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No evidence for parental imprinting of mouse 22q11 gene orthologs

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Abstract

Non-Mendelian factors may influence central nervous system (CNS) phenotypes in patients with 22q11 Deletion Syndrome (22q11DS, also known as DiGeorge or Velocardiofacial Syndrome), and similar mechanisms may operate in mice carrying a deletion of one or more 22q11 gene orthologs. Accordingly, we examined the influence of parent of origin on expression of 25 murine 22q11 orthologs in the developing and mature CNS using single nucleotide polymorphism (SNP)-based analysis in interspecific crosses and quantification of mRNA in a murine model of 22q11DS. We found no evidence for absolute genomic imprinting or silencing. All 25 genes are biallelically expressed in the developing and adult brains. Furthermore, if more subtle forms of allelic biasing are present, they are very small in magnitude and most likely beyond the resolution of currently available quantitative approaches. Given the high degree of similarity of human 22q11 and the orthologous region of mmChr16, genomic imprinting most likely cannot explain apparent parent-of-origin effects in 22q11DS.

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References

  • Albrecht U, Sutcliffe JS, Cattanach BM, Beechey CV, Armstrong D, et al. (1997) Imprinted expression of the murine Angelman syndrome gene, Ube3a, in hippocampal and Purkinje neurons. Nat Genet 17, 75–78

    Article  PubMed  CAS  Google Scholar 

  • Amati F, Conti E, Novelli A, Bengala M, Diglio MC, et al. (1999) Atypical deletions suggest five 22q11.2 critical regions related to the DiGeorge/velo-cardio-facial syndrome. Eur J Hum Genet 7, 903–909

    Article  PubMed  CAS  Google Scholar 

  • Bennett-Baker PE, Wilkowski J, Burke DT (2003) Age-associated activation of epigenetically repressed genes in the mouse. Genetics 165, 2055–2062

    PubMed  CAS  Google Scholar 

  • Carlson C, Sirotkin H, Pandita R, Goldberg R, McKie J, et al. (1997) Molecular definition of 22q11 deletions in 151 velo-cardio-facial syndrome patients. Am J Hum Genet 61, 620–629

    PubMed  CAS  Google Scholar 

  • Chess A, Simon I, Cedar H, Axel R (1994) Allelic inactivation regulates olfactory receptor gene expression. Cell 78, 823–834

    Article  PubMed  CAS  Google Scholar 

  • Deltour L, Montagutelli X, Guenet JL, Jami J, Paldi A (1995) Tissue- and developmental stage-specific imprinting of the mouse proinsulin gene, Ins2. Dev Biol 168, 686–688

    Article  PubMed  CAS  Google Scholar 

  • Digilio MC, Angioni A, De Santis M, Lombardo A, Giannotti A, et al. (2003) Spectrum of clinical variability in familial deletion 22q11.2: from full manifestation to extremely mild clinical anomalies. Clin Genet 63, 308–313

    Article  PubMed  CAS  Google Scholar 

  • Eliez S, Antonarakis SE, Morris MA, Dahoun SP, Reiss AL (2001a) Parental origin of the deletion 22q11.2 and brain development in velocardiofacial syndrome: a preliminary study. Arch Gen Psychiatry 58, 64–68

    Article  CAS  Google Scholar 

  • Eliez S, Schmitt JE, White CD, Wellis VG, Reiss AL (2001b) A quantitative MRI study of posterior fossa development in velocardiofacial syndrome. Biol Psychiatry 49, 540–546

    Article  CAS  Google Scholar 

  • Glaser B, Mumme DL, Blasey C, Morris MA, Dahoun SP, et al. (2002) Language skills in children with velocardiofacial syndrome (deletion 22q11.2). J Pediatr 140, 753–758

    Article  PubMed  Google Scholar 

  • Guris DL, Duester G, Papaioannou VE, Imamoto A (2006) Dose-dependent interaction of Tbx1 and Crkl and locally aberrant RA signaling in a model of del22q11 syndrome. Dev Cell 10, 81–92

