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Sample records for chromosomal deletion encompassing

  1. Distal Deletion of Chromosome 11q Encompassing Jacobsen Syndrome without Platelet Abnormality.

    Science.gov (United States)

    Sheth, Frenny J; Datar, Chaitanya; Andrieux, Joris; Pandit, Anand; Nayak, Darshana; Rahman, Mizanur; Sheth, Jayesh J

    2014-01-01

    Terminal 11q deletion, known as Jacobsen syndrome (JBS), is a rare genetic disorder associated with numerous dysmorphic features. We studied two cases with multiple congenital anomalies that were cytogenetically detected with deletions on 11q encompassing JBS region: 46,XX,der(11) del(11)(q24). Array comparative genomic hybridization (aCGH) analysis confirmed partial deletion of 11.8-11.9 Mb at 11q24.1q25 (case 1) and 13.9-14 Mb deletion at 11q23.3q25 together with 7.3-7.6 Mb duplication at 12q24.32q24.33 (case 2). Dysmorphism because of the partial duplication of 12q was not overtly decipherable over the Jacobsen phenotype except for a triangular facial profile. Aberrant chromosome 11 was inherited from phenotypically normal father, carrier of balanced translocation 46,XY,t(11;12)(q23.3; q24.32). In the present study, both cases had phenotypes that were milder than the ones described in literature despite having large deletion size. Most prominent features in classical JBS is thrombocytopenia, which was absent in both these cases. Therefore, detailed functional analysis of terminal 11q region is warranted to elucidate etiology of JBS and their clinical presentation. PMID:25288895

  2. Distal Deletion of Chromosome 11q Encompassing Jacobsen Syndrome without Platelet Abnormality

    OpenAIRE

    Sheth, Frenny J.; Datar, Chaitanya; Andrieux, Joris; Pandit, Anand; Nayak, Darshana; Rahman, Mizanur; Sheth, Jayesh J.

    2014-01-01

    Terminal 11q deletion, known as Jacobsen syndrome (JBS), is a rare genetic disorder associated with numerous dysmorphic features. We studied two cases with multiple congenital anomalies that were cytogenetically detected with deletions on 11q encompassing JBS region: 46,XX,der(11) del(11)(q24). Array comparative genomic hybridization (aCGH) analysis confirmed partial deletion of 11.8–11.9 Mb at 11q24.1q25 (case 1) and 13.9–14 Mb deletion at 11q23.3q25 together with 7.3–7.6 Mb duplication at 1...

  3. Construction of a yeast artificial chromosome contig encompassing the chromosome 14 Alzheimer`s disease locus

    Energy Technology Data Exchange (ETDEWEB)

    Sharma, V.; Bonnycastle, L.; Poorkai, P. [Univ. of Washington, Seattle, WA (United States)] [and others

    1994-09-01

    We have constructed a yeast artificial chromosome (YAC) contig of chromosome 14q24.3 which encompasses the chromosome 14 Alzheimer`s disease locus (AD3). Determined by linkage analysis of early-onset Alzheimer`s disease kindreds, this interval is bounded by the genetic markers D14S61-D14S63 and spans approximately 15 centimorgans. The contig consists of 29 markers and 74 YACs of which 57 are defined by one or more sequence tagged sites (STSs). The STS markers comprise 5 genes, 16 short tandem repeat polymorphisms and 8 cDNA clones. An additional number of genes, expressed sequence tags and cDNA fragments have been identified and localized to the contig by hybridization and sequence analysis of anonymous clones isolated by cDNA direct selection techniques. A minimal contig of about 15 YACs averaging 0.5-1.5 megabase in length will span this interval and is, at first approximation, in rough agreement with the genetic map. For two regions of the contig, our coverage has relied on L1/THE fingerprint and Alu-PCR hybridization data of YACs provided by CEPH/Genethon. We are currently developing sequence tagged sites from these to confirm the overlaps revealed by the fingerprint data. Among the genes which map to the contig are transforming growth factor beta 3, c-fos, and heat shock protein 2A (HSPA2). C-fos is not a candidate gene for AD3 based on the sequence analysis of affected and unaffected individuals. HSPA2 maps to the proximal edge of the contig and Calmodulin 1, a candidate gene from 4q24.3, maps outside of the region. The YAC contig is a framework physical map from which cosmid or P1 clone contigs can be constructed. As more genes and cDNAs are mapped, a highly resolved transcription map will emerge, a necessary step towards positionally cloning the AD3 gene.

  4. The chromosome 9q subtelomere deletion syndrome

    NARCIS (Netherlands)

    Stewart, D.R.; Kleefstra, T.

    2007-01-01

    The chromosome 9q subtelomere deletion syndrome (9qSTDS) is among the first and most common clinically recognizable syndromes to arise from widespread testing by fluorescent in situ hybridization (FISH) of subtelomere deletions. There are about 50 reported cases worldwide. Affected individuals invar

  5. Type 1 hyperlipoproteinemia in a child with large homozygous deletion encompassing GPIHBP1.

    Science.gov (United States)

    Patni, Nivedita; Brothers, Julie; Xing, Chao; Garg, Abhimanyu

    2016-01-01

    Type I hyperlipoproteinemia (T1HLP) usually presents with extreme hypertriglyceridemia, recurrent episodes of acute pancreatitis, lipemia retinalis, and cutaneous eruptive xanthomas. We report a unique 10-year-old male of Indian origin who presented in neonatal period with transient obstructive jaundice and xanthomas in the pancreas and kidneys. Serum triglycerides stabilized with extremely low-fat diet although he subsequently developed pancreatic atrophy. Extreme hypertriglyceridemia failed to respond to treatment with fenofibrate, fish oil, and orlistat. Whole-exome sequencing of the parents and patient was performed. Copy number variation analysis revealed a large deletion in chromosome 8 containing the entire GPIHBP1, which was confirmed by Sanger sequencing to be 54,623 bp deletion. Review of the literature revealed a slightly higher maximum triglyceride levels in those with homozygous null vs missense mutations suggesting severe disease in those with nonfunctional vs dysfunctional GPIHBP1 protein. Visceral xanthomas and pancreatic atrophy can be part of the spectrum of clinical features in patients with T1HLP. We highlight the need to perform copy number variations analysis of whole-exome sequencing data for finding disease-causing variants. There is also an urgent need to develop novel targeted therapies for patients with T1HLP. PMID:27578137

  6. UBE2A deficiency syndrome: a report of two unrelated cases with large Xq24 deletions encompassing UBE2A gene.

    Science.gov (United States)

    Thunstrom, Sofia; Sodermark, Liv; Ivarsson, Liz; Samuelsson, Lena; Stefanova, Margarita

    2015-01-01

    Intragenic mutations of the UBE2A gene, as well as larger deletions of Xq24 encompassing UBE2A have in recent years been associated with a syndromic form of X-linked intellectual disability called UBE2A deficiency syndrome or X-linked intellectual disability type Nascimento (OMIM#300860). Common clinical features in these patients include moderate to severe intellectual disability (ID), heart defects, dysmorphic features such as high forehead, synophrys, prominent supraorbital ridges, almond-shaped and deep-set eyes, wide mouth, myxedematous appearance, hirsutism, onychodystrophy, and genital anomalies. This study investigates clinical and molecular data of two unrelated, affected males with chromosome Xq24 deletions encompassing UBE2A. Both have been followed from birth until two years of age. A review of the previously published patients with deletions encompassing UBE2A is provided. Besides the common features, the two boys show anomalies not previously described, such as retinal coloboma, esophageal atresia with esophageal fistula, long fingers, camptodactyly, clinodactyly, and long broad toes. Analyses of the phenotype-genotype correlations suggest considerable prevalence of heart defects in the group of patients with larger deletions of Xq24 in comparison to the patients having intragenic UBE2A mutations. However, further studies are needed in order to establish statistically reliable phenotype-genotype correlations of this syndrome. PMID:25287747

  7. Small 6q16.1 Deletions Encompassing POU3F2 Cause Susceptibility to Obesity and Variable Developmental Delay with Intellectual Disability.

    Science.gov (United States)

    Kasher, Paul R; Schertz, Katherine E; Thomas, Megan; Jackson, Adam; Annunziata, Silvia; Ballesta-Martinez, María J; Campeau, Philippe M; Clayton, Peter E; Eaton, Jennifer L; Granata, Tiziana; Guillén-Navarro, Encarna; Hernando, Cristina; Laverriere, Caroline E; Liedén, Agne; Villa-Marcos, Olaya; McEntagart, Meriel; Nordgren, Ann; Pantaleoni, Chiara; Pebrel-Richard, Céline; Sarret, Catherine; Sciacca, Francesca L; Wright, Ronnie; Kerr, Bronwyn; Glasgow, Eric; Banka, Siddharth

    2016-02-01

    Genetic studies of intellectual disability and identification of monogenic causes of obesity in humans have made immense contribution toward the understanding of the brain and control of body mass. The leptin > melanocortin > SIM1 pathway is dysregulated in multiple monogenic human obesity syndromes but its downstream targets are still unknown. In ten individuals from six families, with overlapping 6q16.1 deletions, we describe a disorder of variable developmental delay, intellectual disability, and susceptibility to obesity and hyperphagia. The 6q16.1 deletions segregated with the phenotype in multiplex families and were shown to be de novo in four families, and there was dramatic phenotypic overlap among affected individuals who were independently ascertained without bias from clinical features. Analysis of the deletions revealed a ∼350 kb critical region on chromosome 6q16.1 that encompasses a gene for proneuronal transcription factor POU3F2, which is important for hypothalamic development and function. Using morpholino and mutant zebrafish models, we show that POU3F2 lies downstream of SIM1 and controls oxytocin expression in the hypothalamic neuroendocrine preoptic area. We show that this finding is consistent with the expression patterns of POU3F2 and related genes in the human brain. Our work helps to further delineate the neuro-endocrine control of energy balance/body mass and demonstrates that this molecular pathway is conserved across multiple species. PMID:26833329

  8. Chromosomal instability in Streptomyces avermitilis: major deletion in the central region and stable circularized chromosome

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    Wen Ying

    2010-07-01

    Full Text Available Abstract Background The chromosome of Streptomyces has been shown to be unstable, frequently undergoing gross chromosomal rearrangements. However, the mechanisms underlying this phenomenon remain unclear, with previous studies focused on two chromosomal ends as targets for rearrangements. Here we investigated chromosomal instability of Streptomyces avermitilis, an important producer of avermectins, and characterized four gross chromosomal rearrangement events, including a major deletion in the central region. The present findings provide a valuable contribution to the mechanistic study of genetic instability in Streptomyces. Results Thirty randomly-selected "bald" mutants derived from the wild-type strain all contained gross chromosomal rearrangements of various types. One of the bald mutants, SA1-8, had the same linear chromosomal structure as the high avermectin-producing mutant 76-9. Chromosomes of both strains displayed at least three independent chromosomal rearrangements, including chromosomal arm replacement to form new 88-kb terminal inverted repeats (TIRs, and two major deletions. One of the deletions eliminated the 36-kb central region of the chromosome, but surprisingly did not affect viability of the cells. The other deletion (74-kb was internal to the right chromosomal arm. The chromosome of another bald mutant, SA1-6, was circularized with deletions at both ends. No obvious homology was found in all fusion sequences. Generational stability analysis showed that the chromosomal structure of SA1-8 and SA1-6 was stable. Conclusions Various chromosomal rearrangements, including chromosomal arm replacement, interstitial deletions and chromosomal circularization, occurred in S. avermitilis by non-homologous recombination. The finding of an inner deletion involving in the central region of S. avermitilis chromosome suggests that the entire Streptomyces chromosome may be the target for rearrangements, which are not limited, as previously

  9. Linguistic and Psychomotor Development in Children with Chromosome 14 Deletions

    Science.gov (United States)

    Zampini, Laura; D'Odorico, Laura; Zanchi, Paola; Zollino, Marcella; Neri, Giovanni

    2012-01-01

    The present study focussed on a specific type of rare genetic condition: chromosome 14 deletions. Children with this genetic condition often show developmental delays and brain and neurological problems, although the type and severity of symptoms varies depending on the size and location of the deleted genetic material. The specific aim of the…

  10. A deletion map of the WAGR region on chromosome 11.

    OpenAIRE

    Gessler, M; Thomas, G H; Couillin, P; Junien, C; McGillivray, B C; Hayden, M; Jaschek, G.; Bruns, G. A.

    1989-01-01

    The WAGR (Wilms tumor, aniridia, genitourinary anomalies, and mental retardation) region has been assigned to chromosome 11p13 on the basis of overlapping constitutional deletions found in affected individuals. We have utilized 31 DNA probes which map to the WAGR deletion region, together with six reference loci and 13 WAGR-related deletions, to subdivide this area into 16 intervals. Specific intervals have been correlated with phenotypic features, leading to the identification of individual ...

  11. A 3.7 Mb Deletion Encompassing ZEB2 Causes a Novel Polled and Multisystemic Syndrome in the Progeny of a Somatic Mosaic Bull

    Science.gov (United States)

    Capitan, Aurélien; Allais-Bonnet, Aurélie; Pinton, Alain; Marquant-Le Guienne, Brigitte; Le Bourhis, Daniel; Grohs, Cécile; Bouet, Stéphan; Clément, Laëtitia; Salas-Cortes, Laura; Venot, Eric; Chaffaux, Stéphane; Weiss, Bernard; Delpeuch, Arnaud; Noé, Guy; Rossignol, Marie-Noëlle; Barbey, Sarah; Dozias, Dominique; Cobo, Emilie; Barasc, Harmonie; Auguste, Aurélie; Pannetier, Maëlle; Deloche, Marie-Christine; Lhuilier, Emeline; Bouchez, Olivier; Esquerré, Diane; Salin, Gérald; Klopp, Christophe; Donnadieu, Cécile; Chantry-Darmon, Céline; Hayes, Hélène; Gallard, Yves; Ponsart, Claire; Boichard, Didier; Pailhoux, Eric

    2012-01-01

    Polled and Multisystemic Syndrome (PMS) is a novel developmental disorder occurring in the progeny of a single bull. Its clinical spectrum includes polledness (complete agenesis of horns), facial dysmorphism, growth delay, chronic diarrhea, premature ovarian failure, and variable neurological and cardiac anomalies. PMS is also characterized by a deviation of the sex-ratio, suggesting male lethality during pregnancy. Using Mendelian error mapping and whole-genome sequencing, we identified a 3.7 Mb deletion on the paternal bovine chromosome 2 encompassing ARHGAP15, GTDC1 and ZEB2 genes. We then produced control and affected 90-day old fetuses to characterize this syndrome by histological and expression analyses. Compared to wild type individuals, affected animals showed a decreased expression of the three deleted genes. Based on a comparison with human Mowat-Wilson syndrome, we suggest that deletion of ZEB2, is responsible for most of the effects of the mutation. Finally sperm-FISH, embryo genotyping and analysis of reproduction records confirmed somatic mosaicism in the founder bull and male-specific lethality during the first third of gestation. In conclusion, we identified a novel locus involved in bovid horn ontogenesis and suggest that epithelial-to-mesenchymal transition plays a critical role in horn bud differentiation. We also provide new insights into the pathogenicity of ZEB2 loss of heterozygosity in bovine and humans and describe the first case of male-specific lethality associated with an autosomal locus in a non-murine mammalian species. This result sets PMS as a unique model to study sex-specific gene expression/regulation. PMID:23152852

  12. A YAC contig encompassing the recessive Stargardt disease gene (STGD) on chromosome 1p

    Energy Technology Data Exchange (ETDEWEB)

    Anderson, K.L.; Lewis, R.A.; Chinault, A.C. [Baylor College of Medicine, Houston, TX (United States)] [and others

    1995-12-01

    Stargardt disease (STGD) and fundus flavimaculatus are infrequent autosomal recessive conditions characterized by a juvenile macular dystrophy and variable degrees of peripheral retinal changes. Linkage analysis performed in 47 STGD/fundus flavimaculatus families demonstrated significant linkage to 13 polymorphic DNA markers on chromosome 1p. The maximum combined two-point lod score was 32.7 (maximum recombination fraction [{theta}{sub max}] = .006) with the polymorphic marker D1S188. Our data demonstrate that STGD and fundus flavimaculatus are the same disorder clinically and genetically and provide further evidence for genetic homogeneity of this phenotype. Analysis of recombination on disease chromosomes placed the STGD gene within a 4-cM interval between markers D1S435 and D1S236. A physical map was constructed of a YAC contig flanking STGD, from markers D1S500 to D1S495, and includes the critical interval delineated by historical recombinants. This contig spans {approximately}31 cM, with one gap (3-5 cM) that is outside the 4-cM critical region. Localization of STGD to a single YAC contig will facilitate its positional cloning. 75 refs., 3 figs., 21 tabs.

  13. A locus on chromosome 20 encompassing genes that are highly expressed in the epididymis

    Institute of Scientific and Technical Information of China (English)

    (A)ke Lundwall

    2007-01-01

    During liquefaction of the ejaculate, the semen coagulum proteins semenogelin Ⅰ (SEMG1) and semenogelin Ⅱ (SEMG2) are degraded to low molecular mass fragments by kallikrein-related peptidase 3 (KLK3), also known as prostate-specific antigen. Semenogelin molecules initiate their own destruction by chelating Zn2+ that normally would completely inhibit the proteolytic activity of KLK3. In a similar way, semenogelins might regulate the activity of kallikrein-related peptidases in the epididymis, something that might be of importance for the maturation of spermatozoa or generation of anti-bacterial peptides. Studies on the evolution of semen coagulum proteins have revealed that most of them carry an exon that displays a rapid and unusual evolution. As a consequence, homologous proteins in rodents and primates show almost no conservation in primary structure. Further studies on their evolution suggest that the progenitor of the semen coagulum proteins probably was a protease inhibitor that might have displayed antimicrobial activity. The semenogelin locus on chromosome 20 contains at least 17 homologous genes encoding probable protease inhibitors with homology to semen coagulum proteins. All of these are highly expressed in the epididymis where they, similar to the semenogelins, could affect the maturation of spermatozoa or display antibacterial properties.

  14. Chromosomal deletion unmasking a recessive disease: 22q13 deletion syndrome and metachromatic leukodystrophy

    DEFF Research Database (Denmark)

    Bisgaard, A-M; Kirchhoff, M; Nielsen, J E; Kibaek, M; Lund, A; Schwartz, M; Christensen, E

    2008-01-01

    A deletion on one chromosome and a mutant allele on the other may cause an autosomal recessive disease. We report on two patients with mental retardation, dysmorphic features and low catalytic activity of arylsulfatase A. One patient had a pathogenic mutation in the arylsulfatase A gene (ARSA) and...

  15. Deletion of exons 3-9 encompassing a mutational hot spot in the DMD gene presents an asymptomatic phenotype, indicating a target region for multiexon skipping therapy.

    Science.gov (United States)

    Nakamura, Akinori; Fueki, Noboru; Shiba, Naoko; Motoki, Hirohiko; Miyazaki, Daigo; Nishizawa, Hitomi; Echigoya, Yusuke; Yokota, Toshifumi; Aoki, Yoshitsugu; Takeda, Shin'ichi

    2016-07-01

    Few cases of dystrophinopathy show an asymptomatic phenotype with mutations in the 5' (exons 3-7) hot spot in the Duchenne muscular dystrophy (DMD) gene. Our patient showed increased serum creatine kinase levels at 12 years of age. A muscle biopsy at 15 years of age led to a diagnosis of Becker muscular dystrophy. The patient showed a slight decrease in cardiac function at the age of 21 years and was administered a β-blocker, but there was no muscle involvement even at the age of 27 years. A deletion of exons 3-9 encompassing a mutational hot spot in the DMD gene was detected, and dystrophin protein expression was ∼15% that of control level. We propose that in-frame deletion of exons 3-9 may produce a functional protein, and that multiexon skipping therapy targeting these exons may be feasible for severe dystrophic patients with a mutation in the 5' hot spot of the DMD gene. PMID:27009627

  16. Detailed molecular and clinical investigation of a child with a partial deletion of chromosome 11 (Jacobsen syndrome

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    Peitsidis Panagiotis

    2009-12-01

    Full Text Available Abstract Background Jacobsen syndrome (JBS is a rare chromosomal disorder leading to multiple physical and mental impairment. This syndrome is caused by a partial deletion of chromosome 11, especially subband 11q24.1 has been proven to be involved. Clinical cases may easily escape diagnosis, however pancytopenia or thrombocytopenia may be indicative for JBS. Results We report a 7.5 years old boy presenting with speech development delay, hearing impairment and abnormal platelet function. High resolution SNP oligonucleotide microarray analysis revealed a terminal deletion of 11.4 Mb in size, in the area 11q24.1-11qter. This specific deletion encompasses around 170 genes. Other molecular techniques such as fluorescence in situ hybridization and multiplex ligation-dependent probe amplification were used to confirm the array-result. Discussion Our results suggest that the identification and detailed analysis of similar patients with abnormal platelet function and otherwise mild clinical features will contribute to identification of more patients with 11q deletion and JBS.

  17. Upper limb malformations in chromosome 22q11 deletions

    Energy Technology Data Exchange (ETDEWEB)

    Shalev, S.A.; Dar, H.; Barel, H.; Borochowitz, Z. [Bnai Zion Medical Center, Haifa (Israel)

    1996-03-29

    We read with interest the report of Cormier-Daire et al. in a recent issue of the journal, describing upper limb malformations in DiGeorge syndrome. We observed a family with this group of rare clinical expression of chromosome 22q11 deletions. The proposita was examined in our clinic when she was 4 years old. She was mildly mentally retarded. Clinical evaluation showed normal growth, long thin nose with squared tip, nasal speech, and abundant scalp hair and no cardiac anomalies. The girl was accompanied by her mother. Facial similarities were noted between the two. The mother reported to be treated with oral calcium due to hypoparathyroidism, diagnosed several years ago. Clinical evaluation showed wide flat face, short stature, mild mental retardation, slight hypertelorism, peculiar nose similar to her daughter`s, and nasal speech. No cardiac anomalies were found. Recently, a brother was born. Clinical examination documented large ventriculo-septal defect, retrognathia, narrow palpebral fissures, and long thin nose with squared tip. 1 ref.

  18. A Microdeletion of Chromosome 9q33.3 Encompasses the Entire LMX1B Gene in a Chinese Family with Nail Patella Syndrome

    Science.gov (United States)

    Jiang, Shujuan; Zhang, Jiubin; Huang, Dan; Zhang, Yuanyuan; Liu, Xiaoliang; Wang, Yinzhao; He, Rong; Zhao, Yanyan

    2014-01-01

    Nail patella syndrome (NPS) is an autosomal dominant disorder characterized by nail malformations, patellar apoplasia, or patellar hypoplasia. Mutations within the LMX1B gene are found in 85% of families with NPS; thus, this gene has been characterized as the causative gene of NPS. In this study, we identified a heterozygous microdeletion of the entire LMX1B gene using multiplex ligation-dependent probe amplification (MLPA) in a Chinese family with NPS. The determination of the deletion breakpoints by Illumina genome-wide DNA analysis beadchip showed that the deletion was located in chromosome 9q33.3 and spanned about 0.66 Mb in size. This heterozygous deletion provides strong evidence for haploinsufficiency as the pathogenic mechanism of NPS. PMID:25380522

  19. A Microdeletion of Chromosome 9q33.3 Encompasses the Entire LMX1B Gene in a Chinese Family with Nail Patella Syndrome

    Directory of Open Access Journals (Sweden)

    Shujuan Jiang

    2014-11-01

    Full Text Available Nail patella syndrome (NPS is an autosomal dominant disorder characterized by nail malformations, patellar apoplasia, or patellar hypoplasia. Mutations within the LMX1B gene are found in 85% of families with NPS; thus, this gene has been characterized as the causative gene of NPS. In this study, we identified a heterozygous microdeletion of the entire LMX1B gene using multiplex ligation-dependent probe amplification (MLPA in a Chinese family with NPS. The determination of the deletion breakpoints by Illumina genome-wide DNA analysis beadchip showed that the deletion was located in chromosome 9q33.3 and spanned about 0.66 Mb in size. This heterozygous deletion provides strong evidence for haploinsufficiency as the pathogenic mechanism of NPS.

  20. Interstitial deletion of the short arm of chromosome 4.

    OpenAIRE

    Ray, M; Evans, J.; Rockman-Greenberg, C; Wickstrom, D

    1984-01-01

    A 17 year old girl investigated for mental retardation and minor anomalies was found to have an interstitial deletion of 4p. Her clinical and cytogenetic findings are compared with previous reported case of interstitial 4p deletion and with terminal 4p--deletions (Wolf-Hirschhorn syndrome).

  1. Marfan syndrome with a complex chromosomal rearrangement including deletion of the FBN1 gene

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    Colovati Mileny ES

    2012-01-01

    Full Text Available Abstract Background The majority of Marfan syndrome (MFS cases is caused by mutations in the fibrillin-1 gene (FBN1, mapped to chromosome 15q21.1. Only few reports on deletions including the whole FBN1 gene, detected by molecular cytogenetic techniques, were found in literature. Results We report here on a female patient with clinical symptoms of the MFS spectrum plus craniostenosis, hypothyroidism and intellectual deficiency who presents a 1.9 Mb deletion, including the FBN1 gene and a complex rearrangement with eight breakpoints involving chromosomes 6, 12 and 15. Discussion This is the first report of MFS with a complex chromosome rearrangement involving a deletion of FBN1 and contiguous genes. In addition to the typical clinical findings of the Marfan syndrome due to FBN1 gene haploinsufficiency, the patient presents features which may be due to the other gene deletions and possibly to the complex chromosome rearrangement.

  2. Deletion of chromosome 21 in a girl with congenital hypothyroidism and mild mental retardation

    Energy Technology Data Exchange (ETDEWEB)

    Ahlbom, B.E.; Anneren, G. [Univ. Hospital, Uppsala (Sweden); Sidenvall, R. [Central Hospital of Hudiksvall (Sweden)

    1996-08-23

    We report on a girl with a large interstitial deletion of the long arm of chromosome 21 and with mild mental retardation, congenital hypothyroidism, and hyperopia. The deletion [del(21)(q11.1-q22.1)] extends molecularly from marker D21S215 to D21S213. The distal breakpoint is not clearly defined but is situated between markers D21S213 and IFNAR. This patient has the largest deletion of chromosome 21 known without having severe mental retardation or malformations. The deletion does not involve the {open_quotes}Down syndrome chromosome{close_quotes} region, the region of chromosome 21 which in trisomy causes most of the manifestations of Down syndrome. Apparently, the proximal part of the long arm of chromosome 21 does not include genes that are responsible for severe clinical effects in the event of either deletion or duplication, since several reported patients with either trisomy or deletion of this region have mild phenotypic abnormalities. Congenital hypothyroidism is much more common in Down syndrome than in the average population. Thus, the congenital hypothyroidism of the present patient might indicate that there is one or several genes on the proximal part of chromosome 21, which might be of importance for the thyroid function. 24 refs., 4 figs., 2 tabs.

  3. Microcephaly/lymphedema and terminal deletion of the long arm of chromosome 13

    Energy Technology Data Exchange (ETDEWEB)

    Fryns, J.P. [Univ. of Leuven (Belgium)

    1995-07-03

    Recently, we examined a 2-year-old boy with the association of microcephaly and significant pedal edema that extended to the distal parts of the legs. Prometaphase chromosome studies showed a small terminal deletion in the long arm of chromosome 13 of band 13q34, karyotype 46,XY,del(13)(q34{yields}qter). The present finding of a small terminal 13q34 deletion in this young boy with microcephaly/lymphedema is a first indication that the lymphedema/microcephaly association can be due to a small terminal 13q deletion. 2 refs.

  4. Molecular and cellular pathways associated with chromosome 1p deletions during colon carcinogenesis

    OpenAIRE

    Payne CM; Crowley-Skillicorn C; Bernstein C; Holubec H; Bernstein H

    2011-01-01

    Claire M Payne, Cheray Crowley-Skillicorn, Carol Bernstein, Hana Holubec, Harris BernsteinDepartment of Cell Biology and Anatomy, College of Medicine, University of Arizona Tucson, AZ, USAAbstract: Chromosomal instability is a major pathway of sporadic colon carcinogenesis. Chromosome arm 1p appears to be one of the “hot spots” in the non-neoplastic mucosa that, when deleted, is associated with the initiation of carcinogenesis. Chromosome arm 1p contains genes associated w...

  5. Chromosome 16p11.2 deletions: another piece in the genetic puzzle of childhood obesity

    Directory of Open Access Journals (Sweden)

    del Giudice Emanuele

    2010-06-01

    Full Text Available Abstract Ipercaloric diet and reduced physical activity have driven the rise in the prevalence of childhood obesity over a relatively short time interval. Family and twin studies have led to the conclusion that the strong predicitve value of parental body mass index (BMI mainly stems from genetic rather than environmental factors. Whereas the common polygenic obesity arises when an individual genetic make-up is susceptible to an environment that promotes energy consumption over energy expenditure, monogenic obesity, on the contrary, is the obesity associated with a single gene mutation, which is sufficient by itself to cause weight gain in a food abundant context. Genes involved in the leptin-melanocortin pathway are often mutated in these cases. The cumulative prevalence of monogenic obesity among children with severe obesity is about 5%. Recently, deletions in the region p11.2 of the chromosome 16 encompassing the gene SH2B1, which is involved in the leptin and insulin signaling, have been reported in about 0.5% of children with severe early-onset obesity. These patients show extreme hyperphagia, severe insulin resistance and, in some cases, mild developmental delay.

  6. DNA-based detection of chromosome deletion and amplification: diagnostic and mechanistic significance

    International Nuclear Information System (INIS)

    This paper describes a few of the many possible examples in which application of a molecular cytogenetic approach can ultimately lead to a new, important understanding about the statics and dynamics of human chromosome structure. In the case of retinoblastoma, cytological observations of deletions and linkage analysis have positioned the retinoblastoma locus to bank 13q14. This locus is grossly deleted in some spontaneous tumors. It is still necessary to locate more precisely and characterize the nature of the retinoblastoma locus, as well as the basis for the heterogeneity in deletions removing one copy of this locus. One is left with the possibility that those deletions that may be observed cytologically reflect but the tip of the iceberg of deletions; detection of others may require molecular probes. A related question is the nature of the DNA sequences at the deletion boundaries and the role they play in promoting these deletions

  7. The Role of Dicentric Chromosome Formation and Secondary Centromere Deletion in the Evolution of Myeloid Malignancy

    Science.gov (United States)

    MacKinnon, Ruth N.; Campbell, Lynda J.

    2011-01-01

    Dicentric chromosomes have been identified as instigators of the genome instability associated with cancer, but this instability is often resolved by one of a number of different secondary events. These include centromere inactivation, inversion, and intercentromeric deletion. Deletion or excision of one of the centromeres may be a significant occurrence in myeloid malignancy and other malignancies but has not previously been widely recognized, and our reports are the first describing centromere deletion in cancer cells. We review what is known about dicentric chromosomes and the mechanisms by which they can undergo stabilization in both constitutional and cancer genomes. The failure to identify centromere deletion in cancer cells until recently can be partly explained by the standard approaches to routine diagnostic cancer genome analysis, which do not identify centromeres in the context of chromosome organization. This hitherto hidden group of primary dicentric, secondary monocentric chromosomes, together with other unrecognized dicentric chromosomes, points to a greater role for dicentric chromosomes in cancer initiation and progression than is generally acknowledged. We present a model that predicts and explains a significant role for dicentric chromosomes in the formation of unbalanced translocations in malignancy. PMID:22567363

  8. Cornelia de Lange syndrome caused by heterozygous deletions of chromosome 8q24: comments on the article by Pereza et al. [2012].

    Science.gov (United States)

    Pereza, Nina; Severinski, Srećko; Ostojić, Saša; Volk, Marija; Maver, Aleš; Dekanić, Kristina Baraba; Kapović, Miljenko; Peterlin, Borut

    2015-06-01

    In the March issue of the Journal in 2012, we reported on a girl with Langer-Giedion syndrome (LGS) phenotype and a 7.5 Mb interstitial deletion at 8q23.3q24.13, encompassing the EXT1, but not the TRPS1 gene. Recent discoveries have shown that heterozygous intragenic mutations or contiguous gene deletions including the RAD21 gene, which is located downstream of the TRPS1 gene, are the cause of Cornelia de Lange syndrome-4. Considering that the interstitial deletion in our patient included the RAD21 and 30 other RefSeq genes, we would like to suggest a revision of the diagnosis reported in our previous paper and compare our patient to other reported patients with Cornelia de Lange syndrome-4 caused by heterozygous deletions of chromosome 8q24. © 2015 Wiley Periodicals, Inc. PMID:25899858

  9. Partial 2p deletion in a girl with a complex chromosome rearrangement involving chromosomes 2, 6, 11, and 21.

    OpenAIRE

    Young, R S; M. A. Medrano; Hansen, K L

    1985-01-01

    We describe the clinical and cytogenetic findings of a 9 1/2 month old girl with a complex chromosome rearrangement resulting in a probable deletion of band 2p14. She does not resemble other reported cases of del(2p).

  10. Deletion of chromosome 2q24-q31 causes characteristic digital anomalies: Case report and review

    Energy Technology Data Exchange (ETDEWEB)

    Boles, R.G. [Univ. of Southern California School of Medicine, Los Angeles, CA (United States); Pober, B.R.; Gibson, L.H. [Yale Univ. School of Medicine, New Haven, CT (United States)] [and others

    1995-01-16

    We describe a newborn boy with multiple anomalies, including bilateral split foot and an interstitial deletion of chromosome 2 (q24.2-q31.1). Four additional cases in 2 families involving similar deletions have been reported. Bilateral digital anomalies of hands and feet were seen in all 5 cases, including a wide cleft between the first and second toes, wide halluces, brachsyndactyly of the toes, and camptodactyly of the fingers. Other common manifestations have included postnatal growth and mental retardation, microcephaly, down-slanting palpebral fissures, micrognathia, and apparently low-set ears. Bilateral digital anomalies were reported in 22 of 24 cases with deletions including at least part of region 2q24-q31. Digital anomalies were not prevalent in 18 patients with deletions of chromosome 2q not overlapping 2q24-q31. 2q31.1 appears to be the common deleted segment in all cases with significant digital anomalies, which implies the existence of one or more genes involved in distal limb morphogenesis in this region. HOXD13 and EVX2, located in the proximity of 2q31, were not deleted in our patient by Southern analysis. Bilateral digital malformations of the hands and feet associated with other anomalies should be evaluated by chromosome analysis focused at the 2q24-q31 region. 42 refs., 5 figs., 2 tabs.

  11. Fine-scale genetic characterization of Plasmodium falciparum chromosome 7 encompassing the antigenic var and the drug-resistant pfcrt genes

    Indian Academy of Sciences (India)

    Ruchi Bajaj; Sujata Mohanty; A. P. Dash; Aparup Das

    2008-04-01

    The fact that malaria is still an uncontrolled disease is reflected by the genetic organization of the parasite genome. Efforts to curb malaria should begin with proper understanding of the mechanism by which the parasites evade human immune system and evolve resistance to different antimalarial drugs. We have initiated such a study and presented herewith the results from the in silico understanding of a seventh chromosomal region of the malarial parasite Plasmodium falciparum encompassing the antigenic var genes (coding pfemp1) and the drug-resistant gene pfcrt located at a specified region of the chromosome 7. We found 60 genes of various functions and lengths, majority (61.67%) of them were performing known functions. Almost all the genes have orthologs in other four species of Plasmodium, of which P. chabaudi seems to be the closest to P. falciparum. However, only two genes were found to be paralogous. Interestingly, the drug-resistant gene, pfcrt was found to be surrounded by seven genes coding for several CG proteins out of which six were reported to be responsible for providing drug resistance to P. vivax. The intergenic regions, in this specified region were generally large in size, majority (73%) of them were of more than 500 nucleotide bp length. We also designed primers for amplification of 21 noncoding DNA fragments in the whole region for estimating genetic diversity and inferring the evolutionary history of this region of P. falciparum genome.

  12. Molecular and cellular pathways associated with chromosome 1p deletions during colon carcinogenesis

    Directory of Open Access Journals (Sweden)

    Payne CM

    2011-05-01

    Full Text Available Claire M Payne, Cheray Crowley-Skillicorn, Carol Bernstein, Hana Holubec, Harris BernsteinDepartment of Cell Biology and Anatomy, College of Medicine, University of Arizona Tucson, AZ, USAAbstract: Chromosomal instability is a major pathway of sporadic colon carcinogenesis. Chromosome arm 1p appears to be one of the “hot spots” in the non-neoplastic mucosa that, when deleted, is associated with the initiation of carcinogenesis. Chromosome arm 1p contains genes associated with DNA repair, spindle checkpoint function, apoptosis, multiple microRNAs, the Wnt signaling pathway, tumor suppression, antioxidant activities, and defense against environmental toxins. Loss of 1p is dangerous since it would likely contribute to genomic instability leading to tumorigenesis. The 1p deletion-associated colon carcinogenesis pathways are reviewed at the molecular and cellular levels. Sporadic colon cancer is strongly linked to a high-fat/low-vegetable/low-micronutrient, Western-style diet. We also consider how selected dietary-related compounds (eg, excess hydrophobic bile acids, and low levels of folic acid, niacin, plant-derived antioxidants, and other modulatory compounds might affect processes leading to chromosomal deletions, and to the molecular and cellular pathways specifically altered by chromosome 1p loss.Keywords: chromosome 1p, colon carcinogenesis, molecular pathways, cellular pathways

  13. Genotype/phenotype correlation in women with nonmosaic X chromosome deletions and Turner syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Zinn, A.R. [Univ. of Texas Southwestern Medical School, Dallas, TX (United States)

    1994-09-01

    Turner syndrome is a complex human developmental disorder associated with the absence of the second sex chromosome (monosomy X). Cardinal features of the Turner phenotype include high intrauterine lethality, growth retardation, gonadal failure, and the variable presence of specific somatic abnormalities such as webbed neck, lymphedema, and skeletal abnormalities. Recent observations support the hypothesis that the phenotype associated with monosomy X results from haploid dosage of genes common the X and Y chromosomes that escape X-inactivation ({open_quotes}Turner genes{close_quotes}). Apart from a locus causing short stature that maps to the pseudoautosomal region on the distal short arm, the location of X-linked Turner genes is not known. Karyotype/phenotype correlations in women with partial X deletions have been inconsistent. However, previous studies have focused on sporadic sex chromosome aberrations and may have been confounded by occult mosaicism. In addition, mapping of deletions was limited by the resolution of cytogenetic techniques. I am reexamining genotype/phenotype correlations in partial X monosomy, focusing on a subset of cases in which mosaicism is highly unlikely (e.g., unbalanced X-autosome translocations, familial X deletions), and using molecular techniques to map deletions. I have collected eight cases of nonmosaic X deletions in women with varied manifestations of Turner syndrome. Cytogenetic data suggests that genes responsible for Turner anatomic abnormalities may lie within a critical region of the very proximal portion of the short arm (Xp11). Molecular characterization of the deletions is in progress. Methods include (1) fluorescence in situ hybridization of metaphase spreads from patient-derived cell lines, using cosmid probes that map to known locations on Xp, and (2) sequence tagged site (STS) content mapping of somatic cell hybrids retaining the deleted X chromosomes derived from these cell lines.

  14. Domain Specific Attentional Impairments in Children with Chromosome 22Q11.2 Deletion Syndrome

    Science.gov (United States)

    Bish, Joel P.; Chiodo, Renee; Mattei, Victoria; Simon, Tony J.

    2007-01-01

    One of the defining cognitive characteristics of the chromosome 22q deletion syndrome (DS22q11.2) is visuospatial processing impairments. The purpose of this study was to investigate and extend the specific attentional profile of children with this disorder using both an object-based attention task and an inhibition of return task. A group of…

  15. Chromosome 6q deletion: Report of a new case and review of the literature

    Directory of Open Access Journals (Sweden)

    Boy Raquel

    1998-01-01

    Full Text Available The authors report an additional case of partial monosomy of the long arm of chromosome 6 [46,XY,del (6(q22 ® qter]. Our patient has a large segment beyond 6q25 deleted, then severe psychomotor retardation is expected to occur.

  16. Deletion of short arm of chromosome 18, Del(18p syndrome

    Directory of Open Access Journals (Sweden)

    Prashant Babaji

    2014-01-01

    Full Text Available Deletion of the short arm of chromosome 18 is a rare syndrome clinically presenting with variable mental retardation, growth retardation, low height, pectus excavatum, craniofacial malformations including long ear, ptosis, microcephaly and short neck. This case report presents with characteristic features along with rare feature of single nostril.

  17. Chromosomal deletion, promoter hypermethylation and downregulation of FYN in prostate cancer

    DEFF Research Database (Denmark)

    Sørensen, Karina Dalsgaard; Borre, Michael; Ørntoft, Torben Falck;

    2008-01-01

    G island, consistent with gene silencing, was detected in 2 of 18 tumors (11%). No methylation was found in BPH-1 cells or nonmalignant prostate tissue samples (0 of 7). These results indicate that FYN is downregulated in prostate cancer by both chromosomal deletion and promoter hypermethylation, and...

  18. Familial transmission of a deletion of chromosome 21 derived from a translocation between chromosome 21 and an inverted chromosome 22.

    Science.gov (United States)

    Aviv, H; Lieber, C; Yenamandra, A; Desposito, F

    1997-06-27

    Chromosome analysis of a newborn boy with Down syndrome resulted in the identification of a family with an unusual derivative chromosome 22. The child has 46 chromosomes, including two chromosomes 21, one normal chromosome 22, and a derivative chromosome 22. Giemsa banding and fluorescent in situ hybridization (FISH) studies show that the derivative chromosome is chromosome 22 with evidence of both paracentric and pericentric inversions, joined to the long arm of chromosome 21 from 21q21.2 to qter. The rearrangement results in partial trisomy 21 extending from 21q21.2 to 21q terminus in the patient. The child's mother, brother, maternal aunt, and maternal grandmother are all carriers of the derivative chromosome. All have 45 chromosomes, with one normal chromosome 21, one normal chromosome 22, and the derivative chromosome 22. The rearrangement results in the absence of the short arm, the centromere, and the proximal long arm of chromosome 21 (del 21pter-21q21.2) in carriers. Carriers of the derivative chromosome in this family have normal physical appearance, mild learning disabilities and poor social adjustment. PMID:9182781

  19. Deletion at chromosome 16p13.3 as a cause of Rubinstein-Taybi syndrome: clinical aspects.

    OpenAIRE

    Hennekam, R. C.; Tilanus, M; Hamel, B C; Voshart-van Heeren, H; Mariman, E.C.; van Beersum, S. E.; van den Boogaard, M. J.; Breuning, M H

    1993-01-01

    In the accompanying paper, a chromosomal localization of the Rubinstein-Taybi syndrome by cytogenetic investigations with fluorescence in situ hybridization techniques at chromosome 16p13.3 is described. We investigated 19 of these patients and their parents (a) to ascertain the parental origin of the chromosome with the deletion in families where such a deletion was detected, (b) to disclose whether uniparental disomy plays a role in etiology, and (c) to compare clinical features in patients...

  20. Deletion at chromosome 16p13. 3 as a cause of Rubinstein-Taybi syndrome: Clinical aspects

    Energy Technology Data Exchange (ETDEWEB)

    Hennekam, R.C.M.; Tilanus, M.; Boogaard, M.J.H. van den (State Univ., Utrecht (Netherlands)); Hamel, B.C.J.; Voshart-van Heeren, H.; Mariman, E.C.M.; Beersum, S.E.C. van (University Hospital, Nijmegen (Netherlands)); Breuning, M.H. (Clinical Genetics Center, Rotterdam (Netherlands))

    1993-02-01

    In the accompanying paper, a chromosomal localization of the Rubinstein-Taybi syndrome by cytogenetic investigations with fluorescence in situ hybridization techniques at chromosome 16p13.3 is described. The authors investigated 19 of these patients and their parents (a) to ascertain the parental origin of the chromosome with the deletion in families where such a deletion was detected, (b) to disclose whether uniparental disomy plays a role in etiology, and (c) to compare clinical features in patients with a deletion to those in individuals in whom deletions were not detectable. Molecular studies showed a copy of chromosome 16 from each parent in all 19 patients. Uniparental disomy was also excluded for five other chromosome arms known to be imprinted in mice. None of the probes used for determining the origin of the deleted chromosome proved to be informative. The clinical features were essentially the same in patients with and without visible deletion, with a possible exception for the incidence of microcephaly, angulation of thumbs and halluces, and partial duplication of the halluces. A small deletion at 16p13.3 may be found in some patients with Rubinstein-Taybi syndrome. Cytogenetically undetectable deletions, point mutations, mosaicism, heterogeneity, or phenocopy by a nongenetic cause are the most probable explanations for the absence of cytogenetic or molecular abnormalities in other patients with Rubinstein-Taybi syndrome. 26 refs., 3 tabs., 2 figs.

  1. Sons conceived by assisted reproduction techniques inherit deletions in the azoospermia factor (AZF) region of the Y chromosome and the DAZ gene copy number

    DEFF Research Database (Denmark)

    Mau Kai, Claudia; Juul, A; McElreavey, K;

    2008-01-01

    Deletions in the azoospermia factor (AZF) region of the Y chromosome are frequent in infertile men. The clinical consequences and the mode of inheritance of these deletions are not yet clear.......Deletions in the azoospermia factor (AZF) region of the Y chromosome are frequent in infertile men. The clinical consequences and the mode of inheritance of these deletions are not yet clear....

  2. High rate of deletion of chromosomes 1p and 19q in insular oligodendroglial tumors

    OpenAIRE

    Wu, Adam; Aldape, Kenneth; Lang, Frederick F.

    2009-01-01

    It has been reported recently that oligodendroglial tumors arising in the insula rarely harbor co-deletions of chromosomes 1p and 19q, a molecular signature which is associated with a good prognosis and increased responsiveness to radiation and chemotherapy compared with tumors in which 1p and/or 19q is intact. In the context of this claim, we analyzed a series of insular oligodendroglial tumors in order to determine the frequency of 1p/19q co-deletion in tumors arising in this region. We ide...

  3. Sexual dimorphism in white campion: complex control of carpel number is revealed by Y chromosome deletions

    International Nuclear Information System (INIS)

    Sexual dimorphism in the dioecious plant white campion (Silene latifolia = Melandrium album) is under the control of two main regions on the Y chromosome. One such region, encoding the gynoecium-suppressing function (GSF), is responsible for the arrest of carpel initiation in male flowers. To generate chromosomal deletions, we used pollen irradiation in male plants to produce hermaphroditic mutants (bsx mutants) in which carpel development was restored. The mutants resulted from alterations in at least two GSF chromosomal regions, one autosomal and one located on the distal half of the (p)-arm of the Y chromosome. The two mutations affected carpel development independently, each mutation showing incomplete penetrance and variegation, albeit at significantly different levels. During successive meiotic generations, a progressive increase in penetrance and a reduction in variegation levels were observed and quantified at the level of the Y-linked GSF (GSF-Y). Possible mechanisms are proposed to explain the behavior of the bsx mutations: epigenetic regulation or/and second-site mutation of modifier genes. In addition, studies on the inheritance of the hermaphroditic trait showed that, unlike wild-type Y chromosomes, deleted Y chromosomes can be transmitted through both the male and the female lines. Altogether, these findings bring experimental support, on the one hand, to the existence on the Y chromosome of genic meiotic drive function(s) and, on the other hand, to models that consider that dioecy evolved through multiple mutation events. As such, the GSF is actually a system containing more than one locus and whose primary component is located on the Y chromosome

  4. Association between Y-chromosome AZFc region micro-deletions with recurrent miscarriage

    OpenAIRE

    Saeede Soleimanian; Seyyed Mahdi Kalantar; Mohamad Hasan Sheikhha; Mohamad Ali Zaimy; Azam Rasti; Hossein Fazli

    2013-01-01

    Background: In human, about 25% of implanted embryos are losing 1-2 week following attachment to the uterus. A subset of this population will have three or more consecutive miscarriages which define as repeated pregnancy loss (RPL). Introducing the assisted reproductive technologies (ARTS) made a chance for infertile couples to solve their childless problem. Objective: This study was conducted to evaluate the incidence of Y-chromosome AZF region's micro-deletions in male partners of couples w...

  5. Involvement of phosphatase and tensin homolog deleted from chromosome 10 in rodent model of neuropathic pain

    OpenAIRE

    Huang, Shi-Ying; Sung, Chun-Sung; Chen, Wu-Fu; Chen, Chun-Hong; Feng, Chien-Wei; Yang, San-Nan; Hung, Han-Chun; Chen, Nan-Fu; Lin, Pey-Ru; Chen, San-Cher; Wang, Hui-Min David; Chu, Tian-Huei; Tai, Ming-Hong; Wen, Zhi-Hong

    2015-01-01

    Background Many cancer research studies have extensively examined the phosphatase and tensin homolog deleted from chromosome 10 (PTEN) pathway. There are only few reports that suggest that PTEN might affect pain; however, there is still a lack of evidence to show the role of PTEN for modulating pain. Here, we report a role for PTEN in a rodent model of neuropathic pain. Results We found that chronic constriction injury (CCI) surgery in rats could elicit downregulation of spinal PTEN as well a...

  6. Analysis of chromosome 22 deletions in neurofibromatosis type 2-related tumors

    Energy Technology Data Exchange (ETDEWEB)

    Wolff, R.K.; Frazer, K.A.; Jackler, R.K.; Lanser, M.J.; Pitts, L.H.; Cox, D.R. (Univ. of California, San Francisco, CA (United States))

    1992-09-01

    The neurofibromatosis type 2 (NF2) gene has been hypothesized to be a recessive tumor suppressor, with mutations at the same locus on chromosome 22 that lead to NF2 also leading to sporadic tumors of the types seen in NF2. Flanking markers for this gene have previously been defined as D22S1 centromeric and D22S28 telomeric. Identification of subregions of this interval that are consistently rearranged in the NF2-related tumors would aid in better defining the disease locus. To this end, the authors have compared tumor and constitutional DNAs, isolated from 39 unrelated patients with sporadic and NF2-associated acoustic neuromas, meningiomas, schwannomas, and ependymomas, at eight polymorphic loci on chromosome 22. Two of the tumors studied revealed loss-of-heterozygosity patterns, which is consistent with the presence of chromosome 22 terminal deletions. By using additional polymorphic markers, the terminal deletion breakpoint found in one of the tumors, an acoustic neuroma from an NF2 patient, was mapped within the previously defined NF2 region. The breakpoint occurred between the haplotyped markers D22S41/D22S46 and D22S56. This finding redefines the proximal flanking marker and localizes the NF2 gene between markers D22S41/D22S46 and D22S28. In addition, the authors identified a sporadic acoustic neuroma that reveals a loss-of-heterozygosity pattern consistent with mitotic recombination or deletion and reduplication, which are mechanisms not previously seen in studies of these tumors. This finding, while inconsistent with models of tumorigenesis that invoke single deletions and their gene-dosage effects, lends further support to the recessive tumor-suppressor model. 33 refs., 2 figs., 1 tab.

  7. Deletion of DXZ4 on the human inactive X chromosome alters higher-order genome architecture.

    Science.gov (United States)

    Darrow, Emily M; Huntley, Miriam H; Dudchenko, Olga; Stamenova, Elena K; Durand, Neva C; Sun, Zhuo; Huang, Su-Chen; Sanborn, Adrian L; Machol, Ido; Shamim, Muhammad; Seberg, Andrew P; Lander, Eric S; Chadwick, Brian P; Aiden, Erez Lieberman

    2016-08-01

    During interphase, the inactive X chromosome (Xi) is largely transcriptionally silent and adopts an unusual 3D configuration known as the "Barr body." Despite the importance of X chromosome inactivation, little is known about this 3D conformation. We recently showed that in humans the Xi chromosome exhibits three structural features, two of which are not shared by other chromosomes. First, like the chromosomes of many species, Xi forms compartments. Second, Xi is partitioned into two huge intervals, called "superdomains," such that pairs of loci in the same superdomain tend to colocalize. The boundary between the superdomains lies near DXZ4, a macrosatellite repeat whose Xi allele extensively binds the protein CCCTC-binding factor. Third, Xi exhibits extremely large loops, up to 77 megabases long, called "superloops." DXZ4 lies at the anchor of several superloops. Here, we combine 3D mapping, microscopy, and genome editing to study the structure of Xi, focusing on the role of DXZ4 We show that superloops and superdomains are conserved across eutherian mammals. By analyzing ligation events involving three or more loci, we demonstrate that DXZ4 and other superloop anchors tend to colocate simultaneously. Finally, we show that deleting DXZ4 on Xi leads to the disappearance of superdomains and superloops, changes in compartmentalization patterns, and changes in the distribution of chromatin marks. Thus, DXZ4 is essential for proper Xi packaging. PMID:27432957

  8. Deletion of DXZ4 on the human inactive X chromosome alters higher-order genome architecture

    Science.gov (United States)

    Darrow, Emily M.; Huntley, Miriam H.; Dudchenko, Olga; Stamenova, Elena K.; Durand, Neva C.; Sun, Zhuo; Huang, Su-Chen; Sanborn, Adrian L.; Machol, Ido; Shamim, Muhammad; Seberg, Andrew P.; Lander, Eric S.; Chadwick, Brian P.; Aiden, Erez Lieberman

    2016-01-01

    During interphase, the inactive X chromosome (Xi) is largely transcriptionally silent and adopts an unusual 3D configuration known as the “Barr body.” Despite the importance of X chromosome inactivation, little is known about this 3D conformation. We recently showed that in humans the Xi chromosome exhibits three structural features, two of which are not shared by other chromosomes. First, like the chromosomes of many species, Xi forms compartments. Second, Xi is partitioned into two huge intervals, called “superdomains,” such that pairs of loci in the same superdomain tend to colocalize. The boundary between the superdomains lies near DXZ4, a macrosatellite repeat whose Xi allele extensively binds the protein CCCTC-binding factor. Third, Xi exhibits extremely large loops, up to 77 megabases long, called “superloops.” DXZ4 lies at the anchor of several superloops. Here, we combine 3D mapping, microscopy, and genome editing to study the structure of Xi, focusing on the role of DXZ4. We show that superloops and superdomains are conserved across eutherian mammals. By analyzing ligation events involving three or more loci, we demonstrate that DXZ4 and other superloop anchors tend to colocate simultaneously. Finally, we show that deleting DXZ4 on Xi leads to the disappearance of superdomains and superloops, changes in compartmentalization patterns, and changes in the distribution of chromatin marks. Thus, DXZ4 is essential for proper Xi packaging. PMID:27432957

  9. Deletion of the long arm of chromosome 20 (del(20)(q11)) in myeloid disorders

    Energy Technology Data Exchange (ETDEWEB)

    Testa, J.R.; Kinnealey, A.; Rowley, J.D.; Golde, D.W.; Potter, D.

    1978-11-01

    Detailed clinical and cytogenetic studies were performed in five patients who had abnormal hematopoiesis and an acquired deletion of an F-group chromosome. Cytogenetic analyses, with banding techniques, of cells from bone marrow, spleen, or unstimulated peripheral blood showed a partial deletion of the long arm of one chromosome 20 (del(20)(q11)) in all five patients. Three patients had myeloproliferative disorders of uncertain classification, the fourth had possible preleukemia, and the fifth had acute myelomonocytic leukemia. Although the five cases showed certain similarities, the clinical and hematologic findings seen with the 20q- abnormality were not specific. None of the patients showed evidence of polycythemia vera or idiopathic acquired refractory sideroblastic anemia, two diseases previously associated with the 20q-. Our studies indicate that the 20q-abnormality is not limited to diseases primarily affecting erythropoiesis but that it can be found in the broader spectrum of myeloid disorders. In polycythemia vera, the 20q- has sometimes been regarded as a possible result of previous therapy with cytotoxic agents; however, four of our patients were untreated when the deletion was first noted.

  10. Sexual dimorphism in white campion: deletion on the Y chromosome results in a floral asexual phenotype

    International Nuclear Information System (INIS)

    White campion is a dioecious plant with heteromorphic X and Y sex chromosomes. In male plants, a filamentous structure replaces the pistil, while in female plants the stamens degenerate early in flower development. Asexual (asx) mutants, cumulating the two developmental defects that characterize the sexual dimorphism in this species, were produced by gamma ray irradiation of pollen and screening in the M1 generation. The mutants harbor a novel type of mutation affecting an early function in sporogenous/parietal cell differentiation within the anther. The function is called stamen-promoting function (SPF). The mutants are shown to result from interstitial deletions on the Y chromosome. We present evidence that such deletions tentatively cover the central domain on the (p)-arm of the Y chromosome (Y2 region). By comparing stamen development in wild-type female and asx mutant flowers we show that they share the same block in anther development, which results in the production of vestigial anthers. The data suggest that the SPF, a key function(s) controlling the sporogenous/parietal specialization in premeiotic anthers, is genuinely missing in females (XX constitution). We argue that this is the earliest function in the male program that is Y-linked and is likely responsible for ''male dimorphism'' (sexual dimorphism in the third floral whorl) in white campion. More generally, the reported results improve our knowledge of the structural and functional organization of the Y chromosome and favor the view that sex determination in this species results primarily from a trigger signal on the Y chromosome (Y1 region) that suppresses female development. The default state is therefore the ancestral hermaphroditic state

  11. MCPH1 deletion in a newborn with severe microcephaly and premature chromosome condensation.

    Science.gov (United States)

    Pfau, Ruthann B; Thrush, Devon Lamb; Hamelberg, Elizabeth; Bartholomew, Dennis; Botes, Shaun; Pastore, Matthew; Tan, Christopher; del Gaudio, Daniela; Gastier-Foster, Julie M; Astbury, Caroline

    2013-11-01

    A newborn with severe microcephaly and a history of parental consanguinity was referred for cytogenetic analysis and subsequently for genetic evaluation. While a 46,XY karyotype was eventually obtained, premature chromosome condensation was observed. A head MRI confirmed primary microcephaly. This combination of features focused clinical interest on the MCPH1 gene and directed genetic testing by sequence analysis and duplication/deletion studies disclosed a homozygous deletion of exons 1-11 of the MCPH1 gene. This case illustrates a strength of standard cytogenetic evaluation in directing molecular testing to a single target gene in this disorder, allowing much more rapid diagnosis at a substantial cost savings for this family. PMID:24080358

  12. Early-onset Parkinson's Disease Associated with Chromosome 22q11.2 Deletion Syndrome.

    Science.gov (United States)

    Oki, Mitsuaki; Hori, Shin-ichiro; Asayama, Shinya; Wate, Reika; Kaneko, Satoshi; Kusaka, Hirofumi

    2016-01-01

    We herein report the case of a 43-year-old man with a 4-year history of resting tremor and akinesia. His resting tremor and rigidity were more prominent on the left side. He also presented retropulsion. His symptoms responded to the administration of levodopa. The patient also had a cleft lip and palate, cavum vergae, and hypoparathyroidism. A chromosome analysis disclosed a hemizygous deletion in 22q11.2, and he was diagnosed with early-onset Parkinson's disease associated with 22q11.2 deletion syndrome. However, the patient lacked autonomic nerve dysfunction, and his cardiac uptake of (123)I-metaiodobenzylguanidine was normal, indicating an underlying pathological mechanism that differed to that of sporadic Parkinson's disease. PMID:26831029

  13. Chromosome 17p deletion in human medulloblastoma: a missing checkpoint in the Hedgehog pathway.

    Science.gov (United States)

    De Smaele, Enrico; Di Marcotullio, Lucia; Ferretti, Elisabetta; Screpanti, Isabella; Alesse, Edoardo; Gulino, Alberto

    2004-10-01

    Although deregulation of Hedgehog signalling is considered to play a crucial oncogenic role and commonly occurrs in medulloblastoma, genetic lesions in components of this pathway are observed in a minority of cases. The recent identification of a novel putative tumor suppressor (REN(KCTD11)) on chromosome 17p13.2, a region most frequently lost in human medulloblastoma, highlights the role of allelic deletion of the gene in this brain malignancy, leading to the loss of growth inhibitory activity via suppression of Gli-dependent activation of Hedgehog target genes. The presence on 17p13 of another tumor suppressor gene (p53) whose inactivation cooperates with Hedgehog pathway for medulloblastoma formation, suggests that 17p deletion unveils haploinsufficiency conditions leading to abrogation of either direct and indirect checkpoints of Hedgehog signalling in cancer. PMID:15467454

  14. Interstitial deletion in the long arms of chromosome 1: 46,XY,del(1)(pter leads to q22::q25 leads to qter).

    OpenAIRE

    de Pablo, C E; García Sagredo, J M; Ferro, M T; Ferrando, P.; San Román, C

    1980-01-01

    A child was brought to us with multiple anomalies. On examination we found an interstitial deletion in the long arms of chromosome 1. We studied genetic and chromosome markers, comparing our clinical and cytogenetic findings with other reported cases of chromosome 1 interstitial deletion.

  15. Domain specific attentional impairments in children with chromosome 22q11.2 deletion syndrome

    OpenAIRE

    Bish, Joel P.; Chiodo, Renee; Mattei, Victoria; Simon, Tony J.

    2007-01-01

    One of the defining cognitive characteristics of the chromosome 22q deletion syndrome (DS22q11.2) is visuospatial processing impairments. The purpose of this study was to investigate and extend the specific attentional profile of children with this disorder using both an object-based attention task and an inhibition of return task. A group of children with the disorder was compared in these tasks with a group of age-matched typically developing children. The children with DS22q11.2 demonstrat...

  16. Mapping the chromosome 16 cadherin gene cluster to a minimal deleted region in ductal breast cancer.

    Science.gov (United States)

    Chalmers, I J; Aubele, M; Hartmann, E; Braungart, E; Werner, M; Höfler, H; Atkinson, M J

    2001-04-01

    The cadherin family of cell adhesion molecules has been implicated in tumor metastasis and progression. Eight family members have been mapped to the long arm of chromosome 16. Using radiation hybrid mapping, we have located six of these genes within a cluster at 16q21-q22.1. In invasive lobular carcinoma of the breast frequent LOH and accompanying mutation affect the CDH1 gene, which is a member of this chromosome 16 gene cluster. CDH1 LOH also occurs in invasive ductal carcinoma, but in the absence of gene mutation. The proximity of other cadherin genes to 16q22.1 suggests that they may be affected by LOH in invasive ductal carcinomas. Using the mapping data, microsatellite markers were selected which span regions of chromosome 16 containing the cadherin genes. In breast cancer tissues, a high rate of allelic loss was found over the gene cluster region, with CDH1 being the most frequently lost marker. In invasive ductal carcinoma a minimal deleted region was identified within part of the chromosome 16 cadherin gene cluster. This provides strong evidence for the existence of a second 16q22 suppressor gene locus within the cadherin cluster. PMID:11343777

  17. Detailed molecular and clinical investigation of a child with a partial deletion of chromosome 11 (Jacobsen syndrome)

    OpenAIRE

    Peitsidis Panagiotis; Thomaidis Loretta; Papoulidis Ioannis; Louizou Eirini; Kefalas Konstantinos; Neroutsou Rosita; Orru Sandro; Manolakos Emmanouil; Sotiriou Sotirios; Kitsos George; Tsoplou Panagiota; Petersen Michael B; Metaxotou Aikaterini

    2009-01-01

    Abstract Background Jacobsen syndrome (JBS) is a rare chromosomal disorder leading to multiple physical and mental impairment. This syndrome is caused by a partial deletion of chromosome 11, especially subband 11q24.1 has been proven to be involved. Clinical cases may easily escape diagnosis, however pancytopenia or thrombocytopenia may be indicative for JBS. Results We report a 7.5 years old boy presenting with speech development delay, hearing impairment and abnormal platelet function. High...

  18. Phenotypic variation within European carriers of the Y-chromosomal gr/gr deletion is independent of Y-chromosomal background

    DEFF Research Database (Denmark)

    Krausz, C; Giachini, C; Xue, Y;

    2008-01-01

    of duplications and the Y-chromosomal haplogroup were characterised. Although the study had good power to detect factors that accounted for >or=5.5% of the variation in sperm concentration, no such factor was found. A negative effect of gr/gr deletions followed by b2/b4 duplication was found within...

  19. Chromosome 22q11.2 deletion may contain a locus for recessive early-onset Parkinson’s disease

    OpenAIRE

    Ogaki, Kotaro; Ross, Owen A.

    2014-01-01

    Recently, it has been reported that carriers of a hemizygous chromosome 22q11.2 deletion may be at increased risk of early-onset Parkinson’s disease. Herein, we propose a hypothesis that it is not the microdeletion per se that is responsible for the phenotype but rather a complete loss of function of a gene within the region due to the combination of the deletion and another mutation on the alternate allele. Thus we propose the deletion may be highlighting a novel locus for ...

  20. Interstitial deletion of chromosome 4p associated with mild mental retardation, epilepsy and polymicrogyria of the left temporal lobe

    DEFF Research Database (Denmark)

    Møller, R S; Hansen, C P; Jackson, G D;

    2007-01-01

    In this study, we present a 38-year-old woman with an interstitial deletion of 4p15.1-15.3, mild mental retardation, epilepsy and polymicrogyria adjacent to an arachnoid cyst of the left temporal lobe. The deletion was ascertained through array-comparative genome hybridization screening of patients...... with epilepsy and brain malformations. To date, about 35 patients with cytogenetically visible deletions involving 4p15 and without Wolf-Hirschhorn syndrome have been described, but the extent of the deletions has not been determined in the majority of these cases. The clinical manifestations of the...... patient described in this study were similar but not identical to the previously reported cases with 4p15 interstitial deletions. This finding indicates the presence of one or more genes involved in brain development and epilepsy in this chromosome region....

  1. The RB1 gene is the target of chromosome 13 deletions in malignant fibrous histiocytoma.

    Science.gov (United States)

    Chibon, F; Mairal, A; Fréneaux, P; Terrier, P; Coindre, J M; Sastre, X; Aurias, A

    2000-11-15

    Forty-four malignant fibrous histiocytomas (MFHs) were studied by comparative genomic hybridization. Among the observed imbalances, losses of the 13q14-q21 region were observed in almost all tumors (78%), suggesting that a gene localized in this region could act as a tumor suppressor gene and that its inactivation could be relevant for MFH oncogenesis and/or progression. We determined by CA repeat analyses a consensus region of deletion focusing on the RB1 region. The RB1 gene was then analyzed by protein truncation test, direct sequencing, fluorescence in situ hybridization, Southern blotting, and immunohistochemistry. RB1 mutations and/or homozygous deletions were found in 7 of the 34 tumors analyzed (20%). Among the 35 tumors with comparative genomic hybridization imbalances analyzed by immunohistochemistry, 30 (86%) did not exhibit significant nuclear labeling. The high correlation between chromosome 13 losses and absence of RB1 protein expression and the mutations detected strongly suggest that RB1 gene inactivation is a pivotal event in MFH oncogenesis. Moreover, the observation of a high incidence of MFH in patients previously treated for hereditary retinoblastoma fits well this hypothesis. PMID:11103795

  2. Reciprocal white matter alterations due to 16p11.2 chromosomal deletions versus duplications.

    Science.gov (United States)

    Chang, Yi Shin; Owen, Julia P; Pojman, Nicholas J; Thieu, Tony; Bukshpun, Polina; Wakahiro, Mari L J; Marco, Elysa J; Berman, Jeffrey I; Spiro, John E; Chung, Wendy K; Buckner, Randy L; Roberts, Timothy P L; Nagarajan, Srikantan S; Sherr, Elliott H; Mukherjee, Pratik

    2016-08-01

    Copy number variants at the 16p11.2 chromosomal locus are associated with several neuropsychiatric disorders, including autism, schizophrenia, bipolar disorder, attention-deficit hyperactivity disorder, and speech and language disorders. A gene dosage dependence has been suggested, with 16p11.2 deletion carriers demonstrating higher body mass index and head circumference, and 16p11.2 duplication carriers demonstrating lower body mass index and head circumference. Here, we use diffusion tensor imaging to elucidate this reciprocal relationship in white matter organization, showing widespread increases of fractional anisotropy throughout the supratentorial white matter in pediatric deletion carriers and, in contrast, extensive decreases of white matter fractional anisotropy in pediatric and adult duplication carriers. We find associations of these white matter alterations with cognitive and behavioral impairments. We further demonstrate the value of imaging metrics for characterizing the copy number variant phenotype by employing linear discriminant analysis to predict the gene dosage status of the study subjects. These results show an effect of 16p11.2 gene dosage on white matter microstructure, and further suggest that opposite changes in diffusion tensor imaging metrics can lead to similar cognitive and behavioral deficits. Given the large effect sizes found in this study, our results support the view that specific genetic variations are more strongly associated with specific brain alterations than are shared neuropsychiatric diagnoses. Hum Brain Mapp 37:2833-2848, 2016. © 2016 Wiley Periodicals, Inc. PMID:27219475

  3. Overlapping Numerical Cognition Impairments in Children with Chromosome 22q11.2 Deletion or Turner Syndromes

    Science.gov (United States)

    Simon, T. J.; Takarae, Y.; DeBoer, T.; McDonald-McGinn, D. M.; Zackai, E. H.; Ross, J. L.

    2008-01-01

    Children with one of two genetic disorders (chromosome 22q11.2 deletion syndrome and Turner syndrome) as well typically developing controls, participated in three cognitive processing experiments. Two experiments were designed to test cognitive processes involved in basic aspects numerical cognition. The third was a test of simple manual motor…

  4. Social Skills and Associated Psychopathology in Children with Chromosome 22q11.2 Deletion Syndrome: Implications for Interventions

    Science.gov (United States)

    Shashi, V.; Veerapandiyan, A.; Schoch, K.; Kwapil, T.; Keshavan, M.; Ip, E.; Hooper, S.

    2012-01-01

    Background: Although distinctive neuropsychological impairments have been delineated in children with chromosome 22q11 deletion syndrome (22q11DS), social skills and social cognition remain less well-characterised. Objective: To examine social skills and social cognition and their relationship with neuropsychological function/behaviour and…

  5. Molecular definition of the chromosome 7 deletion in Williams syndrome and parent-of-origin effects on growth

    Energy Technology Data Exchange (ETDEWEB)

    Perez Jurado, L.A.; Peoples, R.; Francke, U. [Stanford Univ. School of Medicine, CA (United States)] [and others

    1996-10-01

    Williams syndrome (WS) is a developmental disorder with variable phenotypic expression associated, in most cases, with a hemizygous deletion of part of chromosomal band 7q11.23 that includes the elastin gene (ELN). We have investigated the frequency and size of the deletions, determined the parental origin, and correlated the molecular results with the clinical findings in 65 WS patients. Hemizygosity at the ELN locus was established by typing of two intragenic polymorphisms, quantitative Southern analysis, and/or FISH. Polymorphic markers covering the deletion and flanking regions were ordered by a combination of genetic and physical mapping. Genotyping of WS patients and available parents for 13 polymorphisms revealed that of 65 clinically defined WS patients, 61 (94%) had a deletion of the ELN locus and were also hemizygous (or non-informative) at loci D7S489B, D7S2476, D7S613, D7S2472, and D7S1870. None of the four patients without ELN deletion was hemizygous at any of the polymorphic loci studied. All patients were heterozygous (or noninformative) for centromeric (D7S1816, D7S1483, and D7S653) and telomeric (D7S489A, D7S675, and D7S669) flanking loci. The genetic distance between the most-centromeric deleted locus, D7S489B, and the most-telomeric one, D7S1870, is 2 cM. The breakpoints cluster at {approximately}1 cM to either side of ELN. In 39 families informative for parental origin, all deletions were de novo, and 18 were paternally and 21 maternally derived. Comparison of clinical data, collected in a standardized quantifiable format, revealed significantly more severe growth retardation and microcephaly in the maternal deletion group. An imprinted locus, silent on the paternal chromosome and contributing to statural growth, may be affected by the deletion. 53 refs., 5 figs., 2 tabs.

  6. The Development of Cognitive Control in Children with Chromosome 22q11.2 Deletion Syndrome

    Directory of Open Access Journals (Sweden)

    Heather M Shapiro

    2014-06-01

    Full Text Available Chromosome 22q11.2 Deletion Syndrome (22q11.2DS is caused by the most common human microdeletion, and it is associated with cognitive impairments across many domains. While impairments in cognitive control have been described in children with 22q11.2DS, the nature and development of these impairments are not clear. Children with 22q11.2DS and typically developing children (TD were tested on four well-validated tasks aimed at measuring specific foundational components of cognitive control: response inhibition, cognitive flexibility, and working memory. Molecular assays were also conducted in order to examine genotype of catechol-O-methyltransferase (COMT, a gene located within the deleted region in 22q11.2DS and hypothesized to play a role in cognitive control. Mixed model regression analyses were used to examine group differences, as well as age-related effects on cognitive control component processes in a cross-sectional analysis. Regression models with COMT genotype were also conducted in order to examine potential effects of the different variants of the gene. Response inhibition, cognitive flexibility, and working memory were impaired in children with 22q11.2DS relative to TD children, even after accounting for global intellectual functioning (as measured by full-scale IQ. When compared with TD individuals, children with 22q11.2DS demonstrated atypical age-related patterns of response inhibition and cognitive flexibility. Both groups demonstrated typical age-related associations with working memory. The results of this cross-sectional analysis suggest a specific aberration in the development of systems mediating response inhibition in a sub-set of children with 22q11.2DS. It will be important to follow up with longitudinal analyses to directly examine these developmental trajectories, and correlate neurocognitive variables with clinical and adaptive outcome measures.

