6 results on '"Onat, O. Emre"'
Search Results
2. Human CRY1 variants associate with attention deficit/hyperactivity disorder
- Author
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Onat, O. Emre, Kars, M. Ece, Gul, Seref, Bilguvar, Kaya, Wu, Yiming, Ozhan, Ayse, Aydin, Cihan, Basak, A. Nazli, Trusso, M. Allegra, Goracci, Arianna, Fallerini, Chiara, Renieri, Alessandra, Casanova, Jean-Laurent, Itan, Yuval, Atbasoglu, Cem E., Saka, Meram C., Kavakli, Halil, and Ozcelik, Tayfun
- Subjects
France. National Research Agency -- Analysis ,Thermo Fisher Scientific Inc. ,Sleep -- Genetic aspects -- Analysis ,Insomnia -- Genetic aspects ,Medical schools -- Analysis ,Scientific equipment industry -- Genetic aspects -- Analysis ,Health care industry ,Bilkent University - Abstract
Attention deficit/hyperactivity disorder (ADHD) is a common and heritable phenotype frequently accompanied by insomnia, anxiety, and depression. Here, using a reverse phenotyping approach, we report heterozygous coding variations in the core circadian clock gene cryptochrome 1 in 15 unrelated multigenerational families with combined ADHD and insomnia. The variants led to functional alterations in the circadian molecular rhythms, providing a mechanistic link to the behavioral symptoms. One variant, CRY1[DELTA]11 c.1657+3A>C, is present in approximately 1% of Europeans, therefore standing out as a diagnostic and therapeutic marker. We showed by exome sequencing in an independent cohort of patients with combined ADHD and insomnia that 8 of 62 patients and 0 of 369 controls carried CRY1[DELTA]11. Also, we identified a variant, CRY1[DELTA]6 c.825+1G>A, that shows reduced affinity for BMAL1/CLOCK and causes an arrhythmic phenotype. Genotype-phenotype correlation analysis revealed that this variant segregated with ADHD and delayed sleep phase disorder (DSPD) in the affected family. Finally, we found in a phenome-wide association study involving 9438 unrelated adult Europeans that CRY1[DELTA]11 was associated with major depressive disorder, insomnia, and anxiety. These results defined a distinctive group of circadian psychiatric phenotypes that we propose to designate as 'circiatric' disorders., Introduction Sleep is genetically regulated by the circadian rhythm. Disruption of this rhythm leads to aberrant sleep patterns (1-4). Sleep is also frequently disturbed in individuals with psychiatric disorders. For [...]
- Published
- 2020
- Full Text
- View/download PDF
3. Human CRY1 variants associate with attention deficit/hyperactivity disorder
- Author
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Department of Chemical and Biological Engineering; Department of Molecular Biology and Genetics, Gül, Şeref; Aydın, Cihan (ORCID 0000-0003-0560-1895 & YÖK ID 214696); Başak, Ayşe Nazlı (ORCID 0000-0001-9257-3540 & YÖK ID 1512); Kavaklı, İbrahim Halil (ORCID 0000-0001-6624-3505 & YÖK ID 40319), Onat, O. Emre; Kars, M. Ece; Bilguvar, Kaya; Wu, Yiming; Özhan, Ayşe; Trusso, M. Allegra; Goracci, Arianna; Fallerini, Chiara; Renieri, Alessandra; Casanova, Jean Laurent; Itan, Yuval; Atbaşoğlu, Cem E.; Saka, Meram C.; Özçelik, Tayfun, Department of Chemical and Biological Engineering; Department of Molecular Biology and Genetics, Gül, Şeref; Aydın, Cihan (ORCID 0000-0003-0560-1895 & YÖK ID 214696); Başak, Ayşe Nazlı (ORCID 0000-0001-9257-3540 & YÖK ID 1512); Kavaklı, İbrahim Halil (ORCID 0000-0001-6624-3505 & YÖK ID 40319), and Onat, O. Emre; Kars, M. Ece; Bilguvar, Kaya; Wu, Yiming; Özhan, Ayşe; Trusso, M. Allegra; Goracci, Arianna; Fallerini, Chiara; Renieri, Alessandra; Casanova, Jean Laurent; Itan, Yuval; Atbaşoğlu, Cem E.; Saka, Meram C.; Özçelik, Tayfun
- Abstract
Attention deficit/hyperactivity disorder (ADHD) is a common and heritable phenotype frequently accompanied by insomnia, anxiety, and depression. Here, using a reverse phenotyping approach, we report heterozygous coding variations in the core circadian clock gene cryptochrome 1 in 15 unrelated multigenerational families with combined ADHD and insomnia. The variants led to functional alterations in the circadian molecular rhythms, providing a mechanistic link to the behavioral symptoms. One variant, CRY1Δ11 c.1657+3A>C, is present in approximately 1% of Europeans, therefore standing out as a diagnostic and therapeutic marker. We showed by exome sequencing in an independent cohort of patients with combined ADHD and insomnia that 8 of 62 patients and 0 of 369 controls carried CRY1Δ11. Also, we identified a variant, CRY1Δ6 c.825+1G>A, that shows reduced affinity for BMAL1/CLOCK and causes an arrhythmic phenotype. Genotype-phenotype correlation analysis revealed that this variant segregated with ADHD and delayed sleep phase disorder (DSPD) in the affected family. Finally, we found in a phenome-wide association study involving 9438 unrelated adult Europeans that CRY1Δ11 was associated with major depressive disorder, insomnia, and anxiety. These results defined a distinctive group of circadian psychiatric phenotypes that we propose to designate as "circiatric" disorders.
