, we found that in the case of duplicates with conserved sequences, the total abundance of proteins encoded by a duplicate pair in S. cerevisiae was similar to that of protein encoded by nonduplicated ortholog in Kluyveromyces yeast. Given the frequency of haploinsufficiency, this observation suggests that conserved duplicate genes, even though minor cases of retained duplicates, do not exhibit a dosage effect in yeast, except for ribosomal proteins. Thus, comparative proteomic analyses across multiple species may reveal not only species-specific characteristics of metabolic processes under

Blink reflex recovery cycle to differentiate Progressive Supranuclear Palsy from Cortico-basal syndrome.

PubMed

Sciacca, Giorgia; Nicoletti, Alessandra; Mostile, Giovanni; Luca, Antonina; Raciti, Loredana; Dibilio, Valeria; Drago, Filippo; Salomone, Salvatore; Zappia, Mario

2018-05-13

Progressive Supranuclear Palsy (PSP) and Cortico-basal syndrome (CBS) may share similar clinical findings and peculiar tests to distinguish between the two disorders could be useful. We evaluated Blink Reflex (BR) and R2 Blink Reflex Recovery Cycle (R2BRRC), determining diagnostic sensitivity, specificity, positive and negative predictive value of R2BRRC in differentiating PSP from CBS patients. This was a prospective data collection study investigating BR and R2BRRC at interstimulus intervals (ISIs) of 100, 150, 200, 300, 400, 500, 750 ms in 12 PSP patients, 8 CBS patients, and 10 controls. Patients with PSP have earlier recruitment of R2BRRC as compared to patients with CBS (ISI 100: p=0.002; ISI 150: p<0.001; ISI 200: p<0.001; ISI 300: p=0.02) and controls (ISI 100: p<0.001; ISI 150: p<0.001; ISI 200: p<0.001; ISI 300: p=0.004). The presence of an early recovery of the R2 differentiated PSP from CBS with specificity and sensitivity of 87.5% and 91.7% respectively. R2BRRC curve might be considered a useful tool in differentiating PSP from CBS patients. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

p53 protects against genome instability following centriole duplication failure

PubMed Central

Lambrus, Bramwell G.; Uetake, Yumi; Clutario, Kevin M.; Daggubati, Vikas; Snyder, Michael; Sluder, Greenfield

2015-01-01

Centriole function has been difficult to study because of a lack of specific tools that allow persistent and reversible centriole depletion. Here we combined gene targeting with an auxin-inducible degradation system to achieve rapid, titratable, and reversible control of Polo-like kinase 4 (Plk4), a master regulator of centriole biogenesis. Depletion of Plk4 led to a failure of centriole duplication that produced an irreversible cell cycle arrest within a few divisions. This arrest was not a result of a prolonged mitosis, chromosome segregation errors, or cytokinesis failure. Depleting p53 allowed cells that fail centriole duplication to proliferate indefinitely. Washout of auxin and restoration of endogenous Plk4 levels in cells that lack centrioles led to the penetrant formation of de novo centrioles that gained the ability to organize microtubules and duplicate. In summary, we uncover a p53-dependent surveillance mechanism that protects against genome instability by preventing cell growth after centriole duplication failure. PMID:26150389

Rai1 duplication causes physical and behavioral phenotypes in a mouse model of dup(17)(p11.2p11.2)

PubMed Central

Walz, Katherina; Paylor, Richard; Yan, Jiong; Bi, Weimin; Lupski, James R.

2006-01-01

Genomic disorders are conditions that result from DNA rearrangements, such as deletions or duplications. The identification of the dosage-sensitive gene(s) within the rearranged genomic interval is important for the elucidation of genes responsible for complex neurobehavioral phenotypes. Smith-Magenis syndrome is associated with a 3.7-Mb deletion in 17p11.2, and its clinical presentation is caused by retinoic acid inducible 1 (RAI1) haploinsufficiency. The reciprocal microduplication syndrome, dup(17)(p11.2p11.2), manifests several neurobehavioral abnormalities, but the responsible dosage-sensitive gene(s) remain undefined. We previously generated a mouse model for dup(17)(p11.2p11.2), Dp(11)17/+, that recapitulated most of the phenotypes observed in human patients. We have now analyzed compound heterozygous mice carrying a duplication [Dp(11)17] in one chromosome 11 along with a null allele of Rai1 in the other chromosome 11 homologue [Dp(11)17/Rai1– mice] in order to study the relationship between Rai1 gene copy number and the Dp(11)17/+ phenotypes. Normal disomic Rai1 gene dosage was sufficient to rescue the complex physical and behavioral phenotypes observed in Dp(11)17/+ mice, despite altered trisomic copy number of the other 18 genes present in the rearranged genomic interval. These data provide a model for variation in copy number of single genes that could influence common traits such as obesity and behavior. PMID:17024248

[Gardner syndrome--parent alienation syndrome (PAS). Diagnosis or family reality?].

PubMed

Namysłowska, Irena; Heitzman, Janusz; Siewierska, Anna

2009-01-01

The authors present characteristics of Parental Alienation Syndrome (PAS) proposed by Gardner as well as data, which may help to differentiate that syndrome with real psychological, physical and sexual abuse. The consequences of Gardner Syndrome for legal decisions in the court cases of child custody and the critique of this syndrome in forensic and psychiatric literature are also discussed, and several questions posed. Authors propose to treat Gardner Syndrome not as as a child disorder but as a specific, dynamic family situation, which occurs sometimes, during divorce and fight about child custody.

Verification and characterization of chromosome duplication in haploid maize.

PubMed

de Oliveira Couto, E G; Resende Von Pinho, E V; Von Pinho, R G; Veiga, A D; de Carvalho, M R; de Oliveira Bustamante, F; Nascimento, M S

2015-06-26

Doubled haploid technology has been used by various private companies. However, information regarding chromosome duplication methodologies, particularly those concerning techniques used to identify duplication in cells, is limited. Thus, we analyzed and characterized artificially doubled haploids using microsatellites molecular markers, pollen viability, and flow cytometry techniques. Evaluated material was obtained using two different chromosome duplication protocols in maize seeds considered haploids, resulting from the cross between the haploid inducer line KEMS and 4 hybrids (GNS 3225, GNS 3032, GNS 3264, and DKB 393). Fourteen days after duplication, plant samples were collected and assessed by flow cytometry. Further, the plants were transplanted to a field, and samples were collected for DNA analyses using microsatellite markers. The tassels were collected during anthesis for pollen viability analyses. Haploid, diploid, and mixoploid individuals were detected using flow cytometry, demonstrating that this technique was efficient for identifying doubled haploids. The microsatellites markers were also efficient for confirming the ploidies preselected by flow cytometry and for identifying homozygous individuals. Pollen viability showed a significant difference between the evaluated ploidies when the Alexander and propionic-carmin stains were used. The viability rates between the plodies analyzed show potential for fertilization.

The investigation and differential diagnosis of Asperger syndrome in adults.

PubMed

Lehnhardt, Fritz-Georg; Gawronski, Astrid; Pfeiffer, Kathleen; Kockler, Hanna; Schilbach, Leonhard; Vogeley, Kai

2013-11-08

As a result of the increased public interest in autism spectrum disorders (ASD), certain core manifestations of ASD--impaired social interaction and communication, bizarre interests--are now commonly recognized as being typical of autism, not only in children, but in adults as well. More often than before, general practitioners, neurologists, and psychiatrists find themselves being asked whether a patient is suffering from previously unrecognized Asperger syndrome (AS). The prevalence of ASD is estimated at 1%, and the ratio of diagnosed to undiagnosed cases at about 3:2. Little is known about the diagnostic evaluation of AS in adulthood. We selectively searched the Medline database for pertinent literature, paying special attention to diagnostic manuals and to the guideline of the United Kingdom's National Institute for Health and Care Excellence (NICE). Centrally important aspects of the diagnosis of AS include an assessment of the patient's ability to assume the emotional perspectives of others, non-verbal modes of expression, repetitive behavior patterns, and childhood social behavioral history. The autism quotient (AQ) is now established as a simple but nonspecific screening test. Up to 70% of all affected adults have comorbid disturbances, most often depression and anxiety disorders. The differential diagnosis includes personality disorders, anxiety disorders, obsessive-compulsive disorder, and attention deficit-hyperactivity disorder. The diagnostic assessment should proceed in stepwise fashion, starting from simple screening in primary care and then moving on to evaluation of the suspected diagnosis by a mental health care specialist, followed by extensive further investigation in an outpatient clinic specifically devoted to patients with autism spectrum disorders. The diagnostic assessment of autism in adults requires knowledge of the core and accompanying manifestations of autism and of their differential diagnoses. More research is needed for the

[Partial facial duplication (a rare diprosopus): Case report and review of the literature].

PubMed

Es-Seddiki, A; Rkain, M; Ayyad, A; Nkhili, H; Amrani, R; Benajiba, N

2015-12-01

Diprosopus, or partial facial duplication, is a very rare congenital abnormality. It is a rare form of conjoined twins. Partial facial duplication may be symmetric or not and may involve the nose, the maxilla, the mandible, the palate, the tongue and the mouth. A male newborn springing from inbred parents was admitted at his first day of life for facial deformity. He presented with hypertelorism, 2 eyes, a tendency to nose duplication (flatted large nose, 2 columellae, 2 lateral nostrils separated in the midline by a third deformed hole), two mouths and a duplicated maxilla. Laboratory tests were normal. The cranio-facial CT confirmed the maxillary duplication. This type of cranio-facial duplication is a rare entity with about 35 reported cases in the literature. Our patient was similar to a rare case of living diprosopus reported by Stiehm in 1972. Diprosopus is often associated with abnormalities of the gastrointestinal tract, the central nervous system, the cardiovascular and respiratory systems and with a high incidence of cleft lip and palate. Surgical treatment consists in the resection of the duplicated components. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Screening of duplicated loci reveals hidden divergence patterns in a complex salmonid genome

USGS Publications Warehouse

Limborg, Morten T.; Larson, Wesley; Seeb, Lisa W.; Seeb, James E.

