Abstract: Provided herein are diagnostic markers and methods for identifying a subject having an increased susceptibility for developing or having dilated cardiomyopathy. The method comprises determining if the subject has a mutation in the TTN nucleic as acid or titin polypeptide. Further provided herein are methods of treating subjects having or at risk of having dilated cardiomyopathy.

Abstract: Provided herein are diagnostic markers and methods for identifying a subject having an increased susceptibility for developing or having dilated cardiomyopathy. The method comprises determining if the subject has a mutation in the TTN nucleic as acid or titin polypeptide. Further provided herein are methods of treating subjects having or at risk of having dilated cardiomyopathy.

Abstract: The invention is directed to methods for using sequence by ligation to sequence DNA immobilized on miniaturized, high density bead-based arrays. Methods are provided to fabricate an array of beads where the beads are coupled directly to a solid support. Methods are also provided to improve signal and reduce background in ligation-mediated DNA sequencing. In addition, methods are provided to improve the accuracy of reported tag counts when performing DNA sequencing by fluorescent nonamer ligation.

Abstract: The present invention relates to a method of identifying drugs or agents which have immuno-suppressive effects through or as a result of their effect on calcineurin, including drugs which affect the calcineurin A&agr; (CNA&agr;) subunit or the calcineurin A&bgr; (CNA&bgr;) subunit. In addition, the present invention relates to a method of identifying drugs which reduce (partially or totally) phosphorylation of the microtubule-associated protein tau, in the nervous system of a mammal; a method of identifying drugs which reduce (partially or totally) paired helical filament formation in the nervous system of a mammal; and a method of identifying drugs which reduce (partially or totally) formation of paired helical filaments, amyloid deposits or both. The present invention also relates to transgenic non-human mammals, such as rodents and particularly mice, which lack a functional calcineurin gene and, thus, have disyrupted calcineurin expression.

Abstract: Homozygotic cells are obtained by employing homologous recombination with a construct comprising a marker gene. The marker gene allows for selection without amplification and by employing elevated levels of the antibiotic to which the marker gene imparts resistance, gene conversion can occur, where in a diploid host, both copies of the target locus will be the same. In this manner, knock-outs of genes can be readily achieved without requiring two steps of homologous recombination.