Observation of null alleles of microsatellite markers in a Chinese population

Introduction Genotyping of a set of microsatellite markers is often necessary to map genes for complex human diseases by linkage analysis. Presence of null alleles (such as a mutation in the primer-binding sequence) can lead to pseudo-deficiency of heterozygosity.

Materials and methods We completed a genomic scan using 367 autosomal markers on 1477 Chinese subjects in a total of 337 nuclear families. Two markers with apparent non-Mendelian inheritance patterns were further investigated: marker GGAA15B08 results were re-scored, and marker GATA29A01 was re-genotyped using redesigned primers.

Results The GGAA15B08 marker was found to contain a relatively frequent (24.4%) 185-bp allele in the Chinese that was previously treated as a ‘null allele’. Marker GATA29A01 contained a null allele due to a mutation within the annealing region of its reverse primer. With a pair of redesigned PCR primers, the null allele diminished. In this study, we have a power > 82% to detect null alleles of frequency 0.04 or greater.

Discussion The presence of GATA29A01 null alleles in this population was quite common (31.4%). Identification of markers with null alleles in our study has great implications in paternity testing, linkage analysis and forensic DNA testing. Particular care should be taken in analysing microsatellite genotype results to avoid this problem.