  7. A coalescence of two syndromes in a girl with terminal deletion and inverted duplication of chromosome 5

    OpenAIRE

    Krgovic, Danijela; Blatnik, Ana; Burmas, Ante; Zagorac, Andreja; Kokalj Vokac, Nadja

    2014-01-01

    Background Rearrangements involving chromosome 5p often result in two syndromes, Cri-du-chat (CdC) and Trisomy 5p, caused by a deletion and duplication, respectively. The 5p15.2 has been defined as a critical region for CdC syndrome; however, genotype-phenotype studies allowed isolation of particular characteristics such as speech delay, cat-like cry and mental retardation, caused by distinct deletions of 5p. A varied clinical outcome was also observed in patients with Trisomy 5p. Duplication...

  8. Deletions of the long arm of chromosome 5 define subgroups of T-cell acute lymphoblastic leukemia

    Science.gov (United States)

    La Starza, Roberta; Barba, Gianluca; Demeyer, Sofie; Pierini, Valentina; Di Giacomo, Danika; Gianfelici, Valentina; Schwab, Claire; Matteucci, Caterina; Vicente, Carmen; Cools, Jan; Messina, Monica; Crescenzi, Barbara; Chiaretti, Sabina; Foà, Robin; Basso, Giuseppe; Harrison, Christine J.; Mecucci, Cristina

    2016-01-01

    Recurrent deletions of the long arm of chromosome 5 were detected in 23/200 cases of T-cell acute lymphoblastic leukemia. Genomic studies identified two types of deletions: interstitial and terminal. Interstitial 5q deletions, found in five cases, were present in both adults and children with a female predominance (chi-square, P=0.012). Interestingly, these cases resembled immature/early T-cell precursor acute lymphoblastic leukemia showing significant down-regulation of five out of the ten top differentially expressed genes in this leukemia group, including TCF7 which maps within the 5q31 common deleted region. Mutations of genes known to be associated with immature/early T-cell precursor acute lymphoblastic leukemia, i.e. WT1, ETV6, JAK1, JAK3, and RUNX1, were present, while CDKN2A/B deletions/mutations were never detected. All patients had relapsed/resistant disease and blasts showed an early differentiation arrest with expression of myeloid markers. Terminal 5q deletions, found in 18 of patients, were more prevalent in adults (chi-square, P=0.010) and defined a subgroup of HOXA-positive T-cell acute lymphoblastic leukemia characterized by 130 up- and 197 down-regulated genes. Down-regulated genes included TRIM41, ZFP62, MAPK9, MGAT1, and CNOT6, all mapping within the 1.4 Mb common deleted region at 5q35.3. Of interest, besides CNOT6 down-regulation, these cases also showed low BTG1 expression and a high incidence of CNOT3 mutations, suggesting that the CCR4-NOT complex plays a crucial role in the pathogenesis of HOXA-positive T-cell acute lymphoblastic leukemia with terminal 5q deletions. In conclusion, interstitial and terminal 5q deletions are recurrent genomic losses identifying distinct subtypes of T-cell acute lymphoblastic leukemia. PMID:27151989

  9. A chromosome 1q44 deletion in a 4-month-old girl; The first report in Korea

    OpenAIRE

    Cho, Joo Hyun; Song, Eun Song; Kim, Hee Na; Oh, Burm Seok; Choi, Young Youn

    2014-01-01

    The deletion of the distal long arm of chromosome 1 is associated with a characteristic facial appearance and a pattern of associated malformations. Characteristic manifestations include a round face with prominent 'cupid's bow' and downturned corners of the mouth, thin vermilion borders of lips, a long upper lip with a smooth philtrum, a short and broad nose, epicanthal folds, apparently low-set ears, micrognathia, microcephaly, abnormal hands and feet, variable cardiac or genital anomalies,...

  10. Sodium Iodide Symporter and Phosphatase and Tensin Homolog Deleted on Chromosome Ten Expression in Cholangiocarcinoma Analysis with Clinicopathological Parameters

    OpenAIRE

    Han, Sang Young; Lee, Sung Wook; Baek, Yang Hyun; Kim, Ha Yoen; Kim, Jong Han; Jeong, Jin Sook; Roh, Young Hoon; Kim, Young Hoon; Park, Byung Ho; Kwon, Hee Jin; Cho, Jin Han; Nam, Kyung Jin

    2012-01-01

    Background/Aims This study was performed to investigate the correlation of sodium iodide symporter (NIS) expression with the functionality and loss of phosphatase and tensin homolog deleted on chromosome ten (PTEN) expression in human cholangiocarcinoma (CCA). Methods Immunohistochemistry for the expression of NIS and PTEN was performed in 60 biopsy specimens of CCA. The clinicopathological parameters were retrospectively identified from medical records. The expression pattern of NIS and loss...

  11. Failure to thrive as primary feature in two patients with subtle chromosomal aneuploidy: Interstitial deletion 2q33

    Energy Technology Data Exchange (ETDEWEB)

    Grace, K.; Mulla, W.; Stump, T. [Children`s Hospital of Philadelpha, PA (United States)] [and others

    1994-09-01

    It is well known that patients with chromosomal aneuploidy present with multiple congenital anomalies and dysmorphia, and that they may have associated failure to thrive. However, rarely is failure to thrive the predominant presenting feature. We report two such patients. Patient 1 had a marked history of failure to thrive, (weight 50% for 5 1/2 months at 20 months, length 50% for 15 months at 20 months). Patient 2 was noted to be growth retarded at 2 months upon presenting to the hospital with respiratory symptoms (weight 50% for a newborn, length 50% for 36 weeks gestation). There was relative head sparing in both patients. Chromosome analysis in patient 1, prompted by a negative work-up for the failure to thrive, and emerging evidence of developmental delay, revealed a 46,XY,del(2)(q32.2q33) karyotype. Chromosome analysis in patient 2, done as part of a complete workup for the failure to thrive, revealed a 46,XX,del(2)(q33.2q33.2 or q33.2q33.3) karyotype. On careful examination, subtle dysmorphic features were seen. In both patients these included a long flat philtrum, thin upper lip and high arched palate. Patient 1 also had a small posterior cleft of the palate. These patients have the smallest interstitial deletions of chromosome 2 so far reported. Their deletions overlap within 2q33 although they are not identical. Review of the literature reveals 15 patients with interstitial deletions which include 2q33. Marked growth retardation is reported in 14 of these cases. Cleft palate/abnormal uvula were frequently associated. These cases illustrate the need to include high resolution chromosomal studies as part of a complete work-up for unexplained failure to thrive.

  12. Distribution of radiation-induced G1 exchange and terminal deletion breakpoints in Chinese hamster chromosomes as detected by G banding

    International Nuclear Information System (INIS)

    A total of 255 chromosomal aberrations induced by X-rays in G1 phase of the cell cycle were scored in 600 G-banded metaphases prepared from Chinese hamster female cells. On the basis of a detailed analysis of these aberrations a total of 441 chromosomal breakpoints were mapped to the individual Chinese hamster chromosomes and their bands. More breakpoints were mapped to G-light (80.5%) than to G-dark (19.5%) bands. These results indicate that radiation-induced exchange and terminal deletion breakpoints, as observed in the first postirradiation metaphase, have different patterns of distribution in Chinese hamster chromosomes. Clustering of terminal deletions in the long arms of X chromosomes, which are entirely occupied by heterochromatin, suggests that chromosomal repair mechanisms responsible for rejoining of chromosomal breaks are less effective in heterochromatic than in other genomic regions. (author)

  13. Sequencing of rhesus macaque Y chromosome clarifies origins and evolution of the DAZ (Deleted in AZoospermia) genes.

    Science.gov (United States)

    Hughes, Jennifer F; Skaletsky, Helen; Page, David C

    2012-12-01

    Studies of Y chromosome evolution often emphasize gene loss, but this loss has been counterbalanced by addition of new genes. The DAZ genes, which are critical to human spermatogenesis, were acquired by the Y chromosome in the ancestor of Old World monkeys and apes. We and our colleagues recently sequenced the rhesus macaque Y chromosome, and comparison of this sequence to human and chimpanzee enables us to reconstruct much of the evolutionary history of DAZ. We report that DAZ arrived on the Y chromosome about 38 million years ago via the transposition of at least 1.1 megabases of autosomal DNA. This transposition also brought five additional genes to the Y chromosome, but all five genes were subsequently lost through mutation or deletion. As the only surviving gene, DAZ experienced extensive restructuring, including intragenic amplification and gene duplication, and has been the target of positive selection in the chimpanzee lineage. Editor's suggested further reading in BioEssays Should Y stay or should Y go: The evolution of non-recombining sex chromosomes Abstract. PMID:23055411

  14. Chromosome abnormalities in colorectal adenomas: two cytogenetic subgroups characterized by deletion of 1p and numerical aberrations

    DEFF Research Database (Denmark)

    Bomme, L; Bardi, G; Pandis, N;

    1996-01-01

    Cytogenetic analysis of short-term cultures from 34 benign colorectal polyps, all histologically verified as adenomas, revealed clonal chromosome aberrations in 21 of them. Eight polyps had structural rearrangements, whereas only numerical changes were found in 13. A combination of structural and...... changes were +20, +13, and monosomy 18, found in six, five, and two adenomas, respectively. Rearrangement of chromosome 1 was the most common structural change. Abnormalities involving 1p were seen in six adenomas, leading to visible loss of material in three. One adenoma had one clone with a large and...... another with a small 1p deletion. In three adenomas, del(1)(p36) was the only cytogenetic aberration, supporting the authors' previous conclusion that loss of one or more gene loci in band 1p36 is a common early change in colorectal tumorigenesis. Chromosome 8 was involved in structural changes in two...

  15. Patients with High-Grade Gliomas Harboring Deletions of Chromosomes 9p and 10q Benefit from Temozolomide Treatment

    Directory of Open Access Journals (Sweden)

    Silke Wemmert

    2005-10-01

    Full Text Available Surgical cure of glioblastomas is virtually impossible and their clinical course is mainly determined by the biologic behavior of the tumor cells and their response to radiation and chemotherapy. We investigated whether response to temozolomide (TMZ chemotherapy differs in subsets of malignant glioblastomas defined by genetic lesions. Eighty patients with newly diagnosed glioblastoma were analyzed with comparative genomic hybridization and loss of heterozygosity. All patients underwent radical resection. Fifty patients received TMZ after radiotherapy (TMZ group and 30 patients received radiotherapy alone (RT group. The most common aberrations detected were gains of parts of chromosome 7 and losses of 10% 9p, or 13q. The spectrum of genetic aberrations did not differ between the TMZ and RT groups. Patients treated with TMZ showed significantly better survival than patients treated with radiotherapy alone (19.5 vs 9.3 months. Genomic deletions on chromosomes 9 and 10 are typical for glioblastoma and associated with poor prognosis. However, patients with these aberrations benefited significantly from TMZ in univariate analysis. In multivariate analysis, this effect was pronounced for 9p deletion and for elderly patients with 10q deletions, respectively. This study demonstrates that molecular genetic and cytogenetic analyses potentially predict responses to chemotherapy in patients with newly diagnosed glioblastomas.

  16. Loss of heterozygosity on chromosome 10q23 and mutation of the phosphatase and tensin homolog deleted from chromosome 10 tumor suppressor gene in Korean hepatocellular carcinoma patients.

    Science.gov (United States)

    Bae, Jei-Jun; Rho, Jin-Woo; Lee, Tae-Jin; Yun, Sung-Su; Kim, Hong-Jin; Choi, Joon-Hyuk; Jeong, Daewon; Jang, Byeong-Churl; Lee, Tae-Yoon

    2007-10-01

    Loss of heterozygosity (LOH) in the 10q23 chromosomal region was analyzed in 18 tissue samples from Korean hepatocellular carcinoma (HCC) patients. LOH at the phosphatase and tensin homolog deleted from chromosome 10 (PTEN) region (D10S215, AFMa086wg9 and D10S541) was found in 8 of the 18 (44.4%) HCCs. LOH (20%) and microsatellite instability (26.7%) were also frequently found at the D10S2177 locus, which is located on the telomere side of the PTEN region. LOH was found in other loci, such as AFM280we1 and D10S2281. The presence of LOH in regions other than the PTEN region on chromosome 10q23 suggested the presence of additional tumor suppressor gene(s). PTEN mutation was found in only a subset of HCCs: A single base insertion at the end of the 5'-end splice signal (AG-GUAAGUU) in intron 5 and a silent mutation in exon 6 (codon 188, CTG-Val to CTA). Our data collectively suggest that the genetic alterations of chromosome 10q23, including the PTEN gene, could be important in hepatocarcinogenesis in the Korean population. PMID:17786367

  17. A Novel Large Deletion Encompassing the Whole of the Galactose-1-Phosphate Uridyltransferase (GALT) Gene and Extending into the Adjacent Interleukin 11 Receptor Alpha (IL11RA) Gene Causes Classic Galactosemia Associated with Additional Phenotypic Abnormalities

    OpenAIRE

    Papachristoforou, Rena; Petrou, Petros P.; Sawyer, Hilary; Williams, Maggie; Drousiotou, Anthi

    2013-01-01

    Objective The characterization of a novel large deletion in the galactose-1-phosphate uridyltransferase (GALT) gene accounting for the majority of disease alleles in Cypriot patients with classic galactosemia.

  18. Bicuspid aortic valve and aortic coarctation are linked to deletion of the X chromosome short arm in Turner syndrome

    Science.gov (United States)

    Bondy, Carolyn; Bakalov, Vladimir K; Cheng, Clara; Olivieri, Laura; Rosing, Douglas R; Arai, Andrew E

    2013-01-01

    Background Congenital heart disease (CHD) is a cardinal feature of X chromosome monosomy, or Turner syndrome (TS). Haploinsufficiency for gene(s) located on Xp have been implicated in the short stature characteristic of the syndrome, but the chromosomal region related to the CHD phenotype has not been established. Design We used cardiac MRI to diagnose cardiovascular abnormalities in four non-mosaic karyotype groups based on 50-metaphase analyses: 45,X (n=152); 46,X,del(Xp) (n=15); 46,X,del(Xq) (n=4); and 46,X,i(Xq) (n=14) from peripheral blood cells. Results Bicuspid aortic valves (BAV) were found in 52/152 (34%) 45,X study subjects and aortic coarctation (COA) in 19/152 (12.5%). Isolated anomalous pulmonary veins (APV) were detected in 15/152 (10%) for the 45,X study group, and this defect was not correlated with the presence of BAV or COA. BAVs were present in 28.6% of subjects with Xp deletions and COA in 6.7%. APV were not found in subjects with Xp deletions. The most distal break associated with the BAV/COA trait was at cytologic band Xp11.4 and ChrX:41,500 000. One of 14 subjects (7%) with the 46,X,i(Xq) karyotype had a BAV and no cases of COA or APV were found in this group. No cardiovascular defects were found among four patients with Xq deletions. Conclusions The high prevalence of BAV and COA in subjects missing only the X chromosome short arm indicates that haploinsufficiency for Xp genes contributes to abnormal aortic valve and aortic arch development in TS. PMID:23825392

  19. Loss of the N-myc oncogene in a patient with a small interstitial deletion of the short arm of chromosome 2

    Energy Technology Data Exchange (ETDEWEB)

    Saal, H.M. [Children`s Hospital Medical Center, Cincinnati, OH (United States); Johnson, R.C.; Carr, A.G.; Samango-Sprouse, C. [George Washington Univ. School of Medicine, Washington, DC (United States)] [and others

    1996-12-30

    To our knowledge, only four previous cases of distal chromosome 2p deletions exist in the literature. We present a patient with minor facial anomalies who had a distal interstitial deletion of the short arm of chromosome 2, del(2)(p24.2p25.1). This patient had many features seen in other patients with distal 2p deletion including short stature, {open_quotes}rectangular{close_quotes} facies, microcephaly, hypotonia, and mental retardation. This patient also has sensorineural hearing loss which has been described in one other patient with a similar deletion. The N-myc oncogene has been mapped to 2p24. By fluorescence in situ hybridization using a cDNA probe for the N-myc oncogene, this patient was found to have a deletion of the N-myc oncogene. This confirms the previous map location for N-myc. 17 refs., 3 figs., 1 tab.

  20. Unbalanced three-way chromosomal translocation leading to deletion 18q and duplication 20p.

    Science.gov (United States)

    Oegema, Renske; van Zutven, Laura J C M; van Hassel, Daniella A C M; Huijbregts, Guido C M; Hoogeboom, A Jeannette M

    2012-04-01

    In 1980, a case report on a boy with cleft palate, club feet, dysmorphic features, and developmental delay was published by Bijlsma as a possible distinct syndrome. This case is listed in the London Medical Databases version 1.0. We have reevaluated this patient at adult age. Using high resolution karyotyping and Affymetrix 250k SNP array analysis we identified an unbalanced three-way translocation with breakpoints at 17q22, 18q22.1, and 20p12.2 leading to deletion 18q and duplication 20p. Also, a 715 kb duplication in 1p34.2 and a 245 kb deletion at 1p21.1 were found. Mental retardation, cleft palate, and club feet have repeatedly been reported in deletion 18q patients and therefore we conclude that most of the patient's features can be explained by an 18q deletion. PMID:22406089

  1. Distinct nonrandom patterns of chromosomal deletions in giant-cell lesions of bone

    Directory of Open Access Journals (Sweden)

    Baruffi Marcelo Razera

    2002-01-01

    Full Text Available Cytogenetic analyses were performed on a bone giant cell reparative granuloma (GCRG and on three bone giant cell tumors (GCT. The present GCRG case is the second to be described cytogenetically. A modal chromosome number of 46 was observed in all samples. Clonal chromosome abnormalities were detected in all cases. The numerical alterations most frequently observed involved the loss of chromosomes 17 and 18. Among the structural anomalies observed, there was preferential involvement of chromosomes 6 and 10. Three GCT cases presented del(10(p13 and two cases presented del(6(q25 (1 GCRG and 1 GCT. These breakpoints mapped on 10p and 6q may harbour genes of importance in the development of bone giant cell tumors.

  2. Meiotic and mitotic behaviour of a ring/deleted chromosome 22 in human embryos determined by preimplantation genetic diagnosis for a maternal carrier

    Directory of Open Access Journals (Sweden)

    Laver Sarah

    2009-01-01

    Full Text Available Abstract Background Ring chromosomes are normally associated with developmental anomalies and are rarely inherited. An exception to this rule is provided by deletion/ring cases. We were provided with a unique opportunity to investigate the meiotic segregation at oogenesis in a woman who is a carrier of a deleted/ring 22 chromosome. The couple requested preimplantation genetic diagnosis (PGD following the birth of a son with a mosaic karyotype. The couple underwent two cycles of PGD. Studies were performed on lymphocytes, single embryonic cells removed from 3 day-old embryos and un-transferred embryos. Analysis was carried out using fluorescence in situ hybridisation (FISH with specific probe sets in two rounds of hybridization. Results In total, 12 embryos were biopsied, and follow up information was obtained for 10 embryos. No embryos were completely normal or balanced for chromosome 22 by day 5. There was only one embryo diagnosed as balanced of 12 biopsied but that accumulated postzygotic errors by day 5. Three oocytes apparently had a balanced chromosome 22 complement but all had the deleted and the ring 22 and not the intact chromosome 22. After fertilisation all the embryos accumulated postzygotic errors for chromosome 22. Conclusion The study of the preimplantation embryos in this case provided a rare and significant chance to study and understand the phenomena associated with this unusual type of anomaly during meiosis and in the earliest stages of development. It is the first reported PGD attempt for a ring chromosome abnormality.

  3. Chromosome aberrations involving 10q22: report of three overlapping interstitial deletions and a balanced translocation disrupting C10orf11

    DEFF Research Database (Denmark)

    Tzschach, Andreas; Bisgaard, Anne-Marie; Kirchhoff, Maria;

    2010-01-01

    and hypotonia. We also report on the results of breakpoint analysis by array painting in a mentally retarded patient with a balanced chromosome translocation 46,XY,t(10;13)(q22;p13)dn. The breakpoint in 10q22 was found to disrupt C10orf11, a brain-expressed gene in the common deleted interval of......Interstitial deletions of chromosome band 10q22 are rare. We report on the characterization of three overlapping de novo 10q22 deletions by high-resolution array comparative genomic hybridization in three unrelated patients. Patient 1 had a 7.9 Mb deletion in 10q21.3-q22.2 and suffered from severe...

  4. Deletions in chromosome 6p22.3-p24.3, including ATXN1, are associated with developmental delay and autism spectrum disorders

    Directory of Open Access Journals (Sweden)

    Celestino-Soper Patrícia BS

    2012-04-01

    Full Text Available Abstract Interstitial deletions of the short arm of chromosome 6 are rare and have been associated with developmental delay, hypotonia, congenital anomalies, and dysmorphic features. We used array comparative genomic hybridization in a South Carolina Autism Project (SCAP cohort of 97 subjects with autism spectrum disorders (ASDs and identified an ~ 5.4 Mb deletion on chromosome 6p22.3-p23 in a 15-year-old patient with intellectual disability and ASDs. Subsequent database queries revealed five additional individuals with overlapping submicroscopic deletions and presenting with developmental and speech delay, seizures, behavioral abnormalities, heart defects, and dysmorphic features. The deletion found in the SCAP patient harbors ATXN1, DTNBP1, JARID2, and NHLRC1 that we propose may be responsible for ASDs and developmental delay.

  5. 46, XX true hermaphroditism associated with a terminal deletion of the short arm of the X chromosome

    Energy Technology Data Exchange (ETDEWEB)

    Barbaux, S.; Vilain, E.; McElreavey, K. [Institut Pasteur, Paris (France)] [and others

    1994-09-01

    Testes are determined by the activity of the SRY gene product encoded by the Y chromosome. Mutations in SRY can lead to XY sex reversal (XY females) and the presence of the SRY gene in some XX individuals can lead either to complete (XX males) or incomplete (XX true hermaphrodites) sex reversal. Approximately 10% of XX true hermaphrodites contain a portion of the Y chromosome, including SRY, in their genome. The etiology of the remaining cases is unestablished but may be caused by mutations in other as yet unidentied sex determining genes downstream of SRY. Here we describe an SRY-negative true hermaphrodite with a 46,X,del(X)(p21.1-pter). The patient also presented with severe mental retardation, abnormal skin pigmentation and below average height. Histological examination of the gonad revealed bilateral ovotestis. We postulate that the Xp deletion has unmasked a recessive allele on the apparently normal X chromosome generating the intersex phenotype. This observation together with recent findings of certain XY females carrying duplications of Xp21.3 suggests that there may be a loci on Xp which acts as a switch in the testis/ovarian determination pathways.

  6. A unique de novo interstitial deletion of chromosome 17, del(17)(q23.2q24.3) in a female newborn with multiple congenital anomalies

    Energy Technology Data Exchange (ETDEWEB)

    Levin, M.L.; Shaffer, L.G.; Lewis, R.A. [Baylor College of Medicine, Houston, TX (United States)] [and others

    1994-09-01

    Contiguous gene or microdeletion syndromes occurring on chromosome 17p include the Smith-Magenis and Miller-Dieker syndromes associated with interstitial deletions of 17p11.2 and 17p13.3, respectively. Other cytogenetically visible interstitial deletions on chromosome 17 are quite rare or unique. We describe a newborn with a novel interstitial deletion of the long arm of chromosome 17 [del(17)(q23.2q24.3)] who died on day of life 17 during a recurrent apneic episode. We have compared our patient`s phenotype and karyotype to two reported patients with deletion 17q with minor clinical overlap. The most striking clinical features of this patient were severe intrauterine growth retardation, widespread skeletal malformations (split sutures, hypoplastic acetabulae and scapulae, vertebral anomalies, and digital hypoplasia), cutis verticis gyrata, dysmorphic facial features, and oropharyngeal malformations (absent uvula and submucous cleft palate). Mild congenital heart disease and anomalous optic nerves were also present. Parental karyotyps were normal. DNA from parents and patient has been collected and cell lines established on both parents. Genes which have been previously mapped to the region that is apparently deleted in this patient include: chorionic somatomammotropin A, growth hormone (normal), acid alpha-glucosidase, apolipoprotein H, and the alpha peptide of type 4 voltage gated sodium channel. As in other clinical cytogenetic syndromes, further descriptions of patients with similar or overlapping rearrangements in this region will be necessary to delineate genotype/phenotype correlations for chromosome 17.

  7. Aplastic anaemia preceding acute lymphoblastic leukaemia in an adult with isolated deletion of chromosome 9q.

    LENUS (Irish Health Repository)

    Kelly, Kevin

    2008-12-01

    Aplastic anaemia (AA) can precede acute lymphoblastic leukaemia (ALL) in 2% of children but this is rarely reported to occur in adults. A 21-year-old male presented with bone marrow failure and bone marrow biopsy showed a profoundly hypocellular marrow. He recovered spontaneously but represented 2 months later when he was diagnosed with pre-B acute lymphoblastic leukaemia. Chromosomal examination revealed 46,XY,del(9)(q13q34). To the best of our knowledge this is the first case to be reported of aplasia preceding ALL with 9q minus as the sole chromosomal abnormality.

  8. Specific deletion of Cdc42 does not affect meiotic spindle organization/migration and homologous chromosome segregation but disrupts polarity establishment and cytokinesis in mouse oocytes

    DEFF Research Database (Denmark)

    Wang, Zhen-Bo; Jiang, Zong-Zhe; Zhang, Qing-Hua;

    2013-01-01

    female infertility in mice. Cdc42 deletion has little effect on meiotic spindle organization and migration to the cortex but inhibits polar body emission, although homologous chromosome segregation occurs. The failure of cytokinesis is due to the loss of polarized Arp2/3 accumulation and actin cap...... polarized actin cap and oocyte polarity, and it determines asymmetric divisions resulting in two polar bodies. Here we investigate the functions of Cdc42 in oocyte meiotic maturation by oocyte-specific deletion of Cdc42 through Cre-loxP conditional knockout technology. We find that Cdc42 deletion causes...

  9. Chromosome 22q11.2 microdeletion in monozygotic twins with discordant phenotype and deletion size

    OpenAIRE

    Halder Ashutosh; Jain Manish; Chaudhary Isha; Varma Binuja

    2012-01-01

    Abstract We report on a pair of male monozygotic twins with 22q11.2 microdeletion, discordant phenotype and discordant deletion size. The second twin had findings suggestive of DiGeorge syndrome, while the first twin had milder anomalies without any cardiac malformation. The second twin had presented with intractable convulsion, cyanosis and cardiovascular failure in the fourth week of life and expired on the sixth week of life, whereas the first twin had some characteristic facial appearance...

  10. Chromosome 10p deletion in a patient with hypoparathyroidism, severe mental retardation, autism and basal ganglia calcifications.

    Science.gov (United States)

    Verri, Annapia; Maraschio, Paola; Devriendt, Koen; Uggetti, Carla; Spadoni, Emanuela; Haeusler, Edward; Federico, Antonio

    2004-01-01

    Chromosome 10p terminal deletions have been associated with a DiGeorge like phenotype. Haploinsufficiency of the region 10p14-pter, results in hypoparathyroidism, sensorineural deafness, renal anomaly, that is the triad that features the HDR syndrome. Van Esch (2000) identified in a HDR patient, within a 200 kb critical region, the GATA3 gene, a transcription factor involved in the embryonic development of the parathyroids, auditory system and kidneys. We describe a new male patient, 33-year-old, with 10p partial deletion affected by hypocalcemia, basal ganglia calcifications and a severe autistic syndrome associated with mental retardation. Neurologically he presented severe impairment of language, hypotonia, clumsiness and a postural dystonic attitude. A peripheral involvement of auditory pathways was documented by auditory evoked potentials alterations. CT scan documented basal ganglia calcifications. Hyperintensity of the lentiform nuclei was evident at the MRI examination. Renal ultrasound scan was normal. Haploinsufficiency for GATA3 gene was documented with FISH analysis using cosmid clone 1.2. Phenotypic spectrum observed in del (10p) is more severe than the classical DGS spectrum. GATA3 has been found to regulate the development of serotoninergic neurons. A serotoninergic dysfunction may be linked with autism in this patient. PMID:15337474

  11. Two subtelomeric chromosomal deletions in forty-six children with idiopathic mental retardation

    Institute of Scientific and Technical Information of China (English)

    李荣; 赵正言

    2004-01-01

    @@ Mental retardation (MR) affects approximately 3% of the population. In infancy and early childhood, mental retardation often presents as developmental delay. Unexplained MR is responsible for more than half of all cases.1,2 There is some evidence that subtle chromosomal rearrangements involved in subtelomeric regions (gene-rich regions), resulting in segmental aneuploidy and gene-dosage imbalance, are significant unrecognized causes of idiopathic mental retardation (IMR).3-10

  12. Detection of complex deletions in chromosomes 13 and 21 in a fetus by noninvasive prenatal testing

    OpenAIRE

    Wang, Ting; Duan, Chengying; Shen, Cong; Xiang, Jingjing; He, Quanze; Ding, Jie; Wen, Ping; Zhang, Qin; Wang, Wei; Liu, Minjuan; LI Hong; Li, Haibo; Zhang, LiLi

    2016-01-01

    Background To detect complex fetal subchromosomal abnormalities by noninvasive prenatal testing (NIPT). Case presentation After routine prenatal serum screening, the plasma of high-risk pregnant women were tested via NIPT, and the NIPT results were further validated by fetal karyotype analysis and array-based comparative genomic hybridization (aCGH) through amniocentesis. In addition, the chromosome karyotypes of the parents were also analyzed. NIPT results indicated subchromosomal abnormalit...

  13. Molecular dissection of a contiguous gene syndrome: Frequent submicroscopic deletions, evolutionarily conserved sequences, and a hypomethylated island in the Miller-Dieker chromosome region

    International Nuclear Information System (INIS)

    The Miller-Dieker syndrome (MDS), composed of characteristic facial abnormalities and a severe neuronal migration disorder affecting the cerebral cortex, is caused by visible or submicroscopic deletions of chromosome band 17p13. Twelve anonymous DNA markers were tested against a panel of somatic cell hybrids containing 17p deletions from seven MDS patients. All patients, including three with normal karyotypes, are deleted for a variable set of 5-12 markers. Two highly polymorphic VNTR (variable number of tandem repeats) probes, YNZ22 and YNH37, are codeleted in all patients tested and make molecular diagnosis for this disorder feasible. By pulsed-field gel electrophoresis, YNZ22 and YNH37 were shown to be within 30 kilobases (kb) of each other. Cosmid clones containing both VNTR sequences were identified, and restriction mapping showed them to be 100 kb were completely deleted in all patients, providing a minimum estimate of the size of the MDS critical region. A hypomethylated island and evolutionarily conserved sequences were identified within this 100-kb region, indications of the presence of one or more expressed sequences potentially involved in the pathophysiology of this disorder. The conserved sequences were mapped to mouse chromosome 11 by using mouse-rat somatic cell hybrids, extending the remarkable homology between human chromosome 17 and mouse chromosome 11 by 30 centimorgans, into the 17p telomere region

  14. Detailed phenotype-genotype study in five patients with chromosome 6q16 deletion : narrowing the critical region for Prader-Willi-like phenotype

    NARCIS (Netherlands)

    Bonaglia, Maria Clara; Ciccone, Roberto; Gimelli, Giorgio; Gimelli, Stefania; Marelli, Susan; Verheij, Joke; Giorda, Roberto; Grasso, Rita; Borgatti, Renato; Pagone, Filomena; Rodriguez, Laura; Martinez-Frias, Maria-Luisa; van Ravenswaaij, Conny; Zuffardi, Orsetta

    2008-01-01

    Most patients with an interstitial deletion of 6q16 have Prader-Willi-like phenotype, featuring obesity, hypotonia, short hands and feet, and developmental delay. In all reported studies, the chromosome rearrangement was detected by karyotype analysis, which provides an overview of the entire genome

  15. Screening of YAC clones and building a map of the chromosome 13 region often deleted during chronic B-cell lymphocytic leucosis

    NARCIS (Netherlands)

    Brodyanskii, VM; Sulimova, GE; Udina, IG; Aitova, SS; Shaikhaev, GO; Sharikova, OA; Zakharev, VM; Fedorova, LI; Zelenin, AV; Eikhorn, S; Baush, C; Laland, M; Ross, M; Yankovskii, NK

    1995-01-01

    Pools of YAC clones from the ICRF library were analyzed by PCR using PBKpt, MGG15, and D13S25 markers that flank the chromosome 13 region often deleted during chronic lymphocytic leukemia. Ten clones were found and described. Nine mega-YAC clones from the CEPH library flanking the region of interest

  16. Deletion of 1p36 as a primary chromosomal aberration in intestinal tumorigenesis

    DEFF Research Database (Denmark)

    Bardi, G; Pandis, N; Fenger, C;

    1993-01-01

    Cytogenetic analysis of short-term cultures from benign intestinal tumors revealed clonal chromosome aberrations in five colorectal adenomas, one adenoma of the papilla Vateri, and one hyperplastic polyp of the rectum. One adenoma had numerical aberrations only, but in all other tumors structural...... hyperplastic polyp. Both adenomas that had additional aberrations beyond the 1p loss showed severe dysplasia. We conclude that cytogenetically detectable loss of genetic information from 1p36 is an early, seemingly primary, premalignant event in intestinal tumorigenesis. The fact that the adenomas with 1p- as...

  17. A method for the analysis of 32 X chromosome insertion deletion polymorphisms in a single PCR

    DEFF Research Database (Denmark)

    Pereira, Rui; Pereira, Vania; Gomes, Iva;

    2012-01-01

    Studies of human genetic variation predominantly use short tandem repeats (STRs) and single nucleotide polymorphisms (SNPs) but Insertion deletion polymorphisms (Indels) are being increasingly explored. They combine desirable characteristics of other genetic markers, especially the possibility of......-Indel multiplex system amplifying 32 biallelic markers in one single PCR. The multiplex includes X-Indels shown to be polymorphic in the major human population groups and follows a short amplicon strategy. The set was applied in the genetic characterization of sub-Saharan African, European and East Asian....... Finally, a segregation analysis was performed using trio constellations of father-mother-daughters in order to address the transmission pattern and assess mutation rates of this type of markers....

  18. A molecular deletion of distal chromosome 4p in two families with a satellited chromosome 4 lacking the Wolf-Hirschhorn syndrome phenotype.

    OpenAIRE

    Estabrooks, L L; Lamb, A.N.; Kirkman, H N; Callanan, N P; Rao, K W

    1992-01-01

    We report two families with a satellited chromosome 4 short arm (4ps). Satellites and stalks normally occur on the short arms of acrocentric chromosomes; however, the literature cites several reports of satellited nonacrocentric chromosomes, which presumably result from a translocation with an acrocentric chromosome. This is the first report of 4ps chromosomes. Our families are remarkable in that both unaffected and affected individuals carry the 4ps chromosome. The phenotypes observed in aff...

  19. Isolation of anonymous DNA sequences from within a submicroscopic X chromosomal deletion in a patient with choroideremia, deafness, and mental retardation

    International Nuclear Information System (INIS)

    Choroideremia, an X-chromosome linked retinal dystrophy of unknown pathogenesis, causes progressive nightblindness and eventual central blindness in affected males by the third to fourth decade of life. Choroideremia has been mapped to Xq13-21 by tight linkage to restriction fragment length polymorphism loci. The authors have recently identified two families in which choroideremia is inherited with mental retardation and deafness. In family XL-62, an interstitial deletion Xq21 is visible by cytogenetic analysis and two linked anonymous DNA markers, DXYS1 and DXS72, are deleted. In the second family, XL-45, an interstitial deletion was suspected on phenotypic grounds but could not be confirmed by high-resolution cytogenetic analysis. They used phenol-enhanced reassociation of 48,XXXX DNA in competition with excess XL-45 DNA to generate a library of cloned DNA enriched for sequences that might be deleted in XL-45. Two of the first 83 sequences characterized from the library were found to be deleted in probands from family XL-45 as well as from family XL-62. Isolation of these sequences proves that XL-45 does contain a submicroscopic deletion and provides a starting point for identifying overlapping genomic sequences that span the XL-45 deletion. Each overlapping sequence will be studied to identify exons from the choroideremia locus

  20. Isolation of anonymous DNA sequences from within a submicroscopic X chromosomal deletion in a patient with choroideremia, deafness, and mental retardation

    Energy Technology Data Exchange (ETDEWEB)

    Nussbaum, R.L.; Lesko, J.G.; Lewis, R.A.; Ledbetter, S.A.; Ledbetter, D.H.

    1987-09-01

    Choroideremia, an X-chromosome linked retinal dystrophy of unknown pathogenesis, causes progressive nightblindness and eventual central blindness in affected males by the third to fourth decade of life. Choroideremia has been mapped to Xq13-21 by tight linkage to restriction fragment length polymorphism loci. The authors have recently identified two families in which choroideremia is inherited with mental retardation and deafness. In family XL-62, an interstitial deletion Xq21 is visible by cytogenetic analysis and two linked anonymous DNA markers, DXYS1 and DXS72, are deleted. In the second family, XL-45, an interstitial deletion was suspected on phenotypic grounds but could not be confirmed by high-resolution cytogenetic analysis. They used phenol-enhanced reassociation of 48,XXXX DNA in competition with excess XL-45 DNA to generate a library of cloned DNA enriched for sequences that might be deleted in XL-45. Two of the first 83 sequences characterized from the library were found to be deleted in probands from family XL-45 as well as from family XL-62. Isolation of these sequences proves that XL-45 does contain a submicroscopic deletion and provides a starting point for identifying overlapping genomic sequences that span the XL-45 deletion. Each overlapping sequence will be studied to identify exons from the choroideremia locus.

  1. Hippocampal volume reduction in children with chromosome 22q11.2 deletion syndrome is associated with cognitive impairment

    Directory of Open Access Journals (Sweden)

    Lee Aaron

    2007-10-01

    Full Text Available Abstract Background Previous investigations of individuals with chromosome 22q11.2 deletion syndrome (DS22q11.2 have reported alterations in both brain anatomy and cognitive function. Neuroanatomical studies have reported multiple abnormalities including changes in both gray and white matter in the temporal lobe, including the amygdala and hippocampus. Separate investigations of cognitive abilities have established the prevalence of general intellectual impairment, although the actual extent to which a single individual is affected varies greatly within the population. The present study was designed to examine structures within the temporal lobe and assess their functional significance in terms of cognition in children with DS22q11.2. Method A total of 72 children (ages 7–14 years participated in the investigation: 36 children (19 female, 17 male tested FISH positive for chromosome 22q11.2 deletion (Mean age = 10 years 9 months, ± 2 yr 4 mo and 36 were age-matched typically developing controls (13 female, 23 male; Mean age = 10 years 6 months, ± 1 yr 11 mo. For each subject, a three-dimensional high-resolution (1 mm isotropic T1-weighted structural MRI was acquired. Neuroanatomical guidelines were used to define borders of the amygdala and hippocampus bilaterally and volumes were calculated based on manual tracings of the regions. The Wechsler Intelligence Scale for Children (WISC was also administered. Results Volumetric reductions in total gray matter, white matter, and both the amygdala and hippocampus bilaterally were observed in children with DS22q11.2. Reductions in the left hippocampus were disproportionate to decreases in gray matter after statistically controlling for group differences in total gray matter, age, and data collection site. This specific reduction in hippocampal volume was significantly correlated with performance on standardized measures of intelligence, whereas the other neuroanatomical measures were not (gray

  2. Tetralogy of Fallot associated with deletion in the DiGeorge region of chromosome 22 (22q11)

    Energy Technology Data Exchange (ETDEWEB)

    D`Angelo, J.A.; Pillers, D.M.; Jett, P.L. [Oregon Health Sciences Univ. Portland, OR (United States)] [and others

    1994-09-01

    Cardiac conotruncal defects, such as Tetralogy of Fallot (TOF), are associated with DiGeorge syndrome which has been mapped to the q11 region of chromosome 22 and includes abnormalities of neural crest and branchial arch development. Patients with conotruncal defects and velo-cardio-facial syndrome may have defects in the 22q11 region but not show the complete DiGeorge phenotype consisting of cardiac, thymus, and parathyroid abnormalities. We report two neonates with TOF and small deletions in the DiGeorge region of chromosome 22 (46,XX,del(22)(q11.21q11.23) and 46,XY,del(22)(q11.2q11.2)) using both high-resolution cytogenetics and fluorescence in situ hybridization (FISH). The first patient is a female with TOF and a family history of congenital heart disease. The mother has pulmonic stenosis and a right-sided aortic arch, one brother has TOF, and a second brother has a large VSD. The patient had intrauterine growth retardation and had thrombocytopenia due to maternal IgG platelet-directed autoantibody. Lymphocyte populations, both T and B cells, were reduced in number but responded normally to stimulation. The findings were not attributed to a DiGeorge phenotype. Although she had transient neonatal hypocalcemia, her parathyroid hormone level was normal. The patient was not dysmorphic in the newborn period but her mother had features consistent with velo-cardio-facial syndrome. The second patient was a male with TOF who was not dysmorphic and had no other significant clinical findings and no family history of heart disease. Lymphocyte testing did not reveal a specific immunodeficiency. No significant postnatal hypocalcemia was noted. These cases illustrate that there is a wide spectrum of clinical features associated with defects of the 22q11 region. We recommend karyotype analysis, including FISH probes specific to the DiGeorge region, in any patient with conotruncal cardiac defects.

  3. Chromosome aberrations involving 10q22: report of three overlapping interstitial deletions and a balanced translocation disrupting C10orf11

    DEFF Research Database (Denmark)

    Tzschach, Andreas; Bisgaard, Anne-Marie; Kirchhoff, Maria; Graul-Neumann, Luitgard M; Neitzel, Heidemarie; Page, Stephanie; Ahmed, Alischo; Müller, Ines; Erdogan, Fikret; Ropers, Hans-Hilger; Kalscheuer, Vera M; Ullmann, Reinhard

    2010-01-01

    Interstitial deletions of chromosome band 10q22 are rare. We report on the characterization of three overlapping de novo 10q22 deletions by high-resolution array comparative genomic hybridization in three unrelated patients. Patient 1 had a 7.9 Mb deletion in 10q21.3-q22.2 and suffered from severe...... feeding problems, facial dysmorphisms and profound mental retardation. Patients 2 and 3 had nearly identical deletions of 3.2 and 3.6 Mb, the proximal breakpoints of which were located at an identical low-copy repeat. Both patients were mentally retarded; patient 3 also suffered from growth retardation...... and hypotonia. We also report on the results of breakpoint analysis by array painting in a mentally retarded patient with a balanced chromosome translocation 46,XY,t(10;13)(q22;p13)dn. The breakpoint in 10q22 was found to disrupt C10orf11, a brain-expressed gene in the common deleted interval of...

  4. Paracentric inversion of chromosome 2 associated with cryptic duplication of 2q14 and deletion of 2q37 in a patient with autism.

    OpenAIRE

    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

    2010-01-01

    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 confirm...

  5. The Involvement of Phosphatase and Tensin Homolog Deleted on Chromosome Ten (PTEN in the Regulation of Inflammation Following Coronary Microembolization

    Directory of Open Access Journals (Sweden)

    Jiangyou Wang

    2014-06-01

    Full Text Available Background/Aims: Growing evidence shows that phosphatase and tensin homolog deleted on chromosome ten (PTEN is involved in regulating inflammation in different pathological conditions. Therefore, we hypothesized that the upregulation of PTEN correlates with the impairment of cardiac function in swine following coronary microembolization (CME. Methods: To possibly disclose an anti-inflammatory effect of PTEN, we induced swine CME by injecting inertia plastic microspheres (42 μm in diameter into the left anterior descending coronary artery and analyzed the myocardial tissue by immunochemistry, qRT-PCR and western blot analyses. In addition, we downregulated PTEN using siRNA. Results: Following CME, PTEN mRNA and protein levels were elevated as early as 3 h, peaked at 12 h, and then continuously decreased at 24 h and 48 h but remained elevated. Through linear correlation analysis, the PTEN protein level positively correlated with cTnI and TNF-α but was negatively correlated with LVEF. Furthermore, PTEN siRNA reduced the microinfarct volume, improved cardiac function (LVEF, reduced the release of cTnI, and suppressed PTEN and TNF-α protein expression. Conclusion: This study demonstrated, for the first time, that PTEN is involved in CME-induced inflammatory injury. The data generated from this study provide a rationale for the development of PTEN-based anti-inflammatory strategies.

  6. From single nucleotide substitutions up to chromosomal deletions: genetic pause of leucism-associated disorders in animals.

    Science.gov (United States)

    Fleck, Katharina; Erhardt, Georg; Lühken, Gesine

    2016-01-01

    Leucism is characterized by a complete or partial white skin and hair in combination with pigmented irides, which can be vivid blue or heterochromatic. This is due to a complete or partial lack of melanocytes. The underlying pathogenesis is a disturbed emigration or differentiation of neural crest-derived cells. Therefore, leucistic phenotypes can be associated with defects, which mainly impair sensory organs and nerves. In humans, a well-known example is the Waardenburg syndrome. Leucism-associated disorders were also described in mouse, rat, hamster, rabbit, mink, cat, dog, pig, sheep, llama, alpaca, cattle and horse. In some of these species already identified causal mutations affect the genes EDN3, EDNRB, KIT, MITF, PAX3, SILV and SOX10. Defect alleles represent different types of genetic variation, ranging from single nucleotide substitutions up to larger chromosomal deletions. Some of the defect alleles produce desired coat color patterns. In some but not all cases, available genetic tests enable breeders to avoid production of animals affected by a leucism-associated disorder. PMID:27529988

  7. Site-specific deletions of chromosomally located DNA segments with the multimer resolution system of broad-host-range plasmid RP4

    DEFF Research Database (Denmark)

    Sternberg, Claus; Eberl, Leo; Sanchezromero, Juan M.;

    1995-01-01

    The multimer resolution system (mrs) of the broad-host-range plasmid RP4 has been exploited to develop a general method that permits the precise excision of chromosomal segments in a variety of gram-negative bacteria. The procedure is based on the site-specific recombination between two directly...... repeated 140-bp resolution (res) sequences of RP4 effected by the plasmid-borne resolvase encoded by the parA gene, The efficiency and accuracy of the mrs system to delete portions of chromosomal DNA flanked by res sites was monitored with hybrid mini-Tn5 transposons in which various colored (beta...... of the parA expression system suggested that just a few molecules of the resolvase are required to achieve the site-specific recombination event, Transient expression of parA from a plasmid unable to replicate in the target bacterium was instrumental to effect differential deletions within complex hybrid...

  8. Partial deletion 11q

    DEFF Research Database (Denmark)

    Hertz, Jens Michael; Tommerup, N; Sørensen, F B;

    1995-01-01

    We describe the cytogenetic findings and the dysmorphic features in a stillborn girl with a large de novo terminal deletion of the long arm of chromosome 11. The karyotype was 46,XX,del(11)(q21qter). By reviewing previous reports of deletion 11q, we found that cleft lip and palate are most...... frequently seen in proximal 11q deletions involving 11q21. Telomeric staining using the PRINS technique demonstrated normal telomeric sequences in the deleted chromosome 11....

  9. CANPMR syndrome and chromosome 1p32-p31 deletion syndrome coexist in two related individuals affected by simultaneous haplo-insufficiency of CAMTA1 and NIFA genes

    OpenAIRE

    Coci, Emanuele G.; Koehler, Udo; Liehr, Thomas; Stelzner, Armin; Fink, Christian; Langen, Hendrik; Riedel, Joachim

    2016-01-01

    Background Non-progressive cerebellar ataxia with mental retardation (CANPMR, OMIM 614756) and chromosome 1p32-p31 deletion syndrome (OMIM 613735) are two very rare inherited disorders, which are caused by mono-allelic deficiency (haplo-insufficiency) of calmodulin-binding transcription activator 1 (CAMTA1) and, respectively, nuclear factor 1 A (NFIA) genes. The yet reported patients affected by mono-allelic CAMTA1 dysfunction presented with neonatal hypotonia, delayed and ataxic gait, cerebe...

  10. Radiation susceptibility of the mouse smalleye mutants, Del(2)Sey3Hpax6 and Del(2)Sey4Hpax6, which delete the chromosome 2 middle regions

    International Nuclear Information System (INIS)

    Full text: LOH at the chromosome 2 middle regions is common in the radiation-induced mouse acute myeloid leukemia (AML). To identify the suppressor or the modifier gene of AML at this region, the mouse deletion mutants, Del(2)Sey3Hpax6and Del(2)Sey3Hpax6 could be the good models, as they deleted the chromosome 2 middle regions hemizygously. The allele of the partially deleted chromosome 2 was paternally generated and maintained hemizygously. The exact deleted regions of the two mutants were mapped by the PCR-based detection of polymorphism of the STS markers. The length of the deletions was 3.01Mb and 10.11MB for Del(2)Sey3Hpax6 and Del(2)Sey3Hpax6, respectively. For the induction of tumors, a radiation, 3.0Gy of Co-60 and a chemical carcinogen, N-methyl-N-nitrosourea were applied to the mutants. Their tumorigenicity was compared with those of control as well as normal sibs by the Kaplan-Meier analysis. Both mutants were found to predispose to small intestinal tumors. Intestinal tumors developed spontaneously with the incidence of 30%. The radiation and the chemical accelerated the malignancy and increased the incidence of the intestinal tumors. Radiation shortened the latency of AML development in the Del(2)Sey3Hpax6 mutant but not in the Del(2)Sey3Hpax6. Spontaneous AML has not been observed, nor any increase in the incidence of induced AMLs. The commonly deleted region of the two mutants, the 3.01Mb region, must be critical for the development of tumors and the high susceptibility to radiation. The role of Pax6 gene should be considered in the intestinal tumorigenesis, as the Pax6 gene plays an important role in the pancreas development during the embryogenesis. The Wt1, a tumor suppressor gene, which is deleted hemizygously in these mutants as well. The screening of homozygous deletion has been started using the induced as well as spontaneously developed tumors

  11. DMBT1, a new member of the SRCR superfamily, on chromosome 10q25.3-26.1 is deleted in malignant brain tumours

    DEFF Research Database (Denmark)

    Mollenhauer, J; Wiemann, S; Scheurlen, W;

    1997-01-01

    Loss of sequences from human chromosome 10q has been associated with the progression of human cancer. Medulloblastoma and glioblastoma multiforme are the most common malignant brain tumours in children and adults, respectively. In glioblastoma multiforme, the most aggressive form, 80% of the...... tumours show loss of 10q. We have used representational difference analysis to identify a homozygous deletion at 10q25.3-26.1 in a medulloblastoma cell line and have cloned a novel gene, DMBT1, spanning this deletion. DMBT1 shows homology to the scavenger receptor cysteine-rich (SRCR) superfamily....... Intragenic homozygous deletions has been detected in 2/20 medulloblastomas and in 9/39 glioblastomas multiformes. Lack of DMBT1 expression has been demonstrated in 4/5 brain-tumour cell lines. We suggest that DMBT1 is a putative tumour-suppressor gene implicated in the carcinogenesis of medulloblastoma and...

  12. Detailed deletion mapping in sporadic breast cancer at chromosomal region 17p13 distal to the TP53 gene: association with clinicopathological parameters.

    Science.gov (United States)

    Seitz, S; Poppe, K; Fischer, J; Nothnagel, A; Estévez-Schwarz, L; Haensch, W; Schlag, P M; Scherneck, S

    2001-07-01

    Chromosome 17p is among the most frequently deleted regions in a variety of human malignancies including breast cancer. This study has further refined the localization of a putative tumour suppressor gene (TSG) at 17p13 distal to the TP53 gene in breast carcinomas. It was found that 73% (37 of 51) of the breast tumours exhibited loss of heterozygosity (LOH) at one or more loci at 17p13. The allelic loss patterns of these tumours suggest the presence of at least seven commonly deleted regions on 17p13. The three most frequently deleted regions were mapped at chromosomal location 17p13.3-17p13.2 between the markers D17S831 and D17S1845 (56% LOH), at 17p13.1 between D17S1810 and D17S1832 (53% LOH), and at 17p13.1 between D17S938 and TP53 (55% LOH). A significant correlation was found between loss at 17p13 and tumour grade, size, proliferative activity, and oestrogen receptor (ER) status. Losses at 17p13 were seen more frequently in large and poorly differentiated tumours with high proliferative activity. These data support and extend previous reports on the presence of a putative TSG(s) at chromosomal region 17p13 distal to the TP53 gene and show that different subsets of LOH are associated with more aggressive tumour behaviour. PMID:11439364

  13. Radiation-induced chromosome aberrations in ataxia telangiectasia cells: high frequency of deletions and misrejoining detected by fluorescence in situ hybridization

    Science.gov (United States)

    Kawata, Tetsuya; Ito, Hisao; George, Kerry; Wu, Honglu; Uno, Takashi; Isobe, Kouichi; Cucinotta, Francis A.

    2003-01-01

    The mechanisms underlying the hyper-radiosensitivity of AT cells were investigated by analyzing chromosome aberrations in the G(2) and M phases of the cell cycle using a combination of chemically induced premature chromosome condensation (PCC) and fluorescence in situ hybridization (FISH) with chromosome painting probes. Confluent cultures of normal fibroblast cells (AG1522) and fibroblast cells derived from an individual with AT (GM02052) were exposed to gamma rays and allowed to repair at 37 degrees C for 24 h. At doses that resulted in 10% survival, GM02052 cells were approximately five times more sensitive to gamma rays than AG1522 cells. For a given dose, GM02052 cells contained a much higher frequency of deletions and misrejoining than AG1522 cells. For both cell types, a good correlation was found between the percentage of aberrant cells and cell survival. The average number of color junctions, which represent the frequency of chromosome misrejoining, was also found to correlate well with survival. However, in a similar surviving population of GM02052 and AG1522 cells, induced by 1 Gy and 6 Gy, respectively, AG1522 cells contained four times more color junctions and half as many deletions as GM02052 cells. These results indicate that both repair deficiency and misrepair may be involved in the hyper-radiosensitivity of AT cells.

  14. Coarctation of the aorta and mild to moderate developmental delay in a child with a de novo deletion of chromosome 15(q21.1q22.2)

    OpenAIRE

    Peters Sarika U; Sanders Merideth E; Sahoo Trilochan; Lalani Seema R; Bejjani Bassem A

    2006-01-01

    Abstract Background Deletion of 15q21q22 is a rare chromosomal anomaly. To date, there have been nine reports describing ten individuals with different segmental losses involving 15q21 and 15q22. Many of these individuals have common features of growth retardation, hypotonia and moderate to severe mental retardation. Congenital heart disease has been described in three individuals with interstitial deletion involving this region of chromosome 15. Case presentation We report a child with coarc...

  15. A 3.2Mb deletion on 18q12 in a patient with childhood autism and high-grade myopia

    DEFF Research Database (Denmark)

    Gilling, M.; Henriksen, K.F.; Lauritsen, M.B.;

    2008-01-01

    susceptibility genes through chromosome rearrangements, we investigated a female patient with childhood autism and high-grade myopia, and an apparently balanced de novo translocation, t(5; 18)(q34; q12.2). Further analyses revealed a 3.2Mb deletion encompassing 17 genes at the 18q break point and an additional...... deletion of 1.27Mb containing two genes on chromosome 4q35. Q-PCR analysis of 14 of the 17 genes deleted on chromosome 18 showed that 11 of these genes were expressed in the brain, suggesting that haploinsufficiency of one or more genes may have contributed to the childhood autism phenotype of the patient...

  16. Genome and gene alterations by insertions and deletions in the evolution of human and chimpanzee chromosome 22

    Directory of Open Access Journals (Sweden)

    Volfovsky Natalia

    2009-01-01

    Full Text Available Abstract Background Understanding structure and function of human genome requires knowledge of genomes of our closest living relatives, the primates. Nucleotide insertions and deletions (indels play a significant role in differentiation that underlies phenotypic differences between humans and chimpanzees. In this study, we evaluated distribution, evolutionary history, and function of indels found by comparing syntenic regions of the human and chimpanzee genomes. Results Specifically, we identified 6,279 indels of 10 bp or greater in a ~33 Mb alignment between human and chimpanzee chromosome 22. After the exclusion of those in repetitive DNA, 1,429 or 23% of indels still remained. This group was characterized according to the local or genome-wide repetitive nature, size, location relative to genes, and other genomic features. We defined three major classes of these indels, using local structure analysis: (i those indels found uniquely without additional copies of indel sequence in the surrounding (10 Kb region, (ii those with at least one exact copy found nearby, and (iii those with similar but not identical copies found locally. Among these classes, we encountered a high number of exactly repeated indel sequences, most likely due to recent duplications. Many of these indels (683 of 1,429 were in proximity of known human genes. Coding sequences and splice sites contained significantly fewer of these indels than expected from random expectations, suggesting that selection is a factor in limiting their persistence. A subset of indels from coding regions was experimentally validated and their impacts were predicted based on direct sequencing in several human populations as well as chimpanzees, bonobos, gorillas, and two subspecies of orangutans. Conclusion Our analysis demonstrates that while indels are distributed essentially randomly in intergenic and intronic genomic regions, they are significantly under-represented in coding sequences. There are

  17. Coarctation of the aorta and mild to moderate developmental delay in a child with a de novo deletion of chromosome 15(q21.1q22.2

    Directory of Open Access Journals (Sweden)

    Peters Sarika U

    2006-02-01

    Full Text Available Abstract Background Deletion of 15q21q22 is a rare chromosomal anomaly. To date, there have been nine reports describing ten individuals with different segmental losses involving 15q21 and 15q22. Many of these individuals have common features of growth retardation, hypotonia and moderate to severe mental retardation. Congenital heart disease has been described in three individuals with interstitial deletion involving this region of chromosome 15. Case presentation We report a child with coarctation of the aorta, partial agenesis of corpus callosum and mild to moderate developmental delay, with a de novo deletion of 15q21.1q22.2, detected by the array Comparative Genomic Hybridization (CGH. We utilized chromosome 15-specific microarray-based CGH to define the chromosomal breakpoints in this patient. Conclusion This is the first description of mapping of an interstitial deletion involving the chromosome 15q21q22 segment using the chromosome 15-specific array-CGH. The report also expands the spectrum of clinical phenotype associated with 15q21q22 deletion.

  18. Micromegakaryocytes in a patient with partial deletion of the long arm of chromosome 11 [del(11)(q24.2qter)] and chronic thrombocytopenic purpura

    Energy Technology Data Exchange (ETDEWEB)

    Gangarossa, S.; Mattina, T.; Romano, V.; Milana, G.; Mollica, F.; Schiliro, G. [Universita di Catania (Italy)

    1996-03-15

    Thrombocytopenia or pancytopenia is frequently reported in patients with partial 11q deletion but there are no reports on bone marrow morphology of these patients. We report on a patient with partial deletion of the long arm of chromosome 11 [del(11)(q24.2qter)] and its classical clinical manifestations including chronic thrombocytopenic purpura in whom micromegakaryocytes were found in the bone marrow aspirate. This is the first report of the presence of micromegakaryocytes in the bone marrow of a patient with 11q deletion. Accurate examination of the bone marrow of other patients with the 11q deletion may clarify whether the observation of micromegakaryocytes is common in these patients. Micromegakaryocytes may indicate a defect of development. Two genes for two DNA binding proteins that are likely to be involved in hematopoiesis map in the 11q region: Ets-1, that maps to 11q24, close to D11S912, and the nuclear-factor-related-kB gene that maps to 11q24-q25. It is possible that these genes, when present in only one copy, result in thrombocytopenia or pancytopenia as observed in this patient. 23 refs., 2 figs., 1 tab.

  19. Micromegakaryocytes in a patient with partial deletion of the long arm of chromosome 11 [del(11)(q24.2qter)] and chronic thrombocytopenic purpura.

    Science.gov (United States)

    Gangarossa, S; Mattina, T; Romano, V; Milana, G; Mollica, F; Schilirò, G

    1996-03-15

    Thrombocytopenia or pancytopenia is frequently reported in patients with partial 11q deletion but there are no reports on bone marrow morphology of these patients. We report on a patient with partial deletion of the long arm of chromosome 11 [del(11)(q24.2qter)] and its classical clinical manifestations including chronic thrombocytopenic purpura in whom micromegakaryocytes were found in the bone marrow aspirate. This is the first report of the presence of micromegakaryocytes in the bone marrow of a patient with 11q deletion. Accurate examination of the bone marrow of other patients with the 11q deletion may clarify whether the observation of micromegakaryocytes is common in these patients. Micromegakaryocytes may indicate a defect of development. Two genes for two DNA binding proteins that are likely to be involved in hematopoiesis map in the 11q region: Ets-1, that maps to 11q24, close to D11S912, and the nuclear-factor-related-kB gene that maps to 11q24-q25. It is possible that these genes, when present in only one copy, result in thrombocytopenia or pancytopenia as observed in this patient. PMID:8882392

  20. A 725 kb deletion at 22q13.1 chromosomal region including SOX10 gene in a boy with a neurologic variant of Waardenburg syndrome type 2.

    Science.gov (United States)

    Siomou, Elisavet; Manolakos, Emmanouil; Petersen, Michael; Thomaidis, Loretta; Gyftodimou, Yolanda; Orru, Sandro; Papoulidis, Ioannis

    2012-11-01

    Waardenburg syndrome (WS) is a rare (1/40,000) autosomal dominant disorder resulting from melanocyte defects, with varying combinations of sensorineural hearing loss and abnormal pigmentation of the hair, skin, and inner ear. WS is classified into four clinical subtypes (WS1-S4). Six genes have been identified to be associated with the different subtypes of WS, among which SOX10, which is localized within the region 22q13.1. Lately it has been suggested that whole SOX10 gene deletions can be encountered when testing for WS. In this study we report a case of a 13-year-old boy with a unique de novo 725 kb deletion within the 22q13.1 chromosomal region, including the SOX10 gene and presenting clinical features of a neurologic variant of WS2. PMID:22842075

  1. Sequencing of rhesus macaque Y chromosome clarifies origins and evolution of the DAZ (Deleted in AZoospermia) genes

    OpenAIRE

    Hughes, Jennifer F.; Skaletsky, Helen; Page, David C.

    2012-01-01

    Studies of Y chromosome evolution often emphasize gene loss, but this loss has been counterbalanced by addition of new genes. The DAZ genes, which are critical to human spermatogenesis, were acquired by the Y chromosome in the ancestor of Old World monkeys and apes. We and our colleagues recently sequenced the rhesus macaque Y chromosome, and comparison of this sequence to human and chimpanzee enables us to reconstruct much of the evolutionary history of DAZ. We report that DAZ arrived on the...

  2. Narrowing of the Hailey-Hailey disease gene region on chromosome 3q and identification of one kindred with a deletion in this region

    Energy Technology Data Exchange (ETDEWEB)

    Peluso, A.M.; Bonifas, J.M.; Ikeda, S.; Hu, Z. [Univ. of California, San Francisco, CA (United States)] [and others

    1995-11-01

    Hailey-Hailey disease is a cutaneous abnormality transmitted as an autosomal dominant trait in which impaired interkeratinocyte adhesion produces recurrent blisters in characteristic skin sites. We report here a confirmation of the initial mapping of the mutant gene to chromosome 3q in an additional seven kindreds, narrowing of the candidate region to the sequences flanked by D3S1589 and D3S1541, and the finding in one family of a genomic DNA deletion whose centromeric end is located between these two flanking markers. 6 refs., 2 figs.

  3. Microdeletion of 6q16.1 encompassing EPHA7 in a child with mild neurological abnormalities and dysmorphic features: case report

    Directory of Open Access Journals (Sweden)

    Rosenfeld Jill A

    2009-08-01

    Full Text Available Abstract Background Of the fewer than 100 cases reported within the literature of constitutional deletions involving the long arm of chromosome 6, only five have been characterized using high-resolution microarray analysis. Reported 6q deletion patients show a high incidence of mental retardation, ear anomalies, hypotonia, and postnatal growth retardation. Results We report a 16-month-old male presenting with developmental delay and dysmorphic features who was found by array-based comparative genomic hybridization (aCGH to have a ~2.16 Mb de novo deletion within chromosome band 6q16.1 that encompasses only two genes. Expression studies of the mouse homologue of one of the genes, the ephrin receptor 7 gene (EPHA7, have shown the gene functions during murine embryogenesis to form cortical domains, determine brain size and shape, and play a role in development of the central nervous system (CNS. Discussion Our results suggest that deletion of EPHA7 plays a role in the neurologic and dysmorphic features, including developmental delay, hypotonia, and ear malformations, observed in some 6q deletion patients.

  4. Concomitant deletion of chromosome 16p13.11 and triplication of chromosome 19p13.3 in a child with developmental disorders, intellectual disability, and epilepsy

    OpenAIRE

    Tassano, Elisa; De Santis, Lucia Rosaia; Corona, Maria Franca; Parmigiani, Stefano; Zanetti, Dalila; Porta, Simona; Gimelli, Giorgio; Cuoco, Cristina

    2015-01-01

    Background Rare copy number variations (CNVs) are today recognized as an important cause of various neurodevelopmental disorders, including mental retardation and epilepsy. In some cases, a second CNV may contribute to a more severe clinical presentation. Results Here we describe a patient with epilepsy, mental retardation, developmental disorders, and dysmorphic features, who inherited a deletion of 16p13.11 and a triplication of 19p13.3 from his father and mother, respectively. The mother p...

  5. Genome and gene alterations by insertions and deletions in the evolution of human and chimpanzee chromosome 22

    OpenAIRE

    Volfovsky Natalia; Oleksyk Taras K; Cruz Kristine C; Truelove Ann L; Stephens Robert M; Smith Michael W

    2009-01-01

    Abstract Background Understanding structure and function of human genome requires knowledge of genomes of our closest living relatives, the primates. Nucleotide insertions and deletions (indels) play a significant role in differentiation that underlies phenotypic differences between humans and chimpanzees. In this study, we evaluated distribution, evolutionary history, and function of indels found by comparing syntenic regions of the human and chimpanzee genomes. Results Specifically, we iden...

  6. Arterial Hypertension in a Child with Williams-Beuren Syndrome (7q11.23 Chromosomal Deletion

    Directory of Open Access Journals (Sweden)

    Cristina de Sylos

    2002-08-01

    Full Text Available We report the case of a 7-year-old male child diagnosed with Williams-Beuren syndrome and arterial hypertension refractory to clinical treatment. The diagnosis was confirmed by genetic study. Narrowing of the descending aorta and stenosis of the renal arteries were also diagnosed. Systemic vascular alterations caused by deletion of the elastin gene may occur early in individuals with Williams-Beuren syndrome, leading to the clinical manifestation of systemic arterial hypertension refractory to drug treatment.

  7. A cross-sectional study of the development of volitional control of spatial attention in children with chromosome 22q11.2 deletion syndrome

    Directory of Open Access Journals (Sweden)

    Shapiro Heather M

    2012-02-01

    Full Text Available Abstract Background Chromosome 22q11.2 deletion syndrome (22q11.2DS results from a 1.5- to 3-megabase deletion on the long arm of chromosome 22 and occurs in approximately 1 in 4000 live births. Previous studies indicate that children with 22q11.2DS are impaired on tasks involving spatial attention. However, the degree to which these impairments are due to volitionally generated (endogenous or reflexive (exogenous orienting of attention is unclear. Additionally, the efficacy of these component attention processes throughout child development in 22q11.2DS has yet to be examined. Methods Here we compared the performance of a wide age range (7 to 14 years of children with 22q11.2DS to typically developing (TD children on a comprehensive visual cueing paradigm to dissociate the contributions of endogenous and exogenous attentional impairments. Paired and two-sample t-tests were used to compare outcome measures within a group or between groups. Additionally, repeated measures regression models were fit to the data in order to examine effects of age on performance. Results We found that children with 22q11.2DS were impaired on a cueing task with an endogenous cue, but not on the same task with an exogenous cue. Additionally, it was younger children exclusively who were impaired on endogenous cueing when compared to age-matched TD children. Older children with 22q11.2DS performed comparably to age-matched TD peers on the endogenous cueing task. Conclusions These results suggest that endogenous but not exogenous orienting of attention is selectively impaired in children with 22q11.2DS. Additionally, the age effect on cueing in children with 22q11.2DS suggests a possible altered developmental trajectory of endogenous cueing.

  8. Interstitial deletion of the short arm of chromosome 3. Fetal pathology and exclusion of the gene for beta-galactosidase-1 (GLB-1) from 3(p11----p14.2)

    DEFF Research Database (Denmark)

    Hertz, Jens Michael; Coerdt, W; Hahnemann, N;

    1988-01-01

    A de novo interstitial deletion of the short arm of chromosome 3 was prenatally diagnosed in a male fetus, karyotype 46,XY,del(3)(pter----p14.2::p11----qter). The fetus had craniofacial dysmorphisms, a single transverse palmar crease, ulnar deviation in the wrists, cardiovascular anomalies, a...

  9. Complex chromosome rearrangement in a child with microcephaly, dysmorphic facial features and mosaicism for a terminal deletion del(18(q21.32-qter investigated by FISH and array-CGH: Case report

    Directory of Open Access Journals (Sweden)

    Kokotas Haris

    2008-11-01

    Full Text Available Abstract We report on a 7 years and 4 months old Greek boy with mild microcephaly and dysmorphic facial features. He was a sociable child with maxillary hypoplasia, epicanthal folds, upslanting palpebral fissures with long eyelashes, and hypertelorism. His ears were prominent and dysmorphic, he had a long philtrum and a high arched palate. His weight was 17 kg (25th percentile and his height 120 cm (50th percentile. High resolution chromosome analysis identified in 50% of the cells a normal male karyotype, and in 50% of the cells one chromosome 18 showed a terminal deletion from 18q21.32. Molecular cytogenetic investigation confirmed a del(18(q21.32-qter in the one chromosome 18, but furthermore revealed the presence of a duplication in q21.2 in the other chromosome 18. The case is discussed concerning comparable previously reported cases and the possible mechanisms of formation.

  10. Chromosomal aberration

    International Nuclear Information System (INIS)

    Chromosomal aberrations are classified into two types, chromosome-type and chromatid-type. Chromosom-type aberrations include terminal deletion, dicentric, ring and interstitial deletion, and chromatid-type aberrations include achromatic lesion, chromatid deletion, isochromatid deletion and chromatid exchange. Clastogens which induce chromosomal aberration are divided into ''S-dependent'' agents and ''S-independent''. It might mean whether they can induce double strand breaks independent of the S phase or not. Double strand breaks may be the ultimate lesions to induce chromosomal aberrations. Caffeine added even in the G2 phase appeared to modify the frequency of chromatid aberrations induced by X-rays and mitomycin C. Those might suggest that the G2 phase involves in the chromatid aberration formation. The double strand breaks might be repaired by ''G2 repair system'', the error of which might yield breakage types of chromatid aberrations and the by-pass of which might yield chromatid exchanges. Chromosome-type aberrations might be formed in the G1 phase. (author)

  11. Prenatal detection of short arm deletion and isochromosome 18 formation investigated by molecular techniques.

    OpenAIRE

    Qumsiyeh, M B; Tomasi, A; Taslimi, M

    1995-01-01

    A patient was referred for amniocentesis because of advanced maternal age and polyhydramnios. The fetal karyotype was a mosaic 46,XX,del(18)(p11.1)/46,XX,-18,+i(18q)de novo. The deletion appeared to encompass the whole short arm as evidenced by G banding and in situ hybridisation. However, telomere sequences were found on both ends of the deleted chromosome as well as the isochromosome. The normal 18 and the isochromosome showed more alphoid sequences than the del(18). Subsequent passages of ...

  12. A cross-sectional analysis of the development of response inhibition in children with Chromosome 22q11.2 Deletion Syndrome

    Directory of Open Access Journals (Sweden)

    Heather M Shapiro

    2013-08-01

    Full Text Available Chromosome 22q11.2 Deletion Syndrome (22q11.2DS is a neurogenetic disorder that is associated with cognitive impairments and significantly elevated risk for developing schizophrenia. While impairments in response inhibition are central to executive dysfunction in schizophrenia, the nature and development of such impairments in children with 22q11.2DS, a group at high risk for the disorder, are not clear. Here we used a classic Go/No-Go paradigm to quantify proactive (anticipatory stopping and reactive (actual stopping response inhibition in 47 children with 22q11.2DS and 36 typically developing (TD children, all ages 7-14. A cross-sectional design was used to examine age-related associations with response inhibition. When compared with TD individuals, children with 22q11.2DS demonstrated typical proactive response inhibition at all ages. By contrast, reactive response inhibition was impaired in children with 22q11.2DS relative to TD children. While older age predicted better reactive response inhibition in TD children, there was no age-related association with reactive response inhibition in children with 22q11.2DS. Closer examination of individual performance data revealed a wide range of performance abilities in older children with 22q11.2DS; some typical and others highly impaired. The results of this cross-sectional analysis suggest an impaired developmental trajectory of reactive response inhibition in some children with 22q11.2DS that might be related to atypical development of neuroanatomical systems underlying this cognitive process. As part of a larger study, this investigation might help identify risk factors for conversion to schizophrenia and lead to early diagnosis and preventive intervention.