2017-01-01

A whole-genome duplication (WGD) doubles the entire genomic content of a species and is thought to have catalysed adaptive radiation in some polyploid-origin lineages. However, little is known about general consequences of a WGD because gene duplicates (i.e., paralogs) are commonly filtered in genomic studies; such filtering may remove substantial portions of the genome in data sets from polyploid-origin species. We demonstrate a new method that enables genome-wide scans for signatures of selection at both nonduplicated and duplicated loci by taking locus-specific copy number into account. We apply this method to RAD sequence data from different ecotypes of a polyploid-origin salmonid (Oncorhynchus nerka) and reveal signatures of divergent selection that would have been missed if duplicated loci were filtered. We also find conserved signatures of elevated divergence at pairs of homeologous chromosomes with residual tetrasomic inheritance, suggesting that joint evolution of some nondiverged gene duplicates may affect the adaptive potential of these genes. These findings illustrate that including duplicated loci in genomic analyses enables novel insights into the evolutionary consequences of WGDs and local segmental gene duplications.

Inferring evolution of gene duplicates using probabilistic models and nonparametric belief propagation.

PubMed

Zeng, Jia; Hannenhalli, Sridhar

2013-01-01

Gene duplication, followed by functional evolution of duplicate genes, is a primary engine of evolutionary innovation. In turn, gene expression evolution is a critical component of overall functional evolution of paralogs. Inferring evolutionary history of gene expression among paralogs is therefore a problem of considerable interest. It also represents significant challenges. The standard approaches of evolutionary reconstruction assume that at an internal node of the duplication tree, the two duplicates evolve independently. However, because of various selection pressures functional evolution of the two paralogs may be coupled. The coupling of paralog evolution corresponds to three major fates of gene duplicates: subfunctionalization (SF), conserved function (CF) or neofunctionalization (NF). Quantitative analysis of these fates is of great interest and clearly influences evolutionary inference of expression. These two interrelated problems of inferring gene expression and evolutionary fates of gene duplicates have not been studied together previously and motivate the present study. Here we propose a novel probabilistic framework and algorithm to simultaneously infer (i) ancestral gene expression and (ii) the likely fate (SF, NF, CF) at each duplication event during the evolution of gene family. Using tissue-specific gene expression data, we develop a nonparametric belief propagation (NBP) algorithm to predict the ancestral expression level as a proxy for function, and describe a novel probabilistic model that relates the predicted and known expression levels to the possible evolutionary fates. We validate our model using simulation and then apply it to a genome-wide set of gene duplicates in human. Our results suggest that SF tends to be more frequent at the earlier stage of gene family expansion, while NF occurs more frequently later on.

Metallothionein Gene Duplications and Metal Tolerance in Natural Populations of Drosophila melanogaster

PubMed Central

Maroni, G.; Wise, J.; Young, J. E.; Otto, E.

1987-01-01

A search for duplications of the Drosophila melanogaster metallothionein gene (Mtn) yielded numerous examples of this type of chromosomal rearrangement. These duplications are distributed widely—we found them in samples from four continents, and they are functional—larvae carrying Mtn duplications produce more Mtn RNA and tolerate increased cadmium and copper concentrations. Six different duplication types were characterized by restriction-enzyme analyses using probes from the Mtn region. The restriction maps show that in four cases the sequences, ranging in size between 2.2 and 6.0 kb, are arranged as direct, tandem repeats; in two other cases, this basic pattern is modified by the insertion of a putative transposable element into one of the repeated units. Duplications of the D. melanogaster metallothionein gene such as those that we found in natural populations may represent early stages in the evolution of a gene family. PMID:2828157

The Evolution of Pepsinogen C Genes in Vertebrates: Duplication, Loss and Functional Diversification

PubMed Central

Gonçalves, Odete; Wilson, Jonathan Mark

2012-01-01

Background Aspartic proteases comprise a large group of enzymes involved in peptide proteolysis. This collection includes prominent enzymes globally categorized as pepsins, which are derived from pepsinogen precursors. Pepsins are involved in gastric digestion, a hallmark of vertebrate physiology. An important member among the pepsinogens is pepsinogen C (Pgc). A particular aspect of Pgc is its apparent single copy status, which contrasts with the numerous gene copies found for example in pepsinogen A (Pga). Although gene sequences with similarity to Pgc have been described in some vertebrate groups, no exhaustive evolutionary framework has been considered so far. Methodology/Principal Findings By combining phylogenetics and genomic analysis, we find an unexpected Pgc diversity in the vertebrate sub-phylum. We were able to reconstruct gene duplication timings relative to the divergence of major vertebrate clades. Before tetrapod divergence, a single Pgc gene tandemly expanded to produce two gene lineages (Pgbc and Pgc2). These have been differentially retained in various classes. Accordingly, we find Pgc2 in sauropsids, amphibians and marsupials, but not in eutherian mammals. Pgbc was retained in amphibians, but duplicated in the ancestor of amniotes giving rise to Pgb and Pgc1. The latter was retained in mammals and probably in reptiles and marsupials but not in birds. Pgb was kept in all of the amniote clade with independent episodes of loss in some mammalian species. Lineage specific expansions of Pgc2 and Pgbc have also occurred in marsupials and amphibians respectively. We find that teleost and tetrapod Pgc genes reside in distinct genomic regions hinting at a possible translocation. Conclusions We conclude that the repertoire of Pgc genes is larger than previously reported, and that tandem duplications have modelled the history of Pgc genes. We hypothesize that gene expansion lead to functional divergence in tetrapods, coincident with the invasion of

Validity and reliability of the Spanish version of the DN4 (Douleur Neuropathique 4 questions) questionnaire for differential diagnosis of pain syndromes associated to a neuropathic or somatic component

PubMed Central

Perez, Concepcion; Galvez, Rafael; Huelbes, Silvia; Insausti, Joaquin; Bouhassira, Didier; Diaz, Silvia; Rejas, Javier

2007-01-01

Background This study assesses the validity and reliability of the Spanish version of DN4 questionnaire as a tool for differential diagnosis of pain syndromes associated to a neuropathic (NP) or somatic component (non-neuropathic pain, NNP). Methods A study was conducted consisting of two phases: cultural adaptation into the Spanish language by means of conceptual equivalence, including forward and backward translations in duplicate and cognitive debriefing, and testing of psychometric properties in patients with NP (peripheral, central and mixed) and NNP. The analysis of psychometric properties included reliability (internal consistency, inter-rater agreement and test-retest reliability) and validity (ROC curve analysis, agreement with the reference diagnosis and determination of sensitivity, specificity, and positive and negative predictive values in different subsamples according to type of NP). Results A sample of 164 subjects (99 women, 60.4%; age: 60.4 ± 16.0 years), 94 (57.3%) with NP (36 with peripheral, 32 with central, and 26 with mixed pain) and 70 with NNP was enrolled. The questionnaire was reliable [Cronbach's alpha coefficient: 0.71, inter-rater agreement coefficient: 0.80 (0.71–0.89), and test-retest intra-class correlation coefficient: 0.95 (0.92–0.97)] and valid for a cut-off value ≥ 4 points, which was the best value to discriminate between NP and NNP subjects. Discussion This study, representing the first validation of the DN4 questionnaire into another language different than the original, not only supported its high discriminatory value for identification of neuropathic pain, but also provided supplemental psychometric validation (i.e. test-retest reliability, influence of educational level and pain intensity) and showed its validity in mixed pain syndromes. PMID:18053212

Error analysis of filtering operations in pixel-duplicated images of diabetic retinopathy

NASA Astrophysics Data System (ADS)

Mehrubeoglu, Mehrube; McLauchlan, Lifford

2010-08-01

In this paper, diabetic retinopathy is chosen for a sample target image to demonstrate the effectiveness of image enlargement through pixel duplication in identifying regions of interest. Pixel duplication is presented as a simpler alternative to data interpolation techniques for detecting small structures in the images. A comparative analysis is performed on different image processing schemes applied to both original and pixel-duplicated images. Structures of interest are detected and and classification parameters optimized for minimum false positive detection in the original and enlarged retinal pictures. The error analysis demonstrates the advantages as well as shortcomings of pixel duplication in image enhancement when spatial averaging operations (smoothing filters) are also applied.

Cost-effectiveness and accuracy of the tests used in the differential diagnosis of Cushing's syndrome.

PubMed

Puig, J; Wägner, A; Caballero, A; Rodríguez-Espinosa, J; Webb, S M

1999-01-01

Establish the minimal biochemical and radiological examinations necessary and their cost-effectiveness to accurately diagnose the etiology of Cushing's syndrome (CS). In 71 patients with CS followed between 1982 and 1997 biochemical studies (basal ACTH, 8 mg dexamethasone suppression test-HDST-, metyrapone stimulation test-MST-, or inferior petrosal sinus catheterization-IPSC-) and radiological investigations (abdominal CT scan, pituitary CT scan or MRI) were performed. Once pathology confirmed the diagnosis (48 pituitary Cushing's disease-CD, 17 adrenal neoplasms, 2 bilateral macronodular hyperplasia-BMH-, and 4 ectopic ACTH syndrome-ES-), the sensitivity, specificity, positive and negative predictive value of the different studies was calculated to establish the most accurate and cost-effective diagnostic protocol. In ACTH-independent CS (ACTH < or = 9 pg/ml; normal 9 to 54) a unilateral tumor was identified on abdominal CT scanning in 17, and BMH in 1; the other BMH had detectable ACTH (43.2 pg/ml). In ACTH-dependent CS, ACTH was > 9 pg/ml and IPSC (performed in 22) correctly identified 20 patients with CD and differentiated them from 2 with an ES (100% specificity and sensitivity). Pituitary MRI or CT did not disclose an adenoma in 41.7% of patients with CD, and was reported to exhibit a microadenoma in 2 of the 4 patients with ES. HDST and MST were of no additional use in the differentiation between CD and ES. Once CS is diagnosed low ACTH and an abdominal CT scan correctly identified all patients of adrenal origin. In ACTH-dependent CS IPSC was the best predictive test to differentiate CD from ES. BMH may behave as ACTH-dependent or independent. The other biochemical and radiological studies performed are not cost-effective and may even be misleading, and should not be routinely performed.

