As no obligate recombinants were identified in either this or our previous study, the H-ras-1 protooncogene remains a candidate for the LQT disease gene.
As no recombination was observed between LQT and H-ras-1, and there is a physiological rationale for its involvement in this disease, ras becomes a candidate for the disease locus.
We prospectively investigated the clinical characteristics and the long-term course of 3,343 individuals from 328 families in which one or more members were identified as affected with LQTS (QTc greater than 0.44 sec1/2).
To determine if the same locus was responsible for LQT in additional families, we performed linkage studies with DNA markers from this region (H ras-1 and MUC2).
Two genomic DNA probes (c-Ha-ras-3'-HVR and insulin-5'-HVR) and one tetranucleotide repeat polymorphism (THZ) derived from chromosome 11p15.5 loci and previously demonstrated to be closely linked to LQT were used as probes to analyze this family.
Among those families that are nearly consistent with Mendelian transmission, linkage between a locus for LQT syndrome and the H-ras-1 locus on the short arm of chromosome 11 has been reported in some families but not in others.
In the 23 families with LQTS analyzed for linkage to the H-ras-1 locus on chromosome 11p15.5, 15 of 23 families had LOD scores consistent with linkage.
The genes for the long QT syndrome (LQTS) linked to chromosomes 3 (LQT3) and 7 (LQT2) were identified as SCN5A, the cardiac Na+ channel gene, and as HERG, a K+ channel gene.