Blood expression profiles for tuberous sclerosis complex 2, neurofibromatosis type 1, and Down's syndrome.

Blood gene expression profiling has been applied to a variety of hematological malignancies, autoimmune disorders, and infectious diseases. This study applies this approach to genetic diseases without obvious blood phenotypes. Three genetic diseases including tuberous sclerosis complex 2, neurofibromatosis type 1, and Down's syndrome were compared with a group of healthy controls. RNA from whole blood was surveyed using Affymetrix U133A arrays. Each disease was associated with a unique gene expression pattern in blood that can be accurately distinguished by a classifier. Genes on chromosome 21 were overexpressed in Down's syndrome, and genes controlling cell cycle and proliferation were associated with tuberous sclerosis complex type 2 or neurofibromatosis type 1. A subset of genes involved in cardiac development or remodeling were overexpressed in patients with Down's syndrome and congenital heart defects. These findings suggest that blood gene expression profiling on a broader basis might be useful for genetic disease screening/diagnosis and might help elucidate mechanisms and pathways that lead to genotype-phenotype differences.

ELF a beta-spectrin is a neuronal precursor cell marker in developing mammalian brain; structure and organization of the elf/beta-G spectrin gene.

Spectrins play a pivotal role in axonal transport, neurite extension, the organization of synaptic vesicles, as well as for protein sorting in the Golgi apparatus and cell membrane. Among spectrins there is great variability in sequence composition, tissue distribution, and function, with two known genes encoding the alpha-chain, and at least five encoding the beta-chain. It remains unclear as to whether novel beta-spectrins such as elf1-4 are distinct genes or beta-G-spectrin isoforms. The role for ELF in the developing nervous system has not been identified to date. In this study we demonstrate the genomic structure of elf-3, as well as the expression of ELF in the developing mouse brain using a peptide specific antibody against its distinctive amino-terminal end. Full genomic structural analyses reveal that elf-3 is composed of 31 exons spanning approximately 67 kb, and confirm that elf and mouse brain beta-G-spectrin share multiple exons, with a complex form of exon/intron usage. In embryonic stages, E9-12, anti-ELF localized to the primary brain vesicular cells that also labeled strongly with anti-nestin but not anti-vimentin. At E12-14, anti-ELF localized to axonal sprouts in the developing neuroblasts of cortex and purkinje cell layer of the cerebellum, as well as in cell bodies in the diencephalon and metencephalon. Double labeling identified significant co-localization of anti-ELF, nestin and dystrophin in sub ventricular zone cells and in stellate-like cells of the developing forebrain. These studies define clearly the expression of ELF, a new isoform of beta-G-spectrin in the developing brain. Based on its expression pattern, ELF may have a role in neural stem cell development and is a marker of axonal sprouting in mid stages of embryonic development.