Dysregulation of DGCR6 and DGCR6L: psychopathological outcomes in chromosome 22q11.2 deletion syndrome
Open accessAbstract
Chromosome 22q11.2 deletion syndrome (22q11DS) is the most common microdeletion syndrome in humans. It is typified by highly variable symptoms, which might be explained by epigenetic regulation of genes in the interval. Using computational algorithms, our laboratory previously predicted that DiGeorge critical region 6 (DGCR6), which lies within the deletion interval, is imprinted in humans. Expression and epigenetic regulation of this gene have not, however, been examined in 22q11DS subjects. The purpose of this study was to determine if the expression levels of DGCR6 and its duplicate copy DGCR6L in 22q11DS subjects are associated with the parent-of-origin of the deletion and childhood psychopathologies. Our investigation showed no evidence of parent-of-origin-related differences in expression of both DGCR6 and DGCR6L. However, we found that the variability in DGCR6 expression was significantly greater in 22q11DS children than in age and gender-matched control individuals. Children with 22q11DS who had anxiety disorders had significantly lower DGCR6 expression, especially in subjects with the deletion on the maternal chromosome, despite the lack of imprinting. Our findings indicate that epigenetic mechanisms other than imprinting contribute to the dysregulation of these genes and the associated childhood psychopathologies observed in individuals with 22q11DS. Further studies are now needed to test the usefulness of DGCR6 and DGCR6L expression and alterations in the epigenome at these loci in predicting childhood anxiety and associated adult-onset pathologies in 22q11DS subjects.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
DGCR6L has been shown to interact with the gamma-aminobutyric acid GABA-B1 receptor subunit and to be related to anxiety in children with chromosome 22q11.2 deletion syndrome as well as to schizophrenia.
“the DiGeorge critical region 6 and its duplication (DGCR6L) have been shown to interact with the gamma-aminobutyric acid GABA-B1 receptor subunit (Zunner et al., 2010) and to be related to anxiety in children with chromosome 22q11.2 deletion syndrome (Das Chakraborty et al., 2012) as well as to schizophrenia (Liu et al., 2002).”
From Epigenome-wide DNA methylation in unipolar depression: predictive biomarker of antidepressant treatment response? (2024) · cites this paper as Das Chakraborty et al., 2012
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Analysis of Relative Gene Expression Data Using Real-Time Quantitative PCR and the 2−ΔΔCT Method
Livak, K. J., & Schmittgen, T. D. (2001) · Methods · doi:10.1006/meth.2001.1262 · Cited by 180,860 · see citing works
McDonald-McGinn, D. M., Sullivan, K. E., Marino, B., Philip, N., Swillen, A., Vorstman, J. A. S., Zackai, E. H., Emanuel, B. S., Vermeesch, J. R., Morrow, B. E., et al. (2015) · Nature Reviews Disease Primers · doi:10.1038/nrdp.2015.71 · Cited by 2,236 · see citing works
Dolinoy, D. C., Huang, D., & Jirtle, R. L. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0703739104 · Cited by 1,369 · see citing works
Self-citationHigh rates of schizophrenia in adults with velo-cardio-facial syndrome
Murphy, K. C., Jones, L. A., & Owen, M. J. (1999) · Archives of General Psychiatry · doi:10.1001/archpsyc.56.10.940 · Cited by 1,024 · see citing works
Schizophrenia susceptibility associated with interstitial deletions of chromosome 22q11.
Karayiorgou, M., Morris, M. A., Morrow, B., Shprintzen, R. J., Goldberg, R., Borrow, J., Gos, A., Nestadt, G., Wolyniec, P. S., & Lasseter, V. K. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.17.7612 · Cited by 628 · see citing works
Erlenmeyer‐Kimling, L., Rock, D., Roberts, S. A., Janal, M. N., Kestenbaum, C. J., Cornblatt, B. A., Adamo, U. H., & Gottesman, I. I. (2000) · American Journal of Psychiatry · doi:10.1176/appi.ajp.157.9.1416 · Cited by 511 · see citing works
Metastable epialleles in mammals
Rakyan, V. K., Blewitt, M. E., Druker, R., Preis, J. I., & Whitelaw, E. (2002) · Trends in Genetics · doi:10.1016/s0168-9525(02)02709-9 · Cited by 499 · see citing works
Clinical features of 78 adults with 22q11 deletion syndrome
Bassett, A. S., Chow, E. W. C., Husted, J., Weksberg, R., Caluseriu, O., Webb, G. D., & Gatzoulis, M. Α. (2005) · American Journal of Medical Genetics Part A · doi:10.1002/ajmg.a.30984 · Cited by 476 · see citing works
Developmental norms for the wisconsin card sorting test
Chelune, G. J., & Baer, R. A. (1986) · Journal of Clinical and Experimental Neuropsychology · doi:10.1080/01688638608401314 · Cited by 467 · see citing works
Velo‐cardio‐facial syndrome: 30 Years of study
Shprintzen, R. J. (2008) · Developmental Disabilities Research Reviews · doi:10.1002/ddrr.2 · Cited by 463 · see citing works
A genetic etiology for DiGeorge syndrome: consistent deletions and microdeletions of 22q11.
