title: Sequencing of theTBX6Gene in Families with Familial Idiopathic Scoliosis.
abstract: METHODS
  A hypothesis-driven study was conducted in a familial cohort to determine the potential association between variants within theTBX6gene and Familial Idiopathic Scoliosis (FIS).
  
  
  OBJECTIVE
  To determine if variants within exons of theTBX6gene segregate with the FIS phenotype within a sample of families with FIS.
  
  
  BACKGROUND
  Idiopathic Scoliosis (IS) is a structural curvature of the spine whose underlying genetic etiology has not been established. IS has been reported to occur at a higher rate than expected in family members of individuals with congenital scoliosis (CS), suggesting that the two diseases might have a shared etiology. TheTBX6gene on chromosome 16p, essential to somite development, has been associated with CS in a Chinese population. Previous studies have identified linkage to this locus in families with FIS, and specifically with rs8060511, located in an intron of theTBX6gene.
  
  
  METHODS
  Parent-offspring trios from 11 families (13 trios, 42 individuals) with FIS were selected for Sanger sequencing of theTBX6gene. Trios were selected from a large population of families with FIS in which a genome-wide scan had resulted in linkage to 16p.
  
  
  RESULTS
  Sequencing analyses of the subset of families resulted in the identification of five coding variants. Three of the five variants were novel; the remaining two variants were previously characterized and account for 90% of the observed variants in these trios. In all cases, there was no correlation between transmission of theTBX6variant allele and FIS phenotype. However, an analysis of regulatory markers in osteoblasts showed that rs8060511 is in a putative enhancer element.
  
  
  CONCLUSIONS
  Although this study did not identify anyTBX6coding variants that segregate with FIS, we identified a variant that is located in a potentialTBX6enhancer element. Therefore, further investigation of the region is needed.
authors.affiliation: Department of Orthopedics, University of Colorado Denver Anschutz Medical Campus, 13001 E 17th Place, Aurora, Colorado 80045, USA.
authors.forename: Erin E
authors.initials: EE
authors.lastname: Baschal
authors.affiliation: Department of Orthopedics, University of Colorado Denver Anschutz Medical Campus, 13001 E 17th Place, Aurora, Colorado 80045, USA.
authors.forename: Kandice
authors.initials: K
authors.lastname: Swindle
authors.affiliation: Genometrics Section, National Human Genome Research Institute, National Institutes of Health, 333 Cassell Drive, Baltimore, Maryland 21224, USA.
authors.forename: Cristina M
authors.initials: CM
authors.lastname: Justice
authors.affiliation: Musculoskeletal Research Center, Children's Hospital Colorado, 13123 East 16 Avenue, Aurora, Colorado, 80045.
authors.forename: Robin M
authors.initials: RM
authors.lastname: Baschal
authors.affiliation: Molecular Biology Facility, Stowers Institute, 1000 E. 50th Street, Kansas City, Missouri 64110, United States.
authors.forename: Anoja
authors.initials: A
authors.lastname: Perera
authors.affiliation: Department of Orthopedics, University of Colorado Denver Anschutz Medical Campus, 13001 E 17th Place, Aurora, Colorado 80045, USA.
authors.forename: Cambria I
authors.initials: CI
authors.lastname: Wethey
authors.affiliation: Department of Orthopedics, University of Colorado Denver Anschutz Medical Campus, 13001 E 17th Place, Aurora, Colorado 80045, USA.
authors.forename: Alex
authors.initials: A
authors.lastname: Poole
authors.affiliation: Department of Cell Biology and Development, Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), 1 rue Laurent Fries, BP 10142, 67404 Illkirch CEDEX, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Pourquié
authors.affiliation: Department of Cell Biology and Development, Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), 1 rue Laurent Fries, BP 10142, 67404 Illkirch CEDEX, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Tassy
authors.affiliation: Department of Orthopedics, University of Colorado Denver Anschutz Medical Campus, 13001 E 17th Place, Aurora, Colorado 80045, USA ; Musculoskeletal Research Center, Children's Hospital Colorado, 13123 East 16 Avenue, Aurora, Colorado, 80045.
authors.forename: Nancy H
authors.initials: NH
authors.lastname: Miller
keywords: DNA sequencing; TBX6 gene; chromosome 16p11.2; congenital scoliosis; idiopathic scoliosis