POSTER NO: 553

Haplotype frequencies of JAG1 SNPs in sixteen populations

¹P.S. Lai, ¹S.L. Low, ²J. Miranda, ³S.G.K. Seah, ¹M.M. Aw, ¹S.H. Quak, ³E.P.H. Yap
¹Dept of Paediatrics, National University of Singapore, Singapore 119074, ²National Neuroscience Institute, Singapore 308433, ³Defence Medical Research Institute, Singapore 118253

The human JAG1 gene codes for a transmembrane receptor which acts as a ligand in the Notch signaling pathway. This evolutionarily conserved pathway was first described in Drosophila and has been found to play a critical role in cell fate determination during differentiation and embryonic development in both vertebrates and non-vertebrates. Mutations in JAG1 gene have been found in patients with Alagille syndrome, a pleiotrophic disease, characterized by abnormal development of the liver, eye, heart and vertebra. JAG1 has also been associated with isolated congenital heart defects such as Fallot's tetralogy and pulmonary stenosis. We have previously reported the identification and characterization of two synonymous SNPs (C3417T and C3528T) in exon 26. We now report a haplotype study using these SNPs involving sixteen population groups, including 10 from Asian populations. The distribution frequencies of the SNPs were similar in most of the Asian populations with the most common haplotype being 3417T-3528C and the rarest being 3417C-3528T. Other haplotypes predominated in the remaining populations (Caucasian, African- American, Middle Eastern, American Indian, Mexican and Puerto Rican). For the JAG1 locus, haplotype frequencies were found to reflect the geographical and ethnic distributions of populations. This data could be useful for genetic linkage and association studies of congenital malformations.