Driscoll, D. A., Budarf, M. L., & Emanuel, B. S. (1992) · PubMed · Cited by 425 · see citing works
Late‐Onset psychosis in the velo‐cardio‐facial syndrome
Shprintzen, R. J., Goldberg, R. B., Golding‐Kushner, K. J., & Marion, R. W. (1992) · American Journal of Medical Genetics · doi:10.1002/ajmg.1320420131 · Cited by 402 · see citing works
Computational and experimental identification of novel human imprinted genesPreprint
Luedi, P. P., Dietrich, F. S., Weidman, J. R., Bosko, J. M., Jirtle, R. L., & Hartemink, A. J. (2007) · Genome Research · doi:10.1101/gr.6584707 · Cited by 397 · see citing works
Self-citationSwillen, A., Devriendt, K., Legius, E., Eyskens, B., Dumoulin, M., Gewillig, M. H. M. L., & Fryns, J. P. (1997) · Journal of Medical Genetics · doi:10.1136/jmg.34.6.453 · Cited by 355 · see citing works
Liu, H., Heath, S. C., Sobin, C., Roos, J. L., Galke, B. L., Blundell, M. L., Lenane, M., Robertson, B., Wijsman, E. M., Rapoport, J. L., et al. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.042700699 · Cited by 323 · see citing works
Choufani, S., Shuman, C. T., & Weksberg, R. (2010) · American Journal of Medical Genetics Part C Seminars in Medical Genetics · doi:10.1002/ajmg.c.30267 · Cited by 305 · see citing works
The Velo-Cardio-Facial Syndrome: A Clinical and Genetic Analysis
Shprintzen, R. J., Goldberg, R. B., Young, D., et al. (1981) · PEDIATRICS · doi:10.1542/peds.67.2.167 · Cited by 297 · see citing works
Cornblatt, B. A., & Erlenmeyer‐Kimling, L. (1985) · Journal of Abnormal Psychology · doi:10.1037/0021-843x.94.4.470 · Cited by 295 · see citing works
Genome-wide prediction of imprinted murine genesPreprint
Luedi, P. P., Hartemink, A. J., & Jirtle, R. L. (2005) · Genome Research · doi:10.1101/gr.3303505 · Cited by 259 · see citing works
Self-citationNeuropsychological profile of children and adolescents with the 22q11.2 microdeletion
Woodin, M. F., Wang, P. P., Aleman, D. O., McDonald‐McGinn, D. M., Zackai, E. H., & Moss, E. (2001) · Genetics in Medicine · doi:10.1097/00125817-200101000-00008 · Cited by 252 · see citing works
Human morbid genetics revisited: relevance of epigenetics
Petronis, A. (2001) · Trends in Genetics · doi:10.1016/s0168-9525(00)02213-7 · Cited by 251 · see citing works
Bearden, C. E., Woodin, M. F., Wang, P. P., Moss, E., McDonald‐McGinn, D. M., Zackai, E. H., Emanuel, B. S., & Cannon, T. D. (2001) · Journal of Clinical and Experimental Neuropsychology · doi:10.1076/jcen.23.4.447.1228 · Cited by 226 · see citing works
Feinstein, C., Eliez, S., Blasey, C. M., & Reiss, A. L. (2002) · Biological Psychiatry · doi:10.1016/s0006-3223(01)01231-8 · Cited by 181 · see citing works
Allele-specific DNA methylation: beyond imprinting
Tycko, B. (2010) · Human Molecular Genetics · doi:10.1093/hmg/ddq376 · Cited by 178 · see citing works
Swillen, A., Vandeputte, L., Cracco, J., Maes, B., Ghesquière, P., Devriendt, K., & Fryns, J. (1999) · Child Neuropsychology · doi:10.1076/0929-7049(199912)05:04;1-r;ft230 · Cited by 176 · see citing works
Prader-Willi and Angelman Syndromes: Disorders of Genomic Imprinting
Cassidy, S. B., & Schwartz, S. (1998) · Medicine · doi:10.1097/00005792-199803000-00005 · Cited by 146 · see citing works
NIMH-MATRICS survey on assessment of neurocognition in schizophrenia
Kern, R. S., Green, M. F., Nuechterlein, K. H., & Deng, B.-H. (2004) · Schizophrenia Research · doi:10.1016/j.schres.2004.09.004 · Cited by 124 · see citing works
Schizophrenic‐like neurocognitive deficits in children and adolescents with 22q11 deletion syndrome
Lewandowski, K. E., Shashi, V., Berry, P. M., & Kwapil, T. R. (2006) · American Journal of Medical Genetics Part B Neuropsychiatric Genetics · doi:10.1002/ajmg.b.30379 · Cited by 115 · see citing works