46 CFR 58.25-60 - Non-duplicated hydraulic rudder actuators.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 2 2010-10-01 2010-10-01 false Non-duplicated hydraulic rudder actuators. 58.25-60... actuators. Non-duplicated hydraulic rudder actuators may be installed in the steering-gear control systems on each vessel of less than 100,000 deadweight tons. These actuators must meet IMO A.467(XII...

Gene duplication in the major insecticide target site, Rdl, in Drosophila melanogaster

PubMed Central

Remnant, Emily J.; Good, Robert T.; Schmidt, Joshua M.; Lumb, Christopher; Robin, Charles; Daborn, Phillip J.; Batterham, Philip

2013-01-01

The Resistance to Dieldrin gene, Rdl, encodes a GABA-gated chloride channel subunit that is targeted by cyclodiene and phenylpyrazole insecticides. The gene was first characterized in Drosophila melanogaster by genetic mapping of resistance to the cyclodiene dieldrin. The 4,000-fold resistance observed was due to a single amino acid replacement, Ala301 to Ser. The equivalent change was subsequently identified in Rdl orthologs of a large range of resistant insect species. Here, we report identification of a duplication at the Rdl locus in D. melanogaster. The 113-kb duplication contains one WT copy of Rdl and a second copy with two point mutations: an Ala301 to Ser resistance mutation and Met360 to Ile replacement. Individuals with this duplication exhibit intermediate dieldrin resistance compared with single copy Ser301 homozygotes, reduced temperature sensitivity, and altered RNA editing associated with the resistant allele. Ectopic recombination between Roo transposable elements is involved in generating this genomic rearrangement. The duplication phenotypes were confirmed by construction of a transgenic, artificial duplication integrating the 55.7-kb Rdl locus with a Ser301 change into an Ala301 background. Gene duplications can contribute significantly to the evolution of insecticide resistance, most commonly by increasing the amount of gene product produced. Here however, duplication of the Rdl target site creates permanent heterozygosity, providing unique potential for adaptive mutations to accrue in one copy, without abolishing the endogenous role of an essential gene. PMID:23959864

Tissue transglutaminase contributes to the all-trans-retinoic acid-induced differentiation syndrome phenotype in the NB4 model of acute promyelocytic leukemia.

PubMed

Csomós, Krisztián; Német, István; Fésüs, László; Balajthy, Zoltán

2010-11-11

Treatment of acute promyelocytic leukemia (APL) with all-trans-retinoic acid (ATRA) results in terminal differentiation of leukemic cells toward neutrophil granulocytes. Administration of ATRA leads to massive changes in gene expression, including down-regulation of cell proliferation-related genes and induction of genes involved in immune function. One of the most induced genes in APL NB4 cells is transglutaminase 2 (TG2). RNA interference-mediated stable silencing of TG2 in NB4 cells (TG2-KD NB4) coupled with whole genome microarray analysis revealed that TG2 is involved in the expression of a large number of ATRA-regulated genes. The affected genes participate in granulocyte functions, and their silencing lead to reduced adhesive, migratory, and phagocytic capacity of neutrophils and less superoxide production. The expression of genes related to cell-cycle control also changed, suggesting that TG2 regulates myeloid cell differentiation. CC chemokines CCL2, CCL3, CCL22, CCL24, and cytokines IL1B and IL8 involved in the development of differentiation syndrome are expressed at significantly lower level in TG2-KD NB4 than in wild-type NB4 cells upon ATRA treatment. Based on our results, we propose that reduced expression of TG2 in differentiating APL cells may suppress effector functions of neutrophil granulocytes and attenuate the ATRA-induced inflammatory phenotype of differentiation syndrome.

The HOPA Gene Dodecamer Duplication Is Not a Significant Etiological Factor in Autism.

ERIC Educational Resources Information Center

Michaelis, Ron C.; Copeland-Yates, Susan A.; Sossey-Alaoui, Khalid; Skinner, Cindy; Friez, Michael J.; Longshore, John W.; Simensen, Richard J.; Schroer, Richard J.; Stevenson, Roger E.

2000-01-01

A study of 202 patients with autism found the incidence of a dodecamer duplication in the HOPA gene was not significantly different between patients and controls. Three female patients inherited the duplication from nonautistic fathers. Also, there was no systematic skewing of X inactivation in female patients with the duplication. (Contains…

The conversion of centrioles to centrosomes: essential coupling of duplication with segregation.

PubMed

Wang, Won-Jing; Soni, Rajesh Kumar; Uryu, Kunihiro; Tsou, Meng-Fu Bryan

2011-05-16

Centrioles are self-reproducing organelles that form the core structure of centrosomes or microtubule-organizing centers (MTOCs). However, whether duplication and MTOC organization reflect innate activities of centrioles or activities acquired conditionally is unclear. In this paper, we show that newly formed full-length centrioles had no inherent capacity to duplicate or to organize pericentriolar material (PCM) but acquired both after mitosis through a Plk1-dependent modification that occurred in early mitosis. Modified centrioles initiated PCM recruitment in G1 and segregated equally in mitosis through association with spindle poles. Conversely, unmodified centrioles segregated randomly unless passively tethered to modified centrioles. Strikingly, duplication occurred only in centrioles that were both modified and disengaged, whereas unmodified centrioles, engaged or not, were "infertile," indicating that engagement specifically blocks modified centrioles from reduplication. These two requirements, centriole modification and disengagement, fully exclude unlimited duplication in one cell cycle. We thus uncovered a Plk1-dependent mechanism whereby duplication and segregation are coupled to maintain centriole homeostasis.

Craniofacial duplication (diprosopus): CT, MR imaging, and MR angiography findings case report.

PubMed

Hähnel, Stefan; Schramm, Peter; Hassfeld, Stefan; Steiner, Hans H; Seitz, Angelika

2003-01-01

Diprosopus is one of the rarest malformations in humans. In addition to the facial structures, the cerebral frontal lobes were duplicated in this case. Three pairs of anterior cerebral arteries were detected, and the rostral parts of the superior sagittal sinus were duplicated. Computed tomography, magnetic resonance (MR) imaging, and MR angiography allowed study of the degree of duplicative changes in diprosopus, especially for planning cosmetic correction. Copyright RSNA, 2002

Detection and correction of false segmental duplications caused by genome mis-assembly

PubMed Central

2010-01-01

Diploid genomes with divergent chromosomes present special problems for assembly software as two copies of especially polymorphic regions may be mistakenly constructed, creating the appearance of a recent segmental duplication. We developed a method for identifying such false duplications and applied it to four vertebrate genomes. For each genome, we corrected mis-assemblies, improved estimates of the amount of duplicated sequence, and recovered polymorphisms between the sequenced chromosomes. PMID:20219098

Mouse Models of Genomic Syndromes as Tools for Understanding the Basis of Complex Traits: An Example with the Smith-Magenis and the Potocki-Lupski Syndromes

PubMed Central

Carmona-Mora, P; Molina, J; Encina, C.A; Walz, K

2009-01-01

Each human's genome is distinguished by extra and missing DNA that can be “benign” or powerfully impact everything from development to disease. In the case of genomic disorders DNA rearrangements, such as deletions or duplications, correlate with a clinical specific phenotype. The clinical presentations of genomic disorders were thought to result from altered gene copy number of physically linked dosage sensitive genes. Genomic disorders are frequent diseases (~1 per 1,000 births). Smith-Magenis syndrome (SMS) and Potocki-Lupski syndrome (PTLS) are genomic disorders, associated with a deletion and a duplication, of 3.7 Mb respectively, within chromosome 17 band p11.2. This region includes 23 genes. Both syndromes have complex and distinctive phenotypes including multiple congenital and neurobehavioral abnormalities. Human chromosome 17p11.2 is syntenic to the 32-34 cM region of murine chromosome 11. The number and order of the genes are highly conserved. In this review, we will exemplify how genomic disorders can be modeled in mice and the advantages that such models can give in the study of genomic disorders in particular and gene copy number variation (CNV) in general. The contributions of the SMS and PTLS animal models in several aspects ranging from more specific ones, as the definition of the clinical aspects of the human clinical spectrum, the identification of dosage sensitive genes related to the human syndromes, to the more general contributions as the definition of genetic locus impacting obesity and behavior and the elucidation of general mechanisms related to the pathogenesis of gene CNV are discussed. PMID:19949547

Paracentric inversion of chromosome 2 associated with cryptic duplication of 2q14 and deletion of 2q37 in a patient with autism.

PubMed

Devillard, Françoise; Guinchat, Vincent; Moreno-De-Luca, Daniel; Tabet, Anne-Claude; Gruchy, Nicolas; Guillem, Pascale; Nguyen Morel, Marie-Ange; Leporrier, Nathalie; Leboyer, Marion; Jouk, Pierre-Simon; Lespinasse, James; Betancur, Catalina

2010-09-01

We describe a patient with autism and a paracentric inversion of chromosome 2q14.2q37.3, with a concurrent duplication of the proximal breakpoint at 2q14.1q14.2 and a deletion of the distal breakpoint at 2q37.3. The abnormality was derived from his mother with a balanced paracentric inversion. The inversion in the child appeared to be cytogenetically balanced but subtelomere FISH revealed a cryptic deletion at the 2q37.3 breakpoint. High-resolution single nucleotide polymorphism array confirmed the presence of a 3.5 Mb deletion that extended to the telomere, and showed a 4.2 Mb duplication at 2q14.1q14.2. FISH studies using a 2q14.2 probe showed that the duplicated segment was located at the telomeric end of chromosome 2q. This recombinant probably resulted from breakage of a dicentric chromosome. The child had autism, mental retardation, speech and language delay, hyperactivity, growth retardation with growth hormone deficiency, insulin-dependent diabetes, and mild facial dysmorphism. Most of these features have been previously described in individuals with simple terminal deletion of 2q37. Pure duplications of the proximal chromosome 2q are rare and no specific syndrome has been defined yet, so the contribution of the 2q14.1q14.2 duplication to the phenotype of the patient is unknown. These findings underscore the need to explore apparently balanced chromosomal rearrangements inherited from a phenotypically normal parent in subjects with autism and/or developmental delay. In addition, they provide further evidence indicating that chromosome 2q terminal deletions are among the most frequently reported cytogenetic abnormalities in individuals with autism.

