Fine Mapping Reveals Sex Bias in Quantitative Trait Loci Affecting Growth, Skeletal Size and Obesity-Related Traits on Mouse Chromosomes 2 and 11

Farber, Charles R.; Medrano, Juan F.

doi:10.1534/genetics.106.063693

Cited by 40 publications

(52 citation statements)

References 48 publications

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“…Such interactions between QTLs and sex were also observed in other obesity-related studies in mice, [42][43][44][45] suggesting that underlying genes were differentially expressed in males and females. For example, estrogens that differ between the two sexes can act as transcription factors and might regulate the QTL alleles in a sex-specific manner.…”

Section: Discussionsupporting

confidence: 76%

A unique genetic defect on chromosome 3 is responsible for juvenile obesity in the Berlin Fat Mouse

et al. 2010

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Objective: This study aimed at the mapping and estimation of genetic and sex effects contributing to the obese phenotype of the Berlin Fat Mouse Inbred line 860 (BFMI860). This mouse line is predisposed for juvenile obesity. BFMI860 mice accumulate 24% total fat mass at 10 weeks of age under a standard maintenance diet. Design: A total of 471 mice of a (BFMI860 Â C57BL/6NCrl) F 2 intercross population were fed a standard maintenance diet and were analysed for body composition at 10 weeks when they finished their rapid growth phase. Results: The most striking result was the identification of a novel obesity locus on chromosome 3 (Chr 3) at 40 Mb, explaining 39% of the variance of total fat mass in the F 2 population under a standard diet. This locus was named jObes1 (juvenile obesity 1). The BFMI860 allele effect was recessive. Males and females homozygous at jObes1 had on average 3.0 and 3.3 g more total fat mass at 10 weeks than the other two genotype classes, respectively. The effect was evident in all white adipose tissues, brown adipose tissue and also in liver. The position of the Chr 3 effect is syntenic to an obesity locus in humans. Additional loci for total fat mass and different white adipose tissue weights with minor effects were detected on mouse Chr 5 and 6. Another locus on Chr 4 had influence especially on liver weight. Many loci including jObes1 affected males and females to a different extent. Conclusion:The major locus on Chr 3 for juvenile obesity and its interaction with sex is unique and makes the BFMI860 mice an interesting resource for the discovery of novel genetic factors predisposing obesity, which might also contribute to obesity in humans. The results suggested that metabolic and regulatory pathways differed between the sexes.

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Section: Discussionsupporting

confidence: 76%

A unique genetic defect on chromosome 3 is responsible for juvenile obesity in the Berlin Fat Mouse

et al. 2010

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“…A significant interaction was also detected for the putative body mass QTL on chromosome 23 but this result remains speculative because of uncertainties regarding the presence of a QTL at that position. QTLs with sex-specific effects have been documented in a variety of organisms (for example, Nuzhdin et al, 1997;Farber and Medrano, 2007;Moghadam et al, 2007) including domestic sheep ), but to our knowledge had never been documented in a free-living wildlife population. The presence of sex-specific QTL effects in bighorn sheep adds to the accumulating evidence suggesting that sexual selection alters the genetic architecture of quantitative traits by promoting the accumulation of sex-specific genetic variance (Moller 1993;Wilkinson 1993;Bonduriansky and Rowe, 2005;Wright et al, 2008;Robinson et al, 2009).…”

