Intra-familial tests of association between familial idiopathic scoliosis and linked regions on 9q31.3-q34.3 and 16p12.3-q22.2

Hum Hered. 2012;74(1):36-44. doi: 10.1159/000343751. Epub 2012 Nov 13.

Abstract

Objective: Custom genotyping of markers in families with familial idiopathic scoliosis were used to fine-map candidate regions on chromosomes 9 and 16 in order to identify candidate genes that contribute to this disorder and prioritize them for next-generation sequence analysis.

Methods: Candidate regions on 9q and 16p-16q, previously identified as linked to familial idiopathic scoliosis in a study of 202 families, were genotyped with a high-density map of single nucleotide polymorphisms. Tests of linkage for fine-mapping and intra-familial tests of association, including tiled regression, were performed on scoliosis as both a qualitative and quantitative trait.

Results and conclusions: Nominally significant linkage results were found for markers in both candidate regions. Results from intra-familial tests of association and tiled regression corroborated the linkage findings and identified possible candidate genes suitable for follow-up with next-generation sequencing in these same families. Candidate genes that met our prioritization criteria included FAM129B and CERCAM on chromosome 9 and SYT1, GNAO1, and CDH3 on chromosome 16.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Chromosome Mapping / methods
  • Chromosomes, Human, Pair 16 / genetics*
  • Chromosomes, Human, Pair 9 / genetics*
  • Female
  • Genetic Heterogeneity
  • Genetic Linkage*
  • Genetic Predisposition to Disease
  • Genotype
  • Humans
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide
  • Scoliosis / genetics*