Evolutionary analyses of KCNQ1 and HERG voltage-gated potassium channel sequences reveal location-specific susceptibility and augmented chemical severities of arrhythmogenic mutations-2

(see methods). Because of a low number of expected mutations in the more variable positions, the Xstatistic was also calculated for pooled data with two bins, 0 and 1+, with 1 degree of freedom. The number of disease mutations observed at completely conserved sites (0-class) in both HERG and KCNQ1 is significantly higher than by chance alone: HERG, X= 37.41, p < 0.001 or X= 34.65, p < 0.001; KCNQ1, X= 50.45, p < 0.001 or X= 49.37, p < 0.001. b) Counts of observed and expected numbers of non-synonymous single nucleotide polymorphisms (nsSNPs). In HERG, fewer nsSNPs occur at completely conserved sites than expected by chance alone (X= 22.94, p < 0.001 or X= 10.07, p < 0.05) whereas in KCNQ1, the distribution is not significantly different from the expected count of neutral variation (X= 1.04, p > 0.05). c) Data were pooled to account for low numbers of expected AAMs at variable sites and significance was confirmed. The distribution of AAMs was significantly different than what would be expected by random chance for both HERG (X= 26.10, p < 0.001 or X= 14.17, p < 0.001) and KCNQ1 (X= 34.74, p < 0.001 or X= 18.15, p < 0.001).<p><b>Copyright information:</b></p><p>Taken from "Evolutionary analyses of KCNQ1 and HERG voltage-gated potassium channel sequences reveal location-specific susceptibility and augmented chemical severities of arrhythmogenic mutations"</p><p>http://www.biomedcentral.com/1471-2148/8/188</p><p>BMC Evolutionary Biology 2008;8():188-188.</p><p>Published online 30 Jun 2008</p><p>PMCID:PMC2483723.</p><p>