Genetic testing for long-QT syndrome: distinguishing pathogenic mutations from benign variants.

Background: Genetic testing for long-QT syndrome (LQTS) has diagnostic, prognostic, and therapeutic implications. Hundreds of causative mutations in 12 known LQTS-susceptibility genes have been identified. Genetic testing that includes the 3 most commonly mutated genes is available clinically.

The structure of common genetic variation in United States populations.

The common-variant/common-disease model predicts that most risk alleles underlying complex health-related traits are common and, therefore, old and found in multiple populations, rather than being rare or population specific. Accordingly, there is widespread interest in assessing the population structure of common alleles. However, such assessments have been confounded by analysis of data sets with bias toward ascertainment of common alleles (e.

Genetic variability and evolution of two pharmacologically important classes of genes.

We have studied the human genetic variability of single nucleotide polymorphisms (SNPs) and haplotypes in two pharmaceutically important classes of genes that might be expected to experience different evolutionary pressures: antigen presentation and processing (APP) and nuclear hormone receptor (NHR) genes. We compared the variation pattern in these two classes of genes with 5119 reference (REF) genes. We assessed this variability by sequencing and discovering SNPs in 5'-upstream, 5'-untranslated region (5'UTR), exon, intron, 3'UTR and 3'-downstream regions of all these genes in 79 unrelated humans from diverse ethnic backgrounds, one chimpanzee (Pan troglodytes) and a gorilla (Gorilla gorilla).

SNP and haplotype variation in the human genome.

We have surveyed and summarized several aspects of DNA variability among humans. The variation described is the result of mutation followed by a combination of drift, migration and selection bringing the frequencies high enough to be observed. This paper describes what we have learned about how DNA variability differs among genes and populations.

DNA variability of human genes.

We have investigated the level of DNA-based variation (both SNPs and haplotypes) for several thousand human genes. In addition, we have characterized how this variation is distributed in a number of biologically and clinically important ways. First, we have determined how SNPs are distributed within human genes: where they occur relative to various functional regions; levels of variability of human SNPs; pattern of the molecular sequence of SNPs; and how these compare with the corresponding sequence of a chimpanzee.