In addition to autosomal imprinted and X-linked genes, a small handful of genes involved in immune and nervous system functions are known to show monoallelic expression. Gimelbrant and colleagues developed an array-based method to survey the extent of monoallelic expression on a genome-wide scale. In their method, the authors extract nuclear RNA, convert it into cDNA and, using Affymetrix genomic arrays, generate a 'transcriptome-derived genotype'. At SNP-containing positions that have a heterozygous sequence genotype, a corresponding homozygous transcriptome-derived genotype indicates monoallelic expression at that locus. This array-based method can be validated using direct sequencing and genotyping of RT-PCR products.
The authors looked at almost 4,000 genes in at least two clonal human B lymphoblast cell lines and found that more than 300 genes showed random monoallelic expression, although most also showed biallelic expression in some cell clones. Corroborating experiments included analyses of freshly isolated cells. Extrapolating from their results, the authors predict that at least 1,000 human autosomal genes might be expressed in this way. Importantly, the levels of transcripts from monoallelically expressed genes are lower than those that are biallelically expressed, as revealed by quantitative real-time RT-PCR; Gimelbrant et al. report that in some cases this difference might contribute to disease processes.
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