Fine-mapping of muscle weight QTL in LG/J and SM/J intercrosses

Lionikas, Arimantas; Cheng, Riyan; Lim, Jackie E.; Palmer, Abraham A.; Blizard, David A.

doi:10.1152/physiolgenomics.00100.2010

Cited by 33 publications

(83 citation statements)

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“…AILs have been employed in several previous studies to successfully map QTL for complex traits in mice, including locomotor activity , muscle weight (Lionikas et al 2010), red blood cell characteristics (Bartnikas et al 2012), body weight , methamphetamine sensitivity (Parker et al 2012a), prepulse inhibition , and the conditioned fear phenotypes studied in this article (Parker et al 2012b). This study makes several key contributions over previous work in this area.…”

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High-Resolution Genetic Mapping of Complex Traits from a Combined Analysis of F2 and Advanced Intercross Mice

et al. 2014

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Genetic influences on anxiety disorders are well documented; however, the specific genes underlying these disorders remain largely unknown. To identify quantitative trait loci (QTL) for conditioned fear and open field behavior, we used an F 2 intercross (n = 490) and a 34th-generation advanced intercross line (AIL) (n = 687) from the LG/J and SM/J inbred mouse strains. The F 2 provided strong support for several QTL, but within wide chromosomal regions. The AIL yielded much narrower QTL, but the results were less statistically significant, despite the larger number of mice. Simultaneous analysis of the F 2 and AIL provided strong support for QTL and within much narrower regions. We used a linear mixed-model approach, implemented in the program QTLRel, to correct for possible confounding due to familial relatedness. Because we recorded the full pedigree, we were able to empirically compare two ways of accounting for relatedness: using the pedigree to estimate kinship coefficients and using genetic marker estimates of "realized relatedness." QTL mapping using the marker-based estimates yielded more support for QTL, but only when we excluded the chromosome being scanned from the marker-based relatedness estimates. We used a forward model selection procedure to assess evidence for multiple QTL on the same chromosome. Overall, we identified 12 significant loci for behaviors in the open field and 12 significant loci for conditioned fear behaviors. Our approach implements multiple advances to integrated analysis of F 2 and AILs that provide both power and precision, while maintaining the advantages of using only two inbred strains to map QTL.

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High-Resolution Genetic Mapping of Complex Traits from a Combined Analysis of F2 and Advanced Intercross Mice

et al. 2014

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“…For example, in a nine-generation advanced intercross used for fine mapping body weight in chickens, BESNIER et al (2011) could only detect five of the nine QTL that were earlier found with the original F2 population. Similar results have been found in advanced crosses of maize (HUANG et al 2010) and mice (WANG et al 2003;LIONIKAS et al 2010).…”

Section: Finer Scale Qtl Localisation and Annotation Of The Qtl-contasupporting

confidence: 87%

“…Although the use of advanced intercross populations for mapping the genetic basis of traits improves accuracy by reducing confidence intervals around QTLs (HUANG et al 2010;LIONIKAS et al 2010), the accumulation of recombination events and subsequent break down of linkage disequilibrium among loci in later generations of an advanced intercross (DARVASI and SOLLER 1995), may lead to significant deviation of QTL effect positions from those observed in earlier (e.g. F2) generations (BESNIER et al 2011).…”

Section: Finer Scale Qtl Localisation and Annotation Of The Qtl-contamentioning

confidence: 99%

“…F2) generations (BESNIER et al 2011). The disruption of linkage within clusters of QTL in coupling phase (easily detectable in early cross conventional mapping population), may fractionate them into several linked loci of small effects that are beyond detection and thus less discoverable in the advanced intercross population (HUANG et al 2010;LIONIKAS et al 2010). Thirdly, even with randomised matings and large effective population sizes, QTLs may also be lost by chance in the development of advanced intercoss lines (IRAQI et al 2000).…”

Section: Finer Scale Qtl Localisation and Annotation Of The Qtl-contamentioning

confidence: 99%

“…and an advanced cross of the same lineage effectively combines the detection power of the former and accuracy of the latter to deliver a superior trait mapping strategy (LIONIKAS et al 2010). This BSA experiment, involving more than a million SNP markers across the whole genome, discounted the possibility of two QTLs and mapped the CHC polymorphism to one region harbouring three adjacent candidate genes.…”

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confidence: 99%

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Genetic dissection of a major polymorphism underlying population divergence in sexually selected pheromones in Drosophila serrata

