title: Fine mapping of genetic susceptibility to polycystic ovary syndrome on chromosome 19p13.2 and tests for regulatory activity.
abstract: BACKGROUND
  Little is known about genes that contribute to polycystic ovary syndrome (PCOS). We previously found linkage and association of PCOS with the dinucleotide marker D19S884 in two independent sets of families; allele 8 of D19S884 confers increased risk.
  
  
  OBJECTIVE
  The objectives of the study were: 1) use the transmission/disequilibrium test (TDT) to assess linkage and association between PCOS and D19S884 (and nearby markers) in a third set of families; and 2) test D19S884 and surrounding DNA sequence for in vitro regulatory activity in lymphoblastoid cell lines (LCLs) and granulosa cells.
  
  
  METHODS
  We studied 98 new families with a PCOS proband, father, mother, and other available offspring. We analyzed data from these families separately and in combination with data obtained previously.
  
  
  METHODS
  Interventions were venipuncture.
  
  
  METHODS
  Measures were transmission frequencies and in vitro functional studies.
  
  
  RESULTS
  The first result we found was that in the 98 new families, the TDT was significant for allele 8 of D19S884 (P = 0.043). In the total collection of 465 families, the TDT evidence is very strong (nominal P < 7 x 10(-5)). Results for all other genetic markers near D19S884 were nonsignificant after correction for multiple testing. The second result was that an approximately 800-bp fragment containing various alleles of D19S884 showed modest but reproducible promoter activity in LCLs. However, no allelic differences were detected. No activity of this fragment was detected in granulosa cells.
  
  
  CONCLUSIONS
  This is the second independent confirmation of linkage and association of D19S884 with PCOS. We found in addition that some sequence in the region of D19S884 confers in vitro promoter activity in LCLs.
authors.affiliation: Department of Genetics, Center for Research on Reproduction and Women's Health, University of Pennsylvania School of Medicine, Philadelphia, PA 19104-6145, USA.
authors.forename: D R
authors.initials: DR
authors.lastname: Stewart
authors.forename: B A
authors.initials: BA
authors.lastname: Dombroski
authors.forename: M
authors.initials: M
authors.lastname: Urbanek
authors.forename: W
authors.initials: W
authors.lastname: Ankener
authors.forename: K G
authors.initials: KG
authors.lastname: Ewens
authors.forename: J R
authors.initials: JR
authors.lastname: Wood
authors.forename: R S
authors.initials: RS
authors.lastname: Legro
authors.forename: J F
authors.initials: JF
authors.lastname: Strauss
authors.forename: A
authors.initials: A
authors.lastname: Dunaif
authors.forename: R S
authors.initials: RS
authors.lastname: Spielman
mesh_terms: D002874:Chromosome Mapping; D002888:Chromosomes, Human, Pair 19; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium; D011085:Polycystic Ovary Syndrome / Q000235:genetics*; D011401:Promoter Regions, Genetic; D012091:Repetitive Sequences, Nucleic Acid