people can derive from lost or duplicated segments of chromosomes, called copy number variants (CNV). Variation in gene copy number can influence the activity of genes and accounts for a significant amount of genetic difference between people [49]. A recent work of Farooqi et al. analyzed the genomes of 300 obese children for missing or duplicated chromosome segments. Mutations in LEPR, POMC, and MC4R genes were previously excluded by direct nucleotide sequencing. The commonest CNV found in these patients was identified in five unrelated children harboring overlapping deletions on chromosome 16p11.2, which encompasses the gene SH2B1 [31]. The phenotype of the children with SH2B1-containing deletions is characterized by extreme hyperphagia and fasting insulin levels disproportionately elevated compared to age- and obesity-matched controls. Deletions on chromosome 16p11.2 have been reported in an adult population with severe obesity [50], further demonstrating the potential importance in SH2B1 gene variation and the development of human obesity.