- Published
- 2020
4. Homozygosity mapping and targeted genomic sequencing reveal the gene responsible for cerebellar hypoplasia and quadrupedal locomotion in a consanguineous kindred
- Author
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Gulsuner, Suleyman, primary, Tekinay, Ayse Begum, additional, Doerschner, Katja, additional, Boyaci, Huseyin, additional, Bilguvar, Kaya, additional, Unal, Hilal, additional, Ors, Aslihan, additional, Onat, O. Emre, additional, Atalar, Ergin, additional, Basak, A. Nazli, additional, Topaloglu, Haluk, additional, Kansu, Tulay, additional, Tan, Meliha, additional, Tan, Uner, additional, Gunel, Murat, additional, and Ozcelik, Tayfun, additional
- Published
- 2011
- Full Text
- View/download PDF
5. Human CRY1 variants associate with attention deficit/hyperactivity disorder
- Author
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I Halil Kavaklı, Arianna Goracci, Yuval Itan, Ayse Ozhan, Chiara Fallerini, Jean-Laurent Casanova, Cihan Aydin, M Ece Kars, O Emre Onat, Yiming Wu, Cem Atbaşoğlu, A. Nazli Basak, Kaya Bilguvar, Alessandra Renieri, Tayfun Ozcelik, M Allegra Trusso, Meram Can Saka, Seref Gul, Gül, Şeref, Aydın, Cihan (ORCID 0000-0003-0560-1895 & YÖK ID 214696), Başak, Ayşe Nazlı (ORCID 0000-0001-9257-3540 & YÖK ID 1512), Kavaklı, İbrahim Halil (ORCID 0000-0001-6624-3505 & YÖK ID 40319), Onat, O. Emre, Kars, M. Ece, Bilguvar, Kaya, Wu, Yiming, Özhan, Ayşe, Trusso, M. Allegra, Goracci, Arianna, Fallerini, Chiara, Renieri, Alessandra, Casanova, Jean Laurent, Itan, Yuval, Atbaşoğlu, Cem E., Saka, Meram C., Özçelik, Tayfun, Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM), Graduate School of Sciences and Engineering, College of Engineering, College of Sciences, Department of Chemical and Biological Engineering, Department of Molecular Biology and Genetics, and Başak, A. N.
- Subjects
Adult ,Male ,0301 basic medicine ,Genetic diseases ,Genetics ,Monogenic diseases ,Psychiatric diseases ,CLOCK Proteins ,Delayed sleep phase ,Bioinformatics ,ARNTL Transcription Factors ,Attention Deficit Disorder with Hyperactivity ,Cryptochromes ,Female ,Genetic Association Studies ,HEK293 Cells ,Humans ,Sleep Disorders, Circadian Rhythm ,Mutation ,03 medical and health sciences ,0302 clinical medicine ,mental disorders ,Insomnia ,Medicine ,Attention deficit hyperactivity disorder ,Circadian rhythm ,Exome sequencing ,Depression (differential diagnoses) ,business.industry ,General Medicine ,medicine.disease ,Circadian Rhythm ,Biology ,030104 developmental biology ,030220 oncology & carcinogenesis ,Anxiety ,Major depressive disorder ,medicine.symptom ,Sleep Disorders ,business ,Research Article - Abstract
Attention deficit/hyperactivity disorder (ADHD) is a common and heritable phenotype frequently accompanied by insomnia, anxiety, and depression. Here, using a reverse phenotyping approach, we report heterozygous coding variations in the core circadian clock gene cryptochrome 1 in 15 unrelated multigenerational families with combined ADHD and insomnia. The variants led to functional alterations in the circadian molecular rhythms, providing a mechanistic link to the behavioral symptoms. One variant, CRY1Δ11 c.1657+3A>C, is present in approximately 1% of Europeans, therefore standing out as a diagnostic and therapeutic marker. We showed by exome sequencing in an independent cohort of patients with combined ADHD and insomnia that 8 of 62 patients and 0 of 369 controls carried CRY1Δ11. Also, we identified a variant, CRY1Δ6 c.825+1G>A, that shows reduced affinity for BMAL1/CLOCK and causes an arrhythmic phenotype. Genotype-phenotype correlation analysis revealed that this variant segregated with ADHD and delayed sleep phase disorder (DSPD) in the affected family. Finally, we found in a phenome-wide association study involving 9438 unrelated adult Europeans that CRY1Δ11 was associated with major depressive disorder, insomnia, and anxiety. These results defined a distinctive group of circadian psychiatric phenotypes that we propose to designate as "circiatric" disorders., NIH Clinical and Translational Science Award (CTSA) Program; NIH; French National Research Agency (ANR) under the “Investments for the future” Program; Integrative Biology of Emerging Infectious Diseases Laboratoire d’Excellence; IEIHSEER Grant; SEAe-Host Factors Grant; PNEUMOID Project Grant; INCA/Cancéropole Ile-de-France; Turkish Academy of Sciences (TÜBA); National Center for Advancing Translational Sciences (NCAST); Rockefeller University, INSERM; HHMI, University of Paris; St. Giles Foundation; Charles Bronfman Institute for Personalized Medicine at the Icahn School of Medicine at Mount Sinai