Formation of new chromatin domains determines pathogenicity of genomic duplications.

PubMed

Franke, Martin; Ibrahim, Daniel M; Andrey, Guillaume; Schwarzer, Wibke; Heinrich, Verena; Schöpflin, Robert; Kraft, Katerina; Kempfer, Rieke; Jerković, Ivana; Chan, Wing-Lee; Spielmann, Malte; Timmermann, Bernd; Wittler, Lars; Kurth, Ingo; Cambiaso, Paola; Zuffardi, Orsetta; Houge, Gunnar; Lambie, Lindsay; Brancati, Francesco; Pombo, Ana; Vingron, Martin; Spitz, Francois; Mundlos, Stefan

2016-10-13

Chromosome conformation capture methods have identified subchromosomal structures of higher-order chromatin interactions called topologically associated domains (TADs) that are separated from each other by boundary regions. By subdividing the genome into discrete regulatory units, TADs restrict the contacts that enhancers establish with their target genes. However, the mechanisms that underlie partitioning of the genome into TADs remain poorly understood. Here we show by chromosome conformation capture (capture Hi-C and 4C-seq methods) that genomic duplications in patient cells and genetically modified mice can result in the formation of new chromatin domains (neo-TADs) and that this process determines their molecular pathology. Duplications of non-coding DNA within the mouse Sox9 TAD (intra-TAD) that cause female to male sex reversal in humans, showed increased contact of the duplicated regions within the TAD, but no change in the overall TAD structure. In contrast, overlapping duplications that extended over the next boundary into the neighbouring TAD (inter-TAD), resulted in the formation of a new chromatin domain (neo-TAD) that was isolated from the rest of the genome. As a consequence of this insulation, inter-TAD duplications had no phenotypic effect. However, incorporation of the next flanking gene, Kcnj2, in the neo-TAD resulted in ectopic contacts of Kcnj2 with the duplicated part of the Sox9 regulatory region, consecutive misexpression of Kcnj2, and a limb malformation phenotype. Our findings provide evidence that TADs are genomic regulatory units with a high degree of internal stability that can be sculptured by structural genomic variations. This process is important for the interpretation of copy number variations, as these variations are routinely detected in diagnostic tests for genetic disease and cancer. This finding also has relevance in an evolutionary setting because copy-number differences are thought to have a crucial role in the evolution of

10 CFR 9.39 - Search and duplication provided without charge.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 10 Energy 1 2014-01-01 2014-01-01 false Search and duplication provided without charge. 9.39... § 9.39 Search and duplication provided without charge. (a) The NRC will search for agency records... the news media. (b) The NRC will search for agency records requested under § 9.23(b) without charges...

10 CFR 9.39 - Search and duplication provided without charge.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 10 Energy 1 2010-01-01 2010-01-01 false Search and duplication provided without charge. 9.39... § 9.39 Search and duplication provided without charge. (a) The NRC will search for agency records... the news media. (b) The NRC will search for agency records requested under § 9.23(b) without charges...

10 CFR 9.39 - Search and duplication provided without charge.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 10 Energy 1 2013-01-01 2013-01-01 false Search and duplication provided without charge. 9.39... § 9.39 Search and duplication provided without charge. (a) The NRC will search for agency records... the news media. (b) The NRC will search for agency records requested under § 9.23(b) without charges...

10 CFR 9.39 - Search and duplication provided without charge.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 10 Energy 1 2011-01-01 2011-01-01 false Search and duplication provided without charge. 9.39... § 9.39 Search and duplication provided without charge. (a) The NRC will search for agency records... the news media. (b) The NRC will search for agency records requested under § 9.23(b) without charges...

Genome-wide site-specific differential methylation in the blood of individuals with Klinefelter Syndrome

PubMed Central

Wan, Emily S.; Qiu, Weiliang; Morrow, Jarrett; Beaty, Terri H.; Hetmanski, Jacqueline; Make, Barry J.; Lomas, David A.; Silverman, Edwin K.; DeMeo, Dawn L.

2015-01-01

Klinefelter syndrome (KS) (47 XXY) is a common sex-chromosome aneuploidy with an estimated prevalence of 1 in every 660 male births. Investigations into the associations between DNA methylation and the highly variable clinical manifestations of KS have largely focused on the supernumerary X chromosome; systematic investigations of the epigenome have been limited. We obtained genome-wide DNA methylation data from peripheral blood using the Illumina HumanMethylation450K platform in 5 KS (47 XXY), 102 male (46 XY), and 113 female (46 XX) control subjects participating in the chronic obstructive pulmonary disease (COPD) Gene Study. Empirical Bayes-mediated models were used to test for differential methylation by KS status. CpG sites with a false-discovery rate <0.05 from the first-generation HumanMethylation27K platform were further examined in an independent replication cohort of 2 KS subjects, 590 male, and 495 female controls drawn from the International COPD Genetics Network (ICGN). Differential methylation at sites throughout the genome were identified, including 86 CpG sites that were differentially methylated in KS subjects relative to both male and female controls. CpG sites annotated to the HEN1 methyltransferase homolog 1 (HENMT1), calcyclin-binding protein (CACYBP), and GTPase-activating protein (SH3 domain)-binding protein 1 (G3BP1) genes were among the “KS-specific” loci that were replicated in ICGN. We therefore conclude that site-specific differential methylation exists throughout the genome in KS. The functional impact and clinical relevance of these differentially methylated loci should be explored in future studies. PMID:25988574

The Use of Duplication-Generating Rearrangements for Studying Heterokaryon Incompatibility Genes in Neurospora

PubMed Central

Perkins, David D.

1975-01-01

Heterokaryon (vegetative) incompatibility, governing the fusion of somatic hyphal filaments to form stable heterokaryons, is of interest because of its widespread occurrence in fungi and its bearing on cellular recognition. Conventional investigations of the genetic basis of heterokaryon incompatibility in N. crassa are difficult because in commonly used stocks differences are present at several het loci, all with similar incompatibility phenotypes. This difficulty is overcome by using duplications (partial diploids) that are unlikely to contain more than one het locus. A phenotypically expressed incompatibility reaction occurs when unlike het alleles are present within the same somatic nucleus, and this parallels the heterokaryon incompatibility reaction that occurs when unlike alleles in different haploid nuclei are introduced into the same somatic hypha by mycelial fusion.—Nontandem duplications were used to confirm that the incompatibility reactions in heterokaryons and in duplications are alternate expressions of the same genes. This was demonstrated for three loci which had previously been established by conventional heterokaryon tests—het-e, het-c and mt. These were each obtained in duplications as recombinant meiotic segregants from crosses heterozygous for duplication-generating chromosome rearrangements. The particular method of producing the duplications is irrelevant so long as the incompatibility alleles are heterozygous.—The duplication technique has made it possible to determine easily the het-e and het-c genotypes of numerous laboratory and wild strains of unknown constitution. In laboratory strains both loci are represented simply by two alleles. Analysis of het-c is more complicated in some wild strains, where differences have been demonstrated at one or more additional het loci within the duplication used and multiple allelism is also possible.—The results show that the duplication method can be used to identify and map additional

Dangerous triplet: Polycystic ovary syndrome, oral contraceptives and Kounis syndrome.

PubMed

Erol, Nurdan; Karaagac, Aysu Turkmen; Kounis, Nicholas G

2014-12-26

Polycystic ovary syndrome is characterized by ovulatory dysfunction, androgen excess and polycystic ovaries and is associated with hypertension, diabetes, metabolic syndrome and cardiovascular events. Oral contraceptives constitute first-line treatment, particularly when symptomatic hyperandrogenism is present. However, these drugs are associated with cardiovascular events and hypersensitivity reactions that pose problem in differential diagnosis and therapy. We present a 14 year-old female with polycystic ovary syndrome taking oral contraceptive and suffering from recurrent coronary ischemic attacks with increased eosinophils, and troponin levels suggesting Kounis syndrome.

A Challenge for Cochlear Implantation: Duplicated Internal Auditory Canal.

PubMed

Binnetoğlu, Adem; Bağlam, Tekin; Sarı, Murat; Gündoğdu, Yavuz; Batman, Çağlar

2016-08-01

Duplication of the internal auditory canal is an uncommon, congenital malformation that can be associated with sensorineural hearing loss owing to aplasia/hypoplasia of the vestibulocochlear nerve. Only 14 such cases have been reported to date. We report the case of a 13-month-old girl with bilateral, congenital, sensorineural hearing loss caused by narrow, duplicated internal auditory canals and discuss the challenges encountered in the diagnosis and treatment of this condition.

Elucidation of the Molecular Mechanism Driving Duplication of the HIV-1 PTAP Late Domain.