  13. Microdeletion del(22(q12.2 encompassing the facial development-associated gene, MN1 (meningioma 1 in a child with Pierre-Robin sequence (including cleft palate and neurofibromatosis 2 (NF2: a case report and review of the literature

    Directory of Open Access Journals (Sweden)

    Davidson Tom B

    2012-03-01

    Full Text Available Abstract Background Pierre-Robin sequence (PRS is defined by micro- and/or retrognathia, glossoptosis and cleft soft palate, either caused by deformational defect or part of a malformation syndrome. Neurofibromatosis type 2 (NF2 is an autosomal dominant syndrome caused by mutations in the NF2 gene on chromosome 22q12.2. NF2 is characterized by bilateral vestibular schwannomas, spinal cord schwannomas, meningiomas and ependymomas, and juvenile cataracts. To date, NF2 and PRS have not been described together in the same patient. Case presentation We report a female with PRS (micrognathia, cleft palate, microcephaly, ocular hypertelorism, mental retardation and bilateral hearing loss, who at age 15 was also diagnosed with severe NF2 (bilateral cerebellopontine schwannomas and multiple extramedullary/intradural spine tumors. This is the first published report of an individual with both diagnosed PRS and NF2. High resolution karyotype revealed 46, XX, del(22(q12.1q12.3, FISH confirmed a deletion encompassing NF2, and chromosomal microarray identified a 3,693 kb deletion encompassing multiple genes including NF2 and MN1 (meningioma 1. Five additional patients with craniofacial dysmorphism and deletion in chromosome 22-adjacent-to or containing NF2 were identified in PubMed and the DECIPHER clinical chromosomal database. Their shared chromosomal deletion encompassed MN1, PITPNB and TTC28. MN1, initially cloned from a patient with meningioma, is an oncogene in murine hematopoiesis and participates as a fusion gene (TEL/MN1 in human myeloid leukemias. Interestingly, Mn1-haploinsufficient mice have abnormal skull development and secondary cleft palate. Additionally, Mn1 regulates maturation and function of calvarial osteoblasts and is an upstream regulator of Tbx22, a gene associated with murine and human cleft palate. This suggests that deletion of MN1 in the six patients we describe may be causally linked to their cleft palates and/or craniofacial

  14. 摩洛哥男性Y染色体的AZF微缺失和AZFc区域的部分缺失%AZF microdeletions and partial deletions of AZFc region on the Y chromosome in Moroccan men

    Institute of Scientific and Technical Information of China (English)

    L.Imken; M.Hassar; K. McElreavey; A.Barakat; H.Rouba; B.El Houate; A.Chafik; H. Nahili; R.Boulouiz; O.Abidi; E.Chadli; N.Louanjli; A.Elfath

    2007-01-01

    Aim: To evaluate for the first time the frequency of Y chromosome microdeletions and the occurrence of the partial deletions of AZFc region in Moroccan men, and to discuss the clinical significance of AZF deletions. Methods: We screened Y chromosome microdeletions and partial deletions of the AZFc region of a consecutive group of infertile men (n = 149) and controls (100 fertile men, 76 normospermic men). AZFa, AZFb, AZFc and partial deletions of the AZFc region were analyzed by polymerase chain reaction (PCR) according to established protocols. Results: Among the 127 infertile men screened for microdeletion, four subjects were found to have microdeletions: two AZFc deletions and two AZFb+AZFc deletions. All the deletions were found only in azoospermic subjects (4/48, 8.33%). The overall AZFc deletion frequency was low (4/127, 3.15%). AZF microdeletions were not observed in either oligoasthenoteratozoospermia (OATS) or the control. Partial deletions of AZFc (gr/gr) were observed in a total of 7 of the 149 infertile men (4.70%) and 7 partial AZFc deletions (gr/gr) were found in the control group (7/176, 3.98%).In addition, two b2/b3 deletions were identified in two azoospermic subjects (2/149, 1.34%) but not in the control group. Conclusion: Our results suggest that the frequency of Y chromosome AZF microdeletions is elevated in individuals with severe spermatogenic failure and that gr/gr deletions are not associated with spermatogenic failure.(Asian J Androl 2007 Sep; 9: 674-678)%目的:首次评价摩洛哥男性Y染色体微缺失和部分AZFc部分缺失的发生频率并讨论AZF缺失的临床意义.方法:我们筛选了不育组(n=149)和对照组(100名可育男性,76名精子正常男性)的Y染色体微缺失和AZFc区部分缺失的情况.根据已建立的方法用PCR分析AZFa、AZFb、AZFc和AZFc部分缺失的区域.结果:在127名不孕男性中进行了微缺失的筛选,其中4例有微缺失:二例AZFc缺失,二例AZFb+AZFc

  15. Third case of 8q23.3-q24.13 deletion in a patient with Langer-Giedion syndrome phenotype without TRPS1 gene deletion.

    Science.gov (United States)

    Pereza, Nina; Severinski, Srećko; Ostojić, Saša; Volk, Marija; Maver, Aleš; Dekanić, Kristina Baraba; Kapović, Miljenko; Peterlin, Borut

    2012-03-01

    Langer-Giedion syndrome (LGS) is a contiguous gene syndrome caused by a hemizygous deletion on chromosome 8q23.3-q24.11 involving TRPS1 and EXT1 genes. We report on a girl with LGS phenotype and a 7.5 Mb interstitial deletion at chromosome 8q23.3-q24.13. Array-comparative genomic hybridization (a-CGH) revealed a deletion encompassing only the EXT1 and not the TRPS1 gene. Even though the deletion of TRPS1 and EXT1 genes is responsible for craniofacial and skeletal features of LGS, there have been previous reports of patients with LGS phenotype and 8q24 deletions leaving the TRPS1 gene intact. To our knowledge, this is the third such case. Our patient differs from previously reported LGS patients without TRPS1 gene deletion in that she has the typical LGS facial dysmorphism and skeletal abnormalities. However, the girl is of normal height and has only a mild developmental delay. Additionally, she has dyslalia and premature adrenarche classified as Tanner stage 3 premature pubarche which have not yet been described as features of LGS. We examine the molecular breakpoints and phenotypes of our patient and previously reported cases. PMID:22315192

  16. Clinical, cytogenetic, and molecular outcomes in a series of 66 patients with Pierre Robin sequence and literature review: 22q11.2 deletion is less common than other chromosomal anomalies.

    Science.gov (United States)

    Gomez-Ospina, Natalia; Bernstein, Jonathan A

    2016-04-01

    Pierre Robin sequence (PRS) is an important craniofacial anomaly that can be seen as an isolated finding or manifestation of multiple syndromes. 22q11.2 deletion and Stickler syndrome are cited as the two most common conditions associated with PRS, but their frequencies are debated. We performed a retrospective study of 66 patients with PRS and reviewed their genetic testing, diagnoses, and clinical findings. The case series is complemented by a comprehensive literature review of the nature and frequency of genetic diagnosis in PRS. In our cohort 65% of patients had associated anomalies; of these, a genetic diagnosis was established in 56%. Stickler syndrome was the most common diagnosis, comprising approximately 11% of all cases, followed by Treacher Collins syndrome (9%). The frequency of 22q11.2 deletion was 1.5%. Chromosome arrays, performed for 72% of idiopathic PRS with associated anomalies, revealed two cases of 18q22→qter deletion, a region not previously reported in association with PRS. A review of the cytogenetic anomalies identified in this population supports an association between the 4q33-qter, 17q24.3, 2q33.1, and 11q23 chromosomal loci and PRS. We found a low frequency of 22q11.2 deletion in PRS, suggesting it is less commonly implicated in this malformation. Our data also indicate a higher frequency of cytogenetic anomalies in PRS patients with associated anomalies, and a potential new link with the 18q22→qter locus. The present findings underscore the utility of chromosomal microarrays in cases of PRS with associated anomalies and suggest that delaying testing for apparently isolated cases should be considered. © 2016 Wiley Periodicals, Inc. PMID:26756138

  17. Atypical Rett syndrome with selective FOXG1 deletion detected by comparative genomic hybridization: case report and review of literature

    OpenAIRE

    Jacob, Francois Dominique; Ramaswamy, Vijay; Andersen, John; Bolduc, Francois V.

    2009-01-01

    Rett syndrome is a severe neurodegenerative disorder characterized by acquired microcephaly, communication dysfunction, psychomotor regression, seizures and stereotypical hand movements. Mutations in methyl CpG binding protein 2 (MECP2) are identified in most patients with classic Rett syndrome. Genetic studies in patients with a Rett variant have expanded the spectrum of underlying genetic etiologies. Recently, a deletion encompassing several genes in the long arm of chromosome 14 has been a...

  18. Expression of phosphatase and tensin homolog deleted on chromosome ten in liver of athymic mice with hepatocellular carcinoma and the effect of Fuzheng Jiedu Decoction

    Institute of Scientific and Technical Information of China (English)

    Li-Rong Yin; Ze-Xiong Chen; Shi-Jun Zhang; Bao-Guo Sun; Yong-Dong Liu; Hong-Zhong Huang

    2008-01-01

    AIM:To explore the expression of phosphatase and tensin homolog deleted on chromosome ten (PTEN) in liver of athymic mice with hepatocellular carcinoma (HCC) and the effect of Fuzheng Jiedu Decoction (FJD). METHODS: Forty eight male BALB/c athymic mice models were built by Bel-7402 with an indirect method. After 24 h of postoperation, the 48 athymic mice were distributed randomly into 4 groups: A, B, C, D, each group had 12 athymic mice. Group A were were treated by intragastric administration with FT207 (Tegafur) for 4 wk. Group B, C and D were treated by intragastric administration with FJD (complex prescription of Chinese crude drug) that had been delegated into 3 kinds of density as the low, middle, and high for 4 wk. At last,athymic mice were put to death, live time, volume of tumors, exponent of tumors and the tumor metastasis in livers were observed; and PTEN was detected in hepatic tissue, latero-cancer tissue and cancer tissue by immunohistochemistry.RESULTS: Four weeks later, the total survival rate in treatment group (A + B + C) was 50% and higher than the control group (0%) treated by FT207, (P 0.05). Tumor metastasis in livers of the treatment group was less than the controls (Fisher's Exact Test, P = 0.021). Thee result of immunohistochemistry showed that the intensity of PTEN in latero-cancer tissue was the highest, and then the hepatic tissue, the lowest was cancer tissue (Kruskal- Wallis test, .67, P = 0.000). It also showed that the intensity of PTEN in treatment groups (A, B, C) was higher than the control group (D) (F = 5.90,P = 0.002 in hepatic tissue and F = 15.99, P = 0.000 in latero-cancer tissue and .08, P = 0.000 in cancer tissue), and group B is the highest in the treatment groups (P 0.05).CONCLUSION: FJD can prolong the survival time and decrease tumor metastasis in livers of these experimental mice. Mechanisms of FJD healing HCC may partially be explained by enhancing the expression of PTEN in liver.

  19. Phenotype and 244k array-CGH characterization of chromosome 13q deletions: an update of the phenotypic map of 13q21.1-qter

    DEFF Research Database (Denmark)

    Kirchhoff, Maria; Bisgaard, Anne-Marie; Stoeva, Radka;

    2009-01-01

    breakpoints in 14 patients with partial deletions of this region. Subsequently, we linked the genotype to the patient's phenotype. Using this approach, we were able to refine the smallest deletion region linked to short stature (13q31.3: 89.5-91.6 Mb), microcephaly (13q33.3-q34), cortical development...

  20. Variants in linkage disequilibrium with the late cornified envelope gene cluster deletion are associated with susceptibility to psoriatic arthritis.

    LENUS (Irish Health Repository)

    Bowes, John

    2010-12-01

    A common deletion mapping to the psoriasis susceptibility locus 4 on chromosome 1q21, encompassing two genes of the late cornified envelope (LCE) gene cluster, has been associated with an increased risk of psoriasis vulgaris (PsV). One previous report found no association of the deletion with psoriatic arthritis (PsA), suggesting it may be a specific risk factor for PsV. Given the genetic overlap between PsA and PsV, a study was undertaken to investigate whether single nucleotide polymorphisms (SNPs) mapping to this locus are risk factors for PsA in a UK and Irish population.

  1. One case of chromosome 16 p11 . 2 deletion syndrome and literature review%16 p11.2缺失综合征1例并文献复习

    Institute of Scientific and Technical Information of China (English)

    葛婷; 崔云; 肖咏梅; 陆燕芬; 张育才; 张婷

    2014-01-01

    Objective To enhance the understanding of clinical characteristics,diagnosis,follow-up and genetic testing of chromosome 16p11. 2 deletion syndrome. Methods The clinical manifestations,laboratory testing,diagnosis,follow-up,and genetic testing of one case with chromosome 16p11. 2 deletion syndrome were reviewed,analyzed and summarized. Meanwhile,relevant literatures of chromosome 16p11. 2 deletion syndrome were reviewed in this article. Results ①A 2-month-and-13-day boy with 20-day fever,cough,and diarrhea was admitted to our hospital. Deformity of six fingers in right palm and scoliosis was found. The total peripheral blood lymphocytes and lymphocyte subsets were lower than the reference levels. Chest X-ray indicated that the sternum shape was abnormal and T9-T12 vertebral bodies were hemivertebrae deformity. The patient was improved with a hyperactive and exciting performance after anti-infection therapy. Follow up after releasing indicated that the count of peripheral blood lymphocytes was improved,however,WBC,N and CD4+ T cells remained low levels. The boy was diagnosed as epilepsy at 5 months old and improved after treatment with anti-epileptic drugs. A deletion of 0. 545 4 Mb in chromosome 16p11. 2 was identified by chromosome chip detection technology and confirmed by high-density oligonucleotide comparative genomic hybridization( CGH)Microarray. The genes located in this deleted region included SPN,QRRT,Cl6orf54,KIF22,MAZ,SEZ6L2,CDIPT,ASPHDl,KCTDl3, TMEM2l9,TAOK2,DOC2A,TBX6. The results of Chromosome chip detection were normal in his parents. Thus,this boy was finally diagnosed as chromosome 16p11. 2 deletion syndrome. ②1 387cases were reported by 95 published articles related with chromosome 16p11. 2 deletion syndrome,involving the nervous system(547,39. 7%),endocrine system(371,26. 9%),growth and skeletal abnormalities(84,6. 1%),urinary and digestive system(10,0. 7%),cardiovascular system(4,0. 3%),immune function(1,0. 07%). The different size of the

  2. Adults with Chromosome 18 Abnormalities.

    Science.gov (United States)

    Soileau, Bridgette; Hasi, Minire; Sebold, Courtney; Hill, Annice; O'Donnell, Louise; Hale, Daniel E; Cody, Jannine D

    2015-08-01

    The identification of an underlying chromosome abnormality frequently marks the endpoint of a diagnostic odyssey. However, families are frequently left with more questions than answers as they consider their child's future. In the case of rare chromosome conditions, a lack of longitudinal data often makes it difficult to provide anticipatory guidance to these families. The objective of this study is to describe the lifespan, educational attainment, living situation, and behavioral phenotype of adults with chromosome 18 abnormalities. The Chromosome 18 Clinical Research Center has enrolled 483 individuals with one of the following conditions: 18q-, 18p-, Tetrasomy 18p, and Ring 18. As a part of the ongoing longitudinal study, we collect data on living arrangements, educational level attained, and employment status as well as data on executive functioning and behavioral skills on an annual basis. Within our cohort, 28 of the 483 participants have died, the majority of whom have deletions encompassing the TCF4 gene or who have unbalanced rearrangement involving other chromosomes. Data regarding the cause of and age at death are presented. We also report on the living situation, educational attainment, and behavioral phenotype of the 151 participants over the age of 18. In general, educational level is higher for people with all these conditions than implied by the early literature, including some that received post-high school education. In addition, some individuals are able to live independently, though at this point they represent a minority of patients. Data on executive function and behavioral phenotype are also presented. Taken together, these data provide insight into the long-term outcome for individuals with a chromosome 18 condition. This information is critical in counseling families on the range of potential outcomes for their child. PMID:25403900

  3. Prader-Willi syndrome - type 1 deletion, a consequence of an unbalanced translocation of chromosomes 13 and 15, easily to be mixed up with a Robertsonian translocation

    OpenAIRE

    Sheth, Frenny; Liehr, Thomas; Shah, Krati; Sheth, Jayesh

    2015-01-01

    Background Prader-Willi syndrome, due to microdeletion of proximal 15q, is a well-known cause of syndromic obesity. Case characteristics A couple with history of repeated first trimester abortions had a son with balanced Robertsonian translocation of chromosomes 13 and 15 according to cytogenetic banding technique. Results Chromosomal analysis for the couple was performed. A balanced translocation involving BP1-BP3 region of proximal 15q was observed in the father. Discussion Investigations o...

  4. Interstitial deletion of chromosome 1q [del(1)(q24q25.3)] identified by fluorescence in situ hybridization and gene dosage analysis of apolipoprotein A-II, coagulation factor V, and antithrombin III

    Energy Technology Data Exchange (ETDEWEB)

    Takano, Takako; Yamanouchi, Yasuko; Mori, Yosuke [Teikyo Univ. School of Medicine, Tokyo (Japan)] [and others

    1997-01-20

    We report on a 12-month-old Japanese boy with an interstitial deletion of the long-arm of chromosome 1 and meningomyelocele, hydrocephalus, anal atresia, atrial septal defect, left renal agenesis, bilateral cryptorchidism, talipes equinovarus, low birth weight, growth/developmental retardation, and many minor anomalies. By conventional GTG-banding, his karyotype was first interpreted as 46,XY,de1(1)(q23q24), but it was corrected as 46,XY.ish del(1)(q24q25.3) by fluorescence in situ hybridization using 11 known cosmid clones as probes. His serum levels of apolipoprotein A-II (gene symbol: APOA2, previously assigned to 1q21-q23) and coagulation factor V (F5, 1q21-q25) were normal, while serum concentration and activity of antithrombin III (AT3, 1q23-q25.1) was low. The results indicated that localization of APOA2 and F5 are proximal to the deleted region and AT3 is located within the deletion extent in the patient. 16 refs., 4 figs.

  5. Chromosome Deletion of 14q32.33 Detected by Array Comparative Genomic Hybridization in a Patient with Features of Dubowitz Syndrome

    Directory of Open Access Journals (Sweden)

    Diana C. Darcy

    2011-01-01

    Full Text Available We report a 4-year-old girl of Mexican origins with a clinical diagnosis of Dubowitz syndrome who carries a de novo terminal deletion at the 14q32.33 locus identified by array comparative genomic hybridization (aCGH. Dubowitz syndrome is a rare condition characterized by a constellation of features including growth retardation, short stature, microcephaly, micrognathia, eczema, telecanthus, blepharophimosis, ptosis, epicanthal folds, broad nasal bridge, round-tipped nose, mild to moderate developmental delay, and high-pitched hoarse voice. This syndrome is thought to be autosomal recessive; however, the etiology has not been determined. This is the first report of this deletion in association with this phenotype; it is possible that this deletion may be causal for a Dubowitz phenocopy.

  6. Association of the Family Environment with Behavioural and Cognitive Outcomes in Children with Chromosome 22q11.2 Deletion Syndrome

    Science.gov (United States)

    Allen, T. M.; Hersh, J.; Schoch, K.; Curtiss, K.; Hooper, S. R.; Shashi, V.

    2014-01-01

    Background: Children with 22q11.2 deletion syndrome (22q11DS) are at risk for social-behavioural and neurocognitive sequelae throughout development. The current study examined the impact of family environmental characteristics on social-behavioural and cognitive outcomes in this paediatric population. Method: Guardians of children with 22q11DS…

  7. Sons conceived by assisted reproduction techniques inherit deletions in the azoospermia factor (AZF) region of the Y chromosome and the DAZ gene copy number

    DEFF Research Database (Denmark)

    Mau Kai, C; Juul, A; McElreavey, K;

    2008-01-01

    number, supplemented with haplogroup typing in deleted patients, were performed, in combination with clinical assessments in 264 fathers and their sons conceived by assisted reproduction techniques (ART), and in 168 fertile men with normal sperm concentration. RESULTS: In the ART fathers group, a...

  8. Molecular cytogenetic and phenotypic characterization of ring chromosome 13 in three unrelated patients

    Science.gov (United States)

    Abdallah-Bouhjar, Inesse B.; Mougou-Zerelli, Soumaya; Hannachi, Hanene; Gmidène, Abir; Labalme, Audrey; Soyah, Najla; Sanlaville, Damien; Saad, Ali; Elghezal, Hatem

    2013-01-01

    We report on the cytogenetic and molecular investigations of constitutional de-novo ring chromosome 13s in three unrelated patients for better understanding and delineation of the phenotypic variability characterizing this genomic rearrangement. The patient’s karyotypes were as follows: 46,XY,r(13)(p11q34) dn for patients 1 and 2 and 46,XY,r(13)(p11q14) dn for patient 3, as a result of the deletion in the telomeric regions of chromosome 13. The patients were, therefore, monosomic for the segment 13q34 → 13qter; in addition, for patient 3, the deletion was larger, encompassing the segment 13q14 → 13qter. Fluorescence in situ hybridization confirmed these rearrangement and array CGH technique showed the loss of at least 2.9 Mb on the short arm and 4.7 Mb on the long arm of the chromosome 13 in patient 2. Ring chromosome 13 (r(13)) is associated with several phenotypic features like intellectual disability, marked short stature, brain and heart defects, microcephaly and genital malformations in males, including undescended testes and hypospadias. However, the hearing loss and speech delay that were found in our three patients have rarely been reported with ring chromosome 13. Although little is known about its etiology, there is interesting evidence for a genetic cause for the ring chromosome 13. We thus performed a genotype-phenotype correlation analysis to ascertain the contribution of ring chromosome 13 to the clinical features of our three cases.

  9. Clinical impact of ABL1 kinase domain mutations and IKZF1 deletion in adults under age 60 with Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL): molecular analysis of CALGB (Alliance) 10001 and 9665.

    Science.gov (United States)

    DeBoer, Rebecca; Koval, Gregory; Mulkey, Flora; Wetzler, Meir; Devine, Steven; Marcucci, Guido; Stone, Richard M; Larson, Richard A; Bloomfield, Clara D; Geyer, Susan; Mullighan, Charles G; Stock, Wendy

    2016-10-01

    Recent studies have identified oncogenic lesions in Philadelphia chromosome-positive (Ph+)  acute lymphoblastic leukemia (ALL) and ABL1 kinase mutations that confer resistance to tyrosine kinase inhibitors. We sought to determine the prevalence and clinical impact of these lesions in patients on CALGB 10001, a previously reported Phase II study of imatinib, chemotherapy, and hematopoietic cell transplant in adult Ph + ALL. Of the 58 enrolled, 22 relapsed. By direct sequencing, an ABL1 kinase mutation known to induce imatinib resistance was present at relapse in 13 of 20. Using quantitative PCR assays, the mutations were detectable at diagnosis or early during treatment in most (62%) relapsed patients. Aberrations in IKZF1, CDKN2A/B, and PAX5 were assessed in 28 samples using SNP arrays and genomic DNA sequencing. Of these, 22 (79%) had IKZF1 deletion. The combination of IKZF1 deletion and p210 BCR-ABL1 (p < 0.0001), high white blood cell count (p = 0.021), and minimal residual disease (p = 0.013) were associated with worse disease-free survival. PMID:26892479

  10. Nuclear gene causing multiple mtDNA deletions in autosomal dominant ophthalmoplegia maps to a distinct chromosomal region - involvement of both nuclear and mitochondrial DNA in a single disorder

    Energy Technology Data Exchange (ETDEWEB)

    Suomalainen, A.; Kaukonen, J.; Timonen, R. [Univ. of Helsinki (Finland)] [and others

    1994-09-01

    Autosomal dominant progressive external ophthalmoplegia (adPEO) is a mitochondrial disease characterized by muscle weakness, most prominent in ocular muscles. The symptoms are caused by accumulation of multiple large deletions of mitochondrial DNA (mtDNA) in the tissues of the patient, especially in those tissues that are most dependent on oxidative metabolism: brain, skeletal muscle and heart. However, the disorder shows autosomal dominant way of transmission, suggesting a primary defect in a nuclear encoded protein, which only secondarily results in mtDNA deletions. The candidate genes could be those actively participating in the mtDNA replication, or those associated with oxidative metabolism and e.g. via overproduction or inefficient elimination of fire oxygen radicals fragmenting mtDNA. We applied random mapping approach to localize the autosomal adPEO gene locus in a large Finnish family. The affected subjects were identified by detection of multiple mtDNA deletions in the Southern blot analysis of DNA extracted from the muscle biopsy specimens. All the family members underwent muscle biopsy. After analysis of 248 highly polymorphic dinucleotide repeat markets dispersed throughout the genome we were able to assign the adPEO gene locus to a distinct chromosomal region with the maximum pairwise lod score of 4.52, recombination fraction 0.0. This is the first evidence that a mutation in a nuclear gene may interfere mtDNA. The pathogenesis of adPEO involves both the genomes: the primary nuclear gene defect leads to secondary mtDNA mutations that cause the symptoms of the patients.

  11. Characterisation of two deletions involving NPC1 and flanking genes in Niemann-Pick type C disease patients.

    Science.gov (United States)

    Rodríguez-Pascau, Laura; Toma, Claudio; Macías-Vidal, Judit; Cozar, Mónica; Cormand, Bru; Lykopoulou, Lilia; Coll, Maria Josep; Grinberg, Daniel; Vilageliu, Lluïsa

    2012-12-01

    Niemann-Pick type C (NPC) disease is an autosomal recessive lysosomal disorder characterised by the accumulation of a complex pattern of lipids in the lysosomal-late endosomal system. More than 300 disease-causing mutations have been identified so far in the NPC1 and NPC2 genes, including indel, missense, nonsense and splicing mutations. Only one genomic deletion, of more than 23 kb, has been previously reported. We describe two larger structural variants, encompassing NPC1 and flanking genes, as a cause of the disease. QMPSF, SNP inheritance and CytoScan® HD Array were used to confirm and further characterise the presence of hemizygous deletions in two patients. One of the patients (NPC-57) bore a previously described missense mutation (p.T1066N) and an inherited deletion that included NPC1, C18orf8 and part of ANKRD29 gene. The second patient (NPC-G1) had a 1-bp deletion (c.852delT; p.F284Lfs*26) and a deletion encompassing the promoter region and exons 1-10 of NPC1 and the adjacent ANKRD29 and LAMA3. This study characterised two novel chromosomal microdeletions at 18q11-q12 that cause NPC disease and provide insight into missing NPC1 mutant alleles. PMID:23142039

  12. Copy number variations due to large genomic deletion in X-linked chronic granulomatous disease.

    Directory of Open Access Journals (Sweden)

    Takashi Arai

    Full Text Available Mutations in genes for any of the six subunits of NADPH oxidase cause chronic granulomatous disease (CGD, but almost 2/3 of CGD cases are caused by mutations in the X-linked CYBB gene, also known as NAD (P H oxidase 2. Approximately 260 patients with CGD have been reported in Japan, of whom 92 were shown to have mutations of the CYBB gene and 16 to have chromosomal deletions. However, there has been very little detailed analysis of the range of the deletion or close understanding of the disease based on this. We therefore analyzed genomic rearrangements in X-linked CGD using array comparative genomic hybridization analysis, revealing the extent and the types of the deletion genes. The subjects were five Japanese X-linked CGD patients estimated to have large base deletions of 1 kb or more in the CYBB gene (four male patients, one female patient and the mothers of four of those patients. The five Japanese patients were found to range from a patient exhibiting deletions only of the CYBB gene to a female patient exhibiting an extensive DNA deletion and the DMD and CGD phenotype manifested. Of the other three patients, two exhibited CYBB, XK, and DYNLT3 gene deletions. The remaining patient exhibited both a deletion encompassing DNA subsequent to the CYBB region following intron 2 and the DYNLT3 gene and a complex copy number variation involving the insertion of an inverted duplication of a region from the centromere side of DYNLT3 into the deleted region.

  13. Chromosome 13q deletion and IgH abnormalities may be both masked by near-tetraploidy in a high proportion of multiple myeloma patients: a combined morphology and I-FISH analysis.

    Science.gov (United States)

    Koren-Michowitz, Maya; Hardan, Izhar; Berghoff, Janina; Yshoev, Galina; Amariglio, Ninette; Rechavi, Gideon; Nagler, Arnon; Trakhtenbrot, Luba

    2007-10-01

    Ploidy status and chromosomal aberrations involving chromosome 13q and the immunoglobulin heavy chain locus (IgH) are important prognostic features in multiple myeloma (MM). However, conventional cytogenetic studies are often not reveling and determination of plasma cells (PC) ploidy status in MM is technically difficult. We have used a combined cell morphology and interphase FISH (I-FISH) analysis in 184 consecutive BM samples from 136 MM patients for the diagnosis of chromosome 13q deletion [del (13q)] and IgH abnormalities. We have found a high prevalence (37%) of near-tetraploid (NT) PC in the BM samples studied. NT status of PC was verified with DNA index (DI) measurements. del (13q) was found in 69% and a total absence of one IgH copy (loss of IgH) in 20% of NT samples. We have shown that the presence of del (13q) and loss of IgH can be masked in NT cases: in 12 NT samples originally identified as normal for del (13q) the abnormality was obscured in the majority of plasma cells due to the presence of NT. Similarly, loss of IgH was masked in four samples with a large population of NT cells. Moreover, in one case the appearance of a 100% tetraploidy during disease progression masked the presence of del (13q), originally present, and could therefore falsely appear as disappearance of this prognostic marker. In conclusion, we have shown that a combination of three abnormalities, i.e., del (13q), loss of IgH and NT, all of potential prognostic significance, can be overlooked unless NT is specifically searched for and ruled out. Therefore, we suggest that a search for NT should be added to the routine BM assessment in MM patients. PMID:17590504

  14. Correlation between chromosome deletion and phenotypes in two cases of ring chromosome 6 syndrome%二例环6号染色体综合征病例染色体缺失片段及其与临床表型的关系

    Institute of Scientific and Technical Information of China (English)

    付杰; 王松涛; 潘虹; 马京梅; 于丽; 杨慧霞

    2014-01-01

    Objective To understand the correlation between chromosome deletion and the phenotypes in cases of ring chromosome 6 syndrome.Methods Two cases of ring chromosome 6 syndrome persented to the Peking University First Hospital in 2013 were studied.Case 1 was a fetus diagnosed as having ring chromosome 6 with karyotype 46,XY,r (6) [14]/46,XY,r (6; 6) [1]/45,XY,-6[15] from a pregnant woman who received prenatal examination because of high risk found in serum screening for Down's syndrome at 21 +1 weeks of gestation.Case 2 was an eight-month-old female infant with growth retardation and congenital facial anomaly,whose karyotype was 46,XX,r (6) /47,XX,r (6) × 2/46,XX,r (6; 6) /45,XX,-6.Multiplex ligation-dependent probe amplification and array-based comparative genomic hybridization were used to detect the location of chromosome telomeric loss and its size,and the correlation between chromosome deletion and the phenotypes was analyzed by reviewing related literatures.Results Case 1 was confirmed to have short-arm terminal deletions on 6p25.3-25.2 (2.42 Mb) which mainly included DUSP22,IRF4,EXOC2,FOXC1,FOXF2 and FOXQ genes,and long-arm terminal deletions on 6q26-27 (7.84 Mb) mainly included PARK2,PACRG,LOC28596 and RPS6KA2 genes.Case 2 had short-arm terminal deletions on 6p25.3-25.1 (5.44 Mb) which included DUSP22,IRF4,EXOC2,FOXC1,FOXF2,FOXQ and SERPINB6 genes,and long-arm terminal deletions on 6q27 (0.16 Mb) which included PSMB1,TBP and PDCD2 genes.Except for the growth retardation,the common feature of "ring syndrome",in both cases,cerebellum hypoplasia was observed in case 1,and microcephaly and esotropia were observed in case 2.Conclusions The difference of phenotypes in patients with a ring chromosome 6 is closely associated with the location and size of the deletion in chromosome 6.%目的 探讨环6号染色体综合征病例染色体缺失片段和定位于其中的基因与临床表型的关系. 方法 2013年就诊于北京大学第一医院的2例环6号染色

  15. Genetics Home Reference: 18q deletion syndrome

    Science.gov (United States)

    ... to severe, but some affected individuals have normal intelligence and development. Seizures, hyperactivity, aggression, and autistic behaviors ... into two types : individuals with deletions near the end of the long arm of chromosome 18 are ...

  16. Deletion 22q13.3 syndrome

    OpenAIRE

    Phelan Mary C

    2008-01-01

    Abstract The deletion 22q13.3 syndrome (deletion 22q13 syndrome or Phelan-McDermid syndrome) is a chromosome microdeletion syndrome characterized by neonatal hypotonia, global developmental delay, normal to accelerated growth, absent to severely delayed speech, and minor dysmorphic features. The deletion occurs with equal frequency in males and females and has been reported in mosaic and non-mosaic forms. Due to lack of clinical recognition and often insufficient laboratory testing, the syndr...

  17. Original Research: Generation of non-deletional hereditary persistence of fetal hemoglobin β-globin locus yeast artificial chromosome transgenic mouse models: -175 Black HPFH and -195 Brazilian HPFH.

    Science.gov (United States)

    Braghini, Carolina A; Costa, Flavia C; Fedosyuk, Halyna; Neades, Renee Y; Novikova, Lesya V; Parker, Matthew P; Winefield, Robert D; Peterson, Kenneth R

    2016-04-01

    Fetal hemoglobin is a major genetic modifier of the phenotypic heterogeneity in patients with sickle cell disease and certain β-thalassemias. Normal levels of fetal hemoglobin postnatally are approximately 1% of total hemoglobin. Patients who have hereditary persistence of fetal hemoglobin, characterized by elevated synthesis of γ-globin in adulthood, show reduced disease pathophysiology. Hereditary persistence of fetal hemoglobin is caused by β-globin locus deletions (deletional hereditary persistence of fetal hemoglobin) or γ-globin gene promoter point mutations (non-deletional hereditary persistence of fetal hemoglobin). Current research has focused on elucidating the pathways involved in the maintenance/reactivation of γ-globin in adult life. To better understand these pathways, we generated new β-globin locus yeast artificial chromosome transgenic mice bearing the (A)γ-globin -175 T > C or -195 C > G hereditary persistence of fetal hemoglobin mutations to model naturally occurring hereditary persistence of fetal hemoglobin. Adult -175 and -195 mutant β-YAC mice displayed a hereditary persistence of fetal hemoglobin phenotype, as measured at the mRNA and protein levels. The molecular basis for these phenotypes was examined by chromatin immunoprecipitation of transcription factor/co-factor binding, including YY1, PAX1, TAL1, LMO2, and LDB1. In -175 HPFH versus wild-type samples, the occupancy of LMO2, TAL1 and LDB1 proteins was enriched in HPFH mice (5.8-fold, 5.2-fold and 2.7-fold, respectively), a result that concurs with a recent study in cell lines showing that these proteins form a complex with GATA-1 to mediate long-range interactions between the locus control region and the (A)γ-globin gene. Both hereditary persistence of fetal hemoglobin mutations result in a gain of (A)γ-globin activation, in contrast to other hereditary persistence of fetal hemoglobin mutations that result in a loss of repression. The mice provide additional tools to

  18. Generation of non-deletional hereditary persistence of fetal hemoglobin β-globin locus yeast artificial chromosome transgenic mouse models: −175 Black HPFH and −195 Brazilian HPFH

    Science.gov (United States)

    Braghini, Carolina A; Costa, Flavia C; Fedosyuk, Halyna; Neades, Renee Y; Novikova, Lesya V; Parker, Matthew P; Winefield, Robert D; Peterson, Kenneth R

    2016-01-01

    Fetal hemoglobin is a major genetic modifier of the phenotypic heterogeneity in patients with sickle cell disease and certain β-thalassemias. Normal levels of fetal hemoglobin postnatally are approximately 1% of total hemoglobin. Patients who have hereditary persistence of fetal hemoglobin, characterized by elevated synthesis of γ-globin in adulthood, show reduced disease pathophysiology. Hereditary persistence of fetal hemoglobin is caused by β-globin locus deletions (deletional hereditary persistence of fetal hemoglobin) or γ-globin gene promoter point mutations (non-deletional hereditary persistence of fetal hemoglobin). Current research has focused on elucidating the pathways involved in the maintenance/reactivation of γ-globin in adult life. To better understand these pathways, we generated new β-globin locus yeast artificial chromosome transgenic mice bearing the Aγ-globin −175 T >C or −195 C >G hereditary persistence of fetal hemoglobin mutations to model naturally occurring hereditary persistence of fetal hemoglobin. Adult −175 and −195 mutant β-YAC mice displayed a hereditary persistence of fetal hemoglobin phenotype, as measured at the mRNA and protein levels. The molecular basis for these phenotypes was examined by chromatin immunoprecipitation of transcription factor/co-factor binding, including YY1, PAX1, TAL1, LMO2, and LDB1. In −175 HPFH versus wild-type samples, the occupancy of LMO2, TAL1 and LDB1 proteins was enriched in HPFH mice (5.8-fold, 5.2-fold and 2.7-fold, respectively), a result that concurs with a recent study in cell lines showing that these proteins form a complex with GATA-1 to mediate long-range interactions between the locus control region and the Aγ-globin gene. Both hereditary persistence of fetal hemoglobin mutations result in a gain of Aγ-globin activation, in contrast to other hereditary persistence of fetal hemoglobin mutations that result in a loss of repression. The mice provide additional tools to study

  19. High proportion of 22q13 deletions and SHANK3 mutations in Chinese patients with intellectual disability.

    Directory of Open Access Journals (Sweden)

    Xiaohong Gong

    Full Text Available Intellectual disability (ID is a heterogeneous disorder caused by chromosomal abnormalities, monogenic factors and environmental factors. 22q13 deletion syndrome is a genetic disorder characterized by severe ID. Although the frequency of 22q13 deletions in ID is unclear, it is believed to be largely underestimated. To address this issue, we used Affymetrix Human SNP 6.0 array to detect the 22q13 deletions in 234 Chinese unexplained ID patients and 103 controls. After the Quality Control (QC test of raw data, 22q13 deletions were found in four out of 230 cases (1.7%, while absent in parents of the cases and 101 controls. A review of genome-wide microarray studies in ID was performed and the frequency of 22q13 deletions from the literatures was 0.24%, much lower than our report. The overlapping region shared by all 4 cases encompasses the gene SHANK3. A heterozygous de novo nonsense mutation Y1015X of SHANK3 was identified in one ID patient. Cortical neurons were prepared from embryonic mice and were transfected with a control plasmid, shank3 wild-type (WT or mutant plasmids. Overexpression of the Y1015 mutant in neurons significantly affected neurite outgrowth compared with shank3 WT. These findings suggest that 22q13 deletions may be a more frequent cause for Chinese ID patients than previously thought, and the SHANK3 gene is involved in the neurite development.

  20. 1p36 deletion syndrome: an update

    Directory of Open Access Journals (Sweden)

    Jordan VK

    2015-08-01

    Full Text Available Valerie K Jordan,1 Hitisha P Zaveri,2 Daryl A Scott1,2 1Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, TX, USA; 2Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA Abstract: Deletions of chromosome 1p36 affect approximately 1 in 5,000 newborns and are the most common terminal deletions in humans. Medical problems commonly caused by terminal deletions of 1p36 include developmental delay, intellectual disability, seizures, vision problems, hearing loss, short stature, distinctive facial features, brain anomalies, orofacial clefting, congenital heart defects, cardiomyopathy, and renal anomalies. Although 1p36 deletion syndrome is considered clinically recognizable, there is significant phenotypic variation among affected individuals. This variation is due, at least in part, to the genetic heterogeneity seen in 1p36 deletions which include terminal and interstitial deletions of varying lengths located throughout the 30 Mb of DNA that comprise chromosome 1p36. Array-based copy number variant analysis can easily identify genomic regions of 1p36 that are deleted in an affected individual. However, predicting the phenotype of an individual based solely on the location and extent of their 1p36 deletion remains a challenge since most of the genes that contribute to 1p36-related phenotypes have yet to be identified. In addition, haploinsufficiency of more than one gene may contribute to some phenotypes. In this article, we review recent successes in the effort to map and identify the genes and genomic regions that contribute to specific 1p36-related phenotypes. In particular, we highlight evidence implicating MMP23B, GABRD, SKI, PRDM16, KCNAB2, RERE, UBE4B, CASZ1, PDPN, SPEN, ECE1, HSPG2, and LUZP1 in various 1p36 deletion phenotypes. Keywords: chromosome 1p36, chromosome deletion, 1p36 deletion syndrome, monosomy 1p36

  1. The DNA sequence and biology of human chromosome 19

    Energy Technology Data Exchange (ETDEWEB)

    Grimwood, J; Gordon, L A; Olsen, A; Terry, A; Schmutz, J; Lamerdin, J; Hellsten, U; Goodstein, D; Couronne, O; Tran-Gyamfi, M

    2004-04-06

    Chromosome 19 has the highest gene density of all human chromosomes, more than double the genome-wide average. The large clustered gene families, corresponding high GC content, CpG islands and density of repetitive DNA indicate a chromosome rich in biological and evolutionary significance. Here we describe 55.8 million base pairs of highly accurate finished sequence representing 99.9% of the euchromatin portion of the chromosome. Manual curation of gene loci reveals 1,461 protein-coding genes and 321 pseudogenes. Among these are genes directly implicated in Mendelian disorders, including familial hypercholesterolemia and insulin-resistant diabetes. Nearly one quarter of these genes belong to tandemly arranged families, encompassing more than 25% of the chromosome. Comparative analyses show a fascinating picture of conservation and divergence, revealing large blocks of gene orthology with rodents, scattered regions with more recent gene family expansions and deletions, and segments of coding and non-coding conservation with the distant fish species Takifugu.

  2. Femoral facial syndrome associated with a de novo complex chromosome 2q37 rearrangement.

    Science.gov (United States)

    Spielmann, Malte; Marx, Sylvie; Barbi, Gotthold; Flöttmann, Ricarda; Kehrer-Sawatzki, Hildegard; König, Rainer; Horn, Denise; Mundlos, Stefan; Nader, Sean; Borck, Guntram

    2016-05-01

    The femoral facial syndrome (FFS) is a rare congenital anomaly syndrome characterized by bilateral femoral hypoplasia and facial dysmorphism. The etiology of FFS is currently unknown but maternal/gestational diabetes has been proposed as a strong risk factor for syndromic femoral hypoplasia. In affected children born to non-diabetic mothers, a genetic contribution to FFS is suspected; however, no chromosomal anomalies or gene mutations have been identified so far. Here, we report on a girl with FFS and a de novo complex chromosome rearrangement of terminal chromosome 2q37.2. Radiographs of the pelvis and lower limbs showed bilateral shortening and bowing of the femur and radiographs of hands and feet revealed a brachydactyly type E (BDE). Using high resolution array-CGH, qPCR, and FISH, we detected a ∼1.9 Mb duplication in the chromosomal region 2q37.2 and a ∼5.4 Mb deletion on chromosome 2q37.3 that were absent in the parents. The duplication contains six genes and the deletion encompasses 68 genes; the latter has previously been shown to cause BDE (through haploinsufficiency for HDAC4) but not femoral hypoplasia. Therefore, we propose that the duplication 2q37.2 could be causative for the femur phenotype. To the best of our knowledge, our report is the first to propose a genetic cause in a case of FFS. © 2016 Wiley Periodicals, Inc. PMID:26822876

  3. A New Case of an Extremely Rare 3p21.31 Interstitial Deletion.

    Science.gov (United States)

    Lovrecic, Luca; Bertok, Sara; Žerjav Tanšek, Mojca

    2016-05-01

    Interstitial 3p21.31 deletions have been very rarely reported. We describe a 7-year-old boy with global developmental delay, specific facial characteristics, hydronephrosis, and hypothyreosis with a de novo deletion of 3p21.31, encompassing 29 OMIM genes. Despite the wide use of microarrays, no similar case has been reported in the literature so far. Five overlapping cases are deposited in the DECIPHER database, 2 of which have significant overlapping chromosomal aberrations. They both share some phenotypic characteristics with our case, e.g. developmental delay, intellectual disability and facial dysmorphism (arched eyebrows, hypertelorism, low-set ears, and a large nose tip). In addition, loss-of-function mutations in the SETD2 gene (OMIM 612778) of the deleted region have been described in 3 patients, presenting with some similar clinical features, namely overgrowth, intellectual disability, speech delay, hypotonia, autism, and epilepsy. Therefore, SETD2 may explain part of the phenotype in our case. We focused on 3 other genes in the deleted region, based on their known functions, namely CSPG5 (OMIM 606775), PTH1R (OMIM 168468) and SMARCC1 (OMIM 601732), and assessed their potentially important role in describing the patient's phenotype. Additional cases with haploinsufficiency of this region are needed to elucidate further genotype-phenotype correlations. PMID:27385966

  4. Physical mapping of the pink-eyed dilution complex in mouse chromosome 7 shows that Atp10c is the only transcript between Gabrb3 and Ube3a.

    Science.gov (United States)

    Dhar, Madhu S; Hauser, Loren J; Nicholls, Robert D; Johnson, Dabney K

    2004-08-01

    Phenotypic analyses of a set of homozygous-lethal deletion mutants at the pink-eyed dilution (p) locus has resulted in the identification of p-linked obesity locus 1 (plo 1), distal to the p locus, as a locus involved in the modulation of body fat and/or affecting lipid metabolism in these mice. The plo 1 region maps to mouse chromosome 7 (MMU 7) between two genes, Gabrb3 and Ube3a, which have been used as anchor points to generate an integrated deletion and physical map of plo 1 that encompasses about 1.2-1.3 Mb. A deletion/physical map was constructed and the genomic DNA between the two loci was sequenced to identify genes mapping to this region. Data show that Atp10c, a novel type IV ATPase a putative phospholipid transporter, is the only coding unit in this region of the chromosome. PMID:15620220

  5. Derivative chromosome 1 and GLUT1 deficiency syndrome in a sibling pair

    Directory of Open Access Journals (Sweden)

    Akarsu Nurten

    2010-05-01

    Full Text Available Abstract Background Genomic imbalances constitute a major cause of congenital and developmental abnormalities. GLUT1 deficiency syndrome is caused by various de novo mutations in the facilitated human glucose transporter 1 gene (1p34.2 and patients with this syndrome have been diagnosed with hypoglycorrhachia, mental and developmental delay, microcephaly and seizures. Furthermore, 1q terminal deletions have been submitted in the recent reports and the absence of corpus callosum has been related to the deletion between C1orf100 and C1orf121 in 1q44. Results This study reports on a sibling pair with developmental delay, mental retardation, microcephaly, hypotonia, epilepsy, facial dysmorphism, ataxia and impaired speech. Chromosome analysis revealed a derivative chromosome 1 in both patients. FISH and MCB analysis showed two interstitial deletions at 1p34.2 and 1q44. SNP array and array-CGH analysis also determined the sizes of deletions detailed. The deleted region on 1p34.2 encompasses 33 genes, among which is GLUT1 gene (SLC2A1. However, the deleted region on 1q44 includes 59 genes and distal-proximal breakpoints were located in the ZNF672 gene and SMYD3 gene, respectively. Conclusion Haploinsufficiency of GLUT1 leads to GLUT1 deficiency syndrome, consistent with the phenotype in patients of this study. Conversely, in the deleted region on 1q44, none of the genes are related to findings in these patients. Additionally, the results confirm previous reports on that corpus callosal development may depend on the critical gene(s lying in 1q44 proximal to the SMYD3 gene.

  6. Encompassing Sexual Medicine within Psychiatry: Pros and Cons

    Science.gov (United States)

    Segraves, Robert Taylor

    2010-01-01

    Objective: This article examines the positive and negative aspects of psychiatry encompassing sexual medicine within its purview. Methods: MEDLINE searches for the period between 1980 to the present were performed with the terms "psychiatry," "sexual medicine," and "sexual dysfunction." In addition, sexual medicine texts were reviewed for chapters…

  7. Educational NASA Computational and Scientific Studies (enCOMPASS)

    Science.gov (United States)

    Memarsadeghi, Nargess

    2013-01-01

    Educational NASA Computational and Scientific Studies (enCOMPASS) is an educational project of NASA Goddard Space Flight Center aimed at bridging the gap between computational objectives and needs of NASA's scientific research, missions, and projects, and academia's latest advances in applied mathematics and computer science. enCOMPASS achieves this goal via bidirectional collaboration and communication between NASA and academia. Using developed NASA Computational Case Studies in university computer science/engineering and applied mathematics classes is a way of addressing NASA's goals of contributing to the Science, Technology, Education, and Math (STEM) National Objective. The enCOMPASS Web site at http://encompass.gsfc.nasa.gov provides additional information. There are currently nine enCOMPASS case studies developed in areas of earth sciences, planetary sciences, and astrophysics. Some of these case studies have been published in AIP and IEEE's Computing in Science and Engineering magazines. A few university professors have used enCOMPASS case studies in their computational classes and contributed their findings to NASA scientists. In these case studies, after introducing the science area, the specific problem, and related NASA missions, students are first asked to solve a known problem using NASA data and past approaches used and often published in a scientific/research paper. Then, after learning about the NASA application and related computational tools and approaches for solving the proposed problem, students are given a harder problem as a challenge for them to research and develop solutions for. This project provides a model for NASA scientists and engineers on one side, and university students, faculty, and researchers in computer science and applied mathematics on the other side, to learn from each other's areas of work, computational needs and solutions, and the latest advances in research and development. This innovation takes NASA science and

  8. Analysis of Y chromosome microdeletions and CFTR gene mutations as genetic markers of infertility in Serbian men

    Directory of Open Access Journals (Sweden)

    Dinić Jelena

    2007-01-01

    Full Text Available Background/Aim. Impaired fertility of a male partner is the main cause of infertility in up to one half of all infertile couples. At the genetic level, male infertility can be caused by chromosome aberrations or gene mutations. The presence and types of Y chromosome microdeletions and cystic fybrosis transmembrane conductance regulator (CFTR gene mutations as genetic cause of male infertility was tested in Serbian men. The aim of this study was to analyze CFTR gene mutations and Y chromosome microdelations as potential causes of male infertility in Serbian patients, as well as to test the hypothesis that CFTR mutations in infertile men are predominantly located in the several last exons of the gene. Methods. This study has encompassed 33 men with oligo- or azoospermia. The screening for Y chromosome microdeletions in the azoospermia factor (AZF region was performed by multiplex PCR analysis. The screening of the CFTR gene was performed by denaturing gradient gel electrophoresis (DGGE method. Results. Deletions on Y chromosome were detected in four patients, predominantly in AZFc region (four of total six deletions. Mutations in the CFTR gene were detected on eight out of 66 analyzed chromosomes of infertile men. The most common mutation was F508del (six of total eight mutations. Conclusion. This study confirmed that both Y chromosome microdeletions and CFTR gene mutations played important role in etiology of male infertility in Serbian infertile men. Genetic testing for Y chromosome microdeletions and CFTR gene mutations has been introduced in routine diagnostics and offered to couples undergoing assisted reproduction techniques. Considering that both the type of Y chromosome microdeletion and the type of CFTR mutation have a prognostic value, it is recommended that AZF and CFTR genotyping should not only be performed in patients with reduced sperm quality before undergoing assisted reproduction, but also for the purpose of preimplantation and

  9. Interstitial 12p deletion involving more than 40 genes in a patient with postnatal microcephaly, psychomotor delay, optic nerve atrophy, and facial dysmorphism

    Directory of Open Access Journals (Sweden)

    Anne Hoppe

    2014-12-01

    Full Text Available Interstitial deletions of chromosome 12p are rare, and the phenotype spectrum is therefore still unknown. The thirteen patients reported so far suffer from developmental delay, optic nerve hypoplasia, micropenis, hypoplastic hair and skin, oligodontia, brachydactyly, and arterial hypertension. We report a de novo 12p12.2–p11.22 deletion of 9.2 Mb detected by array CGH analysis in a boy with global developmental delay, muscular hypotonia, postnatal microcephaly, facial dysmorphism including small ears, epicanthus, broad nasal bridge and hypoplastic nostrils. In addition, the patient had optic nerve atrophy, inverted nipples, micropenis, and a hemangioma. The deleted region encompasses more than 40 reference genes. We compare phenotype and deletion extent of our index patient to that of previous reports and thereby contribute to the understanding of interstitial 12p deletion phenotypes. Knowledge of the pattern of this deletion phenotype will help clinicians to diagnose this abnormality in their patients and to counsel the parents accordingly. Further descriptions may be able to contribute to the clarification.

  10. Speech and language impairment and oromotor dyspraxia due to deletion of 7q31 that involves FOXP2.

    Science.gov (United States)

    Zeesman, Susan; Nowaczyk, Małgorzata J M; Teshima, Ikuko; Roberts, Wendy; Cardy, Janis Oram; Brian, Jessica; Senman, Lili; Feuk, Lars; Osborne, Lucy R; Scherer, Stephen W

    2006-03-01

    We report detailed clinical, cytogenetic, and molecular findings in a girl with a deletion of chromosome 7q31-q32. This child has a severe communication disorder with evidence of oromotor dyspraxia, dysmorphic features, and mild developmental delay. She is unable to cough, sneeze, or laugh spontaneously. Her deletion is on the paternally inherited chromosome and includes the FOXP2 gene, which has recently been associated with speech and language impairment and a similar form of oromotor dyspraxia in at least three other published cases. We hypothesize that our patient's communication disorder and oromotor deficiency are due to haploinsufficiency for FOXP2 and that her dysmorphism and developmental delay are a consequence of the absence of the other genes involved in the microdeletion. We propose that this patient, together with others reported in the literature, may define a new contiguous gene deletion syndrome encompassing the 7q31-FOXP2 region. Cytogenetic and molecular analysis of this region should be considered for other individuals displaying similar characteristics. PMID:16470794

  11. Falência ovariana precoce associada a deleção no braço longo do cromossomo: relato de dois casos e revisão da literatura Premature ovarian failure with a deletion in the long arm of chromosome: report of two cases and review of the literature

    Directory of Open Access Journals (Sweden)

    Mariangela Badalotti

    2006-09-01

    Full Text Available Falência ovariana prematura pode ser idiopática ou estar associada a várias distúrbios auto-imunes ou genéticos, como as deleções do cromossomo X. Relatamos dois novos casos de deleções do braço longo do cromossomo X, em pacientes nuligrávidas apresentando amenorréia secundária e infertilidade. Nenhuma paciente referia história familiar de falência ovariana prematura e relatavam desenvolvimento puberal normal. A avaliação genética mostrou deleção distal no braço longo do cromossomo X, sendo os resultados 46,X,del(Xq22 e 46,X,del(Xq13q28, respectivamente. Após o diagnóstico as pacientes optaram por fertilização in vitro com óvulos doados.Premature ovarian failure may be idiopathic or associated with several autoimmune and genetic disorders as X chromosome deletions. We report two cases of preamture ovarian failure associated with a deletion in the long arm of X chromosome. Both patients were nulligravidas presenting secondary amenorrhea and complaints of infertility, without family history of premature ovarian failure and reporting normal puberal development. Their karyotypes showed deletions of the distal long arm of all X chromosomes and were 46,X, del(Xq22 and 46,X, del(Xq13q28, respectively. After the diagnosis the patients decided to be submitted to an in vitro fertilization with egg donation.

  12. Microdeletion of 6q16.1 encompassing EPHA7 in a child with mild neurological abnormalities and dysmorphic features: case report

    OpenAIRE

    Rosenfeld Jill A; Hudson Beth; Fan Zheng; Traylor Ryan N; Shaffer Lisa G; Torchia Beth S; Ballif Blake C

    2009-01-01

    Abstract Background Of the fewer than 100 cases reported within the literature of constitutional deletions involving the long arm of chromosome 6, only five have been characterized using high-resolution microarray analysis. Reported 6q deletion patients show a high incidence of mental retardation, ear anomalies, hypotonia, and postnatal growth retardation. Results We report a 16-month-old male presenting with developmental delay and dysmorphic features who was found by array-based comparative...

  13. Deletion of the c-kit protooncogene in the human developmental defect piebald trait

    Energy Technology Data Exchange (ETDEWEB)

    Fleischman, R.A.; Stastny, V.; Zneimer, S. (Univ. of Texas, Dallas (United States)); Saltman, D.L. (Genelabs, Inc., Redwood City, CA (United States))

    1991-12-01

    The protooncogene c-kit is critical for development of hematopoietic stem cells, germ cells, and melanoblasts in the mouse. Homozygous mutations of this gene in the mouse cause anemia, infertility, and albinism, whereas heterozygous mutant mice usually exhibit only a white forehead blaze and depigmentation of the ventral body, tail, and feet. The heterozygous mouse phenotype is very similar to human piebald trait, which is characterized by a congenital white hair forelock and ventral and extremity depigmentation. To investigate the possibility that alterations in the human c-kit gene may be a cause of piebald trait, DNA from seven unrelated affected individuals was examined by Southern blot analysis. One subject, although cytogenetically normal, has a heterozygous deletion of the c-kit protooncogene. This deletion encompasses the entire coding region for c-kit and also involves the closely linked gene for platelet-derived growth factor receptor {alpha}. These findings provide molecular evidence mapping piebald trait to the c-kit locus on chromosome 4. Although the authors cannot exclude the involvement of other closely linked genes, the demonstration of a genomic c-kit deletion in one subject with piebald trait and the marked concordance of the human and mouse phenotypes provide strong evidence for the role of c-kit in the development of human melanocytes and in the pathogenesis of piebald trait.

  14. Secondary EWSR1 gene abnormalities in SMARCB1-deficient tumors with 22q11-12 regional deletions: Potential pitfalls in interpreting EWSR1 FISH results.

    Science.gov (United States)

    Huang, Shih-Chiang; Zhang, Lei; Sung, Yun-Shao; Chen, Chun-Liang; Kao, Yu-Chien; Agaram, Narasimhan P; Antonescu, Cristina R

    2016-10-01

    SMARCB1 inactivation occurs in a variety of tumors, being caused by various genetic mechanisms. Since SMARCB1 and EWSR1 genes are located close to each other on chromosome 22, larger SMARCB1 deletions may encompass the EWSR1 locus. Herein, we report four cases with SMARCB1-deletions showing concurrent EWSR1 gene abnormalities by FISH, which lead initially to misinterpretations as EWSR1-rearranged tumors. Our study group included various morphologies: a poorly differentiated chordoma, an extrarenal rhabdoid tumor, a myoepithelial carcinoma, and a proximal-type epithelioid sarcoma. All cases showed loss of SMARCB1 (INI1) by immunohistochemistry (IHC) and displayed characteristic histologic features for the diagnoses. The SMARCB1 FISH revealed homozygous or heterozygous deletions in three and one case, respectively. The co-hybridized EWSR1 probes demonstrated either unbalanced split signals or heterozygous deletion in two cases each. The former suggested bona fide rearrangement, while the latter resembled an unbalanced translocation. However, all the FISH patterns were quite complex and distinct from the simple and uniform split signals seen in typical EWSR1 rearrangements. We conclude that in the context of 22q11-12 regional alterations present in SMARCB1-deleted tumors, simultaneous EWSR1 involvement may be misinterpreted as equivalent to EWSR1 rearrangement. A detailed clinicopathologic correlation and supplementing the EWSR1 FISH assay with complementary methodology is mandatory for correct diagnosis. © 2016 Wiley Periodicals, Inc. PMID:27218413

  15. An all-encompassing study of an authentic court setting

    DEFF Research Database (Denmark)

    Christensen, Tina Paulsen

    Most professional interpreters and interpreting researchers probably see quality or "professiona¬lism" as the main goal of interpreting in general, but still there is no agreement within the inter¬preting community of how to define interpreting quality. Facing the fact that interpreting can not...... necessarily be judged from a particular (subjective) perspective on the communicative event. In this paper I shall address the issue of interpreting quality in an all-encompassing perspective on an authentic Danish courtroom setting. The aim of the empirical case-based survey is unlike that of most existing...... studies which generally have taken either one particular perspective - that of inter¬preters, clients or users - or been experimental in nature - to investigate to which extent different users (judge, defence counsel, prosecutor and non-majority-language speaking user) in a specific courtroom setting...

  16. From Balancing the Numbers to an Encompassing Business Case

    DEFF Research Database (Denmark)

    Labucay, Inéz

    2013-01-01

    The Business Case of Diversity Management has evolved as the predominant concept underlying many diversity studies and practices in the field. In this line of reasoning, corporate bottom line results like an increased return on investment (ROI) are partially explained by the existence of Diversity...... Management programs that aim at increasing both customer retention and employee performance. This rationale tends to overestimate the process gains and at the same time to underestimate the process losses in the face of mixed evidence on the link between diversity and performance (Kochan 2003; Horwitz......, Diversity measurement) are presented in more detail, followed by a summary and conclusion on its applicability and relevance for diversity practitioners. An outlook on further research ensues. The paper aims at delineating an approach to building a more encompassing Business Case....

  17. Characterization of large genomic deletions in the FBN1 gene using multiplex ligation-dependent probe amplification

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    Lewis Tracey

    2011-09-01

    Full Text Available Abstract Background Connective tissue diseases characterized by aortic aneurysm, such as Marfan syndrome, Loeys-Dietz syndrome and Ehlers Danlos syndrome type IV are heterogeneous and despite overlapping phenotypes, the natural history, clinical manifestations and interventional course for each diagnosis can be quite unique. The majority of mutations involved in the etiology of these disorders are missense and nonsense mutations. However, large deletions and duplications undetected by sequencing may be implicated in their pathogenesis, and may explain the apparent lack of genotype-phenotype correlation in a subset of patients. The objective of this study was to search for large pathogenic deletions and/or duplications in the FBN1, TGFβR1, and TGFβR2 genes using multiplex-ligation dependent probe amplification (MLPA in patients with aortopathy, in whom no mutations in the FBN1, TGFβR1, and TGFβR2 genes were identified by sequencing. Methods The study included 14 patients from 11 unrelated families with aortic aneurysm. Of those, six patients (including 3 first-degree relatives, fulfilled the revised Ghent criteria for Marfan syndrome, and eight had predominantly aortic aneurysm/dilatation with variable skeletal and craniofacial involvement. MLPA for FBN1, TGFβR1, and TGFβR2 was carried out in all patients. A 385 K chromosome 15 specific array was used in two patients with a deletion of the entire FBN1 in order to define its size and boundaries. Results We identified two novel large deletions in the FBN1 gene in four patients of two unrelated families who met clinical diagnostic criteria for Marfan syndrome. One patient was found to have a FBN1 deletion encompassing exons 1-5. The other three patients had a 542 Kb deletion spanning the whole FBN1 gene and five additional genes (SLC24A5, MYEF2, CTXN2, SLC12A1, DUT in the chromosome 15. Conclusions Our findings expand the number of large FBN1 deletions, and emphasize the importance of

  18. Subtelomeric study of 132 patients with mental retardation reveals 9 chromosomal anomalies and contributes to the delineation of submicroscopic deletions of 1pter, 2qter, 4pter, 5qter and 9qter

    DEFF Research Database (Denmark)

    Sogaard, Marie; Tümer, Zeynep; Hjalgrim, Helle;

    2005-01-01

    BACKGROUND: Cryptic chromosome imbalances are increasingly acknowledged as a cause for mental retardation and learning disability. New phenotypes associated with specific rearrangements are also being recognized. Techniques for screening for subtelomeric rearrangements are commercially available...

  19. The mouse homologue of the human tuberous sclerosis 2 (TSC2) gene maps to chromosome 17, but does not fall within the t{sup w18} or t{sup h20} deletions

    Energy Technology Data Exchange (ETDEWEB)

    Pilz, A.; Povey, S. [Univ. College London (United Kingdom); Glenister, P. [MRC Radiobiology Unit, Oxon (United Kingdom)] [and others

    1995-03-20

    Tuberous sclerosis, TSC, is an autosomal dominant disorder characterized by a variety of clinical features including mental retardation, epilepsy, facial angiofibroma, shagreen patches on the skin, rhabdomyomas of the myocardium, and renal cysts. Genetic heterogeneity of the disorder has been established, with two distinct genetic loci mapping to 9q34 (TSCI; 4) and 16p13.3 (TSC2; 8). The locus on 16p13 is thought to account for about 60% of cases of TSC. This locus was recently cloned. Five TSC-associated deletions were found using pulsed-field gel electrophoresis (PFGE), covering a region of 120 kb. This region was cloned, and four genes were isolated. One of these had a region of homology to the GTPase-activating protein GAP3, was widely expressed, fell within each of the five deletions identified by PFGE, and displayed intragenic deletions in five more TSC patients, including one de novo deletion. This gene was designated TSC2. Tuberous sclerosis appears, therefore, in 60% of cases, to result from a loss of function of a single allele at the TSC2 locus. This suggests that it might be possible to generate a mouse model for TSC by knocking out a single allele at the homologous mouse locus. Since there are defined deletions corresponding to many regions of the mouse genome (either spontaneous or induced by radiation or chemical mutagenesis), we set out to map the mouse homologue of TSC2 to determine whether deletions of Tsc2 might already in fact exist. 12 refs., 1 fig.

  20. A new microduplication syndrome encompassing the region of the Miller-Dieker (17p13 deletion) syndrome

    DEFF Research Database (Denmark)

    Roos, L; Jønch, A E; Kjaergaard, S;

    2009-01-01

    cases with this duplication. METHODS: Multiplex ligation-dependent probe amplification (MLPA) or array-CGH was used to diagnose three developmentally delayed children with duplications of 17p13. The duplications were characterised further using Agilent array technology, revealing duplication sizes from...

  1. Deletion 22q13.3 syndrome

    Directory of Open Access Journals (Sweden)

    Phelan Mary C

    2008-05-01

    Full Text Available Abstract The deletion 22q13.3 syndrome (deletion 22q13 syndrome or Phelan-McDermid syndrome is a chromosome microdeletion syndrome characterized by neonatal hypotonia, global developmental delay, normal to accelerated growth, absent to severely delayed speech, and minor dysmorphic features. The deletion occurs with equal frequency in males and females and has been reported in mosaic and non-mosaic forms. Due to lack of clinical recognition and often insufficient laboratory testing, the syndrome is under-diagnosed and its true incidence remains unknown. Common physical traits include long eye lashes, large or unusual ears, relatively large hands, dysplastic toenails, full brow, dolicocephaly, full cheeks, bulbous nose, and pointed chin. Behavior is autistic-like with decreased perception of pain and habitual chewing or mouthing. The loss of 22q13.3 can result from simple deletion, translocation, ring chromosome formation and less common structural changes affecting the long arm of chromosome 22, specifically the region containing the SHANK3 gene. The diagnosis of deletion 22q13 syndrome should be considered in all cases of hypotonia of unknown etiology and in individuals with absent speech. Although the deletion can sometimes be detected by high resolution chromosome analysis, fluorescence in situ hybridization (FISH or array comparative genomic hybridization (CGH is recommended for confirmation. Differential diagnosis includes syndromes associated with hypotonia, developmental delay, speech delay and/or autistic-like affect (Prader-Willi, Angelman, Williams, Smith-Magenis, Fragile X, Sotos, FG, trichorhinophalangeal and velocardiofacial syndromes, autism spectrum disorders, cerebral palsy. Genetic counseling is recommended and parental laboratory studies should be considered to identify cryptic rearrangements and detect parental mosaicism. Prenatal diagnosis should be offered for future pregnancies in those families with inherited rearrangements

  2. Neuropathological features in a female fetus with OPHN1 deletion and cerebellar hypoplasia.

    Science.gov (United States)

    Rocas, Delphine; Alix, Eudeline; Michel, Jessica; Cordier, Marie-Pierre; Labalme, Audrey; Guilbert, Hélène; Till, Marianne; Schluth-Bolard, Caroline; de Haas, Pascale; Massardier, Jérôme; Portes, Vincent des; Edery, Patrick; Touraine, Renaud; Guibaud, Laurent; Vasiljevic, Alexandre; Sanlaville, Damien

    2013-05-01

    We report the case of a 33-year-old pregnant woman. The third-trimester ultrasound scan during pregnancy revealed fetal bilateral ventricular dilatation, macrosomia and a transverse diameter of the cerebellum at the 30th centile. A brain MRI scan at 31 weeks of gestation led to a diagnosis of hypoplasia of the cerebellar vermis without hemisphere abnormalities and a non compressive expansion of the cisterna magna. The fetal karyotype was 46,XX. The pregnancy was terminated and array-CGH analysis of the fetus identified a 238 kb de novo deletion on chromosome Xp12, encompassing part of OPHN1 gene. Further studies revealed a completely skewed pattern of X inactivation. OPHN1 is involved in X-linked mental retardation (XLMR) with cerebellar hypoplasia and encodes a Rho-GTPase-activating protein called oligophrenin-1, which is produced throughout the developing mouse brain and in the hippocampus and Purkinje cells of the cerebellum in adult mice. Neuropathological examination of the female fetus revealed cerebellar hypoplasia and the heterotopia of Purkinje cells at multiple sites in the white matter of the cerebellum. This condition mostly affects male fetuses in humans. We report here the first case of a de novo partial deletion of OPHN1, with radiological and neuropathological examination, in a female fetus. PMID:23416624

  3. Gain of Chromosome 4qter and Loss of 5pter: An Unusual Case with Features of Cri du Chat Syndrome

    Directory of Open Access Journals (Sweden)

    Frenny Sheth

    2012-01-01

    Full Text Available Here, we present a case with an unusual chromosomal rearrangement in a child with a predominant phenotype of high-pitched crying showing deletion encompassing CTNND2 due to an unbalanced translocation of chromosomes 4 and 5. This rearrangement led to a duplication of ~35 Mb in 4qter which replaced 18 Mb genetic materials in 5pter. Even though, in this patient, there was no clinically obvious modification to the classical phenotypes of CdCS, and the influence of the 4q-duplication cannot be completely excluded in this case. However, the region 4q34.1–34.3 was previously reported as a region not leading to phenotypic changes if present in three copies, an observation which could possibly be supported by this case. Conclusion. This study showed that in a patient with an unbalanced translocation resulting in 5p deletion, the presence of partial trisomy of chromosome 4q could be clinically insignificant.

  4. Subtelomeric study of 132 patients with mental retardation reveals 9 chromosomal anomalies and contributes to the delineation of submicroscopic deletions of 1pter, 2qter, 4pter, 5qter and 9qter

    Directory of Open Access Journals (Sweden)

    Tommerup Niels

    2005-05-01

    Full Text Available Abstract Background Cryptic chromosome imbalances are increasingly acknowledged as a cause for mental retardation and learning disability. New phenotypes associated with specific rearrangements are also being recognized. Techniques for screening for subtelomeric rearrangements are commercially available, allowing the implementation in a diagnostic service laboratory. We report the diagnostic yield in a series of 132 subjects with mental retardation, and the associated clinical phenotypes. Methods We applied commercially available subtelomeric fluorescence in situ hybridization (FISH. All patients referred for subtelomeric screening in a 5-year period were reviewed and abnormal cases were further characterized clinically and if possible molecularly. Results We identified nine chromosomal rearrangements (two of which were in sisters corresponding to a diagnostic yield of approx. 7%. All had dysmorphic features. Five had imbalances leading to recognizable phenotypes. Conclusion Subtelomeric screening is a useful adjunct to conventional cytogenetic analyses, and should be considered in mentally retarded subjects with dysmorphic features and unknown cause.

  5. Molecular mimicry and clonal deletion: A fresh look.

    Science.gov (United States)

    Rose, Noel R

    2015-06-21

    In this article, I trace the historic background of clonal deletion and molecular mimicry, two major pillars underlying our present understanding of autoimmunity and autoimmune disease. Clonal deletion originated as a critical element of the clonal selection theory of antibody formation in order to explain tolerance of self. If we did have complete clonal deletion, there would be major voids, the infamous "black holes", in our immune repertoire. For comprehensive, protective adaptive immunity, full deletion is necessarily a rare event. Molecular mimicry, the sharing of epitopes among self and non-self antigens, is extraordinary common and provides the evidence that complete deletion of self-reactive clones is rare. If molecular mimicry were not common, protective adaptive immunity could not be all-encompassing. By taking a fresh look at these two processes together we can envision their evolutionary basis and understand the need for regulatory devices to prevent molecular mimicry from progressing to autoimmune disease. PMID:25172771

  6. Familial deletion 18p syndrome: case report

    Directory of Open Access Journals (Sweden)

    Lemyre Emmanuelle

    2006-07-01

    Full Text Available Abstract Background Deletion 18p is a frequent deletion syndrome characterized by dysmorphic features, growth deficiencies, and mental retardation with a poorer verbal performance. Until now, five families have been described with limited clinical description. We report transmission of deletion 18p from a mother to her two daughters and review the previous cases. Case presentation The proband is 12 years old and has short stature, dysmorphic features and moderate mental retardation. Her sister is 9 years old and also has short stature and similar dysmorphic features. Her cognitive performance is within the borderline to mild mental retardation range. The mother also presents short stature. Psychological evaluation showed moderate mental retardation. Chromosome analysis from the sisters and their mother revealed the same chromosomal deletion: 46, XX, del(18(p11.2. Previous familial cases were consistent regarding the transmission of mental retardation. Our family differs in this regard with variable cognitive impairment and does not display poorer verbal than non-verbal abilities. An exclusive maternal transmission is observed throughout those families. Women with del(18p are fertile and seem to have a normal miscarriage rate. Conclusion Genetic counseling for these patients should take into account a greater range of cognitive outcome than previously reported.

