Abstract # 1964 Event # 213:

Scheduled for Saturday, August 19, 2006 08:30 AM-08:45 AM: Session 20 (Regency East #3) Oral Presentation

Hematological and inflammatory traits in pedigreed baboons: Evidence for quantitative trait loci in a region of chromosome 1p

A. Bertin1, L. A. Cox1,2, J. Rogers1,2, J. L. VandeBerg1,2, C. Brugnara3, O. S. Platt3 and M. C. Mahaney1,2
1Department of Genetics , Southwest Foundation for Biomedical Research , San Antonio, TEXAS 78245-0549 , USA, 2Southwest National Primate Research Center, Southwest Foundation for Biomedical Research, 3The Children's Hospital, Harvard University School of Medicine, Boston, Massachusetts
     Multivariate analyses of quantitative traits can facilitate the detection and localization of genes contributing to phenotypic variation in several traits, particularly multifactorial phenotypes, like risk factors for complex diseases. Here, we adopt a multivariate approach for identifying quantitative trait loci (QTLs) related to normal variation in degree of vascular inflammation, an indicator of individual susceptibility to cardiovascular diseases. We analyzed data on standard hematological parameters (peripheral blood cell counts) and serum biomarkers of inflammation in over 500 healthy pedigreed baboons (Papio hamadryas spp.). Estimation of heritabilities and localization of QTLs was assessed by genome-wide scans using maximum likelihood-based variance-component approaches. While univariate linkage screens identified a single significant (LOD>2.7, genome-wide p<0.05) QTL for mean corpuscular volume (LOD=3.52) on baboon chromosome 1p (PHA1p, the ortholog of HSA1p), bivariate linkage analyses localized QTLs for six different pairs of these traits to the same restricted chromosomal region (range of LOD scores: 3.00-4.40). These QTLs influence multiple phenotypes including hematological (red blood cell count, mean corpuscular volume, mean cellular hemoglobin, mean cellular hemoglobin concentration and hematocrit) and serum traits (P-Selectin) and weight; explaining up to 35% of their variance. Our results underline the utility of multivariate linkage approaches and suggest that a limited region of the human ortholog chromosome 1p may harbor genes playing an important role in the normal variation of both inflammatory and hematological traits in baboons.