PubMed

Martins, Angelica N; Waheed, Abdul A; Ablan, Sherimay D; Huang, Wei; Newton, Alicia; Petropoulos, Christos J; Brindeiro, Rodrigo D M; Freed, Eric O

2016-01-15

HIV-1 uses cellular machinery to bud from infected cells. This cellular machinery is comprised of several multiprotein complexes known as endosomal sorting complexes required for transport (ESCRTs). A conserved late domain motif, Pro-Thr-Ala-Pro (PTAP), located in the p6 region of Gag (p6(Gag)), plays a central role in ESCRT recruitment to the site of virus budding. Previous studies have demonstrated that PTAP duplications are selected in HIV-1-infected patients during antiretroviral therapy; however, the consequences of these duplications for HIV-1 biology and drug resistance are unclear. To address these questions, we constructed viruses carrying a patient-derived PTAP duplication with and without drug resistance mutations in the viral protease. We evaluated the effect of the PTAP duplication on viral release efficiency, viral infectivity, replication capacity, drug susceptibility, and Gag processing. In the presence of protease inhibitors, we observed that the PTAP duplication in p6(Gag) significantly increased the infectivity and replication capacity of the virus compared to those of viruses bearing only resistance mutations in protease. Our biochemical analysis showed that the PTAP duplication, in combination with mutations in protease, enhances processing between the nucleocapsid and p6 domains of Gag, resulting in more complete Gag cleavage in the presence of protease inhibitors. These results demonstrate that duplication of the PTAP motif in p6(Gag) confers a selective advantage in viral replication by increasing Gag processing efficiency in the context of protease inhibitor treatment, thereby enhancing the drug resistance of the virus. These findings highlight the interconnected role of PTAP duplications and protease mutations in the development of resistance to antiretroviral therapy. Resistance to current drug therapy limits treatment options in many HIV-1-infected patients. Duplications in a Pro-Thr-Ala-Pro (PTAP) motif in the p6 domain of Gag are

Duplicated Leptin Receptors in Two Species of Eel Bring New Insights into the Evolution of the Leptin System in Vertebrates

PubMed Central

Morini, Marina; Pasquier, Jérémy; Dirks, Ron; van den Thillart, Guido; Tomkiewicz, Jonna; Rousseau, Karine; Dufour, Sylvie; Lafont, Anne-Gaëlle

2015-01-01

Since its discovery in mammals as a key-hormone in reproduction and metabolism, leptin has been identified in an increasing number of tetrapods and teleosts. Tetrapods possess only one leptin gene, while most teleosts possess two leptin genes, as a result of the teleost third whole genome duplication event (3R). Leptin acts through a specific receptor (LEPR). In the European and Japanese eels, we identified two leptin genes, and for the first time in vertebrates, two LEPR genes. Synteny analyses indicated that eel LEPRa and LEPRb result from teleost 3R. LEPRb seems to have been lost in the teleost lineage shortly after the elopomorph divergence. Quantitative PCRs revealed a wide distribution of leptins and LEPRs in the European eel, including tissues involved in metabolism and reproduction. Noticeably, leptin1 was expressed in fat tissue, while leptin2 in the liver, reflecting subfunctionalization. Four-month fasting had no impact on the expression of leptins and LEPRs in control European eels. This might be related to the remarkable adaptation of silver eel metabolism to long-term fasting throughout the reproductive oceanic migration. In contrast, sexual maturation induced differential increases in the expression of leptins and LEPRs in the BPG-liver axis. Leptin2 was strikingly upregulated in the liver, the central organ of the reproductive metabolic challenge in teleosts. LEPRs were differentially regulated during sexual maturation, which may have contributed to the conservation of the duplicated LEPRs in this species. This suggests an ancient and positive role of the leptin system in the vertebrate reproductive function. This study brings new insights on the evolutionary history of the leptin system in vertebrates. Among extant vertebrates, the eel represents a unique case of duplicated leptins and leptin receptors as a result of 3R. PMID:25946034

Expression, subcellular localization, and cis-regulatory structure of duplicated phytoene synthase genes in melon (Cucumis melo L.).

PubMed

Qin, Xiaoqiong; Coku, Ardian; Inoue, Kentaro; Tian, Li

2011-10-01

Carotenoids perform many critical functions in plants, animals, and humans. It is therefore important to understand carotenoid biosynthesis and its regulation in plants. Phytoene synthase (PSY) catalyzes the first committed and rate-limiting step in carotenoid biosynthesis. While PSY is present as a single copy gene in Arabidopsis, duplicated PSY genes have been identified in many economically important monocot and dicot crops. CmPSY1 was previously identified from melon (Cucumis melo L.), but was not functionally characterized. We isolated a second PSY gene, CmPSY2, from melon in this work. CmPSY2 possesses a unique intron/exon structure that has not been observed in other plant PSYs. Both CmPSY1 and CmPSY2 are functional in vitro, but exhibit distinct expression patterns in different melon tissues and during fruit development, suggesting differential regulation of the duplicated melon PSY genes. In vitro chloroplast import assays verified the plastidic localization of CmPSY1 and CmPSY2 despite the lack of an obvious plastid target peptide in CmPSY2. Promoter motif analysis of the duplicated melon and tomato PSY genes and the Arabidopsis PSY revealed distinctive cis-regulatory structures of melon PSYs and identified gibberellin-responsive motifs in all PSYs except for SlPSY1, which has not been reported previously. Overall, these data provide new insights into the evolutionary history of plant PSY genes and the regulation of PSY expression by developmental and environmental signals that may involve different regulatory networks.

Identifying duplicate content using statistically improbable phrases

PubMed Central

Errami, Mounir; Sun, Zhaohui; George, Angela C.; Long, Tara C.; Skinner, Michael A.; Wren, Jonathan D.; Garner, Harold R.

2010-01-01

Motivation: Document similarity metrics such as PubMed's ‘Find related articles’ feature, which have been primarily used to identify studies with similar topics, can now also be used to detect duplicated or potentially plagiarized papers within literature reference databases. However, the CPU-intensive nature of document comparison has limited MEDLINE text similarity studies to the comparison of abstracts, which constitute only a small fraction of a publication's total text. Extending searches to include text archived by online search engines would drastically increase comparison ability. For large-scale studies, submitting short phrases encased in direct quotes to search engines for exact matches would be optimal for both individual queries and programmatic interfaces. We have derived a method of analyzing statistically improbable phrases (SIPs) for assistance in identifying duplicate content. Results: When applied to MEDLINE citations, this method substantially improves upon previous algorithms in the detection of duplication citations, yielding a precision and recall of 78.9% (versus 50.3% for eTBLAST) and 99.6% (versus 99.8% for eTBLAST), respectively. Availability: Similar citations identified by this work are freely accessible in the Déjà vu database, under the SIP discovery method category at http://dejavu.vbi.vt.edu/dejavu/ Contact: merrami@collin.edu PMID:20472545

Diprosopus (partially duplicated head) associated with anencephaly: a case report.

PubMed

al Muti Zaitoun, A; Chang, J; Booker, M

1999-01-01

Craniofacial duplication (diprosopus) is a rare form of conjoined twin. A 16 year old mother with a twin pregnancy delivered one normally formed baby boy and one diprosopus male. The malformed baby was 33 weeks of gestation with a single trunk, normal limbs and various degrees of facial duplication. Of the following structures there were two of each: noses, eyes, ears (and one dimple), mouths, tongues and, with bilateral central cleft lips and cleft palates. This was associated with holoprosencephaly and craniorachischisis. Internal organs showed no duplication. There were multiple congenital anomalies including diaphragmatic hernia, small lungs, two lobes of the right lung, ventricular septal defect, small adrenal gland and small left kidney with short ureter. The body also had a short neck, small chest cavities and kyphosis. X-ray revealed duplication of the vertebral column. The case presented here represents a type II of diprosopia of Rating (1933) and is the least common type reported. We also reviewed 22 recently reported cases of diprosopus. In addition to facial duplication, anencephaly, neural tube defect and cardiac malformations represent the more common congenital abnormalities associated with diprosopus. The pathogenesis of diprosopus is not well understood. Factors that play a role in diprosopus are probably similar to those factors (genetic, environmental and abnormal placental circulation) which affect monozoygotic twins as observed in this case report. Early ultrasonography diagnosis of diprosopus permits one to consider a vaginal therapeutic abortion.

Independent Origin and Global Distribution of Distinct Plasmodium vivax Duffy Binding Protein Gene Duplications

PubMed Central

Hostetler, Jessica B.; Lo, Eugenia; Kanjee, Usheer; Amaratunga, Chanaki; Suon, Seila; Sreng, Sokunthea; Mao, Sivanna; Yewhalaw, Delenasaw; Mascarenhas, Anjali; Kwiatkowski, Dominic P.; Ferreira, Marcelo U.; Rathod, Pradipsinh K.; Yan, Guiyun; Fairhurst, Rick M.; Duraisingh, Manoj T.; Rayner, Julian C.

2016-01-01

Background Plasmodium vivax causes the majority of malaria episodes outside Africa, but remains a relatively understudied pathogen. The pathology of P. vivax infection depends critically on the parasite’s ability to recognize and invade human erythrocytes. This invasion process involves an interaction between P. vivax Duffy Binding Protein (PvDBP) in merozoites and the Duffy antigen receptor for chemokines (DARC) on the erythrocyte surface. Whole-genome sequencing of clinical isolates recently established that some P. vivax genomes contain two copies of the PvDBP gene. The frequency of this duplication is particularly high in Madagascar, where there is also evidence for P. vivax infection in DARC-negative individuals. The functional significance and global prevalence of this duplication, and whether there are other copy number variations at the PvDBP locus, is unknown. Methodology/Principal Findings Using whole-genome sequencing and PCR to study the PvDBP locus in P. vivax clinical isolates, we found that PvDBP duplication is widespread in Cambodia. The boundaries of the Cambodian PvDBP duplication differ from those previously identified in Madagascar, meaning that current molecular assays were unable to detect it. The Cambodian PvDBP duplication did not associate with parasite density or DARC genotype, and ranged in prevalence from 20% to 38% over four annual transmission seasons in Cambodia. This duplication was also present in P. vivax isolates from Brazil and Ethiopia, but not India. Conclusions/Significance PvDBP duplications are much more widespread and complex than previously thought, and at least two distinct duplications are circulating globally. The same duplication boundaries were identified in parasites from three continents, and were found at high prevalence in human populations where DARC-negativity is essentially absent. It is therefore unlikely that PvDBP duplication is associated with infection of DARC-negative individuals, but functional tests

Y-type urethral duplication: an unusual variant of a rare anomaly.

PubMed

Kumaravel, S; Senthilnathan, R; Sankkarabarathi, C; Bagdi, R K; Soundararajan, S; Prasad, N

2004-12-01

Urethral duplications are rare anomalies. We present a 3-year-old continent boy passing urine since birth per anus while voiding from penis. Micturating cystourethrogram, retrograde urethrogram and cystoscopy revealed a Y connection between the posterior urethra and anal canal. The accessory channel was excised by a perineal approach. Histopathology revealed that the tract was lined by transitional epithelium, proving that it was indeed a case of urethral duplication; hence, we suggest that all urethroanal fistulas are not variants of anorectal malformations. Certain of these fistulas should be considered as variants of Y-type urethral duplication even if the orthotopic urethra is normal.