  7. Deletion affecting band 7q36 not associated with holoprosencephaly

    Energy Technology Data Exchange (ETDEWEB)

    Ebrahim, S.A.D.; Krivchenia, E.; Mohamed, A.N. [Wayne State Univ., Detroit, MI (United States)] [and others

    1994-09-01

    Although the appearance of 7q36 aberrations have been postulated to be responsible for holoprosencephaly (HPE), the presence of a de novo 7q36 deletion in fetus without HPE has not been reported. We report the first case of a fetus with 7q36 deletion but lacking HPE. Ultrasound examination of a 25-year-old G3P1 Caucasian female showed small head circumference with microcephaly at 28 weeks. Decreased amniotic fluid volume, bilateral renal dilatation and abnormal facial features were also noted. Chromosome analysis after cordocentesis showed an abnormal female karyotype with a deletion involving the chromosome band 7q36, 46,XX,del(7)(q36). Chromosome studies on the biological parents were normal. In view of the chromosome finding and after extensive counseling, the couple elected to terminate the pregnancy. The chromosome findings were confirmed by fetal blood chromosome analysis at termination. Post-mortem examination confirmed dysmorphic features including a depressed nasal bridge and large flat ears with no lobules, but no cleft lip or palate was noted. Internal abnormalities included a bicuspid pulmonary valve and abnormally located lungs. The brain weighed 190g (249 {plus_minus} 64g expected) and had symmetric cerebral hemispheres without evidence of HPE or other gross or microscopic malformation, except focal cerebellar cortical dysplasia. In summary, our patient showed a deletion of the same chromosomal band implicated in HPE but lacked HPE. This finding indicates that 7q36 deletion may be seen in the absence of HPE and suggests that other genetic mechanisms may be responsible for HPE in this setting.

  8. 3p deletion syndrome.

    Science.gov (United States)

    Kaur, Anupam; Khetarpal, S

    2013-08-01

    3p deletion is a rare cytogenetic finding. Here we describe a 3 months old male with congenital malformations. His karyotype revealed 3p deletion 46,XY,del(3)(p25-pter). The child had flexion deformity of wrist and elbow which has never been reported before. PMID:24036645

  9. Ectrodactyly and proximal/intermediate interstitial deletion 7q

    Energy Technology Data Exchange (ETDEWEB)

    McElveen, C.; Carvajal, M.V.; Moscatello, D. [Louisiana State Univ. Medical Center, New Orleans, LA (United States)] [and others

    1995-03-13

    We report on an individual with severe mental retardation, seizures, microcephaly, unusual face, scoliosis, and cleft feet and cleft right hand. The chromosomal study showed a proximal interstitial deletion 7q (q11.23q22). From our review of the literature, 11 patients have been reported with ectrodactyly (split hand/split foot malformation) and proximal/intermediate interstitial deletions or rearrangements of 7q. The critical segment for ectrodactyly seems to be located between 7q21.2 and 7q22.1. This malformation is present in 41% of the patients whose deletion involves the critical segment. 37 refs., 3 figs., 1 tab.

  10. Making chromosome abnormalities treatable conditions.

    Science.gov (United States)

    Cody, Jannine DeMars; Hale, Daniel Esten

    2015-09-01

    Individuals affected by the classic chromosome deletion syndromes which were first identified at the beginning of the genetic age, are now positioned to benefit from genomic advances. This issue highlights five of these conditions (4p-, 5p-, 11q-, 18p-, and 18q-). It focuses on the increased in understanding of the molecular underpinnings and envisions how these can be transformed into effective treatments. While it is scientifically exciting to see the phenotypic manifestations of hemizygosity being increasingly understood at the molecular and cellular level, it is even more amazing to consider that we are now on the road to making chromosome abnormalities treatable conditions. PMID:26351122

  11. Deletion mutations of bacteriophage

    International Nuclear Information System (INIS)

    Resolution of mutation mechanism with structural changes of DNA was discussed through the studies using bacteriophage lambda. One of deletion mutations inductions of phage lambda is the irradiation of ultraviolet ray. It is not clear if the inductions are caused by errors in reparation of ultraviolet-induced damage or by the activation of int gene. Because the effective site of int gene lies within the regions unnecessary for existing, it is considered that int gene is connected to deletion mutations induction. A certain system using prophage complementarity enables to detect deletion mutations at essential hereditary sites and to solve the relations of deletion mutations with other recombination system, DNA reproduction and repairment system. Duplication and multiplication of hereditary elements were discussed. If lambda deletion mutations of the system, which can control recombination, reproduction and repairment of added DNA, are constructed, mutations mechanism with great changes of DNA structure can be solved by phage lambda. (Ichikawa, K.)

  12. A de novo 10p11.23-p12.1 deletion recapitulates the phenotype observed in WAC mutations and strengthens the role of WAC in intellectual disability and behavior disorders.

    Science.gov (United States)

    Abdelhedi, Fatma; El Khattabi, Laila; Essid, Nouha; Viot, Geraldine; Letessier, Dominique; Lebbar, Aziza; Dupont, Jean-Michel

    2016-07-01

    Chromosomal microarray analysis has become a powerful diagnostic tool in the investigation of patients with intellectual disability leading to the discovery of dosage sensitive genes implicated in the manifestation of various genomic disorders. Interstitial deletions of the short arm of chromosome 10 represent rare genetic abnormalities, especially those encompassing the chromosomal region 10p11-p12. To date, only 10 postnatal cases with microdeletion of this region have been described, and all patients shared a common phenotype, including intellectual disability, abnormal behavior, distinct dysmorphic features, visual impairment, and cardiac malformations. WAC was suggested to be the main candidate gene for intellectual disability associated with 10 p11-p12 deletion syndrome. Here, we describe a new case of de novo 10p11.23-p12.1 microdeletion in a patient with intellectual disability, abnormal behavior, and distinct dysmorphic features. Our observation allows us to redefine the smallest region of overlap among patients reported so far, with a size of 80 Kb and which contains only the WAC gene. These findings strengthen the hypothesis that haploinsufficency of WAC gene might be likely responsible for intellectual disability and behavior disorders. Our data also led us to propose a clinical pathway for patients with this recognizable genetic syndrome depending on the facial dysmorphisms. © 2016 Wiley Periodicals, Inc. PMID:27119754

  13. Role of DNA deletion length in mutation and cell survival

    International Nuclear Information System (INIS)

    A model is presented which is based on the assumption that malignant transformation, mutation, chromosome aberration, and reproductive death of cells are all manifestations of radiation induced deletions in the DNA of the cell, and that the size of the deletion in relation to the spacing of essential genes determines the consequences of that deletion. It is assumed that two independent types of potentially lethal lesions can result in DNA deletions, and that the relative numbers of these types of damage is dependent on radiation quality. The repair of the damage reduces the length of a deletion, but does not always eliminate it. The predictions of this model are in good agreement with a wide variety of experimental evidence. (author)

  14. Mechanisms of ring chromosome formation in 11 cases of human ring chromosome 21

    DEFF Research Database (Denmark)

    McGinniss, M J; Kazazian, H H; Stetten, G;

    1992-01-01

    ), resulting in deletion of varying amounts of 21q22.1 to 21qter. The data from one individual who had a Down syndrome phenotype were consistent with asymmetric breakage and reunion of 21q sequences from an intermediate isochromosome or Robertsonian translocation chromosome as reported by Wong et al. Another......We studied the mechanism of ring chromosome 21 (r(21)) formation in 13 patients (11 unique r(21)s), consisting of 7 from five families with familial r(21) and 6 with de novo r(21). The copy number of chromosome 21 sequences in the rings of these patients was determined by quantitative dosage......). The phenotype of patients correlated well with the extent of deletion or duplication of chromosome 21 sequences. These data demonstrate three mechanisms of r(21) formation and show that the phenotype of r(21) patients varies with the extent of chromosome 21 monosomy or trisomy....

  15. Quantum deletion: Beyond the no-deletion principle

    International Nuclear Information System (INIS)

    Suppose we are given two identical copies of an unknown quantum state and we wish to delete one copy from among the given two copies. The quantum no-deletion principle restricts us from perfectly deleting a copy but it does not prohibit us from deleting a copy approximately. Here we construct two types of a 'universal quantum deletion machine' which approximately deletes a copy such that the fidelity of deletion does not depend on the input state. The two types of universal quantum deletion machines are (1) a conventional deletion machine described by one unitary operator and (2) a modified deletion machine described by two unitary operators. Here it is shown that the modified deletion machine deletes a qubit with fidelity 3/4, which is the maximum limit for deleting an unknown quantum state. In addition to this we also show that the modified deletion machine retains the qubit in the first mode with average fidelity 0.77 (approx.) which is slightly greater than the fidelity of measurement for two given identical states, showing how precisely one can determine its state [S. Massar and S. Popescu, Phys. Rev. Lett. 74, 1259 (1995)]. We also show that the deletion machine itself is input state independent, i.e., the information is not hidden in the deleting machine, and hence we can delete the information completely from the deletion machine

  16. Ring chromosome 9 in a girl with developmental delay and dysmorphic features

    DEFF Research Database (Denmark)

    la Cour Sibbesen, Else; Jespersgaard, Cathrine; Alosi, Daniela; Bisgaard, Anne-Marie; Tümer, Zeynep

    2013-01-01

    In this report, we describe a female child with dysmorphic features and developmental delay. Chromosome microarray analysis followed by conventional karyotyping revealed a ring chromosome 9 with a 12 Mb deletion at 9pter-p23 and a 540 kb deletion at 9q34.3-qter. Four percent of the analyzed cells...

  17. Deletions and candidate genes in Williams syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Perez Jurado, L.A.; Peoples, R.; Francke, U. [Stanford Univ. CA (United States)] [and others

    1994-09-01

    Hemizygosity at the elastin locus (ELN) on chromosome 7q11.23 has recently been reported in several familial and sporadic cases of the developmental disorder, Williams syndrome (WS). Because the deletion is greater than the span of the ELN gene, a contiguous gene deletion syndrome has been suggested as the probable molecular basis for this condition. Thus far, neither the size of the deletion(s), nor other genes within it are known. We have analyzed samples from 27 sporadic WS patients by genotyping two multiallelic ELN intragenic polymorphisms, detectable by PCR amplification, and by Southern blotting for ELN gene dosage. Twenty four patients were hemizygous at the ELN locus while 3 showed no deletion or detectable rearrangement. Genotype studies on parental DNA were informative in 12 of the deletions. All 12 were due to de novo events, 8 in the maternal and 4 in the paternal chromosome. In an attempt to identify genes involved in WS we are also using a candidate gene approach. Delayed clearance of an exogenous calcium load with normal or slightly increased calcitonin levels in serum has been documented in WS patients suggesting a defective calcitonin action or calcium sensing function. The calcitonin receptor (CTR) gene is, therefore, a good candidate since CTR has a dual role as a hormonal receptor for calcitonin and an extracellular calcium sensor. We have mapped the CTR gene to chromosome 7q21.1 by PCR-SSCA of somatic cell hybrids and FISH analysis. Using two color FISH with probes for ELN and CTR, both loci are located on 7q at a distance of {approximately}10 Mb, CTR being telomeric. Our CTR probe does not detect any genomic abnormality by FISH or Southern blot in the patients` samples analyzed. We have identified a diallelic polymorphism in the CTR cDNA and are currently testing the hypothesis of an impaired CTR expression as responsible for some of the clinical features of WS by analysing the CTR transcripts by RT-PCR.

  18. Analysis of partial AZFc deletions in Malaysian infertile male subjects.

    Science.gov (United States)

    Almeamar, Hussein Ali; Ramachandran, Vasudevan; Ismail, Patimah; Nadkarni, Prashan; Fawzi, Nora

    2013-04-01

    Complete deletions in the AZF (a, b, and c) sub-regions of the Y-chromosome have been shown to contribute to unexplained male infertility. However, the role of partial AZFc deletions in male infertility remains to be verified. Three types of partial AZFc deletions have been identified. They are gr/gr, b1/b3, and b2/b3 deletions. A recent meta-analysis showed that ethnic and geographical factors might contribute to the association of partial AZFc deletions with male infertility. This study analyzed the association of partial AZFc deletions in Malaysian infertile males. Fifty two oligozoospermic infertile males and 63 fertile controls were recruited to this study. Screening for partial AZFc deletions was done using the two sequence-tagged sites approach (SY1291 and SY1191) which were analyzed using both the conventional PCR gel-electrophoresis and the high resolution melt, HRM method. Gr/gr deletions were found in 11.53% of the cases and 9.52% of the controls (p = 0.725). A B2/b3 deletion was found in one of the cases (p = 0.269). No B1/b3 deletions were identified in this study. The results of HRM analysis were consistent with those obtained using the conventional PCR gel-electrophoresis method. The HRM analysis was highly repeatable (95% limit of agreement was -0.0879 to 0.0871 for SY1191 melting temperature readings). In conclusion, our study showed that partial AZFc deletions were not associated with male infertility in Malaysian subjects. HRM analysis was a reliable, repeatable, fast, cost-effective, and semi-automated method which can be used for screening of partial AZFc deletions. PMID:23231020

  19. Deletions of the elastin gene in Williams Syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Greenberg, F.; Nickerson, E.; McCaskill, C. [Baylor College of Medicine, Houston, TX (United States)] [and others

    1994-09-01

    To investigate deletions in the elastin gene in patients with Williams Syndrome (WS), we screened 37 patients and their parents for deletions in the elastin gene by both fluorescence in situ hybridization (FISH) using cosmid cELN272 containing the 5{prime} end of the elastin gene and by polymerase chain reaction (PCR) using a primer pair which amplifies intron 17 in the elastin gene, producing a polymorphic amplification product. Thirty-two patients have been investigated by both the FISH and PCR techniques, one patient was studied only by PCR, and 4 patients were studied only by FISH. Overall, 34 of 37 patients (92%) were deleted for the elastin gene. Using the PCR marker, 14 patients were informative and 12 were shown to be deleted [maternal (n=5) and paternal (n=7)]. Using cosmid cELN272, 33 of 36 patients demonstrated a deletion of chromosome 7q11.23. In one family, both the mother and daughter were deleted due to an apparently de novo deletion arising in the mother. Three patients were not deleted using the elastin cosmid; 2 of these patients have classic WS. Another non-deleted patient has the typical facial features and hypercalcemia but normal intelligence. These three patients will be important in delineating the critical region(s) responsible for the facial features, hypercalcemia, mental retardation and supravalvular aortic stenosis (SVAS). There was not an absolute correlation between deletions in elastin and SVAS, although these individuals may be at risk for other cardiovascular complications such as hypertention. Since the majority of WS patients are deleted for a portion of the elastin gene, most likely this marker will be an important diagnostic tool, although more patients will need to be studied. Those patients who are not deleted but clinically have WS will be missed using only this one marker. Expansion of the critical region to other loci and identification of additional markers will be essential for identifying all patients with WS.

  20. Rare human diseases: 9p deletion syndrome

    Directory of Open Access Journals (Sweden)

    Galagan V.O.

    2014-09-01

    Full Text Available Objective of the study was to review the anamnesis, pheno - and genotype in patients with rare chromosome disorders such as 9p deletion syndrome. Genetic methods of investigation (clinical and genealogical, cytogenetic, FISH- method, paraclinical and instrumental methods of examination were used. Karyotyping was performed by the G-method of differential staining of chromosomes. Only three cases of pathology were diagnosed in the Medical Genetics Center over the last 10 years. By anamnesis data nobody in the probands’ families had bad habits, was exposed to occupational hazards, took part in the elimination of the Chernobyl accident or lived in contaminated areas. Clinical signs of diseases have not been identified in probands’ parents. All probands had trigonocephaly, bilateral epicanthal folds, ocular hypertelorism, downslanting palpebral fissures, long philtrum, flat face and nasal bridge, low set ears with malformed auricles. Two patients of three ones had exophthalmos, contracture of the second and third fingers, abnormal external genitalia. In all three cases there was monosomy of chromosome 9 of critical segment p 24. Normal karyotypes were seen in all parents, so there were three cases of new mutations of 9p deletion syndrome. Retardation of physical, psycho-spech, mental development in proband with or without congenital anomalies requires medical genetic counseling in a specialized institution. Cases of reproductive loss in anamnesis require cytogenetic investigation of fetal membranes and amniotic fluid.

  1. Frequency of heterozygous TET2 deletions in myeloproliferative neoplasms

    Directory of Open Access Journals (Sweden)

    Joseph Tripodi

    2010-09-01

    Full Text Available Joseph Tripodi1, Ronald Hoffman1, Vesna Najfeld2, Rona Weinberg31The Myeloproliferative Disorders Program, Tisch Cancer Institute, Department of Medicine and 2Department of Medicine and Pathology, Mount Sinai School of Medicine, 3The Myeloproliferative Disorders Program, Cellular Therapy Laboratory, The New York Blood Center, New York, NY, USAAbstract: The Philadelphia chromosome (Ph-negative myeloproliferative neoplasms (MPNs, including polycythemia vera, essential thrombocythemia, and primary myelofibrosis, are a group of clonal hematopoietic stem cell disorders with overlapping clinical and cytogenetic features and a variable tendency to evolve into acute leukemia. These diseases not only share overlapping chromosomal abnormalities but also a number of acquired somatic mutations. Recently, mutations in a putative tumor suppressor gene, ten-eleven translocation 2 (TET2 on chromosome 4q24 have been identified in 12% of patients with MPN. Additionally 4q24 chromosomal rearrangements in MPN, including TET2 deletions, have also been observed using conventional cytogenetics. The goal of this study was to investigate the frequency of genomic TET2 rearrangements in MPN using fluorescence in situ hybridization as a more sensitive method for screening and identifying genomic deletions. Among 146 MPN patients, we identified two patients (1.4% who showed a common 4q24 deletion, including TET2. Our observations also indicated that the frequency of TET2 deletion is increased in patients with an abnormal karyotype (5%.Keywords: TET2, myeloproliferative neoplasms, fluorescence in situ hybridization, cytogenetics

  2. Genetics Home Reference: 22q11.2 deletion syndrome

    Science.gov (United States)

    ... Seattle, Washington Children's Hospital of Philadelphia Cincinnati Children's Hospital Medical Center Disease InfoSearch: 22q11.2 Deletion Syndrome Emory University School of Medicine Genetics Education Materials for School Success (GEMSS) MalaCards: chromosome 22q11. ...

  3. Chromosome Architecture and Genome Organization

    Science.gov (United States)

    Bernardi, Giorgio

    2015-01-01

    How the same DNA sequences can function in the three-dimensional architecture of interphase nucleus, fold in the very compact structure of metaphase chromosomes and go precisely back to the original interphase architecture in the following cell cycle remains an unresolved question to this day. The strategy used to address this issue was to analyze the correlations between chromosome architecture and the compositional patterns of DNA sequences spanning a size range from a few hundreds to a few thousands Kilobases. This is a critical range that encompasses isochores, interphase chromatin domains and boundaries, and chromosomal bands. The solution rests on the following key points: 1) the transition from the looped domains and sub-domains of interphase chromatin to the 30-nm fiber loops of early prophase chromosomes goes through the unfolding into an extended chromatin structure (probably a 10-nm “beads-on-a-string” structure); 2) the architectural proteins of interphase chromatin, such as CTCF and cohesin sub-units, are retained in mitosis and are part of the discontinuous protein scaffold of mitotic chromosomes; 3) the conservation of the link between architectural proteins and their binding sites on DNA through the cell cycle explains the “mitotic memory” of interphase architecture and the reversibility of the interphase to mitosis process. The results presented here also lead to a general conclusion which concerns the existence of correlations between the isochore organization of the genome and the architecture of chromosomes from interphase to metaphase. PMID:26619076

  4. CRIPT exonic deletion and a novel missense mutation in a female with short stature, dysmorphic features, microcephaly, and pigmentary abnormalities.

    Science.gov (United States)

    Leduc, Magalie S; Niu, Zhiyv; Bi, Weimin; Zhu, Wenmiao; Miloslavskaya, Irene; Chiang, Theodore; Streff, Haley; Seavitt, John R; Murray, Stephen A; Eng, Christine; Chan, Audrey; Yang, Yaping; Lalani, Seema R

    2016-08-01

    Mutations in CRIPT encoding cysteine-rich PDZ domain-binding protein are rare, and to date have been reported in only two patients with autosomal recessive primordial dwarfism and distinctive facies. Here, we describe a female with biallelic mutations in CRIPT presenting with postnatal growth retardation, global developmental delay, and dysmorphic features including frontal bossing, high forehead, and sparse hair and eyebrows. Additional clinical features included high myopia, admixed hyper- and hypopigmented macules primarily on the face, arms, and legs, and syndactyly of 4-5 toes bilaterally. Using whole exome sequencing (WES) and chromosomal microarray analysis (CMA), we detected a c.8G>A (p.C3Y) missense variant in exon 1 of the CRIPT gene inherited from the mother and a 1,331 bp deletion encompassing exon 1, inherited from the father. The c.8G>A (p.C3Y) missense variant in CRIPT was apparently homozygous in the proband due to the exon 1 deletion. Our findings illustrate the clinical utility of combining WES with copy number variant (CNV) analysis to provide a molecular diagnosis to patients with rare Mendelian disorders. Our findings also illustrate the clinical spectrum of CRIPT related mutations. © 2016 Wiley Periodicals, Inc. PMID:27250922

  5. A versatile reporter system for CRISPR-mediated chromosomal rearrangements

    OpenAIRE

    Li, Yingxiang; Park, Angela I.; Mou, Haiwei; Colpan, Cansu; Bizhanova, Aizhan; Akama-Garren, Elliot; Joshi, Nik; Hendrickson, Eric A; Feldser, David; Yin, Hao; Anderson, Daniel G.; Jacks, Tyler; Weng, Zhiping; Xue, Wen

    2015-01-01

    Although chromosomal deletions and inversions are important in cancer, conventional methods for detecting DNA rearrangements require laborious indirect assays. Here we develop fluorescent reporters to rapidly quantify CRISPR/Cas9-mediated deletions and inversions. We find that inversion depends on the non-homologous end-joining enzyme LIG4. We also engineer deletions and inversions for a 50 kb Pten genomic region in mouse liver. We discover diverse yet sequence-specific indels at the rearrang...

  6. A Case of ADHD and a Major Y Chromosome Abnormality

    Science.gov (United States)

    Mulligan, Aisling; Gill, Michael; Fitzgerald, Michael

    2008-01-01

    Background: ADHD is a common, heritable disorder of childhood. Sex chromosome abnormalities are relatively rare conditions that are sometimes associated with behavioral disorders. Method: The authors present a male child with ADHD and a major de-novo Y chromosome abnormality consisting of deletion of the long arm and duplication of the short arm.…

  7. Synthetic chromosomes.

    Science.gov (United States)

    Schindler, Daniel; Waldminghaus, Torsten

    2015-11-01

    What a living organism looks like and how it works and what are its components-all this is encoded on DNA, the genetic blueprint. Consequently, the way to change an organism is to change its genetic information. Since the first pieces of recombinant DNA have been used to transform cells in the 1970s, this approach has been enormously extended. Bigger and bigger parts of the genetic information have been exchanged or added over the years. Now we are at a point where the construction of entire chromosomes becomes a reachable goal and first examples appear. This development leads to fundamental new questions, for example, about what is possible and desirable to build or what construction rules one needs to follow when building synthetic chromosomes. Here we review the recent progress in the field, discuss current challenges and speculate on the appearance of future synthetic chromosomes. PMID:26111960

  8. Characterization of a complex rearrangement involving duplication and deletion of 9p in an infant with craniofacial dysmorphism and cardiac anomalies

    OpenAIRE

    Di Bartolo Daniel L; El Naggar Mohamed; Owen Renius; Sahoo Trilochan; Gilbert Fred; Pulijaal Venkat R; Mathew Susan

    2012-01-01

    Abstract Partial duplication and partial deletion of the short arm of chromosome 9 have each been reported in the literature as clinically recognizable syndromes. We present clinical, cytogenetic, and molecular findings on a five-week-old female infant with concomitant duplication and terminal deletion of the short arm of chromosome 9. To our knowledge ten such cases have previously been reported. Conventional cytogenetic analysis identified additional material on chromosome 9 at band p23. FI...

  9. X-chromosome workshop.

    Science.gov (United States)

    Paterson, A D

    1998-01-01

    Researchers presented results of ongoing research to the X-chromosome workshop of the Fifth World Congress on Psychiatric Genetics, covering a wide range of disorders: X-linked infantile spasms; a complex phenotype associated with deletions of Xp11; male homosexuality; degree of handedness; bipolar affective disorder; schizophrenia; childhood onset psychosis; and autism. This report summarizes the presentations, as well as reviewing previous studies. The focus of this report is on linkage findings for schizophrenia and bipolar disorder from a number of groups. For schizophrenia, low positive lod scores were obtained for markers DXS991 and DXS993 from two studies, although the sharing of alleles was greatest from brother-brother pairs in one study, and sister-sister in the other. Data from the Irish schizophrenia study was also submitted, with no strong evidence for linkage on the X chromosome. For bipolar disease, following the report of a Finnish family linked to Xq24-q27, the Columbia group reported some positive results for this region from 57 families, however, another group found no evidence for linkage to this region. Of interest, is the clustering of low positive linkage results that point to regions for possible further study. PMID:9686435

  10. Phenotypic and molecular assessment of seven patients with 6p25 deletion syndrome: Relevance to ocular dysgenesis and hearing impairment

    Directory of Open Access Journals (Sweden)

    Ritch Robert

    2004-06-01

    Full Text Available Abstract Background Thirty-nine patients have been described with deletions involving chromosome 6p25. However, relatively few of these deletions have had molecular characterization. Common phenotypes of 6p25 deletion syndrome patients include hydrocephalus, hearing loss, and ocular, craniofacial, skeletal, cardiac, and renal malformations. Molecular characterization of deletions can identify genes that are responsible for these phenotypes. Methods We report the clinical phenotype of seven patients with terminal deletions of chromosome 6p25 and compare them to previously reported patients. Molecular characterization of the deletions was performed using polymorphic marker analysis to determine the extents of the deletions in these seven 6p25 deletion syndrome patients. Results Our results, and previous data, show that ocular dysgenesis and hearing impairment are the two most highly penetrant phenotypes of the 6p25 deletion syndrome. While deletion of the forkhead box C1 gene (FOXC1 probably underlies the ocular dysgenesis, no gene in this region is known to be involved in hearing impairment. Conclusions Ocular dysgenesis and hearing impairment are the two most common phenotypes of 6p25 deletion syndrome. We conclude that a locus for dominant hearing loss is present at 6p25 and that this locus is restricted to a region distal to D6S1617. Molecular characterization of more 6p25 deletion patients will aid in refinement of this locus and the identification of a gene involved in dominant hearing loss.

  11. How to diagnose the 22q11.2 deletion syndrome in patients with schizophrenia: a case report

    OpenAIRE

    Ohi, Kazutaka; Hashimoto, Ryota; Yamamori, Hidenaga; Yasuda, Yuka; Fujimoto, Michiko; Nakatani, Noriko; Kamino, Kouzin; Takeda, Masatoshi

    2013-01-01

    The 22q11.2 deletion syndrome is caused by a microdeletion of chromosome 22. One third of all patients with 22q11.2 deletion develop schizophrenia-like symptoms. In general, the prevalence of 22q11.2 deletion in patients with schizophrenia is 1%–2%. The 22q11.2 deletion is one of the major known genetic risk factors for schizophrenia. However, clinical differences in the phenotypes between patients with schizophrenia who are 22q11.2 deletion carriers and those who are not are still unknown. T...

  12. Comparison of facial features of DiGeorge syndrome (DGS) due to deletion 10p13-10pter with DGS due to 22q11 deletion

    Energy Technology Data Exchange (ETDEWEB)

    Goodship, J.; Lynch, S.; Brown, J. [Univ. of Newcastle, Tyne (United Kingdom)] [and others

    1994-09-01

    DiGeorge syndrome (DGS) is a congenital anomaly consisting of cardiac defects, aplasia or hypoplasia of the thymus and parathroid glands, and dysmorphic facial features. The majority of DGS cases have a submicroscopic deletion within chromosome 22q11. However there have been a number of reports of DGS in association with other chromosomal abnormalities including four cases with chromosome 10p deletions. We describe a further 10p deletion case and suggest that the facial features in children with DGS due to deletions of 10p are different from those associated with chromosome 22 deletions. The propositus was born at 39 weeks gestation to unrelated caucasian parents, birth weight 2580g (10th centile) and was noted to be dysmorphic and cyanosed shortly after birth. The main dysmorphic facial features were a broad nasal bridge with very short palpebral fissures. Echocardiography revealed a large subsortic VSD and overriding aorta. She had a low ionised calcium and low parathroid hormone level. T cell subsets and PHA response were normal. Abdominal ultrasound showed duplex kidneys and on further investigation she was found to have reflux and raised plasma creatinine. She had an anteriorly placed anus. Her karyotype was 46,XX,-10,+der(10)t(3;10)(p23;p13)mat. The dysmorphic facial features in this baby are strikingly similar to those noted by Bridgeman and Butler in child with DGS as the result of a 10p deletion and distinct from the face seen in children with DiGeorge syndrome resulting from interstitial chromosome 22 deletions.

  13. Absence epilepsy and the CHD2 gene: an adolescent male with moderate intellectual disability, short-lasting psychoses, and an interstitial deletion in 15q26.1–q26.2

    Science.gov (United States)

    Verhoeven, Willem MA; Egger, Jos IM; Knegt, Alida C; Zuydam, José; Kleefstra, Tjitske

    2016-01-01

    Deletions of the 15q26 region encompassing the chromodomain helicase DNA binding domain 2 (CHD2) gene have been associated with intellectual disability, behavioral problems, and several types of epilepsy. Including the cases mentioned in ECARUCA (European cytogeneticists association register of unbalanced chromosome aberrations) and DECIPHER (database of genomic variation and phenotype in humans using ensembl resources), so far, a total of 13 intellectually disabled patients with a genetically proven deletion of the CHD2 gene are described, of whom eleven had a history of severe forms of epilepsy starting from a young age. In this article, a moderately intellectually disabled 15-year-old male with a 15q26.1–q26.2 interstitial deletion is reported, who was referred for analysis of two recent short-lasting psychotic episodes that were nonresponsive to antipsychotic treatment and recurrent disinhibited behaviors since early infancy. Careful interdisciplinary assessment revealed that the psychotic phenomena originated from a previously unrecognized absence epilepsy. Treatment with valproic acid was started which resulted in full remission of psychotic symptoms, and consequently, substantial improvement of behavior. It was concluded that in case of (rare) developmental disorders with genetically proven etiology, a detailed inventory of anamnestic data and description of symptomatology over time may elucidate epilepsy-related psychopathology for which a specific treatment regimen is needed.

  14. Engineering Mouse Chromosomes with Cre-loxP: Range, Efficiency, and Somatic Applications

    OpenAIRE

    Zheng, Binhai; Sage, Marijke; Sheppeard, Elizabeth A.; Jurecic, Vesna; Bradley, Allan

    2000-01-01

    Chromosomal rearrangements are important resources for genetic studies. Recently, a Cre-loxP-based method to introduce defined chromosomal rearrangements (deletions, duplications, and inversions) into the mouse genome (chromosome engineering) has been established. To explore the limits of this technology systematically, we have evaluated this strategy on mouse chromosome 11. Although the efficiency of Cre-loxP-mediated recombination decreases with increasing genetic distance when the two endp...

  15. Double helicase II (uvrD)-helicase IV (helD) deletion mutants are defective in the recombination pathways of Escherichia coli.

    OpenAIRE

    Mendonca, V M; Kaiser-Rogers, K; Matson, S W

    1993-01-01

    The Escherichia coli helD (encoding helicase IV) and uvrD (encoding helicase II) genes have been deleted, independently and in combination, from the chromosome and replaced with genes encoding antibiotic resistance. Each deletion was verified by Southern blots, and the location of each deletion was confirmed by P1-mediated transduction. Cell strains containing the single and double deletions were viable, indicating that helicases II and IV are not essential for viability. Cell strains lacking...

  16. Analysis of the Ceratitis capitata y chromosome using in situ hybridization to mitotic chromosomes

    International Nuclear Information System (INIS)

    In Ceratitis capitata the Y chromosome is responsible for sex-determination. We used fluorescence in situ hybridization (FISH) for cytogenetic analysis of mitotic chromosomes. FISH with the wild-type strain EgyptII and two repetitive DNA probes enabled us to differentiate between the short and the long arm of the Y chromosome and gives a much better resolution than C-banding of mitotic chromosomes. We identified the Y-chromosomal breakpoints in Y-autosome translocations using FISH. Even more complex rearrangements i.e. deletions and insertions in some translocation strains were detected by this method. A strategy for mapping the primary sex determination factor in Ceratitis capitata by FISH is presented. (author)

  17. Mouse acute myeloid leukemia and abnormality in chromosome II

    International Nuclear Information System (INIS)

    This review described abnormality in chromosome II that is characteristic in the radiation-induced leukemia in the title (AML) in mice. The disease is reportedly increased in A-bomb survivors. AML occurs in mice of RFM, CBA and other strains 1-1.5 years after whole body irradiation. The incidence increases dependently on dose, however, it decreases over around the dose of 3 Gy of X- and γ-ray. The incidence (20-25%) is higher in males. Abnormality seen in chromosome II is classified in types I-IV and II-IV types involve terminal deletion, interstitial deletion and translocation. The deleted region common on the chromosome (marker chromosome) is about 1 cM long, which corresponds to human 11p11-12 region frequently deleted in AML patients. The AML marker chromosome is suggested to be yielded by genomic instability induced by radiation. It is also suggested that there are fragile sites in the chromosome II. Future investigations are conceivably to be concentrated for identification of the AML causing gene. (K.H.)

  18. Chromosome Microarray.

    Science.gov (United States)

    Anderson, Sharon

    2016-01-01

    Over the last half century, knowledge about genetics, genetic testing, and its complexity has flourished. Completion of the Human Genome Project provided a foundation upon which the accuracy of genetics, genomics, and integration of bioinformatics knowledge and testing has grown exponentially. What is lagging, however, are efforts to reach and engage nurses about this rapidly changing field. The purpose of this article is to familiarize nurses with several frequently ordered genetic tests including chromosomes and fluorescence in situ hybridization followed by a comprehensive review of chromosome microarray. It shares the complexity of microarray including how testing is performed and results analyzed. A case report demonstrates how this technology is applied in clinical practice and reveals benefits and limitations of this scientific and bioinformatics genetic technology. Clinical implications for maternal-child nurses across practice levels are discussed. PMID:27276104

  19. Schizophrenia in an Adult With 6p25 Deletion Syndrome

    OpenAIRE

    Caluseriu, O; Mirza, G.; J. Ragoussis; Chow, E. W. C.; MacCrimmon, D.; Bassett, A S

    2006-01-01

    Chromosomal deletions at 6p25-p24 are rare findings in patients with developmental delay. There is limited information about the adult phenotype. We present a 36-year-old patient with schizophrenia, mild mental retardation, progressive hearing deficits, and characteristic facial features. Ocular (Axenfeld–Rieger anomaly) abnormalities were diagnosed in infancy; vision, however, has remained unimpaired. There were no other major congenital anomalies. Brain imaging showed only minor changes. Th...

  20. Recombinant Chromosome 4 from a Familial Pericentric Inversion: Prenatal and Adulthood Wolf-Hirschhorn Phenotypes

    Directory of Open Access Journals (Sweden)

    Francesca Malvestiti

    2013-01-01

    Full Text Available Pericentric inversion of chromosome 4 can give rise to recombinant chromosomes by duplication or deletion of 4p. We report on a familial case of Wolf-Hirschhorn Syndrome characterized by GTG-banding karyotypes, FISH, and array CGH analysis, caused by a recombinant chromosome 4 with terminal 4p16.3 deletion and terminal 4q35.2 duplication. This is an aneusomy due to a recombination which occurred during the meiosis of heterozygote carrier of cryptic pericentric inversion. We also describe the adulthood and prenatal phenotypes associated with the recombinant chromosome 4.

  1. Chromosomal mechanisms in murine radiation acute myeloid leukemogenesis

    International Nuclear Information System (INIS)

    Chromosome 2 abnormalities, particularly interstitial deletions, characterize murine radiation-induced acute myeloid leukaemias (AMLs). Here, G-band analyses in CBA/H mice of early (1-6 month) post 3 Gy X-radiation events in bone marrow cells in vivo and karyotype evolution in one unusual AML are presented. The early event analysis showed that all irradiated animals carry chromosome 2 abnormalities, that chromosome 2 abnormalities are more frequent than expected and that interstitial deletions are more common in chromosome 2 than in the remainder of the genome. On presentation AML case N122 carried a t(2; 11) terminal translocation which, with passaging, evolved into a del2(C3F3). Therefore two pathways in leukaemogenesis might exist, one deletion-driven, the other terminal tranlocation-driven involving interstitial genes and terminal genes respectively of chromosome 2. As all irradiated individuals carried chromosome 2 abnormalities, the formation of these aberrations does not determine individual leukaemogenic sensitivity as only 20-25% of animals would be expected to develop AML. Similar lines of argument suggest that chromosome 2 abnormalities are necessary but not sufficient for radiation leukaemogenesis in CBA/H nor are they rate limiting in leukaemogenesis. (Author)

  2. Chromosomal mechanisms in murine radiation acute myeloid leukemogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Bouffler, S.D.; Breckon, G.; Cox, R. [National Radiological Protection Board, Chilton (United Kingdom)

    1996-04-01

    Chromosome 2 abnormalities, particularly interstitial deletions, characterize murine radiation-induced acute myeloid leukaemias (AMLs). Here, G-band analyses in CBA/H mice of early (1-6 month) post 3 Gy X-radiation events in bone marrow cells in vivo and karyotype evolution in one unusual AML are presented. The early event analysis showed that all irradiated animals carry chromosome 2 abnormalities, that chromosome 2 abnormalities are more frequent than expected and that interstitial deletions are more common in chromosome 2 than in the remainder of the genome. On presentation AML case N122 carried a t(2; 11) terminal translocation which, with passaging, evolved into a del2(C3F3). Therefore two pathways in leukaemogenesis might exist, one deletion-driven, the other terminal tranlocation-driven involving interstitial genes and terminal genes respectively of chromosome 2. As all irradiated individuals carried chromosome 2 abnormalities, the formation of these aberrations does not determine individual leukaemogenic sensitivity as only 20-25% of animals would be expected to develop AML. Similar lines of argument suggest that chromosome 2 abnormalities are necessary but not sufficient for radiation leukaemogenesis in CBA/H nor are they rate limiting in leukaemogenesis. (Author).

  3. A case of 3p deletion syndrome associated with cerebellar hemangioblastoma.

    Science.gov (United States)

    Suzuki-Muromoto, Sato; Hino-Fukuyo, Naomi; Haginoya, Kazuhiro; Kikuchi, Atsuo; Sato, Hiroki; Sato, Yuko; Nakayama, Tojo; Kubota, Yuki; Kakisaka, Yosuke; Uematsu, Mitsugu; Kumabe, Toshihiro; Md, Shigeo Kure

    2016-02-01

    We described clinical course of a 24-year-old woman with 3p deletion syndrome associated with cerebellar hemangioblastoma at the age of 16 years old. She presented dysmorphic facial features, growth retardation and severe psychomotor retardation associated with 3p deletion syndrome. We identified de novo 3p deletion encompassing p25 by using array-based comparative genomic hybridization, where causative gene of von Hippel-Lindau (VHL) disease located. Surgical therapy for cerebellar hemangioblastoma was performed, and histological examination was consistent in cerebellar hemangioblastoma. She showed no other tumors associated VHL disease till 24 years old. This is the first case report of a patient with 3p deletion syndrome whose cerebellar hemangioblastoma may be associated with VHL disease. Repeat imaging studies were recommended for the patients with 3p deletion syndrome. PMID:26365017

  4. Investigation of deletions at 7q11.23 in 44 patients referred for Williams-Beuren syndrome, using FISH and four DNA polymorphisms

    DEFF Research Database (Denmark)

    Brøndum-Nielsen, K; Beck, B; Gyftodimou, J; Hørlyk, H; Liljenberg, U; Pedersen, W; Petersen, M B; Sand, A; Skovby, F; Stafanger, G; Zetterqvist, P; Tommerup, Niels

    1997-01-01

    Williams syndrome (WS) is associated with a submicroscopic deletion of the elastin gene (ELN) at 7q11.23. The deletion encompasses closely linked DNA markers. We have investigated 44 patients referred for possible WS using fluorescence in situ hybridization (FISH) analysis with a P1 clone...

  5. High-resolution mapping of the [gamma]-aminobutyric acid receptor subunit [beta]3 and [alpha]5 gene cluster on chromosome 15q11-q13, and localization of breakpoints in two Angelman syndrome patients

    Energy Technology Data Exchange (ETDEWEB)

    Sinnett, D.; Wagstaff, J.; Woolf, E. (Children' s Hospital, Boston, MA (United States) Harvard Medical School, Boston, MA (United States)); Glatt, K. (Children' s Hospital, Boston, MA (United States)); Kirkness, E.J. (National Inst. of Alcohol Abuse and Alcoholism, Rockville, MD (United States))Lalande, M. (Children' s Hospital, Boston, MA (United States) Harvard Medical School, Boston, MA (United States) Howard Hughes Medical Inst., Boston, MA (United States))

    1993-06-01

    The [gamma]-aminobutyric acid (GABA[sub A]) receptors are a family of ligand-gated chloride channels constituting the major inhibitory neurotransmitter receptors in the nervous system. In order to determine the genomic organization of the GABA[sub A] receptor [beta]3 subunit gene (GABRB3) and [alpha]5 subunit gene (GABRA5) in chromosome 15q11-q13, the authors have constructed a high-resolution physical map using the combined techniques of field-inversion gel electrophoresis and phage genomic library screening. This map, which covers nearly 1.0 Mb, shows that GABRB3 and GABRA5 are separated by less than 100 kb and are arranged in a head-to-head configuration. GABRB3 encompasses approximately 250 kb, while GABRA5 is contained within 70 kb. This difference in size is due in large part to an intron of 150 kb within GABRB3. The authors have also identified seven putative CpG islands within a 600-kb interval. Chromosomal rearrangement breakpoints -- in one Angelman syndrome (AS) patient with an unbalanced translocation and in another patient with a submicroscopic deletion -- are located within the large GABRB3 intron. These findings will facilitate chromosomal walking strategies for cloning the regions disrupted by the DNA rearrangements in these AS patients and will be valuable for mapping new genes to the AS chromosomal region. 64 refs., 6 figs., 2 tabs.

  6. 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

    OpenAIRE

    Hannes, F.D.; Sharp, A. J.; Mefford, H.C.; Ravel, de, T.; Ruivenkamp, C A; Breuning, M.H.; Fryns, J P; Devriendt, K; Buggenhout, van, G.; Vogels, A.; Stewart, H. H.; Hennekam, R. C.; Cooper, G M; Regan, R.; Knight, S.J.

    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 ...

  7. Nonrandom chromosomal changes in human malignant cells

    Energy Technology Data Exchange (ETDEWEB)

    Rowley, J D

    1977-01-01

    The role of chromosomal changes in human malignant cells has been the subject of much debate. The observation of nonrandom chromosomal changes has become well recognized in chronic myelogenous leukemia, and more recently in acute myelogenous leukemia. In the present report, data are presented on the sites of duplication of chromosome No. 1 in hematologic disorders. Trisomy for region lq25 to lq32 was observed in every one of 34 patients whose cells showed duplication of some part of chromosome No. 1. Adjacent regions lq21 to lq25, and lq32 to lqter, also were trisomic in the majority of patients. Two patients had deletions, one of lq32 to qter, and the other, of lp32 to pter. The sites of chromosomal breaks leading to trisomy differ from those involved in balanced reciprocal translocations. Some of these sites are sometimes, but not always, vulnerable in constitutional chromosomal abnormalities. The nature of the proliferative advantage conferred on myeloid cells by these chromosomal changes is unknown.

  8. Use of chromosome aberrations for predicting genetic hazards to man

    International Nuclear Information System (INIS)

    The question of the use of chromosome aberrations for predicting genetic hazards to man is discussed under the following headings: interspecific comparisons of dicentric and deletion production in peripheral leukocytes; comparison of dicentric yields in leukocytes to reciprocal translocation yield in spermatogonia; recovery of spermatogonia induced translocations in the sons of irradiated males; cytologically and genetically detected deletions; and current gaps in our knowledge and problems of future interest

  9. MINIMUM VARIANCE HEDGING AND THE ENCOMPASSING PRINCIPLE: ASSESSING THE EFFECTIVENESS OF FUTURES HEDGES

    OpenAIRE

    Manfredo, Mark R.; Sanders, Dwight R.

    2003-01-01

    An empirical methodology is developed for statistically testing the hedging effectiveness among competing futures contracts. The presented methodology is based on the encompassing principle, widely used in the forecasting literature, and applied here to minimum variance hedging regressions. Intuitively, the test is based on an alternative futures contract's ability to reduce residual basis risk by offering either diversification or a smaller absolute level of basis risk than a preferred futur...

  10. Cultural respect encompassing simulation training: being heard about health through broadband

    OpenAIRE

    Phyllis Min-yu Lau; Robyn Woodward-Kron; Karen Livesay; Kristine Elliott; Patricia Nicholson

    2016-01-01

    Background. Cultural Respect Encompassing Simulation Training (CREST) is a learning program that uses simulation to provide health professional students and practitioners with strategies to communicate sensitively with culturally and linguistically diverse (CALD) patients. It consists of training modules with a cultural competency evaluation framework and CALD simulated patients to interact with trainees in immersive simulation scenarios. The aim of this study was to test the feasibility of e...

  11. Cultural Respect Encompassing Simulation Training: Being Heard About Health Through Broadband

    OpenAIRE

    Min-Yu Lau, Phyllis; Woodward-Kron, Robyn; Livesay, Karen; Elliott, Kristine; Nicholson, Patricia

    2016-01-01

    Background Cultural Respect Encompassing Simulation Training (CREST) is a learning program that uses simulation to provide health professional students and practitioners with strategies to communicate sensitively with culturally and linguistically diverse (CALD) patients. It consists of training modules with a cultural competency evaluation framework and CALD simulated patients to interact with trainees in immersive simulation scenarios. The aim of this study was to test the feasibility of ex...

  12. Edit Distance with Block Deletions

    OpenAIRE

    Dana Shapira; Storer, James A.

    2011-01-01

    Several variants of the edit distance problem with block deletions are considered. Polynomial time optimal algorithms are presented for the edit distance with block deletions allowing character insertions and character moves, but without block moves. We show that the edit distance with block moves and block deletions is NP-complete (Nondeterministic Polynomial time problems in which any given solution to such problem can be verified in polynomial time, and any NP problem can be converted into...

  13. Cerebellar and brainstem hypoplasia in a child with a partial monosomy for the short arm of chromosome 5 and partial trisomy for the short arm of chromosome 10

    NARCIS (Netherlands)

    Arts, W F M; Hofstee, Y; Drejer, G F; Beverstock, G C; Oosterwijk, J C

    1995-01-01

    A child with hypoplasia of the cerebellum and brainstem in association with an unbalanced translocation, resulting in a partial deletion of the short arm of chromosome 5 and a partial trisomy of the short arm of chromosome 10, is described. A balanced translocation was present in his mother and mate

  14. Familial occurrence of the aniridia-Wilms tumor syndrome with deletion 11p13-14.1.

    Science.gov (United States)

    Yunis, J J; Ramsay, N K

    1980-06-01

    A report of a family with two half-brothers and a maternal aunt affected with the aniridia-Wilms tumor syndrome is presented. The proband showed a deletion of most of band 11p13 and of subband 11p14.1 of one chromosome 11, and the proband's mother and an older brother, both phenotypically normal, showed a balanced chromosomal rearrangement. This family demonstrates that deletion of a small chromosome segment (11p13-14.1) is responsible for the aniridia-Wilms tumor syndrome and, that in some cases, the syndrome can be familial. PMID:6246230

  15. Cytogenetic analysis of chromosomal abnormalities in Sri Lankan children

    Institute of Scientific and Technical Information of China (English)

    Colombo; Sri Lanka

    2015-01-01

    Background: Cytogenetic analysis is a valuable investigation in the diagnostic work up of children with suspected chromosomal disorders. The objective of this study was to describe the prevalence of various types of chromosomal abnormalities in Sri Lankan children undergoing cytogenetic analysis. Methods: Cytogenetic reports of 1554 consecutive children with suspected chromosomal disorders who underwent karyotyping in two genetic centers in Sri Lanka from January 2006 to December 2011 were reviewed retrospectively. Results: A total of 1548 children were successfully karyotyped. Abnormal karyotypes were found in 783 (50.6%) children. Numerical and structural abnormalities accounted for 90.8% and 9.2%, respectively. Down syndrome was the commonest aneuploidy identifi ed. Other various autosomal and sex chromosomal aneuploidies as well as micro-deletion syndromes were also detected. Conclusions: The prevalence of chromosomal abnormalities in Sri Lankan children undergoing cytogenetic analysis for suspected chromosomal disorders was relatively higher than that in Caucasian and other Asian populations.

  16. Chromosome Aberrations by Heavy Ions

    Science.gov (United States)

    Ballarini, Francesca; Ottolenghi, Andrea

    It is well known that mammalian cells exposed to ionizing radiation can show different types of chromosome aberrations (CAs) including dicentrics, translocations, rings, deletions and complex exchanges. Chromosome aberrations are a particularly relevant endpoint in radiobiology, because they play a fundamental role in the pathways leading either to cell death, or to cell conversion to malignancy. In particular, reciprocal translocations involving pairs of specific genes are strongly correlated (and probably also causally-related) with specific tumour types; a typical example is the BCR-ABL translocation for Chronic Myeloid Leukaemia. Furthermore, aberrations can be used for applications in biodosimetry and more generally as biomarkers of exposure and risk, that is the case for cancer patients monitored during Carbon-ion therapy and astronauts exposed to space radiation. Indeed hadron therapy and astronauts' exposure to space radiation represent two of the few scenarios where human beings can be exposed to heavy ions. After a brief introduction on the main general features of chromosome aberrations, in this work we will address key aspects of the current knowledge on chromosome aberration induction, both from an experimental and from a theoretical point of view. More specifically, in vitro data will be summarized and discussed, outlining important issues such as the role of interphase death/mitotic delay and that of complex-exchange scoring. Some available in vivo data on cancer patients and astronauts will be also reported, together with possible interpretation problems. Finally, two of the few available models of chromosome aberration induction by ionizing radiation (including heavy ions) will be described and compared, focusing on the different assumptions adopted by the authors and on how these models can deal with heavy ions.

  17. Proximal 21q deletion as a result of a de novo unbalanced t(12;21) translocation in a patient with dysmorphic features, hepatomegaly, thick myocardium and delayed psychomotor development

    DEFF Research Database (Denmark)

    Jespersgaard, Cathrine; Damgaard, Ida N; Cornelius, Nanna;

    2016-01-01

    BACKGROUND: IInterstitial 21q deletions can cause a wide spectrum of symptoms depending on the size and the location of the deletion. It has previously been suggested that the long arm of chromosome 21 can be divided into three regions based on the clinical severity of the patients and deletion of......, but subsequent chromosome microarray analysis suggested an approximately 18 Mb partial monosomy. Re-evaluation of the karyotype and fluorescence in situ hybridization revealed deletion of the proximal 21q11.2-q22.11 segment and insertion of 21q22.11-qter to 12qter. The deletion of the present case...

  18. Asymmetry and skin pigmentary anomalies in chromosome mosaicism.

    OpenAIRE

    WOODS, C. G.; BANKIER, A.; J Curry; Sheffield, L J; Slaney, S F; Smith, K.; Voullaire, L; Wellesley, D.

    1994-01-01

    We report six persons mosaic for a chromosome anomaly. All were mentally retarded and dysmorphic. Unilateral or asymmetrical features were found in all cases, in one an unusual transverse terminal limb anomaly, and in the others various degrees of hemiatrophy of the left side of the body. Five of the subjects had skin pigmentary anomalies which were distributed in the lines of Blaschko. The abnormal cell lines found were ring chromosome 22, trisomy 22, a large acrocentric marker, a deletion o...

  19. Deletion analysis of spinal muscular atrophy in southern Indian population

    Directory of Open Access Journals (Sweden)

    Swaminathan Bhairavi

    2008-01-01

    Full Text Available Background: Proximal spinal muscular atrophy (SMA is a genetically heterogeneous disease with paresis and muscle atrophy due to loss of anterior horn cell function. The survival of motor neuron gene (SMN and neuronal apoptosis inhibitory protein (NAIP play a primary role. Both the gene homologues exist as inverted duplications on Chromosome 5q. The telomeric/functional (SMN1 and the centromeric (SMN2 copies differ from each other in eight nucleotides. The C→T transition (at Codon 280 within Exon 7 of SMN2 causes disruption of an exonic splicing enhancer (ESE and/or creates an exonic splicing silencer (ESS leading to abnormal splicing and a truncated protein. Objective: To determine the molecular genetics of SMN1 and NAIP genes in SMA from southern India. Materials and Methods: In the present study, 37 patients from the neuromuscular disorders clinic of National Institute of Mental Health and Neurosciences were assayed for the deletions in the SMN1 and NAIP genes using PCR-RFLP methods. Results: Among the SMA Type I patients, 43% showed deletions of SMN1 and NAIP. In patients Type II SMA, 57% showed deletions of the SMN1 exons. Conclusion: Thus, deletions were found to occur in 47.8% of the Type I and II patients. Lower sensitivity of gene deletion study in clinically suspected SMA needs further study as clinical diagnosis of SMA is not gold standard. However, the results do correlate with other studies conducted in India.

  20. Involvement of multiple loci on chromosome 3 in renal cell cancer development

    NARCIS (Netherlands)

    van den Berg, Anke; Buys, CHCM

    1997-01-01

    In renal cell carcinoma (RCC), mostly occurring as sporadic cases, the short arm of chromosome 3 is a frequent target of deletion events. Taking into account cytological classifications of RCC, the deletions appear to be characteristic of clear cell or nonpapillary RCC only. This subtype constitutes

  1. Chronic granulomatous disease, the McLeod phenotype and the contiguous gene deletion syndrome-a review

    Directory of Open Access Journals (Sweden)

    Watkins Casey E

    2011-11-01

    Full Text Available Abstract Chronic Granulomatous Disease (CGD, a disorder of the NADPH oxidase system, results in phagocyte functional defects and subsequent infections with bacterial and fungal pathogens (such as Aspergillus species and Candida albicans. Deletions and missense, frameshift, or nonsense mutations in the gp91phox gene (also termed CYBB, located in the Xp21.1 region of the X chromosome, are associated with the most common form of CGD. When larger X-chromosomal deletions occur, including the XK gene deletion, a so-called "Contiguous Gene Deletion Syndrome" may result. The contiguous gene deletion syndrome is known to associate the Kell phenotype/McLeod syndrome with diseases such as X-linked chronic granulomatous disease, Duchenne muscular dystrophy, and X-linked retinitis pigmentosa. These patients are often complicated and management requires special attention to the various facets of the syndrome.

  2. Chromosomes. A comprehensive Xist interactome reveals cohesin repulsion and an RNA-directed chromosome conformation.

    Science.gov (United States)

    Minajigi, Anand; Froberg, John E; Wei, Chunyao; Sunwoo, Hongjae; Kesner, Barry; Colognori, David; Lessing, Derek; Payer, Bernhard; Boukhali, Myriam; Haas, Wilhelm; Lee, Jeannie T

    2015-07-17

    The inactive X chromosome (Xi) serves as a model to understand gene silencing on a global scale. Here, we perform "identification of direct RNA interacting proteins" (iDRiP) to isolate a comprehensive protein interactome for Xist, an RNA required for Xi silencing. We discover multiple classes of interactors-including cohesins, condensins, topoisomerases, RNA helicases, chromatin remodelers, and modifiers-that synergistically repress Xi transcription. Inhibiting two or three interactors destabilizes silencing. Although Xist attracts some interactors, it repels architectural factors. Xist evicts cohesins from the Xi and directs an Xi-specific chromosome conformation. Upon deleting Xist, the Xi acquires the cohesin-binding and chromosomal architecture of the active X. Our study unveils many layers of Xi repression and demonstrates a central role for RNA in the topological organization of mammalian chromosomes. PMID:26089354

  3. Origin and evolution of X chromosome inactivation.

    Science.gov (United States)

    Gribnau, Joost; Grootegoed, J Anton

    2012-06-01

    Evolution of the mammalian sex chromosomes heavily impacts on the expression of X-encoded genes, both in marsupials and placental mammals. The loss of genes from the Y chromosome forced a two-fold upregulation of dose sensitive X-linked homologues. As a corollary, female cells would experience a lethal dose of X-linked genes, if this upregulation was not counteracted by evolution of X chromosome inactivation (XCI) that allows for only one active X chromosome per diploid genome. Marsupials rely on imprinted XCI, which inactivates always the paternally inherited X chromosome. In placental mammals, random XCI (rXCI) is the predominant form, inactivating either the maternal or paternal X. In this review, we discuss recent new insights in the regulation of XCI. Based on these findings, we propose an X inactivation center (Xic), composed of a cis-Xic and trans-Xic that encompass all elements and factors acting to control rXCI either in cis or in trans. We also highlight that XCI may have evolved from a very small nucleation site on the X chromosome in the vicinity of the Sox3 gene. Finally, we discuss the possible evolutionary road maps that resulted in imprinted XCI and rXCI as observed in present day mammals. PMID:22425180

  4. The prevalence of Y chromosome microdeletions in Pakistani infertile men

    Directory of Open Access Journals (Sweden)

    Rubina Tabassum Siddiqui

    2013-01-01

    Full Text Available Background: Microdeletions of the azoospermia factor locus of the long arm of Y chromosome are an etiological factor of severe oligozoospermia or azoospermia. Objective: The aim of this study was to investigate the prevalence of Y-chromosome microdeletions in AZF region and their role in infertility in Pakistani population. Materials and Methods: The type of deletions in AZF locus were detected in infertile men (n=113 and the association of Y chromosome microdeletions with male infertility was assessed by including men (50 with normal karyotype and having children. Y chromosome microdeletions were detected by multiplex PCR using 10 sequence tagged sites namely sY81, sY130, sY141, sY142, sY155, sY157, sY160, sY182, sY231, and sY202 that covered all three regions of AZF. Results: Individuals with severe oligozoospermia showed 2.86% deletion frequency in AZFc region as compared to azoospermic males (5.5%. Conclusion: The results of our study showed that deletions in Y chromosome are not playing major part in male infertility. Moreover, multiplex-PCR strategy might preferably be employed for the detection of Y chromosome microdeletions allied to male infertility.

  5. A YAC contig encompassing the XRCC5 (Ku80) DNA repair gene and complementation of defective cells by YAC protoplast fusion

    Energy Technology Data Exchange (ETDEWEB)

    Blunt, T.; Priestley, A.; Hafezparast, M.; McMillan, T. [Univ. of Sussex, Brighton (United Kingdom)] [and others

    1995-11-20

    The Chinese hamster ovary xrs mutants are sensitive to ionizing radiation, defective in DNA double-strand break rejoining, and unable to carry out V(D)J recombination effectively. Recently, the gene defective in these mutants, XRCC5, has been shown to encode Ku80, a component of the Ku protein and DNA-dependent protein kinase. We present here a YAC contig involving 25 YACs mapping to the region 2q33-q34, which encompasses the XRCC5 gene. Eight new markers for this region of chromosome 2 are identified. YACs encoding the Ku80 gene were transferred to xrs cells by protoplast fusion, and complementation of all the defective phenotypes has been obtained with two YACs. We discuss the advantages and disadvantages of this approach as a strategy for cloning human genes complementing defective rodent cell lines. 44 refs., 2 figs., 4 tabs.

  6. Occurrence of two different intragenic deletions in two male relatives affected with Duchenne muscular dystrophy

    Energy Technology Data Exchange (ETDEWEB)

    Mostacciuolo, M.L.; Miorin, M.; Vitiello, L.; Rampazzo, A.; Fanin, M.; Angelini, C.; Danieli, G.A. [Univ. of Padua (Italy)

    1994-03-01

    The occurrence of 2 different intragenic deletions (exons 10-44 and exon 45, respectively) is reported in 2 male relatives affected with Duchenne muscular dystrophy, both showing the same haplotype for DNA markers not included in the deleted segment. The 2 different deletions seem to have occurred independently in the same X chromosome. This finding, together with other reports, suggests possibly an increased predisposition to mutations within the DMD locus in some families. Therefore, when dealing with prenatal diagnosis, the investigation on fetal DNA cannot be restricted only to the region in which a mutation was previously identified in the family. 14 refs., 1 fig.

  7. Prevalence of the Prefoldin Subunit 5 Gene Deletion in Canine Mammary Tumors

    OpenAIRE

    Silvia Hennecke; Julia Beck; Kirsten Bornemann-Kolatzki; Stephan Neumann; Hugo Murua Escobar; Ingo Nolte; Susanne Conradine Hammer; Marion Hewicker-Trautwein; Johannes Junginger; Franz-Josef Kaup; Bertram Brenig; Ekkehard Schütz

    2015-01-01

    Background A somatic deletion at the proximal end of canine chromosome 27 (CFA27) was recently reported in 50% of malignant mammary tumors. This region harbours the tumor suppressor gene prefoldin subunit 5 (PFDN5) and the deletion correlated with a higher Ki-67 score. PFDN5 has been described to repress c-MYC and is, therefore, a candidate tumor-suppressor and cancer-driver gene in canine mammary cancer. Aim of this study was to confirm the recurrent deletion in a larger number of tumors. Me...

  8. The role of the TCF4 gene in the phenotype of individuals with 18q segmental deletions

    OpenAIRE

    Hasi, Minire; Soileau, Bridgette; Sebold, Courtney; Hill, Annice; Hale, Daniel E.; O’Donnell, Louise; Cody, Jannine D.

    2011-01-01

    The goal of this study is to define the effects of TCF4 hemizygosity in the context of a larger segmental deletion of chromosome 18q. Our cohort included 37 individuals with deletions of 18q. Twenty-seven had deletions including TCF4 (TCF4+/−); nine had deletions that did not include TCF4 (TCF4+/+); and one individual had a microdeletion that included only the TCF4 gene. We compared phenotypic data from the participants’ medical records, survey responses, and in-person evaluations. Features u...

  9. The complete sequence of human chromosome 5

    Energy Technology Data Exchange (ETDEWEB)

    Schmutz, Jeremy; Martin, Joel; Terry, Astrid; Couronne, Olivier; Grimwood, Jane; Lowry, State; Gordon, Laurie A.; Scott, Duncan; Xie, Gary; Huang, Wayne; Hellsten, Uffe; Tran-Gyamfi, Mary; She, Xinwei; Prabhakar, Shyam; Aerts, Andrea; Altherr, Michael; Bajorek, Eva; Black, Stacey; Branscomb, Elbert; Caoile, Chenier; Challacombe, Jean F.; Chan, Yee Man; Denys, Mirian; Detter, Chris; Escobar, Julio; Flowers, Dave; Fotopulos, Dea; Glavina, Tijana; Gomez, Maria; Gonzales, Eidelyn; Goodstenin, David; Grigoriev, Igor; Groza, Matthew; Hammon, Nancy; Hawkins, Trevor; Haydu, Lauren; Israni, Sanjay; Jett, Jamie; Kadner, Kristen; Kimbal, Heather; Kobayashi, Arthur; Lopez, Frederick; Lou, Yunian; Martinez, Diego; Medina, Catherine; Morgan, Jenna; Nandkeshwar, Richard; Noonan, James P.; Pitluck, Sam; Pollard, Martin; Predki, Paul; Priest, James; Ramirez, Lucia; Rash, Sam; Retterer, James; Rodriguez, Alex; Rogers, Stephanie; Salamov, Asaf; Salazar, Angelica; Thayer, Nina; Tice, Hope; Tsai, Ming; Ustaszewska, Anna; Vo, Nu; Wheeler, Jeremy; Wu, Kevin; Yang, Joan; Dickson, Mark; Cheng, Jan-Fang; Eichler, Evan E.; Olsen, Anne; Pennacchio, Len A.; Rokhsar, Daniel S.; Richardson, Paul; Lucas, Susan M.; Myers, Richard M.; Rubin, Edward M.

    2004-04-15

    Chromosome 5 is one of the largest human chromosomes yet has one of the lowest gene densities. This is partially explained by numerous gene-poor regions that display a remarkable degree of noncoding and syntenic conservation with non-mammalian vertebrates, suggesting they are functionally constrained. In total, we compiled 177.7 million base pairs of highly accurate finished sequence containing 923 manually curated protein-encoding genes including the protocadherin and interleukin gene families and the first complete versions of each of the large chromosome 5 specific internal duplications. These duplications are very recent evolutionary events and play a likely mechanistic role, since deletions of these regions are the cause of debilitating disorders including spinal muscular atrophy (SMA).

  10. Chromosomal abnormalities in a psychiatric population

    Energy Technology Data Exchange (ETDEWEB)

    Lewis, K.E.; Lubetsky, M.J.; Wenger, S.L.; Steele, M.W. [Univ. of Pittsburgh Medical Center, PA (United States)

    1995-02-27

    Over a 3.5 year period of time, 345 patients hospitalized for psychiatric problems were evaluated cytogenetically. The patient population included 76% males and 94% children with a mean age of 12 years. The criteria for testing was an undiagnosed etiology for mental retardation and/or autism. Cytogenetic studies identified 11, or 3%, with abnormal karyotypes, including 4 fragile X positive individuals (2 males, 2 females), and 8 with chromosomal aneuploidy, rearrangements, or deletions. While individuals with chromosomal abnormalities do not demonstrate specific behavioral, psychiatric, or developmental problems relative to other psychiatric patients, our results demonstrate the need for an increased awareness to order chromosomal analysis and fragile X testing in those individuals who have combinations of behavioral/psychiatric, learning, communication, or cognitive disturbance. 5 refs., 1 fig., 2 tabs.

  11. A role for the fission yeast Rqh1 helicase in chromosome segregation

    DEFF Research Database (Denmark)

    Win, Thein Z; Mankouri, Hocine W; Hickson, Ian D;

    2005-01-01

    DNA repeat by deletion of reb1+ partially suppresses rqh1delta phenotypes. These data are consistent with the function of the Top3-RecQ complex in maintenance of the rDNA structure by processing aberrant chromosome structures arising from DNA replication. The chromosome segregation defects seen...

  12. A high-throughput method for the detection of homoeologous gene deletions in hexaploid wheat

    Directory of Open Access Journals (Sweden)

    Li Zhongyi

    2010-11-01

    Full Text Available Abstract Background Mutational inactivation of plant genes is an essential tool in gene function studies. Plants with inactivated or deleted genes may also be exploited for crop improvement if such mutations/deletions produce a desirable agronomical and/or quality phenotype. However, the use of mutational gene inactivation/deletion has been impeded in polyploid plant species by genetic redundancy, as polyploids contain multiple copies of the same genes (homoeologous genes encoded by each of the ancestral genomes. Similar to many other crop plants, bread wheat (Triticum aestivum L. is polyploid; specifically allohexaploid possessing three progenitor genomes designated as 'A', 'B', and 'D'. Recently modified TILLING protocols have been developed specifically for mutation detection in wheat. Whilst extremely powerful in detecting single nucleotide changes and small deletions, these methods are not suitable for detecting whole gene deletions. Therefore, high-throughput methods for screening of candidate homoeologous gene deletions are needed for application to wheat populations generated by the use of certain mutagenic agents (e.g. heavy ion irradiation that frequently generate whole-gene deletions. Results To facilitate the screening for specific homoeologous gene deletions in hexaploid wheat, we have developed a TaqMan qPCR-based method that allows high-throughput detection of deletions in homoeologous copies of any gene of interest, provided that sufficient polymorphism (as little as a single nucleotide difference amongst homoeologues exists for specific probe design. We used this method to identify deletions of individual TaPFT1 homoeologues, a wheat orthologue of the disease susceptibility and flowering regulatory gene PFT1 in Arabidopsis. This method was applied to wheat nullisomic-tetrasomic lines as well as other chromosomal deletion lines to locate the TaPFT1 gene to the long arm of chromosome 5. By screening of individual DNA samples from

  13. Pathogenesis of vestibular schwannoma in ring chromosome 22

    Directory of Open Access Journals (Sweden)

    Debiec-Rychter Maria

    2009-09-01

    Full Text Available Abstract Background Ring chromosome 22 is a rare human constitutional cytogenetic abnormality. Clinical features of neurofibromatosis type 1 and 2 as well as different tumour types have been reported in patients with ring chromosome 22. The pathogenesis of these tumours is not always clear yet. Methods We report on a female patient with a ring chromosome 22 presenting with severe mental retardation, autistic behaviour, café-au-lait macules and facial dysmorphism. Peripheral blood lymphocytes were karyotyped and array CGH was performed on extracted DNA. At the age of 20 years she was diagnosed with a unilateral vestibular schwannoma. Tumour cells were analyzed by karyotyping, array CGH and NF2 mutation analysis. Results Karyotype on peripheral blood lymphocytes revealed a ring chromosome 22 in all analyzed cells. A 1 Mb array CGH experiment on peripheral blood DNA showed a deletion of 5 terminal clones on the long arm of chromosome 22. Genetic analysis of vestibular schwannoma tissue revealed loss of the ring chromosome 22 and a somatic second hit in the NF2 gene on the remaining chromosome 22. Conclusion We conclude that tumours can arise by the combination of loss of the ring chromosome and a pathogenic NF2 mutation on the remaining chromosome 22 in patients with ring chromosome 22. Our findings indicate that patients with a ring 22 should be monitored for NF2-related tumours starting in adolescence.

  14. Roles of the Y chromosome genes in human cancers

    Directory of Open Access Journals (Sweden)

    Tatsuo Kido

    2015-06-01

    Full Text Available Male and female differ genetically by their respective sex chromosome composition, that is, XY as male and XX as female. Although both X and Y chromosomes evolved from the same ancestor pair of autosomes, the Y chromosome harbors male-specific genes, which play pivotal roles in male sex determination, germ cell differentiation, and masculinization of various tissues. Deletions or translocation of the sex-determining gene, SRY, from the Y chromosome causes disorders of sex development (previously termed as an intersex condition with dysgenic gonads. Failure of gonadal development results not only in infertility, but also in increased risks of germ cell tumor (GCT, such as gonadoblastoma and various types of testicular GCT. Recent studies demonstrate that either loss of Y chromosome or ectopic expression of Y chromosome genes is closely associated with various male-biased diseases, including selected somatic cancers. These observations suggest that the Y-linked genes are involved in male health and diseases in more frequently than expected. Although only a small number of protein-coding genes are present in the male-specific region of Y chromosome, the impacts of Y chromosome genes on human diseases are still largely unknown, due to lack of in vivo models and differences between the Y chromosomes of human and rodents. In this review, we highlight the involvement of selected Y chromosome genes in cancer development in men.

  15. Incomplete chromosome exchanges are not fingerprints of high LET neutrons

    International Nuclear Information System (INIS)

    A new fluorescence in situ hybridisation (FISH) technique combining whole chromosome specific DNA libraries with pan-centromeric DNA and telomeric PNA probes was introduced to investigate the induction of chromosome exchanges in human lymphocytes after exposure to low (4 Gy X rays) and high (1 Gy neutrons) linear energy transfer radiation. This combination of probes allowed accurate detection of exchange aberrations involving the painted chromosomes and an unambiguous discrimination between complete and incomplete exchanges, as well as terminal and interstitial deletions. Data obtained in the present study using combined FISH assay with telomeres detection showed no differences between two types of radiation regarding the induction of incomplete exchanges. (author)

  16. Mitotic chromosome structure

    International Nuclear Information System (INIS)

    Mounting evidence is compiling linking the physical organizational structure of chromosomes and the nuclear structure to biological function. At the base of the physical organizational structure of both is the concept of loop formation. This implies that physical proximity within chromosomes is provided for otherwise distal genomic regions and thus hierarchically organizing the chromosomes. Together with entropy many experimental observations can be explained with these two concepts. Among the observations that can be explained are the measured physical extent of the chromosomes, their shape, mechanical behavior, the segregation into territories (chromosomal and territories within chromosomes), the results from chromosome conformation capture experiments, as well as linking gene expression to structural organization.

  17. Deletion of 7q33-q35 in a Patient with Intellectual Disability and Dysmorphic Features: Further Characterization of 7q Interstitial Deletion Syndrome

    Directory of Open Access Journals (Sweden)

    Kristen Dilzell

    2015-01-01

    Full Text Available This case report concerns a 16-year-old girl with a 9.92 Mb, heterozygous interstitial chromosome deletion at 7q33-q35, identified using array comparative genomic hybridization. The patient has dysmorphic facial features, intellectual disability, recurrent infections, self-injurious behavior, obesity, and recent onset of hemihypertrophy. This patient has overlapping features with previously reported individuals who have similar deletions spanning the 7q32-q36 region. It has been difficult to describe an interstitial 7q deletion syndrome due to variations in the sizes and regions in the few patients reported in the literature. This case contributes to the further characterization of an interstitial distal 7q deletion syndrome.

