One man's junk is another man's treasure: GWAS, ENCODE, and the search for control of the heart

摘要

Genetic studies of cardiac electrocardiographical parameters such as heart rate, atrioventricular conduction, ventricular depolarization, or repolarization have focused either on rare families with Mendelian inheritance of severe phenotypes (familial sinus bradycardia, conduction disease, or repolarization abnormalities such as long QT syndrome) or on large cohorts of ostensibly normal individuals assessing small inter-individual differences in these electrocardiogram measurements. The earliest studies (1990s) assessed microsatellite markers (repeated sequences of 2-5 nucleotides) that have a higher rate of mutations and thus generate multiple polymorphisms (alleles) and occur every few thousand base pairs. Single nucleotide polymorphisms (SNPs) occur approximately every thousand base pairs but typically have only 2 alleles and low heterozygote frequencies. Nevertheless, SNP mapping has become a popular technique for both the analysis of segregation of a phenotype within families and the genome-wide association study (GWAS) within populations.