Replication of long-bone length QTL in the F9-F10 LG,SM advanced intercross

Replication of long-bone length QTL in the F9-F10 LG,SM advanced intercross Quantitative trait locus (QTL) mapping techniques are frequently used to identify genomic regions associated with variation in phenotypes of interest. However, the F2 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 F9 and F10 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 F2-F3 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 F2-F3 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. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Mammalian Genome Springer Journals
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Publisher
Springer-Verlag
Copyright
Copyright © 2009 by Springer Science+Business Media, LLC
Subject
Life Sciences; Zoology ; Anatomy ; Cell Biology
ISSN
0938-8990
eISSN
1432-1777
D.O.I.
10.1007/s00335-009-9174-9
Publisher site
See Article on Publisher Site

Abstract

Quantitative trait locus (QTL) mapping techniques are frequently used to identify genomic regions associated with variation in phenotypes of interest. However, the F2 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 F9 and F10 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 F2-F3 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 F2-F3 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.

Journal

Mammalian GenomeSpringer Journals

Published: Mar 21, 2009

References

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