  18. Autosomal deletion mapping in man.

    Science.gov (United States)

    Nance, W E; Engel, E

    1967-02-10

    Two families were observed in which morphologically similar dele tions involving a G-group chromosome were associated in the propositi with con spicuous abnormalities in ossification of the skull. The findings suggest that specific genetic information relating to morphogenesis of the skull may be located on a G-group chromosome. PMID:4959670

  19. Kaposi's sarcoma herpesvirus C-terminal LANA concentrates at pericentromeric and peri-telomeric regions of a subset of mitotic chromosomes

    International Nuclear Information System (INIS)

    The Kaposi's sarcoma-associated herpesvirus (KSHV) latency-associated nuclear antigen (LANA) tethers KSHV terminal repeat (TR) DNA to mitotic chromosomes to efficiently segregate episomes to progeny nuclei. LANA contains N- and C-terminal chromosome binding regions. We now show that C-terminal LANA preferentially concentrates to paired dots at pericentromeric and peri-telomeric regions of a subset of mitotic chromosomes through residues 996-1139. Deletions within C-terminal LANA abolished both self-association and chromosome binding, consistent with a requirement for self-association to bind chromosomes. A deletion abolishing TR DNA binding did not affect chromosome targeting, indicating LANA's localization is not due to binding its recognition sequence in chromosomal DNA. LANA distributed similarly on human and non-human mitotic chromosomes. These results are consistent with C-terminal LANA interacting with a cell factor that concentrates at pericentromeric and peri-telomeric regions of mitotic chromosomes

  20. ATLAS DQ2 DELETION SERVICE

    CERN Document Server

    Oleynik, D; The ATLAS collaboration; Garonne, V; Campana, S

    2012-01-01

    ATLAS DQ2 Deletion service is a sub system of the ATLAS Distributed Data Management (DDM) project DQ2. DDM DQ2 responsible for the replication, access and bookkeeping of ATLAS data across more than 130 distributed grid sites. It also enforces data management policies decided on by the collaboration and defined in the ATLAS computing model. Responsibility of ATLAS DQ2 Deletion service is serving deletion requests on the grid by interacting with grid middleware and the DQ2 catalogues. Furthermore, it also takes care of retry strategies, check-pointing transactions, load management and fault tolerance. In this talk special attention is paid to the technical details, which are used to achieve the high performance of service, accomplished without overloading either site storage, catalogues or other DQ2 components. Also specialty of database backend implementation will be described. Special section will be devote to the deletion monitoring service that allows operators a detailed view of the working system.

  1. ATLAS DQ2 Deletion Service

    CERN Document Server

    OLEYNIK, D; The ATLAS collaboration; GARONNE, V; CAMPANA, S

    2012-01-01

    The ATLAS Distributed Data Management project DQ2 is responsible for the replication, access and bookkeeping of ATLAS data across more than 100 distributed grid sites. It also enforces data management policies decided on by the collaboration and defined in the ATLAS computing model. The DQ2 deletion service is one of the most important DDM services. This distributed service interacts with 3rd party grid middleware and the DQ2 catalogs to serve data deletion requests on the grid. Furthermore, it also takes care of retry strategies, check-pointing transactions, load management and fault tolerance. In this paper special attention is paid to the technical details which are used to achieve the high performance of service (peaking at more than 4 millions files deleted per day), accomplished without overloading either site storage, catalogs or other DQ2 components. Special attention is also paid to the deletion monitoring service that allows operators a detailed view of the working system.

  2. A versatile reporter system for CRISPR-mediated chromosomal rearrangements.

    Science.gov (United States)

    Li, Yingxiang; Park, Angela I; Mou, Haiwei; Colpan, Cansu; Bizhanova, Aizhan; Akama-Garren, Elliot; Joshi, Nik; Hendrickson, Eric A; Feldser, David; Yin, Hao; Anderson, Daniel G; Jacks, Tyler; Weng, Zhiping; Xue, Wen

    2015-01-01

    Although chromosomal deletions and inversions are important in cancer, conventional methods for detecting DNA rearrangements require laborious indirect assays. Here we develop fluorescent reporters to rapidly quantify CRISPR/Cas9-mediated deletions and inversions. We find that inversion depends on the non-homologous end-joining enzyme LIG4. We also engineer deletions and inversions for a 50 kb Pten genomic region in mouse liver. We discover diverse yet sequence-specific indels at the rearrangement fusion sites. Moreover, we detect Cas9 cleavage at the fourth nucleotide on the non-complementary strand, leading to staggered instead of blunt DNA breaks. These reporters allow mechanisms of chromosomal rearrangements to be investigated. PMID:26018130

  3. Fetal chromosome analysis: screening for chromosome disease?

    DEFF Research Database (Denmark)

    Philip, J; Tabor, Ann; Bang, J;

    1983-01-01

    A + B). Pregnant women 35 years of age, women who previously had a chromosomally abnormal child, families with translocation carriers or other heritable chromosomal disease, families where the father was 50 years or more and women in families with a history of Down's syndrome (group A), were...... unbalanced chromosome abnormality in group A (women with elevated risk) is significantly higher than in group B + C (women without elevated risk) (relative risk 2.4). Women with a known familial translocation and women 40 years or more have a relative risk of 5.7 of having an unbalanced chromosome......The aim of the study was to investigate the rationale of the current indications for fetal chromosome analysis. 5372 women had 5423 amniocentesis performed, this group constituting a consecutive sample at the chromosome laboratory, Rigshospitalet, Copenhagen from March 1973 to September 1980 (Group...

  4. De Novo 13q13.3-21.31 deletion involving RB1 gene in a patient with hemangioendothelioma of the liver

    OpenAIRE

    Rapini, Novella; Lidano, Roberta; Pietrosanti, Silvia; Vitiello, Giuseppina; Grimaldi, Chiara; Postorivo, Diana; Nardone, Anna Maria; Del Bufalo, Francesca; Brancati, Francesco; Manca Bitti, Maria Luisa

    2014-01-01

    Interstitial deletions of the long arm of chromosome 13 (13q) are related with variable phenotypes, according to the size and the location of the deleted region. The main clinical features are moderate/severe mental and growth retardation, cranio-facial dysmorphism, variable congenital defects and increased susceptibility to tumors. Here we report a 3-year-old girl carrying a de novo 13q13.3-21.32 interstitial deletion. She showed developmental delay, growth retardation and mild dysmorphism i...

  5. A persistent mitochondrial deletion reduces fitness and sperm performance in heteroplasmic populations of C. elegans

    Directory of Open Access Journals (Sweden)

    Chin Kara

    2007-03-01

    Full Text Available Abstract Background Mitochondrial DNA (mtDNA mutations are of increasing interest due to their involvement in aging, disease, fertility, and their role in the evolution of the mitochondrial genome. The presence of reactive oxygen species and the near lack of repair mechanisms cause mtDNA to mutate at a faster rate than nuclear DNA, and mtDNA deletions are not uncommon in the tissues of individuals, although germ-line mtDNA is largely lesion-free. Large-scale deletions in mtDNA may disrupt multiple genes, and curiously, some large-scale deletions persist over many generations in a heteroplasmic state. Here we examine the phenotypic effects of one such deletion, uaDf5, in Caenorhabditis elegans (C. elegans. Our study investigates the phenotypic effects of this 3 kbp deletion. Results The proportion of uaDf5 chromosomes in worms was highly heritable, although uaDf5 content varied from worm to worm and within tissues of individual worms. We also found an impact of the uaDf5 deletion on metabolism. The deletion significantly reduced egg laying rate, defecation rate, and lifespan. Examination of sperm bearing the uaDf5 deletion revealed that sperm crawled more slowly, both in vitro and in vivo. Conclusion Worms harboring uaDf5 are at a selective disadvantage compared to worms with wild-type mtDNA. These effects should lead to the rapid extinction of the deleted chromosome, but it persists indefinitely. We discuss both the implications of this phenomenon and the possible causes of a shortened lifespan for uaDf5 mutant worms.

  6. Y Chromosome Microdeletions in Idiopathic Infertile Men from West Azarbaijan

    Directory of Open Access Journals (Sweden)

    Kiarash Attar

    2006-03-01

    Full Text Available Introduction: Although assisted reproduction techniques are used extensively in Iran, screening for Y chromosome microdeletions before intracytoplasmic sperm injection is often undervalued. Our aim was to investigate Y chromosome microdeletions in men with idiopathic azoospermia or severe oligospermia.Materials and Methods: In 99 selected patients with azoospermia or severe oligospermia and elevated levels of follicle-stimulating hormone and luteinizing hormone in combination with low serum testosterone levels, 20 pairs of sequence-tagged site-based primer sets specific for the Y microdeletion loci were analyzed. Primers were chosen to cover azoospermia factor (AZF regions as well as deleted in azoospermia (DAZ and the sex-determining region on Y chromosome (SRY genes. Also, 100 healthy men served as a control group.Results: Twenty-four patients (24.2% had microdeletions in AZF genes, but no microdeletions were found in men in the control group. In 15 patients (62.5%, 1 deletion was found. Six patients (25% had 2, and 3 (12.5% had 3 deletions. The deletions mainly comprised the AZFc region (in 21 of 24 patients; 87.5%, which corresponds to the DAZ gene. Deletions in AZFb were found in 7 patients (29.2%, and 4 (16.7% had deletions in the proximal part of AZF regions near SRY gene. No microdeletions were seen in the AZFa or SRY gene. Conclusion: Our results emphasize that Y chromosome microdeletion analysis should be carried out in all patients with idiopathic azoospermia or severe oligospermia who are candidates for intracytoplasmic sperm injection.

  7. Cell-autonomous correction of ring chromosomes in human induced pluripotent stem cells

    Science.gov (United States)

    Bershteyn, Marina; Hayashi, Yohei; Desachy, Guillaume; Hsiao, Edward C.; Sami, Salma; Tsang, Kathryn M.; Weiss, Lauren A.; Kriegstein, Arnold R.; Yamanaka, Shinya; Wynshaw-Boris, Anthony

    2014-03-01

    Ring chromosomes are structural aberrations commonly associated with birth defects, mental disabilities and growth retardation. Rings form after fusion of the long and short arms of a chromosome, and are sometimes associated with large terminal deletions. Owing to the severity of these large aberrations that can affect multiple contiguous genes, no possible therapeutic strategies for ring chromosome disorders have been proposed. During cell division, ring chromosomes can exhibit unstable behaviour leading to continuous production of aneuploid progeny with low viability and high cellular death rate. The overall consequences of this chromosomal instability have been largely unexplored in experimental model systems. Here we generated human induced pluripotent stem cells (iPSCs) from patient fibroblasts containing ring chromosomes with large deletions and found that reprogrammed cells lost the abnormal chromosome and duplicated the wild-type homologue through the compensatory uniparental disomy (UPD) mechanism. The karyotypically normal iPSCs with isodisomy for the corrected chromosome outgrew co-existing aneuploid populations, enabling rapid and efficient isolation of patient-derived iPSCs devoid of the original chromosomal aberration. Our results suggest a fundamentally different function for cellular reprogramming as a means of `chromosome therapy' to reverse combined loss-of-function across many genes in cells with large-scale aberrations involving ring structures. In addition, our work provides an experimentally tractable human cellular system for studying mechanisms of chromosomal number control, which is of critical relevance to human development and disease.

  8. Deletion of ABL/BCR on der(9 associated with severe basophilia

    Directory of Open Access Journals (Sweden)

    Shantashri Vaidya

    2011-01-01

    Full Text Available Chronic basophilic leukemia is a rare form in chronic myeloid leukemia patients. Only limited number of reports are available. Herein, we describe a patient who presented with fatigue, weight loss, leucocytosis, prominent basophilia, and mild eosinophilia. On biopsy, bone marrow was hypercellular with marked basophils. The immunophenotype showed abnormal expression of CD7, which is suggestive of basophilic maturation. Chromosomal analysis from GTG-banded metaphases revealed Ph positivity, and fluorescence in situ hybridization (FISH with BCR/ABL dual color, dual fusion probe showed single fusion on the der(22 chromosome and ABL/BCR fusion was deleted on the der(9 chromosome. The deletion (ABL/BCR on der(9 may be associated with basophilia which may be also indicative of the transformation of CML to acute myeloid leukemia.

  9. A novel 3q29 deletion associated with autism, intellectual disability, psychiatric disorders, and obesity.

    Science.gov (United States)

    Biamino, Elisa; Di Gregorio, Eleonora; Belligni, Elga Fabia; Keller, Roberto; Riberi, Evelise; Gandione, Marina; Calcia, Alessandro; Mancini, Cecilia; Giorgio, Elisa; Cavalieri, Simona; Pappi, Patrizia; Talarico, Flavia; Fea, Antonio M; De Rubeis, Silvia; Cirillo Silengo, Margherita; Ferrero, Giovanni Battista; Brusco, Alfredo

    2016-03-01

    Copy number variation (CNV) has been associated with a variety of neuropsychiatric disorders, including intellectual disability/developmental delay (ID/DD), autism spectrum disorder (ASD), and schizophrenia (SCZ). Often, individuals carrying the same pathogenic CNV display high clinical variability. By array-CGH analysis, we identified a novel familial 3q29 deletion (1.36 Mb), centromeric to the 3q29 deletion region, which manifests with variable expressivity. The deletion was identified in a 3-year-old girl diagnosed with ID/DD and autism and segregated in six family members, all affected by severe psychiatric disorders including schizophrenia, major depression, anxiety disorder, and personality disorder. All individuals carrying the deletion were overweight or obese, and anomalies compatible with optic atrophy were observed in three out of four cases examined. Amongst the 10 genes encompassed by the deletion, the haploinsufficiency of Optic Atrophy 1 (OPA1), associated with autosomal dominant optic atrophy, is likely responsible for the ophthalmological anomalies. We hypothesize that the haploinsufficiency of ATPase type 13A4 (ATP13A4) and/or Hairy/Enhancer of Split Drosophila homolog 1 (HES1) contribute to the neuropsychiatric phenotype, while HES1 deletion might underlie the overweight/obesity. In conclusion, we propose a novel contiguous gene syndrome due to a proximal 3q29 deletion variably associated with autism, ID/DD, psychiatric traits and overweight/obesity. PMID:26620927

  10. Genotype-phenotype correlation in 22q11.2 deletion syndrome

    Directory of Open Access Journals (Sweden)

    Michaelovsky Elena

    2012-12-01

    Full Text Available Abstract Background The 22q11.2 deletion syndrome (22q11.2DS is caused by hemizygous microdeletions on chromosome 22q11.2 with highly variable physical and neuropsychiatric manifestations. We explored the genotype-phenotype relationship in a relatively large 22q11.2DS cohort treated and monitored in our clinic using comprehensive clinical evaluation and detailed molecular characterization of the deletion. Methods Molecular analyses in 142 subjects with 22q11.2DS features were performed by FISH and MLPA methods. Participants underwent clinical assessment of physical symptoms and structured psychiatric and cognitive evaluation. Results Deletions were found in 110 individuals including one with an atypical nested distal deletion which was missed by the FISH test. Most subjects (88.2% carried the 3Mb typically deleted region and 11.8% carried 4 types of deletions differing in size and location. No statistically significant genotype-phenotype correlations were found between deletion type and clinical data although some differences in hypocalcemia and cardiovascular anomalies were noted. Analysis of the patient with the distal nested deletion suggested a redundancy of genes causing the physical and neuropsychiatric phenotype in 22q11.2DS and indicating that the psychiatric and cognitive trajectories may be governed by different genes. Conclusions MLPA is a useful and affordable molecular method combining accurate diagnosis and detailed deletion characterization. Variations in deletion type and clinical manifestations impede the detection of significant differences in samples of moderate size, but analysis of individuals with unique deletions may provide insight into the underlying biological mechanisms. Future genotype-phenotype studies should involve large multicenter collaborations employing uniform clinical standards and high-resolution molecular methods.

  11. Cultural Respect Encompassing Simulation Training: Being Heard About Health Through Broadband

    Science.gov (United States)

    Min-Yu Lau, Phyllis; Woodward-Kron, Robyn; Livesay, Karen; Elliott, Kristine; Nicholson, Patricia

    2016-01-01

    Background Cultural Respect Encompassing Simulation Training (CREST) is a learning program that uses simulation to provide health professional students and practitioners with strategies to communicate sensitively with culturally and linguistically diverse (CALD) patients. It consists of training modules with a cultural competency evaluation framework and CALD simulated patients to interact with trainees in immersive simulation scenarios. The aim of this study was to test the feasibility of expanding the delivery of CREST to rural Australia using live video streaming; and to investigate the fidelity of cultural sensitivity – defined within the process of cultural competency which includes awareness, knowledge, skills, encounters and desire – of the streamed simulations. Design and Methods In this mixed-methods evaluative study, health professional trainees were recruited at three rural academic campuses and one rural hospital to pilot CREST sessions via live video streaming and simulation from the city campus in 2014. Cultural competency, teaching and learning evaluations were conducted. Results Forty-five participants rated 26 reliable items before and after each session and reported statistically significant improvement in 4 of 5 cultural competency domains, particularly in cultural skills (Ptraining and the quality of the simulation training provided remotely by CREST. Conclusions Cultural sensitivity education using live video-streaming and simulation can contribute to health professionals’ learning and is effective in improving cultural competency. CREST has the potential to be embedded within health professional curricula across Australian universities to address issues of health inequalities arising from a lack of cultural sensitivity training. Significance for public health There are significant health inequalities for migrant populations. They commonly have poorer access to health services and poorer health outcomes than the Australian-born population

  12. Successful long-term growth hormone therapy in a girl with haploinsufficiency of the insulin-like growth factor-I receptor due to a terminal 15q26.2-> qter deletion detected by multiplex ligation probe amplification

    NARCIS (Netherlands)

    Walenkamp, Marie J. E.; Keizer-Schrama, Sabine M. P. F. de Muinck; de Mos, Marianne; Kalf, Margot E.; van Duyvenvoorde, Hermine A.; Boot, Annemieke M.; Kant, Sarina G.; White, Stefan J.; Losekoot, Monique; Den Dunnen, Johan T.; Karperien, Marcel; Wit, Jan M.

    2008-01-01

    Context: Microscopically visible heterozygous terminal 15q deletions encompassing the IGF1R gene are rare and usually associated with intrauterine growth retardation and short stature. The incidence of submicroscopic deletions is unknown, as is the effect of GH therapy in this condition. Objective:

  13. Successful long-term growth hormone therapy in a girl with haploinsufficiency of the insulin-like growth factor-I receptor due to a terminal 15q26.2->qter deletion detected by multiplex ligation probe amplification

    NARCIS (Netherlands)

    M.J.E. Walenkamp (Marie); S.M.P.F. de Muinck Keizer-Schrama (Sabine); M. de Mos (Marianne); M.E. Kalf (Margot); H.A. van Duyvenvoorde (Hermine); A.M. Boot (Annemieke); S.G. Kant (Sarina); S.J. White (Stefan); M. Losekoot (Monique); J.T. den Dunnen (Johan); M. Karperien (Marcel); J.M. Wit (Jan)

    2008-01-01

    textabstractContext: Microscopically visible heterozygous terminal 15q deletions encompassing the IGF1R gene are rare and usually associated with intrauterine growth retardation and short stature. The incidence of submicroscopic deletions is unknown, as is the effect of GH therapy in this condition.

  14. High-resolution array copy number analyses for detection of deletion, gain, amplification and copy-neutral LOH in primary neuroblastoma tumors: Four cases of homozygous deletions of the CDKN2A gene

    Directory of Open Access Journals (Sweden)

    Kogner Per

    2008-07-01

    Full Text Available Abstract Background Neuroblastoma is a very heterogeneous pediatric tumor of the sympathetic nervous system showing clinically significant patterns of genetic alterations. Favorable tumors usually have near-triploid karyotypes with few structural rearrangements. Aggressive stage 4 tumors often have near-diploid or near-tetraploid karyotypes and structural rearrangements. Whole genome approaches for analysis of genome-wide copy number have been used to analyze chromosomal abnormalities in tumor samples. We have used array-based copy number analysis using oligonucleotide single nucleotide polymorphisms (SNP arrays to analyze the chromosomal structure of a large number of neuroblastoma tumors of different clinical and biological subsets. Results Ninety-two neuroblastoma tumors were analyzed with 50 K and/or 250 K SNP arrays from Affymetrix, using CNAG3.0 software. Thirty percent of the tumors harbored 1p deletion, 22% deletion of 11q, 26% had MYCN amplification and 45% 17q gain. Most of the tumors with 1p deletion were found among those with MYCN amplification. Loss of 11q was most commonly seen in tumors without MYCN amplification. In the case of MYCN amplification, two types were identified. One type displayed simple continuous amplicons; the other type harbored more complex rearrangements. MYCN was the only common gene in all cases with amplification. Complex amplification on chromosome 12 was detected in two tumors and three different overlapping regions of amplification were identified. Two regions with homozygous deletions, four cases with CDKN2A deletions in 9p and one case with deletion on 3p (the gene RBMS3 were also detected in the tumors. Conclusion SNP arrays provide useful tools for high-resolution characterization of significant chromosomal rearrangements in neuroblastoma tumors. The mapping arrays from Affymetrix provide both copy number and allele-specific information at a resolution of 10–12 kb. Chromosome 9p, especially the gene

  15. Phenotypic Spectrum of 20 Novel Patients With Molecularly Defined Supernumerary Marker Chromosomes 15 and a Review of the Literature

    NARCIS (Netherlands)

    Kleefstra, Tjitske; de Leeuw, Nicole; Wolf, Roy; Nillesen, Willy M.; Schobers, Gaby; Mieloo, Hanneke; Willemsen, Marjolein; Perrotta, Concetta Simona; Poddighe, Pino J.; Feenstra, Ilse; Draaisma, Jos; van Ravenswaaij-Arts, Conny M. A.

    2010-01-01

    Supernumerary marker chromosomes (SMC) originating from chromosome 15 are the most common SMCs. They encompass clinically irrelevant SMC(15)s containing only heterochromatin and 15p material, and clinically relevant SMC(15)s that consist of both eu- and heterochromatic 15q material. On the basis of

  16. Newly Elaborated Multipurpose Polymer Electrolyte Encompassing RTILs for Smart Energy-Efficient Devices.

    Science.gov (United States)

    Nair, Jijeesh R; Porcarelli, Luca; Bella, Federico; Gerbaldi, Claudio

    2015-06-17

    Profoundly ion-conducting, self-standing, and tack-free ethylene oxide-based polymer electrolytes encompassing a room-temperature ionic liquid (RTIL) with specific amounts of lithium salt are successfully prepared via a rapid and easily upscalable process including a UV irradiation step. All prepared materials are thoroughly characterized in terms of their physical, chemical, and morphological properties and eventually galvanostatically cycled in lab-scale lithium batteries (LIBs) exploiting a novel direct polymerization procedure to get intimate electrode/electrolyte interfacial characteristics. The promising multipurpose characteristics of the newly elaborated materials are demonstrated by testing them in dye-sensitized solar cells (DSSCs), where the introduction of the iodine/iodide-based redox mediator in the polymer matrix assured the functioning of a lab-scale test cell with conversion efficiency exceeding 6% at 1 sun. The reported results enlighten the promising prospects of the material to be successfully implemented as stable, durable, and efficient electrolyte in next-generation energy conversion and storage devices. PMID:26020809

  17. A unifying graph-cut image segmentation framework: algorithms it encompasses and equivalences among them

    Science.gov (United States)

    Ciesielski, Krzysztof Chris; Udupa, Jayaram K.; Falcão, A. X.; Miranda, P. A. V.

    2012-02-01

    We present a general graph-cut segmentation framework GGC, in which the delineated objects returned by the algorithms optimize the energy functions associated with the lp norm, 1 graph cut GC (such as the min-cut/max-flow algorithm) and the relative fuzzy connectedness algorithms RFC (including iterative RFC, IRFC). The norm-based description of GGC provides more elegant and mathematically better recognized framework of our earlier results from [18, 19]. Moreover, it allows precise theoretical comparison of GGC representable algorithms with the algorithms discussed in a recent paper [22] (min-cut/max-flow graph cut, random walker, shortest path/geodesic, Voronoi diagram, power watershed/shortest path forest), which optimize, via lp norms, the intermediate segmentation step, the labeling of scene voxels, but for which the final object need not optimize the used lp energy function. Actually, the comparison of the GGC representable algorithms with that encompassed in the framework described in [22] constitutes the main contribution of this work.

  18. Seasonal Monitoring of Cardiovascular and Antiulcer Agents’ Concentrations in Stream Waters Encompassing a Capital City

    Directory of Open Access Journals (Sweden)

    Renáta Varga

    2013-01-01

    Full Text Available Nowadays monitoring pharmaceutical residues from surface waters is a widespread analytical task. Most of the studies are conducted from river waters or sewage treatment plants and mainly in Western Europe or North America. Such studies are seldom published from Eastern Europe, especially from stream waters, even though the prescription and consumption patterns of drugs as well as wastewater treatment procedures are very dissimilar. In Hungary the active substance of the most often prescribed drugs are cardiovascular and antiulcer agents. Hence in our study compounds belonging to these two groups were seasonally monitored in two main streams encompassing the Buda side of the Hungarian capital city and flowing into the Danube. To obtain data on the occurrence, fate, and seasonal variation of the compounds, samples were taken from altogether eleven points located near wastewater treatment plants and confluences. The results gave no identifiable pattern in the seasonal variation of concentrations but the contribution of the tributaries and wastewater treatment plants could be followed as expected. From the runoff corrected estuary concentrations the annual contribution of these streams to pharmaceutical pollution of the Danube could be estimated to be in excess of 1 kilogram for atenolol, famotidine, metoprolol, ranitidine, and sotalol.

  19. Chromosome 15q24 microdeletion syndrome

    Directory of Open Access Journals (Sweden)

    Magoulas Pilar L

    2012-01-01

    Full Text Available Abstract Chromosome 15q24 microdeletion syndrome is a recently described rare microdeletion syndrome that has been reported in 19 individuals. It is characterized by growth retardation, intellectual disability, and distinct facial features including long face with high anterior hairline, hypertelorism, epicanthal folds, downslanting palpebral fissures, sparse and broad medial eyebrows, broad and/or depressed nasal bridge, small mouth, long smooth philtrum, and full lower lip. Other common findings include skeletal and digital abnormalities, genital abnormalities in males, hypotonia, behavior problems, recurrent infections, and eye problems. Other less frequent findings include hearing loss, growth hormone deficiency, hernias, and obesity. Congenital malformations, while rare, can be severe and include structural brain anomalies, cardiovascular malformations, congenital diaphragmatic hernia, intestinal atresia, imperforate anus, and myelomeningocele. Karyotypes are typically normal, and the deletions were detected in these individuals by array comparative genomic hybridization (aCGH. The deletions range in size from 1.7-6.1 Mb and usually result from nonallelic homologous recombination (NAHR between paralogous low-copy repeats (LCRs. The majority of 15q24 deletions have breakpoints that localize to one of five LCR clusters labeled LCR15q24A, -B, -C, -D, and -E. The smallest region of overlap (SRO spans a 1.2 Mb region between LCR15q24B to LCR15q24C. There are several candidate genes within the SRO, including CYP11A1, SEMA7A, CPLX3, ARID3B, STRA6, SIN3A and CSK, that may predispose to many of the clinical features observed in individuals with 15q24 deletion syndrome. The deletion occurred as a de novo event in all of the individuals when parents were available for testing. Parental aCGH and/or FISH studies are recommended to provide accurate genetic counseling and guidance regarding prognosis, recurrence risk, and reproductive options. Management

  20. Chromosomal abnormalities in patients with sperm disorders

    Directory of Open Access Journals (Sweden)

    L. Y. Pylyp

    2013-02-01

    of sex chromosome aneuploidy and 2 cases of terminal deletion of Y chromosome. Klinefelter syndrome was detected in 67% of patients with azoospermia. A significant increase in the frequency of numerical chromosomal abnormalities was observed in a group of patients with azoospermia (P < 0.001. No differences were detected in the frequency of structural abnormalities in subgroups of patients. An increase in the frequency of chromosomal abnormalities with the decrease of sperm count was observed. Chromosomal abnormalities were detected with frequency 1.1% in a group of patients with normospermia, 1.9% in a group of patients with asthenozoospermia, 4.3% in patients with asthenoteratozoospermia, 6.5% in patients with oligoasthenozoospermia, 11.6% in patients with oligoasthenoteratozoospermia and 35% in a group of patients with azoospermia. Significant increase of the prevalence of chromosomal abnormalities was detected in subgroups of patients with azoospermia (P < 0.001 and oligozoospermia (P = 0.001 as compared to patients with normozoospermia. These results are considered to be criteria for selection of patients in need of cytogenetic studies before in vitro fertilization cycles because of the highest risk of chromosomal abnormalities detection.

  1. An Assay to Detect In Vivo Y Chromosome Loss in Drosophila Wing Disc Cells

    OpenAIRE

    Szabad, Janos; Bellen, Hugo J.; Venken, Koen J. T.

    2012-01-01

    Loss of the Y chromosome in Drosophila has no impact on cell viability and therefore allows us to assay the impact of environmental agents and genetic alterations on chromosomal loss. To detect in vivo chromosome loss in cells of the developing Drosophila wing primordia, we first engineered a Y chromosome with an attP docking site. By making use of the ΦC31 integrase system, we site-specifically integrated a genomic transgene encompassing the multiple wing hair ( mwh ) locus into this attP si...

  2. ATLAS DQ2 Deletion Service

    CERN Document Server

    OLEYNIK, D; The ATLAS collaboration; GARONNE, V; CAMPANA, S

    2012-01-01

    The ATLAS Distributed Data Management project DQ2 is responsible for the replication, access and bookkeeping of ATLAS data across more than 100 distributed grid sites. It also enforces data management policies decided on by the collaboration and defined in the ATLAS computing model. The DQ2 Deletion Service is one of the most important DDM services. This distributed service interacts with 3rd party grid middleware and the DQ2 catalogues to serve data deletion requests on the grid. Furthermore, it also takes care of retry strategies, check-pointing transactions, load management and fault tolerance. In this paper special attention is paid to the technical details which are used to achieve the high performance of service, accomplished without overloading either site storage, catalogues or other DQ2 components. Special attention is also paid to the deletion monitoring service that allows operators a detailed view of the working system.

  3. Mapping of metastasis suppressor genes for prostate cancer by microcell-mediated chromosome transfer

    Institute of Scientific and Technical Information of China (English)

    TomohikoICHIKAWA; ShigeruHOSOKI; HiroyoshiSUZUKI; KoichiroAKAKURA; TatsuoIGARASHI; YuzoFURUYA; MitsuoOSHIMURA; CarrieW.RINKER-SCHAEFFER; NaokiNIHEI; JohnT.ISAACS; HaruoITO

    2000-01-01

    Aim: To identify the metastasis suppressor genes for prostate cancer. Methods: A copy of human chromosomes was introduced into the highly metastatic Dunning R-3327 rat prostate cancer cells by the use of microcell-mediated chromosome transfer. Relationships between the size of human chromosomes introduced into microcell hybrid clones and the number of lung metastases produced by the clones were analyzed to determine which part of human chromosomes contained the metastasis suppressor gene (s) for prostate cancer. To determine portions of human chromosomes introduced, G-banding chromosomal analysis, fluorescence in situ hybridization analysis, and polymerase chain reaction analysis were performed. Results: Each of microcell hybrid clones containing human chromosomes 7, 8, 10, 11, 12, or 17 showed decreased ability to metastasize to the lung without any loss of ttmaorigenicity. This demonstrates that these human chromosomes contain metastasis suppressor genes for prostate cancer. Spontaneous deletion of portions of human chromosomes was observed in the human chromosome 7, 10, 11, 12, and 17 studies. In the human chromosome 8 study, irradiated microcell-mediated chromosome transfer was performed to enrich chromosomal ann deletions of human chromosome 8. Molecular and cytogenetic analyses of microcell hybrid clones demonstrated that metastasis suppressor genes on human chromosomes were located on 7q21-22, 7q31.2-32, 8p21-12, 10q11-22, 11p13-11.2, 12p11-q13, 12q24-ter, and 17pter-q23. KAI1 and MKK4/SEKI were identified as metastasis suppressor genes from 11p11.2 and 17p12, respectively. Conclusion: This assay system is useful to identify metastasis suppressor gene (s) for prostate cancer.

  4. Chromosome painting in plants.

    NARCIS (Netherlands)

    Schubert, I.; Fransz, P.F.; Fuchs, J.; Jong, de J.H.

    2001-01-01

    The current 'state-of-art' as to chromosome painting in plants is reviewed. We define different situations described as painting so far: i) Genomic in situ hybridisation (GISH) with total genomic DNA to distinguish alien chromosomes on the basis of divergent dispersed repeats, ii) 'Chromosomal in si

  5. Complex Variant of Philadelphia Translocation Involving Chromosomes 9, 12, and 22 in a Case with Chronic Myeloid Leukaemia

    Directory of Open Access Journals (Sweden)

    F. Malvestiti

    2014-01-01

    Full Text Available Chronic myeloid leukemia (CML is a hematopoietic stem cell disorder included in the broader diagnostic category of myeloproliferative neoplasms, associated with fusion by BCR gene at chromosome 22q11 to ABL1 gene at chromosome 9q34 with the formation of the Philadelphia (Ph chromosome. In 2–10% of CML cases, the fusion gene arises in connection with a variant translocation, involving chromosomes 9, 22, and one or more different chromosomes; consequently, the Ph chromosome could be masked within a complex chromosome rearrangement. In cases with variant Ph translocation a deletion on der(9 may be more frequently observed than in cases with the classical one. Herein we describe a novel case of CML with complex variant Ph translocation involving chromosomes 9, 12, and 22. We present the hematologic response and cytogenetic response after Imatinib treatment. We also speculated the mechanism which had originated the chromosome rearrangement.

  6. Proteomic and genetic analysis of wheat endosperm albumins and globulins using deletion lines of cultivar Chinese Spring

    DEFF Research Database (Denmark)

    Merlino, Marielle; Bousbata, Sabrina; Svensson, Birte;

    2012-01-01

    identified using mass spectrometry and data mining. Salt-soluble endosperm proteins from 67 CS deletion lines were also separated by 2DE (four gels per line). Image analysis of the 268 2DE gels as compared to the CS reference proteome allowed the detection of qualitative and quantitative variations in...... endosperm proteins due to chromosomal deletions. This differential analysis of spots allowed structural or regulatory genes, encoding 211 proteins, to be located on segments of the 21 wheat chromosomes. In addition, variance analysis of quantitative variations in spot volume showed that the expression of...

  7. Human Pumilio-2 is expressed in embryonic stem cells and germ cells and interacts with DAZ (Deleted in AZoospermia) and DAZ-Like proteins

    Science.gov (United States)

    Moore, Frederick L.; Jaruzelska, Jadwiga; Fox, Mark S.; Urano, Jun; Firpo, Meri T.; Turek, Paul J.; Dorfman, David M.; Pera, Renee A. Reijo

    2003-01-01

    Early in development, a part of the embryo is set aside to become the germ cell lineage that will ultimately differentiate to form sperm and eggs and transmit genetic information to the next generation. Men with deletions encompassing the Y-chromosome DAZ genes have few or no germ cells but are otherwise healthy, indicating they harbor specific defects in formation or maintenance of germ cells. A DAZ homolog, DAZL (DAZ-Like), is found in diverse organisms, including humans and is required for germ cell development in males and/or females. We identified proteins that interact with DAZ proteins to better understand their function in human germ cells. Here, we show that PUM2, a human homolog of Pumilio, a protein required to maintain germ line stem cells in Drosophila and Caenorhabditis elegans, forms a stable complex with DAZ through the same functional domain required for RNA binding, protein–protein interactions and rescue of Pumilio mutations in flies. We also show that PUM2 is expressed predominantly in human embryonic stem cells and germ cells and colocalizes with DAZ and DAZL in germ cells. These data implicate PUM2 as a component of conserved cellular machinery that may be required for germ cell development. PMID:12511597

  8. Cultural respect encompassing simulation training: being heard about health through broadband

    Directory of Open Access Journals (Sweden)

    Phyllis Min-yu Lau

    2016-04-01

    Full Text Available Background. Cultural Respect Encompassing Simulation Training (CREST is a learning program that uses simulation to provide health professional students and practitioners with strategies to communicate sensitively with culturally and linguistically diverse (CALD patients. It consists of training modules with a cultural competency evaluation framework and CALD simulated patients to interact with trainees in immersive simulation scenarios. The aim of this study was to test the feasibility of expanding the delivery of CREST to rural Australia using live video streaming; and to investigate the fidelity of cultural sensitivity – defined within the process of cultural competency which includes awareness, knowledge, skills, encounters and desire – of the streamed simulations. Design and Methods. In this mixed-methods evaluative study, health professional trainees were recruited at three rural academic campuses and one rural hospital to pilot CREST sessions via live video streaming and simulation from the city campus in 2014. Cultural competency, teaching and learning evaluations were conducted. Results. Forty-five participants rated 26 reliable items before and after each session and reported statistically significant improvement in 4 of 5 cultural competency domains, particularly in cultural skills (P<0.05. Qualitative data indicated an overall acknowledgement amongst participants of the importance of communication training and the quality of the simulation training provided remotely by CREST. Conclusions. Cultural sensitivity education using live video-streaming and simulation can contribute to health professionals’ learning and is effective in improving cultural competency. CREST has the potential to be embedded within health professional curricula across Australian universities to address issues of health inequalities arising from a lack of cultural sensitivity training.

  9. Different molecular mechanisms causing 9p21 deletions in acute lymphoblastic leukemia of childhood.

    Science.gov (United States)

    Novara, Francesca; Beri, Silvana; Bernardo, Maria Ester; Bellazzi, Riccardo; Malovini, Alberto; Ciccone, Roberto; Cometa, Angela Maria; Locatelli, Franco; Giorda, Roberto; Zuffardi, Orsetta

    2009-10-01

    Deletion of chromosome 9p21 is a crucial event for the development of several cancers including acute lymphoblastic leukemia (ALL). Double strand breaks (DSBs) triggering 9p21 deletions in ALL have been reported to occur at a few defined sites by illegitimate action of the V(D)J recombination activating protein complex. We have cloned 23 breakpoint junctions for a total of 46 breakpoints in 17 childhood ALL (9 B- and 8 T-lineages) showing different size deletions at one or both homologous chromosomes 9 to investigate which particular sequences make the region susceptible to interstitial deletion. We found that half of 9p21 deletion breakpoints were mediated by ectopic V(D)J recombination mechanisms whereas the remaining half were associated to repeated sequences, including some with potential for non-B DNA structure formation. Other mechanisms, such as microhomology-mediated repair, that are common in other cancers, play only a very minor role in ALL. Nucleotide insertions at breakpoint junctions and microinversions flanking the breakpoints have been detected at 20/23 and 2/23 breakpoint junctions, respectively, both in the presence of recombination signal sequence (RSS)-like sequences and of other unspecific sequences. The majority of breakpoints were unique except for two cases, both T-ALL, showing identical deletions. Four of the 46 breakpoints coincide with those reported in other cases, thus confirming the presence of recurrent deletion hotspots. Among the six cases with heterozygous 9p deletions, we found that the remaining CDKN2A and CDKN2B alleles were hypermethylated at CpG islands. PMID:19484265

  10. The 15q13.3 deletion syndrome: Deficient α(7)-containing nicotinic acetylcholine receptor-mediated neurotransmission in the pathogenesis of neurodevelopmental disorders.

    Science.gov (United States)

    Deutsch, Stephen I; Burket, Jessica A; Benson, Andrew D; Urbano, Maria R

    2016-01-01

    Array comparative genomic hybridization (array CGH) has led to the identification of microdeletions of the proximal region of chromosome 15q between breakpoints (BP) 3 or BP4 and BP5 encompassing CHRNA7, the gene encoding the α7-nicotinic acetylcholine receptor (α7nAChR) subunit. Phenotypic manifestations of persons with these microdeletions are variable and some heterozygous carriers are seemingly unaffected, consistent with their variable expressivity and incomplete penetrance. Nonetheless, the 15q13.3 deletion syndrome is associated with several neuropsychiatric disorders, including idiopathic generalized epilepsy, intellectual disability, autism spectrum disorders (ASDs) and schizophrenia. Haploinsufficient expression of CHRNA7 in this syndrome has highlighted important roles the α7nAChR plays in the developing brain and normal processes of attention, cognition, memory and behavior throughout life. Importantly, the existence of the 15q13.3 deletion syndrome contributes to an emerging literature supporting clinical trials therapeutically targeting the α7nAChR in disorders such as ASDs and schizophrenia, including the larger population of patients with no evidence of haploinsufficient expression of CHRNA7. Translational clinical trials will be facilitated by the existence of positive allosteric modulators (PAMs) of the α7nAChR that act at sites on the receptor distinct from the orthosteric site that binds acetylcholine and choline, the receptor's endogenous ligands. PAMs lack intrinsic efficacy by themselves, but act where and when the endogenous ligands are released in response to relevant social and cognitive provocations to increase the likelihood they will result in α7nAChR ion channel activation. PMID:26257138

  11. Evidence for a distinct region causing a cat-like cry in patients with 5p deletions

    Energy Technology Data Exchange (ETDEWEB)

    Gersh, M.; Goodart, S.A.; Overhauser, J. [Thomas Jefferson Univ., Philadelphia, PA (United States)] [and others

    1995-06-01

    The cri-du-chat syndrome is a contiguous gene syndrome that results from a deletion of the short arm of chromosome 5 (5p). Patients present with a cat-like cry at birth, which is usually considered diagnostic of this syndrome. Additional features of the syndrome include failure to thrive, microcephaly, hypertelorism, epicanthal folds, hypotonia, and severe mental retardation. We report on four families in which patients with 5p deletions have only the characteristic cat-like cry, with normal to mildly delayed development. The precise locations of the deletions in each family were determined by FISH using lambda phage and cosmic clones. All of the deletion breakpoints map distal to a chromosomal region that is implicated with the facial features and severe mental and developmental delay in the cri-du-chat syndrome. DNA clones mapping in the chromosomal region associated with the cat-like cry feature will be useful diagnostic tools. They will allow for the distinction between 5p deletions that will result in the severe delay observed in most cri-du-chat syndrome patients and those deletions that result in the isolated cat-like cry feature, which is associated with a better prognosis. 19 refs., 5 figs., 1 tab.

  12. Positional and functional mapping of a neuroblastoma differentiation gene on chromosome 11

    Directory of Open Access Journals (Sweden)

    Bader Scott

    2005-07-01

    Full Text Available Abstract Background Loss of chromosome 11q defines a subset of high-stage aggressive neuroblastomas. Deletions are typically large and mapping efforts have thus far not lead to a well defined consensus region, which hampers the identification of positional candidate tumour suppressor genes. In a previous study, functional evidence for a neuroblastoma suppressor gene on chromosome 11 was obtained through microcell mediated chromosome transfer, indicated by differentiation of neuroblastoma cells with loss of distal 11q upon introduction of chromosome 11. Interestingly, some of these microcell hybrid clones were shown to harbour deletions in the transferred chromosome 11. We decided to further exploit this model system as a means to identify candidate tumour suppressor or differentiation genes located on chromosome 11. Results In a first step, we performed high-resolution arrayCGH DNA copy-number analysis in order to evaluate the chromosome 11 status in the hybrids. Several deletions in both parental and transferred chromosomes in the investigated microcell hybrids were observed. Subsequent correlation of these deletion events with the observed morphological changes lead to the delineation of three putative regions on chromosome 11: 11q25, 11p13->11p15.1 and 11p15.3, that may harbour the responsible differentiation gene. Conclusion Using an available model system, we were able to put forward some candidate regions that may be involved in neuroblastoma. Additional studies will be required to clarify the putative role of the genes located in these chromosomal segments in the observed differentiation phenotype specifically or in neuroblastoma pathogenesis in general.

  13. Amplified and homozygously deleted genes in glioblastoma: impact on gene expression levels.

    Directory of Open Access Journals (Sweden)

    Inês Crespo

    Full Text Available BACKGROUND: Glioblastoma multiforme (GBM displays multiple amplicons and homozygous deletions that involve relevant pathogenic genes and other genes whose role remains unknown. METHODOLOGY: Single-nucleotide polymorphism (SNP-arrays were used to determine the frequency of recurrent amplicons and homozygous deletions in GBM (n = 46, and to evaluate the impact of copy number alterations (CNA on mRNA levels of the genes involved. PRINCIPAL FINDINGS: Recurrent amplicons were detected for chromosomes 7 (50%, 12 (22%, 1 (11%, 4 (9%, 11 (4%, and 17 (4%, whereas homozygous deletions involved chromosomes 9p21 (52% and 10q (22%. Most genes that displayed a high correlation between DNA CNA and mRNA levels were coded in the amplified chromosomes. For some amplicons the impact of DNA CNA on mRNA expression was restricted to a single gene (e.g., EGFR at 7p11.2, while for others it involved multiple genes (e.g., 11 and 5 genes at 12q14.1-q15 and 4q12, respectively. Despite homozygous del(9p21 and del(10q23.31 included multiple genes, association between these DNA CNA and RNA expression was restricted to the MTAP gene. CONCLUSIONS: Overall, our results showed a high frequency of amplicons and homozygous deletions in GBM with variable impact on the expression of the genes involved, and they contributed to the identification of other potentially relevant genes.

  14. Familial deletion of 18p associated with Turner like clinical features

    Energy Technology Data Exchange (ETDEWEB)

    Say, B.; Gopal Rao, V.V.N.; Harris, S. [H.A. Chapman Institute of Medical Genetics, Tulsa, OK (United States)] [and others

    1994-09-01

    The authors report the first occurrence to our knowledge of a familial deletion of the short arm of chromosome 18 in a mother and daughter. The proband is an 18-year-old female referred for chromosomal analysis because of mental retardation and short stature. She is the only offspring. Her birth weight was 3 pounds 10 ounces (below 5th percentile). As a child, she had delayed milestones. Her IQ is 69 and she is in classes for the educable mentally handicapped. Her height is 145.6 cm and weight 38.7 kg (both below 5th percentile). Physical examination revealed a low nuchal hairline. She has myopia. Chromosome analysis from peripheral blood lymphocytes revealed a 46,XX,del(18)(p11.21) karyotype. Since some of the same clinical features are also seen in the mother including short stature (157 cm), mental retardation, ocular problems like cataracts, exotropia and refractive error, chromosome analysis was performed which showed the same 46,XX,del(18)(p11.21) karyotype. A familial case like this has great implications in genetic counseling. Since the syndrome is not associated with sterility, the recurrence risk for the offspring is 50%. Patients with deletion (18p) syndrome are reported to have findings suggestive of Turner syndrome with varying degrees of mental retardation. We recommend that in patients with such clinical features associated with mental retardation, normal menstrual history and/or fertility, the possibility of deletion (18p) syndrome be considered.

  15. Deletions at 22q11.2 in idiopathic Parkinson's disease: a combined analysis of genome-wide association data

    OpenAIRE

    Mok, K. Y.; Sheerin, U.; Simón-Sánchez, J.; Salaka, A.; Chester, L.; Escott-Price, V; Mantripragada, K.; Doherty, K M; Noyce, A. J.; Mencacci, N. E.; Lubbe, S. J.; International Parkinson's Disease Genomics Consortium (IPDGC); Williams-Gray, C. H.; Barker, R. A.; Dijk, K.D. van

    2016-01-01

    Summary Background Parkinson's disease has been reported in a small number of patients with chromosome 22q11.2 deletion syndrome. In this study, we screened a series of large, independent Parkinson's disease case-control studies for deletions at 22q11.2. Methods We used data on deletions spanning the 22q11.2 locus from four independent case-control Parkinson's disease studies (UK Wellcome Trust Case Control Consortium 2, Dutch Parkinson's Disease Genetics Consortium, US National Institute on ...

  16. 7q11.23 deletions in Williams syndrome arise as a consequence of unequal meiotic crossover

    Energy Technology Data Exchange (ETDEWEB)

    Urban, Z.; Csiszar, K.; Boyd, C.D. [and others

    1996-10-01

    Williams syndrome (WS) is a multisystem disorder characterized by mental retardation, a specific neurobehavioral profile, characteristic facies, infantile hypercalcemia, cardiovascular abnormalities, progressive joint limitation, hermas, and soft skin. Recent studies have shown that hemizygosity at the elastin (ELN) gene locus on chromosome 7q is associated with WS. Furthermore, two FISH studies using cosmid recombinants containing the 5{prime} or the 3{prime} end of the ELN gene revealed deletion of the entire ELN gene in 90%-96% of classical WS cases. However, the size of the 7q11.23 deletions and the mechanism by which these deletions arise are not known. 15 refs., 2 figs., 1 tab.

  17. X-radiation-induced chromosome breakage in retinoblastoma lymphocytes

    International Nuclear Information System (INIS)

    The authors have examined the spontaneous and X-radiation-induced chromosomal damage in normal humans and in patients with retinoblastoma using the BudR-Giemsa technique in lymphocytes cultured for 48 h. 9 sporadic unilateral non-hereditary cases, 11 hereditary cases and 20 healthy individuals were studied simultaneously. No difference in the spontaneous frequency of chromatid and chromosome aberrations was observed between patients and controls. The results suggest that: (a) There is no relationship between spontaneous chromosome fragility and retinoblastoma. (b) Sporadic unilateral non-hereditary retinoblastoma has normal chromosome sensitivity to X-irradiation. (c) Some hereditary cases of retinoblastoma are sensitive to X-rays while others behave like normals. A mutation or a submicroscopic deletion at a DNA repair locus which is independent of the retinoblastoma gene may cause this radiosensitivity. (Auth.)

  18. hSNF5/INI1 inactivation is mainly associated with homozygous deletions and mitotic recombinations in rhabdoid tumors.

    Science.gov (United States)

    Rousseau-Merck, M F; Versteege, I; Legrand, I; Couturier, J; Mairal, A; Delattre, O; Aurias, A

    1999-07-01

    The chromatin-remodeling hSNF5/INI1 gene has recently been shown to act as a tumor suppressor gene in rhabdoid tumors (RTs). In an attempt to further characterize the main chromosomal mechanisms involved in hSNF5/INI1 inactivation in RTs, we report here the molecular cytogenetic data obtained in 12 cell lines harboring hSNF5/INI1 mutations and/or deletions in relation to the molecular genetic analysis using polymorphic markers extended to both extremities of chromosome 22q. On the whole, mitotic recombination occurring in the proximal part of chromosome 22q, as demonstrated in five cases, and nondisjunction/duplication, highly suspected in two cases (processes leading respectively to partial or complete isodisomy), appear to be major mechanisms associated with hSNF5/INI1 inactivation. Such isodisomy accompanies each of the RTs exhibiting two cytogenetically normal chromosomes 22. This results in homozygosity for the mutation at the hSNF5/INI1 locus. An alternate mechanism accounting for hSNF5/INI1 inactivation observed in these tumors is homozygous deletion in the rhabdoid consensus region. This was observed in each of the four tumors carrying a chromosome 22q abnormality and, in particular, in the three tumors with chromosomal translocations. Only one case of our series illustrates the mutation/deletion classical model proposed for the double-hit inactivation of a tumor suppressor gene. PMID:10397258

  19. A case report of 22q11 deletion syndrome confirmed by array-CGH method

    Directory of Open Access Journals (Sweden)

    Maryam Sedghi

    2012-01-01

    Full Text Available Velo-cardio-facial syndrome (VCFS is caused by a submicroscopic deletion on the long arm of chromosome 22 and affects approximately 1 in 4000 persons, making it the second most prevalent genetic syndrome after Down syndrome and the most common genetic syndrome associated with cleft palate. Most of the 22q11.2 deletion cases are new occurrences or sporadic; however, in about 10 % of families, the deletion is inherited and other family members are affected or at risk for passing this deletion to their children. This report describes a 1.5 years-old male child with clinical signs of velo-cardio-facial syndrome (VCFS presented with heart defect, soft cleft palate, developmental delay, acrocephaly, seizure, MRI abnormalities and descriptive facial feature, such as hypertelorism. Array-CGH test was done to confirm the diagnosis; the result revealed a 2.6 Mbp deletion in 22q11.2 chromosome that containing TBX1 and COMT genes. Our data suggest that haploinsufficiency of TBX1 gene is probably a major contributor to some of the syndrome characteristic signs, such as heart defect. Because of developmental delay and dysmorphic facial feature were observed in the index′s mother and relatives, inherited autosomal dominant form of VCF is probable, and MLPA (multiplex ligation-dependent probe amplification test should be performed for parents to estimate the recurrent risk in next pregnancy.

  20. Chimpanzee chromosome 12 is homologous to human chromosome 2q

    Energy Technology Data Exchange (ETDEWEB)

    Sun, N. C.; Sun, C. R.Y.; Ho, T.

    1977-01-01

    Most of the 46 human chromosomes find their counterparts in the 48 chimpanzee chromosomes except for chromosome 2 which has been hypothesized to have been derived from a centric fusion of two chimpanzee acrocentric chromosomes. These two chromosomes correspond to the human chromosomes 2p and 2g. This conclusion is based primarily on chromosome banding techniques, and the somatic cell hybridization technique has also been used. (HLW)

  1. Chromosome anomalies in mouse oocytes after irradiation

    International Nuclear Information System (INIS)

    We investigated the cytogenetic effects of X-rays on unfertilized mouse oocytes. NMRI females received an irradiation with 0, 22.2, 66.6, 200, and 600 R during the preovulatory phase 3 hrs after HCG (human chorionic gonadotrophin). This is a stage during oogenesis in which the oocytes pass from late dictyotene to diakinesis. Chromosome anlysis was per formed after ovulation at metaphase II. From these experiments we can draw the following conclusions: X-rays induced during the preovulatory phase a high number of chromosome anomalies. Among these, structural anomalies prevail. 7 out of 144 ovulated oocytes in matched controls carried such an abnormality, whereas after irradiation we observed with 22.2, 66.6, 200, and 600 R, 11 out of 72, 34 out of 108, 89 out of 102, and 122 out of 124, respectively. Irradiation seems also to affect the chromosome segregation during the 1. meiotic division, as we observed after 22.2, 66.6 and 200 R a total of 6 oocytes out of 204 with a supernummary chromosome. In controls, however, no hyperploidy was found in 143 ova. This increase, however, was not significant. Chromosome anomalies, e.g. breaks and deletions that go back to a one-break event increased linearly with increasing dose. Exchanges, however, going back to two-break events fittet best to the linear-quadratic dose-response model. The dose of 600 R seems to represent a kind of borderline in this experiment, because nearly all (122 out 124) carried at least one structural chromosome anomaly. It is also this dose after which the highest frequency of reciprocal translocations was observed in a humpshaped slope in spermatocytes after irradiation of spermatogonia (Preston and Brewen, 1973). With an increasing dosage up to 1,200 R the frequency of translocations decrease again. The elimination of cells, crossing this borderline, might be due to genetic or non-genetic effects. (orig./GSE)

  2. Y chromosome microdeletions in Turkish infertile men

    Directory of Open Access Journals (Sweden)

    Zamani Ayse

    2006-01-01

    Full Text Available AIMS: To detect the frequency and types of both chromosomal abnormalities and Y chromosome microdeletions in infertile men attending to our university intracytoplasmic sperm injection ICSI/IVF centre and fertile control subjects in our patient population. SETTINGS AND DESIGN: A total of 50 infertile men who were referred to IVF center of Meram medical faculty were selected for the molecular azospermia factor (AZF screening program. MATERIALS AND METHODS: Karyotype analysis and polymerase chain reaction amplification using 15 Y-specific sequence-tagged sites of AZF region were done. RESULTS: The total prevalence of chromosomal abnormalities was found to be 10% (5/50, including 4 patients with numerical and 1 patient with structural abnormalities. Overall, 4 of the 50 patients tested (8% exhibited deletions of the Y chromosome, 3 of them being azospermic and 1 of them oligospermic men. The frequency of the microdeletions in subgroups with azospermia and oligozoospermia was found to be 10.7% (3/29 and 4.7% (1/21 respectively. Microdeletions of AZFb and AZFc regions were detected in all of the 4 patients. Neither AZFa nor AZFd microdeletions were indicated. CONCLUSIONS: Our findings suggest that one must know whether there is a genetic cause for male infertility before patients can be subjected to ISCI or testicular sperm extraction (TESE/ISCI treatment.

  3. De novo interstitial deletions of 9q22.1-22.3 in two unrelated cases with different phenotype

    Energy Technology Data Exchange (ETDEWEB)

    Mohamed, A.N.; Bawle, E.; Conard, J. [Wayne State Univ., Detroit, MI (United States)] [and others

    1994-09-01

    Deletions involving the long arm of chromosome 9 are rare. A recent review, particularly with deletions of 9q22-32 region, failed to recognize a distinct pattern of dysmorphies and malformations. Herein, we described two phenotypically abnormal unrelated cases with interstitial deletion of chromosome 9 at band q22.1-q22.3. Parents of both cases exhibited normal karyotypes, indicating that the deletions were de novo events. Therefore, the clinical features present in these two cases can be attributed to partial monosomy for the deleted band 9q22. The first case was a 2-day-old baby with ambiguous genitalia, hydrocephalus, cleft palate and lip, polycystic kidney, absence of uterus on ultrasound and one gonad in the labiosacral region. Chromosome analysis showed a male karyotype, 46,XY,del(9)(q22.1q22.3). The absence of monosomy X cell line and the normal histology of testicular tissue were against the diagnosis of mixed gonadal dysgenesis or XY gonadal dysgenesis. The second 3-day-old newborn baby girl presented with right side hypoplastic heart and pulmonary atresia. In addition, the patient showed multiple dysmorphic features including epicanthal fold, low-set ears, depressed nasal bridge, hypertelorism, and micrognathia. The uvula is absent with slight cleft palate. Bilateral clinodactyly of 5th fingers and severe club feet were also present. The external genitalia was of a normal female phenotype. Chromosome study also indicated interstatial deletion of band 9q22. Although both cases appeared to have the same chromosomal anomalies, neither a discrete facial appearance nor a common pattern of malformations was noted.

  4. Molecular basis of human growth hormone gene deletions

    International Nuclear Information System (INIS)

    Crossover sites resulting from unequal recombination within the human growth hormone (GH) gene cluster that cause GH1 gene deletions and isolated GH deficiency type 1A were localized in nine patients. In eight unrelated subjects homozygous for 6.7-kilobase (kb) deletions, the breakpoints are within two blocks of highly homologous DNA sequences that lie 5' and 3' to the GH1 gene. In seven of these eight cases, the breakpoints map within a 1,250-base-pair (bp) region composed of 300-bp Alu sequences of 86% homology and flanking non-Alu sequences that are 600 and 300 bp in length and are of 96% and 88% homology, respectively. In the eighth patient, the breakpoints are 5' to these Alu repeats and are most likely within a 700-bp-region of 96% homologous DNA sequences. In the ninth patient homozygous for a 7.6-kb deletion, the breakpoints are contained with a 29-bp perfect repeat lying 5' to GH1 and the human chorionic somatomammotropin pseudogene (CSHP1). Together, these results indicate that the presence of highly homologous DNA sequences flanking GH1 predispose to recurrent unequal recombinational events presumably through chromosomal misalignment

  5. Copy Number Variations Due to Large Genomic Deletion in X-Linked Chronic Granulomatous Disease

    OpenAIRE

    Arai, Takashi; Oh-ishi, Tsutomu; Yamamoto, Hideaki; Nunoi, Hiroyuki; Kamizono, Junji; Uehara, Masahiko; Kubota, Takeo; Sakurai, Takuya; Kizaki, Takako; Ohno, Hideki

    2012-01-01

    Mutations in genes for any of the six subunits of NADPH oxidase cause chronic granulomatous disease (CGD), but almost 2/3 of CGD cases are caused by mutations in the X-linked CYBB gene, also known as NAD (P) H oxidase 2. Approximately 260 patients with CGD have been reported in Japan, of whom 92 were shown to have mutations of the CYBB gene and 16 to have chromosomal deletions. However, there has been very little detailed analysis of the range of the deletion or close understanding of the dis...

  6. Abnormal auditory and language pathways in children with 16p11.2 deletion

    OpenAIRE

    Berman, Jeffrey I.; Darina Chudnovskaya; Lisa Blaskey; Emily Kuschner; Pratik Mukherjee; Randall Buckner; Srikantan Nagarajan; Chung, Wendy K.; Spiro, John E; Sherr, Elliott H; Roberts, Timothy P. L.

    2015-01-01

    Copy number variations at chromosome 16p11.2 contribute to neurodevelopmental disorders, including autism spectrum disorder (ASD). This study seeks to improve our understanding of the biological basis of behavioral phenotypes common in ASD, in particular the prominent and prevalent disruption of spoken language seen in children with the 16p11.2 BP4–BP5 deletion. We examined the auditory and language white matter pathways with diffusion MRI in a cohort of 36 pediatric deletion carriers and 45 ...

  7. Spontaneous and mutagen-induced deletions: mechanistic studies in Salmonella tester strain TA102.

    OpenAIRE

    Levin, D E; Marnett, L J; Ames, B N

    1984-01-01

    Salmonella tester strain TA102 carries the hisG428 ochre mutation on the multicopy plasmid pAQ1. DNA sequence analysis of 45 spontaneous revertants of hisG428 on the chromosome in the presence of pKM101 (strain TA103) indicates that hisG428 revertants fall into three major categories: (i) small, in-frame deletions (3 or 6 base pairs) that remove part or all of the ochre triplet; (ii) base substitution mutations at the ochre site; (iii) extragenic ochre suppressors. Deletion revertants are ide...

  8. Whole Xp Deletion in a Girl with Mental Retardation, Epilepsy, and Biochemical Features of OTC Deficiency

    OpenAIRE

    Joost, K.; Tammur, P.; Teek, R.; Žilina, O.; Peters, M; Kreile, M.; Lace, B.; Žordania, R.; Talvik, I.; Õunap, K.

    2011-01-01

    Background: Females with a total or partial deletion of the short arm of the X chromosome have variable features of Turner syndrome, but mental retardation (MR) rarely occurs. The haploinsufficiency of deleted genes that escape X-inactivation may explain the occurrence of MR and autism. Ornithine transcarbamylase (OTC) deficiency is the most common urea cycle disorder and is inherited in an X-linked semi-dominant trait, and the OTC gene maps to Xp21. Methods: We report on a girl with MR, epil...

  9. Frontonasal malformation with tetralogy of Fallot associated with a submicroscopic deletion of 22q11

    Energy Technology Data Exchange (ETDEWEB)

    Stratton, R.F. [South Texas Genetics Center, San Antonio, TX (United States); Payne, R.M. [Central Texas Genetics Center, Austin, TX (United States)

    1997-03-31

    We report on a 14-month-old girl with bifid nasal tip and tetralogy of Fallot. Several similar patients have been described with CNS or eye abnormalities. Chromosome analysis with FISH, using Oncor DiGeorge probes, confirmed a submicroscopic deletion of 22q11. Many patients with Shprintzen (velo-cardio-facial) syndrome have a similar deletion with conotruncal cardiac defects and an abnormal nasal shape, suggesting that a gene in this area, possibly affecting neural crest cells, influences facial and other midline development. 13 refs., 1 fig.

  10. SEM of canine chromosomes: normal structure and the effects of whole-body irradiation

    International Nuclear Information System (INIS)

    Canine chromosomes are not only numerous (38 autosomal pairs), but they are small (compared to human chromosomes) and morphologically similar as well. Analysis of the canine karyotype by light microscopy (LM) of banded chromosomes is, thus, difficult, and the literature on the canine karyotype is scanty. In this study, we describe examination of chromosomes from normal and chronically irradiated dogs with the scanning electron microscope (SEM). Metaphase chromosomes from bone marrow aspirates were Giemsa-banded with either 0.025% trypsin alone or 0.1% trypsin preceded by 10% H2O2 and prepared for SEM. Examination of chromosomes from normal dogs revealed cylindrical chromosome profiles with well-defined chromatids and centromeres. The chromosome arms were consistently marked by periodic grooves that had complementary structures on sister chromatids and may represent the trypsin-sensitive chromatic regions. The quality of the preservation varied from preparation to preparation and depended on the concentration and time of trypsin treatment. Chromosomes from irradiated dogs revealed translocations, deletions, and gaps. We conclude that SEM produces images superior to LM images of canine chromosomes; SEM images can be used not only to identify individual chromosomes, but also to identify genetic lesions in the chromosomes of chronically irradiated dogs. We further conclude that the two Giemsa-banding protocols used in the present study produced variable results, although 0.025% trypsin alone appeared to give better and more consistent results than 0.1% trypsin preceded by 10% H2O2

  11. Alternative Splicing of CHEK2 and Codeletion with NF2 Promote Chromosomal Instability in Meningioma

    Directory of Open Access Journals (Sweden)

    Hong Wei Yang

    2012-01-01

    Full Text Available Mutations of the NF2 gene on chromosome 22q are thought to initiate tumorigenesis in nearly 50% of meningiomas, and 22q deletion is the earliest and most frequent large-scale chromosomal abnormality observed in these tumors. In aggressive meningiomas, 22q deletions are generally accompanied by the presence of large-scale segmental abnormalities involving other chromosomes, but the reasons for this association are unknown. We find that large-scale chromosomal alterations accumulate during meningioma progression primarily in tumors harboring 22q deletions, suggesting 22q-associated chromosomal instability. Here we show frequent codeletion of the DNA repair and tumor suppressor gene, CHEK2, in combination with NF2 on chromosome 22q in a majority of aggressive meningiomas. In addition, tumor-specific splicing of CHEK2 in meningioma leads to decreased functional Chk2 protein expression. We show that enforced Chk2 knockdown in meningioma cells decreases DNA repair. Furthermore, Chk2 depletion increases centrosome amplification, thereby promoting chromosomal instability. Taken together, these data indicate that alternative splicing and frequent codeletion of CHEK2 and NF2 contribute to the genomic instability and associated development of aggressive biologic behavior in meningiomas.

  12. Flow sorting of the Y sex chromosome in the dioecious plant Melandrium album

    Energy Technology Data Exchange (ETDEWEB)

    Veuskens, J.; Jacobs, M.; Negrutiu, I. [Free Univ. of Brussels (Belgium)] [and others

    1995-12-01

    The preparation of stable chromosome suspensions and flow cytometric sorting of both the Y sex chromosome of the white campion, Melandrium album, and the deleted Y chromosome of an asexual mutant, 5K63, is described. The principle has been to maintain transformed roots in vitro, synchronize and block mitosis, reduce cells to protoplasts, and lyse these to release chromosomes. Such in vitro material, unlike many cell suspensions, showed a stable karyotype. Factors critical to producing high-quality chromosome suspensions from protoplasts include osmolality of isolation solutions and choice of spindle toxin and of lysis buffer. Agrobacterium rhizogenes transformed young growing root cultures were synchronized at G1/S with 50 {mu}M aphidicolin for 24 h and released to a mitotic block with 30 {mu}M oryzalin for 11 h. Protoplast preparations from such tissue routinely had metaphase indices reaching 15%. Suspensions of intact metaphase chromosomes, with few chromatids, were obtained by lysing swollen mitotic protoplasts in a citric acid/disodium phosphate buffer. Except for the presence of clumps of autosomal chromosomes near the X and Y chromosome zones, monoparametric histograms of fluorescence intensities of suspensions stained with 4{prime},6-diamidino-2-phenylindole showed profiles similar to theoretical flow karyotypes. Two types of Y chromosomes, one full-length and one partially deleted (from the asexual mutant), could be sorted at 90% purity (21-fold enrichment of Y). These results are discussed in the context of sex determination and differentiation in higher plants. 45 refs., 6 figs., 2 tabs.

  13. Seven gene deletions in seven days

    DEFF Research Database (Denmark)

    Ingemann Jensen, Sheila; Lennen, Rebecca; Herrgard, Markus;

    2015-01-01

    enables growth at 37 °C, thereby facilitating removal of integrated antibiotic cassettes and deletion of additional genes in the same day. Phosphorothioated primers were demonstrated to enable simultaneous deletions during one round of electroporation. Utilizing these methods, we constructed strains in...... deletion of multiple genes in several E. coli variants. The method enables deletion of up to seven genes in as little as seven days....

  14. 76 FR 22680 - Procurement List; Deletions

    Science.gov (United States)

    2011-04-22

    ... INFORMATION: Deletions On 2/25/2011 (76 FR 10571), the Committee for Purchase From People Who Are Blind or... PEOPLE WHO ARE BLIND OR SEVERELY DISABLED Procurement List; Deletions AGENCY: Committee for Purchase From People Who Are Blind or Severely Disabled. ACTION: Deletions from the Procurement List. SUMMARY:...

  15. Strong correlation of elastin deletions, detected by FISH, with Williams syndrome: Evaluation of 235 patients

    Energy Technology Data Exchange (ETDEWEB)

    Lowery, M.C.; Brothman, L.J.; Leonard, C.O. [Univ. of Utah Health Sciences Center, Salt Lake City, UT (United States)] [and others

    1995-07-01

    Williams syndrome (WS) is generally characterized by mental deficiency, gregarious personality, dysmorphic facies, supravalvular aortic stenosis, and idiopathic infantile hypercalcemia. Patients with WS show allelic loss of elastin (ELN), exhibiting a submicroscopic deletion, at 7q11.23, detectable by FISH. Hemizygosity is likely the cause of vascular abnormalities in WS patients. A series of 235 patients was studied, and molecular cytogenetic deletions were seen in 96% of patients with classic WS. Patients included 195 solicited through the Williams Syndrome Association (WSA), plus 40 clinical cytogenetics cases referred by primary-care physicians. Photographs and medical records of most WSA subjects were reviewed, and patients were identified as {open_quotes}classic{open_quotes} (n = 114) or{open_quotes}uncertain{close_quotes} (n = 39). An additional 42 WSA patients were evaluated without clinical information. FISH was performed with biotinylated ELN cosmids on metaphase cells from immortalized lymphoblastoid lines from WSA patients and after high-resolution banding analysis on clinical referral patients. An alpha-satellite probe for chromosome 7 was included in hybridizations, as an internal control. Ninety-six percent of the patients with classic WS showed a deletion in one ELN allele; four of these did not show a deletion. Of the uncertain WS patients, only 3 of 39 showed a deletion. Of the 42 who were not classified phenotypically, because of lack of clinical information, 25 patients (60%) showed a deletion. Thirty-eight percent (15/40) of clinical cytogenetics cases showed an ELN deletion and no cytogenetic deletion by banded analysis. These results support the usefulness of FISH for the detection of elastin deletions as an initial diagnostic assay for WS. 14 refs., 2 figs., 4 tabs.

  16. A new physical mapping approach refines the sex-determining gene positions on the Silene latifolia Y-chromosome

    Science.gov (United States)

    Kazama, Yusuke; Ishii, Kotaro; Aonuma, Wataru; Ikeda, Tokihiro; Kawamoto, Hiroki; Koizumi, Ayako; Filatov, Dmitry A.; Chibalina, Margarita; Bergero, Roberta; Charlesworth, Deborah; Abe, Tomoko; Kawano, Shigeyuki

    2016-01-01

    Sex chromosomes are particularly interesting regions of the genome for both molecular genetics and evolutionary studies; yet, for most species, we lack basic information, such as the gene order along the chromosome. Because they lack recombination, Y-linked genes cannot be mapped genetically, leaving physical mapping as the only option for establishing the extent of synteny and homology with the X chromosome. Here, we developed a novel and general method for deletion mapping of non-recombining regions by solving “the travelling salesman problem”, and evaluate its accuracy using simulated datasets. Unlike the existing radiation hybrid approach, this method allows us to combine deletion mutants from different experiments and sources. We applied our method to a set of newly generated deletion mutants in the dioecious plant Silene latifolia and refined the locations of the sex-determining loci on its Y chromosome map.

  17. ABCA7 frameshift deletion associated with Alzheimer disease in African Americans

    Science.gov (United States)

    Cukier, Holly N.; Kunkle, Brian W.; Vardarajan, Badri N.; Rolati, Sophie; Hamilton-Nelson, Kara L.; Kohli, Martin A.; Whitehead, Patrice L.; Dombroski, Beth A.; Van Booven, Derek; Lang, Rosalyn; Dykxhoorn, Derek M.; Farrer, Lindsay A.; Cuccaro, Michael L.; Vance, Jeffery M.; Gilbert, John R.; Beecham, Gary W.; Martin, Eden R.; Carney, Regina M.; Mayeux, Richard; Schellenberg, Gerard D.; Byrd, Goldie S.; Haines, Jonathan L.

    2016-01-01

    Objective: To identify a causative variant(s) that may contribute to Alzheimer disease (AD) in African Americans (AA) in the ATP-binding cassette, subfamily A (ABC1), member 7 (ABCA7) gene, a known risk factor for late-onset AD. Methods: Custom capture sequencing was performed on ∼150 kb encompassing ABCA7 in 40 AA cases and 37 AA controls carrying the AA risk allele (rs115550680). Association testing was performed for an ABCA7 deletion identified in large AA data sets (discovery n = 1,068; replication n = 1,749) and whole exome sequencing of Caribbean Hispanic (CH) AD families. Results: A 44-base pair deletion (rs142076058) was identified in all 77 risk genotype carriers, which shows that the deletion is in high linkage disequilibrium with the risk allele. The deletion was assessed in a large data set (531 cases and 527 controls) and, after adjustments for age, sex, and APOE status, was significantly associated with disease (p = 0.0002, odds ratio [OR] = 2.13 [95% confidence interval (CI): 1.42–3.20]). An independent data set replicated the association (447 cases and 880 controls, p = 0.0117, OR = 1.65 [95% CI: 1.12–2.44]), and joint analysis increased the significance (p = 1.414 × 10−5, OR = 1.81 [95% CI: 1.38–2.37]). The deletion is common in AA cases (15.2%) and AA controls (9.74%), but in only 0.12% of our non-Hispanic white cohort. Whole exome sequencing of multiplex, CH families identified the deletion cosegregating with disease in a large sibship. The deleted allele produces a stable, detectable RNA strand and is predicted to result in a frameshift mutation (p.Arg578Alafs) that could interfere with protein function. Conclusions: This common ABCA7 deletion could represent an ethnic-specific pathogenic alteration in AD. PMID:27231719

  18. Velocardiofacial syndrome in father and daughter: What is the mechanism for the deletion 22(q11.2q11.2) in only the daughter?

