Deletion and duplication of DNA sequences is associated with the embryonic lethal phenotype of the t9 complementation group of the mouse t complex.

We have analyzed the genomic structure of three mouse t haplotypes of the t9 complementation group. Each of these t haplotypes, tw18, t4, and tks1, is known to have resulted from a rare recombination event between a complete t haplotype and a wild-type chromosome. Using molecular probes that identify sequences in the distal portion of the t complex, we have shown that each of these t haplotypes contains a similar (perhaps identical) deletion of one group of t complex sequences, and duplication of another group. These data suggest that the recombination events that produced these three t haplotypes involved similar unequal crossovers within the distal inversion. The deletion and duplication of genetic material associated with all members of the t9 complementation group tested provides a molecular explanation for the recessive lethal mutation associated with these t haplotypes

Polycystic kidney disease: the complete structure of the PKD1 gene and its protein

Mutations in the PKD1 gene are the most common cause of autosomal dominant polycystic kidney disease (ADPKD). Other PKD1-like loci on chromosome 16 are approximately 97% identical to PKD1. To determine the authentic PKD1 sequence, we obtained the genomic sequence of the PKD1 locus and assembled a PKD1 transcript from the sequence of 46 exons. The 14.5 kb PKD1 transcript encodes a 4304 amino acid protein that has a novel domain architecture. The amino-terminal half of the protein consists of a mosaic of previously described domains, including leucine-rich repeats flanked by characteristic cysteine-rich structures, LDL-A and C-type lectin domains, and 14 units of a novel 80 amino acid domain. The presence of these domains suggests that the PKD1 protein is involved in adhesive protein-protein and protein-carbohydrate interactions in the extracellular compartment. We propose a hypothesis that links the predicted properties of the protein with the diverse phenotypic features of ADPKD