Aneuploidy is a common feature of many congenital disorders such as DownÂ’s Syndrome, or Trisomy21. It is an extremely common feature in cancer, and nearly all solid tumors and almost half of hematopoetic cancers are aneuploid. The current gold standard for assessment of aneugen activity is the micronucleus assay. We are developing a novel molecular assay for aneuploidy using single cell RNA sequencing (scRNAseq). The assay will indicate whether a cell is euploid or aneuploid, which chromosome(s) affected, and how a toxicant has affected the target cell transcriptome, either independent of or in conjunction with one or more aneuploid chromosomes. Elucidation of the affected or predictive pathways, gene families and cellular processes will provide a rich, highly detailed global view of the consequences of compound exposure on a cell, and may lead to a molecular understanding of different fates for different chromosome aneuploidies.
Public Health Relevance Statement: Aneuploidy is the gain or loss of an entire chromosome in a cell. It is a hallmark of cancers and many reproductive abnormalities, but is paradoxically also a part of normal fetal development. Despite its importance, aneuploidy is not as well studied as other types of genetic alterations. We are developing a novel, high throughput assay to characterize chemicals that cause aneuploidy and their impact at the single cell level.
Project Terms: Acute; Affect; Aneugens; Aneuploid Cells; Aneuploidy; Automobile Driving; Biological Assay; Biology; Cell Line; Cell physiology; Cells; Chemicals; Chromosomes; Complex; Congenital Disorders; Down Syndrome; Evaluation; experimental study; Family Process; Fetal Development; Gene Expression Profile; Gene Family; Genes; Goals; Gold; Government; high throughput screening; in vitro Assay; innovation; Lead; Malignant Neoplasms; Micronucleus Tests; Molecular; Mutation; Nature; nerve stem cell; novel; Nuclear Pore Complex; Pathway interactions; Persons; Phase; Phenotype; Population; Process; reproductive; response; Rotenone; single-cell RNA sequencing; Small Business Innovation Research Grant; Solid Neoplasm; Testing; toxicant; Toxicology; trait; transcriptome; transcriptome sequencing