    Energy Technology Data Exchange (ETDEWEB)

    Magenis, R.E.; Gunter, K.; Toth-Fejel, S. [Oregon Health Sciences Univ., Portland, OR (United States)] [and others

    1994-09-01

    E.G. had marked feeding difficulty noted at birth; the cause was determined to be a paralyzed palate. In 1992 chromosome studies were performed because of the provisional diagnosis of velocardiofacial syndrome, and a small interstitial deletion of chromosome 22 was found. Recently the family was seen in our Genetics Clinic. The father had unusual facial features shared by his daughter, a paralyzed upper lip and a history of repaired Tetralogy of Fallot. His chromosomes appeared normal. FISH studies were performed on the child`s peripheral blood using the ONCOR DiGeorge region probe (D22S75) and the deletion verified. However, the father`s chromosomes were not deleted for the ONCOR probe (D22S75) and probe DO832 sent to us by Peter Scambler. Skin cells were then obtained and no deletion was detected in a total of 66 cells examined using both probes. Several questions arise from these data: does the father have velocardiofacial syndrome? Does he have occult mosaicism? Does he have a molecular deletion not detected by the probes used? And was this deletion somehow {open_quotes}amplified{close_quotes} in his daughter?

  19. Chronic lymphocytic leukemia-associated chromosomal abnormalities and miRNA deregulation

    Directory of Open Access Journals (Sweden)

    Kiefer Y

    2012-03-01

    Full Text Available Yvonne Kiefer1, Christoph Schulte2, Markus Tiemann2, Joern Bullerdiek11Center for Human Genetics, University of Bremen, Bremen, Germany; 2Hematopathology Hamburg, Hamburg, GermanyAbstract: Chronic lymphocytic leukemia is the most common leukemia in adults. By cytogenetic investigations major subgroups of the disease can be identified that reflect different routes of tumor development. Of these chromosomal deviations, trisomy 12 and deletions of parts of either the long arm of chromosome 13, the long arm of chromosome 11, or the short arm of chromosome 17 are most commonly detected. In some of these aberrations the molecular target has been identified as eg, ataxia telangiectasia mutated (ATM in case of deletions of chromosomal region 11q22~23 and the genes encoding microRNAs miR-15a/16-1 as likely targets of deletions of chromosomal band 13q14.3. Of note, these aberrations do not characterize independent subgroups but often coexist within the metaphases of one tumor. Generally, complex aberrations are associated with a worse prognosis than simple karyotypic alterations. Due to smaller sizes of the missing segment the detection of recurrent deletions is not always possible by means of classical cytogenetics but requires more advanced techniques as in particular fluorescence in situ hybridization (FISH. Nevertheless, at this time it is not recommended to replace classical cytogenetics by FISH because this would miss additional information given by complex or secondary karyotypic alterations. However, the results of cytogenetic analyses allow the stratification of prognostic and predictive groups of the disease. Of these, the group characterized by deletions involving TP53 is clinically most relevant. In the future refined methods as eg, array-based comparative genomic hybridization will supplement the existing techniques to characterize CLL. Keywords: chronic lymphocytic leukemia, chromosomal abnormality, miRNA deregulation

  20. The Draft Genome Sequence of Paenibacillus polymyxa Strain CCI-25 Encompasses High Potential for Secondary Metabolite Production.

    Science.gov (United States)

    Aleti, Gajender; Antonielli, Livio; Corretto, Erika; Nikolić, Branislav; Sessitsch, Angela; Brader, Günter

    2016-01-01

    We report here the draft genome sequence of Paenibacillus polymyxa strain CCI-25, which displays strong antifungal and antibacterial activities in vitro The genome encompasses nonribosomal peptide synthetases predicted to encode a tridecaptin, polymyxin, fusaricidin, an iturin-like synthetase, a lantibiotic similar to paenicidin A, as well as a type 1 polyketide synthase. PMID:27198015

  1. Interstitial deletion 1p as a result of a de novo reciprocal 1p;2p translocation

    DEFF Research Database (Denmark)

    Hertz, Jens Michael; Jensen, P H

    1985-01-01

    A 5-month-old female patient with psychomotor retardation and minor dysmorphisms is described. Cytogenetic analysis using high-resolution banding technique revealed an interstitial deletion of the short arm of one chromosome 1 (p21----p22.2) resulting from a de novo translocation t(1;2)(p22;p25)....

  2. A Longitudinal Examination of the Psychoeducational, Neurocognitive, and Psychiatric Functioning in Children with 22q11.2 Deletion Syndrome

    Science.gov (United States)

    Hooper, Stephen R.; Curtiss, Kathleen; Schoch, Kelly; Keshavan, Matcheri S.; Allen, Andrew; Shashi, Vandana

    2013-01-01

    The present study sought to examine the longitudinal psychoeducational, neurocognitive, and psychiatric outcomes of children and adolescents with chromosome 22q11.2 deletion syndrome (22q11DS), a population with a high incidence of major psychiatric illnesses appearing in late adolescence/early adulthood. Little is known of the developmental…

  3. 16p11.2 Deletion Mice Display Cognitive Deficits in Touchscreen Learning and Novelty Recognition Tasks

    Science.gov (United States)

    Yang, Mu; Lewis, Freeman C.; Sarvi, Michael S.; Foley, Gillian M.; Crawley, Jacqueline N.

    2015-01-01

    Chromosomal 16p11.2 deletion syndrome frequently presents with intellectual disabilities, speech delays, and autism. Here we investigated the Dolmetsch line of 16p11.2 heterozygous (+/-) mice on a range of cognitive tasks with different neuroanatomical substrates. Robust novel object recognition deficits were replicated in two cohorts of 16p11.2…

  4. Emotion Regulation and Development in Children with Autism and 22q13 Deletion Syndrome: Evidence for Group Differences

    Science.gov (United States)

    Glaser, Sarah E.; Shaw, Steven R.

    2011-01-01

    Emotion regulation (ER) abilities and developmental differences were investigated among 19 children with autism and 18 children with 22q13 Deletion Syndrome (a rare chromosomal disorder with certain autistic symptoms). The purpose of this study was to examine the phenotypic similarities between the two disorders. ER was measured by the Temperament…

  5. Deletion of a conserved regulatory element required for Hmx1 expression in craniofacial mesenchyme in the dumbo rat: a newly identified cause of congenital ear malformation

    Directory of Open Access Journals (Sweden)

    Lely A. Quina

    2012-11-01

    Hmx1 is a homeodomain transcription factor expressed in the developing eye, peripheral ganglia, and branchial arches of avian and mammalian embryos. Recent studies have identified a loss-of-function allele at the HMX1 locus as the causative mutation in the oculo-auricular syndrome (OAS in humans, characterized by ear and eye malformations. The mouse dumbo (dmbo mutation, with similar effects on ear and eye development, also results from a loss-of-function mutation in the Hmx1 gene. A recessive dmbo mutation causing ear malformation in rats has been mapped to the chromosomal region containing the Hmx1 gene, but the nature of the causative allele is unknown. Here we show that dumbo rats and mice exhibit similar neonatal ear and eye phenotypes. In midgestation embryos, dumbo rats show a specific loss of Hmx1 expression in neural-crest-derived craniofacial mesenchyme (CM, whereas Hmx1 is expressed normally in retinal progenitors, sensory ganglia and in CM, which is derived from mesoderm. High-throughput resequencing of 1 Mb of rat chromosome 14 from dmbo/dmbo rats, encompassing the Hmx1 locus, reveals numerous divergences from the rat genomic reference sequence, but no coding changes in Hmx1. Fine genetic mapping narrows the dmbo critical region to an interval of ∼410 kb immediately downstream of the Hmx1 transcription unit. Further sequence analysis of this region reveals a 5777-bp deletion located ∼80 kb downstream in dmbo/dmbo rats that is not apparent in 137 other rat strains. The dmbo deletion region contains a highly conserved domain of ∼500 bp, which is a candidate distal enhancer and which exhibits a similar relationship to Hmx genes in all vertebrate species for which data are available. We conclude that the rat dumbo phenotype is likely to result from loss of function of an ultraconserved enhancer specifically regulating Hmx1 expression in neural-crest-derived CM. Dysregulation of Hmx1 expression is thus a candidate mechanism for congenital ear

  6. Copy number variations of chromosome 16p13.1 region associated with schizophrenia

    DEFF Research Database (Denmark)

    Ingason, A; Rujescu, D; Cichon, S;

    2011-01-01

    Deletions and reciprocal duplications of the chromosome 16p13.1 region have recently been reported in several cases of autism and mental retardation (MR). As genomic copy number variants found in these two disorders may also associate with schizophrenia, we examined 4345 schizophrenia patients an...... hyperactivity disorder and dyslexia. Candidate genes in the region include NTAN1 and NDE1. We conclude that duplications and perhaps also deletions of chromosome 16p13.1, previously reported to be associated with autism and MR, also confer risk of schizophrenia....

  7. 5q14.3 deletion neurocutaneous syndrome: Contiguous gene syndrome caused by simultaneous deletion of RASA1 and MEF2C: A progressive disease.

    Science.gov (United States)

    Ilari, Rita; Agosta, Guillermo; Bacino, Carlos

    2016-03-01

    We report the case of a young girl who was presented with complex clinical symptoms caused by the deletion of contiguous genes: RASA1 and MEF2C, located on chromosome 5q14.3. Specifically, the diagnosis of her skin disorder and vascular malformations involving central nervous system is consistent with a RASopathy. The child's neurological manifestations are observed in most patients suffering from 5q14.3 by deletion or mutation of the MEF2C gene. A review of the literature allowed us to conclude that the contiguous deletion of genes RASA1 and MEF2C fulfills the criteria for the diagnosis of a Neurocutaneous syndrome as proposed by Carr et al. [2011]. We also assessed the penetrance of RASA1 and clinical manifestations of MEF2C according to the type of deletion. This child described presents the complete symptomatology of both deleted genes. We would also like to highlight the progression of the disorder. PMID:26774077

  8. Prevalence of the Prefoldin Subunit 5 Gene Deletion in Canine Mammary Tumors.

    Directory of Open Access Journals (Sweden)

    Silvia Hennecke

    Full Text Available A somatic deletion at the proximal end of canine chromosome 27 (CFA27 was recently reported in 50% of malignant mammary tumors. This region harbours the tumor suppressor gene prefoldin subunit 5 (PFDN5 and the deletion correlated with a higher Ki-67 score. PFDN5 has been described to repress c-MYC and is, therefore, a candidate tumor-suppressor and cancer-driver gene in canine mammary cancer. Aim of this study was to confirm the recurrent deletion in a larger number of tumors.Droplet digital PCR for PFDN5 was performed in DNA from 102 malignant, 40 benign mammary tumors/dysplasias, 11 non-neoplastic mammary tissues and each corresponding genomic DNA from leukocytes. The copy number of PFDN5 was normalized to a reference amplicon on canine chromosome 32 (CFA32. Z-scores were calculated, based on Gaussian distributed normalized PFDN5 copy numbers of the leukocyte DNA. Z-scores ≤ -3.0 in tissue were considered as being indicative of the PFDN5 deletion and called as such. The Ki-67 proliferation index was assessed in a subset of 79 tissue samples by immunohistochemistry.The deletion was confirmed in 24% of all malignant tumors, detected in only 7.5% of the benign tumors and was not present in any normal mammary tissue sample. The subgroup of solid carcinomas (n = 9 showed the highest frequency of the deletion (67% and those malignomas without microscopical high fraction of benign tissue (n = 71 had a 32% frequency (p<0.01 vs. benign samples. The Ki-67 score was found to be significantly higher (p<0.05 in the PFDN5-deleted group compared to malignant tumors without the deletion.A somatic deletion of the PFDN5 gene is recurrently present in canine mammary cancer, supporting a potential role in carcinogenesis. The association of this deletion with higher Ki-67 indicates an increased proliferation rate and thus a link to tumor aggressiveness can be hypothesized. The confirmation of earlier results warrants further studies on PFDN5 as cancer

  9. Mutagenic Inverted Repeats Assisted Genome Engineering (MIRAGE) in Saccharomyces cerevisiae: deletion of gal7.

    Science.gov (United States)

    Nair, Nikhil U; Zhao, Huimin

    2012-01-01

    MIRAGE is a unique in vivo genome editing technique that exploits the inherent instability of inverted repeats (palindromes) in the Saccharomyces cerevisiae chromosome. As a technique able to quickly create deletions as well as precise point mutations, it is valuable in applications that require creation of designer strains of this yeast. In particular, it has various potential applications in metabolic engineering, systems biology, synthetic biology, and molecular genetics. PMID:22144353

  10. RENKCTD11 is a suppressor of Hedgehog signaling and is deleted in human medulloblastoma

    OpenAIRE

    Di Marcotullio, Lucia; Ferretti, Elisabetta; De Smaele, Enrico; Argenti, Beatrice; Mincione, Claudia; Zazzeroni, Francesca; Gallo, Rita; Masuelli, Laura; Napolitano, Maddalena; Maroder, Marella; Modesti, Andrea; Giangaspero, Felice; Screpanti, Isabella; Alesse, Edoardo; Gulino, Alberto

    2004-01-01

    Hedgehog signaling is suggested to be a major oncogenic pathway in medulloblastoma, which arises from aberrant development of cerebellar granule progenitors. Allelic loss of chromosome 17p has also been described as the most frequent genetic defect in this human neoplasia. This observation raises the question of a possible interplay between 17p deletion and the Hedgehog tumorigenic pathway. Here, we identify the human orthologue of mouse RENKCTD11, previously reported to be expressed in diffe...

  11. Multicolour FISH and quantitative PCR can detect submicroscopic deletions in holoprosencephaly patients with a normal karyotype

    OpenAIRE

    Bendavid, C.; Haddad, B.R.; Griffin, A; Huizing, M; Dubourg, C; Gicquel, I.; Cavalli, L.R.; Pasquier, L.; Shanske, A L; Long, R.; Ouspenskaia, M.; Odent, S; Lacbawan, F; David, V.; Muenke, M

    2006-01-01

    Holoprosencephaly (HPE) is the most common structural malformation of the developing forebrain. At birth, nearly 50% of children with HPE have cytogenetic anomalies. Approximately 20% of infants with normal chromosomes have sequence mutations in one of the four main HPE genes (SHH, ZIC2, SIX3, and TGIF). The other non‐syndromic forms of HPE may be due to environmental factors or mutations in other genes, or potentially due to submicroscopic deletions of HPE genes. We used two complementary as...

  12. High Frequency of Large Intragenic Deletions in the Fanconi Anemia Group A Gene

    OpenAIRE

    Morgan, Neil V.; Tipping, Alex J.; Joenje, Hans; Mathew, Christopher G.

    1999-01-01

    Fanconi anemia (FA) is an autosomal recessive disorder exhibiting chromosomal fragility, bone-marrow failure, congenital abnormalities, and cancer. At least eight complementation groups have been described, with group A accounting for 60%–65% of FA patients. Mutation screening of the group A gene (FANCA) is complicated by its highly interrupted genomic structure and heterogeneous mutation spectrum. Recent reports of several large deletions of FANCA, coupled with modest mutation-detection rate...

  13. Triplex targeted genomic crosslinks enter separable deletion and base substitution pathways

    OpenAIRE

    Richards, Sally; Liu, Su-ting; Majumdar, Alokes; Liu, Ji-Lan; Nairn, Rodney S.; Bernier, Michel; Maher, Veronica; Seidman, Michael M.

    2005-01-01

    We have synthesized triple helix forming oligonucleotides (TFOs) that target a psoralen (pso) interstrand crosslink to a specific chromosomal site in mammalian cells. Mutagenesis of the targeted crosslinks results in base substitutions and deletions. Identification of the gene products involved in mutation formation is important for developing practical applications of pso-TFOs, and may be informative about the metabolism of other interstrand crosslinks. We have studied mutagenesis of a pso-T...

  14. Numt-mediated double-strand break repair mitigates deletions during primate genome evolution.

    Directory of Open Access Journals (Sweden)

    Einat Hazkani-Covo

    2008-10-01

    Full Text Available Non-homologous end joining (NHEJ is the major mechanism of double-strand break repair (DSBR in mammalian cells. NHEJ has traditionally been inferred from experimental systems involving induced double strand breaks (DSBs. Whether or not the spectrum of repair events observed in experimental NHEJ reflects the repair of natural breaks by NHEJ during chromosomal evolution is an unresolved issue. In primate phylogeny, nuclear DNA sequences of mitochondrial origin, numts, are inserted into naturally occurring chromosomal breaks via NHEJ. Thus, numt integration sites harbor evidence for the mechanisms that act on the genome over evolutionary timescales. We have identified 35 and 55 lineage-specific numts in the human and chimpanzee genomes, respectively, using the rhesus monkey genome as an outgroup. One hundred and fifty two numt-chromosome fusion points were classified based on their repair patterns. Repair involving microhomology and repair leading to nucleotide additions were detected. These repair patterns are within the experimentally determined spectrum of classical NHEJ, suggesting that information from experimental systems is representative of broader genetic loci and end configurations. However, in incompatible DSBR events, small deletions always occur, whereas in 54% of numt integration events examined, no deletions were detected. Numts show a statistically significant reduction in deletion frequency, even in comparison to DSBR involving filler DNA. Therefore, numts show a unique mechanism of integration via NHEJ. Since the deletion frequency during numt insertion is low, native overhangs of chromosome breaks are preserved, allowing us to determine that 24% of the analyzed breaks are cohesive with overhangs of up to 11 bases. These data represent, to the best of our knowledge, the most comprehensive description of the structure of naturally occurring DSBs. We suggest a model in which the sealing of DSBs by numts, and probably by other filler

  15. Further phenotypic delineation of subtelomeric (terminal) 4q deletion with emphasis on intracranial and reproductive anatomy

    OpenAIRE

    Dyer CS; Kephart Lisa L; Carroll Lisa P; Parker Laurinda D; Burns MJ; Sills Eric; Papenhausen Peter R; Davis Jessica G

    2007-01-01

    Abstract Objective To describe selected morphological and developmental features associated with subtelomeric deletion at chromosome 4q. Materials and methods A 21-year old female was brought for gynecologic evaluation of menorrhagia. High-resolution metaphase karyotype and subtelomere fluorescent in-situ hybridization (FISH) analysis were used for genotype determination. Pelvic anatomy was characterized via CT and laparoscopy; MR and CT were used for intracranial imaging. Results A de novo d...

  16. 7q36 deletion and 9p22 duplication: effects of a double imbalance

    OpenAIRE

    Pelegrino Karla de; Sugayama Sofia; Catelani Ana; Lezirovitz Karina; Kok Fernando; Chauffaille Maria de

    2013-01-01

    Abstract The etiology of mental retardation/developmental delay (MRDD) remains a challenge to geneticists and clinicians and can be correlated to environmental and genetic factors. Chromosomal aberrations are common causes of moderate to severe mental retardation and may represent 10% of these occurrences. Here we report the case of a boy with development delay, hypoplasia of corpus callosum, microcephaly, muscular hypotonia, and facial dysmorphisms. A deletion of 7q36.1 → 36.3 and duplicatio...

  17. Refinement of the critical 2p25.3 deletion region

    DEFF Research Database (Denmark)

    De Rocker, Nina; Vergult, Sarah; Koolen, David;

    2015-01-01

    PURPOSE: Submicroscopic deletions of chromosome band 2p25.3 are associated with intellectual disability and/or central obesity. Although MYT1L is believed to be a critical gene responsible for intellectual disability, so far no unequivocal data have confirmed this hypothesis. METHODS: In this stu...... syndromal intellectual disability. Moreover, because 17 patients present with obesity/overweight, haploinsufficiency of MYT1L might predispose to weight problems with childhood onset.Genet Med 17 6, 460-466....

  18. Cryptic 13q34 and 4q35.2 Deletions in an Italian Family.

    Science.gov (United States)

    Riccardi, Federica; Rivolta, Gianna F; Uliana, Vera; Grati, Francesca R; La Starza, Roberta; Marcato, Livia; Di Perna, Caterina; Quintavalle, Gabriele; Garavelli, Livia; Rosato, Simonetta; Sammarelli, Gabriella; Neri, Tauro M; Tagliaferri, Annarita; Martorana, Davide

    2015-01-01

    Variations of DNA sequences in the human genome range from large, microscopically visible chromosome anomalies to single nucleotide changes. Submicroscopic genomic copy number variations, i.e. chromosomal imbalances which are undetectable by conventional cytogenetic analysis, play an intriguing clinical role. In this study, we describe the clinical consequences of the concurrent presence of an interstitial deletion in 13q34 and a terminal deletion in 4q35.2 in an Italian family. The index patient, a 19-year-old male, as well as his 12-year-old sister are carriers of both deletions, one of maternal and the other of paternal origin. The phenotype includes language delay, multiorgan involvement and bleeding diathesis with mild deficiency of factors X and VII. In the sister, the concomitant presence of Noonan syndrome may partly explain the clinical symptoms. The deleted region on chromosome 13 involves several genes (ATP11A, MCF2L, F7, F10, PROZ, PCID2, CUL4A, and LAMP1); some of these seem to play a role in the proband's phenotype. The terminal deletion in 4q35.2 contains other OMIM genes (FRG1, FRG2 and DBET); moreover, the 4q region is reported as a susceptibility locus for Crohn's disease, diagnosed in the proband's father. To our knowledge, this is the first report of a family with these 2 submicroscopic copy number changes. We tried to relate the clinical phenotype of the proband and his family to the molecular function of the involved genes. PMID:26645620

  19. Further phenotypic delineation of subtelomeric (terminal 4q deletion with emphasis on intracranial and reproductive anatomy

    Directory of Open Access Journals (Sweden)

    Dyer CS

    2007-02-01

    Full Text Available Abstract Objective To describe selected morphological and developmental features associated with subtelomeric deletion at chromosome 4q. Materials and methods A 21-year old female was brought for gynecologic evaluation of menorrhagia. High-resolution metaphase karyotype and subtelomere fluorescent in-situ hybridization (FISH analysis were used for genotype determination. Pelvic anatomy was characterized via CT and laparoscopy; MR and CT were used for intracranial imaging. Results A de novo deletion [46,XX del(4(q32] was identified cytogenetically and confirmed as a terminal loss via subtelomere FISH. Hand/foot malformation characteristic of deletion at this segment was present. Pelvic CT and laparoscopy revealed normal uterine anatomy. Fallopian tubes appeared grossly unremarkable, and a right ovarian cyst was excised without difficulty. Bilateral broad ligament fibroadipose nodularities were noted adjacent to the uterus between round ligament and fallopian tube. Neurological exam revealed no focal defects, although brain MR identified an abnormal signal intensity at the inferior margin of the globus pallidus, consistent with old lacunar infarct and gliosis. Developmental delay was supported by an observed level of general intellectual function estimated at age seven. Conclusion Terminal deletion of the long arm of chromosome 4 is a rare genetic event associated with a distinctive phenotype dependent on the size of the deletion. Chromosomal losses that span the 4q32 band include mental retardation and mild craniofacial anomalies. Here, further characterization of this disorder is offered including precise quantification of the DNA loss, information on brain morphology and pelvic anatomy. Additional studies will be required to characterize the full developmental and physiologic implications of this unusual genetic disorder.

  20. Plant sex chromosome evolution.

    Science.gov (United States)

    Charlesworth, Deborah

    2013-01-01

    It is now well established that plants have an important place in studies of sex chromosome evolution because of the repeated independent evolution of separate sexes and sex chromosomes. There has been considerable recent progress in studying plant sex chromosomes. In this review, I focus on how these recent studies have helped clarify or answer several important questions about sex chromosome evolution, and I shall also try to clarify some common misconceptions. I also outline future work that will be needed to make further progress, including testing some important ideas by genetic, molecular, and developmental approaches. Systems with different ages can clearly help show the time course of events during changes from an ancestral co-sexual state (hermaphroditism or monoecy), and I will also explain how different questions can be studied in lineages whose dioecy or sex chromosomes evolved at different times in the past. PMID:23125359

  1. Cognitive-behavioral characteristics and developmental trajectories in children with deletion 11qter (Jacobsen syndrome), and their relation to deletion size.

    Science.gov (United States)

    Fisch, Gene S

    2015-01-01

    Subtelomeric deletions represent an important class of abnormalities to be considered when investigating genetic links to intellectual disability (ID). One subtelomeric deletion found on the long arm of chromosome 11q produces a characteristic phenotype that includes ID and is often referred to as Jacobsen syndrome (JBS). Previously, researchers found an inverse relationship between IQ and deletion size. While useful, IQ does not provide a comprehensive picture of the cognitive-behavioral strengths and weaknesses in JBS, nor does it reveal how the profiles evolve as these individuals age. One purpose of this study was to confirm the relationship between IQ or adaptive behavior (DQ) and deletion size. We also examined cognitive-behavioral profiles of children with JBS and the extent to which they changed over time. Initially, at T1, we examined 10 children, ages 5-20 years, diagnosed with JBS. Cognitive ability was assessed with the Stanford-Binet (4th Edition). Adaptive behavoir was evaluated with the Vineland Adaptive Behavior Scales (VABS). Eight children were reassessed 2 years later (T2). Results show a negative but non-significant correlation between IQ and deletion size. There was no statistically significant relationship between DQ and deletion size. As for our second aim, IQ and DQ scores were stable from T1 to T2. Cognitive profiles were not significantly different from T1 to T2. However, there were significant changes in adaptive behavior domain scores from T1 to T2. Lack of a significant relationship between cognitive-behavioral measures and deletion size, as well as changes in cognitive-behavioral profiles are discussed. PMID:25425441

  2. A novel Xq22.1 deletion in a male with multiple congenital abnormalities and respiratory failure.

    Science.gov (United States)

    Cao, Yang; Aypar, Umut

    2016-05-01

    Here we report the first male case of a novel Xq22.1 deletion. An 8-week-old boy with multiple congenital abnormalities and respiratory failure was referred to the Mayo Clinic Cytogenetics laboratory for testing. Chromosomal microarray analysis identified a novel 1.1 Mb deletion at Xq22.1. A similar deletion has only been described once in the literature in a female patient and her mother; both have intellectual disability and dysmorphic facial features. In addition, the mother had a son who died at 15 days due to breathing failure. Recently, a mouse model revealed that a 0.35 Mb sub-region, containing 4 genes, is sufficient to cause majority of the Xq22.1 deletion phenotypes. The deleted intervals in our male patient and the female patients contain 15 common genes, including the four described in the 0.35 Mb sub-region. Male mice with deletion of the 0.35 Mb sub-region died perinatally from respiratory failure due to pulmonary hypoplasia, consistent with the breathing problem and potential neonatal fatality in male patients. The phenotypes of the mouse models and the patients are strikingly similar; therefore, the deletion of these five genes (ARMCX5, ARMCX5-GPRASP2, GPRASP1, GPRASP2, and BHLHB9) is likely responsible for the novel Xq22.1 deletion syndrome. PMID:26995686

  3. Vibrio chromosomes share common history

    OpenAIRE

    Gevers Dirk; Chang Sarah; Chang LeeAnn; Kirkup Benjamin C; Polz Martin F

    2010-01-01

    Abstract Background While most gamma proteobacteria have a single circular chromosome, Vibrionales have two circular chromosomes. Horizontal gene transfer is common among Vibrios, and in light of this genetic mobility, it is an open question to what extent the two chromosomes themselves share a common history since their formation. Results Single copy genes from each chromosome (142 genes from chromosome I and 42 genes from chromosome II) were identified from 19 sequenced Vibrionales genomes ...

  4. Quantification of the DNA content of structurally abnormal X chromosomes and X chromosome aneuploidy using high resolution bivariate flow karyotyping.

    Science.gov (United States)

    Trask, B; van den Engh, G; Nussbaum, R; Schwartz, C; Gray, J

    1990-01-01

    Quantification of the Hoechst and chromomycin A3 fluorescence intensities of mitotic human chromosomes isolated from karyotypically normal and abnormal cells was performed with a dual beam flow cytometer. The resultant flow karyotypes contain information about the relative DNA content and base composition of chromosomes and their relative frequencies in the mitotic cell sample. The relative copy number of X and Y chromosomes was determined for 38 normal males and females and 6 cell lines with X or Y chromosome aneuploidy. Flow karyotype diagnoses corresponded with conventional cytogenetic results in all cases. We show that chromosome DNA content can be derived from peak position in Hoechst vs. chromomycin flow karyotypes. These values are linearly related to propidium iodide staining intensity as measured with flow cytometry and to the binding of gallocyanin chrome alum to phosphate groups as measured with slide-based scanning photometry. Cell lines with deleted or dicentric X chromosomes ranging in length from 0.53 to 1.95 times normal were analyzed by using flow cytometry. The measured difference in DNA content between a normal X and each of the structurally abnormal chromosomes was linearly correlated to the difference predicted from cytogenetics and/or probe analyses. Deletions of 3-5 Mb, which were at and below the detection limits of conventional cytogenetics, could be quantified by flow karyotyping in individuals with X-linked diseases such as Duchenne muscular dystrophy, choroideremia, and ocular albinism/ichthyosis. The results show that the use of flow karyotyping to quantify the size of restricted regions of the genome can complement conventional cytogenetics and other physical mapping techniques in the study of genetic disorders. PMID:2106419

  5. Velo-Cardio-Facial syndrome and DiGeorge sequence with meningomyelocele and deletions of the 22q11 region

    Energy Technology Data Exchange (ETDEWEB)

    Nickel, R.E.; Pillers, D.M.; Merkens, M.; Magenis, R.E.; Zonana, J. [Oregon Health Sciences Univ., Portland, OR (United States); Driscoll, D.A.; Emanuel, B.S. [Univ. of Pennsylvania Medical Center, Philadelphia, PA (United States)

    1994-10-01

    Approximately 5% of children with neural tube defects (NTDs) have a congenital heart defect and/or cleft lip and palate. The cause of isolated meningomyelocele, congenital heart defects, or cleft lip and palate has been largely thought to be multifactorial. However, chromosomal, teratogenic, and single gene causes of combinations of NTDs with congenital heart defects and/or cleft lip and palate have been reported. We report on 3 patients with meningomyelocele, congenital heart defects, and 22q11 deletions. Two of the children had the clinical diagnosis of velo-cardio-facial syndrome (VCFS); both have bifid uvula. The third child had DiGeorge sequence (DGS). The association of NTDs with 22q11 deletion has not been reported previously. An accurate diagnosis of the 22q11 deletion is critical as this micro-deletion and its associated clinical problems is transmitted as an autosomal dominant trait due to the inheritance of the deletion-bearing chromosome. We recommend that all children with NTDs and congenital heart defects, with or without cleft palate, have cytogenetic and molecular studies performed to detect 22q11 deletions. 31 refs., 3 figs.

  6. Partial Gene Deletions of PMP22 Causing Hereditary Neuropathy with Liability to Pressure Palsies

    Directory of Open Access Journals (Sweden)

    Sun-Mi Cho

    2014-01-01

    Full Text Available Hereditary neuropathy with liability to pressure palsies (HNPP is an autosomal neuropathy that is commonly caused by a reciprocal 1.5 Mb deletion on chromosome 17p11.2, at the site of the peripheral myelin protein 22 (PMP22 gene. Other patients with similar phenotypes have been shown to harbor point mutations or small deletions, although there is some clinical variation across these patients. In this report, we describe a case of HNPP with copy number changes in exon or promoter regions of PMP22. Multiplex ligation-dependent probe analysis revealed an exon 1b deletion in the patient, who had been diagnosed with HNPP in the first decade of life using molecular analysis.

  7. Age-related differences in 1p and 19q deletions in oligodendrogliomas

    Directory of Open Access Journals (Sweden)

    Del Bigio Marc R

    2003-12-01

    Full Text Available Abstract Background Recent reports indicate that anaplastic oligodendrogliomas frequently show allelic losses on chromosome arms 1p and 19q, and that these deletions are associated with better chemotherapeutic response and overall patient survival. Because of the diversified genetic makeup of the population and the centralized provincial referral system for brain tumor patients in Manitoba, the epidemiological features of such tumors sometimes differ from the published data acquired from non-community based settings. In this study, we assessed the prevalence of allelic deletions for chromosome arms 1p and 19q in anaplastic and in low-grade oligodendrogliomas in the Manitoba population. Methods Loss of heterozygosity (LOH analysis of brain tumors was carried out using 4 microsatellite markers (D1S508, D1S2734, D19S219 and D19S412 and a PCR based assay. The tumors were consecutively acquired during the period September 1999–March 2001 and a total of 63 tumors were assessed. Results We found that allelic loss of chromosome 1p and 19q was higher in oligodendrogliomas than in other diffuse gliomas and that for anaplastic oligodendrogliomas, younger patients exhibited significantly more deletions than older patients (>60 years of age. Conclusions These studies suggest that age may be a factor in the genetic alterations of oligodendrogliomas. In addition, these studies demonstrate that this assay can easily be carried out in a cost-effective manner in a small tertiary center.

  8. An improved method for rapid generation of unmarked Pseudomonas aeruginosa deletion mutants

    Directory of Open Access Journals (Sweden)

    Schweizer Herbert P

    2005-05-01

    Full Text Available Abstract Background Traditional gene replacement procedures are still time-consuming. They usually necessitate cloning of the gene to be mutated, insertional inactivation of the gene with an antibiotic resistance cassette and exchange of the plasmid-borne mutant allele with the bacterial chromosome. PCR and recombinational technologies can be exploited to substantially accelerate virtually all steps involved in the gene replacement process. Results We describe a method for rapid generation of unmarked P. aeruginosa deletion mutants. Three partially overlapping DNA fragments are amplified and then spliced together in vitro by overlap extension PCR. The resulting DNA fragment is cloned in vitro into the Gateway vector pDONR221 and then recombined into the Gateway-compatible gene replacement vector pEX18ApGW. The plasmid-borne deletions are next transferred to the P. aeruginosa chromosome by homologous recombination. Unmarked deletion mutants are finally obtained by Flp-mediated excision of the antibiotic resistance marker. The method was applied to deletion of 25 P. aeruginosa genes encoding transcriptional regulators of the GntR family. Conclusion While maintaining the key features of traditional gene replacement procedures, for example, suicide delivery vectors, antibiotic resistance selection and sucrose counterselection, the method described here is considerably faster due to streamlining of some of the key steps involved in the process, especially plasmid-borne mutant allele construction and its transfer into the target host. With appropriate modifications, the method should be applicable to other bacteria.

  9. The mouse and human excitatory amino acid transporter gene (EAAT1) maps to mouse chromosome 15 and a region of syntenic homology on human chromosome 5

    Energy Technology Data Exchange (ETDEWEB)

    Kirschner, M.A.; Arriza, J.L.; Amara, S.G. [Oregon Health Sciences Univ., Portland, OR (United States)] [and others

    1994-08-01

    The gene for human excitatory amino acid transporter (EAAT1) was localized to the distal region of human chromosome 5p13 by in situ hybridization of metaphase chromosome spreads. Interspecific backcross analysis identified the mouse Eaat1 locus in a region of 5p13 homology on mouse chromosome 15. Markers that are linked with EAAT1 on both human and mouse chromosomes include the receptors for leukemia inhibitory factor, interleukin-7, and prolactin. The Eaat1 locus appears not be linked to the epilepsy mutant stg locus, which is also on chromosome 15. The EAAT1 locus is located in a region of 5p deletions that have been associated with mental retardation and microcephaly. 22 refs., 2 figs.

  10. Molecular nature of ultraviolet B light-induced deletions in the murine epidermis.

    Science.gov (United States)

    Horiguchi, M; Masumura, K I; Ikehata, H; Ono, T; Kanke, Y; Nohmi, T

    2001-05-15

    Depletion of the stratospheric ozone layer leads to an increase in ambient UV loads, which are expected to raise skin cancer incidences. Tumor development in the skin could be a multistep process in which various genetic alterations, such as point mutations and deletions, occur successively. Here, we demonstrate that UVB irradiation efficiently induces deletions in the epidermis using a novel transgenic mouse, gpt delta. In this mouse model, deletions in lambda DNA integrated in the chromosome are preferentially selected as Spi(-) (sensitive to P2 interference) phages, which can then be subjected to molecular analysis. The mice were exposed to UVB at single doses of 0.3, 0.5, 1.0, 1.5, and 2.0 kJ/m(2). After 4 weeks, lambda phage was rescued from the genomic DNA of the epidermis by in vitro packaging reactions. The mutant frequencies of Spi(-) with large deletions in the epidermis increased >15-fold at a UVB dose of 0.5 kJ/m(2) over the control. Molecular sizes of most of the large deletions were >1000 bp. More than one-half of the large deletions occurred between short direct-repeat sequences from 1 to 6 bp, and the remainder had flush ends. In the unirradiated mouse, almost all of the Spi(-) mutants were 1-bp frameshifts in runs of identical bases. These results suggest that UVB irradiation induces deletions in the murine epidermis, and most of the deletions are generated through end-joining of double strand breaks in DNA. PMID:11358805

  11. Frequent deletions of JARID2 in leukemic transformation of chronic myeloid malignancies.

    Science.gov (United States)

    Puda, Ana; Milosevic, Jelena D; Berg, Tiina; Klampfl, Thorsten; Harutyunyan, Ashot S; Gisslinger, Bettina; Rumi, Elisa; Pietra, Daniela; Malcovati, Luca; Elena, Chiara; Doubek, Michael; Steurer, Michael; Tosic, Natasa; Pavlovic, Sonja; Guglielmelli, Paola; Pieri, Lisa; Vannucchi, Alessandro M; Gisslinger, Heinz; Cazzola, Mario; Kralovics, Robert

    2012-03-01

    Chronic myeloproliferative neoplasms (MPN) and myelodysplastic syndromes (MDS) have an inherent tendency to progress to acute myeloid leukemia (AML). Using high-resolution SNP microarrays, we studied a total of 517 MPN and MDS patients in different disease stages, including 77 AML cases with previous history of MPN (N = 46) or MDS (N = 31). Frequent chromosomal deletions of variable sizes were detected, allowing the mapping of putative tumor suppressor genes involved in the leukemic transformation process. We detected frequent deletions on the short arm of chromosome 6 (del6p). The common deleted region on 6p mapped to a 1.1-Mb region and contained only the JARID2 gene--member of the polycomb repressive complex 2 (PRC2). When we compared the frequency of del6p between chronic and leukemic phase, we observed a strong association of del6p with leukemic transformation (P = 0.0033). Subsequently, analysis of deletion profiles of other PRC2 members revealed frequent losses of genes such as EZH2, AEBP2, and SUZ12; however, the deletions targeting these genes were large. We also identified two patients with homozygous losses of JARID2 and AEBP2. We observed frequent codeletion of AEBP2 and ETV6, and similarly, SUZ12 and NF1. Using next generation exome sequencing of 40 patients, we identified only one somatic mutation in the PRC2 complex member SUZ12. As the frequency of point mutations in PRC2 members was found to be low, deletions were the main type of lesions targeting PRC2 complex members. Our study suggests an essential role of the PRC2 complex in the leukemic transformation of chronic myeloid disorders. PMID:22190018

  12. Interstitial 1q23.3q24.1 deletion in a patient with renal malformation, congenital heart disease, and mild intellectual disability.

    Science.gov (United States)

    Mackenroth, Luisa; Hackmann, Karl; Klink, Barbara; Weber, Julia Sara; Mayer, Brigitte; Schröck, Evelin; Tzschach, Andreas

    2016-09-01

    Interstitial deletions including chromosome region 1q23.3q24.1 are rare. Only eight patients with molecularly characterized deletions have been reported to date. Their phenotype included intellectual disability/developmental delay, growth retardation, microcephaly, congenital heart disease, and renal malformations. We report on a female patient with mild developmental delay, congenital heart disease, and bilateral renal hypoplasia in whom an interstitial de novo deletion of approximately 2.7 Mb in 1q23.3q24.1 was detected by array CGH. This is the smallest deletion described in this region so far. Genotype-phenotype comparison with previously published patients allowed us to propose LMX1A and RXRG as potential candidate genes for intellectual disability, PBX1 as a probable candidate gene for renal malformation, and enabled us to narrow down a chromosome region associated with microcephaly. © 2016 Wiley Periodicals, Inc. PMID:27255444

  13. Cybersemiotics: Suggestion for a Transdisciplinary Framework Encompassing Natural, Life, and Social Sciences as Well as Phenomenology and Humanities

    OpenAIRE

    Søren Brier

    2014-01-01

    The modern evolutionary paradigm combined with phenomenology forces us to view human consciousness as a product of evolution as well as accepting humans as observers from “within the universe”. The knowledge produced by science has first-person embodied consciousness combined with second-person meaningful communication in language as a prerequisite for third-person fallibilist scientific knowledge. Therefore, the study of consciousness forces us theoretically to encompass the natural and soci...

  14. Surrounded by Safety: Safety As An Encompassing Policy Concept in The Netherlands. European Journal of Policing Studies.

    OpenAIRE

    Resodihardjo, S.; Prins, R.S.

    2014-01-01

    Safety used to be a pretty straightforward concept: governments need to safeguard the country from invasion and its citizens from crime. Over time, additional issues became to be defined as a safety problem. Even so, the safety problems and their accompanying policies remained clearly demarcated – safety revolved, for example, around product safety. Recently, an encompassing safety concept has become popular in the Netherlands. No longer referring to a clearly demarcated policy issue, the con...

  15. Sequential cloning of chromosomes

    Energy Technology Data Exchange (ETDEWEB)

    Lacks, S.A.

    1991-12-31

    A method for sequential cloning of chromosomal DNA and chromosomal DNA cloned by this method are disclosed. The method includes the selection of a target organism having a segment of chromosomal DNA to be sequentially cloned. A first DNA segment, having a first restriction enzyme site on either side. homologous to the chromosomal DNA to be sequentially cloned is isolated. A first vector product is formed by ligating the homologous segment into a suitably designed vector. The first vector product is circularly integrated into the target organism`s chromosomal DNA. The resulting integrated chromosomal DNA segment includes the homologous DNA segment at either end of the integrated vector segment. The integrated chromosomal DNA is cleaved with a second restriction enzyme and ligated to form a vector-containing plasmid, which is replicated in a host organism. The replicated plasmid is then cleaved with the first restriction enzyme. Next, a DNA segment containing the vector and a segment of DNA homologous to a distal portion of the previously isolated DNA segment is isolated. This segment is then ligated to form a plasmid which is replicated within a suitable host. This plasmid is then circularly integrated into the target chromosomal DNA. The chromosomal DNA containing the circularly integrated vector is treated with a third, retrorestriction enzyme. The cleaved DNA is ligated to give a plasmid that is used to transform a host permissive for replication of its vector. The sequential cloning process continues by repeated cycles of circular integration and excision. The excision is carried out alternately with the second and third enzymes.

  16. A boy with mild mental retardation, mild sensorineural hearing loss and mild facial dysmorphism caused by a 19p13.2 deletion: a case report and review of the literature.

    Science.gov (United States)

    Schwemmle, Cornelia; Rost, Imma; Spranger, Stephanie; Jungheim, Michael; Ptok, Martin

    2014-07-01

    The investigation of patients with congenital anomalies and/or intellectual disability with modern genetic methods allows the recognition of an increasing number of cases with these chromosomal rearrangements. Here, we present a mildly mentally retarded boy with mild facial dysmorphism, language development delay, mild sensorineural hearing loss due to a deletion of 1,14 Mb on chromosome 19p 13.2. The deletion was de novo and familial history negative for this disorder. To our knowledge this is the first description of a patient with symptoms mentioned above associated with a 19p13.2-p13.2 deletion. PMID:24814572

  17. Screening of ′Y′ chromosome microdeletions in Iranian infertile males

    Directory of Open Access Journals (Sweden)

    Ali Mohammad Malekasgar

    2008-01-01

    Full Text Available Background : It has been hypothesized that microdeletions of Yq may account for a significant proportion of men with infertility. Three nonoverlapping regions, referred to as "azoospermia factors" (AZFa, b, c from proximal to distal Yq have been defined as spermatogenesis loci and deletions in these regions have been shown to be pathogenically involved in male infertility associated with azoospermia or severe oligospermia. Aims: Evaluation the frequency of Y chromosome microdeletions in Iranian population. Materials and Methods: Fifty infertile men were selected. Semen analysis was done and on the basis of the mean sperm count, all patients were categorized into azoospermia and oligozoospermia, groups. Blood samples were obtained for DNA extraction and chromosomal analysis. Genomic DNA was extracted from blood lymphocytes and amplified by sequence tagged sites-polymerase chain reaction (STS-PCR method to determine the presence of microdeletions in AZF locus. A total of 34 STS primers including two controls were selected to identify microdeletions of Y chromosome on each subject. Results and Conclusion: 26/50 cases (52% showed deletion of at least one of the STS Marker. Totally 41 microdeletions was observed. A total of 17 cases (34% had deletion in one STS. Four oligospermia cases (8% had deletion in 2 STS site. Three azoospermia cases (6% had again deletion in 2 STS site, but in different STSs. One case had three deletions in three STS site and finally one individual had seven deletions in AZF locus. The overall frequency of Y chromosome microdeletions observed in the present study was found to be 26/50 (52%. Comparison of our data with the result of other investigators world wide shows that the incidence of Yq microdeletions in Iranian population is much higher than international frequency. Our data agree with other studies regarding microdeletions of AZFc, but for microdeletions of AZFa (14.6% our results is much higher and differ

  18. A new chromosome was born: comparative chromosome painting in Boechera.

    Science.gov (United States)

    Koch, Marcus A

    2015-09-01

    Comparative chromosome painting is a powerful tool to study the evolution of chromosomes and genomes. Analyzing karyotype evolution in cruciferous plants highlights the origin of aberrant chromosomes in apomictic Boechera and further establishes the cruciferous plants as important model system for our understanding of plant chromosome and genome evolution. PMID:26228436

  19. Chromosomal abnormalities and environmental exposures in acute nonlymphocytic leukemia

    International Nuclear Information System (INIS)

    Chromosomal abnormalities are present in bone marrow of approximately 50% of newly diagnostic acute nonlymphatic leukemia (ANLL) patients, but their etiologic significance, if any, is unclear. The frequency of environmental exposures, gathered by questionnaire from patients or relatives, was compared in 127 newly diagnosed ANLL patients with marrow abnormalities (AA) and 109 ANLL patients with cytogenetically normal marrow. These represented 73% of de novo patients treated at M. D. Anderson Hospital between 1976 and 1983. AA patients were more likely than NN patients to: report cytotoxic treatment for prior medical conditions, smoke cigarettes, drink alcoholic beverages, and work at occupations with possible exposure to mutagens. No statistically significant associations between aneuploidy and use of other tobacco, avocational exposure to chemicals or exposure to animals were present. Associations between specific abnormalities and prior cytotoxic therapy (deletion of chromosome 7), smoking (extra chromosome 8, inversion chromosome 16), and occupation at the time of diagnosis (translocation between chromosomes 8 and 21) were noted. No association between occupational exposure to benzene or ionizing radiation and the 6 most common chromosomal abnormalities in ANLL patients were noted, although these agents are known to be leukemogenic. Problems with interpreting the above associations, including the high nonresponse rate, a high proportion of surrogate respondents, and the large number of significance tests that were performed, are discussed. These results are consistent with those from previously reported series, and suggest that tumor-specific markers may be present for some exposures in this disease

  20. A 380-kb Duplication in 7p22.3 Encompassing the LFNG Gene in a Boy with Asperger Syndrome

    NARCIS (Netherlands)

    Vulto-van Silfhout, A.T.; Brouwer, A.F. de; Leeuw, N. de; Obihara, C.C.; Brunner, H.G.; Vries, B.B. de

    2012-01-01

    De novo genomic aberrations are considered an important cause of autism spectrum disorders. We describe a de novo 380-kb gain in band p22.3 of chromosome 7 in a patient with Asperger syndrome. This duplicated region contains 9 genes including the LNFG gene that is an important regulator of NOTCH sig

  1. Deficits in microRNA-mediated Cxcr4/Cxcl12 signaling in neurodevelopmental deficits in a 22q11 deletion syndrome mouse model.

    OpenAIRE

    Toritsuka, Michihiro; Kimoto, Sohei; Muraki, Kazue; Landek-Salgado, Melissa A.; Yoshida, Atsuhiro; Yamamoto, Norio; Horiuchi, Yasue; Hiyama, Hideki; Tajinda, Katsunori; Keni, Ni; Illingworth, Elizabeth; Iwamoto, Takashi; Kishimoto, Toshifumi; Sawa, Akira; Tanigaki, Kenji

    2013-01-01

    22q11 deletion syndrome (22q11DS) frequently accompanies psychiatric conditions, some of which are classified as schizophrenia and bipolar disorder in the current diagnostic categorization. However, it remains elusive how the chromosomal microdeletion leads to the mental manifestation at the mechanistic level. Here we show that a 22q11DS mouse model with a deletion of 18 orthologous genes of human 22q11 (Df1/+ mice) has deficits in migration of cortical interneurons and hippocampal dentate pr...

  2. Interstitial 14q24.3 to q31.3 deletion in a 6-year-old boy with a non-specific dysmorphic phenotype

    OpenAIRE

    Riegel, Mariluce; Moreira, Lilia MA; Espirito Santo, Layla D; Maria Betânia P. Toralles; Schinzel, Albert

    2014-01-01

    Background Few patients with interstitial deletions in the distal long arm of chromosome 14 have been reported, and these patients showed rather indistinct features, including growth and mental retardation and phenotypic alterations. Results We describe a de novo 14q interstitial deletion in a 6-year-old boy with dysmorphic facial traits such as hypertelorism, short and narrow palpebral fissures, broad nose with anteverted nostrils, long philtrum, thin upper lip with cupid’s bow, prominent an...

  3. Interstitial 14q24.3 to q31.3 deletion in a 6-year-old boy with a non-specific dysmorphic phenotype

    OpenAIRE

    Riegel, Mariluce; Moreira, Lilia M; Espirito Santo, Layla D; Toralles, Maria B P; Schinzel, Albert

    2014-01-01

    BACKGROUND: Few patients with interstitial deletions in the distal long arm of chromosome 14 have been reported, and these patients showed rather indistinct features, including growth and mental retardation and phenotypic alterations. RESULTS: We describe a de novo 14q interstitial deletion in a 6-year-old boy with dysmorphic facial traits such as hypertelorism, short and narrow palpebral fissures, broad nose with anteverted nostrils, long philtrum, thin upper lip with cupid's bow, promine...

  4. Y chromosome specific probes identify breakpoint in a 45,X/46,X,del(Y)(pter----q11.1:) karyotype of an infertile male.

    OpenAIRE

    Beverstock, G C; Macfarlane, J D; Veenema, H; Hoekman, H; Goodfellow, P J

    1989-01-01

    An infertile male patient with a 45,X peripheral blood karyotype and a 45,X/46,X,del(Y)(pter----q11.1:) mosaic skin fibroblast karyotype is described. Steroid sulphatase (STS) activity was normal. Recombinant DNA studies using Y chromosome specific probes suggest that almost the entire long arm of the Y chromosome is deleted.

  5. Structural organization of the inactive X chromosome in the mouse.

    Science.gov (United States)

    Giorgetti, Luca; Lajoie, Bryan R; Carter, Ava C; Attia, Mikael; Zhan, Ye; Xu, Jin; Chen, Chong Jian; Kaplan, Noam; Chang, Howard Y; Heard, Edith; Dekker, Job

    2016-07-28

    X-chromosome inactivation (XCI) involves major reorganization of the X chromosome as it becomes silent and heterochromatic. During female mammalian development, XCI is triggered by upregulation of the non-coding Xist RNA from one of the two X chromosomes. Xist coats the chromosome in cis and induces silencing of almost all genes via its A-repeat region, although some genes (constitutive escapees) avoid silencing in most cell types, and others (facultative escapees) escape XCI only in specific contexts. A role for Xist in organizing the inactive X (Xi) chromosome has been proposed. Recent chromosome conformation capture approaches have revealed global loss of local structure on the Xi chromosome and formation of large mega-domains, separated by a region containing the DXZ4 macrosatellite. However, the molecular architecture of the Xi chromosome, in both the silent and expressed regions,remains unclear. Here we investigate the structure, chromatin accessibility and expression status of the mouse Xi chromosome in highly polymorphic clonal neural progenitors (NPCs) and embryonic stem cells. We demonstrate a crucial role for Xist and the DXZ4-containing boundary in shaping Xi chromosome structure using allele-specific genome-wide chromosome conformation capture (Hi-C) analysis, an assay for transposase-accessible chromatin with high throughput sequencing (ATAC-seq) and RNA sequencing. Deletion of the boundary disrupts mega-domain formation, and induction of Xist RNA initiates formation of the boundary and the loss of DNA accessibility. We also show that in NPCs, the Xi chromosome lacks active/inactive compartments and topologically associating domains (TADs), except around genes that escape XCI. Escapee gene clusters display TAD-like structures and retain DNA accessibility at promoter-proximal and CTCF-binding sites. Furthermore, altered patterns of facultative escape genes indifferent neural progenitor clones are associated with the presence of different TAD

  6. Chimpanzee chromosome 13 is homologous to human chromosome 2p

    Energy Technology Data Exchange (ETDEWEB)

    Sun, N. C.; Sun, C. R.Y.; Ho, T.

    1977-01-01

    Similarities between human and chimpanzee chromosomes are shown by chromosome banding techniques and somatic cell hybridization techniques. Cell hybrids were obtained from the chimpanzee lymphocyte LE-7, and the Chinese hamster mutant cell, Gal-2. Experiments showed that the ACPL, MDHs, and Gal-Act genes could be assigned to chimpanzee chromosome 13, and since these genes have been assigned to human chromosme 2p, it is suggested that chimpanzee chromosome 13 is homologous to human chromosome 2p. (HLW)

  7. Chromosome condensation and segmentation

    International Nuclear Information System (INIS)

    Some aspects of chromosome condensation in mammalians -humans especially- were studied by means of cytogenetic techniques of chromosome banding. Two further approaches were adopted: a study of normal condensation as early as prophase, and an analysis of chromosome segmentation induced by physical (temperature and γ-rays) or chemical agents (base analogues, antibiotics, ...) in order to show out the factors liable to affect condensation. Here 'segmentation' means an abnormal chromosome condensation appearing systematically and being reproducible. The study of normal condensation was made possible by the development of a technique based on cell synchronization by thymidine and giving prophasic and prometaphasic cells. Besides, the possibility of inducing R-banding segmentations on these cells by BrdU (5-bromodeoxyuridine) allowed a much finer analysis of karyotypes. Another technique was developed using 5-ACR (5-azacytidine), it allowed to induce a segmentation similar to the one obtained using BrdU and identify heterochromatic areas rich in G-C bases pairs

  8. Chromosomal abnormalities and autism

    Directory of Open Access Journals (Sweden)

    Farida El-Baz

    2016-01-01

    Conclusion: Chromosomal abnormalities were not detected in the studied autistic children, and so the relation between the genetics and autism still needs further work up with different study methods and techniques.

  9. Behavioral Abnormalities and Circuit Defects in the Basal Ganglia of a Mouse Model of 16p11.2 Deletion Syndrome

    OpenAIRE

    Thomas Portmann; Mu Yang; Rong Mao; Georgia Panagiotakos; Jacob Ellegood; Gul Dolen; Patrick L. Bader; Brad A. Grueter; Carleton Goold; Elaine Fisher; Katherine Clifford; Pavitra Rengarajan; David Kalikhman; Darren Loureiro; Nay L. Saw

    2014-01-01

    A deletion on human chromosome 16p11.2 is associated with autism spectrum disorders. We deleted the syntenic region on mouse chromosome 7F3. MRI and high-throughput single-cell transcriptomics revealed anatomical and cellular abnormalities, particularly in cortex and striatum of juvenile mutant mice (16p11+/−). We found elevated numbers of striatal medium spiny neurons (MSNs) expressing the dopamine D2 receptor (Drd2+) and fewer dopamine-sensitive (Drd1+) neurons in deep layers of cortex. Ele...

  10. Chromosome numbers in Bromeliaceae

    OpenAIRE

    2000-01-01

    The present study reports chromosome numbers of 17 species of Bromeliaceae, belonging to the genera Encholirium, Bromelia, Orthophytum, Hohenbergia, Billbergia, Neoglaziovia, Aechmea, Cryptanthus and Ananas. Most species present 2n = 50, however, Bromelia laciniosa, Orthophytum burle-marxii and O. maracasense are polyploids with 2n = 150, 2n = 100 and 2n = 150, respectively, while for Cryptanthus bahianus, 2n = 34 + 1-4B. B chromosomes were observed in Bromelia plumieri and Hohenbergia aff. u...

  11. Micromechanics of human mitotic chromosomes

    International Nuclear Information System (INIS)

    Eukaryote cells dramatically reorganize their long chromosomal DNAs to facilitate their physical segregation during mitosis. The internal organization of folded mitotic chromosomes remains a basic mystery of cell biology; its understanding would likely shed light on how chromosomes are separated from one another as well as into chromosome structure between cell divisions. We report biophysical experiments on single mitotic chromosomes from human cells, where we combine micromanipulation, nano-Newton-scale force measurement and biochemical treatments to study chromosome connectivity and topology. Results are in accord with previous experiments on amphibian chromosomes and support the 'chromatin network' model of mitotic chromosome structure. Prospects for studies of chromosome-organizing proteins using siRNA expression knockdowns, as well as for differential studies of chromosomes with and without mutations associated with genetic diseases, are also discussed

  12. Vibrio chromosomes share common history

    Directory of Open Access Journals (Sweden)

    Gevers Dirk

    2010-05-01

    Full Text Available Abstract Background While most gamma proteobacteria have a single circular chromosome, Vibrionales have two circular chromosomes. Horizontal gene transfer is common among Vibrios, and in light of this genetic mobility, it is an open question to what extent the two chromosomes themselves share a common history since their formation. Results Single copy genes from each chromosome (142 genes from chromosome I and 42 genes from chromosome II were identified from 19 sequenced Vibrionales genomes and their phylogenetic comparison suggests consistent phylogenies for each chromosome. Additionally, study of the gene organization and phylogeny of the respective origins of replication confirmed the shared history. Conclusions Thus, while elements within the chromosomes may have experienced significant genetic mobility, the backbones share a common history. This allows conclusions based on multilocus sequence analysis (MLSA for one chromosome to be applied equally to both chromosomes.

  13. Molecular and clinical characterization of patients with overlapping 10p deletions.

    Science.gov (United States)

    Lindstrand, Anna; Malmgren, Helena; Verri, Annapia; Benetti, Elisa; Eriksson, Maud; Nordgren, Ann; Anderlid, Britt-Marie; Golovleva, Irina; Schoumans, Jacqueline; Blennow, Elisabeth

    2010-05-01

    Chromosome 10p terminal deletions have been associated with DiGeorge phenotype, and within the same genomic region haploinsufficiency of GATA3 causes the HDR syndrome (hypoparathyroidism, sensorineural deafness, renal dysplasia). We have performed detailed molecular analysis of four patients with partial overlapping 10p deletions by using FISH-mapping, array-CGH, and custom-designed high-resolution oligonucleotide array. All four patients had mental retardation and speech impairment and three of them showed variable signs of HDR syndrome. In addition, two patients had autistic behaviors and had similar dysmorphic features giving them a striking physical resemblance. A review of the literature identified 10 previously published cases with similar 10p deletions and reliable molecular or molecular cytogenetic mapping data. The combined information of present and previous cases suggests that partial deletions of 10p14-p15 represent a syndrome with a distinct and more severe phenotype than previously assumed. The main characteristics include severe mental retardation, language impairment, autistic behavior, and characteristic clinical features. A critical region involved in mental retardation and speech impairment is defined within 1.6 Mb in 10p15.3. In addition, deletion of 4.3 Mb within 10p14 is associated with autism and characteristic clinical findings. PMID:20425828

  14. Size unlimited markerless deletions by a transconjugative plasmid-system in Bacillus licheniformis.

    Science.gov (United States)

    Rachinger, Michael; Bauch, Melanie; Strittmatter, Axel; Bongaerts, Johannes; Evers, Stefan; Maurer, Karl-Heinz; Daniel, Rolf; Liebl, Wolfgang; Liesegang, Heiko; Ehrenreich, Armin

    2013-09-20

    Conjugative shuttle vectors of the pKVM series, based on an IncP transfer origin and the pMAD vector with a temperature sensitive replication were constructed to establish a markerless gene deletion protocol for Bacilli without natural competence such as the exoenzyme producer Bacillus licheniformis. The pKVM plasmids can be conjugated to strains of B. licheniformis and B. subtilis. For chromosomal gene deletion, regions flanking the target gene are fused and cloned in a pKVM vector prior to conjugative transfer from Escherichia coli to B. licheniformis. Appropriate markers on the vector backbone allow for the identification of the integration at the target locus and thereafter the vector excision, both events taking place via homologous recombination. The functionality of the deletion system was demonstrated with B. licheniformis by a markerless 939 bp in-frame deletion of the yqfD gene and the deletion of a 31 kbp genomic segment carrying a PBSX-like prophage. PMID:23916947

  15. Abnormal auditory and language pathways in children with 16p11.2 deletion

    Directory of Open Access Journals (Sweden)

    Jeffrey I. Berman

    2015-01-01

    Full Text Available Copy number variations at chromosome 16p11.2 contribute to neurodevelopmental disorders, including autism spectrum disorder (ASD. This study seeks to improve our understanding of the biological basis of behavioral phenotypes common in ASD, in particular the prominent and prevalent disruption of spoken language seen in children with the 16p11.2 BP4–BP5 deletion. We examined the auditory and language white matter pathways with diffusion MRI in a cohort of 36 pediatric deletion carriers and 45 age-matched controls. Diffusion MR tractography of the auditory radiations and the arcuate fasciculus was performed to generate tract specific measures of white matter microstructure. In both tracts, deletion carriers exhibited significantly higher diffusivity than that of controls. Cross-sectional diffusion parameters in these tracts changed with age with no group difference in the rate of maturation. Within deletion carriers, the left-hemisphere arcuate fasciculus mean and radial diffusivities were significantly negatively correlated with clinical language ability, but not non-verbal cognitive ability. Diffusion metrics in the right-hemisphere arcuate fasciculus were not predictive of language ability. These results provide insight into the link between the 16p11.2 deletion, abnormal auditory and language pathway structures, and the specific behavioral deficits that may contribute to neurodevelopmental disorders such as ASD.

  16. 35-Year Follow-Up of a Case of Ring Chromosome 2

    DEFF Research Database (Denmark)

    Sarri, Catherine; Douzgou, Sofia; Kontos, Haris; Anagnostopoulou, Katherine; Tümer, Zeynep; Grigoriadou, Maria; Petersen, Michael B; Kokotas, Haris; Merou, Konstantina; Pandelia, Efi; Giouroukou, Elena; Papanikolaou, Katerina; Côté, Gilbert B; Gyftodimou, Yolanda

    2015-01-01

    mild to moderate mental retardation. We reconsidered the ring chromosome 2 case previously published by Côté et al. [1981], and we characterized it by array CGH, polymorphic markers as well as subtelomere MLPA and FISH analysis. A terminal deletion (q37.3qter) of maternal origin of the long arm of the...

  17. A Fetus with Hb Bart's Disease Due to Maternal Uniparental Disomy for Chromosome 16.

    Science.gov (United States)

    Au, Patrick K C; Kan, Anita S Y; Tang, Mary H Y; Leung, Kwok Y; Chan, Kelvin Y K; Tang, Tommy W F; Lau, Elizabeth T

    2016-01-01

    We here report an unusual case of Hb Bart's (γ4) disease. Thalassemia screening of a couple showed that the wife was an α(0)-thalassemia (α(0)-thal) carrier and her husband's mean corpuscular volume (MCV) was normal. Chorionic villus sampling (CVS) was performed at 13 weeks' gestation for positive Down syndrome screening and chromosomal study of the cultured CVS showed a normal karyotype. Ultrasound examination at 22 weeks' gestation showed fetal cardiomegaly and raised middle cerebral artery peak systolic velocity. Cordocentesis confirmed fetal anemia and showed Hb Bart's disease. Multiplex gap-polymerase chain reaction (gap-PCR) for α-thal deletions on DNA extracted from the CVS showed the presence of a homozygous α(0)-thal - -(SEA) (Southeast Asian) deletion. The husband was found to be a carrier of the α(+)-thal -α(3.7) (rightward) deletion. Non paternity was excluded by fluorescent PCR using short tandem repeat (STR) markers on chromosomes 13, 18 and 21. A de novo terminal deletion of chromosome 16 was excluded by array comparative genomic hybridization (aCGH). Detection of uniparental disomy (UPD), using STR markers on chromosome 16 showed maternal uniparental isodisomy from 16pter to 16p13.2, and uniparental heterodisomy from 16p13.13 to 16qter. PMID:26574185

  18. Deletion of GOLGA2P3Y but not GOLGA2P2Y is a risk factor for oligozoospermia.

    Science.gov (United States)

    Sen, Sanjukta; Agarwal, Rupesh; Ambulkar, Prafulla; Hinduja, Indira; Zaveri, Kusum; Gokral, Jyotsna; Pal, Asoke; Modi, Deepak

    2016-02-01

    The AZFc locus on the human Y chromosome harbours several multicopy genes, some of which are required for spermatogenesis. It is believed that deletion of one or more copies of these genes is a cause of infertility in some men. GOLGA2LY is one of the genes in the AZFc locus and it exists in two copies, GOLGA2P2Y and GOLGA2P3Y. The involvement of GOLGA2LY gene copy deletions in male infertility, however, is unknown. This study aimed to investigate the association of deletions of GOLGA2P2Y and GOLGA2P3Y gene copies with male infertility and with sperm concentration and motility. The frequency of GOLGA2P3Y deletion was significantly higher in oligozoospermic men compared with normozoospermic men (7.7% versus 1.2%; P = 0.0001), whereas the frequency of GOLGA2P2Y deletion was comparable between oligozoospermic and normozoospermic men (10.3% versus 11.3%). The deletion of GOLGA2P3Y but not GOLGA2P2Y was significantly higher (P = 0.03) in men with gr/gr rearrangements, indicating that GOLGA2P3Y deletions increase the susceptibility of men with gr/gr rearrangements to oligozoospermia. Furthermore, men with GOLGA2P3Y deletion had reduced sperm concentration and motility compared with men without deletion or with deletion of GOLGA2P2Y. These findings indicate GOLGA2P3Y gene copy may be candidate AZFc gene for male infertility. PMID:26655651

  19. Cri-Du-Chat Syndrome: Clinical Profile and Chromosomal Microarray Analysis in Six Patients.

    Science.gov (United States)

    Espirito Santo, Layla Damasceno; Moreira, Lília Maria Azevedo; Riegel, Mariluce

    2016-01-01

    Cri-du-chat syndrome is a chromosomal disorder caused by a deletion of the short arm of chromosome 5. The disease severity, levels of intellectual and developmental delay, and patient prognosis have been related to the size and position of the deletion. Aiming to establish genotype-phenotype correlations, we applied array-CGH to evaluate six patients carrying cytogenetically detected deletions of the short arm of chromosome 5 who were followed at a genetics community service. The patients' cytogenetic and clinical profiles were reevaluated. A database review was performed to predict additional genes and regulatory elements responsible for the characteristic phenotypic and behavioral traits of this disorder. Array-CGH analysis allowed for delineation of the terminal deletions, which ranged in size from approximately 11.2 Mb to 28.6 Mb, with breakpoints from 5p15.2 to 5p13. An additional dup(8)(p23) (3.5 Mb), considered to be a benign copy number variation, was also observed in one patient. The correlation coefficient value (ρ = 0.13) calculated indicated the presence of a weak relationship between developmental delay and deletion size. Genetic background, family history, epigenetic factors, quantitative trait locus polymorphisms, and environmental factors may also affect patient phenotype and must be taken into account in genotype-phenotype correlations. PMID:27144168

  20. 3p22.1p21.31 microdeletion identifies CCK as Asperger syndrome candidate gene and shows the way for therapeutic strategies in chromosome imbalances

    OpenAIRE

    Iourov, Ivan Y; Vorsanova, Svetlana G; Voinova, Victoria Y.; Yurov, Yuri B.

    2015-01-01

    Background In contrast to other autism spectrum disorders, chromosome abnormalities are rare in Asperger syndrome (AS) or high-functioning autism. Consequently, AS was occasionally subjected to classical positional cloning. Here, we report on a case of AS associated with a deletion of the short arm of chromosome 3. Further in silico analysis has identified a candidate gene for AS and has suggested a therapeutic strategy for manifestations of the chromosome rearrangement. Results Using array c...

  1. Characterization of an APC Promoter 1B deletion in a Patient Diagnosed with Familial Adenomatous Polyposis via Whole Genome Shotgun Sequencing [v1; ref status: indexed, http://f1000r.es/5i1

    Directory of Open Access Journals (Sweden)

    Ted Kalbfleisch

    2015-06-01

    Full Text Available Recently, deletions have been identified and published as causal for Familial Adenomatous Polyposis in the 1B promoter region of the APC gene.  Those deletions were measured using multiplex ligation-dependent probe amplification.  Here, we present and characterize an ~11kb deletion identified by whole genome shotgun sequencing.  The deletion occurred in a patient diagnosed with Familial Adenomatous Polyposis, and was located on chr5, between bases 112,034,824 and 112,045,845, fully encompassing the 1B promoter region of the APC gene.   Results are presented here that include the sequence evidence supporting the presence of the deletion as well as base level characterization of the deletion site.  These results demonstrate the capacity of whole genome sequencing for the detection of large structural variants in single individuals.

  2. 78 FR 56679 - Procurement List; Deletions

    Science.gov (United States)

    2013-09-13

    ... 8/2/2013 (78 FR 46927-46928), the Committee for Purchase From People Who Are Blind or Severely... PEOPLE WHO ARE BLIND OR SEVERELY DISABLED Procurement List; Deletions AGENCY: Committee for Purchase From People Who Are Blind or Severely Disabled. ACTION: Deletions from the Procurement List. SUMMARY:...

  3. 13Q DELETIONS IN LYMPHOID MALIGNANCIES

    NARCIS (Netherlands)

    HERMANSON, M; GRANDER, D; MERUP, M; WU, XS; HEYMAN, M; RASOOL, O; JULIUSSON, G; GAHRTON, G; DETLOFSSON, R; NIKIFOROVA, N; BUYS, C; SODERHALL, S; YANKOVSKY, N; ZABAROVSKY, E; EINHORN, S

    1995-01-01

    Previous studies have indicated that a candidate tumor suppressor gene resides telomeric of the RB1 gene at 13q14, a region that is commonly deleted in B-cell chronic lymphocytic leukemia (B-CLL). In this study, we have evaluated the frequency and minimal region of overlap for 13q deletions in malig

  4. A sex chromosomal restriction-fragment-length marker linked to melanoma-determining Tu loci in Xiphophorus.

    Science.gov (United States)

    Schartl, M

    1988-07-01

    In Xiphophorus, the causative genetic information for melanoma formation has been assigned by classical genetics to chromosomal loci, which are located on the sex chromosomes. In our attempts to molecularly clone these melanoma-determining loci, named Tu, we have looked for restriction-fragment-length markers (RFLMs) linked to the Tu loci. These RFLMs should be useful in obtaining a physical map of a Tu locus, which will aid in the cloning of the corresponding sequences. DNA samples from various Xiphophorus strains and hybrids including those bearing different Tu wild-type, deletion and translocation chromosomes, were screened for the presence of random RFLMs using homologous or heterologous sequences as hybridization probes. We find an EcoRI restriction fragment which shows limited crosshybridization to the v-erb B gene--but not representing the authentic c-erb B gene of Xiphophorus--to be polymorphic with respect to different sex chromosomes. Linkage analysis revealed that a 5-kb fragment is linked to the Tu-Sd locus on the X chromosome, a 7-kb fragment is linked to the Tu-Sr locus on the Y chromosome, both of Xiphophorus maculatus, and that a 12-kb fragment is linked to the Tu-Li locus on the X chromosome of Xiphophorus variatus. Using different chromosomal mutants this RFLM has been mapped to a frequent deletion/translocation breakpoint of the X chromosome, less than 0.3 cM apart from the Tu locus. PMID:2841190

  5. Type I oculocutaneous albinism (OCA1) associated with a large deletion of the tyrosinase (TYR) gene

    Energy Technology Data Exchange (ETDEWEB)

    Spritz, R.A.; Wick, P.A.; Holmes, S.A.; Schnur, R.E. [Univ. of Wisconsin, Madison, WI (United States)]|[Children`s Hospital of Philadelphia, PA (United States)

    1994-09-01

    OCA1 is an autosomal recessive disorder in which the biosynthesis of melanin is reduced or absent in skin, hair, and eyes, due to deficient enzymatic activity of tyrosinase. TYR consists of 5 exons spanning over 65 kb at 11q14-q21. Analyses of TYR in >400 unrelated patients with OCA1 have identified more than 50 different point mutations; however, no large deletions have been detected. Here we report a large deletion of TYR in a Caucasian boy with OCA1B. Simultaneous SSCP/heteroduplex screening and DNA sequence analysis indicated that the patient was apparently homozygous for a previously described TYR mutation, adjacent to the 3` splice site of IVS2 (-7, t{r_arrow}a). To distinguish between possible gene deletion vs. maternal uniparental isodisomy, we characterized several chromosome 11 polymorphisms. Maternal uniparental isodisomy was excluded by the patient`s heterozygosity for alleles at D11S35 (11q21-122) and HBG2 (11p15.5). In addition, the patient failed to inherit paternal alleles at an MboI RFLP in exon 1 of TYR and at a TaqI RFLP in the promoter region of the gene. To detect a possible submicroscopic deletion, we performed quantitative Southern blot hybridization using a full length TYR cDNA. Compared with controls, both the patient and his father appeared deleted for two or three TYR-derived PstI fragments; the two TYRL-derived fragments appeared normal. These data indicate that the patient and his father have a partial TYR deletion, including at least exons 1, 2, and IVS2. Based on the organization of the gene, this deletion is at least 50 kb in size. The patient is thus hemizygous for the maternally-inherited mutation in IVS2, accounting for his OCA1B phenotype.

