Mutations in the KCNE1 gene encoding human minK which cause arrhythmia susceptibility thereby establishing KCNE1 as an LQT gene

A method for detecting the presence of a polymorphism in a human KCNE1 gene, the coding region of which is bases 193-579 of SEQ ID NO:3, which causes long QT syndrome, wherein said method comprises obtaining a sample from a human subject and detecting said polymorphism in said sample by means which identify the presence of said polymorphism, wherein said polymorphism in the human KCNE1 gene encodes a KCNE1 polypeptide having an Asn at residue 76, with respect to SEQ ID NO:

• 4, and wherein said means comprises one or more of the following procedures:
• (a) performing single stranded conformation analysis;
• (b) hybridizing a KCNE1 gene probe to genomic DNA isolated from said sample under conditions suitable for hybridization of said probe to said genomic DNA;
• (c) determining hybridization of an allele-specific probe to genomic DNA from said sample;
• (d) amplifying all or part of the KCNE1 gene from said sample to produce an amplified sequence and sequencing the amplified sequence;
• (e) determining by nucleic acid amplification the presence of a specific KCNE1 polymorphic allele in said sample, wherein the polymorphic allele encodes for an Asn at residue 76 of a KCNE1 polypeptide;
• (f) molecularly cloning all or part of the KCNE1 gene from said sample to produce a cloned sequence and sequencing the cloned sequence;
• (g) determining whether there is a mismatch between molecules (1) KCNE1 genomic DNA or KCNE1 mRNA isolated from said sample, and (2) a nucleic acid probe complementary to a human wild-type KCNE1 gene DNA, when molecules (1) and (2) are hybridized to each other to form a duplex;
• (h) amplifying KCNE1 gene sequences in said sample and hybridizing the amplified sequences to nucleic acid probes which comprise wild-type KCNE1 gene sequences;
• (i) amplifying KCNE1 gene sequences in said sample and hybridizing the amplified sequences to nucleic acid probes which comprise mutant KCNE1 gene sequences encoding an Asn at residue 76 of a KCNE1 polypeptide, wherein said sample is a tissue;
• (j) screening for a point mutation, wherein the point mutation is the polymorphism;
• (k) determining in situ hybridization of the KCNE1 gene in said sample with one or more nucleic acid probes which comprise a KCNE1 gene sequence or a polymorphic KCNE1 gene sequence;
• (l) performing an RNase assay;
• (m) sequencing the human KCNE1 gene present in said sample;
• and
• (n) sequencing a KCNE1 polypeptide encoded by said KCNE1 gene present in said sample.