Electrocardiography cannot reliably differentiate transient left ventricular apical ballooning syndrome from anterior ST-segment elevation myocardial infarction.

PubMed

Bybee, Kevin A; Motiei, Arashk; Syed, Imran S; Kara, Tomas; Prasad, Abhiram; Lennon, Ryan J; Murphy, Joseph G; Hammill, Stephen C; Rihal, Charanjit S; Wright, R Scott

2007-01-01

The presentation and electrocardiographic (ECG) characteristics of transient left ventricular apical ballooning syndrome (TLVABS) can be similar to that of anterior ST-segment elevation myocardial infarction (STEMI). We tested the hypothesis that the ECG on presentation could reliably differentiate these syndromes. Between January 1, 2002 and July 31, 2004, we identified 18 consecutive patients with TLVABS who were matched with 36 subjects presenting with acute anterior STEMI due to atherothrombotic left anterior descending coronary artery occlusion. All patients with TLVABS were women (mean age, 72.0 +/- 13.1 years). The heart rate, PR interval, QRS duration, and corrected QT interval were similar between groups. Distribution of ST elevation was similar, but patients with anterior STEMI exhibited greater ST elevation. Regressive partitioning analysis indicated that the combination of ST elevation in lead V2 of less than 1.75 mm and ST-segment elevation in lead V3 of less than 2.5 mm was a suggestive predictor of TLVABS (sensitivity, 67%; specificity, 94%). Conditional logistic regression indicated that the formula: (3 x ST-elevation lead V2) + (ST-elevation V3) + (2 x ST-elevation V5) allowed possible discrimination between TLVABS and anterior STEMI with an optimal cutoff level of less than 11.5 mm for TLVABS (sensitivity, 94%; specificity, 72%). Patients with TLVABS were less likely to have concurrent ST-segment depression (6% vs 44%; P = .003). Women presenting with TLVABS have similar ECG findings to patients with anterior infarct but with less-prominent ST-segment elevation in the anterior precordial ECG leads. These ECG findings are relatively subtle and do not have sufficient predictive value to allow reliable emergency differentiation of these syndromes.

Sas-4 proteins are required during basal body duplication in Paramecium

PubMed Central

Gogendeau, Delphine; Hurbain, Ilse; Raposo, Graca; Cohen, Jean; Koll, France; Basto, Renata

2011-01-01

Centrioles and basal bodies are structurally related organelles composed of nine microtubule (MT) triplets. Studies performed in Caenorhabditis elegans embryos have shown that centriole duplication takes place in sequential way, in which different proteins are recruited in a specific order to assemble a procentriole. ZYG-1 initiates centriole duplication by triggering the recruitment of a complex of SAS-5 and SAS-6, which then recruits the final player, SAS-4, to allow the incorporation of MT singlets. It is thought that a similar mechanism (that also involves additional proteins) is present in other animal cells, but it remains to be investigated whether the same players and their ascribed functions are conserved during basal body duplication in cells that exclusively contain basal bodies. To investigate this question, we have used the multiciliated protist Paramecium tetraurelia. Here we show that in the absence of PtSas4, two types of defects in basal body duplication can be identified. In the majority of cases, the germinative disk and cartwheel, the first structures assembled during duplication, are not detected. In addition, if daughter basal bodies were formed, they invariably had defects in MT recruitment. Our results suggest that PtSas4 has a broader function than its animal orthologues. PMID:21289083

The conversion of centrioles to centrosomes: essential coupling of duplication with segregation

PubMed Central

Wang, Won-Jing; Soni, Rajesh Kumar; Uryu, Kunihiro

2011-01-01

Centrioles are self-reproducing organelles that form the core structure of centrosomes or microtubule-organizing centers (MTOCs). However, whether duplication and MTOC organization reflect innate activities of centrioles or activities acquired conditionally is unclear. In this paper, we show that newly formed full-length centrioles had no inherent capacity to duplicate or to organize pericentriolar material (PCM) but acquired both after mitosis through a Plk1-dependent modification that occurred in early mitosis. Modified centrioles initiated PCM recruitment in G1 and segregated equally in mitosis through association with spindle poles. Conversely, unmodified centrioles segregated randomly unless passively tethered to modified centrioles. Strikingly, duplication occurred only in centrioles that were both modified and disengaged, whereas unmodified centrioles, engaged or not, were “infertile,” indicating that engagement specifically blocks modified centrioles from reduplication. These two requirements, centriole modification and disengagement, fully exclude unlimited duplication in one cell cycle. We thus uncovered a Plk1-dependent mechanism whereby duplication and segregation are coupled to maintain centriole homeostasis. PMID:21576395

The sea lamprey meiotic map improves resolution of ancient vertebrate genome duplications.

PubMed

Smith, Jeramiah J; Keinath, Melissa C

2015-08-01

It is generally accepted that many genes present in vertebrate genomes owe their origin to two whole-genome duplications that occurred deep in the ancestry of the vertebrate lineage. However, details regarding the timing and outcome of these duplications are not well resolved. We present high-density meiotic and comparative genomic maps for the sea lamprey (Petromyzon marinus), a representative of an ancient lineage that diverged from all other vertebrates ∼550 million years ago. Linkage analyses yielded a total of 95 linkage groups, similar to the estimated number of germline chromosomes (1n ∼ 99), spanning a total of 5570.25 cM. Comparative mapping data yield strong support for the hypothesis that a single whole-genome duplication occurred in the basal vertebrate lineage, but do not strongly support a hypothetical second event. Rather, these comparative maps reveal several evolutionarily independent segmental duplications occurring over the last 600+ million years of chordate evolution. This refined history of vertebrate genome duplication should permit more precise investigations of vertebrate evolution. © 2015 Smith and Keinath; Published by Cold Spring Harbor Laboratory Press.

Duplicated Enhancer Region Increases Expression of CTSB and Segregates with Keratolytic Winter Erythema in South African and Norwegian Families.

PubMed

Ngcungcu, Thandiswa; Oti, Martin; Sitek, Jan C; Haukanes, Bjørn I; Linghu, Bolan; Bruccoleri, Robert; Stokowy, Tomasz; Oakeley, Edward J; Yang, Fan; Zhu, Jiang; Sultan, Marc; Schalkwijk, Joost; van Vlijmen-Willems, Ivonne M J J; von der Lippe, Charlotte; Brunner, Han G; Ersland, Kari M; Grayson, Wayne; Buechmann-Moller, Stine; Sundnes, Olav; Nirmala, Nanguneri; Morgan, Thomas M; van Bokhoven, Hans; Steen, Vidar M; Hull, Peter R; Szustakowski, Joseph; Staedtler, Frank; Zhou, Huiqing; Fiskerstrand, Torunn; Ramsay, Michele

2017-05-04

Keratolytic winter erythema (KWE) is a rare autosomal-dominant skin disorder characterized by recurrent episodes of palmoplantar erythema and epidermal peeling. KWE was previously mapped to 8p23.1-p22 (KWE critical region) in South African families. Using targeted resequencing of the KWE critical region in five South African families and SNP array and whole-genome sequencing in two Norwegian families, we identified two overlapping tandem duplications of 7.67 kb (South Africans) and 15.93 kb (Norwegians). The duplications segregated with the disease and were located upstream of CTSB, a gene encoding cathepsin B, a cysteine protease involved in keratinocyte homeostasis. Included in the 2.62 kb overlapping region of these duplications is an enhancer element that is active in epidermal keratinocytes. The activity of this enhancer correlated with CTSB expression in normal differentiating keratinocytes and other cell lines, but not with FDFT1 or NEIL2 expression. Gene expression (qPCR) analysis and immunohistochemistry of the palmar epidermis demonstrated significantly increased expression of CTSB, as well as stronger staining of cathepsin B in the stratum granulosum of affected individuals than in that of control individuals. Analysis of higher-order chromatin structure data and RNA polymerase II ChIA-PET data from MCF-7 cells did not suggest remote effects of the enhancer. In conclusion, KWE in South African and Norwegian families is caused by tandem duplications in a non-coding genomic region containing an active enhancer element for CTSB, resulting in upregulation of this gene in affected individuals. Copyright © 2017 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

Recurrent reciprocal deletions and duplications of 16p13.11: the deletion is a risk factor for MR/MCA while the duplication may be a rare benign variant

PubMed Central

Hannes, F D; Sharp, A J; Mefford, H C; de Ravel, T; Ruivenkamp, C A; Breuning, M H; Fryns, J-P; Devriendt, K; Van Buggenhout, G; Vogels, A; Stewart, H; Hennekam, R C; Cooper, G M; Regan, R; Knight, S J L; Eichler, E E; Vermeesch, J R

2009-01-01

Background: Genomic disorders are often caused by non-allelic homologous recombination between segmental duplications. Chromosome 16 is especially rich in a chromosome-specific low copy repeat, termed LCR16. Methods and Results: A bacterial artificial chromosome (BAC) array comparative genome hybridisation (CGH) screen of 1027 patients with mental retardation and/or multiple congenital anomalies (MR/MCA) was performed. The BAC array CGH screen identified five patients with deletions and five with apparently reciprocal duplications of 16p13 covering 1.65 Mb, including 15 RefSeq genes. In addition, three atypical rearrangements overlapping or flanking this region were found. Fine mapping by high-resolution oligonucleotide arrays suggests that these deletions and duplications result from non-allelic homologous recombination (NAHR) between distinct LCR16 subunits with >99% sequence identity. Deletions and duplications were either de novo or inherited from unaffected parents. To determine whether these imbalances are associated with the MR/MCA phenotype or whether they might be benign variants, a population of 2014 normal controls was screened. The absence of deletions in the control population showed that 16p13.11 deletions are significantly associated with MR/MCA (p = 0.0048). Despite phenotypic variability, common features were identified: three patients with deletions presented with MR, microcephaly and epilepsy (two of these had also short stature), and two other deletion carriers ascertained prenatally presented with cleft lip and midline defects. In contrast to its previous association with autism, the duplication seems to be a common variant in the population (5/1682, 0.29%). Conclusion: These findings indicate that deletions inherited from clinically normal parents are likely to be causal for the patients’ phenotype whereas the role of duplications (de novo or inherited) in the phenotype remains uncertain. This difference in knowledge regarding the

Circular DNA Intermediate in the Duplication of Nile Tilapia vasa Genes

PubMed Central

Fujimura, Koji; Conte, Matthew A.; Kocher, Thomas D.