Section: Sexâqtl Interactionsmentioning

confidence: 91%

QTL mapping for sexually dimorphic fitness-related traits in wild bighorn sheep

et al. 2011

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Dissecting the genetic architecture of fitness-related traits in wild populations is key to understanding evolution and the mechanisms maintaining adaptive genetic variation. We took advantage of a recently developed genetic linkage map and phenotypic information from wild pedigreed individuals from Ram Mountain, Alberta, Canada, to study the genetic architecture of ecologically important traits (horn volume, length, base circumference and body mass) in bighorn sheep. In addition to estimating sex-specific and cross-sex quantitative genetic parameters, we tested for the presence of quantitative trait loci (QTLs), colocalization of QTLs between bighorn sheep and domestic sheep, and sexÂQTL interactions. All traits showed significant additive genetic variance and genetic correlations tended to be positive. Linkage analysis based on 241 microsatellite loci typed in 310 pedigreed animals resulted in no significant and five suggestive QTLs (four for horn dimension on chromosomes 1, 18 and 23, and one for body mass on chromosome 26) using genome-wide significance thresholds (Logarithm of odds (LOD) 43.31 and 41.88, respectively). We also confirmed the presence of a horn dimension QTL in bighorn sheep at the only position known to contain a similar QTL in domestic sheep (on chromosome 10 near the horns locus; nominal Po0.01) and highlighted a number of regions potentially containing weight-related QTLs in both species. As expected for sexually dimorphic traits involved in male-male combat, loci with sex-specific effects were detected. This study lays the foundation for future work on adaptive genetic variation and the evolutionary dynamics of sexually dimorphic traits in bighorn sheep.

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“…Likewise, two other QTLs were novel (Bwtq13 and Adip19), although in the case of Adip19, there were a few points to consider before we concluded that this was a novel QTL. There were three previous reports of QTLs near Adip19 but all previous QTLs had features that made it unlikely that they captured the same underlying genetic variation (Carlborg et al 2005;Collin et al 2005;Farber and Medrano 2007). Determining whether a QTL replicates is subject to some uncertainty regarding its location, confidence interval, and its effects on a particular genetic background, and thus the term "novel QTL" is applied here only with these considerations in mind.…”

Section: Novel Qtlsmentioning

confidence: 99%

“…In addition to the types of obesity measures used, the strength of sex-by-genotype (Farber and Medrano 2007) and gene-gene interactions (Brockmann et al 2000) influence the trait. These types of interactions may be as important as additive genetic effects in their contribution to the heritability of body composition.…”

Section: Introductionmentioning

confidence: 99%

Genetic loci affecting body weight and fatness in a C57BL/6J × PWK/PhJ mouse intercross

2007

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To determine the genetic variation that contributes to body composition in the mouse, we interbred a wild-derived strain (PWK/PhJ; PWK) with a common laboratory strain (C57BL/6J; B6). The parental, F 1 , and F 2 mice were phenotyped at 18 weeks old for body weight and composition using dual-energy X-ray absorptiometry (DEXA). A total of 479 (244 male and 235 female) F 2 mice were genotyped for 117 polymorphic markers spanning the autosomes. Twenty-eight suggestive or significant linkages for four traits (body weight, adjusted lean and fat weight, and percent fat) were detected. Of these, three QTLs were novel: one on the proximal portion of Chr 5 for body weight (Bwq8; LOD = 4.7), one on Chr 3 for lean weight (Bwtq13; LOD = 3.6), and one on Chr 11 for percent fat (Adip19; LOD = 5.8). The remaining QTLs overlapped previously identified linkages, e.g., Adip5 on Chr 9. One QTL was sex-specific (present in males only) and seven were sex-biased (more prominent in one sex than the other). Most alleles that increased body weight were contributed by the B6 strain, and most alleles that increased percent fat were contributed by the PWK strain. Eight pairs of interacting loci were identified, none of which exactly overlapped the main-effect QTLs. Many of the QTLs found in the B6 × PWK cross map to the location of previously reported linkages, suggesting that some QTLs are common to many strains (consensus QTLs), but three new QTLs appear to be particular to the PWK strain. The location and type of QTLs detected in this new cross will assist in future efforts to identify the genetic variation that determines the ratio of lean to fat weight as well as body size in mice.

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Fine Mapping Reveals Sex Bias in Quantitative Trait Loci Affecting Growth, Skeletal Size and Obesity-Related Traits on Mouse Chromosomes 2 and 11

Cited by 40 publications

References 48 publications

A unique genetic defect on chromosome 3 is responsible for juvenile obesity in the Berlin Fat Mouse

A unique genetic defect on chromosome 3 is responsible for juvenile obesity in the Berlin Fat Mouse

QTL mapping for sexually dimorphic fitness-related traits in wild bighorn sheep

Genetic loci affecting body weight and fatness in a C57BL/6J × PWK/PhJ mouse intercross

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