Imprinting disorders: non-Mendelian mechanisms affecting growth.
Most autosomal genes are expressed from both maternal and paternal alleles. However, imprinted genes are an example of non-Mendelian genetics, in which only one member of the gene pair is expressed and expression is determined by the parent of origin. Imprinted genes may account for 0.1-1% of all mammalian genes. At least 50 imprinted genes have been identified in humans, and imprinted genes frequently cluster under the control of an imprinting center. Many imprinted genes contribute to growth, either as growth factors, such as insulin-like growth factors (IGF2 in Beckwith-Wiedemann syndrome), or as growth inhibitors, such as the GRB10 gene in Russell-Silver syndrome. Imprinted genes have evolved over time in mammals to fine-tune the growth of the fetus. Paternally expressed genes generally enhance growth, whereas maternally expressed genes appear to suppress growth. In addition, normal and abnormal genomic imprinting and loss of heterozygosity contribute to a wide range of malignancies. A common process for controlling gene activity is methylation, which can be changed during male or female gametogenesis. Examples of classic human disorders related to genomic imprinting are Beckwith-Wiedemann syndrome (chromosome 11), Prader-Willi/Angelman syndromes (chromosome 15), Russell-Silver syndrome (chromosome 7), and Albright hereditary osteodystrophy (chromosome 20). Several of these disorders are discussed and illustrated.
Butler
Merlin G
MG
Section of Medical Genetics and Molecular Medicine, Children 's Mercy Hospitals and Clinics and The University of Missouri-Kansas City School of Medicine, Kansas City, MO 64108, USA. mgbutler@cmh.edu
D001506:Beckwith-Wiedemann Syndrome / Q000235:genetics*; D019175:DNA Methylation; D005260:Female; D051383:GRB10 Adaptor Protein; D018392:Genomic Imprinting; D006128:Growth / Q000235:genetics*; D006130:Growth Disorders / Q000235:genetics*; D006801:Humans; D007335:Insulin-Like Growth Factor II; D008297:Male; D011218:Prader-Willi Syndrome / Q000235:genetics*; D011506:Proteins / Q000235:genetics
D011506:Proteins; D051383:GRB10 Adaptor Protein; D007335:Insulin-Like Growth Factor II