| First Author | Hanlon P | Year | 2006 |
| Journal | Physiol Genomics | Volume | 26 |
| Issue | 1 | Pages | 46-54 |
| PubMed ID | 16782841 | Mgi Jnum | J:111693 |
| Mgi Id | MGI:3654734 | Doi | 10.1152/physiolgenomics.00247.2005 |
| Citation | Hanlon P, et al. (2006) Three-locus and four-locus QTL interactions influence mouse insulin-like growth factor-I. Physiol Genomics 26(1):46-54 |
| abstractText | A previous analysis of serum insulin-like growth factor I (IGF-I) levels in a mouse population (n = 961) derived from a cross of (BALB/cJ x C57BL/6J) F1 females and (C3H/HeJ x DBA/2J) F1 males documented quantitative trait loci (QTL) on chromosomes 1, 10, and 17. We employed a newly developed, random walk-based method to search for three- and four-way allelic combinations that might influence IGF-I levels through nonadditive (conditional or epistatic) interactions among 185 genotyped biallelic loci and with significance defined by experiment-wide permutation (P < 0.05). We documented a three-locus combination in which an epistatic interaction between QTL on paternal-derived chromosomes 5 and 18 had an opposite effect on the phenotype based on the allele inherited at a third locus on maternal-derived chromosome 17. The search also revealed three four-locus combinations that influence IGF-I levels through nonadditive genetic interactions. In two cases, the four-allele combinations were associated with animals having high levels of IGF-I, and, in the third case, a four-allele combination was associated with animals having low IGF-I levels. The multiple-locus genome scan algorithm revealed new IGF-I QTL on chromosomes 2, 4, 5, 7, 8, and 12 that had not been detected in the single-locus genome search and showed that levels of this hormone can be regulated by complex, nonadditive interactions among multiple loci. The analysis method can detect multilocus interactions in a genome scan experiment and may provide new ways to explore the genetic architecture of complex physiological phenotypes. |
