title: Genome-wide linkage in a highly consanguineous pedigree reveals two novel loci on chromosome 7 for non-syndromic familial Premature Ovarian Failure.
abstract: BACKGROUND
  The human condition known as Premature Ovarian Failure (POF) is characterized by loss of ovarian function before the age of 40. A majority of POF cases are sporadic, but 10-15% are familial, suggesting a genetic origin of the disease. Although several causal mutations have been identified, the etiology of POF is still unknown for about 90% of the patients.
  
  
  RESULTS
  We report a genome-wide linkage and homozygosity analysis in one large consanguineous Middle-Eastern POF-affected family presenting an autosomal recessive pattern of inheritance. We identified two regions with a LOD(max) of 3.26 on chromosome 7p21.1-15.3 and 7q21.3-22.2, which are supported as candidate regions by homozygosity mapping. Sequencing of the coding exons and known regulatory sequences of three candidate genes (DLX5, DLX6 and DSS1) included within the largest region did not reveal any causal mutations.
  
  
  CONCLUSIONS
  We detect two novel POF-associated loci on human chromosome 7, opening the way to the identification of new genes involved in the control of ovarian development and function.
authors.affiliation: Institut Jacques Monod, Université Denis Diderot, CNRS UMR7592, Paris, France. caburet.sandrine@ijm.univ-paris-diderot.fr
authors.forename: Sandrine
authors.initials: S
authors.lastname: Caburet
authors.forename: Petra
authors.initials: P
authors.lastname: Zavadakova
authors.forename: Ziva
authors.initials: Z
authors.lastname: Ben-Neriah
authors.forename: Kamal
authors.initials: K
authors.lastname: Bouhali
authors.forename: Aurélie
authors.initials: A
authors.lastname: Dipietromaria
authors.forename: Céline
authors.initials: C
authors.lastname: Charon
authors.forename: Céline
authors.initials: C
authors.lastname: Besse
authors.forename: Paul
authors.initials: P
authors.lastname: Laissue
authors.forename: Vered
authors.initials: V
authors.lastname: Chalifa-Caspi
authors.forename: Sophie
authors.initials: S
authors.lastname: Christin-Maitre
authors.forename: Daniel
authors.initials: D
authors.lastname: Vaiman
authors.forename: Giovanni
authors.initials: G
authors.lastname: Levi
authors.forename: Reiner A
authors.initials: RA
authors.lastname: Veitia
authors.forename: Marc
authors.initials: M
authors.lastname: Fellous
mesh_terms: D018912:Arabs; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics*; D003241:Consanguinity; D005260:Female; D008040:Genetic Linkage / Q000235:genetics*; D056426:Genetic Loci / Q000235:genetics*; D006801:Humans; D008126:Lod Score; D018895:Microsatellite Repeats / Q000235:genetics; D010375:Pedigree; D016649:Primary Ovarian Insufficiency / Q000235:genetics*; D017422:Sequence Analysis, DNA