are inherited, the residual protein levels falls below that required for normal function, and disease phenotype is present. Copy number variation (CNV) refers to the differences in the number of copies of a particular region of the genome. This leads to too many or too few of the dosage sensitive genes. The genomic rearrangements, that is, deletions or duplications, are caused by the mechanism of non-allelic homologous recombination (NAHR). In the case of the Williams Syndrome, the microdeletion includes the ELN gene. The hemizygosity of the elastin is responsible for supravalvular aortic stenosis, the obstruction in the left ventricular outflow of blood in the heart. Methods of detection The most direct method to detect haploinsufficiency is the heterozygous deletion of one allele in a model organism. This can be done in tissue culture cells or in single-celled organisms such as yeast (Saccharomyces cerevisiae). Haploinsufficiency in humans About 3,000 human genes cannot tolerate loss of one of the two alleles. Human diseases caused by haploinsufficiency These include: Some cancers 1q21.1 deletion syndrome 5q- syndrome in myelodysplastic syndrome (MDS) 22q11.2 deletion syndrome CHARGE syndrome Cleidocranial dysostosis Ehlers–Danlos syndrome Frontotemporal dementia caused by mutations in progranulin GLUT1 deficiency (DeVivo syndrome) Haploinsufficiency of A20 Holoprosencephaly caused by haploinsufficiency in the Sonic Hedgehog gene Holt–Oram syndrome Marfan syndrome Phelan–McDermid syndrome Polydactyly Dravet Syndrome ZTTK FOXP1 Syndrome NR4A2-related syndrome References Further reading Genetics