Localization of the fast skeletal muscle troponin I gene (TNNI2) to 11p15.5: genes for troponin I and T are organized in pairs

Abstract

We have localized the gene encoding the fast skeletal muscle isoform of troponin I (TNNI2) to 11p15.5 by PCR‐based analysis of somatic cell hybrid panels: based on the Genebridge4 radiation hybrid panel, TNNI2 is coincident with the marker D11S922. The gene encoding the fast skeletal muscle troponin T gene (TNNT3) has been previously assigned to 11p15.5 suggesting that TNNI2 and TNNT3 may be closely linked. The overall location of genes encoding troponin I and T isoforms now reveals that they are organized at three loci each containing a troponin I/troponin T gene pair. This organization contrasts with all other sarcomeric protein genes and has implications for the evolution of these two gene families, for their regulation and for the analysis of mutations suspected to result in cardiomyopathy.

Preserved Close Linkage Between the Genes Encoding Troponin I and Troponin T, Reflecting an Evolution of Adapter Proteins Coupling the Ca2+ Signaling of Contractility

“…Together with the potentially similar linkages found between the fast skeletal muscle TnI and the fast skeletal muscle TnT genes (Barton et al 1997) and between the slow skeletal muscle TnI and the cardiac TnT genes (Tiso et al 1997), the genomic location of all six TnI and TnT genes in three pairs supports the assumption that the split of the TnI and TnT genes was an early event, prior to the divergence of the muscle fiber type-specific members in the modern TnI and TnT gene families. The functionally independent linkage of the cTnI and sTnT genes thus suggests that a synchronized evolution for members of the TnI-TnT gene superfamily does not rely on their physical linkage.…”

“…This result shows that the genes encoding the muscle fiber type-specific isoforms of a troponin subunit have been dispersed in the vertebrate genome since their duplication, indicating an early divergence and a lack of functional selection for their linkage. On the other hand, genes encoding fast skeletal muscle TnI and fast skeletal muscle TnT are found at the same chromosomal location (11p15.5) in the human genome (Barton et al 1997), although the actual distance is not determined. This pattern indicates that the TnI and TnT genes may be evolutionarily linked due to their interdependent functions.…”

Altered Regulation of Cardiac Muscle Contraction by Troponin T Mutations That Cause Familial Hypertrophic Cardiomyopathy

“…Familial hypertrophic cardiomyopathy (FHC) is an autosomal dominant disease which has been shown to be caused by mutations in almost every major sarcomeric protein, including myosin heavy chain (9 -11), ␣-tropomyosin (12)(13)(14), myosin-binding protein C (15)(16)(17), ventricular myosin light chains 1 and 2 (18 -20), human cardiac TnT (HCTnT) (12,13,(21)(22)(23)(24)(25)(26)(27), and TnI (HCTnI) (28). Whereas individuals with myosin heavy chain mutations, in general, have a higher level of cardiac hypertrophy, those with HCTnT mutations have less hypertrophy, but a higher incidence of sudden cardiac death at a young age (13,29,30).…”

Close Physical Linkage of Human Troponin Genes: Organization, Sequence, and Expression of the Locus Encoding Cardiac Troponin I and Slow Skeletal Troponin T

“…Current HGMP nomenclature is as shown above. Adapted from Barton et al (1997). nants (Genome Systems Inc.) containing the cardiac troponin T gene by direct screening using a previously described cDNA for this isoform (Townsend et al, 1994). Two independent clones were identified and in both cases contained the whole of both the slow skeletal troponin I and cardiac troponin T genes, as determined by hybridization with oligonucleotides corresponding to 5Ј and 3Ј exon sequences (Figs.…”

“…Based on mapping studies, we have previously reported that the genes for the troponin I and troponin T subunits of the complex are organized as paralogous pairs at three dispersed chromosomal sites, each containing a troponin I-troponin T gene pair (Barton et al, 1997). In contrast, the two genes encoding fast skeletal and cardiac/slow-skeletal troponin C are not linked to each other or to other troponin genes (Townsend et al, 1997a,b).…”