The transcribed genome and the heritable basis of essential hypertension.
Gene expression can be now assessed quantitatively and comprehensively. In addition to reflecting the specialized differentiation of the cell or tissue type from which gene expression is sampled, it also manifests patterns determined by inheritance. Thus gene expression is a phenotypic trait, at least when assessed comprehensively. This trait shows familial aggregation and segregation patterns indicative of an inherited contribution. The molecular evolution of genes includes mutations affecting regulatory sequences in the genome that influence gene expression in cis and in trans. Such mutations may increase in frequency in a population either by genetic drift or by selection. Traits of gene expression, acting alone or in concert with other gene expression traits, may generate phenotypes that extend beyond transcript abundance. Indeed, the divergence of species and the traits that distinguish related species appear to rely importantly on inherited divergence in the control of gene expression. Variation in gene expression may contribute to the pathogenesis of a prevalent human disease trait that shows heritability--essential hypertension. Along with other common heritable diseases, hypertension susceptibility arises from the actions of multiple genome sequence variations. The identity of such variation has proven elusive when sought by methods that have been successfully applied to Mendelian diseases. This review explores the potential to uncover hypertension genes by exploiting quantitative variation in the heritable control of gene expression.
Doris
Peter A
PA
Institute of Molecular Medicine, University of Texas Health Science Center, Houston, TX 77030, USA. peter.a.doris@uth.tmc.edu
Fornage
Myriam
M
D000818:Animals; D018955:CD36 Antigens / Q000235:genetics / Q000502:physiology; D002874:Chromosome Mapping; D004851:Epoxide Hydrolases / Q000235:genetics / Q000502:physiology; D015894:Genome, Human; D006801:Humans; D006973:Hypertension / Q000235:genetics* / Q000503:physiopathology; D006977:Hypertension, Renal / Q000235:genetics / Q000503:physiopathology; D007668:Kidney / Q000503:physiopathology; D024821:Metabolic Syndrome / Q000235:genetics / Q000503:physiopathology; D010641:Phenotype; D040901:Proteomics; D051381:Rats; D014158:Transcription, Genetic / Q000502:physiology
D018955:CD36 Antigens; D004851:Epoxide Hydrolases