Linkage analysis between BCL3 and nearby genes on 19q13.2 and non-syndromic cleft lip with or without cleft palate in multigenerational Japanese families.

OBJECTIVE

To investigate the linkage between candidate genes on chromosome 19 and cleft lip with or without cleft palate in Japanese using a parametric method.

MATERIALS AND METHODS

After informed consent was obtained, blood samples were drawn from 90 individuals in 14 families, 30 of whom were affected, and genomic DNAs were extracted. PCR-amplified products using four microsatellite markers, D19S178, BCL3, APOC2[007/008] and APOC2[AC1/AC2] located in 19q13.2, were separated by 8% polyacrylamide gel electrophoresis. Linkage analysis was carried out using the MLINK and LINKMAP programs, and logarithm of odds (LOD) scores were calculated for each family.

RESULTS

Before undertaking linkage analysis, we analyzed 74 healthy Japanese subjects and found racial differences in that the observed number of alleles and their heterozygosity were lower in Japanese than in Caucasians, and that both populations tended to show a different allele distribution. In 14 families, two-point maximum LOD score (Zmax) for BCL3 was 0.341 and multi-point Zmax was less than -2 excluding linkage. But in 9 families with left and bilateral CL/P, two-point Zmax for APOC2[AC1/AC2] was 1.701 and multi-point Zmax at APOC2 locus was 1.909.

CONCLUSION

The LOD score was relatively high but provided no evidence of linkage for CL/P to BCL3 and nearby genes in Japanese subjects.