Oxytocin Gene and Peptide Analysis in Children with Autism: A Preliminary Case Study
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Jan 17, 2015
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Abstract
Autism is a neurodevelopmental disorder in which afflicted individuals exhibit characteristic impairments in social interaction, communication, cognition, imagination, and behavior. Though the root cause of autism is unknown, a defect in the oxytocin peptide hormone has previously been proposed to play a possible role in the development of autism. In this study we sequenced the oxytocin gene of two autistic children and eight non-autistic control individuals. There was a lack of sequence polymorphism within the three exons of the oxytocin gene from patient samples and the control group. SELDI-TOF mass spectrometric analysis of the oxytocin peptide in the plasma revealed the presence of mature oxytocin. Other forms or extended forms of oxytocin were not observed. We conclude that in these patients, defects within the oxytocin peptide do not play a role in autism.
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GRUNWALD, JR., William C. et al.
Oxytocin Gene and Peptide Analysis in Children with Autism: A Preliminary Case Study.
Medical Research Archives, [S.l.], n. 1, jan. 2015.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/19>. Date accessed: 19 apr. 2024.
Keywords
Autism, Oxytocin, SELDI-TOF Mass Spectrometry, gene analysis
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Section
Research Articles
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
References
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Corpet, F. 1988. "Multiple sequence alignment with hierarchical clustering." Nucleic Acids Research 16 (22):10881-10890.
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Hook, V. Y. 1985. "Differential distribution of carboxypeptidase-processing enzyme activity and immunoreactivity in membrane and soluble components of chromaffin granules." J. Neurochem. 45 (3):987-989.
Hutchens, T. W., and T. T. Yip. 1993. "New desorption strategies for the mass spectrometric analysis of macromolecules." Rapid Commun. Mass Spectrum 7:576-580.
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Insel, T.R., and L.E. Shapiro. 1992. "Oxytocin receptor distribution reflects social organization in monogamous and polygamous voles." Proc. Natl. Acad. Sci (USA) 89:5981-5985.
Issaq, H.J., T. D. Veenstra, T. P. Conrads, and D. Felschow. 2002. "The SELDI-TOF MS approach to proteomics: protein profiling and biomarker identification." Biochem. Biophys. Res. Commun. 292:587-592.
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Nishioka, T., J. Anselmo-Franci, P. Li, F. Callahan, and M. Morris. 1998. "Stress increases oxytocin release within the hypothalamic paraventricular nucleus." Brain Research 781:57-61.
Pickles, Andrew, P. Bolton, H. MacDonald, A. Bailey, A. Le Couteur, C.-H. Sim, and M. Rutter. 1995. "Latent-class analysis of recurrence risks for complex phenotypes with selection and measurement error: A twin and family history study of autism." American Journal of Human Genetics 57 (3):717-726.
Samson, W., M. Lumpkin, and S. Mccann. 1986. "Evidence for a physiological role for oxytocin in the control of prolactin secretion." Endocrinology 119:554-560.
Sausville, E., D. Carney, and J. Battey. 1985. "The human vasopressin gene is linked to the oxytocin gene and is selectively expressed in a cultured lung cell line." J. Biol. Chem. 260:10236-10241.
Schopler, E., R.J. Reichler, R.F. DeVellis, and K. Daly. 1980. "Toward objective classification of childhood autism: Childhood Autism Rating Scale (CARS)." Journal of Autism & Developmental Disorders 10:91-103.
Seidah, NG, L Gaspar, P Mion, M Marcinkiewicz, M Mbikay, and M Chretien. 1990. "cDNA Sequence of two distinct pituitary proteins homologous to Kex2 and Furin gene products: tissue-specific mRNAs encoding candidates for pro-hormone processing proteinases." DNA and Cell Biol. 9 (6):415-424.
Steiner, D.F., S.P. Smeekens, S. Ohagi, and S.J. Chan. 1992. "The new enzymology of precursor processing endoproteases." J. Biol. Chem. 267 (33):23435-23438.
Utsunomiya, N., S. Ohagi, T. Sanke, H. Tatsuta, T. Hanabusa, and K. Nanjo. 1998. "Organization of the human carboxypeptidase E gene and molecular scanning for mutations in Japanese subjects with NIDDM or obesity." Diabetologica 41:701-705.
van Wimersma Greidanus, T. B., and C. Maigret. 1996a. "The role of limbic vasopressin and oxytocin in social recognition." Brain Research 713:152-159.
van Wimersma Greidanus, T. B., and C. Maigret. 1996b. "The role of limbic vasopressin and oxytocin in social recognition." Brain Research 713:153-159.
Varlamov, O., E. H. Leiter, and L. Fricker. 1996. "Induced and spontaneous mutations at Ser202 of carboxypeptidase E." J. Biol. Chem. 271 (24):13981-13986.
Wing, L. 1997. "The autistic spectrum." Lancet 350:1761-1766.
Wing, L. , and J. GOuld. 1979. "Severe impairments of social interaction and associated abnormalities in children: epidemiology and classification." J. Autism Develop. Disorders 9:11-29.
