New techniques to understand chromosome dosage: mouse models of aneuploidy.
Aberrations in human chromosome copy number and structure are common and extremely deleterious. Their downstream effects on phenotype are caused by aberrant dosage of sequences in the affected regions. However, we know little about why the abnormal gene copy number causes disease or why specific features result from deficits in specific chromosomes. Mice are the organism of choice to help us try to tease apart the complex relationships between genotype and phenotype in aneuploidy and segmental aneusomy syndromes. As new technologies such as chromosome engineering and the creation of transchromosomic mice become routine, these will help us identify individual dosage-sensitive genes that are causative in specific syndromes and will enable us to produce mouse models to accurately recapitulate human chromosomal disorders.
Tybulewicz
Victor L J
VL
Division of Immune Cell Biology, MRC National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK. vtybule@nimr.mrc.ac.uk
Fisher
Elizabeth M C
EM
D000782:Aneuploidy; D000818:Animals; D005260:Female; D018628:Gene Dosage; D020440:Gene Duplication; D005818:Genetic Engineering; D005821:Genetic Techniques; D006801:Humans; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D023421:Models, Animal; D008957:Models, Genetic; D009030:Mosaicism; D016296:Mutagenesis; D010641:Phenotype