Replication and discovery of musculoskeletal QTLs in LG/J and SM/J advanced intercross lines

Ana I Hernandez Cordero, Peter Carbonetto, Gioia Riboni Verri, Jennifer S Gregory, David J Vandenbergh, Joseph P Gyekis, David A Blizard, Arimantas Lionikas

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Abstract

The genetics underlying variation in health-related musculoskeletal phenotypes can be investigated in a mouse model. Quantitative trait loci (QTLs) affecting musculoskeletal traits in the LG/J and SM/J strain lineage remain to be refined and corroborated. The aim of this study was to map muscle and bone traits in males (n = 506) of the 50th filial generation of advanced intercross lines (LG/SM AIL) derived from the two strains. Genetic contribution to variation in all musculoskeletal traits was confirmed; the SNP heritability of muscle mass ranged between 0.46 and 0.56; and the SNP heritability of tibia length was 0.40. We used two analytical software, GEMMA and QTLRel, to map the underlying QTLs. GEMMA required substantially less computation and recovered all the QTLs identified by QTLRel. Seven significant QTLs were identified for muscle weight (Chr 1, 7, 11, 12, 13, 15, and 16), and two for tibia length, (Chr 1 and 13). Each QTL explained 4–5% of phenotypic variation. One muscle and both bone loci replicated previous findings; the remaining six were novel. Positional candidates for the replicated QTLs were prioritized based on in silico analyses and gene expression in muscle tissue. In summary, we replicated existing QTLs and identified novel QTLs affecting muscle weight, and replicated bone length QTLs in LG/SM AIL males. Heritability estimates substantially exceed the cumulative effect of the QTLs, hence a richer genetic architecture contributing to muscle and bone variability could be uncovered with a larger sample size.
Original languageEnglish
Article number13561
JournalPhysiological reports
Volume6
Issue number4
Early online date26 Feb 2018
DOIs
Publication statusPublished - Feb 2018

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Quantitative Trait Loci
Muscles
Bone and Bones
Tibia
Single Nucleotide Polymorphism
Weights and Measures
Computer Simulation
Sample Size
Software
Phenotype
Gene Expression

Keywords

  • bone
  • gene expression
  • QTL
  • skeletal muscle

Cite this

Replication and discovery of musculoskeletal QTLs in LG/J and SM/J advanced intercross lines. / Hernandez Cordero, Ana I; Carbonetto, Peter ; Verri, Gioia Riboni; Gregory, Jennifer S; Vandenbergh, David J; Gyekis, Joseph P; Blizard, David A; Lionikas, Arimantas.

In: Physiological reports, Vol. 6, No. 4, 13561, 02.2018.

Research output: Contribution to journalArticle

Hernandez Cordero, AI, Carbonetto, P, Verri, GR, Gregory, JS, Vandenbergh, DJ, Gyekis, JP, Blizard, DA & Lionikas, A 2018, 'Replication and discovery of musculoskeletal QTLs in LG/J and SM/J advanced intercross lines', Physiological reports, vol. 6, no. 4, 13561. https://doi.org/10.14814/phy2.13561
Hernandez Cordero, Ana I ; Carbonetto, Peter ; Verri, Gioia Riboni ; Gregory, Jennifer S ; Vandenbergh, David J ; Gyekis, Joseph P ; Blizard, David A ; Lionikas, Arimantas. / Replication and discovery of musculoskeletal QTLs in LG/J and SM/J advanced intercross lines. In: Physiological reports. 2018 ; Vol. 6, No. 4.
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abstract = "The genetics underlying variation in health-related musculoskeletal phenotypes can be investigated in a mouse model. Quantitative trait loci (QTLs) affecting musculoskeletal traits in the LG/J and SM/J strain lineage remain to be refined and corroborated. The aim of this study was to map muscle and bone traits in males (n = 506) of the 50th filial generation of advanced intercross lines (LG/SM AIL) derived from the two strains. Genetic contribution to variation in all musculoskeletal traits was confirmed; the SNP heritability of muscle mass ranged between 0.46 and 0.56; and the SNP heritability of tibia length was 0.40. We used two analytical software, GEMMA and QTLRel, to map the underlying QTLs. GEMMA required substantially less computation and recovered all the QTLs identified by QTLRel. Seven significant QTLs were identified for muscle weight (Chr 1, 7, 11, 12, 13, 15, and 16), and two for tibia length, (Chr 1 and 13). Each QTL explained 4–5{\%} of phenotypic variation. One muscle and both bone loci replicated previous findings; the remaining six were novel. Positional candidates for the replicated QTLs were prioritized based on in silico analyses and gene expression in muscle tissue. In summary, we replicated existing QTLs and identified novel QTLs affecting muscle weight, and replicated bone length QTLs in LG/SM AIL males. Heritability estimates substantially exceed the cumulative effect of the QTLs, hence a richer genetic architecture contributing to muscle and bone variability could be uncovered with a larger sample size.",
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AU - Gyekis, Joseph P

AU - Blizard, David A

AU - Lionikas, Arimantas

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