Witt, D. M. 1995. "Oxytocin and rodent sociosexual responses: from behavior to gene expression." Neurosci Biobehav. Rev. 19 (315-324).
Wright, G. L., L. H. Cazares, S. M. Leung, S. Nasim, B. L. Adam, T. T. Yip, P. F. Schellhammer, L. Gong, and A. Vlahou. 1999. "Proteinchip surface enhanced laser desorption/ionization (SELDI) mass spectrometry: a novel protein biochip technology for detection of prostate cancer biomarkers in complex protein mixtures." Prost. Can. Prostat. Dis. 2:264-276.
Young, L. J. 2001. "Oxytocin and Vasopressin as Candidate Genes for Psychiatric Disorders: Lessons from Animal Models." Am. J. Med. Genet. 105:53-54.
Young, Larry J., Miranda M. Lim, Brenden Gingrich, and Thomas R. Insel. 2001. "Cellular mechanisms of social attachment." Hormones and Behavior 40 (2):133-138.
Bailey, A. J., and M. L. Rutter. 1991. "Autism." Science Progress 75 (298):389-402.
Barberis, C., and E. Tribollet. 1996. "Vasopressin and oxytocin recetpors in the central nervous system." Crit. Rev. Neurobiol. 10:119-154.
Brownstein, M. J. 1983. "Biosynthesis of vasopressin and oxytocin." Annu Rev. Physiol. 45:129-135.
Carter, C. S. 1992. "Oxytocin and sexual behavior." Neurosci Biobehav. Rev. 16 (131-144).
Chauvet, M T, D Hurpet, J Chauvet, and R Acher. 1983. "Identification of hyman neurophysins complete amino-acid sequences of MSEL and VLDV neurophysins." Proc.Natl. Acad. Sci.USA 80 (10):2839-2843.
Cook, E. H., R. Y. Courchesne, N. J. Cox, C. Lord, D. Gonen, S. J. Guter, A. Lincoln, K. Nix, R. Haas, B. L. Leventhal, and E. Courchesne. 1998. "Linkage-disequilibrium mapping of autistic diosrder with 15q11-13 markers." Am. J. Hum. Genet. 62:1077-1083.
Cool, D. R., and D. DeBrosse. 2003. "Extraction of oxytocin and arginine-vasopressin from serum and plasma for radioimmunoassay and surface enhanced laser desorption-ionization time of flight mass spectrometry." J. Chromatography B 792:375-380.
Corpet, F. 1988. "Multiple sequence alignment with hierarchical clustering." Nucleic Acids Research 16 (22):10881-10890.
Fricker, L. D. 1991. Peptide processing exopeptidases: amino-and carboxy-peptidases involved with peptide biosynthesis. Edited by L.D. Fricker, Peptide biosynthesis and processing. Boca Raton: CRC Press.
Fricker, L. D., Y. L. Berman, E. H. Leiter, and L. A. Devi. 1996. "Carboxypeptidase E activity is deficient in mice with the fat mutation. Effect on peptide processing." J Biol Chem 271 (48):30619-24.
Fricker, L. D., and S. H. Snyder. 1983. "Purification and characterization of enkephalin convertase, an enkephalin-synthesizing carboxypeptidase." J. Biol. Chem. 258 (18):10950-10955.
Fricker, LD. 1988. "Carboxypeptidase E." Annu. Rev. Physiol. 50:309-321.
Green, LeeAnne, Deborah Fein, Charlotte Modahl, Carl Feinstein, Lynn Waterhouse, and Mariana Morris. 2001. "Oxytocin and autistic disorder: Alterations in peptide forms." Biol. Psych. 50 (8):609-613.
Hook, V. Y. 1985. "Differential distribution of carboxypeptidase-processing enzyme activity and immunoreactivity in membrane and soluble components of chromaffin granules." J. Neurochem. 45 (3):987-989.
Hutchens, T. W., and T. T. Yip. 1993. "New desorption strategies for the mass spectrometric analysis of macromolecules." Rapid Commun. Mass Spectrum 7:576-580.
Insel, T. R. 1997. "A neurobiological basis of social attachment." Am. J. Psychiatry 154 (6):726-735.
Insel, T. R., D. J. O'Brien, and J. F. Leckman. 1999. "Oxytocin, vasopressin and autism: is there a connection?" Biol. Psychiatry 45:145-157.
Insel, T.R. 1992. "Oxytocin: a neuropeptide for affiliation-evidence from behavioral, receptor autoradiographic and comparative studies." Psychoneuroendocrinology 17:3-33.
Insel, T.R., and L.E. Shapiro. 1992. "Oxytocin receptor distribution reflects social organization in monogamous and polygamous voles." Proc. Natl. Acad. Sci (USA) 89:5981-5985.
Issaq, H.J., T. D. Veenstra, T. P. Conrads, and D. Felschow. 2002. "The SELDI-TOF MS approach to proteomics: protein profiling and biomarker identification." Biochem. Biophys. Res. Commun. 292:587-592.
Kanner, L. 1943. "Autistic disturbances of affective contact. ." Nervous Child 2:217-250.
