title: Replication of long-bone length QTL in the F9-F10 LG,SM advanced intercross.
abstract: Quantitative trait locus (QTL) mapping techniques are frequently used to identify genomic regions associated with variation in phenotypes of interest. However, the F(2) intercross and congenic strain populations usually employed have limited genetic resolution resulting in relatively large confidence intervals that greatly inhibit functional confirmation of statistical results. Here we use the increased resolution of the combined F(9) and F(10) generations (n = 1455) of the LG,SM advanced intercross to fine-map previously identified QTL associated with the lengths of the humerus, ulna, femur, and tibia. We detected 81 QTL affecting long-bone lengths. Of these, 49 were previously identified in the combined F(2)-F(3) population of this intercross, while 32 represent novel contributors to trait variance. Pleiotropy analysis suggests that most QTL affect three to four long bones or serially homologous limb segments. We also identified 72 epistatic interactions involving 38 QTL and 88 novel regions. This analysis shows that using later generations of an advanced intercross greatly facilitates fine-mapping of confidence intervals, resolving three F(2)-F(3) QTL into multiple linked loci and narrowing confidence intervals of other loci, as well as allowing identification of additional QTL. Further characterization of the biological bases of these QTL will help provide a better understanding of the genetics of small variations in long-bone length.
authors.affiliation: Department of Anatomy and Neurobiology, Washington University School of Medicine, Box 8108, 660 South Euclid Avenue, St. Louis, MO 63110, USA. enorgard@artsci.wustl.edu
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Norgard
authors.forename: Joseph P
authors.initials: JP
authors.lastname: Jarvis
authors.forename: Charles C
authors.initials: CC
authors.lastname: Roseman
authors.forename: Taylor J
authors.initials: TJ
authors.lastname: Maxwell
authors.forename: Jane P
authors.initials: JP
authors.lastname: Kenney-Hunt
authors.forename: Kaitlin E
authors.initials: KE
authors.lastname: Samocha
authors.forename: L Susan
authors.initials: LS
authors.lastname: Pletscher
authors.forename: Bing
authors.initials: B
authors.lastname: Wang
authors.forename: Gloria L
authors.initials: GL
authors.lastname: Fawcett
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Leatherwood
authors.forename: Jason B
authors.initials: JB
authors.lastname: Wolf
authors.forename: James M
authors.initials: JM
authors.lastname: Cheverud
mesh_terms: D000818:Animals; D001842:Bone and Bones / Q000033:anatomy & histology* / Q000737:chemistry; D003433:Crosses, Genetic; D004261:DNA Replication; D005260:Female; D006824:Hybridization, Genetic; D008297:Male; D051379:Mice; D009929:Organ Size / Q000235:genetics*; D040641:Quantitative Trait Loci