- Published
- 2020
6. Homozygosity mapping and targeted genomic sequencing reveal the gene responsible for cerebellar hypoplasia and quadrupedal locomotion in a consanguineous kindred
- Author
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Haluk Topaloglu, Aslihan Ors, Suleyman Gulsuner, Huseyin Boyaci, O Emre Onat, A. Nazli Basak, Murat Gunel, Katja Doerschner, Kaya Bilguvar, Tayfun Ozcelik, Ayse B. Tekinay, Hilal Unal, Üner Tan, Meliha Tan, Ergin Atalar, Tulay Kansu, Çukurova Üniversitesi, Gulsuner, Süleyman, Tekinay, Ayşe Begüm, Doerschner, Katja, Boyaci, Hüseyin, Ünal, Hilal, Örs, Aslıhan, Onat, O. Emre, Atalar, Ergin, Özçelik, Tayfun, and Nöroloji
- Subjects
Male ,Cerebellum ,family ,Turkey ,consanguineous marriage ,tractography ,Corpus callosum ,Turkey (republic) ,corpus callosum ,0302 clinical medicine ,Missense mutation ,membrane protein ,nuclear magnetic resonance imaging ,Gait ,developmental disorder ,Genetics (clinical) ,Genetics & Heredity ,Genetics ,clinical article ,0303 health sciences ,primary motor cortex ,quadruped gait ,Homozygote ,article ,Disease gene identification ,Magnetic Resonance Imaging ,Hypoplasia ,female ,medicine.anatomical_structure ,priority journal ,cerebellum hypoplasia ,Female ,Adult ,Biochemistry & Molecular Biology ,phenotype ,brain region ,Posture ,chromosome 17p ,gene sequence ,Biology ,superior cerebellar peduncle ,03 medical and health sciences ,Atrophy ,middle cerebellar peduncle ,mental deficiency ,diffusion weighted imaging ,medicine ,Humans ,controlled study ,human ,gene ,030304 developmental biology ,carboxy terminal sequence ,Research ,missense mutation ,Genetic Diseases, Inborn ,Precentral gyrus ,nucleotide sequence ,medicine.disease ,Radiography ,Biotechnology & Applied Microbiology ,nervous system ,Genetic Loci ,amino terminal sequence ,Cerebellar hypoplasia (non-human) ,homozygosity ,inferior cerebellar peduncle ,brain atrophy ,030217 neurology & neurosurgery ,Chromosomes, Human, Pair 17 - Abstract
The biological basis for the development of the cerebro-cerebellar structures required for posture and gait in humans is poorly understood. We investigated a large consanguineous family from Turkey exhibiting an extremely rare phenotype associated with quadrupedal locomotion, mental retardation, and cerebro-cerebellar hypoplasia, linked to a 7.1-Mb region of homozygosity on chromosome 17p13.1–13.3. Diffusion weighted imaging and fiber tractography of the patients' brains revealed morphological abnormalities in the cerebellum and corpus callosum, in particular atrophy of superior, middle, and inferior peduncles of the cerebellum. Structural magnetic resonance imaging showed additional morphometric abnormalities in several cortical areas, including the corpus callosum, precentral gyrus, and Brodmann areas BA6, BA44, and BA45. Targeted sequencing of the entire homozygous region in three affected individuals and two obligate carriers uncovered a private missense mutation, WDR81 p.P856L, which cosegregated with the condition in the extended family. The mutation lies in a highly conserved region of WDR81, flanked by an N-terminal BEACH domain and C-terminal WD40 beta-propeller domains. WDR81 is predicted to be a transmembrane protein. It is highly expressed in the cerebellum and corpus callosum, in particular in the Purkinje cell layer of the cerebellum. WDR81 represents the third gene, after VLDLR and CA8, implicated in quadrupedal locomotion in humans.
- Published
- 2011
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