2011-01-01

vasa is a highly conserved RNA helicase involved in animal germ cell development. Among vertebrate species, it is typically present as a single copy per genome. Here we report the isolation and sequencing of BAC clones for Nile tilapia vasa genes. Contrary to a previous report that Nile tilapia have a single copy of the vasa gene, we find evidence for at least three vasa gene loci. The vasa gene locus was duplicated from the original site and integrated into two distant novel sites. For one of these insertions we find evidence that the duplication was mediated by a circular DNA intermediate. This mechanism of gene duplication may explain the origin of isolated gene duplicates during the evolution of fish genomes. These data provide a foundation for studying the role of multiple vasa genes in the development of tilapia gonads, and will contribute to investigations of the molecular mechanisms of sex determination and evolution in cichlid fishes. PMID:22216289

Reducing duplicate testing: a comparison of two clinical decision support tools.

PubMed

Procop, Gary W; Keating, Catherine; Stagno, Paul; Kottke-Marchant, Kandice; Partin, Mary; Tuttle, Robert; Wyllie, Robert

2015-05-01

Unnecessary duplicate laboratory testing is common and costly. Systems-based means to avert unnecessary testing should be investigated and employed. We compared the effectiveness and cost savings associated with two clinical decision support tools to stop duplicate testing. The Hard Stop required telephone contact with the laboratory and justification to have the duplicate test performed, whereas the Smart Alert allowed the provider to bypass the alert at the point of order entry without justification. The Hard Stop alert was significantly more effective than the Smart Alert (92.3% vs 42.6%, respectively; P < .0001). The cost savings realized per alert activation was $16.08/alert for the Hard Stop alert vs $3.52/alert for the Smart Alert. Structural and process changes that require laboratory contact and justification for duplicate testing are more effective than interventions that allow providers to bypass alerts without justification at point of computerized physician order entry. Copyright© by the American Society for Clinical Pathology.

Differentiated protection method in passive optical networks based on OPEX

NASA Astrophysics Data System (ADS)

Zhang, Zhicheng; Guo, Wei; Jin, Yaohui; Sun, Weiqiang; Hu, Weisheng

2011-12-01

Reliable service delivery becomes more significant due to increased dependency on electronic services all over society and the growing importance of reliable service delivery. As the capability of PON increasing, both residential and business customers may be included in a PON. Meanwhile, OPEX have been proven to be a very important factor of the total cost for a telecommunication operator. Thus, in this paper, we present the partial protection PON architecture and compare the operational expenditures (OPEX) of fully duplicated protection and partly duplicated protection for ONUs with different distributed fiber length, reliability requirement and penalty cost per hour. At last, we propose a differentiated protection method to minimize OPEX.

Whole-Genome Duplication and the Functional Diversification of Teleost Fish Hemoglobins

PubMed Central

Opazo, Juan C.; Butts, G. Tyler; Nery, Mariana F.; Storz, Jay F.; Hoffmann, Federico G.

2013-01-01

Subsequent to the two rounds of whole-genome duplication that occurred in the common ancestor of vertebrates, a third genome duplication occurred in the stem lineage of teleost fishes. This teleost-specific genome duplication (TGD) is thought to have provided genetic raw materials for the physiological, morphological, and behavioral diversification of this highly speciose group. The extreme physiological versatility of teleost fish is manifest in their diversity of blood–gas transport traits, which reflects the myriad solutions that have evolved to maintain tissue O2 delivery in the face of changing metabolic demands and environmental O2 availability during different ontogenetic stages. During the course of development, regulatory changes in blood–O2 transport are mediated by the expression of multiple, functionally distinct hemoglobin (Hb) isoforms that meet the particular O2-transport challenges encountered by the developing embryo or fetus (in viviparous or oviparous species) and in free-swimming larvae and adults. The main objective of the present study was to assess the relative contributions of whole-genome duplication, large-scale segmental duplication, and small-scale gene duplication in producing the extraordinary functional diversity of teleost Hbs. To accomplish this, we integrated phylogenetic reconstructions with analyses of conserved synteny to characterize the genomic organization and evolutionary history of the globin gene clusters of teleosts. These results were then integrated with available experimental data on functional properties and developmental patterns of stage-specific gene expression. Our results indicate that multiple α- and β-globin genes were present in the common ancestor of gars (order Lepisoteiformes) and teleosts. The comparative genomic analysis revealed that teleosts possess a dual set of TGD-derived globin gene clusters, each of which has undergone lineage-specific changes in gene content via repeated duplication and

The Evolutionary Fates of a Large Segmental Duplication in Mouse

PubMed Central

Morgan, Andrew P.; Holt, J. Matthew; McMullan, Rachel C.; Bell, Timothy A.; Clayshulte, Amelia M.-F.; Didion, John P.; Yadgary, Liran; Thybert, David; Odom, Duncan T.; Flicek, Paul; McMillan, Leonard; de Villena, Fernando Pardo-Manuel

2016-01-01

Gene duplication and loss are major sources of genetic polymorphism in populations, and are important forces shaping the evolution of genome content and organization. We have reconstructed the origin and history of a 127-kbp segmental duplication, R2d, in the house mouse (Mus musculus). R2d contains a single protein-coding gene, Cwc22. De novo assembly of both the ancestral (R2d1) and the derived (R2d2) copies reveals that they have been subject to nonallelic gene conversion events spanning tens of kilobases. R2d2 is also a hotspot for structural variation: its diploid copy number ranges from zero in the mouse reference genome to >80 in wild mice sampled from around the globe. Hemizygosity for high copy-number alleles of R2d2 is associated in cis with meiotic drive; suppression of meiotic crossovers; and copy-number instability, with a mutation rate in excess of 1 per 100 transmissions in some laboratory populations. Our results provide a striking example of allelic diversity generated by duplication and demonstrate the value of de novo assembly in a phylogenetic context for understanding the mutational processes affecting duplicate genes. PMID:27371833

Social network analysis of duplicative prescriptions: One-month analysis of medical facilities in Japan.

PubMed

Takahashi, Yoshimitsu; Ishizaki, Tatsuro; Nakayama, Takeo; Kawachi, Ichiro

2016-03-01

Duplicative prescriptions refer to situations in which patients receive medications for the same condition from two or more sources. Health officials in Japan have expressed concern about medical "waste" resulting from this practices. We sought to conduct descriptive analysis of duplicative prescriptions using social network analysis and to report their prevalence across ages. We analyzed a health insurance claims database including 1.24 million people from December 2012. Through social network analysis, we examined the duplicative prescription networks, representing each medical facility as nodes, and individual prescriptions for patients as edges. The prevalence of duplicative prescription for any drug class was strongly correlated with its frequency of prescription (r=0.90). Among patients aged 0-19, cough and colds drugs showed the highest prevalence of duplicative prescriptions (10.8%). Among people aged 65 and over, antihypertensive drugs had the highest frequency of prescriptions, but the prevalence of duplicative prescriptions was low (0.2-0.3%). Social network analysis revealed clusters of facilities connected via duplicative prescriptions, e.g., psychotropic drugs showed clustering due to a few patients receiving drugs from 10 or more facilities. Overall, the prevalence of duplicative prescriptions was quite low - less than 10% - although the extent of the problem varied by drug class and age group. Our approach illustrates the potential utility of using a social network approach to understand these practices. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

40 CFR 710.55 - Duplicative reporting.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Duplicative reporting. 710.55 Section 710.55 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC SUBSTANCES CONTROL ACT TSCA CHEMICAL INVENTORY REGULATIONS Inventory Update Reporting for 2006 and Beyond § 710.55...

Differentiating Alström from Bardet-Biedl syndrome (BBS) using systematic ciliopathy genes sequencing.

PubMed

Aliferis, K; Hellé, S; Gyapay, G; Duchatelet, S; Stoetzel, C; Mandel, J L; Dollfus, H

2012-03-01

Early onset retinal degeneration associated with obesity can present a diagnostic challenge in paediatric ophthalmology practice. Clinical overlap between Bardet-Biedl syndrome (BBS) and Alström syndrome has been described, although the two entities are genetically distinct. To date, 16 genes are known to be associated with BBS (BBS1-16) and only one gene has been identified for Alström syndrome (ALMS1). In collaboration with the French National Center for Sequencing (CNS, Evry), all coding exons and flanking introns were sequenced for 27 ciliopathy genes (BBS1-12, MGC1203, TTC21b, AHI1, NPHP2-8 (NPHP6=BBS14), MKS1(BBS13), MKS3, C2ORF86, SDCCAG8, ALMS1) in 96 patients referred with a clinical diagnosis of BBS. ALMS1 gene analysis included sequencing of all coding exons. BBS known gene mutations were found in 44 patients (36 with two mutations and 8 heterozygous). ALMS1 mutations were found in four cases. The rate of ALMS1 mutations among patients suspected of having BBS was 4.2%. Clinically, all four patients presented early-onset severe retinal degeneration with congenital nystagmus associated with obesity. The difficult early differential diagnosis between the two syndromes is outlined. One mutation had already been reported (c.11310delAGAG/p.R3770fsX) and three were novel (c.2293C > T/p.Q765X, c.6823insA/p.R2275fsX, c.9046delA/p.N3016fsX). Ciliopathy genes sequencing can be very helpful in providing a timely diagnosis in this group of patients, hence appropriate genetic counselling for families and adequate medical follow-up for affected children.

Giant T-shaped duplication of the transverse colon. A case report.