    Article  PubMed  CAS  Google Scholar 

  • Jong MT, Carey AH, Caldwell KA, Lau MH, Handel MA, et al. (1999) Imprinting of a RING zinc-finger encoding gene in the mouse chromosome region homologous to the Prader–Willi syndrome genetic region. Hum Mol Genet 8, 795–803

    Article  PubMed  CAS  Google Scholar 

  • Lindsay EA, Vitelli F, Su H, Morishima M, Huynh T, et al. (2001) Tbx1 haploinsufficiency in the DiGeorge syndrome region causes aortic arch defects in mice. Nature 410, 97–101

    Article  PubMed  CAS  Google Scholar 

  • Lund J, Chen F, Hua A, Roe B, Budarf M, et al. (2000) Comparative sequence analysis of 634 kb of the mouse chromosome 16 region of conserved synteny with the human velocardiofacial syndrome region on chromosome 22q11.2. Genomics 63, 374–383

    Article  PubMed  CAS  Google Scholar 

  • Matsuoka R, Kimura M, Scambler PJ, Morrow BE, Imamura S, et al. (1998) Molecular and clinical study of 183 patients with conotruncal anomaly face syndrome. Hum Genet 103, 70–80

    Article  PubMed  CAS  Google Scholar 

  • Maynard TM, Haskell GT, Bhasin N, Lee JM, Gassman AA, et al. (2002a) RanBP1, a velocardiofacial/DiGeorge syndrome candidate gene, is expressed at sites of mesenchymal/epithelial induction. Mech Dev 111, 177–180

    Article  CAS  Google Scholar 

  • Maynard TM, Haskell GT, Lieberman JA, LaMantia AS (2002b) 22q11 DS: genomic mechanisms and gene function in DiGeorge/velocardiofacial syndrome. Int J Dev Neurosci 20, 407–419

    Article  CAS  Google Scholar 

  • Maynard TM, Haskell GT, Peters AZ, Sikich L, Lieberman JA, et al. (2003) A comprehensive analysis of 22q11 gene expression in the developing and adult brain. Proc Natl Acad Sci U S A 100, 14433–14438

    Article  PubMed  CAS  Google Scholar 

  • Meechan D, Maynard TM, Peters AZ, LaMantia AS (submitted) Analysis of haploinsufficiency in mouse 22q11 orthologs

  • Merscher S, Funke B, Epstein JA, Heyer J, Puech A, et al. (2001) TBX1 is responsible for cardiovascular defects in velo-cardio-facial/DiGeorge syndrome. Cell 104, 619–629

    Article  PubMed  CAS  Google Scholar 

  • Moon AM, Guris DL, Seo JH, Li L, Hammond J, et al. (2006) Crkl deficiency disrupts fgf8 signaling in a mouse model of 22q11 deletion syndromes. Dev Cell 10, 71–80

    Article  PubMed  CAS  Google Scholar 

  • Morison IM, Ramsay JP, Spencer HG (2005) A census of mammalian imprinting. Trends Genet 21, 457–465

    Article  PubMed  CAS  Google Scholar 

  • Puech A, Saint-Jore B, Funke B, Gilbert DJ, Sirotkin H, et al. (1997) Comparative mapping of the human 22q11 chromosomal region and the orthologous region in mice reveals complex changes in gene organization. Proc Natl Acad Sci U S A 94, 14608–14613

    Article  PubMed  CAS  Google Scholar 

  • Roe BA, Lau C, Oommen S, Li J, Hua A, et al. (2003) Comparative analysis of human chromosome 22q11.1–q12.3 with syntenic regions in the chimpanzee, baboon, bovine, mouse, pufferfish, and zebrafish genomes. Cold Spring Harb Symp Quant Biol 68, 265–274

    Article  PubMed  CAS  Google Scholar 

  • Shaikh TH, Kurahashi H, Emanuel BS (2001) Evolutionarily conserved low copy repeats (LCRs) in 22q11 mediate deletions, duplications, translocations, and genomic instability: an update and literature review. Genet Med 3, 6–13

