title: Single nucleotide polymorphism discovery in TBX1 in individuals with and without 22q11.2 deletion syndrome.
abstract: BACKGROUND
  Children with 22q11.2 deletion syndrome (22q11.2DS) have a wide range of clinical features. TBX1 has been proposed as a candidate gene for some of the features in this condition. Polymorphisms in the nondeleted TBX1, which may affect the function of the sole TBX1 gene in individuals with the 22q11.2DS, may be a key to understanding the phenotypic variability among individuals with a shared deletion. Comprehensive single nucleotide polymorphism (SNP) discovery by resequencing candidate genes can identify genetic variants that influence a given phenotype. The purpose of this study was to further characterize the sequence variability in TBX1 by identifying all common SNPs in this gene.
  
  
  METHODS
  We resequenced TBX1 in 29 children with a documented 22q11.2 deletion and 95 nondeleted, healthy individuals. We estimated allele frequencies, performed tagSNP selection, and inferred haplotypes. We also compared SNP frequencies between 22q11.2DS and control samples.
  
  
  RESULTS
  We identified 355 biallelic markers among the 190 chromosomes resequenced in the control panel. The vast majority of the markers identified were SNPs (n = 331), and the remainder indels (n = 24). We did not identify SNPs or indels in the cis- regulatory element (FOX-binding site) upstream of TBX1. In children with 22q11.2DS we detected 187 biallelic markers, six of which were indels. Four of the seven coding SNPs identified in the controls were identified in children with 22q11.2DS.
  
  
  CONCLUSIONS
  This comprehensive SNP discovery data can be used to select SNPs to genotype for future association studies assessing the role of TBX1 and phenotypic variability in individuals with 22q11.2DS.
authors: Department of Pediatrics, Division of Craniofacial Medicine, University of Washington and Seattle Children's Hospital, Seattle, Washington 98105-5371, USA. carrie.heike@seattlechildrens.org
authors: Carrie L
authors: CL
authors: Heike
authors: Jacqueline R
authors: JR
authors: Starr
authors: Mark J
authors: MJ
authors: Rieder
authors: Michael L
authors: ML
authors: Cunningham
authors: Karen L
authors: KL
authors: Edwards
authors: Ian B
authors: IB
authors: Stanaway
authors: Dana C
authors: DC
authors: Crawford
mesh_terms: D000015:Abnormalities, Multiple / Q000208:ethnology / Q000235:genetics*; D002648:Child; D002872:Chromosome Deletion; D002892:Chromosomes, Human, Pair 22; D005006:Ethnicity / Q000208:ethnology / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide; D013577:Syndrome; D020825:T-Box Domain Proteins / Q000235:genetics* / Q000378:metabolism; D014861:Washington / Q000453:epidemiology
chemical_list: D020825:T-Box Domain Proteins; C108625:TBX1 protein, human