Fine mapping of the 9q31 Hirschsprung’s disease locus

• DOI: 10.1007/s00439-010-0813-8
• Publication Date: 2010-04-01T07:25:17Z
• Authors: C. S. Tang; Y. Sribudiani; X. P. Miao; A. R. de Vries; G. Burzynski; M. T. So; Y. Y. Leon; B. H. Yip; J. Osinga; K. J. W. S. Hui; J. B. G. M. Verheij; S. S. Cherny; P. K. H. Tam; P. C. Sham; R. M. W. Hofstra; M. M. Garcia-Barceló
• Keywords: Penetrance

Hirschsprung's disease (HSCR) is a congenital disorder characterised by the absence of ganglia along variable lengths intestine. The RET gene major HSCR gene. Reduced penetrance mutations and phenotypic variability suggest involvement additional modifying genes in disease. A RET-dependent modifier locus was mapped to 9q31 families bearing no coding sequence (CDS) mutations. Yet, causative be identified. To fine-map region, we genotyped 301 tag-SNPs spanning 7 Mb on 137 Dutch trios. This revealed two HSCR-associated regions that were further investigated 173 Chinese patients 436 controls using genotype data obtained from genome-wide association study recently conducted. Within one identified SVEP1 SNPs found associated with ratifies reported linkage region CDS However, this finding could not replicated. In Chinese, IKBKAP. contrast, stronger carrying p = 5.10 × 10−6 [OR 3.32 (1.99, 5.59)] after replication. HSCR-association for IKBKAP suggests population specificity implies mutation carriers may have an risk. Our supported role development nervous system.