Uncovering genes and regulatory pathways related to urinary albumin excretion. J Am Soc Nephrol 2011 Jan;22(1):73-81
Date
10/30/2010Pubmed ID
21030601Pubmed Central ID
PMC3014036DOI
10.1681/ASN.2010050561Scopus ID
2-s2.0-78651381769 (requires institutional sign-in at Scopus site) 11 CitationsAbstract
Identifying the genes underlying quantitative trait loci (QTL) for disease is difficult, mainly because of the low resolution of the approach and the complex genetics involved. However, recent advances in bioinformatics and the availability of genetic resources now make it possible to narrow the genetic intervals, test candidate genes, and define pathways affected by these QTL. In this study, we mapped three significant QTL and one suggestive QTL for an increased albumin-to-creatinine ratio on chromosomes (Chrs) 1, 4, 15, and 17, respectively, in a cross between the inbred MRL/MpJ and SM/J strains of mice. By combining data from several sources and by utilizing gene expression data, we identified Tlr12 as a likely candidate for the Chr 4 QTL. Through the mapping of 33,881 transcripts measured by microarray on kidney RNA from each of the 173 male F2 animals, we identified several downstream pathways associated with these QTL, including the glycan degradation, leukocyte migration, and antigen-presenting pathways. We demonstrate that by combining data from multiple sources, we can identify not only genes that are likely to be causal candidates for QTL but also the pathways through which these genes act to alter phenotypes. This combined approach provides valuable insights into the causes and consequences of renal disease.
Author List
Hageman RS, Leduc MS, Caputo CR, Tsaih SW, Churchill GA, Korstanje RAuthor
Shirng-Wern Tsaih Research Scientist II in the Obstetrics and Gynecology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AlbuminsAlbuminuria
Animals
Cell Movement
Creatinine
Female
Leukocytes
Male
Mice
Mice, Inbred Strains
Models, Animal
Polysaccharides
Quantitative Trait Loci
Signal Transduction
Toll-Like Receptors
