Biomedical subjects

Jeremy L Peirce

Publications and source records attributed to Jeremy L Peirce.

5 recordsLinked to original sources

PubMed2006

Combining gene expression QTL mapping and phenotypic spectrum analysis to uncover gene regulatory relationships.

Gene expression QTL (eQTL) mapping can suggest candidate regulatory relationships between genes. Recent advances in mammalian phenotype annotation such as mammalian phenotype ontology (MPO) enable systematic analysis of the phenotypic spectrum subserved by many genes. In this study we combined eQTL mapping and phenotypic spectrum analysis to predict gene regulatory relationships. Five pairs of genes with similar phenotypic effects and potential regulatory relationships suggested by eQTL mapping were identified. Lines of evidence supporting some of the predicted regulatory relationships were obtained from biological literature. A particularly notable example is that promoter sequence analysis and real-time PCR assays support the predicted regulation of protein kinase C epsilon (Prkce) by cAMP responsive element binding protein 1 (Creb1). Our results show that the combination of gene eQTL mapping and phenotypic spectrum analysis may provide a valuable approach to uncovering gene regulatory relations underlying mammalian phenotypes.

Animals↗

PubMed2006

How replicable are mRNA expression QTL?

Applying quantitative trait analysis methods to genome-wide microarray-derived mRNA expression phenotypes in segregating populations is a valuable tool in the attempt to link high-level traits to their molecular causes. The massive multiple-testing issues involved in analyzing these data make the correct level of confidence to place in mRNA abundance quantitative trait loci (QTL) a difficult problem. We use a unique resource to directly test mRNA abundance QTL replicability in mice: paired recombinant inbred (RI) and F(2) data sets derived from C57BL/6J (B6) and DBA/2J (D2) inbred strains and phenotyped using the same Affymetrix arrays. We have one forebrain and one striatum data set pair. We describe QTL replication at varying stringencies in these data. For instance, 78% of mRNA expression QTL (eQTL) with genome-wide adjusted p < or = 0.0001 in RI data replicate at a genome-wide adjusted p < 0.05 or better. Replicated QTL are disproportionately putatively cis-acting, and approximately 75% have higher apparent expression levels associated with B6 genotypes, which may be partly due to probe set generation using B6 sequence. Finally, we note that while trans-acting QTL do not replicate well between data sets in general, at least one cluster of trans-acting QTL on distal Chr 1 is notably preserved between data sets.

Animals↗

PubMed2005

Genetic analysis of barrel field size in the first somatosensory area (SI) in inbred and recombinant inbred strains of mice.

We measured the combined area of posterior medial barrel subfield (PMBSF) and anterior lateral barrel subfield (ALBSF) areas in four common inbred strains (C3H/HeJ, A /J, C57BL /6J, DBA/2J), B6D2F1, and ten recombinant inbred (RI) strains generated from C57BL/6J and DBA/2J progenitors (BXD) as an initial attempt to examine the genetic influences underlying natural variation in barrel field size in adult mice. These two subfields are associated with the representation of the whisker pad and sinus hairs on the contralateral face. Using cytochrome oxidase labeling to visualize the barrel field, we measured the size of the combined subfields in each mouse strain. We also measured body weight and brain weight in each strain. We report that DBA/2J mice have a larger combined PMBSF/ALBSF area (6.15 +/- 0.10 mm(2), n = 7) than C57BL /6J (5.48 +/- 0.13 mm(2), n = 10), C3H/HeJ (5.37 +/- 0.16 mm(2), n = 10), and A/J mice (5.04 +/- 0.09 mm(2), n = 15), despite the fact that DBA/2J mice have smaller average brain and body sizes. This finding may reflect dissociation between systems that control brain size with those that regulate barrel field area. In addition, BXD strains (average n = 4) and parental strains showed considerable and continuous variation in PMBSF/ALBSF area, suggesting that this trait is polygenic. Furthermore, brain, body, and cortex weights have heritable differences between inbred strains and among BXD strains. PMBSF/ALBSF pattern appears similar among inbred and BXD strains, suggesting that somatosensory patterning reflects a common plan of organization. This data is an important first step in the quantitative genetic analysis of the parcellation of neocortex into diverse cytoarchitectonic zones that vary widely within and between species, and in identifying the genetic factors underlying barrel field size using quantitative trait locus (QTL) analyses.

Aging↗

PubMed2004

A new set of BXD recombinant inbred lines from advanced intercross populations in mice.

BACKGROUND: Recombinant inbred (RI) strains are an important resource for mapping complex traits in many species. While large RI panels are available for Arabidopsis, maize, C. elegans, and Drosophila, mouse RI panels typically consist of fewer than 30 lines. This is a severe constraint on the power and precision of mapping efforts and greatly hampers analysis of epistatic interactions. RESULTS: In order to address these limitations and to provide the community with a more effective collaborative RI mapping panel we generated new BXD RI strains from two independent advanced intercrosses (AI) between C57BL/6J (B6) and DBA/2J (D2) progenitor strains. Progeny were intercrossed for 9 to 14 generations before initiating inbreeding, which is still ongoing for some strains. Since this AI base population is highly recombinant, the 46 advanced recombinant inbred (ARI) strains incorporate approximately twice as many recombinations as standard RI strains, a fraction of which are inevitably shared by descent. When combined with the existing BXD RI strains, the merged BXD strain set triples the number of previously available unique recombinations and quadruples the total number of recombinations in the BXD background. CONCLUSION: The combined BXD strain set is the largest mouse RI mapping panel. It is a powerful tool for collaborative analysis of quantitative traits and gene function that will be especially useful to study variation in transcriptome and proteome data sets under multiple environments. Additional strains also extend the value of the extensive phenotypic characterization of the previously available strains. A final advantage of expanding the BXD strain set is that both progenitors have been sequenced, and approximately 1.8 million SNPs have been characterized. This provides unprecedented power in screening candidate genes and can reduce the effective length of QTL intervals. It also makes it possible to reverse standard mapping strategies and to explore downstream effects of known sequence variants.

Animals↗

PubMed2003

The nature and identification of quantitative trait loci: a community's view.

This white paper by eighty members of the Complex Trait Consortium presents a community's view on the approaches and statistical analyses that are needed for the identification of genetic loci that determine quantitative traits. Quantitative trait loci (QTLs) can be identified in several ways, but is there a definitive test of whether a candidate locus actually corresponds to a specific QTL?

Animals↗