Genetic characterization of a new set of recombinant inbred lines (LGXSM) formed from the intercross of SM/J and LG/J inbred mouse strains

Hrbek, Tomas; Brito, Reinaldo Alves de; Wang, B.; Pletscher, L. Susan; Cheverud, James M.

doi:10.1007/s00335-005-0038-7

Cited by 56 publications

(65 citation statements)

References 57 publications

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“…Because there is more power to detect postnatal compared to prenatal maternal effects (Table S3), the finding of more prenatal maternal effects than postnatal effects cannot be attributed to a simple difference in power and is in direct opposition to the difference in power. Although it may appear surprising that prenatal effects are more persistent than postnatal effects, these results are consistent with those reported by Jarvis et al (2005) for adult obesity and diabetes-related traits in the LGXSM recombinant inbred strains (Hrbek et al 2006).…”

Section: Discussionsupporting

confidence: 88%

Disentangling Prenatal and Postnatal Maternal Genetic Effects Reveals Persistent Prenatal Effects on Offspring Growth in Mice

et al. 2011

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Mothers are often the most important determinant of traits expressed by their offspring. These "maternal effects" (MEs) are especially crucial in early development, but can also persist into adulthood. They have been shown to play a role in a diversity of evolutionary and ecological processes, especially when genetically based. Although the importance of MEs is becoming widely appreciated, we know little about their underlying genetic basis. We address the dearth of genetic data by providing a simple approach, using combined genotype information from parents and offspring, to identify "maternal genetic effects" (MGEs) contributing to natural variation in complex traits. Combined with experimental cross-fostering, our approach also allows for the separation of pre-and postnatal MGEs, providing rare insights into prenatal effects. Applying this approach to an experimental mouse population, we identified 13 ME loci affecting body weight, most of which (12/13) exhibited prenatal effects, and nearly half (6/13) exhibiting postnatal effects. MGEs contributed more to variation in body weight than the direct effects of the offsprings' own genotypes until mice reached adulthood, but continued to represent a major component of variation through adulthood. Prenatal effects always contributed more variation than postnatal effects, especially for those effects that persisted into adulthood. These results suggest that MGEs may be an important component of genetic architecture that is generally overlooked in studies focused on direct mapping from genotype to phenotype. Our approach can be used in both experimental and natural populations, providing a widely practicable means of expanding our understanding of MGEs.

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Section: Discussionsupporting

confidence: 88%

Disentangling Prenatal and Postnatal Maternal Genetic Effects Reveals Persistent Prenatal Effects on Offspring Growth in Mice

et al. 2011

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“…The SM/J strain is maintained by forced heterozygosity at the agouti locus on mouse chromosome 2. Attempts to fix the strain for either the nonagouti (a) allele or the whitebellied agouti allele (A w ) have ended in strain failure (Hrbek et al, 2006).…”

Section: Materials and Methods Samplesmentioning

confidence: 99%

Fine-mapping quantitative trait loci affecting murine external ear tissue regeneration in the LG/J by SM/J advanced intercross line

et al. 2014

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External ear hole closure in LG/J mice represents a model of regenerative response. It is accompanied by the formation of a blastema-like structure and the re-growth of multiple tissues, including cartilage. The ability to regenerate tissue is heritable. An F34 advanced intercross line of mice (Wustl:LG,SM-G34) was generated to identify genomic loci involved in ear hole closure over a 30-day healing period. We mapped 19 quantitative trait loci (QTL) for ear hole closure. Individual gene effects are relatively small (0.08 mm), and most loci have co-dominant effects with phenotypically intermediate heterozygotes. QTL support regions were limited to a median size of 2 Mb containing a median of 19 genes. Positional candidate genes were evaluated using differential transcript expression between LG/J and SM/J healing tissue, function analysis and bioinformatic analysis of single-nucleotide polymorphisms in and around positional candidate genes of interest. Analysis of the set of 34 positional candidate genes and those displaying expression differences revealed over-representation of genes involved in cell cycle regulation/DNA damage, cell migration and adhesion, developmentally related genes and metabolism. This indicates that the healing phenotype in LG/J mice involves multiple physiological mechanisms.

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“…In our laboratory, adult LG/J animals are 16 to 20 g heavier than SM/J animals. The strains show genetic variation for body weight, growth, skeletal morphology, obesity, glucose and insulin levels, and response to a high-fat diet (49 -51) among other features (52). QTL mapping studies of phenotypes used in this study have found that genetic variation is attributable to many loci (6, 7, 11-14, 33, 38, 39, 53) (R.H., J.M.C., C.R., and J.B.W., unpublished work) of relatively small effect (a Ͻ 0.3 SD) with variable dominance, epistatic interactions, and modular pleiotropic gene effects (54).…”

Section: Methodsmentioning

confidence: 99%

“…These SNP markers (see SI Table 4) were chosen from the 4,200 polymorphic markers scored as part of the CTC/Oxford genotyping consortium (www.well.ox.ac.uk/mouse/INBREDS/; ref. 52), which resulted in markers being placed every 4 -5 cM along the genome except in regions that seem to be nonpolymorphic between LG/J and SM/J (52). Genotypes were obtained for all F 2 animals and their F3 offspring.…”

Section: Methodsmentioning

confidence: 99%

Genomic imprinting effects on adult body composition in mice

Cheverud

Hager

Roseman³

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

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Genomic imprinting results in the differential expression of genes, depending on which allele is inherited from the mother and which from the father. The effects of such differential gene expression are reflected in phenotypic differences between the reciprocal heterozygotes (Aa vs. aA). Although many imprinted genes have been identified and play a key role in development, little is known about the contribution of imprinting to quantitative variation in trait expression. Here, we examine this problem by mapping imprinting effects on adult body composition traits in the F 3 generation of an intercross between the Large (LG/J) and Small (SM/J) inbred mouse strains. We identified eight pleiotropic imprinted quantitative trait loci (iQTL) located throughout the genome. Most iQTL are in novel locations that have not previously been associated with imprinting effects, but those on chromosomes 7, 12, and centromeric 18 lie in regions previously identified as containing imprinted genes. Our results show that the effects of genomic imprinting are relatively small, with reciprocal heterozygotes differing by Ϸ0.25 standard deviation units and the effects at each locus accounting for 1% to 4% of the phenotypic variance. We detected a variety of imprinting patterns, with paternal expression being the most common. These results indicate that genomic imprinting has small, but detectable, effects on the normal variation of complex traits in adults and is likely to be more common than usually thought.epigenetics ͉ mouse ͉ obesity ͉ quantitative trait loci ͉ organs

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Genetic characterization of a new set of recombinant inbred lines (LGXSM) formed from the intercross of SM/J and LG/J inbred mouse strains

Cited by 56 publications

References 57 publications

Disentangling Prenatal and Postnatal Maternal Genetic Effects Reveals Persistent Prenatal Effects on Offspring Growth in Mice

Disentangling Prenatal and Postnatal Maternal Genetic Effects Reveals Persistent Prenatal Effects on Offspring Growth in Mice

Fine-mapping quantitative trait loci affecting murine external ear tissue regeneration in the LG/J by SM/J advanced intercross line

Genomic imprinting effects on adult body composition in mice

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