Rapid screening for chromosomal aneuploidies using array-MLPA

We developed a method of array-based MLPA to rapidly screen for common aneuploidies. We designed 116 universal tag-probes covering chromosomes 13, 18, 21, X, and Y, and 8 control autosomal genes. We performed MLPA and hybridized the products on a 4-well flow-through microarray system. We determined chromosome copy numbers by analyzing the relative signals of the chromosome-specific probes.In a blind study of 161 peripheral blood and 12 amniotic fluid samples previously karyotyped, 169 of 173 (97.7%) including all the amniotic fluid samples were correctly identified by array-MLPA. Furthermore, we detected two chromosome X monosomy mosaic cases in which the mosaism rates estimated by array-MLPA were basically consistent with the results from karyotyping. Additionally, we identified five Y chromosome abnormalities in which G-banding could not distinguish their origins for four of the five cases.Our study demonstrates the successful application and strong potential of array-MLPA in clinical diagnosis and prenatal testing for rapid and sensitive chromosomal aneuploidy screening. Furthermore, we have developed a simple and rapid procedure for screening copy numbers on chromosomes 13, 18, 21, X, and Y using array-MLPA.Chromosome abnormalities are a well-established cause of pregnancy loss. The most common are autosomal aneuploidy (~75%), followed by polyploidy (~13%), sex chromosome abnormalities (~8%) and structural imbalance (~4%) [1,2]. Trisomy of chromosome 21, 13, or 18 as well as sex chromosome aneuploidy account for 60-80% of abnormal fetal karyotypes detected in cultured amniotic fluid cells [3].For non-mosaic standard trisomy, cultured karyotype analysis has been considered a reliable detector of fetal abnormality [4]. However, the sensitivity of karyotyping depends on the number of cells established in a particular culture, and results are usually not available for 3-4 days or more. Furthermore, it is very difficult to identify chromosome microdeletions. In addit