Self-citationLanguage skills in children with velocardiofacial syndrome (deletion 22q11.2)
Glaser, B., Mumme, D. L., Blasey, C. M., Morris, M. A., Dahoun, S. P., Antonarakis, S. E., Reiss, A. L., & D, S. E. M. (2002) · The Journal of Pediatrics · doi:10.1067/mpd.2002.124774 · Cited by 94 · see citing works
Imprinting evolution and human health
Das, R., Hampton, D. D., & Jirtle, R. L. (2009) · Mammalian Genome · doi:10.1007/s00335-009-9229-y · Cited by 89 · see citing works
Self-citationHartmer, R. (2003) · Nucleic Acids Research · doi:10.1093/nar/gng047 · Cited by 89 · see citing works
Genomic imprinting in the development and evolution of psychotic spectrum conditions
Crespi, B. J. (2008) · Biological reviews/Biological reviews of the Cambridge Philosophical Society · doi:10.1111/j.1469-185x.2008.00050.x · Cited by 86 · see citing works
Evidence for Sustained Attention and Working Memory in Schizophrenia Sharing a Common Mechanism
Silver, H., & Feldman, P. (2005) · Journal of Neuropsychiatry · doi:10.1176/jnp.17.3.391 · Cited by 73 · see citing works
Parental Origin of the Deletion 22q11.2 and Brain Development in Velocardiofacial Syndrome
D, S. E. M., Antonarakis, S. E., Morris, M. A., Dahoun, S. P., & Reiss, A. L. (2001) · Archives of General Psychiatry · doi:10.1001/archpsyc.58.1.64 · Cited by 69 · see citing works
Cytosine Methylation Profiles as a Molecular Marker in Non–Small Cell Lung Cancer
Ehrich, M., Field, J. K., Liloglou, T., Xinarianos, G., Oeth, P. A., Nelson, M. R., Cantor, C. R., & van den Boom, D. (2006) · Cancer Research · doi:10.1158/0008-5472.can-06-0400 · Cited by 58 · see citing works
Okajima, K., Robinson, L. K., Hart, M. A., Abuelo, D. N., Cowan, L. S., Hasegawa, T., Maumenee, I. H., & Jabs, E. W. (1999) · American Journal of Medical Genetics · doi:10.1002/(sici)1096-8628(19990716)85:2 · Cited by 57 · see citing works
Proton Magnetic Resonance Spectroscopy in 22q11 Deletion Syndrome
Alves, F. D. S., Boot, E., Schmitz, N., Nederveen, A. J., Vorstman, J. A. S., Lavini, C., Pouwels, P. J. W., de Haan, L., LINSZEN, D. H., & van Amelsvoort, T. (2011) · PLoS ONE · doi:10.1371/journal.pone.0021685 · Cited by 51 · see citing works
Otto, M. W., Bruder, G. E., D, M. F. M., Delis, D. C., Quitkin, F. M., & Rosenbaum, J. F. (1994) · Archives of Clinical Neuropsychology · doi:10.1093/arclin/9.1.81 · Cited by 50 · see citing works
22q11 DS: genomic mechanisms and gene function in DiGeorge/velocardiofacial syndrome
Maynard, T. M., Haskell, G., Lieberman, J. A., & LaMantia, A. (2002) · International Journal of Developmental Neuroscience · doi:10.1016/s0736-5748(02)00050-3 · Cited by 47 · see citing works
Evidence of gray matter reduction and dysfunction in chromosome 22q11.2 deletion syndrome
Shashi, V., Kwapil, T. R., Kaczorowski, J. A., Berry, M. N., Santos, C. S., Howard, T. D., Goradia, D. D., Prasad, K. M. R., Vaibhav, D., Rajarethinam, R., et al. (2009) · Psychiatry Research Neuroimaging · doi:10.1016/j.pscychresns.2009.07.003 · Cited by 47 · see citing works
Self-citationThe potential role of gene duplications in the evolution of imprinting mechanisms
Walter, J., & Paulsen, M. (2003) · Human Molecular Genetics · doi:10.1093/hmg/ddg296 · Cited by 46 · see citing works
A Chicken Model for DGCR6 as a Modifier Gene in the DiGeorge Critical Region
Hierck, B. P., Molin, D. G. M., Boot, M. J., Poelmann, R. E., & Groot, A. C. G. (2004) · Pediatric Research · doi:10.1203/01.pdr.0000136151.50127.1c · Cited by 39 · see citing works
Edelmann, L., Stankiewicz, P., Spiteri, E., Pandita, R., Shaffer, L. G., Lupski, J., & Morrow, B. E. (2001) · Genome Research · doi:10.1101/gr.gr-1431r · Cited by 37 · see citing works
Comorbid anxiety in patients with psychosis.
