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New insights into the pathogenic mechanisms associated with CNVs: duplication of 17p13.3, mirror effect in 16p11.2 and recessive phenotype in 22q11.22

von Dott. Mafalda Mucciolo

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[1.] Mmu/Fragment 066 11 - Diskussion
Zuletzt bearbeitet: 2014-11-19 20:01:25 Singulus
BauernOpfer, Fragment, Gesichtet, Mmu, SMWFragment, Schutzlevel sysop, Sha et al 2009

Typus
BauernOpfer
Bearbeiter
Hindemith
Gesichtet
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Untersuchte Arbeit:
Seite: 66, Zeilen: 11-24
Quelle: Sha et al 2009
Seite(n): 4, 5, Zeilen: 4: 17 ff.; 5: 1 ff.
The PPYR1 gene is a key regulator of energy homeostasis and directly involved in the regulation of food intake. PPYR1, also named as neuropeptide Y receptor or pancreatic polypeptide 1, is a member of the seven transmembrane domain-G-protein coupled receptor family. Genetic variation studies have reinforced the potential influence of PPYR1 on body weight in humans. Pancreatic polypeptide is the preferential PPYR1 agonist. Peripheral administration of pancreatic polypeptide inhibits gastric emptying and decreases food intake in humans (Sha 2009). This effect is mediated by direct action on local PPYR1 within the arcuate nucleus. Sha et al, demonstrated that subjects with 10q11.22 loss had 12.4% higher BMI value, and subjects with 10q11.22 gain had 5.4% lower BMI value when compared to normal diploid subjects. PPYR1 null animals showed, for instance, an opposite result. Knockout mice displayed lower body weight and reduced white adipose tissue accompanied with increased plasma levels of pancreatic polypeptide (Sainsbury et al. 2002).

19. Sainsbury A, Schwarzer C, Couzens M, Fetissov S, Furtinger S, Jenkins A, Cox HM, Sperk G, Hökfelt T, Herzog H. Important role of hypothalamic Y2 receptors in body weight regulation revealed in conditional knockout mice. Proc Natl Acad Sci U S A. 2002 Jun 25;99(13):8938-43. Epub 2002 Jun 18.

21. Sha BY, Yang TL, Zhao LJ, Chen XD, Guo Y, Chen Y, Pan F, Zhang ZX, Dong SS, Xu XH, Deng HW. Genome-wide association study suggested copy number variation may be associated with body mass index in the Chinese population. J Hum Genet. 2009 Apr;54(4):199-202. Epub 2009 Feb 20.

Association analyses showed that the CNV 10q11.22 loss was significantly associated with higher BMI. Compared with the 567 subjects with two gene copy numbers (normal diploid), subjects with CNV 10q11.22 loss had 12.4% higher BMI value, and subjects with CNV 10q11.22 gain had 5.4% lower BMI value (Figure 2). [...]

[...]

[...] The PPYR1 gene was a key regulator of energy homeostasis and directly involved in the regulation of food intake.25 PPYR1, also named as neuropeptide Y receptor or pancreatic polypeptide 1, was a member of the seven transmembrane domain-G-protein coupled receptor family. Genetic variation studies have reinforced the potential influence of PPYR1 on body weight in humans.26 Pancreatic polypeptide is the preferential PPYR1 agonist.27 Peripheral administration of pancreatic polypeptide inhibits gastric emptying and decreases food intake in humans.28,29

[page 5]

Sainsbury A et al.25 reported that PPYR1 knockout mice displayed lower body weight and reduced white adipose tissue accompanied with increased plasma levels of pancreatic polypeptide.


25. Sainsbury A, Schwarzer C, Couzens M, Jenkins A, Oakes S, Ormandy C, et al. Y4 receptor knockout rescues fertility in ob/ob mice. Genes Dev 2002;16:1077–1088. [PubMed: 12000791]

26. Kamiji M, Inui A. Neuropeptide y receptor selective ligands in the treatment of obesity. Endocr. Rev 2007;28:664–684. [PubMed: 17785427]

27. Berglund M, Hipskind P, Gehlert D. Recent developments in our understanding of the physiological role of PP-fold peptide receptor subtypes. Exp. Biol. Med. (Maywood.) 2003;228:217–244. [PubMed: 12626767]

28. Batterham R, Le Roux C, Cohen M, Park A, Ellis S, Patterson M, et al. Pancreatic polypeptide reduces appetite and food intake in humans. J. Clin. Endocrinol. Metab 2003;88:3989–3992. [PubMed: 12915697]

29. Schmidt P, Naslund E, Gryback P, Jacobsson H, Holst J, Hilsted L, et al. Arole for pancreatic polypeptide in the regulation of gastric emptying and short-term metabolic control. J. Clin. Endocrinol. Metab 2005;90:5241–5246. [PubMed: 15998783]

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Sichter
(Hindemith), SleepyHollow02


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