  6. Clinical comparison of 10q26 overlapping deletions: delineating the critical region for urogenital anomalies.

    Science.gov (United States)

    Vera-Carbonell, Ascensión; López-González, Vanesa; Bafalliu, Juan Antonio; Ballesta-Martínez, María J; Fernández, Asunción; Guillén-Navarro, Encarna; López-Expósito, Isabel

    2015-04-01

    The 10q26 deletion syndrome is a clinically heterogeneous disorder. The most common phenotypic characteristics include pre- and/or postnatal growth retardation, microcephaly, developmental delay/intellectual disability and a facial appearance consisting of a broad nasal bridge with a prominent nose, low-set malformed ears, strabismus, and a thin vermilion of the upper lip. In addition, limb and cardiac anomalies as well as urogenital anomalies are occasionally observed. In this report, we describe three unrelated females with 10q26 terminal deletions who shared clinical features of the syndrome, including urogenital defects. Cytogenetic studies showed an apparently de novo isolated deletion of the long arm of chromosome 10, with breakpoints in 10q26.1, and subsequent oligo array-CGH analysis confirmed the terminal location and defined the size of the overlapping deletions as ∼ 13.46, ∼ 9.31 and ∼ 9.17 Mb. We compared the phenotypic characteristics of the present patients with others reported to have isolated deletions and we suggest that small 10q26.2 terminal deletions may be associated with growth retardation, developmental delay/intellectual disability, craniofacial features and external genital anomalies whereas longer terminal deletions affecting the 10q26.12 and/or 10q26.13 regions may be responsible for renal/urinary tract anomalies. We propose that the haploinsufficiency of one or several genes located in the 10q26.12-q26.13 region may contribute to the renal or urinary tract pathogenesis and we highlight the importance of FGFR2 and probably of CTBP2 as candidate genes. PMID:25655674

  7. The prevalence of azoospermia factor microdeletion on the Y chromosome of Chinese infertile men detected by multi-analyte suspension array technology

    Institute of Scientific and Technical Information of China (English)

    Yi-Jian Zhu; Si-Yao Liu; Huan Wang; Ping Wei; Xian-Ping Ding

    2008-01-01

    Aim: To develop a high-throughput multiplex, fast and simple assay to scan azoospermia factor (AZF) region microdeletions on the Y chromosome and establish the prevalence of Y chromosomal microdeletions in Chinese infertile males with azoospermia or oligozoospermia. Methods: In total, 178 infertile patients with azoospemua (non-obstructed), 134 infertile patients with oligozoospermia as well as 40 fertile man controls were included in the present study. The samples were screened for AZF microdeletion using optimized multi-analyte suspension array (MASA) technology. Results: Of the 312 patients, 36 (11.5%) were found to have deletions in the AZF region. The microdeletion frequency was 14% (25/178) in the azoospermia group and 8.2% (11/134) in the oligospennia group. Among 36 patients with microdeletions, 19 had deletions in the AZFc region, seven had deletions in AZFa and six had deletions in AZFb. In addition, four patients had both AZFb and AZFc deletions. No deletion in the AZF region was found in the 40 fertile controls. Conclusion: There is a high prevalence of Y chromosomal microdeletions in Chinese infertile males with azoospermia or oligozoospermia. The MASA technology, which has been established in the present study,provides a sensitive and high-throughput method for detecting the deletion of the Y chromosome. And the results suggest that genetic screening should be advised to infertile men before starting assisted reproductive treatments.

  8. Fluorescence in situ hybridization (FISH screening for the 22q11.2 deletion in patients with clinical features of velocardiofacial syndrome but without cardiac anomalies

    Directory of Open Access Journals (Sweden)

    Paula Sandrin-Garcia

    2007-01-01

    Full Text Available The velocardiofacial syndrome (VCFS, a condition associated with 22q11.2 deletions, is characterized by a typical facies, palatal anomalies, learning disabilities, behavioral disturbances and cardiac defects. We investigated the frequency of these chromosomal deletions in 16 individuals with VCFS features who presented no cardiac anomalies, one of the main characteristics of VCFS. Fluorescent in situ hybridization (FISH with the N25 (D22S75; 22q11.2 probe revealed deletions in ten individuals (62%. Therefore, even in the absence of cardiac anomalies testing for the 22q11.2 microdeletions in individuals showing other clinical features of this syndrome is recommended.

  9. A Physical Map, Including a BAC/PAC Clone Contig, of the Williams-Beuren Syndrome–Deletion Region at 7q11.23

    OpenAIRE

    Peoples, Risa; Franke, Yvonne; Wang, Yu-Ker; Pérez-Jurado, Luis; Paperna, Tamar; Cisco, Michael; Francke, Uta

    2000-01-01

    Williams-Beuren syndrome (WBS) is a developmental disorder caused by haploinsufficiency for genes in a 2-cM region of chromosome band 7q11.23. With the exception of vascular stenoses due to deletion of the elastin gene, the various features of WBS have not yet been attributed to specific genes. Although ⩾16 genes have been identified within the WBS deletion, completion of a physical map of the region has been difficult because of the large duplicated regions flanking the deletion. We present ...

  10. Human Cone Visual Pigment Deletions Spare Sufficient Photoreceptors to Warrant Gene Therapy

    OpenAIRE

    Cideciyan, Artur V.; Hufnagel, Robert B.; Carroll, Joseph; Sumaroka, Alexander; Luo, Xunda; Schwartz, Sharon B.; Dubra, Alfredo; Land, Megan; Michaelides, Michel; Gardner, Jessica C.; Hardcastle, Alison J.; Moore, Anthony T.; Sisk, Robert A; Ahmed, Zubair M.; Kohl, Susanne

    2013-01-01

    Human X-linked blue-cone monochromacy (BCM), a disabling congenital visual disorder of cone photoreceptors, is a candidate disease for gene augmentation therapy. BCM is caused by either mutations in the red (OPN1LW) and green (OPN1MW) cone photoreceptor opsin gene array or large deletions encompassing portions of the gene array and upstream regulatory sequences that would predict a lack of red or green opsin expression. The fate of opsin-deficient cone cells is unknown. We know that rod opsin...

  11. Sex chromosomes and karyotype of the (nearly) mythical creature, the Gila monster, Heloderma suspectum (Squamata: Helodermatidae).

    Science.gov (United States)

    Johnson Pokorná, Martina; Rovatsos, Michail; Kratochvíl, Lukáš

    2014-01-01

    A wide variety of sex determination systems exist among squamate reptiles. They can therefore serve as an important model for studies of evolutionary transitions among particular sex determination systems. However, we still have only a limited knowledge of sex determination in certain important lineages of squamates. In this respect, one of the most understudied groups is the family Helodermatidae (Anguimorpha) encompassing the only two venomous species of lizards which are potentially lethal to human beings. We uncovered homomorphic ZZ/ZW sex chromosomes in the Gila monster (Heloderma suspectum) with a highly heterochromatic W chromosome. The sex chromosomes are morphologically similar to the ZZ/ZW sex chromosomes of monitor lizards (Varanidae). If the sex chromosomes of helodermatids and varanids are homologous, female heterogamety may be ancestral for the whole Anguimorpha group. Moreover, we found that the karyotype of the Gila monster consists of 2n = 36 chromosomes (14 larger metacentric chromosomes and 22 acrocentric microchromosomes). 2n = 36 is the widely distributed chromosomal number among squamates. In his pioneering works representing the only previous cytogenetic examination of the family Helodermatidae, Matthey reported the karyotype as 2n = 38 and suggested a different chromosomal morphology for this species. We believe that this was probably erroneously. We also discovered a strong accumulation of telomeric sequences on several pairs of microchromosomes in the Gila monster, which is a trait documented relatively rarely in vertebrates. These new data fill an important gap in our understanding of the sex determination and karyotype evolution of squamates. PMID:25119263

  12. Sex chromosomes and karyotype of the (nearly mythical creature, the Gila monster, Heloderma suspectum (Squamata: Helodermatidae.

    Directory of Open Access Journals (Sweden)

    Martina Johnson Pokorná

    Full Text Available A wide variety of sex determination systems exist among squamate reptiles. They can therefore serve as an important model for studies of evolutionary transitions among particular sex determination systems. However, we still have only a limited knowledge of sex determination in certain important lineages of squamates. In this respect, one of the most understudied groups is the family Helodermatidae (Anguimorpha encompassing the only two venomous species of lizards which are potentially lethal to human beings. We uncovered homomorphic ZZ/ZW sex chromosomes in the Gila monster (Heloderma suspectum with a highly heterochromatic W chromosome. The sex chromosomes are morphologically similar to the ZZ/ZW sex chromosomes of monitor lizards (Varanidae. If the sex chromosomes of helodermatids and varanids are homologous, female heterogamety may be ancestral for the whole Anguimorpha group. Moreover, we found that the karyotype of the Gila monster consists of 2n = 36 chromosomes (14 larger metacentric chromosomes and 22 acrocentric microchromosomes. 2n = 36 is the widely distributed chromosomal number among squamates. In his pioneering works representing the only previous cytogenetic examination of the family Helodermatidae, Matthey reported the karyotype as 2n = 38 and suggested a different chromosomal morphology for this species. We believe that this was probably erroneously. We also discovered a strong accumulation of telomeric sequences on several pairs of microchromosomes in the Gila monster, which is a trait documented relatively rarely in vertebrates. These new data fill an important gap in our understanding of the sex determination and karyotype evolution of squamates.

  13. Dbl2 Regulates Rad51 and DNA Joint Molecule Metabolism to Ensure Proper Meiotic Chromosome Segregation.

    Science.gov (United States)

    Polakova, Silvia; Molnarova, Lucia; Hyppa, Randy W; Benko, Zsigmond; Misova, Ivana; Schleiffer, Alexander; Smith, Gerald R; Gregan, Juraj

    2016-06-01

    To identify new proteins required for faithful meiotic chromosome segregation, we screened a Schizosaccharomyces pombe deletion mutant library and found that deletion of the dbl2 gene led to missegregation of chromosomes during meiosis. Analyses of both live and fixed cells showed that dbl2Δ mutant cells frequently failed to segregate homologous chromosomes to opposite poles during meiosis I. Removing Rec12 (Spo11 homolog) to eliminate meiotic DNA double-strand breaks (DSBs) suppressed the segregation defect in dbl2Δ cells, indicating that Dbl2 acts after the initiation of meiotic recombination. Analyses of DSBs and Holliday junctions revealed no significant defect in their formation or processing in dbl2Δ mutant cells, although some Rec12-dependent DNA joint molecules persisted late in meiosis. Failure to segregate chromosomes in the absence of Dbl2 correlated with persistent Rad51 foci, and deletion of rad51 or genes encoding Rad51 mediators also suppressed the segregation defect of dbl2Δ. Formation of foci of Fbh1, an F-box helicase that efficiently dismantles Rad51-DNA filaments, was impaired in dbl2Δ cells. Our results suggest that Dbl2 is a novel regulator of Fbh1 and thereby Rad51-dependent DSB repair required for proper meiotic chromosome segregation and viable sex cell formation. The wide conservation of these proteins suggests that our results apply to many species. PMID:27304859

  14. De novo 13q13.3-21.31 deletion involving RB1 gene in a patient with hemangioendothelioma of the liver.

    Science.gov (United States)

    Rapini, Novella; Lidano, Roberta; Pietrosanti, Silvia; Vitiello, Giuseppina; Grimaldi, Chiara; Postorivo, Diana; Nardone, Anna Maria; Del Bufalo, Francesca; Brancati, Francesco; Manca Bitti, Maria Luisa

    2014-01-01

    Interstitial deletions of the long arm of chromosome 13 (13q) are related with variable phenotypes, according to the size and the location of the deleted region. The main clinical features are moderate/severe mental and growth retardation, cranio-facial dysmorphism, variable congenital defects and increased susceptibility to tumors. Here we report a 3-year-old girl carrying a de novo 13q13.3-21.32 interstitial deletion. She showed developmental delay, growth retardation and mild dysmorphism including curly hair, high forehead, short nose, thin upper lip and long philtrum. An abnormal mass was surgically removed from her liver resulting in a hemangioendothelioma. Array analysis allowed us to define a deleted region of about 27.87 Mb, which includes the RB1 gene. This is the first report of a 13q deletion associated with infantile hemangioendothelioma of the liver. PMID:24433316

  15. Y-chromosome STR haplotypes in Danes

    DEFF Research Database (Denmark)

    Hallenberg, Charlotte; Nielsen, Karsten; Simonsen, Bo Thisted;

    2005-01-01

    A total of 185 unrelated Danish males were typed for the Y-chromosome STRs DYS19, DYS385a/b, DYS389-I, DYS389-II, DYS390, DYS391, DYS392, DYS393, DYS437, DYS438 and DYS439 using the kits PowerPlex Y (Promega), ReliaGene Y-Plex 6 and ReliaGene Y-Plex 5 (Reliagene Technologies). A total of 163...... different haplotypes were observed and among these, 144 haplotypes were unique. The gene diversity was 0.9985. In DYS392, a variant allele migrating as a 10.2 allele was observed. Sequencing of the allele showed a deletion upstream the repeated area....

  16. SNP array and phenotype correlation shows that FLI1 deletion per se is not responsible for thrombocytopenia development in Jacobsen syndrome.

    Science.gov (United States)

    Trkova, Marie; Becvarova, Vera; Hynek, Martin; Hnykova, Lenka; Hlavova, Eva; Kreckova, Gabriela; Kulovany, Eduard; Cutka, David; Zatloukalova, Jitka; Markova, Kristyna; Sukova, Martina; Horacek, Jiri; Stejskal, David

    2012-10-01

    Jacobsen syndrome (JBS) is a rare chromosomal disorder caused by terminal deletion of the long arm of chromosome 11. We report on four prenatally diagnosed patients with JBS with variable prenatal and postnatal phenotypes and 11q deletions of varying sizes. Precise characterization of the deleted region in three patients was performed by SNP arrays. The severity of both the prenatal and postnatal phenotypes did not correlate with the size of the haploinsufficient region. Despite the large difference in the deletion size (nearly 6 Mb), both of the live-born patients had similar phenotypes corresponding to JBS. However, one of the most prominent features of JBS, thrombocytopenia, was only present in the live-born boy. The girl, who had a significantly longer deletion spanning all four genes suspected of being causative of JBS-related thrombocytopenia (FLI1, ETS1, NFRKB, and JAM3), did not manifest a platelet phenotype. Therefore, our findings do not support the traditional view of deletion size correlation in JBS or the causative role of FLI1, ETS1, NFRKB, and JAM3 deletion per se for the development of disease-related thrombocytopenia. PMID:22887642

  17. 22q11 deletion syndrome: a review of the neuropsychiatric features and their neurobiological basis

    Directory of Open Access Journals (Sweden)

    Squarcione C

    2013-12-01

    Full Text Available Chiara Squarcione, Maria Chiara Torti, Fabio Di Fabio, Massimo Biondi Department of Neurology and Psychiatry, Sapienza University of Rome, Rome, Italy Abstract: The 22q11.2 deletion syndrome (22q11DS is caused by an autosomal dominant microdeletion of chromosome 22 at the long arm (q 11.2 band. The 22q11DS is among the most clinically variable syndromes, with more than 180 features related with the deletion, and is associated with an increased risk of psychiatric disorders, accounting for up to 1%–2% of schizophrenia cases. In recent years, several genes located on chromosome 22q11 have been linked to schizophrenia, including those encoding catechol-O-methyltransferase and proline dehydrogenase, and the interaction between these and other candidate genes in the deleted region is an important area of research. It has been suggested that haploinsufficiency of some genes within the 22q11.2 region may contribute to the characteristic psychiatric phenotype and cognitive functioning of schizophrenia. Moreover, an extensive literature on neuroimaging shows reductions of the volumes of both gray and white matter, and these findings suggest that this reduction may be predictive of increased risk of prodromal psychotic symptoms in 22q11DS patients. Experimental and standardized cognitive assessments alongside neuroimaging may be important to identify one or more endophenotypes of schizophrenia, as well as a predictive prodrome that can be preventively treated during childhood and adolescence. In this review, we summarize recent data about the 22q11DS, in particular those addressing the neuropsychiatric and cognitive phenotypes associated with the deletion, underlining the recent advances in the studies about the genetic architecture of the syndrome. Keywords: 22q11 deletion syndrome, microdeletion, neuropsychiatric disorders, cognitive impairments

  18. Chromosome Studies in Patients with Polycythaemia Vera after Treatment with 32P

    International Nuclear Information System (INIS)

    The chromosomes of bone-marrow cells and blood lymphocytes of forty-six patients with polycythaemia vera were analysed to trace the sequence of events leading to the development of bone-marrow failure or 'leukaemia'. All except one of the patients had received radiophosphorus (32P). It might be expected that the yield of chromosomal aberrations of the two-break type (translocations etc.) from the low dose-rate beta radiation of 32P would be small. However, 'unstable' types of abnormality (dicentrics, fragments) and stable types (translocations, inversions, deletions) were observed in 6-25% of the blood lymphocytes; there was no evidence of clones of abnormal cells. In the majority of patients the bone marrow was predominantly normal diploid; occasional sporadic cells with 'stable' chromosomal abnormalities were seen in two-thirds of the cases, but 'unstable' aberrations were rare. In seven cases there were clones of cells characterised by deletions or translocations. All these chromosomal changes are probably radiation-induced. Clones of cells with a similar abnormality, an apparent deletion of one of the F-group chromosomes, were observed in the bone marrow in ten patients. Eight of these had received 32P and two busulphan. In two cases the clone appeared to develop after treatment. A similar anomaly has been reported in several cases of idiopathic sideroblastic anaemia who had not been irradiated. Progression into the leukaemic phase of the disease is associated in some cases with gross chromosomal abnormalities, such as shift of the stem line chromosome number and bizarre chromosome 'markers'. In other cases, some of whom have not been irradiated for several years, the chromosomal changes are less pronounced and may result from non-disjunctional gain of one or more chromosomes or chromosome loss. One case showed a step-by-step clonal evolution over a two-year period. None of the chromosomal abnormalities in the 'leukaemic' phase appear to be a direct result of

  19. Paternal uniparental isodisomy for human chromosome 20 and absence of external ears

    Energy Technology Data Exchange (ETDEWEB)

    Spinner, N.B.; Rand, E.; McDonald-McGinn, D.M. [Childrens Hospital of Philadelphia, PA (United States)] [and others

    1994-09-01

    Uniparental disomy can cause disease if the involved chromosomal region contains imprinted genes. Uniparental disomy for portions of human chromosomes 6, 7, 9, 11, 14 and 15 have been associated with abnormal phenotypes. We studied a patient with multiple abnormalities including an absent left ear with a small right ear remnant, microcephaly, congenital heart disease and Hirschprung`s disease. Cytogenetics revealed a 45,XY,-20,-20,+ter rea(20;20)(p13;p13) in 10/10 cells from bone marrow and 20/20 cells from peripheral blood. Analysis of a skin culture revealed a second cell line with trisomy 20 resulting from an apparently normal chromosome 20 in addition to the terminally rearranged chromosome, in 8/100 cells studied. The unusual phenotype of our patient was not consistent with previously reported cases of deletions of 20p or mosaic trisomy 20. We hypothesized that the patient`s phenotype could either result from deletion of both copies of a gene near the p arm terminus of chromosome 20 or from uniparental disomy of chromosome 20. There were no alterations or rearrangements of PTP-alpha (which maps to distal 20p) by Southern or Northern blot analysis. A chromosome 20 sub-telomeric probe was found to be present on the rearranged 20 by FISH suggesting that subtelomeric sequences have not been lost as a consequece of this rearrangement. To determine the parental origin of the 2 chromosome 20`s in the terminal rearrangement, we studied the genotypes of the proband and his parents in lymphoblastoid cell lines at 8 polymorphic loci. Genotypes at D20S115, D20S186, and D20S119 indicated that there was paternal isodisomy. Other loci were uninformative. This is the first example of uniparental disomy for chromosome 20. Further studies are warranted to correlate phenotype with uniparental inheritance of this chromosome.

  20. Chromosome-specific staining to detect genetic rearrangements associated with chromosome 3 and/or chromosome 17

    Energy Technology Data Exchange (ETDEWEB)

    Gray, Joe W.; Pinkel, Daniel; Kallioniemi, Olli-Pekka; Kallioniemi, Anne; Sakamoto, Masaru

    2009-10-06

    Methods and compositions for staining based upon nucleic acid sequence that employ delete-start id="DEL-S-00001" date="20091006" ?>nudeicdelete-end id="DEL-S-00001" ?> nucleic acid probes are provided. Said methods produce staining patterns that can be tailored for specific cytogenetic analyses. Said probes are appropriate for in situ hybridization and stain both interphase and metaphase chromosomal material with reliable signals. The nucleic acid probes are typically of a complexity greater than 50 kb, the complexity depending upon the cytogenetic application. Methods and reagents are provided for the detection of genetic rearrangements. Probes and test kits are provided for use in detecting genetic rearrangements, particularly for use in tumor cytogenetics, in the detection of disease related loci, specifically cancer, such as chronic myelogenous leukemia (CML), retinoblastoma, ovarian and uterine cancers, and for biological dosimetry. Methods and reagents are described for cytogenetic research, for the differentiation of cytogenetically similar but genetically different diseases, and for many prognostic and diagnostic applications.

  1. ParMap, an algorithm for the identification of small genomic insertions and deletions in nextgen sequencing data

    Directory of Open Access Journals (Sweden)

    Palomero Teresa

    2010-05-01

    Full Text Available Abstract Background Next-generation sequencing produces high-throughput data, albeit with greater error and shorter reads than traditional Sanger sequencing methods. This complicates the detection of genomic variations, especially, small insertions and deletions. Findings Here we describe ParMap, a statistical algorithm for the identification of complex genetic variants, such as small insertion and deletions, using partially mapped reads in nextgen sequencing data. Conclusions We report ParMap's successful application to the mutation analysis of chromosome X exome-captured leukemia DNA samples.

  2. Deletion of 8q24 in an Adult with Mild Dysmorphic Features, Developmental Delay, and Ketotic Hypoglycemia

    OpenAIRE

    Solomon, Benjamin D.; Lange, Eileen; Shubrook, Jay; Service, F John; Herman, Gail; Karne, Rajaram J.; Gorden, Phillip; Muenke, Maximilian; Stratakis, Constantine A.

    2010-01-01

    We present a 56-year-old female with a history of carbohydrate intolerance and ketotic hypoglycemia, dysmorphic features, mild developmental delay, lymphedema, altered pain sensation, and frequent fractures, who was found to have a heterozygous 8.09 Mb deletion of chromosome 8q24.11q24.13 containing more than 39 genes, as well as a duplication of 20q11.23 containing one gene. The deleted region overlaps that of two previously reported patients, who share a subset of clinical characteristics w...

  3. Chromosome numbers in Bromeliaceae

    Directory of Open Access Journals (Sweden)

    Cotias-de-Oliveira Ana Lúcia Pires

    2000-01-01

    Full Text Available The present study reports chromosome numbers of 17 species of Bromeliaceae, belonging to the genera Encholirium, Bromelia, Orthophytum, Hohenbergia, Billbergia, Neoglaziovia, Aechmea, Cryptanthus and Ananas. Most species present 2n = 50, however, Bromelia laciniosa, Orthophytum burle-marxii and O. maracasense are polyploids with 2n = 150, 2n = 100 and 2n = 150, respectively, while for Cryptanthus bahianus, 2n = 34 + 1-4B. B chromosomes were observed in Bromelia plumieri and Hohenbergia aff. utriculosa. The chromosome number of all species was determined for the first time, except for Billbergia chlorosticta and Cryptanthus bahianus. Our data supports the hypothesis of a basic number of x = 25 for the Bromeliaceae family and decreasing aneuploidy in the genus Cryptanthus.

  4. Those amazing dinoflagellate chromosomes

    Institute of Scientific and Technical Information of China (English)

    PETER J RIZZO

    2003-01-01

    Dinoflagellates are a very large and diverse group of eukaryotic algae that play a major role in aquatic food webs of both fresh water and marine habitats. Moreover, the toxic members of this group pose a health threat in the form of red tides. Finally, dinoflagellates are of great evolutionary importance,because of their taxonomic position, and their unusual chromosome structure and composition. While the cytoplasm of dinoflagellates is typically eukaryotic, the nucleus is unique when compared to the nucleus of other eukaryotes. More specifically, while the chromosomes of all other eukaryotes contain histones,dinoflagellate chromosomes lack histones completely. There are no known exceptions to this observation: all dinoflagellates lack histones, and all other eukaryotes contain histones. Nevertheless, dinoflagellates remain a relatively unstudied group of eukaryotes.

  5. Rapid molecular cytogenetic analysis of X-chromosomal microdeletions: Fluorescence in situ hybridization (FISH) for complex glycerol kinase deficiency

    Energy Technology Data Exchange (ETDEWEB)

    Worley, K.C.; Lindsay, E.A.; McCabe, E.R.B. [Baylor College of Medicine, Houston, TX (United States)] [and others

    1995-07-17

    Diagnosis of X-chromosomal microdeletions has relied upon the traditional methods of Southern blotting and DNA amplification, with carrier identification requiring time-consuming and unreliable dosage calculations. In this report, we describe rapid molecular cytogenetic identification of deleted DNA in affected males with the Xp21 contiguous gene syndrome (complex glycerol kinase deficiency, CGKD) and female carriers for this disorder. CGKD deletions involve the genes for glycerol kinase, Duchenne muscular dystrophy, and/or adrenal hypoplasia congenita. We report an improved method for diagnosis of deletions in individuals with CGKD and for identification of female carriers within their families using fluorescence in situ hybridization (FISH) with a cosmid marker (cosmid 35) within the glycerol kinase gene. When used in combination with an Xq control probe, affected males demonstrate a single signal from the control probe, while female carriers demonstrate a normal chromosome with two signals, as well as a deleted chromosome with a single signal from the control probe. FISH analysis for CGKD provides the advantages of speed and accuracy for evaluation of submicroscopic X-chromosome deletions, particularly in identification of female carriers. In addition to improving carrier evaluation, FISH will make prenatal diagnosis of CGKD more readily available. 17 refs., 2 figs.

  6. Chromosomal aberrations as etiological factors of intrauterine growth retardation

    Directory of Open Access Journals (Sweden)

    Petrović Bojana

    2008-01-01

    Full Text Available Background/Aim. Intrauterine growth retardation (IUGR is a pathological condition of pregnancy characterised by birth weight below the 10th centile. A number of fetal, placental and maternal causes can lead to IUGR; although, in most cases no specific causes can be identified. The aim of this study was to determine the part of chromosomal abnormalities in IUGR etiology. Methods. Fetal blood karyotype taken by cordocentesis from 168 fetuses with diagnosed IUGR was analyzed. Results. Chromosomal rearrangements both numerical and structural were detected in 14 cases (12.2%. Two cases were triploid. Patau syndrome, Edwards syndrome and Down syndrome were found in two cases each. There was one case of trisomy 7 (47, XY, +7 and one case of trisomy 16 (47, XX, +16; one translocation, 46, XY, t (2; 14(q23; q32 and a deletion 46, XYdel (12 (p12 as well as two cases of sex chromosomes abnormalities, 45, X (Turner syndrome and 47, XYY. Conclusion. These findings suggest that a consistent number of symmetrical IUGR cases (about 12% can be associated with chromosomal rearrangements. Chromosomal aberrations that cause IUGR are heterogeneous, aberration of autosomes, mostly autosomal trisomies, being the most common.

  7. Radiation-induced chromosomal instability in human mammary epithelial cells

    Science.gov (United States)

    Durante, M.; Grossi, G. F.; Yang, T. C.

    1996-01-01

    Karyotypes of human cells surviving X- and alpha-irradiation have been studied. Human mammary epithelial cells of the immortal, non-tumorigenic cell line H184B5 F5-1 M/10 were irradiated and surviving clones isolated and expanded in culture. Cytogenetic analysis was performed using dedicated software with an image analyzer. We have found that both high- and low-LET radiation induced chromosomal instability in long-term cultures, but with different characteristics. Complex chromosomal rearrangements were observed after X-rays, while chromosome loss predominated after alpha-particles. Deletions were observed in both cases. In clones derived from cells exposed to alpha-particles, some cells showed extensive chromosome breaking and double minutes. Genomic instability was correlated to delayed reproductive death and neoplastic transformation. These results indicate that chromosomal instability is a radiation-quality-dependent effect which could determine late genetic effects, and should therefore be carefully considered in the evaluation of risk for space missions.

  8. The Role of the CRL4Cdt2 Target Spd1 in Chromosome Segregation in Fission Yeast

    DEFF Research Database (Denmark)

    Landvad, Katrine

    Ddb1, a component of the E3 ubiquitin ligase CRL4Cdt2, is needed for proper chromosome segregation in fission yeast as ddb1 deleted cells show unequal distribution of DNA to daughter cells and sensitivity to the microtubule destabilising drug TBZ. In this study we show that Δddb1 cells have....... Concomitant deletion of spd1, a known target of CRL4Cdt2, substantially reduces the observed defects of the ddb1 single mutant, indicating that degradation of Spd1 is important to ensure proper chromosome segregation. Spd1 is degraded on proliferating cell nuclear antigen (PCNA) and we propose that...

  9. Y chromosome microdeletion in a case with Klinefelter's Syndrome.

    Science.gov (United States)

    Samli, H; Samli, M M; Azgoz, A; Solak, M

    2006-01-01

    In male infertility, the frequency of genetic factors is high. Klinefelter's Syndrome is the most frequent sex chromosomal abnormality detected in male infertility. In this study we report a patient diagnosed with Klinefelter's Syndrome with a deletion of the Yq interval. The patient was 24-years old with primary infertility. Semen analyses carried out in triplicate indicated azoospermia. The plasma leutenizing hormone (LH) and follicle stimulating hormone (FSH) levels were abnormally high and the testosterone level was lower than the usual range. Each of his testes had a volume of 3 cc. Peripheral blood karyotype analysis showed Klinefelter's Syndrome (47, XXY) pattern. Polymerase chain reaction amplification of DNA was performed using the following primers; AZFa (sY81, sY82, sY84), AZFb (sY127, sY142, sY164, RBM1), AZFc (CDY, BPY, sY254, sY255, sY277), AZFd (sY152, sY145, sY153). Analysis revealed a single deletion of AZFa region (sY84). Deletion of the AZFa region may be an additional factor for absolute azoospermia in men with Klinefelter's Syndrome. For individuals with Klinefelter's Syndrome who plan to undergo assisted reproduction techniques, Y chromosome microdeletion screening can diagnostically be convenient. PMID:17028090

  10. Analysis of 22q11.2 deletions by FISH in a series of velocardiofacial syndrome patients

    Energy Technology Data Exchange (ETDEWEB)

    Ravnan, J.B.; Golabi, M.; Lebo, R.V. [Univ. of California, San Francisco, CA (United States)

    1994-09-01

    Deletions in chromosome 22 band q11.2 have been associated with velocardiofacial (VCF or Shprintzen) syndrome and the DiGeorge anomaly. A study of VCF patients evaluated at the UCSF Medical Center was undertaken to correlate disease phenotype with presence or absence of a deletion. Patients referred for this study had at least two of the following: dysmorphic facial features, frequent ear infections or hearing loss, palate abnormalities, thymic hypoplasia, hypocalcemia, congenital heart defect, hypotonia, and growth or language delay. Fluorescence in situ hybridization (FISH) using the DiGeorge critical region probe N25 was used to classify patients according to the presence or absence of a deletion in 22q11.2, and the results were compared to clinical characteristics. We have completed studies on 58 patients with features of VCF. Twenty-one patients (36%) were found to have a deletion in 22q11.2 by FISH. A retrospective study of archived slides from 14 patients originally studied only by prometaphase GTG banding found six patients had a deletion detected by FISH; of these, only two had a microscopically visible chromosome deletion. Our study of 11 sets of parents of children with the deletion found two clinically affected mothers with the deletion, including one with three of three children clinically affected. A few patients who did not fit the classical VCF description had a 22q11.2 deletion detected by FISH. These included one patient with both cleft lip and palate, and another with developmental delay and typical facial features but no cardiac or palate abnormalities. Both patients with the DiGeorge anomaly as part of VCF had the deletion. On the other hand, a number of patients diagnosed clinically with classical VCF did not have a detectable deletion. This raises the question whether they represent a subset of patients with a defect of 22q11.2 not detected by the N25 probe, or whether they represent a phenocopy of VCF.

  11. Chromosomal rearrangements in cattle and pigs revealed by chromosome microdissection and chromosome painting

    Directory of Open Access Journals (Sweden)

    Yerle Martine

    2003-11-01

    Full Text Available Abstract A pericentric inversion of chromosome 4 in a boar, as well as a case of (2q-;5p+ translocation mosaicism in a bull were analysed by chromosome painting using probes generated by conventional microdissection. For the porcine inversion, probes specific for p arms and q arms were produced and hybridised simultaneously on metaphases of a heterozygote carrier. In the case of the bovine translocation, two whole chromosome probes (chromosome 5, and derived chromosome 5 were elaborated and hybridised independently on chromosomal preparations of the bull who was a carrier of the mosaic translocation. The impossibility of differentiating chromosomes 2 and der(2 from other chromosomes of the metaphases did not allow the production of painting probes for these chromosomes. For all experiments, the quality of painting was comparable to that usually observed with probes obtained from flow-sorted chromosomes. The results obtained allowed confirmation of the interpretations proposed with G-banding karyotype analyses. In the bovine case, however, the reciprocity of the translocation could not be proven. The results presented in this paper show the usefulness of the microdissection technique for characterising chromosomal rearrangements in species for which commercial probes are not available. They also confirmed that the main limiting factor of the technique is the quality of the chromosomal preparations, which does not allow the identification of target chromosomes or chromosome fragments in all cases.

  12. Dystrophin gene deletions in South Indian Duchenne muscular dystrophy patients.

    OpenAIRE

    Mallikarjuna Rao G; Hussain T.; Geetha Devi N; Jain S; Chandak G; Ananda Raj M

    2003-01-01

    66 unrelated patients from Southern India with Duchenne Muscular Dystrophy (DMD) were studied for intragenic deletion in 18 exons and Pm region of the DMD gene using multiplex PCR. Of these 41 (62.1%) showed intragenic deletions. 78% of the deletions were located at the distal hotspot region (44-55 exons) and 22% of the deletions were located at the proximal region (exon 2-19). Exon 50 is most frequently deleted. Deletions in isolated cases were significantly more compare...

  13. Deletion (X)(q26.1-->q28) in a proband and her mother: molecular characterization and phenotypic-karyotypic deductions.

    Science.gov (United States)

    Tharapel, A T; Anderson, K P; Simpson, J L; Martens, P R; Wilroy, R S; Llerena, J C; Schwartz, C E

    1993-01-01

    During a routine prenatal diagnosis we detected a female fetus with an apparent terminal deletion of an X chromosome with a karyotype 46,X,del(X)(q25); the mother, who later underwent premature ovarian failure, had the same Xq deletion. To further delineate this familial X deletion and to determine whether the deletion was truly terminal or, rather, interstitial (retaining a portion of the terminal Xq28), we used a combination of fluorescence in situ hybridization (FISH) and Southern analyses. RFLP analyses and dosage estimation by densitometry were performed with a panel of nine probes (DXS3, DXS17, DXS11, DXS42, DXS86, DXS144E, DXS105, DXS304, and DXS52) that span the region Xq21 to subtelomeric Xq28. We detected a deletion involving the five probes spanning Xq26-Xq28. FISH with a cosmid probe (CLH 128) that defined Xq28 provided further evidence of a deletion in that region. Analysis with the X chromosome-specific cocktail probes spanning Xpter-qter showed hybridization signal all along the abnormal X, excluding the possibility of a cryptic translocation. However, sequential FISH with the X alpha-satellite probe DXZ1 and a probe for total human telomeres showed the presence of telomeres on both the normal and deleted X chromosomes. From the molecular and FISH analyses we interpret the deletion in this family as 46,X,del(X) (pter-->q26::qter). In light of previous phenotypic-karyotypic correlations, it can be deduced that this region contains a locus responsible for ovarian maintenance. Images p[466]-a Figure 1 Figure 3 Figure 4 PMID:8095365

  14. Deletion (X)(q26. 1[r arrow]q28) in a proband and her mother: Molecular characterization and phenotypic-karyotypic deductions

    Energy Technology Data Exchange (ETDEWEB)

    Tharapel, A.T.; Simpson, J.L.; Martens, P.R.; Wilroy, R.S. Jr.; Llerena, J.C. Jr. (Univ. of Tennessee, Memphis (United States)); Anderson, K.P.; Schwartz, C.E. (Greenwood Genetics Center, SC (United States))

    1993-03-01

    During a routine pernatal diagnosis the authors detected a female fetus with an apparent terminal deletion of an X chromosome with a karyotype 46,X,del(X)(q25); the mother, who later underwent premature ovarian failure, had the same Xq deletion. To further delineate this familial X deletion and to determine whether the deletion was truly terminal or, rather, interstitial (retaining a portion of the terminal Xq28), the authors used a combination of fluorescence in situ hybridization (FISH) and Southern analyses. RFLP analyses and dosage estimation by densitometry were performed with a panel of nine probes (DXS3, DXS17, DXS11, DXS42, DXS86, DXS144E, DXS105, DXS304, and DXS52) that span the region Xq21 to subtelomeric Xq28. They detected a deletion involving the five probes spanning Xq26-Xq28. FISH with a cosmid probe (CLH 128) that defined Xq28 provided further evidence of a deletion in that region. Analysis with the X chromosome-specific cocktail probes spanning Xpter-qter showed hybridization signal all along the abnormal X, excluding the possibility of a cryptic translocation. However, sequential FISH with the X [alpha]-satellite probe DXZ1 and a probe for total human telomeres showed the presence of telomeres on both the normal and deleted X chromosomes. From the molecular and FISH analyses they interpret the deletion in this family as 46,X,del(X)(pter[r arrow]q26::qter). In light of previous phenotypic-karyotypic correlations, it can be deduced that this region contains a locus responsible for ovarian maintenance. 32 refs., 4 figs., 2 tabs.

  15. Characterization of a complex rearrangement involving duplication and deletion of 9p in an infant with craniofacial dysmorphism and cardiac anomalies

    Directory of Open Access Journals (Sweden)

    Di Bartolo Daniel L

    2012-07-01

    Full Text Available Abstract Partial duplication and partial deletion of the short arm of chromosome 9 have each been reported in the literature as clinically recognizable syndromes. We present clinical, cytogenetic, and molecular findings on a five-week-old female infant with concomitant duplication and terminal deletion of the short arm of chromosome 9. To our knowledge ten such cases have previously been reported. Conventional cytogenetic analysis identified additional material on chromosome 9 at band p23. FISH analysis aided in determining the additional material consisted of an inverted duplication with a terminal deletion of the short arm. Microarray analysis confirmed this interpretation and further characterized the abnormality as a duplication of about 32.7 Mb, from 9p23 to 9p11.2, and a terminal deletion of about 11.5 Mb, from 9p24.3 to 9p23. The infant displayed characteristic features of Duplication 9p Syndrome (hypotonia, bulbous nose, single transverse palmar crease, cranial anomalies, as well as features associated with Deletion 9p Syndrome (flat nasal bridge, long philtrum, cardiac anomalies despite the deletion being distal to the reported critical region for this syndrome. This case suggests that there are genes or regulatory elements that lie outside of the reported critical region responsible for certain phenotypic features associated with Deletion 9p Syndrome. It also underscores the importance of utilizing array technology to precisely define abnormalities involving the short arm of 9p in order to further refine genotype/phenotype associations and to identify additional cases of duplication/deletion.

  16. 576 kb deletion in 1p36.33-p36.32 containing SKI is associated with limb malformation, congenital heart disease and epilepsy.

    Science.gov (United States)

    Zhu, Xin; Zhang, Yi; Wang, Jian; Yang, Jin-Fu; Yang, Yi-Feng; Tan, Zhi-Ping

    2013-10-10

    1p36 deletion (monosomy 1p36) is one of the most common terminal deletions observed in humans, characterized by special facial features, mental retardation, heart defects, development delay and epilepsy. Previously, we reported molecular findings in patients with limb, congenital heart disease (CHD) and other malformations with SNP-array. In a syndromic patient of the same cohort, we detected a small deletion of 1p36.33-p36.32 containing SKI (Sloan-Kettering Institute protooncoprotein). Recently, dominant mutations in SKI were identified to be correlated with Shprintzen-Goldberg syndrome. Retrospective examination revealed this patient with limb malformations, CHD, epilepsy and mild development delay. Together with previous reports, our study suggests that the 1p36.33-1p36.32 deletion encompassing SKI may represents a previous undescribed microdeletion disorder. PMID:23892090

  17. Array-CGH characterization and genotype-phenotype analysis in a patient with a ring chromosome 6

    OpenAIRE

    Ciocca, Laura; Surace, Cecilia; Digilio, Maria Cristina; Roberti, Maria Cristina; Sirleto, Pietro; Lombardo, Antonietta; Russo, Serena; Brizi, Valerio; Grotta, Simona; Cini, Claudio; Angioni, Adriano

    2013-01-01

    Background Ring chromosome 6 is a rare constitutional abnormality that generally occurs de novo. The related phenotype may be highly variable ranging from an almost normal phenotype to severe malformations and mental retardation. These features are mainly present when genetic material at the end of the chromosome is lost. The severity of the phenotype seems to be related to the size of the deletion. About 25 cases have been described to date, but the vast majority reports only conventional cy...

  18. The Comorbidity of Autism with the Genomic Disorders of Chromosome 15q11.2-q13

    OpenAIRE

    Hogart, Amber; Wu, David; LaSalle, Janine M.; Schanen, N. Carolyn

    2008-01-01

    A cluster of low copy repeats on the proximal long arm of chromosome 15 mediate various forms of stereotyped deletions and duplication events that cause a group of neurodevelopmental disorders that are associated with autism or autism spectrum disorders (ASD). The region is subject to genomic imprinting and the behavioral phenotypes associated with the chromosome 15q11.2-q13 disorders show a parent-of-origin specific effect that suggests that increased copy number of maternally derived allele...

  19. Ring chromosome 13

    DEFF Research Database (Denmark)

    Brandt, C A; Hertz, Jens Michael; Petersen, M B; Vogel, F; Noer, H; Mikkelsen, M

    1992-01-01

    A stillborn male child with anencephaly and multiple malformations was found to have the karyotype 46,XY,r(13) (p11q21.1). The breakpoint at 13q21.1, determined by high resolution banding, is the most proximal breakpoint ever reported in patients with ring chromosome 13. In situ hybridisation with...

  20. The Y Chromosome

    Science.gov (United States)

    Offner, Susan

    2010-01-01

    The Y chromosome is of great interest to students and can be used to teach about many important biological concepts in addition to sex determination. This paper discusses mutation, recombination, mammalian sex determination, sex determination in general, and the evolution of sex determination in mammals. It includes a student activity that…

  1. Chromosomes, cancer and radiosensitivity

    Energy Technology Data Exchange (ETDEWEB)

    Samouhos, E.

    1983-08-01

    Some specific chromosomal abnormalities are associated with certain cancers. The earliest description of such a specific association is the one of the Philadelphia chromosome and myelogenous leukemia (1960). Other congenital karyotype abnormalities are associated with specific cancers. Examples of these are Down's syndrome with leukemia and Klinefelter's syndrome with male breast cancer. Genetic diseases of increased chromosome breakage, or of defective chromosome repair, are associated with greatly increased cancer incidence. Three such diseases have been recognized: 1) Fanconi's anemia, associated with leukemias and lymphomas, 2) Bloom's syndrome, associated with acute leukemias and lymphosarcoma, and 3) ataxia telangiectasia, associated with Hodgkin's disease, leukemia, and lymphosarcomas. Ten percent of individuals with ataxia telangiectasia will develop one of these neoplasms. Individuals with certain of these syndromes display an unusually high radiosensitivity. Radiation therapy for cancers has been fatal in patients who received as low as 3000 rad. This remarkable radiosensitivity has been quantitated in cell cultures from such cases. Evidence suggests that the apparent sensitivity may reflect subnormal ability to repair radiation damage. The rapid proliferation of information in this field stems from the interdigitation of many disciplines and specialties, including cytogenetics, cell biology, molecular biology, epidemiology, radiobiology, and several others. This paper is intended for clinicians; it presents a structured analytic scheme for correlating and classifying this multidisciplinary information as it becomes available.

  2. Chromosomes, cancer and radiosensitivity

    International Nuclear Information System (INIS)

    Some specific chromosomal abnormalities are associated with certain cancers. The earliest description of such a specific association is the one of the Philadelphia chromosome and myelogenous leukemia (1960). Other congenital karyotype abnormalities are associated with specific cancers. Examples of these are Down's syndrome with leukemia and Klinefelter's syndrome with male breast cancer. Genetic diseases of increased chromosome breakage, or of defective chromosome repair, are associated with greatly increased cancer incidence. Three such diseases have been recognized: 1) Fanconi's anemia, associated with leukemias and lymphomas, 2) Bloom's syndrome, associated with acute leukemias and lymphosarcoma, and 3) ataxia telangiectasia, associated with Hodgkin's disease, leukemia, and lymphosarcomas. Ten percent of individuals with ataxia telangiectasia will develop one of these neoplasms. Individuals with certain of these syndromes display an unusually high radiosensitivity. Radiation therapy for cancers has been fatal in patients who received as low as 3000 rad. This remarkable radiosensitivity has been quantitated in cell cultures from such cases. Evidence suggests that the apparent sensitivity may reflect subnormal ability to repair radiation damage. The rapid proliferation of information in this field stems from the interdigitation of many disciplines and specialties, including cytogenetics, cell biology, molecular biology, epidemiology, radiobiology, and several others. This paper is intended for clinicians; it presents a structured analytic scheme for correlating and classifying this multidisciplinary information as it becomes available

  3. Chromosome Morphology in Kniphofia.

    Directory of Open Access Journals (Sweden)

    J. M. J de Wet

    1960-12-01

    Full Text Available A number of species and varieties of the genus  Kniphofia (Liliaceae were studied cytologically. The somatic chromosome number is  2n = 12 in all the species. This is also true in  Notosceptrum natalense Baker.

  4. A genome-wide map of aberrantly expressed chromosomal islands in colorectal cancer

    Directory of Open Access Journals (Sweden)

    Castanos-Velez Esmeralda

    2006-09-01

    Full Text Available Abstract Background Cancer development is accompanied by genetic phenomena like deletion and amplification of chromosome parts or alterations of chromatin structure. It is expected that these mechanisms have a strong effect on regional gene expression. Results We investigated genome-wide gene expression in colorectal carcinoma (CRC and normal epithelial tissues from 25 patients using oligonucleotide arrays. This allowed us to identify 81 distinct chromosomal islands with aberrant gene expression. Of these, 38 islands show a gain in expression and 43 a loss of expression. In total, 7.892 genes (25.3% of all human genes are located in aberrantly expressed islands. Many chromosomal regions that are linked to hereditary colorectal cancer show deregulated expression. Also, many known tumor genes localize to chromosomal islands of misregulated expression in CRC. Conclusion An extensive comparison with published CGH data suggests that chromosomal regions known for frequent deletions in colon cancer tend to show reduced expression. In contrast, regions that are often amplified in colorectal tumors exhibit heterogeneous expression patterns: even show a decrease of mRNA expression. Because for several islands of deregulated expression chromosomal aberrations have never been observed, we speculate that additional mechanisms (like abnormal states of regional chromatin also have a substantial impact on the formation of co-expression islands in colorectal carcinoma.

  5. Telomere dysfunction and chromosome instability

    Energy Technology Data Exchange (ETDEWEB)

    Murnane, John P., E-mail: jmurnane@radonc.ucsf.edu [Department of Radiation Oncology, University of California San Francisco, 2340 Sutter Street, San Francisco, CA 94143-1331 (United States)

    2012-02-01

    The ends of chromosomes are composed of a short repeat sequence and associated proteins that together form a cap, called a telomere, that keeps the ends from appearing as double-strand breaks (DSBs) and prevents chromosome fusion. The loss of telomeric repeat sequences or deficiencies in telomeric proteins can result in chromosome fusion and lead to chromosome instability. The similarity between chromosome rearrangements resulting from telomere loss and those found in cancer cells implicates telomere loss as an important mechanism for the chromosome instability contributing to human cancer. Telomere loss in cancer cells can occur through gradual shortening due to insufficient telomerase, the protein that maintains telomeres. However, cancer cells often have a high rate of spontaneous telomere loss despite the expression of telomerase, which has been proposed to result from a combination of oncogene-mediated replication stress and a deficiency in DSB repair in telomeric regions. Chromosome fusion in mammalian cells primarily involves nonhomologous end joining (NHEJ), which is the major form of DSB repair. Chromosome fusion initiates chromosome instability involving breakage-fusion-bridge (B/F/B) cycles, in which dicentric chromosomes form bridges and break as the cell attempts to divide, repeating the process in subsequent cell cycles. Fusion between sister chromatids results in large inverted repeats on the end of the chromosome, which amplify further following additional B/F/B cycles. B/F/B cycles continue until the chromosome acquires a new telomere, most often by translocation of the end of another chromosome. The instability is not confined to a chromosome that loses its telomere, because the instability is transferred to the chromosome donating a translocation. Moreover, the amplified regions are unstable and form extrachromosomal DNA that can reintegrate at new locations. Knowledge concerning the factors promoting telomere loss and its consequences is

  6. Organization of the bacterial chromosome.

    OpenAIRE

    Krawiec, S.; Riley, M

    1990-01-01

    Recent progress in studies on the bacterial chromosome is summarized. Although the greatest amount of information comes from studies on Escherichia coli, reports on studies of many other bacteria are also included. A compilation of the sizes of chromosomal DNAs as determined by pulsed-field electrophoresis is given, as well as a discussion of factors that affect gene dosage, including redundancy of chromosomes on the one hand and inactivation of chromosomes on the other hand. The distinction ...

  7. Seevolution: visualizing chromosome evolution

    OpenAIRE

    Esteban-Marcos, Andrés; Darling, Aaron E.; Ragan, Mark A.

    2009-01-01

    Summary: Genome evolution underpins all of biology, yet its principles can be difficult to communicate to the non-specialist. To facilitate broader understanding of genome evolution, we have designed an interactive 3D environment that enables visualization of diverse genome evolution processes. The system can intuitively and interactively animate mutation histories involving genome rearrangement, point mutation, recombination, insertion and deletion. Multiple organisms related by a phylogeny ...

  8. Evolution of the DAZ gene and the AZFc region on primate Y chromosomes

    Directory of Open Access Journals (Sweden)

    Yu Jane-Fang

    2008-03-01

    Full Text Available Abstract Background The Azoospermia Factor c (AZFc region of the human Y chromosome is a unique product of segmental duplication. It consists almost entirely of very long amplicons, represented by different colors, and is frequently deleted in subfertile men. Most of the AZFc amplicons have high sequence similarity with autosomal segments, indicating recent duplication and transposition to the Y chromosome. The Deleted in Azoospermia (DAZ gene within the red-amplicon arose from an ancestral autosomal DAZ-like (DAZL gene. It varies significantly between different men regarding to its copy number and the numbers of RNA recognition motif and DAZ repeat it encodes. We used Southern analyses to study the evolution of DAZ and AZFc amplicons on the Y chromosomes of primates. Results The Old World monkey rhesus macaque has only one DAZ gene. In contrast, the great apes have multiple copies of DAZ, ranging from 2 copies in bonobos and gorillas to at least 6 copies in orangutans, and these DAZ genes have polymorphic structures similar to those of their human counterparts. Sequences homologous to the various AZFc amplicons are present on the Y chromosomes of some but not all primates, indicating that they arrived on the Y chromosome at different times during primate evolution. Conclusion The duplication and transposition of AZFc amplicons to the human Y chromosome occurred in three waves, i.e., after the branching of the New World monkey, the gorilla, and the chimpanzee/bonobo lineages, respectively. The red-amplicon, one of the first to arrive on the Y chromosome, amplified by inverted duplication followed by direct duplication after the separation of the Old World monkey and the great ape lineages. Subsequent duplication/deletion in the various lineages gave rise to a spectrum of DAZ gene structure and copy number found in today's great apes.

  9. Large deletions within the spinal muscular atrophy gene region in a patient with spinal muscular atrophy type 3

    Institute of Scientific and Technical Information of China (English)

    Wei Wei; Chunyue Chen; Wenting Liu; Zhenfang Du; Xiaoling Chen; Xianning Zhang

    2011-01-01

    Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder characterized by degeneration and loss of anterior horn cells in the spinal cord and brain stem nuclei, leading to progressive limb and trunk paralysis and muscular atrophy. Depending on the age of onset and maximum muscular function achieved, SMA is recognized as SMA1, SMA2, SMA3 or SMA4, and most patients have a deletion or truncation of the survival motor neuron 1 (SMN1) gene. In this report, we present a patient with a mild SMA phenotype, SMA3, and define his genetic abnormality. Tetra-primer amplification refractory mutation system PCR combined with restriction fragment length polymorphism analysis and array comparative genomic hybridization were used to determine the genetic variations in this patient. A 500 kb deletion in chromosome 5q13.2, including homozygous deletion of neuronal apoptosis inhibitory protein, and heterozygous deletion of occludin and B-double prime 1 was identified. This SMA region deletion did not involve SMN, indicating that SMN was likely to function normally. The phenotype was dependent of the large deletion and neuronal apoptosis inhibitory protein, occludin and B-double prime 1 may be candidate genes for SMA3.

  10. A high number of losses in 13q14 chromosome band is associated with a worse outcome and biological differences in patients with B-cell chronic lymphoid leukemia

    OpenAIRE

    Hernández, José Ángel; Rodríguez, Ana Eugenia; González, Marcos; Benito, Rocío; Fontanillo, Celia; Sandoval, Virgilio; Romero, Mercedes; Martín-Núñez, Guillermo; de Coca, Alfonso García; Fisac, Rosa; Galende, Josefina; Recio, Isabel; Ortuño, Francisco; García, Juan Luis; De Las Rivas, Javier

    2009-01-01

    In B-cell chronic lymphoid leukemia, patients with 13q14 deletion generally have a favorable outcome. The findings of this study suggest that the number of malignant cells with 13q14 deletion may influence the outcome of patients with this cytogenetic abnormality as a single chromosomal aberration. A high number of malignant cells carrying the 13q14 deletion, as assessed by FISH, appears to be associated with short overall survival and time to progression.

  11. Damage effect of intermittent high glucose on rat islet cell tumor cell line Ins-1 and its impacts on the expression of phosphatase and tensin homologue deleted on chromosome 10 in those cells%间歇性高糖对大鼠胰岛细胞瘤细胞系Ins-1的损伤作用及对第10号染色体缺失的张力同源性磷酸酶表达的影响

    Institute of Scientific and Technical Information of China (English)

    邵晨; 王晓黎; 王涤非; 李国姣; 郭妍; 董玉梅

    2015-01-01

    目的 探讨间歇性高糖对大鼠胰岛细胞瘤细胞系Ins-1的损伤作用及对第10号染色体缺失的张力同源性磷酸酶(PTEN)表达的影响.方法 将Ins-1细胞分为正常组(CG组,11.1 mmol/L葡萄糖培养)、持续高糖组(SHG组,33.3 mmol/L葡萄糖培养)、间歇性高糖组(IHG组,11.1 mmol/L及33.3 mmol/L葡萄糖交替培养12h),3组细胞均培养3d.欧文比色法(MTS)测定细胞增殖活性,膜联蛋白V-异硫氰酸荧光素/碘化丙啶(Annexin V/PI)双染细胞后,以流式细胞仪测定各组细胞的凋亡率,放免法测各组细胞胰岛素分泌,2′,7′-二氯荧光黄双乙酸盐(DCFH-DA)荧光探针测定各组细胞内活性氧簇(ROS)水平,倒置相差显微镜下观察各组细胞形态,钙离子荧光探针法(Fluo 3-AM)测定细胞内钙离子浓度,Western blotting法测定各组细胞PTEN蛋白表达.各组内均数比较采用单因素方差分析.结果 SHG组细胞凋亡率、细胞内ROS水平、细胞内钙离子浓度及PTEN表达均较CG组显著增加(t=8.310、10.261、17.890、5.123,均P<0.05),细胞增殖活性、胰岛素分泌均较CG组显著降低(t=-19.630、-2.053,均P<0.05).IHG组细胞凋亡率、细胞内ROS水平以及钙离子浓度及PTEN表达均较CG组及SHG显著增加(t=6.200~18.227,均P<0.05),细胞增殖活性、胰岛素分泌均较CG组及SHG组均显著降低(t=-27.800、-2.790、-8.167、-1.503,均P<0.05).IHG组较SHG组及CG组Ins-1细胞异型性明显、细胞数量显著减少且排列紊乱.结论 氧化应激参与高糖对Ins-1细胞的损伤作用,可能与PTEN表达增高有关,间歇性高糖对INS-1细胞的损伤作用较持续性高糖严重.%Objective To study the effect of intermittent hyperglycemia on rat insulinoma cell line Ins-1 apoptosis and the expression of phosphatase and tensin homologue-deleted chromosome ten gene (PTEN) in those cells.Methods Ins-1 cells were divided into three groups:control group (CG,cultured in 11.1 mmol/L glucose

  12. Molecular characterization of two proximal deletion breakpoint regions in both Prader-Willi and Angelman syndrome patients

    Energy Technology Data Exchange (ETDEWEB)

    Christian, S.L.; Huang, B.; Ledbetter, D.H. [National Institutes of Health, Bethesda, MD (United States)] [and others

    1995-07-01

    Prader-Willi syndrome (PWS) and Angelman syndrome (AS) are distinct mental retardation syndromes caused by paternal and maternal deficiencies, respectively, in chromosome 15q11{minus}q13. Approximately 70% of these patients have a large deletion of {approximately}4 Mb extending from D15S9 (ML34) through D15S12 (IR10A). To further characterize the deletion breakpoints proximal to D15S9, three new polymorphic microsatellite markers were developed that showed observed heterozygosities of 60%-87%. D15S541 and D15S542 were isolated for YAC A124A3 containing the D15S18 (IR39) locus. D15S543 was isolated from a cosmid cloned from the proximal right end of YAC 254B5 containing the D15S9 (ML34) locus. Gene-centromere mapping of these markers, using a panel of ovarian teratomas of known meiotic origin, extended the genetic map of chromosome 15 by 2-3 cM toward the centromere. Analysis of the more proximal S541/S542 markers on 53 Prader-Willi and 33 Angelman deletion patients indicated two classes of patients: 44% (35/80) of the informative patients were deleted for these markers (class I), while 56% (45/80) were not deleted (class II), with no difference between PWS and AS. In contrast, D15S543 was deleted in all informative patients (13/48) or showed the presence of a single allele (in 35/48 patients), suggesting that this marker is deleted in the majority of PWS and AS cases. These results confirm the presence of two common proximal deletion breakpoint regions in both Prader-Willi and Angelman syndromes and are consistent with the same deletion mechanism being responsible for paternal and maternal deletions. One breakpoint region lies between D15S541/S542 and D15S543, with an additional breakpoint region being proximal to D15S541/S542. 46 refs., 2 figs., 3 tabs.

  13. Is 1p36 deletion associated with anterior body wall defects?

    Science.gov (United States)

    Çöllü, Medis; Yüksel, Şirin; Şirin, Başak Kumbasar; Abbasoğlu, Latif; Alanay, Yasemin

    2016-07-01

    Epispadias and exstrophy of the cloaca, also known as OEIS complex (omphalocele, exstrophy, imperforate anus, spinal defects), respectively constitute the most benign and severe ends of the bladder exstrophy-epispadias complex (BEEC) spectrum. In 2009, El-Hattab et al. reported the first patient with OEIS complex associated with a chromosome 1p36 deletion. Here we report a second patient with 1p36 deletion who also has classic bladder exstrophy, supporting the possible role of genes in this region in the development of BEEC. The absence of omphalocele and imperforate anus in our patient places him toward classic bladder exstrophy while presence of spina bifida and the absence of coccyx suggest an overlap with OEIS complex. An additional differential diagnosis is the pentalogy of Cantrell in our patient as he also has a diaphragmatic hernia and an incomplete sternum. This is the second observation of a ventral midline birth defect in association with 1p36 deletion syndrome, following El-Hattab et al.'s report [2009]. The three genes (NOCL2, DVL1, and MMP23B) discussed as possible candidates are also among the deleted ones in our patient, supporting the possible role of these genes in BEEC spectrum. © 2016 Wiley Periodicals, Inc. PMID:27144803

  14. Social Cognition in Williams Syndrome: Genotype/phenotype Insights from Partial Deletion Patients

    Directory of Open Access Journals (Sweden)

    AnnetteKarmiloff-Smith

    2012-05-01

    Full Text Available Identifying genotype-phenotype relations in human social cognition has been enhanced by the study of Williams syndrome (WS. Indeed, individuals with WS present with a particularly strong social drive, and researchers have sought to link deleted genes in the WS Critical Region (WSCR of chromosome 7q11.23 to this unusual social profile. In this paper, we provide details of two case studies of children with partial genetic deletions in the WSCR: an 11-year-old female with a deletion of 24 of the 28 WS genes, and a 14-year-old male who presents with the opposite profile, i.e. the deletion of only 4 genes at the telomeric end of the WSCR. We tested these two children on a large battery of standardised and experimental social perception and social cognition tasks - both implicit and explicit - as well as standardised social questionnaires and general psychometric measures. Our findings reveal a partial WS socio-cognitive profile in the female, contrasted with a more autistic-like profile in the male. We discuss the implications of these findings for genotype/phenotype relations, as well as the advantages and limitations of animal models and of case study approaches.

  15. A de novo POU3F3 deletion in a boy with intellectual disability and dysmorphic features

    OpenAIRE

    Dheedene, Annelies; MAES, MICHAELA; Vergult, Sarah; Menten, Björn

    2014-01-01

    We describe a boy presenting with intellectual disability and dysmorphic features in whom a cryptic microdeletion in chromosome band 2q12.1 was identified with array CGH. The deletion results in a loss of the POU3F3 and MRPS9 genes. In this paper, we discuss the possible role of POU3F3 haploinsufficiency in relation to the boy's phenotype.

  16. Two cases of 5q deletions in patients with familial adenomatous polyposis: possible link with Caroli's disease.

    OpenAIRE

    Hodgson, S V; Coonar, A S; P. J. Hanson; Cottrell, S; Scriven, P N; Jones, T; Hawley, P R; Wilkinson, M L

    1993-01-01

    Two cases are reported of patients with deletions of chromosome 5q. Both have familial adenomatous polyposis (FAP) and mild mental retardation. In both, macroscopic polyposis was confined to the proximal colon in adult life (in their thirties) although microscopic adenomatosis was shown in the more distal colon with occasional single polyps. Both subjects had dermoid cysts, and congenital hypertrophy of the retinal pigment epithelium (CHRPE) was seen in case 2. Case 1 has gastroduodenal polyp...

  17. Karyotype analysis of virulent Plasmodium falciparum strains propagated in Saimiri sciureus: strain adaptation leads to deletion of the RESA gene.

    OpenAIRE

    Hinterberg, K; Muanza, K; Hernandez-Rivas, R; Gay, F.; Gysin, J; D. Mattei; Scherf, A

    1995-01-01

    The squirrel monkey, Saimiri sciureus, is an important experimental model for the study of the human malaria parasite Plasmodium falciparum. A detailed karyotype analysis of four different P. falciparum strains propagated in S. sciureus was done using various subtelomeric antigen gene probes. We observed deletion of the complete RESA gene from chromosome 1 in all four strains. Interestingly, a loss of RESA was observed immediately upon adaptation to the squirrel monkey, suggesting that this D...

  18. [Chromosomal organization of the genomes of small-chromosome plants].

    Science.gov (United States)

    Muravenko, O V; Zelenin, A V

    2009-11-01

    An effective approach to study the chromosome organization in genomes of plants with small chromosomes and/or with low-informative C-banding patterns was developed in the course of investigation of the karyotypes of cotton plant, camomile, flax, and pea. To increase the resolving power of chromosome analysis, methods were worked out for revealing early replication patterns on chromosomes and for artificial impairment of mitotic chromosome condensation with the use of a DNA intercalator, 9-aminoacridine (9-AMA). To estimate polymorphism of the patterns of C-banding of small chromosomes on preparations obtained with the use of 9-AMA, it is necessary to choose a length interval that must not exceed three average sizes of metaphase chromosomes without the intercalator. The use of 9-AMA increases the resolution of differential C- and OR-banding and the precision of physical chromosome mapping by the FISH method. Of particular importance in studying small chromosomes is optimization of the computer-aided methods used to obtain and process chromosome images. The complex approach developed for analysis of the chromosome organization in plant genomes was used to study the karyotypes of 24 species of the genus Linum L. It permitted their chromosomes to be identified for the first time, and, in addition, B chromosomes were discovered and studied in the karyotypes of the species of the section Syllinum. By similarity of the karyotypes, the studied flax species were distributed in eight groups in agreement with the clusterization of these species according to the results of RAPD analysis performed in parallel. Systematic positions and phylogenetic relationships of the studied flax species were verified. Out results can serve as an important argument in favour of the proposal to develop a special program for sequencing the genome of cultivated flax (L. usitatissimum L.), which is a major representative of small-chromosome species. PMID:20058798

  19. Following tetraploidy in maize, a short deletion mechanism removed genes preferentially from one of the two homologs.

    Directory of Open Access Journals (Sweden)

    Margaret R Woodhouse

    Full Text Available Previous work in Arabidopsis showed that after an ancient tetraploidy event, genes were preferentially removed from one of the two homologs, a process known as fractionation. The mechanism of fractionation is unknown. We sought to determine whether such preferential, or biased, fractionation exists in maize and, if so, whether a specific mechanism could be implicated in this process. We studied the process of fractionation using two recently sequenced grass species: sorghum and maize. The maize lineage has experienced a tetraploidy since its divergence from sorghum approximately 12 million years ago, and fragments of many knocked-out genes retain enough sequence similarity to be easily identifiable. Using sorghum exons as the query sequence, we studied the fate of both orthologous genes in maize following the maize tetraploidy. We show that genes are predominantly lost, not relocated, and that single-gene loss by deletion is the rule. Based on comparisons with orthologous sorghum and rice genes, we also infer that the sequences present before the deletion events were flanked by short direct repeats, a signature of intra-chromosomal recombination. Evidence of this deletion mechanism is found 2.3 times more frequently on one of the maize homologs, consistent with earlier observations of biased fractionation. The over-fractionated homolog is also a greater than 3-fold better target for transposon removal, but does not have an observably higher synonymous base substitution rate, nor could we find differentially placed methylation domains. We conclude that fractionation is indeed biased in maize and that intra-chromosomal or possibly a similar illegitimate recombination is the primary mechanism by which fractionation occurs. The mechanism of intra-chromosomal recombination explains the observed bias in both gene and transposon loss in the maize lineage. The existence of fractionation bias demonstrates that the frequency of deletion is modulated

  20. Alternative Lengthening of Telomeres: Recurrent Cytogenetic Aberrations and Chromosome Stability under Extreme Telomere Dysfunction

    Directory of Open Access Journals (Sweden)

    Despoina Sakellariou

    2013-11-01

    Full Text Available Human tumors using the alternative lengthening of telomeres (ALT exert high rates of telomere dysfunction. Numerical chromosomal aberrations are very frequent, and structural rearrangements are widely scattered among the genome. This challenging context allows the study of telomere dysfunction-driven chromosomal instability in neoplasia (CIN in a massive scale. We used molecular cytogenetics to achieve detailed karyotyping in 10 human ALT neoplastic cell lines.We identified 518 clonal recombinant chromosomes affected by 649 structural rearrangements. While all human chromosomes were involved in random or clonal, terminal, or pericentromeric rearrangements and were capable to undergo telomere healing at broken ends, a differential recombinatorial propensity of specific genomic regions was noted.We show that ALT cells undergo epigenetic modifications rendering polycentric chromosomes functionally monocentric, and because of increased terminal recombinogenicity, they generate clonal recombinant chromosomes with interstitial telomeric repeats. Losses of chromosomes 13, X, and 22, gains of 2, 3, 5, and 20, and translocation/deletion events involving several common chromosomal fragile sites (CFSs were recurrent. Long-term reconstitution of telomerase activity in ALT cells reduced significantly the rates of random ongoing telomeric and pericentromeric CIN. However, the contribution of CFS in overall CIN remained unaffected, suggesting that in ALT cells whole-genome replication stress is not suppressed by telomerase activation. Our results provide novel insights into ALT-driven CIN, unveiling in parallel specific genomic sites that may harbor genes critical for ALT cancerous cell growth.

  1. Alternative lengthening of telomeres: recurrent cytogenetic aberrations and chromosome stability under extreme telomere dysfunction.

    Science.gov (United States)

    Sakellariou, Despoina; Chiourea, Maria; Raftopoulou, Christina; Gagos, Sarantis

    2013-11-01

    Human tumors using the alternative lengthening of telomeres (ALT) exert high rates of telomere dysfunction. Numerical chromosomal aberrations are very frequent, and structural rearrangements are widely scattered among the genome. This challenging context allows the study of telomere dysfunction-driven chromosomal instability in neoplasia (CIN) in a massive scale. We used molecular cytogenetics to achieve detailed karyotyping in 10 human ALT neoplastic cell lines. We identified 518 clonal recombinant chromosomes affected by 649 structural rearrangements. While all human chromosomes were involved in random or clonal, terminal, or pericentromeric rearrangements and were capable to undergo telomere healing at broken ends, a differential recombinatorial propensity of specific genomic regions was noted. We show that ALT cells undergo epigenetic modifications rendering polycentric chromosomes functionally monocentric, and because of increased terminal recombinogenicity, they generate clonal recombinant chromosomes with interstitial telomeric repeats. Losses of chromosomes 13, X, and 22, gains of 2, 3, 5, and 20, and translocation/deletion events involving several common chromosomal fragile sites (CFSs) were recurrent. Long-term reconstitution of telomerase activity in ALT cells reduced significantly the rates of random ongoing telomeric and pericentromeric CIN. However, the contribution of CFS in overall CIN remained unaffected, suggesting that in ALT cells whole-genome replication stress is not suppressed by telomerase activation. Our results provide novel insights into ALT-driven CIN, unveiling in parallel specific genomic sites that may harbor genes critical for ALT cancerous cell growth. PMID:24339742

  2. An Xp22 microdeletion associated with ocular albinism and ichthyosis: approximation of breakpoints and estimation of deletion size by using cloned DNA probes and flow cytometry.

    Science.gov (United States)

    Schnur, R E; Trask, B J; van den Engh, G; Punnett, H H; Kistenmacher, M; Tomeo, M A; Naids, R E; Nussbaum, R L

    1989-11-01

    Ocular albinism of the Nettleship-Falls type (OA1) and X-linked ichthyosis (XI) due to steroid sulfatase (STS) deficiency are cosegregating in three cytogenetically normal half-brothers. The mother has patchy fundal hypopigmentation consistent with random X inactivation in an OA1 carrier. Additional phenotypic abnormalities that have been observed in other STS "deletion syndromes" are not present in this family. STS is entirely deleted on Southern blot in the affected males, but the loci MIC2X, DXS31, DXS143, DXS85, DXS43, DXS9, and DXS41 are not deleted. At least part of DXS278 is retained. Flow cytometric analysis of cultured lymphoblasts from one of the XI/OA1 males and his mother detected a deletion of about 3.5 million bp or about 2% of the X chromosome. Southern blot and RFLP analysis in the XI/OA1 family support the order tel-[STS-OA1-DXS278]-DXS9-DXS41-cen. An unrelated patient with the karyotype 46,X,t(X;Y) (p22;q11) retains the DXS143 locus on the derivative X chromosome but loses DXS278, suggesting that DXS278 is the more distal locus and is close to an XI/OA1 deletion boundary. If a contiguous gene deletion is responsible for the observed XI/OA1 phenotype, it localizes OA1 to the Xp22.3 region. PMID:2573275

  3. A yeast artificial chromosome contig of the critical region for cri-du-chat syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Goodart, S.A.; Rojas, K.; Overhauser, J. [Thomas Jefferson Univ., Philadelphia, PA (United States)] [and others

    1994-11-01

    Cri-du-chat is a chromosomal deletion syndrome characterized by partial deletion of the short arm of chromosome 5. The clinical symptoms include growth and mental retardation, microcephaly, hypertelorism, epicanthal folds, hyptonia, and a high-pitched monochromatic cry that is usually considered diagnostic for the syndrome. Recently, a correlation between clinical features and the extent of the chromosome 5 deletions has identified two regions of the short arm that appear to be critical for the abnormal development manifested in this syndrome. Loss of a small region in 5p15.2 correlates with all of the clinical features of cri-du-chat with the exception of the cat-like cry, which maps to 5p15.3. Here the authors report the construction of a YAC contig that spans the chromosomal region in 5p15.2 that plays a major role in the etiology of the cri-du-chat syndrome. YACs that span the 2-Mb cri-du-chat critical region have been identified and characterized. This YAC contig lays the groundwork for the construction of a transcriptional map of this region and the eventual identification of genes involved in the clinical features associated with the cri-du-chat syndrome. It also provides a new diagnostic tool for cri-du-chat in the shape of a YAC clone that may span the entire critical region. 24 refs., 4 figs., 2 tabs.