Land, H., M. Grez, S. Ruppert, H. Schmale, M. Rehbein, D. Richter, and G. Schutz. 1983. "Deduced amino acid sequence from the bovine oxytocin-neurophysin I precursor cDNA." Nature 302:342-344.
Lindberg, I. 1991. "The new eukaryotic precursor processing proteinases." Molecular Endocrinol. 5 (10):1361-1365.
Merchant, M, and S R Weinberger. 2000. "Recent advancements in surface-enhanced laser desorption/ionization-time of flight-mass spectrometry." Electrophoresis 21 (Apr):1164-77.
Modahl, Charlotte, Leeanne Green, Deborah Fein, Mariana Morris, Lynn Waterhouse, Carl Feinstein, and Harriet Levin. 1998. "Plasma oxytocin levels in autistic children." Biological Psychiatry 43 (4):270-277.
Naggert, J. K., L. D. Fricker, O. Varlamov, P. M. Nishina, Y. Rouille, D. F. Steiner, R. J. Carroll, B. J. Paigen, and E. H. Leiter. 1995. "Hyperproinsulinemia in obese fat/fat mice associated with a carboxypeptidase E mutation which reduces enzyme activity." Nature Gen. 10:135-142.
Nishioka, T., J. Anselmo-Franci, P. Li, F. Callahan, and M. Morris. 1998. "Stress increases oxytocin release within the hypothalamic paraventricular nucleus." Brain Research 781:57-61.
Pickles, Andrew, P. Bolton, H. MacDonald, A. Bailey, A. Le Couteur, C.-H. Sim, and M. Rutter. 1995. "Latent-class analysis of recurrence risks for complex phenotypes with selection and measurement error: A twin and family history study of autism." American Journal of Human Genetics 57 (3):717-726.
Samson, W., M. Lumpkin, and S. Mccann. 1986. "Evidence for a physiological role for oxytocin in the control of prolactin secretion." Endocrinology 119:554-560.
Sausville, E., D. Carney, and J. Battey. 1985. "The human vasopressin gene is linked to the oxytocin gene and is selectively expressed in a cultured lung cell line." J. Biol. Chem. 260:10236-10241.
Schopler, E., R.J. Reichler, R.F. DeVellis, and K. Daly. 1980. "Toward objective classification of childhood autism: Childhood Autism Rating Scale (CARS)." Journal of Autism & Developmental Disorders 10:91-103.
Seidah, NG, L Gaspar, P Mion, M Marcinkiewicz, M Mbikay, and M Chretien. 1990. "cDNA Sequence of two distinct pituitary proteins homologous to Kex2 and Furin gene products: tissue-specific mRNAs encoding candidates for pro-hormone processing proteinases." DNA and Cell Biol. 9 (6):415-424.
Steiner, D.F., S.P. Smeekens, S. Ohagi, and S.J. Chan. 1992. "The new enzymology of precursor processing endoproteases." J. Biol. Chem. 267 (33):23435-23438.
Utsunomiya, N., S. Ohagi, T. Sanke, H. Tatsuta, T. Hanabusa, and K. Nanjo. 1998. "Organization of the human carboxypeptidase E gene and molecular scanning for mutations in Japanese subjects with NIDDM or obesity." Diabetologica 41:701-705.
van Wimersma Greidanus, T. B., and C. Maigret. 1996a. "The role of limbic vasopressin and oxytocin in social recognition." Brain Research 713:152-159.
van Wimersma Greidanus, T. B., and C. Maigret. 1996b. "The role of limbic vasopressin and oxytocin in social recognition." Brain Research 713:153-159.
Varlamov, O., E. H. Leiter, and L. Fricker. 1996. "Induced and spontaneous mutations at Ser202 of carboxypeptidase E." J. Biol. Chem. 271 (24):13981-13986.
Wing, L. 1997. "The autistic spectrum." Lancet 350:1761-1766.
Wing, L. , and J. GOuld. 1979. "Severe impairments of social interaction and associated abnormalities in children: epidemiology and classification." J. Autism Develop. Disorders 9:11-29.
Witt, D. M. 1995. "Oxytocin and rodent sociosexual responses: from behavior to gene expression." Neurosci Biobehav. Rev. 19 (315-324).
Wright, G. L., L. H. Cazares, S. M. Leung, S. Nasim, B. L. Adam, T. T. Yip, P. F. Schellhammer, L. Gong, and A. Vlahou. 1999. "Proteinchip surface enhanced laser desorption/ionization (SELDI) mass spectrometry: a novel protein biochip technology for detection of prostate cancer biomarkers in complex protein mixtures." Prost. Can. Prostat. Dis. 2:264-276.
Young, L. J. 2001. "Oxytocin and Vasopressin as Candidate Genes for Psychiatric Disorders: Lessons from Animal Models." Am. J. Med. Genet. 105:53-54.
Young, Larry J., Miranda M. Lim, Brenden Gingrich, and Thomas R. Insel. 2001. "Cellular mechanisms of social attachment." Hormones and Behavior 40 (2):133-138.