Item type:Thesis, Open Access

Hauptgeneffekt auf die Entstehung exzremer Adipositas bei Kindern und Jugendlichen durch funktionell relevante Mutationen des Melanocortin 4 Rezeptor-Gens

Thumbnail Image

Files

dcmv.pdf (4.15 MB)

Date

2004-11-03

relationships.isAuthorOf

Publisher

Philipps-Universität Marburg
DOI

item.page.supervisor-of-thesis

Abstract

We initially performed a mutation screen of the coding region of the MC4R in 808 extremely obese children and adolescents and 327 underweight or normal-weight controls allowing for a case-control study. A total of 16 different missense, nonsense, and frameshift mutations were found in the obese study group; five of these have not been observed previously. In vitro assays revealed that nine [the haplotype (Y35X; D37V) was counted as one mutation] of the 16 mutations led to impaired cAMP responses, compared with wild-type receptor constructs. In contrast, only one novel missense mutation was detected in the controls, which did not alter receptor function. The association test based on functionally relevant mutations was positive (P = 0.006, Fisher s exact test, one-sided). We proceeded by screening a total of 1040 parents of 520 of the aforementioned obese young index patients to perform transmission disequilibrium tests. The 11 parental carriers of functionally relevant mutations transmitted the mutation in 81.8% (P = 0.033; exact one-sided McNemar test). These results support the hypothesis that these MC4R mutations represent major gene effects for obesity.

Review

Metadata

Contributors
Supervisor:
Dates
Created: 2004Issued: 2004-11-03Updated: 2011-08-10
DOI
https://doi.org/10.17192/z2004.0497
Faculty
Medizin
Publisher
Philipps-Universität Marburg
Language
ger
Data types
DoctoralThesis
Keywords
GenotypeMutationTransmissionTransmissions Disequilibrium TestObesityMelanocortin-4-receptor
DFG-subjects
MutationTransmissionskoeffizientPolymerase-KettenreaktionGenmutationFettsuchtMelanocortin-4-Rezeptor
DDC-Numbers
610
License
https://rightsstatements.org/vocab/InC-NC/1.0/
URI
https://open.uni-marburg.de/handle/10.17192/z2004.0497
show more
Vogel, Constanze Martina: Hauptgeneffekt auf die Entstehung exzremer Adipositas bei Kindern und Jugendlichen durch funktionell relevante Mutationen des Melanocortin 4 Rezeptor-Gens. : Philipps-Universität Marburg 2004-11-03. DOI: https://doi.org/10.17192/z2004.0497.

License

item.page.license.under-copyright
This item has been published with the following license: In Copyright