PubMed

Trotovsek, Blaz; Hribernik, Marija; Gvardijancic, Diana; Jelenc, Franc

2006-01-01

A case of long diverticular colonic duplication producing acute abdominal pain in a 6-year-old girl is presented. Physical examination showed no signs of acute abdomen at the initial presentation. After a pain-free interval, there was a sudden onset of severe abdominal pain and a large tumor in the lower abdomen was observed. A plain x-ray showed an enormously dilated colonic pouch filled with gas. Excision of the T-shaped duplication and small part of the transverse colon was successful. Because of extensive fibrotic changes in the colon near the opening of duplication, a resection margin of at least 2 cm is recommended.

Fluency disorders in genetic syndromes.

PubMed

Van Borsel, John; Tetnowski, John A

2007-01-01

The characteristics of various genetic syndromes have included "stuttering" as a primary symptom associated with that syndrome. Specifically, Down syndrome, fragile X syndrome, Prader-Willi syndrome, Tourette syndrome, Neurofibromatosis type I, and Turner syndrome all list "stuttering" as a characteristic of that syndrome. An extensive review of these syndromes indicated clients diagnosed with these syndromes do show evidence of nonfluency patterns, but not all would be considered stuttering. Many of the syndromes are marked by degrees of mental retardation that probably contribute to a higher than average prevalence of stuttering, as well as a higher than average prevalence of other fluency disorders (when compared to the population at large). An in-depth analysis of the available data indicates that some of these genetic syndromes show patterns of stuttering that may be indicative of only that syndrome (or similar syndromes) that can be differentially diagnosed from developmental stuttering. Among these patterns are the word-final nonfluencies noted in Prader-Willi syndrome; the presence of stuttering in the absence of secondary behaviors noted in Prader-Willi syndrome and; the presence of palilalia, word-final and word-medial nonfluencies, and word-medial and word-final nonfluencies in Tourette syndrome. Implications for future research are discussed in light of these findings. The reader will be able to: (1) describe the various different genetic syndromes that are associated with fluency disorders; (2) describe the types of nonfluencies that are associated with the major types of genetic syndromes that have fluency disorders; (3) describe the behaviors that may assist in differentially diagnosing different types of speech characteristics associated with various genetic syndromes.

Major COL4A5 gene rearrangements in patients with juvenile type Alport syndrome

DOE Office of Scientific and Technical Information (OSTI.GOV)

Renieri, A.; Galli, L.; Bruttini, M.

1995-11-20

Mutations in the COL4A5 gene, which encodes the {alpha}5 chain of type IV collagen, are found in a large fraction of patients with X-linked Alport syndrome. The recently discovered COL4A6, tightly linked and highly homologous to COL4A5, represents a second candidate gene for Alport syndrome. We analyzed 177 Italian Alport syndrome families by Southern blotting using cDNA probes from both COL4A5 and COL4A6. Nine unrelated families, accounting for 5% of the cases, were found to have a rearrangement in COL4A5. No rearrangements were found in COL4A6, with the exception of a deletion encompassing the 5{prime} ends of both COL4A5 andmore » COL4A6 genes in a patient with Alport syndrome and leiomyomatosis. COL4A5 rearrangements were all intragenic and included 1 duplication and 7 deletions. Polymerase chain reaction (PCR) analysis was carried out to characterize deletion and duplication boundaries and to predict the resulting protein abnormality. The two smallest deletions involved a single exon (exons 17 and 40, respectively), while the largest ones spanned exons 1 to 36. The clinical phenotype of patients in whom a rearrangement in COL4A5 was detected was severe, with progression to end-stage renal failure in juvenile age and hypoacusis occurring in most cases. These data have some important implications in the diagnosis of patients with Alport syndrome. 34 refs., 3 figs., 1 tab.« less

Bilateral striatal necrosis caused by ADAR mutations in two siblings with dystonia and freckles-like skin changes that should be differentiated from Leigh syndrome.

PubMed

Piekutowska-Abramczuk, Dorota; Mierzewska, Hanna; Bekiesińska-Figatowska, Monika; Ciara, Elżbieta; Trubicka, Joanna; Pronicki, Maciej; Rokicki, Dariusz; Rydzanicz, Małgorzata; Płoski, Rafał; Pronicka, Ewa

2016-01-01

Pathogenic molecular variants in the ADAR gene are a known cause of rare diseases, autosomal recessive Aicardi- Goutières syndrome type 6, severe infantile encephalopathy with intracranial calcifications and dominant dyschromatosis symmetrica hereditaria, demonstrated mainly in Asian adults. Recently, they have been also found in patients with nonsyndromic bilateral striatal necrosis accompanied by skin changes of the freckles-like type. Here, we present Polish siblings with acute onset and slowly progressive extrapyramidal syndrome with preserved intellectual abilities and basal ganglia changes found in MRI. A Leigh syndrome was considered for a long time as the most frequent cause of such lesions in children. Finally, two molecular variants in non-mitochondria-related ADAR gene c.3202+1G>A (p.?) and c.577C>G (p.Pro193Ala) were revealed by whole exome sequencing. We suggest that bilateral striatal necrosis should be always differentiated from LS to prevent the diagnosis delay. The striatal involvement accompanied by the presence of freckles-like skin changes should direct differential diagnosis to the ADAR gene mutations screening.

Large tubular colonic duplication in an adult treated with a small midline incision

PubMed Central

Yong, Yuen Geng; Jung, Kyung Uk; Cho, Yong Beom; Yun, Seong Hyeon; Kim, Hee Cheol; Lee, Woo Yong

2012-01-01

Tubular colonic duplication presenting in adults is rare and difficult to diagnose preoperatively. Only a few cases have been reported in the literature. We report a case of a 29-year-old lady presenting with a long history of chronic constipation, abdominal mass and repeated episodes of abdominal pain. The abdominal-pelvic computed tomography scan showed segmental bowel wall thickening thought to be small bowel, and dilatation with stasis of intraluminal content. The provisional diagnosis was small bowel duplication. She was scheduled for single port laparoscopic resection. However, a T-shaped tubular colonic duplication at sigmoid colon was found intraoperatively. Resection of the large T-shaped tubular colonic duplication containing multiple impacted large fecaloma and primary anastomosis was performed. There was no perioperative complication. We report, herein, the case of a T-shaped tubular colonic duplication at sigmoid colon in an adult who was successfully treated through mini-laparotomy assisted by single port laparoscopic surgery. PMID:22403754

Impact of gene gains, losses and duplication modes on the origin and diversification of vertebrates.

PubMed

Cañestro, Cristian; Albalat, Ricard; Irimia, Manuel; Garcia-Fernàndez, Jordi

2013-02-01

The study of the evolutionary origin of vertebrates has been linked to the study of genome duplications since Susumo Ohno suggested that the successful diversification of vertebrate innovations was facilitated by two rounds of whole-genome duplication (2R-WGD) in the stem vertebrate. Since then, studies on the functional evolution of many genes duplicated in the vertebrate lineage have provided the grounds to support experimentally this link. This article reviews cases of gene duplications derived either from the 2R-WGD or from local gene duplication events in vertebrates, analyzing their impact on the evolution of developmental innovations. We analyze how gene regulatory networks can be rewired by the activity of transposable elements after genome duplications, discuss how different mechanisms of duplication might affect the fate of duplicated genes, and how the loss of gene duplicates might influence the fate of surviving paralogs. We also discuss the evolutionary relationships between gene duplication and alternative splicing, in particular in the vertebrate lineage. Finally, we discuss the role that the 2R-WGD might have played in the evolution of vertebrate developmental gene networks, paying special attention to those related to vertebrate key features such as neural crest cells, placodes, and the complex tripartite brain. In this context, we argue that current evidences points that the 2R-WGD may not be linked to the origin of vertebrate innovations, but to their subsequent diversification in a broad variety of complex structures and functions that facilitated the successful transition from peaceful filter-feeding non-vertebrate ancestors to voracious vertebrate predators. Copyright © 2013 Elsevier Ltd. All rights reserved.

A unique phenotype in a patient with a rare triplication of the 22q11.2 region and new clinical insights of the 22q11.2 microduplication syndrome: a report of two cases.

PubMed

Vaz, Sara O; Pires, Renato; Pires, Luís M; Carreira, Isabel M; Anjos, Rui; Maciel, Paula; Mota-Vieira, Luisa

2015-08-22

The rearrangements of the 22q11.2 chromosomal region, most frequently deletions and duplications, have been known to be responsible for multiple congenital anomaly disorders. These rearrangements are implicated in syndromes that have some phenotypic resemblances. While the 22q11.2 deletion, also known as DiGeorge/Velocardiofacial syndrome, has common features that include cardiac abnormalities, thymic hypoplasia, characteristic face, hypocalcemia, cognitive delay, palatal defects, velopharyngeal insufficiency, and other malformations, the microduplication syndrome is largely undetected. This is mainly because phenotypic appearance is variable, milder, less characteristic and unpredictable. In this paper, we report the clinical evaluation and follow-up of two patients affected by 22q11.2 rearrangements, emphasizing new phenotypic features associated with duplication and triplication of this genomic region. Patient 1 is a 24 year-old female with 22q11.2 duplication who has a heart defect (ostium secundum atrial septal defect) and supernumerary teeth (hyperdontia), a feature previously not reported in patients with 22q11.2 microduplication syndrome. Her monozygotic twin sister, who died at the age of one month, had a different heart defect (truncus arteriousus). Patient 2 is a 20 year-old female with a 22q11.2 triplication who had a father with 22q11.2 duplication. In comparison to the first case reported in the literature, she has an aggravated phenotype characterized by heart defects (restrictive VSD and membranous subaortic stenosis), and presented other facial dysmorphisms and urogenital malformations (ovarian cyst). Additionally, she has a hemangioma planum on the right side of her face, a feature of Sturge-Weber syndrome. In this report, we described hyperdontia as a new feature of 22q11.2 microdeletion syndrome. Moreover, this syndrome was diagnosed in a patient who had a deceased monozygotic twin affected with a different heart defect, which corresponds to a