  4. Deletion of 8q24 in an adult with mild dysmorphic features, developmental delay, and ketotic hypoglycemia.

    Science.gov (United States)

    Solomon, Benjamin D; Lange, Eileen; Shubrook, Jay; Service, F John; Herman, Gail; Karne, Rajaram J; Gorden, Phillip; Muenke, Maximilian; Stratakis, Constantine A

    2010-06-01

    We present a 56-year-old female with a history of carbohydrate intolerance and ketotic hypoglycemia, dysmorphic features, mild developmental delay, lymphedema, altered pain sensation, and frequent fractures, who was found to have a heterozygous 8.09 Mb deletion of chromosome 8q24.11q24.13 containing more than 39 genes, as well as a duplication of 20q11.23 containing one gene. The deleted region overlaps that of two previously reported patients, who share a subset of clinical characteristics with the patient described here. Some of this patient's clinical features are consistent with the loss of genes in the deleted region. The diagnostic work-up of this patient clearly demonstrates the evolution of genetic testing techniques. PMID:20503333

  5. Hearing loss, coloboma and left ventricular enlargement in a boy with an interstitial 10q26 deletion.

    Science.gov (United States)

    Ramos, Maria; Wilkens, Alisha; Krantz, Ian D; Wu, Yaning

    2016-06-01

    Distal deletion of the long arm of chromosome 10 with breakpoints mapped at 10q26 is a well-recognized contiguous genomic disorder. A wide spectrum of clinical findings is seen in affected individuals and the common clinical features include craniofacial dysmorphia, developmental delay, intellectual disability, hypotonia, cardiovascular defects, and urogenital malformations. We report herein on a male patient with a 5.5 Mb interstitial deletion of 10q26.11q2613 and compare his clinical presentation to previously reported cases. Apart from characteristic phenotypes seen in 10q26 deletion syndrome, he presents with colobomas and left ventricle enlargement. These are cardiovascular and ophthalmological findings that have not been described in prior cases. © 2016 Wiley Periodicals, Inc. PMID:27125467

  6. Delineation of a recognizable phenotype for the recurrent LCR22-C to D/E atypical 22q11.2 deletion.

    Science.gov (United States)

    Bengoa-Alonso, Amaya; Artigas-López, Mercè; Moreno-Igoa, María; Cattalli, Claudio; Hernández-Charro, Blanca; Ramos-Arroyo, Maria Antonia

    2016-06-01

    The 22q11.2 deletion syndrome is typically caused by haploinsufficiency of a 3 Mb region that extends from LCR22-A until LCR22-D, while the recurrent recombination between any of the LCR22-D to H causes the 22q11.2 distal deletion syndrome. Here, we describe three patients with a de novo atypical ∼1.4 Mb 22q11.2 deletion that involves LCR22-C to a region beyond D (LCR22-C to D/E), encompassing the distal portion of the typical deleted region and the proximal portion of the distal deletion. We also review six previous published patients with the same rearrangement and compare their features with those found in patients with overlapping deletions. Patients with LCR22-C to D/E deletion present a recognizable phenotype characterized by facial dysmorphic features, high frequency of cardiac defects, including conotruncal defects, prematurity, growth restriction, microcephaly, and mild developmental delay. Genotype-phenotype analysis of the patients indicates that CRKL and MAPK1 genes play an important role as causative factors for the main clinical features of the syndrome. In particular, CRKL gene seems to be involved in the occurrence of conotruncal cardiac anomalies, mainly tetralogy of Fallot. © 2016 Wiley Periodicals, Inc. PMID:26991864

  7. Diagnosis and fine mapping of a deletion in distal 11q in two Chinese patients with developmental delay.

    Science.gov (United States)

    Ji, Taoyun; Wu, Ye; Wang, Huifang; Wang, Jingmin; Jiang, Yuwu

    2010-08-01

    Jacobsen syndrome (JBS) is a haploinsufficiency syndrome caused by partial deletion of the long arm of chromosome 11. It is characterized by developmental delay (DD)/mental retardation (MR), physical growth retardation, facial dysmorphism, visceral malformations and thrombocytopenia. We report two JBS patients from China out of a total of 451 patients with unexplained DD/MR. The genotypes of these patients were compared with earlier reported patients in North America and Europe. Both patients presented with severe DD, microcephaly and facial dysmorphism; one patient had a low birth weight, congenital heart disease and structural brain abnormalities. Neither patient was thrombocytopenic at the time of diagnosis. The two deletions were 4.1 and 12.8 Mb. The 4.1 Mb deletion is the smallest of all pathogenic regions earlier reported in JBS. Therefore, the critical region underlying DD/MR might be located in the distal portion of the chromosomal segment within 4.1 Mb of the telomere. Candidate genes for DD/MR in this region include SNX19, THYN1, OPCML, NCAPD3 and NTM. One of the critical regions for craniofacial abnormalities may be within 130.3-134.4 Mb in chromosome 11q. Further analysis of Chinese JBS patients would elucidate the relation of phenotype to genotype further. PMID:20520618

  8. Cytogenetic and molecular studies on a recombinant human X chromosome: implications for the spreading of X chromosome inactivation

    International Nuclear Information System (INIS)

    A pericentric inversion of human X chromosome and a recombinant X chromosome [rec(X)] derived from crossing-over within the inversion was identified in a family. The rec(X) had a duplication of the segment Xq26.3 → Xqter and a deletion of Xp22.3 → Xpter and was interpreted to be Xqter → Xq26.3::Xp22.3 → Xqter. To characterize the rec(X) chromosome, dosage blots were done on genomic DNA from carriers of this rearranged X chromosome using a number of X chromosome probes. Results showed that anonymous sequences from the distal end of the long arm to which probes 4D8, Hx120A, DX13, and St14 bind as well as the locus for glucose-6-phosphate dehydrogenase (G6PD) wee duplicated on the rec(X). Mouse-human cell hybrids were constructed that retained the rec(X) in the active or inactive state. Analyses of these hybrid clones for markers from the distal short arm of the X chromosome showed that the rec(X) retained the loci for steroid sulfatase (STS) and the cell surface antigen 12E7 (MIC2); but not the pseudoautosomal sequence 113D. These molecular studies confirm that the rec(X) is a duplication-deficiency chromosome as expected. In the inactive state in cell hybrids, STS and MIC2 (which usually escape X chromosome inactivation) were expressed from the rec(X), whereas G6PD was not. Therefore, in the rec(X) X chromosome inactivation has spread through STS and MIC2 leaving these loci unaffected and has inactivated G6PD in the absence of an inactivation center in the q26.3 → qter region of the human X chromosome. The mechanism of spreading of inactivation appears to operate in a sequence-specific fashion. Alternatively, STS and MIC2 may have undergone inactivation initially but could not be maintained in an inactive state

  9. Cytogenetic and molecular studies on a recombinant human X chromosome: implications for the spreading of X chromosome inactivation

    Energy Technology Data Exchange (ETDEWEB)

    Mohandas, T.; Geller, R.L.; Yen, P.H.; Rosendorff, J.; Bernstein, R.; Yoshida, A.; Shapiro, L.J.

    1987-07-01

    A pericentric inversion of human X chromosome and a recombinant X chromosome (rec(X)) derived from crossing-over within the inversion was identified in a family. The rec(X) had a duplication of the segment Xq26.3 ..-->.. Xqter and a deletion of Xp22.3 ..-->.. Xpter and was interpreted to be Xqter ..-->.. Xq26.3::Xp22.3 ..-->.. Xqter. To characterize the rec(X) chromosome, dosage blots were done on genomic DNA from carriers of this rearranged X chromosome using a number of X chromosome probes. Results showed that anonymous sequences from the distal end of the long arm to which probes 4D8, Hx120A, DX13, and St14 bind as well as the locus for glucose-6-phosphate dehydrogenase (G6PD) wee duplicated on the rec(X). Mouse-human cell hybrids were constructed that retained the rec(X) in the active or inactive state. Analyses of these hybrid clones for markers from the distal short arm of the X chromosome showed that the rec(X) retained the loci for steroid sulfatase (STS) and the cell surface antigen 12E7 (MIC2); but not the pseudoautosomal sequence 113D. These molecular studies confirm that the rec(X) is a duplication-deficiency chromosome as expected. In the inactive state in cell hybrids, STS and MIC2 (which usually escape X chromosome inactivation) were expressed from the rec(X), whereas G6PD was not. Therefore, in the rec(X) X chromosome inactivation has spread through STS and MIC2 leaving these loci unaffected and has inactivated G6PD in the absence of an inactivation center in the q26.3 ..-->.. qter region of the human X chromosome. The mechanism of spreading of inactivation appears to operate in a sequence-specific fashion. Alternatively, STS and MIC2 may have undergone inactivation initially but could not be maintained in an inactive state.

  10. Hidden chromosomal abnormalities in pleuropulmonary blastomas identified by multiplex FISH

    International Nuclear Information System (INIS)

    Pleuropulmonary blastoma (PPB) is a rare childhood dysontogenetic intrathoracic neoplasm associated with an unfavourable clinical behaviour. We report pathological and cytogenetic findings in two cases of PPB at initial diagnosis and recurrence. Both tumors were classified as type III pneumoblastoma and histological findings were similar at diagnosis and relapse. In both cases, conventional cytogenetic techniques revealed complex numerical and structural chromosomal abnormalities. Molecular cytogenetic analysis (interphase/metaphase FISH and multicolor FISH) identified accurately chromosomal aberrations. In one case, TP53 gene deletion was detected on metaphase FISH. To date, only few cytogenetic data have been published about PPB. The PPB genetic profile remains to be established and compared to others embryonal neoplasia. Our cytogenetic data are discussed reviewing cytogenetics PPBs published cases, illustrating the contribution of multicolor FISH in order to identify pathogenetically important recurrent aberrations in PPB

  11. Chromosome 19 International Workshop

    Energy Technology Data Exchange (ETDEWEB)

    Pericak-Vance, M.A. (Duke Univ., Durham, NC (United States). Medical Center); Ropers, H.H. (Univ. Hospital Nijmegen, (The Netherlands). Dept. of Human Genetics); Carrano, A.J. (Lawrence Livermore National Lab., CA (United States))

    1993-01-04

    The Second International Workshop on Human Chromosome 19 was hosted on January 25 and 26, 1992, by the Department of Human Genetics, University Hospital Nijmegen, The Netherlands, at the 'Meerdal Conference Center'. The workshop was supported by a grant from the European Community obtained through HUGO, the Dutch Research Organization (NWO) and the Muscular Dystrophy Association (MDA). Travel support for American participants was provided by the Department of Energy. The goals of this workshop were to produce genetic, physical and integrated maps of chromosome 19, to identify inconsistencies and gaps, and to discuss and exchange resources and techniques available for the completion of these maps. The second day of the meeting was largely devoted to region or disease specific efforts. In particular, the meeting served as a platform for assessing and discussing the recent progress made into the molecular elucidation of myotonic dystrophy.

  12. Molecular analysis and comparison of radiation-induced large deletions of the HPRT locus in primary human skin fibroblasts

    Science.gov (United States)

    Yamada, Y.; Park, M. S.; Okinaka, R. T.; Chen, D. J.

    1996-01-01

    Genetic alterations in gamma-ray- and alpha-particle-induced HPRT mutants were examined by multiplex polymerase chain reaction (PCR) analysis. A total of 39-63% of gamma-ray-induced and 31-57% of alpha-particle-induced mutants had partial or total deletions of the HPRT gene. The proportion of these deletion events was dependent on radiation dose, and at the resolution limits employed there were no significant differences between the spectra induced by equitoxic doses of alpha particles (0.2-0.4 Gy) and gamma rays (3 Gy). The molecular nature of the deletions was analyzed by the use of sequence tagged site (STS) primers and PCR amplification as a "probe" for specific regions of the human X chromosome within the Xq26 region. These STSs were closely linked and spanned regions approximately 1.7 Mbp from the telomeric side and 1.7 Mbp from the centromeric side of the HPRT gene. These markers include: DXS53, 299R, DXS79, yH3L, 3/19, PR1, PR25, H2, yH3R, 1/44, 1/67, 1/1, DXS86, D8C6, DXS10 and DXS144. STS analyses indicated that the maximum size of total deletions in radiation-induced HPRT mutants can be greater than 2.7 Mbp and deletion size appears to be dependent on radiation dose. There were no apparent differences in the sizes of the deletions induced by alpha particles or gamma rays. On the other hand, deletions containing portions of the HPRT gene were observed to be 800 kbp or less, and the pattern of the partial deletion induced by alpha particles appeared to be different from that induced by gamma rays.

  13. PREVALENCE OF Y CHROMOSOME MICRODELETIONS IN IRANIAN INFERTILE MEN

    Directory of Open Access Journals (Sweden)

    F. Akbari Asbagh

    2003-07-01

    Full Text Available This study was designed to determine the frequency of Y chromosome AZF (Azoospermia Factor subregions, microdeletions in patients with idiopathic nonobstructive azoospermia and severe oligozoospermia. Subjects included 40 men who had been referred to infertility clinics for assisted reproduction, 37 were azoospermic and 3 had severe oligospermia. Medical history and physical exam revealed no evidence of infection, obstruction of seminal tract, endocrine failure or chromosomal anomalies. Hormonal study was performed for all patients. Twenty six men had biopsies of the testes including 11 patients with hypospermatogenesis, 9 patients with maturation arrest, 4 patients with sertoli cell only syndrome and 2 patients with tubular sclerosis. In 14 men who did not have a testicular biopsy multiple, epididymal and testicular sperm aspirations under anesthesia failed and testicular sperm extraction was subsequently performed for ICSI. DNA was isolated from blood samples. Polymerase chain reaction (PCR amplification of 11 loci spanning the AZFa, AZFb and AZFc subregions of the Y chromosome using sY81, sY83, sY127, sY130, sY131, sY147, sY149, sY157, sY158, sY254 and sY276 was performed. Microdeletions of the Y chromosome were found in two of the patients (5%, who had azoospermia. Deletions were restricted to DAZ (deleted in azoospermia locus in AZFc subregion. One of the patients had a history of cryptorchidism and the second had undergone a left side varicocelectomy. Testicular pathology showed sertoli cell only syndrome in both of them. Our experience adds to the current logic that men with azoospermia or severe oligospermia should be evaluated for Yq11 microdeletions before deciding to operate varicoceles or else scheduling them for assisted reproductive techniques.

  14. Chromosomal jumping from the DXS165 locus allows molecular characterization of four microdeletions and a de novo chromosome X/13 translocation associated with choroideremia.

    OpenAIRE

    Cremers, F P; van de Pol, D J; Wieringa, B; Collins, F S; Sankila, E M; Siu, V. M.; Flintoff, W F; Brunsmann, F.; Blonden, L A; Ropers, H H

    1989-01-01

    Choroideremia (tapeto-choroidal dystrophy, TCD), an X chromosome-linked disorder of retina and choroid, causes progressive nightblindness and central blindness in affected males by the third to fourth decade of life. Recently, we have been able to map the TCD gene to a small region of overlap between five different, male-viable Xq21 deletions that were found in patients with TCD and other clinical features. Two families were identified in which classical, nonsyndromic TCD is associated with s...

  15. Gene deletion analysis of a Chinese boy with Xp21 contiguous gene deletion syndrome

    Institute of Scientific and Technical Information of China (English)

    麻宏伟; 姜俊; 王岳平; 王志超; 陈丽英; 松尾雅文

    2004-01-01

    @@ Xp21 contiguous gene deletion syndrome, sometimes called complex glycerol kinase deficiency, is associated with variable size Xp21 deletions that usually include the glycerol kinase gene and span multiple Xp21 disease gene loci in the region. The order of the potentially affected loci are as follows:

  16. Chromosome aberrations in ataxia telangiectasia cells exposed to heavy ions

    Science.gov (United States)

    Kawata, T.; Cucinotta, F.; George, K.; Wu, H.; Shigematsu, N.; Furusawa, Y.; Uno, T.; Isobe, K.; Ito, H.

    Understanding of biological effects of heavy ions is important to assess healt h risk in space. One of the most important issues may be to take into account individual susceptibility. Ataxia telangiectasia (A-T) cells are known to exhibit abnormal responses to radiations but the mechanism of hyper radiosensitivity of A-T still remains unknown. We report chromosome aberrations in normal human fibroblasts and AT fibroblasts exposed to low- and high-LET radiations. A chemical-induced premature chromosome condensation (PCC) technique combined with chromosome- painting technique was applied to score chromosome aberrations in G2/M-phase cells. Following gamma irradiation, GM02052 cells were approximately 5 times more sensitive to g-rays than AG1522 cells. GM02052 cells had a much higher frequency of deletions and misrejoining than AG1522 cells. When the frequency of complex type aberrations was compared, GM02052 cells showed more than 10 times higher frequency than AG1522 cells. The results will be compared with those obtained from high-LET irradiations.

  17. ETOPOSIDE INDUCES CHROMOSOMAL ABNORMALITIES IN SPERMATOCYTES AND SPERMATOGONIAL STEM CELLS

    Energy Technology Data Exchange (ETDEWEB)

    Marchetti, F; Pearson, F S; Bishop, J B; Wyrobek, A J

    2005-07-15

    Etoposide (ET) is a chemotherapeutic agent widely used in the treatment of leukemia, lymphomas and many solid tumors, such as testicular and ovarian cancers, that affect patients in their reproductive years. The purpose of the study was to use sperm FISH analyses to characterize the long-term effects of ET on male germ cells. We used a mouse model to characterize the induction of chromosomal aberrations (partial duplications and deletions) and whole chromosomal aneuploidies in sperm of mice treated with a clinical dose of ET. Semen samples were collected at 25 and 49 days after dosing to investigate the effects of ET on meiotic pachytene cells and spermatogonial stem-cells, respectively. ET treatment resulted in major increases in the frequencies of sperm carrying chromosomal aberrations in both meiotic pachytene (27- to 578-fold) and spermatogonial stem-cells (8- to 16-fold), but aneuploid sperm were induced only after treatment of meiotic cells (27-fold) with no persistent effects in stem cells. These results demonstrate that male meiotic germ cells are considerably more sensitive to ET than spermatogonial stem-cell and that increased frequencies of sperm with structural aberrations persist after spermatogonial stem-cell treatment. These findings predict that patients who undergo chemotherapy with ET may have transient elevations in the frequencies of aneuploid sperm, but more importantly, may have persistent elevations in the frequencies of sperm with chromosomal aberrations, placing them at higher risk for abnormal reproductive outcomes long after the end of their chemotherapy.

  18. Phenotypic correlations in a patient with ring chromosome 22

    Directory of Open Access Journals (Sweden)

    Demirhan Osman

    2010-01-01

    Full Text Available Ring chromosome 22, a rare cytogenetic anomaly, has been described in over 60 cases in the medical literature. The aim of this report was to present a case carrying ring chromosome 22, and her family. It is a case report of a patient presented at Medical Faculty of Ηukurova University in Turkey. An 8-year-old girl with ring chromosome 22 and her family were evaluated cytogenetically and clinically. A chromosome analysis of the proband revealed a de novo 46,XX,r(22(p11.2;q13 karyotype. Our subject demonstrated the prominent features of this syndrome including profound mental retardation, language impairment, dysmorphic features, lack of speech, hyperactivity, and behavioral disorders. There is lack of consistency between the physical abnormalities that we observed in our subject and those observed for such patients in the literature. The wide range of manifestations observed in patients with this cytogenetic alteration is probably due to size differences in the deleted region.

  19. Deletions at 22q11.2 in idiopathic Parkinson's disease: a combined analysis of genome-wide association data

    Science.gov (United States)

    Mok, Kin Y; Sheerin, Una; Simón-Sánchez, Javier; Salaka, Afnan; Chester, Lucy; Escott-Price, Valentina; Mantripragada, Kiran; Doherty, Karen M; Noyce, Alastair J; Mencacci, Niccolo E; Lubbe, Steven J; Williams-Gray, Caroline H; Barker, Roger A; van Dijk, Karin D; Berendse, Henk W; Heutink, Peter; Corvol, Jean-Christophe; Cormier, Florence; Lesage, Suzanne; Brice, Alexis; Brockmann, Kathrin; Schulte, Claudia; Gasser, Thomas; Foltynie, Thomas; Limousin, Patricia; Morrison, Karen E; Clarke, Carl E; Sawcer, Stephen; Warner, Tom T; Lees, Andrew J; Morris, Huw R; Nalls, Mike A; Singleton, Andrew B; Hardy, John; Abramov, Andrey Y; Plagnol, Vincent; Williams, Nigel M; Wood, Nicholas W

    2016-01-01

    Summary Background Parkinson's disease has been reported in a small number of patients with chromosome 22q11.2 deletion syndrome. In this study, we screened a series of large, independent Parkinson's disease case-control studies for deletions at 22q11.2. Methods We used data on deletions spanning the 22q11.2 locus from four independent case-control Parkinson's disease studies (UK Wellcome Trust Case Control Consortium 2, Dutch Parkinson's Disease Genetics Consortium, US National Institute on Aging, and International Parkinson's Disease Genomics Consortium studies), which were independent of the original reports of chromosome 22q11.2 deletion syndrome. We did case-control association analysis to compare the proportion of 22q11.2 deletions found, using the Fisher's exact test for the independent case-control studies and the Mantel-Haenszel test for the meta-analyses. We retrieved clinical details of patients with Parkinson's disease who had 22q11.2 deletions from the medical records of these patients. Findings We included array-based copy number variation data from 9387 patients with Parkinson's disease and 13 863 controls. Eight patients with Parkinson's disease and none of the controls had 22q11.2 deletions (p=0·00082). In the 8451 patients for whom age at onset data were available, deletions at 22q11.2 were associated with Parkinson's disease age at onset (Mann-Whitney U test p=0·001). Age at onset of Parkinson's disease was lower in patients carrying a 22q11.2 deletion (median 37 years, 95% CI 32·0–55·5; mean 42·1 years [SD 11·9]) than in those who did not carry a deletion (median 61 years, 95% CI 60·5–61·0; mean 60·3 years [SD 12·8]). A 22q11.2 deletion was present in more patients with early-onset (p<0·0001) and late-onset Parkinson's disease (p=0·016) than in controls, and in more patients with early-onset than late-onset Parkinson's disease (p=0·005). Interpretation Clinicians should be alert to the possibility of 22q11.2 deletions in

  20. High-Throughput Analysis of Subtelomeric Chromosome Rearrangements by Use of Array-Based Comparative Genomic Hybridization

    OpenAIRE

    Veltman, Joris A; Schoenmakers, Eric F.P.M.; Eussen, Bert H; Janssen, Irene; Merkx, Gerard; van Cleef, Brigitte; van Ravenswaaij, Conny M.; Brunner, Han G.; Smeets, Dominique; van Kessel, Ad Geurts

    2002-01-01

    Telomeric chromosome rearrangements may cause mental retardation, congenital anomalies, and miscarriages. Automated detection of subtle deletions or duplications involving telomeres is essential for high-throughput diagnosis, but impossible when conventional cytogenetic methods are used. Array-based comparative genomic hybridization (CGH) allows high-resolution screening of copy number abnormalities by hybridizing differentially labeled test and reference genomes to arrays of robotically spot...

  1. Mechanisms of ring chromosome formation, ring instability and clinical consequences

    Directory of Open Access Journals (Sweden)

    Guilherme Roberta S

    2011-12-01

    Full Text Available Abstract Background The breakpoints and mechanisms of ring chromosome formation were studied and mapped in 14 patients. Methods Several techniques were performed such as genome-wide array, MLPA (Multiplex Ligation-Dependent Probe Amplification and FISH (Fluorescent in situ Hybridization. Results The ring chromosomes of patients I to XIV were determined to be, respectively: r(3(p26.1q29, r(4(p16.3q35.2, r(10(p15.3q26.2, r(10(p15.3q26.13, r(13(p13q31.1, r(13(p13q34, r(14(p13q32.33, r(15(p13q26.2, r(18(p11.32q22.2, r(18(p11.32q21.33, r(18(p11.21q23, r(22(p13q13.33, r(22(p13q13.2, and r(22(p13q13.2. These rings were found to have been formed by different mechanisms, such as: breaks in both chromosome arms followed by end-to-end reunion (patients IV, VIII, IX, XI, XIII and XIV; a break in one chromosome arm followed by fusion with the subtelomeric region of the other (patients I and II; a break in one chromosome arm followed by fusion with the opposite telomeric region (patients III and X; fusion of two subtelomeric regions (patient VII; and telomere-telomere fusion (patient XII. Thus, the r(14 and one r(22 can be considered complete rings, since there was no loss of relevant genetic material. Two patients (V and VI with r(13 showed duplication along with terminal deletion of 13q, one of them proved to be inverted, a mechanism known as inv-dup-del. Ring instability was detected by ring loss and secondary aberrations in all but three patients, who presented stable ring chromosomes (II, XIII and XIV. Conclusions We concluded that the clinical phenotype of patients with ring chromosomes may be related with different factors, including gene haploinsufficiency, gene duplications and ring instability. Epigenetic factors due to the circular architecture of ring chromosomes must also be considered, since even complete ring chromosomes can result in phenotypic alterations, as observed in our patients with complete r(14 and r(22.

  2. Multiplex ligation-dependent probe amplification detection of an unknown large deletion of the CREB-binding protein gene in a patient with Rubinstein-Taybi syndrome.

    Science.gov (United States)

    Calì, F; Failla, P; Chiavetta, V; Ragalmuto, A; Ruggeri, G; Schinocca, P; Schepis, C; Romano, V; Romano, C

    2013-01-01

    Rubinstein-Taybi syndrome is a rare autosomal dominant congenital disorder characterized by postnatal growth retardation, psychomotor developmental delay, skeletal anomalies, peculiar facial morphology, and tumorigenesis. Mutations in the gene encoding the cAMP response element-binding protein (CREB, also known as CREBBP or CBP) on chromosome 16p13.3 have been identified. In addition, some patients with low intelligence quotients and autistic features bear large deletions. Based on these observations, we used multiplex ligation-dependent probe amplification to search for large deletions affecting the CREBBP gene in a Rubinstein-Taybi syndrome patient. We identified a novel heterozygote deletion removing five exons (exons 17-21), encoding the histone acetyltransferase domain. We propose the use of multiplex ligation-dependent probe amplification as a fast, accurate and cheap test for detecting large deletions in the CREBBP gene in the sub-group of Rubinstein-Taybi syndrome patients with low intelligence quotients and autistic features. PMID:23315884

  3. 9q22 Deletion - First Familial Case

    Directory of Open Access Journals (Sweden)

    Yamamoto Toshiyuki

    2011-06-01

    Full Text Available Abstract Background Only 29 cases of constitutional 9q22 deletions have been published and all have been sporadic. Most associate with Gorlin syndrome or nevoid basal cell carcinoma syndrome (NBCCS, MIM #109400 due to haploinsufficiency of the PTCH1 gene (MIM *601309. Methods and Results We report two mentally retarded female siblings and their cognitively normal father, all carrying a similar 5.3 Mb microdeletion at 9q22.2q22.32, detected by array CGH (244 K. The deletion does not involve the PTCH1 gene, but instead 30 other gene,s including the ROR2 gene (MIM *602337 which causing both brachydactyly type 1 (MIM #113000 and Robinow syndrome (MIM #268310, and the immunologically active SYK gene (MIM *600085. The deletion in the father was de novo and FISH analysis of blood lymphocytes did not suggest mosaicism. All three patients share similar mild dysmorphic features with downslanting palpebral fissures, narrow, high bridged nose with small nares, long, deeply grooved philtrum, ears with broad helix and uplifted lobuli, and small toenails. All have significant dysarthria and suffer from continuous middle ear and upper respiratory infections. The father also has a funnel chest and unilateral hypoplastic kidney but the daughters have no malformations. Conclusions This is the first report of a familial constitutional 9q22 deletion and the first deletion studied by array-CGH which does not involve the PTCH1 gene. The phenotype and penetrance are variable and the deletion found in the cognitively normal normal father poses a challenge in genetic counseling.

  4. Deletion of 4.4 Mb at 2q33.2q33.3 May Cause Growth Deficiency in a Patient with Mental Retardation, Facial Dysmorphic Features and Speech Delay.

    Science.gov (United States)

    Papoulidis, Ioannis; Paspaliaris, Vassilis; Papageorgiou, Elena; Siomou, Elissavet; Dagklis, Themistoklis; Sotiriou, Sotirios; Thomaidis, Loretta; Manolakos, Emmanouil

    2015-01-01

    A patient with a rare interstitial deletion of chromosomal band 2q33.2q33.3 is described. The clinical features resembled the 2q33.1 microdeletion syndrome (Glass syndrome), including mental retardation, facial dysmorphism, high-arched narrow palate, growth deficiency, and speech delay. The chromosomal aberration was characterized by whole genome BAC aCGH. A comparison of the current patient and Glass syndrome features revealed that this case displayed a relatively mild phenotype. Overall, it is suggested that the deleted region of 2q33 causative for Glass syndrome may be larger than initially suggested. PMID:25925190

  5. Molecular fundamentals of chromosomal mutagenesis

    International Nuclear Information System (INIS)

    Precise quantitative correlation between the yield of chromosome structure damages and the yield of DNA damages is shown when comparing data on molecular and cytogenetic investigations carried out in cultural Mammalia cells. As the chromosome structure damage is to be connected with the damage of its carcass structure, then it is natural that DNA damage in loop regions is not to affect considerably the structure, while DNA damage lying on the loop base and connected with the chromosome carcass is to play a determining role in chromosomal mutagenesis. This DNA constitutes 1-2% from the total quantity of nuclear DNA. If one accepts that damages of these regions of DNA are ''hot'' points of chromosomal mutagenesis, then it becomes clear why 1-2% of preparation damages in a cell are realized in chromosome structural damages

  6. Electochemical detection of chromosome translocation

    DEFF Research Database (Denmark)

    Kwasny, Dorota; Dimaki, Maria; Silahtaroglu, Asli;

    2014-01-01

    Cytogenetics is a study of the cell structure with a main focus on chromosomes content and their structure. Chromosome abnormalities, such as translocations may cause various genetic disorders and heametological malignancies. Chromosome translocations are structural rearrangements of two...... hybridization approach developed for label-free detection of the chromosome translocations. For specific translocation detection it is necessary to determine that the two DNA sequences forming a derivative chromosome are connected, which is achieved by two subsequent hybridization steps. The electrochemical...... impedance spectroscopy was selected as the sensing method on a microfabricated chip with array of 12 electrode sets. Two independent chips (Chip1 and Chip2) were used for targeting the chromosomal fragments involved in the translocation. Each chip was differentially functionalized with DNA probes matching...

  7. Intersections of certain deleted digits sets

    CERN Document Server

    Pedersen, Steen

    2011-01-01

    We consider some properties of the intersection of deleted digits Cantor sets with their translates. We investigate conditions on the set of digits such that, for any t between zero and the dimension of the deleted digits Cantor set itself, the set of translations such that the intersection has Hausdorff dimension equal to t is dense in the set F of translations such that the intersection is non-empty. We make some simple observations regarding properties of the set F, in particular, we characterize when F is an interval, in terms of conditions on the digit set.

  8. Loss of heterozygosity on chromosome 3, bands q24----qter, in a diploid meningioma.

    Science.gov (United States)

    Färber, U; Schneider, G; Schrell, U M; Fahlbusch, P; Adams, E F; Blin, N; Henn, W

    1991-01-01

    Cytogenetic analysis of a meningioma from a 46-year-old female patient exhibited as the sole cytogenetic aberration a deletion on the long arm of one chromosome 3 involving bands 3q24----qter. To verify this finding, RFLP analysis was performed with two polymorphic probes, MOX2 and D3S5. The patient was informative for both single copy probes and demonstrated loss of heterozygosity in the region above whereas chromosome 22 displayed no loss of heterozygosity as judged by a proximal and a distal probe. PMID:1680607

  9. Intraspecific chromosome variability

    Directory of Open Access Journals (Sweden)

    N Dubinin

    2010-12-01

    Full Text Available (Editorial preface. The publication is presented in order to remind us of one of dramatic pages of the history of genetics. It re-opens for the contemporary reader a comprehensive work marking the priority change from plant cytogenetics to animal cytogenetics led by wide population studies which were conducted on Drosophila polytene chromosomes. The year of the publication (1937 became the point of irretrievable branching between the directions of Old World and New World genetics connected with the problems of chromosome variability and its significance for the evolution of the species. The famous book of T. Dobzhansky (1937 was published by Columbia University in the US under the title “Genetics and the origin of species”, and in the shadow of this American ‘skybuilding’ all other works grew dim. It is remarkable that both Dobzhansky and Dubinin come to similar conclusions about the role of chromosomes in speciation. This is not surprising given that they both might be considered as representatives of the Russian genetic school, by their birth and education. Interestingly, Dobzhansky had never referred to the full paper of Dubinin et al. (1937, though a previous short communication in Nature (1936 was included together with all former papers on the related subject. In full, the volume of the original publication printed in the Biological Journal in Moscow comprised 47 pages, in that number 41 pages of the Russian text accompanied by 16 Figs, a table and reference list, and, above all, 6 pages of the English summary. This final part in English is now reproduced in the authors’ version with the only addition being the reference list in the originally printed form.

  10. Reference-assisted chromosome assembly

    OpenAIRE

    Kim, Jaebum; Larkin, Denis M; Cai, Qingle; Asan,; Zhang, Yongfen; Ge, Ri-Li; Auvil, Loretta; Capitanu, Boris; Zhang, Guojie; Lewin, Harris A.; Ma, Jian

    2013-01-01

    One of the most difficult problems in modern genomics is the assembly of full-length chromosomes using next generation sequencing (NGS) data. To address this problem, we developed “reference-assisted chromosome assembly” (RACA), an algorithm to reliably order and orient sequence scaffolds generated by NGS and assemblers into longer chromosomal fragments using comparative genome information and paired-end reads. Evaluation of results using simulated and real genome assemblies indicates that ou...

  11. Idiopathic cases of male infertility from a region in India show low incidence of Y-chromosome microdeletion

    Indian Academy of Sciences (India)

    R Ambasudhan; K Singh; J K Agarwal; S K Singh; A Khanna; R K Sah; I Singh; R Raman

    2003-09-01

    Chromosomal and Y-chromosomal microdeletion analysis has been done in cases of idiopathic infertility with the objective of evaluating the frequency of chromosomal and molecular anomaly as the causal factor of infertility. Barring a few cases of Klinefelter syndrome (XXY or XY/XXY mosaics), no chromosomal anomaly was encountered. Y-microdeletion was analysed by PCR-screening of STSs from different regions of the AZF (AZFa, AZFb, AZFc) on the long arm of the Y, as well as by using DNA probes of the genes RBM, DAZ (Yq), DAZLA (an autosomal homologue of DAZ) and SRY (Yp; sex determining gene). Out of 177 cases examined, 9 (azoospermia – 8 and oligoasthenospermia – 1) showed partial deletion of AZF. The size of deletion varied among patients but AZFc was either totally or partially removed in all of them. In contrast, no deletion was detected in AZFa. Testis biopsy done on a limited number of cases (50) showed diverse stages of spermatogenic arrest with no specific correlation with the genotype. The frequency of Y-chromosome microdeletion in our samples (∼ 5%) is much lower than the frequency (∼ 10%) reported globally and the two previous reports from India. We contend that the frequency may be affected by population structures in different geographical regions.

  12. Some analogies between quantum cloning and quantum deleting

    International Nuclear Information System (INIS)

    We further verify the impossibility of deleting an arbitrary unknown quantum state, and also show it is impossible to delete two nonorthogonal quantum states as a consequence of unitarity of quantum mechanics. A quantum approximate (deterministic) deleting machine and a probabilistic (exact) deleting machine are constructed. The estimation for the global fidelity characterizing the efficiency of the quantum approximate deleting is given. We then demonstrate that unknown nonorthogonal states chosen from a set with their multiple copies can evolve into a linear superposition of multiple deletions and failure branches by a unitary process if and only if the states are linearly independent. It is notable that the proof for necessity is somewhat different from Pati's [Phys. Rev. Lett. 83, 2849 (1999)]. Another deleting machine for the input states that are unnecessarily linearly independent is also presented. The bounds on the success probabilities of these deleting machines are derived. So we expound some preliminary analogies between quantum cloning and deleting

  13. Large, rare chromosomal deletions associated with severe early-onset obesity

    OpenAIRE

    Bochukova, Elena G; Huang, Ni; Keogh, Julia; Henning, Elana; Purmann, Carolin; Blaszczyk, Kasia; Saeed, Sadia; Hamilton-Shield, Julian; Clayton-Smith, Jill; O’Rahilly, Stephen; Hurles, Matthew E; Farooqi, I. Sadaf

    2009-01-01

    Obesity is a highly heritable and genetically heterogeneous disorder1. Here we investigated the contribution of copy number variation to obesity in 300 Caucasian patients with severe early-onset obesity, 143 of whom also had developmental delay. Large (>500 kilobases), rare (

  14. LOSS OF HETEROZYGOSITY ON CHROMOSOME 13 IN SQUAMOUS CELL CARCINOMAS OF THE LARYNX

    Institute of Scientific and Technical Information of China (English)

    Bai Sujuan; Zhang Xue; Wang Jun; Sun Kailai; Fei Shengzhong

    1998-01-01

    Objective: To locate lost region of tumor suppressor gene on chromosome 13q in squamous cell carcinoma of the larynx (LSCC) and to provide clues and evidence for discovering and locating new suppressor gene.Methods: Loss of heterozygosity (LOH) on chromosome 13q was analyzed in 58 LSCC patients by microsatellite polymorphic sequences in loci D13S765 (13q13), RB1.20(13q14.2), D13S133 (13q14.3) and D13S318 (13q21) on chromosome 13 by PCR. Results: There weren't any LOH on chromosome 13q in 3 cases with preinvasive LSCC. Forty-five percentage (24/53) of the 53 invasive LSCC cases showed LOH at one or more loci on chromosome 13q region. The highest percentage of LOH on chromosome 13q was 52% (22/53) at D13S765locus. Conclusion: The deletion region on chromosome 13q was located near by D13S765 locus which is centromeric to RB1. In this region there is suppressor gene, which is related to the genesis and development of LSCC, possibly including RB1. The inactivation of these suppressor genes may be related to the genesis and development of invasive LSCC.

  15. Chromosomal context and replication properties of ARS plasmids in Schizosaccharomyces pombe

    Indian Academy of Sciences (India)

    Aditya S Pratihar; Vishnu P Tripathi; Mukesh P Yadav; Dharani D Dubey

    2015-12-01

    Short, specific DNA sequences called as Autonomously Replicating Sequence (ARS) elements function as plasmid as well as chromosomal replication origins in yeasts. As compared to ARSs, different chromosomal origins vary greatly in their efficiency and timing of replication probably due to their wider chromosomal context. The two Schizosaccharomyces pombe ARS elements, ars727 and ars2OO4, represent two extremities in their chromosomal origin activity - ars727 is inactive and late replicating, while ars2OO4 is a highly active, early-firing origin. To determine the effect of chromosomal context on the activity of these ARS elements, we have cloned them with their extended chromosomal context as well as in the context of each other in both orientations and analysed their replication efficiency by ARS and plasmid stability assays. We found that these ARS elements retain their origin activity in their extended/altered context. However, deletion of a 133-bp region of the previously reported ars727-associated late replication enforcing element (LRE) caused advancement in replication timing of the resulting plasmid. These results confirm the role of LRE in directing plasmid replication timing and suggest that the plasmid origin efficiency of ars2OO4 or ars727 remains unaltered by the extended chromosomal context.

  16. Simulation of the Formation of DNA Double Strand Breaks and Chromosome Aberrations in Irradiated Cells

    Science.gov (United States)

    Plante, Ianik; Ponomarev, Artem L.; Wu, Honglu; Blattnig, Steve; George, Kerry

    2014-01-01

    The formation of DNA double-strand breaks (DSBs) and chromosome aberrations is an important consequence of ionizing radiation. To simulate DNA double-strand breaks and the formation of chromosome aberrations, we have recently merged the codes RITRACKS (Relativistic Ion Tracks) and NASARTI (NASA Radiation Track Image). The program RITRACKS is a stochastic code developed to simulate detailed event-by-event radiation track structure: [1] This code is used to calculate the dose in voxels of 20 nm, in a volume containing simulated chromosomes, [2] The number of tracks in the volume is calculated for each simulation by sampling a Poisson distribution, with the distribution parameter obtained from the irradiation dose, ion type and energy. The program NASARTI generates the chromosomes present in a cell nucleus by random walks of 20 nm, corresponding to the size of the dose voxels, [3] The generated chromosomes are located within domains which may intertwine, and [4] Each segment of the random walks corresponds to approx. 2,000 DNA base pairs. NASARTI uses pre-calculated dose at each voxel to calculate the probability of DNA damage at each random walk segment. Using the location of double-strand breaks, possible rejoining between damaged segments is evaluated. This yields various types of chromosomes aberrations, including deletions, inversions, exchanges, etc. By performing the calculations using various types of radiations, it will be possible to obtain relative biological effectiveness (RBE) values for several types of chromosome aberrations.

  17. Mechanisms of induction of chromosomal aberrations and their detection by fluorescence in situ hybridization

    International Nuclear Information System (INIS)

    Recently introduced fluorescence in situ hybridization (FISH) technique employing chromosome specific DNA libraries as well as region specific DNA probes (e.g., centromere, telomere) have helped to analyse chromosomal aberrations in great detail and thus have given some new insights into the mechanisms of induction of chromosomal aberrations. The relative proportion of induction of translocations and dicentrics by ionising radiation was studied in human, mice and Chinese hamster cells. Many of the studies point to the differences between the mechanisms of induction of dicentrics and translocations. Preliminary results obtained in our laboratory using arm specific probes for human chromosomes 1 and 3 indicate that the aberrations between the arms appear to be more than expected on a random basis. By employing telomeric probes the frequencies of interstitial deletions were found to be high and similar to the frequencies of dicentrics both in human and mouse lymphocytes. A recent study with human chromosome specific probes clearly shows variation of sensitivity of chromosomes for the induction of exchange aberrations. Radiation response studies with Chinese hamster cells using telomeric probes, suggest that telomeric sequences, especially interstitial ones appear to be an important factor in the origin of both spontaneous and induced chromosomal aberrations

  18. The urgent necessity for an all-encompassing ideal of re­form for South Africa 1

    Directory of Open Access Journals (Sweden)

    P. J. van Niekerk

    1986-03-01

    Full Text Available In view of the ironies of the realisation of the democratic ideal, which often do not answer to the exaggerated expectations of the participants, the idea of the regstaat is investigated as an "overriding purpose or transcending value" for reform in South Africa . Important facets emerge with regard to the concept of the regstaat in the legal and political development of the Greeks and Romans w ith the institutionalization of the idea th a t the state is a res publica, and especially the influence of the Roman ius gentium is visible in the legal and political development in Western Europe via the reception of Roman law in the development of the modern differentiated civil law which is based on the fundamental human rights of civil freedom and equality (independent of nationality, public legal status, race, religion etc. of all people and all societal forms within the territory of the state. A study of the development of the regstaat in England indicates that the institutionalization of the concept of rule of law developed during the "Glorious Revolution" prior to the actual development of the individual political right of the English citizen. Through this it becomes clear that the institutionalization of the regstaat is not necessarily dependent on democracy. While the idea of democracy stresses political freedom and participation, the concept of rule of law goes much further and encompasses not only the sphere of public law (within which political rights constitute apart but also the sphere of civil law and the curtailment of the power of government with respect to the sphere of internal jurisdiction of the non-state societal forms. Be­ cause of the problems which reform in South Africa faces, the emphasis on political participation for the immediate future can be counter-productive for the institutionalization of the regstaat. The concept of the regstaat which has to be incorporated in a declaration of intent will link reform in South Africa

  19. Birth of a child with Down syndrome in a family transmitting an unusual chromosome 22 arising from a translocation between chromosomes 21 and an inverted chromosome 22

    Energy Technology Data Exchange (ETDEWEB)

    Aviv, H.A.; Desposito, F. [UMDNJ-NJ Medical School, Newark, NJ (United States); Lieber, C. [Hackensack Medical Center, NJ (United States)

    1994-09-01

    Chromosomal analysis of a child with Down syndrome resulted in the identification of a family with an unusual translocation and in the definition of the translocation breakpoints. Studies were performed on the child, his siblings, mother, mother`s sister, and grandmother. All of the family members were carriers of the translocation. We performed G-banding, silver stain, C-banding, and hybridization with the following FISH probes (Oncor): {alpha}-satellite 13/21; {beta}-satellite, coatasome 21 and 22, and the probes for chromosome 22 at 22q11 (DiGeorge region) and 22q13.3 (control region). Using the banding techniques and probes, we characterized the karyotype as: 45,XX,-21,-22,+der(22),t(21;22)(22qter{r_arrow}22q11.2::22p13{r_arrow}22q11.2::21q11.2{r_arrow}21qter). The effect of deletion of 21q11.2 and the break of chromosome 22 in the DiGeorge region in this family is not clear. However, the presence of the translocation increases the risk of family members of conceiving children with Down syndrome.

  20. Chromosome Connections: Compelling Clues to Common Ancestry

    Science.gov (United States)

    Flammer, Larry

    2013-01-01

    Students compare banding patterns on hominid chromosomes and see striking evidence of their common ancestry. To test this, human chromosome no. 2 is matched with two shorter chimpanzee chromosomes, leading to the hypothesis that human chromosome 2 resulted from the fusion of the two shorter chromosomes. Students test that hypothesis by looking for…

  1. Positional cloning of disease genes on chromosome 16

    Energy Technology Data Exchange (ETDEWEB)

    Doggett, N. [Los Alamos National Lab., NM (United States); Bruening, M. [Leiden Univ. (Netherlands); Callen, D. [Adelaide Women`s and Children`s Hospital, North Adelaide, South Australia (Australia); Gardiner, M. [University Coll., London (United Kingdom); Lerner, T. [Massachusetts General Hospital, Boston, MA (United States)

    1996-04-01

    The project seeks to elucidate the molecular basis of an important genetic disease (Batten`s disease) by molecular cloning of the affected gene by utilizing an overlapping clone map of chromosome 16. Batten disease (also known as juvenile neuronal ceroid lipofuscinosis) is a recessively inherited neurodegenerative disorder of childhood characterized by progressive loss of vision, seizures, and psychomoter disturbances. The Batten disease gene was genetically mapped to the chromosome region 16p 12.1 in close linkage with the genetic markers D16S299 and D16S298. Exon amplification of a cosmid containing D16S298 yielded a candidate gene that was disrupted by a 1 kb genomic deletion in all patients containing the most common haplotype for the disease. Two separate deletions and a point mutation altering a splice site in three unrelated families have confirmed the gene as the Batten disease gene. The disease gene encodes a novel 438 amino acid membrane binding protein of unknown function.

  2. YAC and cosmid contigs encompassing the Fukuyama-type congenital muscular dystrophy (FCMD) candidate region on 9q31

    Energy Technology Data Exchange (ETDEWEB)

    Miyake, Masashi; Nakahori, Yutaka; Matsushita, Ikumi [Univ. of Tokyo (Japan)] [and others

    1997-03-01

    Fukuyama-type congenital muscular dystrophy (FCMD), the second most common form of childhood muscular dystrophy in Japan, is an autosomal recessive severe muscular dystrophy associated with an anomaly of the brain. We had mapped the FCMD gene to an approximately 5-cM interval between D9S127 and D9S2111 on 9q31-q33 and had also found evidence for linkage disequilibrium between FCMD and D9S306 in this candidate region. Through further analysis, we have defined another marker, D9S172, which showed stronger linkage disequilibrium than D9S306. A yeast artificial chromosome (YAC) contig spanning 3.5 Mb, which includes this D9S306-D9S172 interval on 9q31, has been constructed by a combination of sequence-tagged site, Alu-PCR, and restriction mapping. Also, cosmid clones subcloned from the YAC were assembled into three contigs, one of which contains D9S2107, which showed the strongest linkage disequilibrium with FCMD. These contigs also allowed us to order the markers as follows: cen-D9S127-({approximately}800 kb)-D9S306 (identical to D9S53)-({approximately}700 kb)-A107XF9-({approximately}500 kb)-D9S172-({approximately}30 kb)-D9S299 (identical to D9S774)-({approximately}120 kb)-WI2269-tel. Thus, we have constructed the first high-resolution physical map of the FCMD candidate region. The YAC and cosmid contigs established here will be a crucial resource for identification of the FCMD gene and other genes in this region. 37 refs., 7 figs., 2 tabs.

  3. Microarray based analysis of an inherited terminal 3p26.3 deletion, containing only the CHL1 gene, from a normal father to his two affected children

    Directory of Open Access Journals (Sweden)

    Lerone Margherita

    2011-04-01

    Full Text Available Abstract Background terminal deletions of the distal portion of the short arm of chromosome 3 cause a rare contiguous gene disorder characterized by growth retardation, developmental delay, mental retardation, dysmorphisms, microcephaly and ptosis. The phenotype of individuals with deletions varies from normal to severe. It was suggested that a 1,5 Mb minimal terminal deletion including the two genes CRBN and CNTN4 is sufficient to cause the syndrome. In addition the CHL1 gene, mapping at 3p26.3 distally to CRBN and CNTN4, was proposed as candidate gene for a non specific mental retardation because of its high level of expression in the brain. Methods and Results we describe two affected siblings in which array-CGH analysis disclosed an identical discontinuous terminal 3p26.3 deletion spanning less than 1 Mb. The deletion was transmitted from their normal father and included only the CHL1 gene. The two brothers present microcephaly, light mental retardation, learning and language difficulties but not the typical phenotype manifestations described in 3p- syndrome. Conclusion a terminal 3p26.3 deletion including only the CHL1 gene is a very rare finding previously reported only in one family. The phenotype of the affected individuals in the two families is very similar and the deletion has been inherited from an apparently normal parent. As already described for others recurrent syndromes with variable phenotype, these findings are challenging in genetic counselling because of an evident variable penetrance.

  4. Chromosome analysis and sorting

    Czech Academy of Sciences Publication Activity Database

    Doležel, Jaroslav; Kubaláková, Marie; Suchánková, Pavla; Kovářová, Pavlína; Bartoš, Jan; Šimková, Hana

    Weinheim : Wiley-VCH, 2007 - (Doležel, J.; Greilhuber, J.; Suda, J.), s. 373-403 ISBN 978-3-527-31487-4 R&D Projects: GA ČR GA521/04/0607; GA ČR GP521/05/P257; GA ČR GD521/05/H013; GA MŠk(CZ) LC06004 Grant ostatní: Mendelova zemědělská a lesnická univerzita v Brně / Agronomická fakulta(CZ) ME 844 Institutional research plan: CEZ:AV0Z5038910 Source of funding: V - iné verejné zdroje ; V - iné verejné zdroje ; V - iné verejné zdroje ; V - iné verejné zdroje ; V - iné verejné zdroje Keywords : Plant flow cytometry * chromosome sorting * flow cytogenetics Subject RIV: EB - Genetics ; Molecular Biology http://books. google .com/books?id=3cwakORieqUC&pg=PA373&lpg=PA373&dq=Chromosome+analysis+and+sorting&source=web&ots=8IyvJlBQyq&sig=_NlXyQQgBCwpj1pTC9YITvvVZqU

  5. Deletion of GPIHBP1 causing severe chylomicronemia.

    Science.gov (United States)

    Rios, Jonathan J; Shastry, Savitha; Jasso, Juan; Hauser, Natalie; Garg, Abhimanyu; Bensadoun, André; Cohen, Jonathan C; Hobbs, Helen H

    2012-05-01

    Lipoprotein lipase (LPL) is a hydrolase that cleaves circulating triglycerides to release fatty acids to the surrounding tissues. The enzyme is synthesized in parenchymal cells and is transported to its site of action on the capillary endothelium by glycophosphatidylinositol (GPI)-anchored high-density lipoprotein-binding protein 1 (GPIHBP1). Inactivating mutations in LPL; in its cofactor, apolipoprotein (Apo) C2; or in GPIHBP1 cause severe hypertriglyceridemia. Here we describe an individual with complete deficiency of GPIHBP1. The proband was an Asian Indian boy who had severe chylomicronemia at 2 months of age. Array-based copy-number analysis of his genomic DNA revealed homozygosity for a 17.5-kb deletion that included GPIHBP1. A 44-year-old aunt with a history of hypertriglyceridemia and pancreatitis was also homozygous for the deletion. A bolus of intravenously administered heparin caused a rapid increase in circulating LPL and decreased plasma triglyceride levels in control individuals but not in two GPIHBP1-deficient patients. Thus, short-term treatment with heparin failed to attenuate the hypertriglyceridemia in patients with GPIHBP1 deficiency. The increasing resolution of copy number microarrays and their widespread adoption for routine cytogenetic analysis is likely to reveal a greater role for submicroscopic deletions in Mendelian conditions. We describe the first neonate with complete GPIHBP1 deficiency due to homozygosity for a deletion of GPIHBP1. PMID:22008945

  6. Sequence analysis of 17 NRXN1 deletions

    DEFF Research Database (Denmark)

    Hoeffding, Louise Kristine Enggaard; Hansen, Thomas; Ingason, Andrés;

    2014-01-01

    molecular mechanisms governing such genomic rearrangements may increase our understanding of disease pathology and evolutionary processes. Here we analyse 17 carriers of non-recurrent deletions in the NRXN1 gene, which have been associated with neurodevelopmental disorders, e.g. schizophrenia, autism and...

  7. Union-Find with Constant Time Deletions

    DEFF Research Database (Denmark)

    Alstrup, Stephen; Thorup, Mikkel; Gørtz, Inge Li;

    2014-01-01

    operations performed, and α_M/N_(n) is a functional inverse of Ackermann’s function. They left open the question whether delete operations can be implemented more efficiently than find operations, for example, in o(log n) worst-case time. We resolve this open problem by presenting a relatively simple...

  8. Rubinstein-Taybi syndrome caused by submicroscopic deletions within 16p13. 3

    Energy Technology Data Exchange (ETDEWEB)

    Breuning, M.H.; Dauwerse, H.G.; Fugazza, G.; Saris, J.J.; Spruit, L.; Winjnen, H.; Beverstock, G.C.; Ommen, G.J.B. van (Leiden Univ. (Netherlands)); Tommerup, N. (John F. Kennedy Inst., Glostrup (Denmark) Avd. for Medisinsk Genetikk, Oslo (Norway)); Hagen, C.B. van der (John F. Kennedy Inst., Glostrup (Denmark)); Imaizumi, Kiyoshi; Kuroki, Yoshikazu (Kanagawa Children' s Medical Center, Yokohama (Japan)); Boogaard, M.J. van den; Pater, J.M. de; Hennekam, R.C.M. (Clinical Genetics Center, Utrecht (Netherlands)); Mariman, E.C.M.; Hamel, B.C.J. (University Hospital, Nijmegen (Netherlands)); Himmelbauer, H.; Frischauf, A.M. (Imperial Cancer Research Fund Laboratories, London (United Kingdom)); Stallings, R.L. (Los Alamos National Lab., NM (United States))

    1993-02-01

    The Rubinstein-Taybi syndrome (RTS) is a well-defined complex of congenital malformations characterized by facial abnormalities, broad thumbs and big toes, and mental retardation. The breakpoint of two distinct reciprocal translocations occurring in patients with a clinical diagnosis of RTS was located to the same interval on chromosome 16, between the cosmids N2 and RT1, in band 16p13.3. By using two-color fluorescence in situ hybridization, the signal from RT1 was found to be missing from one chromosome 16 in 6 of 24 patients with RTS. The parents of five of these patients did not show a deletion of RT1, indicating a de novo rearrangement. RTS is caused by submicroscopic interstitial deletions within 16p13.3 in approximately 25% of the patients. The detection of microdeletions will allow the objective confirmation of the clinical diagnosis in new patients and provides an excellent tool for the isolation of the gene causally related to the syndrome. 32 refs., 2 figs.

  9. Deletion of the App-Runx1 region in mice models human partial monosomy 21

    Directory of Open Access Journals (Sweden)

    Thomas Arbogast

    2015-06-01

    Full Text Available Partial monosomy 21 (PM21 is a rare chromosomal abnormality that is characterized by the loss of a variable segment along human chromosome 21 (Hsa21. The clinical phenotypes of this loss are heterogeneous and range from mild alterations to lethal consequences, depending on the affected region of Hsa21. The most common features include intellectual disabilities, craniofacial dysmorphology, short stature, and muscular and cardiac defects. As a complement to human genetic approaches, our team has developed new monosomic mouse models that carry deletions on Hsa21 syntenic regions in order to identify the dosage-sensitive genes that are responsible for the symptoms. We focus here on the Ms5Yah mouse model, in which a 7.7-Mb region has been deleted from the App to Runx1 genes. Ms5Yah mice display high postnatal lethality, with a few surviving individuals showing growth retardation, motor coordination deficits, and spatial learning and memory impairments. Further studies confirmed a gene dosage effect in the Ms5Yah hippocampus, and pinpointed disruptions of pathways related to cell adhesion (involving App, Cntnap5b, Lgals3bp, Mag, Mcam, Npnt, Pcdhb2, Pcdhb3, Pcdhb4, Pcdhb6, Pcdhb7, Pcdhb8, Pcdhb16 and Vwf. Our PM21 mouse model is the first to display morphological abnormalities and behavioural phenotypes similar to those found in affected humans, and it therefore demonstrates the major contribution that the App-Runx1 region has in the pathophysiology of PM21.

  10. Large fragment deletion using a CRISPR/Cas9 system in Saccharomyces cerevisiae.

    Science.gov (United States)

    Hao, Huanhuan; Wang, Xiaofei; Jia, Haiyan; Yu, Miao; Zhang, Xiaoyu; Tang, Hui; Zhang, Liping

    2016-09-15

    Large chromosomal modifications have been performed in natural and laboratory evolution studies and hold tremendous potential for use in foundational research, medicine, and biotechnology applications. Recently, the type II bacterial Clustered Regularly Interspaced Short Palindromic Repeat and CRISPR-associated (CRISPR/Cas9) system has emerged as a powerful tool for genome editing in various organisms. In this study, we applied the CRISPR/Cas9 system to preform large fragment deletions in Saccharomyces cerevisiae and compared the performance activity to that of a traditional method that uses the Latour system. Here we report in S. Cerevisiae the CRIPR/Cas9 system has been used to delete fragments exceeding 30 kb. The use of the CRISPR/Cas9 system for generating chromosomal segment excision showed some potential advantages over the Latour system. All the results indicated that CRISPR/Cas9 system was a rapid, efficient, low-cost, and versatile method for genome editing and that it can be applied in further studies in the fields of biology, agriculture, and medicine. PMID:27402178

  11. Diagnostic Detection of Allelic Losses and Imbalances by Next-Generation Sequencing: 1p/19q Co-Deletion Analysis of Gliomas.

    Science.gov (United States)

    Dubbink, Hendrikus J; Atmodimedjo, Peggy N; van Marion, Ronald; Krol, Niels M G; Riegman, Peter H J; Kros, Johan M; van den Bent, Martin J; Dinjens, Winand N M

    2016-09-01

    Cancer cells are genomically unstable and accumulate tumor type-specific molecular aberrations, which may represent hallmarks for predicting prognosis and targets for therapy. Co-deletion of chromosomes 1p and 19q marks gliomas with an oligodendroglioma component and predicts a better prognosis and response to chemotherapy. In the current study, we present a novel method to detect chromosome 1p/19q co-deletion or loss of heterozygosity (LOH) in a diagnostic setting, based on single-nucleotide polymorphism (SNP) analysis and next-generation sequencing (NGS). We selected highly polymorphic SNPs distributed evenly over both chromosome arms. To experimentally determine the sensitivity and specificity of targeted SNP analysis, we used DNAs extracted from 49 routine formalin-fixed, paraffin-embedded glioma tissues and compared the outcome with diagnostic microsatellite-based LOH analysis and calculated estimates. We show that targeted SNP analysis by NGS allows reliable detection of 1p and/or 19q deletion in a background of 70% of normal cells according to calculated outcomes, is more sensitive than microsatellite-based LOH analysis, and requires much less DNA. This specific and sensitive SNP assay is broadly applicable for simultaneous allelic imbalance analysis of multiple genomic regions and can be incorporated easily into NGS mutation analyses. The combined mutation and chromosomal imbalance analysis in a single NGS assay is suited perfectly for routine glioma diagnostics and other diagnostic molecular pathology applications. PMID:27461031

  12. Disruption of the ProSAP2 Gene in a t(12;22)(q24.1;q13.3) Is Associated with the 22q13.3 Deletion Syndrome

    OpenAIRE

    Bonaglia, Maria Clara; Giorda, Roberto; Borgatti, Renato; Felisari, Giorgio; Gagliardi, Chiara; Selicorni, Angelo; Zuffardi, Orsetta

    2001-01-01

    The terminal 22q13.3 deletion syndrome is characterized by severe expressive-language delay, mild mental retardation, hypotonia, joint laxity, dolichocephaly, and minor facial dysmorphisms. We identified a child with all the features of 22q13.3 deletion syndrome. The patient's karyotype showed a de novo balanced translocation between chromosomes 12 and 22, with the breakpoint in the 22q13.3 critical region of the 22q distal deletion syndrome [46, XY, t(12;22)(q24.1;q13.3)]. FISH investigation...

  13. Deletion mutation as a means of isolating avirulence genes in flax rust.

    Science.gov (United States)

    Timmis, J N; Whisson, D L; Binns, A M; Mayo, M J; Mayo, G M

    1990-05-01

    The interaction between flax rust,Melampsora lini, and its host, flax,Linum usitatissimum, has been extensively studied, and certain genetic features make the system an appropriate choice to utilize in isolating genes conferring avirulence in rust. A mutant that was selected for virulence on Lx plants was isolated, after treatment with gamma rays, from a strain that is genotypicallyA-L5,A-L6,A-L7,A-Lx/A-L5,A-L6,a-L7,a-Lx. These four specificities are tightly linked. Breeding tests showed that this mutant was genotypicallyA-L5,A-L6,a-L7,a-Lx/a-L5,a-L6,a-L7,a-Lx and, when made homozygous for the mutant chromosome, was virulent onL5,L6,L7, andLx. This result excludes somatic recombination as a source of the mutation and indicates deletion as a likely cause. A 250 bp genomic sequence from a strain of rust homozygous for these four linked avirulence genes (A-L5,A-L6,A-L7,A-Lx) was isolated, using a method that allows the differential cloning of the specific DNA sequences located within a deletion in the mutant genome. This clone hybridized to two EcoRI bands in genomic DNA from the strain homozygous for the four linked avirulence genes and from the strain homozygousA-L5 andA-L6 and heterozygousA-L7 andA-Lx, but showed no homology to DNA from the strain carrying the putative chromosomal deletion. The correlation between the genetically characterized deletion mutation and the isolation of a sequence from within a region of chromosome missing from this strain of rust suggests that this 250 bp tract may be part of, or closely linked to, the defined set of avirulence genes. PMID:24226362

  14. The gene for replication factor C subunit 2 (RFC2) is within the 7q11.23 Williams syndrome deletion

    Energy Technology Data Exchange (ETDEWEB)

    Peoples, R.; Perez-Jurado, L.; Francke, U.; Yu-Ker Wang [Stanford Univ. Medical Center, CA (United States); Kaplan, P. [Children`s Hospital of Philadelphia, PA (United States)

    1996-06-01

    Williams syndrome (WS) is a developmental disorder with multiple system manifestations, including supraval var aortic stenosis (SVAS), peripheral pulmonic stenosis, connective tissue abnormalities, short stature, characteristic personality profile and cognitive deficits, and variable hypercalcemia in infancy. It is caused by heterozygosity for a chromosomal deletion of part of band 7q11.23 including the elastin locus (ELN). Since disruption of the ELN gene causes autosomal dominant SVAS, it is assumed that ELN haploinsufficiency is responsible for the cardiovascular features of WS. The deletion that extends from the ELN locus in both directions is {ge}200 kb in size, although estimates of {ge}2 Mb are suggested by high-resolution chromosome banding and physical mapping studies. We have searched for additional dosage-sensitive genes within the deletion that may be responsible for the noncardiovascular features. We report here that the gene for replication factor C subunit 2 (RFC2) maps within the WS deletion region and was found to be deleted in all of 18 WS patients studied. The protein product of RFC2 is part of a multimeric complex involved in DNA elongation during replication. 14 refs., 3 figs.

  15. Delineating Rearrangements in Single Yeast Artificial Chromosomes by Quantitative DNA Fiber Mapping

    OpenAIRE

    Weier, Heinz-Ulrich G.; Greulich-Bode, Karin M.; Wu, Jenny; Duell, Thomas

    2009-01-01

    Cloning of large chunks of human genomic DNA in recombinant systems such as yeast or bacterial artificial chromosomes has greatly facilitated the construction of physical maps, the positional cloning of disease genes or the preparation of patient-specific DNA probes for diagnostic purposes. For this process to work efficiently, the DNA cloning process and subsequent clone propagation need to maintain stable inserts that are neither deleted nor otherwise rearranged. Some regions of the human g...

  16. Y-Chromosome Variation in Hominids: Intraspecific Variation Is Limited to the Polygamous Chimpanzee

    OpenAIRE

    Gabriele Greve; Evguenia Alechine; Pasantes, Juan J.; Christine Hodler; Wolfram Rietschel; Robinson, Terence J.; Werner Schempp

    2011-01-01

    BACKGROUND: We have previously demonstrated that the Y-specific ampliconic fertility genes DAZ (deleted in azoospermia) and CDY (chromodomain protein Y) varied with respect to copy number and position among chimpanzees (Pan troglodytes). In comparison, seven Y-chromosomal lineages of the bonobo (Pan paniscus), the chimpanzee's closest living relative, showed no variation. We extend our earlier comparative investigation to include an analysis of the intraspecific variation of these genes in go...

  17. Y-Chromosome Variation in Hominids: Intraspecific Variation Is Limited to the Polygamous Chimpanzee

    OpenAIRE

    Greve, Gabriele; Alechine, Evguenia; Pasantes, Juan J.; Hodler, Christine; Rietschel, Wolfram; Robinson, Terence J; Schempp, Werner

    2011-01-01

    Background We have previously demonstrated that the Y-specific ampliconic fertility genes DAZ (deleted in azoospermia) and CDY (chromodomain protein Y) varied with respect to copy number and position among chimpanzees (Pan troglodytes). In comparison, seven Y-chromosomal lineages of the bonobo (Pan paniscus), the chimpanzee's closest living relative, showed no variation. We extend our earlier comparative investigation to include an analysis of the intraspecific variation of these genes in gor...

  18. Screening for Y chromosome microdeletions in idiopathic and nonidiopathic infertile men with varicocele and cryptorchidism

    Institute of Scientific and Technical Information of China (English)

    SONG Ning-hong; WU Hong-fei; ZHANG Wei; ZHUO Zuo-min; QIAN Li-xing; HUA Li-xing; GUO Lin; FENG Ning-han

    2005-01-01

    Background Cytogenetic and molecular studies of azoospermic and oligozoospermic males have suggested the presence of azoospermia factors (AZF) in the Y chromosome. Deletion in AZF regions has been reported to disrupt spermatogenesis and cause infertility. Several candidate genes responsible for spermatogenesis have been identified in this region and some of them are thought to be functional in human spermatogenesis. And we reported clinical and molecular studies of Y chromosome microdeletions in Chinese. This study aimed at assessing the frequency of microdeletions in Chinese men with idiopathic and nonidiopathic infertility problems and dicussing the clinical significance of the AZF region.Methods In this study, we screened 143 infertile men (62 with idiopathic infertilitas and 81 with nonidiopathic infertilitas), in whom karyotype, sperm count, hormonal parameters and fine needle aspiration cytology were evaluated. Genomic DNA was extracted from the peripheral leukocytes. Molecular analysis was performed by two multiplex polymerase chain reactions (PCR) using a set of a sequence tagged sites (STS) from 3 different regions of the Y chromosome: AZFa (sY84, sY86), AZFb (sY127, sY134), AZFc (sY254, sY255).Results Nineteen point four percent of idiopathic males (12/62, 19.4%) had microdeletions of either the AZFa, AZFb, AZFc or AZFb+c region. Significantly, a high frequency of microdeletions (9/81, 11.1%) was found in nonidiopathic patients with varicocele and cryptorchidism. No deletions were found in healthy fertile men. There were no significant differences in the localization and extent of deletions between idiopathic and nonidiopathic patients.Conclusions The knowledge of the presence of these deletions in idiopathic and nonidiopathic cases is important to understand the prognosis, better management and counsel these patients accordingly. Furthermore, a more extended screening for Y chromosome microdeletions in idiopathic and nonidiopathic men, particularly

  19. Chromosomal changes detected by fluorescence in situ hybridization in patients with acute lymphoblastic leukemia

    Institute of Scientific and Technical Information of China (English)

    ZHANG Lijun 张丽君; PARKHURST JB; KERN WF; SCOTT KV; NICCUM D; MULVIHILL JJ; LI Shibo 李师伯

    2003-01-01

    Objectives To investigate patients with acute lymphoblastic leukemia (ALL) for TEL/AML1 fusion, BCR/ABL fusion, MLL gene rearrangements, and numerical changes of chromosomes 4, 10, 17 and 21 by fluorescence in situ hybridization (FISH) and to determine the relationship and the significance of those findings.Methods Fifty-one American patients (34 men and 17 women) were included in this study. Of them there were 41 patients with pro-B cell type ALL, 9 with B cell type ALL and 1 with T cell type ALL. Chromosome metaphases of each sample were prepared according to standard protocols. Fluorescence in situ hybridization was performed using commercially available DNA probes, including whole chromosome painting probes, locus specific probes, specific chromosome centromere probes and dual color/multiple color translocation fusion probes. The digital image analysis was carried out using Cytovision and Quips FISH programs.Results An overall incidence of chromosomal anomalies, including t (9;22), MLL gene rearrangements, t (12;21), and numerical chromosomal anomalies of chromosomes 4, 10, 17 and 21 was found in 33 patients (65%). Thirty-one of them were pediatric patients and two adults. The t (12;21) was the commonest chromosomal anomaly detected in this population; 14 out of the 45 pediatric patients (31%) were positive for TEL/AML1 fusion, among which three had an additional derivative 21 [t (12;21)], four had a deletion of 12p and two had an extra copy of chromosome 21. All 14 patients with positive TEL/AML1 fusion had ALL pre-B cell or B-cell lineage according to standard immunotyping. The percentage of cells with fusion signals ranged from 20% to 80%. All fourteen patients positive for TEL/AML1 gene fusion were mosaic. Three out of the 14 patients positive for the TEL/AML1 gene fusion were originally reported to be culture failures and none of the remaining eleven samples had been found to have chromosome 12 abnormalities by conventional cytogenetic techniques. All

  20. Chromosome Aberrations of East Asian Bullfrog (Hoplobatrachus rugulosus around a Gold Mine Area with Arsenic Contamination

    Directory of Open Access Journals (Sweden)

    Atidtaya Suttichaiya

    2016-01-01

    Full Text Available The objectives of this study are to investigate the chromosome aberrations of the East Asian Bullfrog (Hoplobatrachus rugulosus in the gold mine area compared to an unaffected area. Three H. rugulosus were collected, and chromosome aberrations were studied using bone marrow. The level of arsenic was measured in water, sediment and H. rugulosus samples. The average concentrations of arsenic in the water and sediment samples from the gold mine and unaffected areas were 0.03 ± 0.003 mg/l and not detected in water as well as 351.59 ± 5.73 and 1.37 ± 1.07 mg/kg in sediment, respectively. The gold mine values were higher than the permissible limit of the water and soil quality standards, but the arsenic concentrations in the samples from the unaffected area were within prescribed limit. The average concentrations of arsenic in H. rugulosus samples from the gold mine and unaffected areas were 0.39 ± 0.30 and 0.07 ± 0.01 mg/kg, respectively, which were both lower than the standard of arsenic contamination in food. The diploid chromosome number of H. rugulosus in both areas was 2n=26, and the percentage of chromosome breakages of H. rugulosus in the gold mine area were higher than the unaffected area. There were eight types of chromosome aberrations, including a single chromatid gap, isochromatid gap, single chromatid break, isochromatid break, centric fragmentation, deletion, fragmentation and translocation. The most common chromosome aberration in the samples from the affected area was deletion. The difference in the percentage of chromosome breakages in H. rugulosus from both areas was statistically significant (p<0.05.