Contribution of maternal effect QTL to genetic architecture of early growth in mice

Wolf, Jason B.; Vaughn, Ty T.; Pletscher, L. Susan; Cheverud, James M.

doi:10.1038/sj.hdy.6800140

Cited by 71 publications

(69 citation statements)

References 39 publications

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“…This maternal effect gene was identified by determining weights of F3 pups cared for by F2 mothers, when half the pups for each female were fostered and half were left with their biological mother. 24 The results demonstrated that maternal effect genes have significant effects on growth and that one of these QTLs is included within the B6.C-H1 congenic strain. We also cannot distinguish between the possibilities that imprinted genes or nonimprinted genes expression in mothers underlies the apparent maternal effect.…”

Section: Discussionmentioning

confidence: 86%

Multiple linked mouse chromosome 7 loci influence body fat mass

Diament

Warden

2003

Int J Obes

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BACKGROUND: Congenic mouse strains contain donor mouse strain DNA in genomes otherwise identical to a background strain. They can be used to identify defined chromosomal regions containing obesity genes with small effects. OBJECTIVE: The objective of this study was to discover congenic strains containing genes that influence body fat in mice and to examine interactions between these genes. DESIGN: A survey of congenic strains showed that the B6.C-Tyr c H1 b Hbb d /By (B6.C-H1) congenic strain, with a 24 centiMorgan (cM) donor region from strain BALB/cBy on chromosome 7, had 50% less fat than background C57BL/6By (B6By) mice. The congenic donor region was then divided into 11 smaller overlapping subcongenic regions. Genotype effects on obesity traits in the subcongenics were determined by breeding heterozygotes for each line and comparing phenotypes of littermates with different donor genotypes. RESULTS: At least three subcongenic strains, two with overlapping donor regions and one with a nonoverlapping donor strain region, were found to exhibit significant influences of donor region genotype on obesity. A cross of the two overlapping subcongenics demonstrated that a single gene in the overlap region could not account for the observed obesity effects. We also observed significant obesity differences between genetically identical progeny that were contingent on the genotype of their subcongenic mothers.CONCLUSIONS: These results demonstrate the existence of at least three genes influencing obesity in three subcongenic strains with donor strain chromosomal regions whose size ranges from 0.5 to 5 cM. A maternal effect gene influencing obesity may be present in some subcongenic strains. IntroductionIdentification of natural alleles for complex traits such as obesity remains difficult but important because these studies survey the cumulative effects of evolution. While quantitative trait locus (QTL) mapping can identify broad chromosomal regions containing genes influencing complex traits, isolation of the specific underlying genes requires production of monogenic models. Congenic mouse strains can be used as monogenic models of complex traits. 1 Breeding two inbred strains to each other, and repeatedly backcrossing the progeny to the background strain for at least 10 generations produce congenic strains. The final congenic strain is identical to the background strain except for a selected donor region of highly variable size, and any unintended passenger donor regions (perhaps on other chromosomes) and spontaneous mutations occurring during breeding of the congenics. Although size, number and frequency of passenger donor chromosomal regions are usually unknown, their existence cannot be ruled out except by appropriate control experiments, such as those described in this manuscript.The congenic mouse strains surveyed for obesity traits in this study were originally produced by investigators studying histocompatability responses. 2 Historically, genes underlying the complex trait of tissue rejection were identified in...

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Section: Discussionmentioning

confidence: 86%

Multiple linked mouse chromosome 7 loci influence body fat mass

Diament

Warden

2003

Int J Obes

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“…The F 2 males and females were then randomly mated to produce 200 full-sibling F 3 families with a total of 1,632 F3 animals. One hundred fifty-eight of the 200 F 3 families participated in a cross-fostering protocol in which half of the pups from a pair of litters born on the same day were reciprocally exchanged between mothers (43,45). Thus, for approximately half of the population of pups, the normal correlation between postnatal maternal and offspring genotypes was negated.…”

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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“…No interaction between genetic background and effect size was detected regardless of whether the untransformed data were analysed (yielding the absolute effect size in grams) or whether the data were first scaled to the within-line variation (yielding an estimate in phenotypic standard deviation units). Evidence of epistasis is found frequently in genome-wide QTL analyses of body size [1,17,24,30] although in most cases not all QTL are involved in epistatic interactions (but see [5]). The lack of interaction between genetic background and the QTL identified in this study may indicate that this particular QTL does not participate in epistatic interactions with other loci, or that its interactions with a number of loci negate each other.…”

Section: Discussionmentioning

confidence: 99%

“…However, it would be expected that the effects of QTL would depend on the genetic background, given that the expressivity, penetrance and dominance of Mendelian mutations are frequently found to be affected by modifier genes [22]. Although a number of studies have found evidence of epistasis between QTL or marker loci (e.g., [1,5,17,24,30]), the statistical power to detect epistasis is generally very low [20] making it difficult to study specific interactions [24,30]. An alternative to examining pair-wise interactions between loci in a mapping population is to focus on a single QTL and to introgress the QTL alleles into different genetic backgrounds.…”

Section: Introductionmentioning

confidence: 99%

Identification and reciprocal introgression of a QTL affecting body mass in mice

et al. 2004

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-The aim of this study was to examine the effects of a QTL in different genetic backgrounds. A QTL affecting body mass on chromosome 6 was identified in an F 2 cross between two lines of mice that have been divergently selected for this trait. The effect of the QTL on mass increased between 6 and 10 weeks of age and was not sex-specific. Body composition analysis showed effects on fat-free dry body mass and fat mass. To examine the effect of this QTL in different genetic backgrounds, the high body mass sixth chromosome was introgressed into the low body mass genetic background and vice versa by repeated marker-assisted backcrossing. After three generations of backcrossing, new F 2 populations were established within each of the introgression lines by crossing individuals that were heterozygous across the sixth chromosome. The estimated additive effect of the QTL on 10-week body mass was similar in both genetic backgrounds and in the original F 2 population (i.e., ∼0.4 phenotypic standard deviations); no evidence of epistatic interaction with the genetic background was found. The 95% confidence interval for the location of the QTL was refined to a region of approximately 7 cM between D6Mit268 and D6Mit123. quantitative trait loci / introgression / epistasis / body mass

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Contribution of maternal effect QTL to genetic architecture of early growth in mice

Cited by 71 publications

References 39 publications

Multiple linked mouse chromosome 7 loci influence body fat mass

Multiple linked mouse chromosome 7 loci influence body fat mass

Genomic imprinting effects on adult body composition in mice

Identification and reciprocal introgression of a QTL affecting body mass in mice

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