Pathogenic aberrations revealed exclusively by single nucleotide polymorphism (SNP) genotyping data in 5000 samples tested by molecular karyotyping

Background Several recent studies have demonstrated the use of single nucleotide polymorphism ( SNP) arraysfor the investigation of intellectual disability, developmental delay, autism or congenital abnormalities. In addition to LogR ‘copy number’ data, these arrays provide SNP genotypingdata for gene level autozygosity mapping, estimating low levels of mosaicism, assessing long continuous stretches of homozygosity (LCSH), detection of uniparental disomy, and ‘autozygous’ regions. However, there remains little specific information on the clinical utility of this genotyping data. Methods Molecular karyotyping, using SNP array, was performed on 5000 clinical samples. Results Clinically significant‘LogR neutral’ genotyping abnormalities were detected in 0.5% of cases. Among these were a single case of chimerism, 12 cases with low level chromosome mosaicism, and 11 cases with an LCSH associated with uniparental disomy. In addition, the genotyping data revealed several LCSH associated with clinically relevant ‘recessive type’ genetic defects. Conclusions These results demonstrate the utility of SNP genotypingdata for detection of clinically significantabnormalities, including chimerism/ mosaicismand recessive Mendelian disordersassociated with autozygosity. The incidence of clinically significantlow level mosaicisminferred from these cases suggests that this has hitherto been underestimated and chromosome mosaicismfrequently occurs in the absence of indicative clinical features. The growing appreciation among clinicians and demand for SNP genotypingdata poses significant challenges for the interpretation of LCSH, especially where there is no detailed phenotypic description to direct laboratory analysis. Finally, reporting of unexpected or hidden consanguinity revealed by SNP arrayanalysis raises potential ethical and legal issues.