Rusuwa¹

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With the advent of QTL mapping in the late 1980s, evolutionary geneticists have actively dissected the genetic basis of adaptive phenotypes. In recent times, advances in whole genome sequencing have allowed for finer scale mapping of traits that have diverged due to natural selection. These relatively inexpensive sequencing technologies have also greatly facilitated adaptive trait dissection in non-model species that exhibit especially interesting patterns of adaptation. One class of trait that has largely escaped the attention of the next generation ecological and evolutionary genomics research programme, are sexually-selected traits. Sexual selection is a strong form of directional selection in nature and is thought to be responsible for the evolution of elaborate sexual ornaments and armaments. However we still know comparatively little of the genetic basis of such traits.The cuticular hydrocarbons (CHCs) of Drosophila serrata provide an opportunity for dissecting the divergence of sexually selected traits. Populations along the eastern Australian coast exhibit latitudinal variation in these traits in association with climatic factors and consistent with the action of divergent natural selection. Under experimental settings, divergent sexual as well as natural selection has been implicated in the evolution of CHCs. Natural populations of D. serrata along the northern part of the Eastern Australian coast have recently been observed to exhibit a polymorphism in three of their CHC compounds representing the shortest carbon chains; 5,9-tetracosadiene (5,9-C 24 ), 5,9-pentacosadiene (5,9-C 25 ) and 9-pentacosene (9-C 25 ). One class of phenotype only expresses these three compounds in trace amounts ('low' phenotype) whereas the other has normal levels ('high' phenotype). These short-chained CHCs also exhibit strong genetically-based latitudinal clines up to, but not beyond, 20 degrees south of the equator. Based on both traditional QTL and modern sequence-based genomic mapping approaches, the aim of this study was to dissect the genetic basis of the polymorphism in D. serrata CHCs and to examine its adaptive significance within the context of sexual and natural selection.Through F2 QTL mapping based on a cross between two inbred lines, from the opposite ends of the D. serrata CHC cline, one a 'low' phenotype and the other a 'high' phenotype, the genetic basis of all CHCs in this species was mapped to twenty two overlapping QTLs on chromosomes 2 and 3.The short-chain CHC polymorphism was traced to two major effect recessive QTLs on the right arm of chromosome 3, which including their interaction, accounted for more than 70% of the variance in the polymorphism (Chapter 2). Fine mapping of this major polymorphism was then conducted using next generation DNA sequencing and bulk segregant analysis of an advanced F60 cross of the same founding lines. Bulk segregant analysis revealed a single peak of genetic differentiation on chromosome 3R (~20kb), harbouring three adjacent fatty acyl-CoA reductase ii genes (Cha...

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Heritability of articular cartilage regeneration and its association with ear wound healing in mice

Farooq

Hashimoto

Johnson

et al. 2012

Arthritis & Rheumatism

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Objective Emerging evidence suggests that genetic components contribute significantly to cartilage degeneration in osteoarthritis pathophysiology but little evidence is available on genetics of cartilage regeneration. Therefore, we investigated cartilage regeneration in genetic murine models using common inbred strains and a set of recombinant inbred lines generated from LG/J (healer of ear-wounds) and SM/J (non-healer) inbred strains. Methods An acute full-thickness cartilage injury was introduced through microsurgery in the trochlear groove of 8-weeks old mice (N=265). Knee joints were sagittally sectioned and stained with toluidine blue to evaluate regeneration. For ear-wound phenotype, a bilateral 2-mm through-and-through puncture was made (N=229) at 6-weeks and healing outcomes measured after 30-days. Broad-sense heritability and genetic correlations were calculated for both phenotypes. Results Time-course studies from recombinant inbred lines show no significant regeneration until 16-weeks post-surgery; at that time, the strains can be segregated into three categories: good, intermediate and poor healers. Heritability (H2) showed that both cartilage regeneration (H2=26%; p=0.006) and ear-wound closure (H2=53%; p<0.00001) are significantly heritable. The genetic correlations between the two healing phenotypes for common inbred strains (r=0.92) and recombinant inbred lines (r=0.86) were found to be extremely high. Conclusion We report that i) articular cartilage regeneration is heritable, ii) the differences between the lines being due to genetic differences and iii) a strong genetic correlation between the two phenotypes exists indicating that they plausibly share a common genetic basis. We, therefore, surmise that LG/J by SM/J intercross can be used to dissect the genetic basis of variation in cartilage regeneration.

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Fine-mapping of muscle weight QTL in LG/J and SM/J intercrosses

Abstract: Lionikas A, Cheng R, Lim JE, Palmer AA, Blizard DA. Finemapping of muscle weight QTL in LG/J and SM/J intercrosses.

Cited by 33 publications

References 44 publications

High-Resolution Genetic Mapping of Complex Traits from a Combined Analysis of F2 and Advanced Intercross Mice

High-Resolution Genetic Mapping of Complex Traits from a Combined Analysis of F2 and Advanced Intercross Mice

Genetic dissection of a major polymorphism underlying population divergence in sexually selected pheromones in Drosophila serrata

Heritability of articular cartilage regeneration and its association with ear wound healing in mice

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