    Article  PubMed  CAS  Google Scholar 

  • Sutherland HF, Kim UJ, Scambler PJ (1998) Cloning and comparative mapping of the DiGeorge syndrome critical region in the mouse. Genomics 52, 37–43

    Article  PubMed  CAS  Google Scholar 

  • van Amelsvoort T, Daly E, Robertson D, Suckling J, Ng V, et al. (2001) Structural brain abnormalities associated with deletion at chromosome 22q11: quantitative neuroimaging study of adults with velo-cardio-facial syndrome. Br J Psychiatry 178, 412–419

    Article  PubMed  Google Scholar 

  • Wang Z, Fan H, Yang HH, Hu Y, Buetow KH, et al. (2004) Comparative sequence analysis of imprinted genes between human and mouse to reveal imprinting signatures. Genomics 83, 395–401

    Article  PubMed  CAS  Google Scholar 

  • Weber M, Milligan L, Delalbre A, Antoine E, Brunel C, et al. (2001) Extensive tissue-specific variation of allelic methylation in the Igfz gene during mouse fetal development: relation to expression and imprinting. Mech Dev 101, 133–141

    Article  PubMed  CAS  Google Scholar 

  • Yang T, Adamson TE, Resnick JL, Leff S, Wevrick R, et al. (1998) A mouse model for Prader–Willi syndrome imprinting-centre mutations. Nat Genet 19, 25–31

    PubMed  CAS  Google Scholar 

  • Yevtodiyenko A, Carr MS, Patel N, Schmidt JV (2002) Analysis of candidate imprinted genes linked to Dlk1–Gtl2 using a congenic mouse line. Mamm Genome 13, 633–638

    Article  PubMed  CAS  Google Scholar 

  • Zhang J, Wheeler DA, Yakub I, Wei S, Sood R, et al. (2005) SNPdetector: A Software Tool for Sensitive and Accurate SNP Detection. PLoS Comput Biol 1, e53

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This project was supported by NICHD 042182 (ASL) and a NIMH Silvio Conte Center for Mental Disorders grant (JAL), and a NARSAD Independent Investigator Award (ASL).

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Author notes

  1. Jeffrey A. Lieberman

    Present address: Department of Psychiatry, Columbia University and NYS Psychiatric Institute, 1051 Riverside Drive, New York, NY, 10032, USA

Authors and Affiliations

  1. UNC Silvio O. Conte Center for the Neuroscience of Mental Disorders, University of North Carolina, Chapel Hill, North Carolina, 27599, USA

    Thomas M. Maynard, Daniel W. Meechan, Robert M. Hamer & Anthony-Samuel LaMantia

  2. Department of Psychiatry, University of North Carolina, Chapel Hill, North Carolina, 27599, USA

    Jeffrey A. Lieberman

  3. Department of Biostatistics, University of North Carolina, Chapel Hill, North Carolina, 27599, USA

    Robert M. Hamer

  4. Department of Cell and Molecular Physiology, University of North Carolina, Chapel Hill, North Carolina, 27599, USA

    Thomas M. Maynard, Daniel W. Meechan, Clifford C. Heindel, Amanda Z. Peters & Anthony-Samuel LaMantia

  5. UNC Neuroscience Center, University of North Carolina, Chapel Hill, North Carolina, 27599, USA

    Anthony-Samuel LaMantia

  6. Department of Cell and Molecular Physiology, 260 MSRB, CB#7545, University of North Carolina, Chapel Hill, NC, 27599, USA

    Anthony-Samuel LaMantia

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  1. Thomas M. Maynard
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Correspondence to Anthony-Samuel LaMantia.

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Maynard, T.M., Meechan, D.W., Heindel, C.C. et al. No evidence for parental imprinting of mouse 22q11 gene orthologs. Mamm Genome 17, 822–832 (2006). https://doi.org/10.1007/s00335-006-0011-0

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  • DOI: https://doi.org/10.1007/s00335-006-0011-0

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