Dernovšek, M. Z., & Šprah, L. (2009) · PubMed · Cited by 33 · see citing works
COMT and anxiety and cognition in children with chromosome 22q11.2 deletion syndrome
Shashi, V., Howard, T. D., Keshavan, M. S., Kaczorowski, J. A., Berry, M. N., Schoch, K., Spence, E. J., & Kwapil, T. R. (2010) · Psychiatry Research · doi:10.1016/j.psychres.2010.04.048 · Cited by 23 · see citing works
Self-citationGABAB receptor subunit 1 binds to proteins affected in 22q11 deletion syndrome
Zunner, D., Deschermeier, C., & Kornau, H.-C. (2010) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2009.12.120 · Cited by 11 · see citing works
Edelmann, L. J., Stankiewicz, P., Spiteri, E. J., et al. (2001) · Genome Research · Cited by 8 · see citing works
No evidence for parental imprinting of mouse 22q11 gene orthologs
Maynard, T. M., Meechan, D. W., Heindel, C., et al. (2006) · Mammalian Genome · doi:10.1007/s00335-006-0011-0 · Cited by 7 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Schiele, M. A., Crespo Salvador, O., Lipovsek, J., Schwarte, K., Schlosser, P., Zwanzger, P., Arolt, V., Baune, B. T., Köttgen, A., & Domschke, K. (2024) · International Journal of Neuropsychopharmacology · doi:10.1093/ijnp/pyae045 · Cited by 13 · see citing works
- Authors
- Chakraborty, D., Bernal, A. J., Schoch, K., Howard, T. D., Ip, E. H., Hooper, S. R., Keshavan, M. S., Jirtle, R. L., & Shashi, V
- Affiliations
- Duke Medical Center (US)
- Wake Forest University Health Sciences (US)
- University of North Carolina at Chapel Hill (US)
- Harvard University (US)
- Corresponding author
- Shashi, V
- Venue
- Translational Psychiatry
- Published
- 2012-04-24
- Volume
- 2
- Issue
- 4
- Pages
- e105-e105
- ISSN
- 2158-3188 (ISSN-L)
- PMC
- PMC3337078
- OpenAlex
- W2133181020
- Cited by
- 30
- References
- 49
- Citations by year
- 2024: 5 · 2022: 4 · 2021: 6 · 2020: 5 · 2019: 1 · 2017: 2 · 2016: 1 · 2015: 3 · 2013: 2 · 2012: 1
- FWCI
- 1.15
- Type
- journal article
- Language
- en
- Update notices
- erratum (2012-05-29)
- Open access
- gold
- doi.org
- Licence
- cc-by-nc-nd
- www.springer.com/tdm (unspecified)
- Locations
- Translational Psychiatry (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- OSTI OAI (U.S. Department of Energy Office of Scientific and Technical Information) (submittedVersion, cc-by-nc-nd)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
- Funders
- U.S. Department of Energy (DEFG0205ER64101)
- National Institutes of Health
- National Institute of Mental Health (R01MH078015)
- National Institute of Environmental Health Sciences (R21ES013053, R01ES015165, R01ES13053)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomic variations and chromosomal abnormalities
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Syndromes and Imprinting
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Keywords
- 22q11.2 deletion syndrome, parent-of-origin expression, epigenetic regulation, gene expression variation, childhood anxiety disorders, microdeletion syndromes, epigenome
- MeSH terms
- Abnormalities, Multiple, Adolescent, Algorithms, Anxiety Disorders, Child, Chromosome Deletion, Chromosomes, Human, Pair 22, DiGeorge Syndrome, Female, Genotype, Humans, Male, Nuclear Proteins, Proteins, Psychopathology, Reference Values, Schizophrenia, Schizophrenic Psychology, Gene Expression, Extracellular Matrix Proteins, Genomic Imprinting, Computational Biology, Polymorphism, Single Nucleotide, Epigenesis, Genetic
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
