Deciphering genetic disease in the genomic era: the model of GnRH deficiency.

Details

Serval ID
serval:BIB_B55BBC53A8DE
Type
Article: article from journal or magazin.
Publication sub-type
Review (review): journal as complete as possible of one specific subject, written based on exhaustive analyses from published work.
Collection
Publications
Institution
Title
Deciphering genetic disease in the genomic era: the model of GnRH deficiency.
Journal
Science Translational Medicine
Author(s)
Sykiotis G.P., Pitteloud N., Seminara S.B., Kaiser U.B., Crowley W.F.
ISSN
1946-6242 (Electronic)
ISSN-L
1946-6234
Publication state
Published
Issued date
2010
Peer-reviewed
Oui
Volume
2
Number
32
Pages
32rv2
Language
english
Notes
Publication types: Journal Article ; Research Support, American Recovery and Reinvestment Act ; Research Support, N.I.H., Extramural ; Review
Publication Status: ppublish
Abstract
Isolated gonadotropin-releasing hormone (GnRH) deficiency is a treatable albeit rare form of reproductive failure that has revealed physiological mechanisms controlling human reproduction, but despite substantial progress in discovering pathogenic single-gene defects, most of the genetic basis of GnRH deficiency remains uncharted. Although unbiased genetic investigations of affected families have identified mutations in previously unsuspected genes as causes of this disease in some cases, their application has been severely limited because of the negative effect of GnRH deficiency on fertility; moreover, relatively few of the many candidate genes nominated because of biological plausibility from in vitro or animal model experiments were subsequently validated in patients. With the advent of exciting technological platforms for sequencing, homozygosity mapping, and detection of structural variation at the whole-genome level, human investigations are again assuming the leading role for gene discovery. Using human GnRH deficiency as a paradigm and presenting original data from the screening of numerous candidate genes, we discuss the emerging model of patient-focused clinical genetic research and its complementarities with basic approaches in the near future.
Keywords
Animals, Cooperative Behavior, Fertility/genetics, Genetic Association Studies, Genetic Markers, Genetic Predisposition to Disease, Genetic Testing, Genomics/methods, Gonadotropin-Releasing Hormone/deficiency, Gonadotropin-Releasing Hormone/genetics, Humans, Infertility/genetics, Infertility/physiopathology, International Cooperation, Mutation, Pedigree, Phenotype, Translational Medical Research
Pubmed
Web of science
Create date
09/03/2011 9:04
Last modification date
20/08/2019 15:23
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