A Loss or a Gain, Is It Not All the Same?

[摘要] The human genome contains numerous loci of which losses or gains provoke clinical phenotypes, albeit often of quite a different nature. Apparently, the genes within these loci have to exist in exactly 2 copies. If there are 3 copies, due to a duplication, or only 1 copy, after a deletion, genes within the locus may exert ‘dosage-sensitive’ effects. This can only be the case if both alleles are being transcribed. If transcripts and proteins of only one copy were to be produced, this would result in haploinsufficiency. Also in the reciprocal situation, in which the cell transcribes 3 copies, transcript imbalance may arise. The gene dosage balance hypothesis provides a molecular framework for how genes encoding transcription factors and proteins involved in signal transduction and macromolecular complexes in general may cause clinical phenotypes [Veitia and Birchler, 2010; Poot et al., 2011].

[学科分类] 基础医学