CXM: a new tool for mapping breast cancer risk in the tumor microenvironment.

The majority of causative variants in familial breast cancer remain unknown. Of the known risk variants, most are tumor cell autonomous, and little attention has been paid yet to germline variants that may affect the tumor microenvironment. In this study, we developed a system called the Consomic Xenograft Model (CXM) to map germline variants that affect only the tumor microenvironment.

Refined mapping of a hypertension susceptibility locus on rat chromosome 12.

Previously, we found that transferring 6.1 Mb of salt-sensitive (SS) chromosome 12 (13.4-19.

SORCS1 contributes to the development of renal disease in rats and humans.

Many lines of evidence demonstrate that genetic variability contributes to chronic kidney disease susceptibility in humans as well as rodent models. Little progress has been made in discovering causal kidney disease genes in humans mainly due to genetic complexity. Here, we use a minimal congenic mapping strategy in the FHH (fawn hooded hypertensive) rat to identify Sorcs1 as a novel renal disease candidate gene.

Identification of hypertension susceptibility loci on rat chromosome 12.

Previous studies have identified multiple blood pressure and renal disease quantitative trait loci located on rat chromosome 12. In the present study, we narrowed blood pressure loci using a series of overlapping Dahl salt-sensitive/Mcwi (SS)-12 Brown Norway (BN) congenic lines. We found that transferring 6.

A 4.1-Mb congenic region of Rf-4 contributes to glomerular permeability.

The combined transfer of two renal function quantitative trait loci (QTLs), Rf-1 (rat chromosome 1) and Rf-4 (rat chromosome 14), from the Fawn-hooded hypertensive rat onto the August Copenhagen Irish genetic background significantly increases proteinuria and demonstrates an interaction between these QTLs. Because the original Rf-4 congenic region is 61.9 Mbp, it is necessary to reduce this interval to feasibly search for variants responsible for renal susceptibility in this region.

Characterization of the genomic structure and function of regions influencing renin and angiogenesis in the SS rat.

Impaired regulation of renin in Dahl salt-sensitive rats (SS/JRHsdMcwi, SS) contributes to attenuated angiogenesis in this strain. This study examined angiogenic function and genomic structure of regions surrounding the renin gene using subcongenic strains of the SS and BN/NHsdMcwi (BN) rat to identify important genomic variations between SS and BN involved in angiogenesis. Three candidate regions on Chr 13 were studied: two congenic strains containing 0.