Quantitative Trait Loci For Body Weight Research Articles

Further characterization of diabetes mellitus and body weight loss in males of the congenic mouse strain DDD.Cg-A(y.).

The Ay allele at the agouti locus causes obesity and promotes linear growth in mice. However, body weight gain stops between 16 and 17 weeks after birth, and then, body weight decreases gradually in DDD.Cg-Ay male mice. Body weight loss is a consequence of diabetes mellitus, which is genetically controlled mainly by a quantitative trait locus (QTL) on chromosome 4. This study aimed to further characterize diabetes mellitus and body weight loss in DDD.Cg-Ay males. The number of β-cells was markedly reduced, and plasma insulin levels were very low in the DDD.Cg-Ay males. Using a backcross progeny of DDD × (B6 × DDD.Cg-Ay) F1-Ay, we identified one significant QTL for plasma insulin levels on distal chromosome 4, which was coincidental with QTL for hyperglycemia and lower body weight. The DDD allele was associated with decreased plasma insulin levels. When the DDD.Cg-Ay males were housed under three different housing conditions [group housing (4 or 5 DDD.Cg-Ay and DDD males), individual housing (single DDD.Cg-Ay male) and single male housing with females (single DDD.Cg-Ay male with DDD.Cg-Ay or DDD females)], diabetes mellitus and body weight loss were most severely expressed in individually housed mice. Thus, the severity of diabetes and body weight loss in the DDD.Cg-Ay males was strongly influenced by the housing conditions. These results demonstrate that both genetic and nongenetic environmental factors are involved in the development of diabetes mellitus and body weight loss in the DDD.Cg-Ay males.

QTL mapping for economically important traits of common carp (Cyprinus carpio L.).

Quantitative trait loci (QTL) were analyzed for three economically important traits, i.e., body weight (BW), body length (BL), and body thickness (BT), in an F1 family of common carp holding the 190 progeny. A genetic linkage map spanning 3,301 cM in 50 linkage groups with 627 markers and an average distance of 5.6 cM was utilized for QTL mapping. Sixteen QTLs associated with all three growth-related traits were scattered across ten linkage groups, LG6, LG10, LG17, LG19, LG25, LG27, LG28, LG29, LG30, and LG39. Six QTLs for BW and five each for BL and BT explained phenotypic variance in the range 17.0-32.1%. All the nearest markers of QTLs were found to be significantly (p ≤ 0.05) related with the trait. Among these QTLs, a total of four, two (qBW30 and qBW39) related with BW, one (qBL39) associated with BL, and one (qBT29) related to BT, were found to be the major QTLs with a phenotypic variance of >20%. qBW30 and qBW39 with the nearest markers HLJ1691 and HLJ1843, respectively, show significant values of 0.0038 and 0.0031, correspondingly. QTLs qBL39 and qBT29 were found to have significant values of 0.0047 and 0.0015, respectively. Three QTLs (qBW27, qBW30, qBW39) of BW, two for BL (qBL19, qBL39), and two for BT (qBT6, qBT25) found in this study were similar to populations with different genetic backgrounds. In this study, the genomic region controlling economically important traits were located. These genomic regions will be the major sources for the discovery of important genes and pathways associated with growth-related traits in common carp.

Linking cellular zinc status to body weight and fat mass: mapping quantitative trait loci in Znt7 knockout mice.

Zinc transporter 7 (Znt7, Slc30a7) knockout (KO) mice display abnormalities in body weight gain and body adiposity. Regulation of body weight and body fat accumulation is complex, involving multiple genetic and environmental factors. To understand how zinc homeostasis influences body weight and fat deposit and to identify quantitative trait loci (QTLs) that link zinc metabolism to growth and adiposity, we conducted a genome-wide mapping study using male F2 Znt7 KO mice and wild-type (WT) littermates with a mixed 129P1/ReJ and C57BL/6J genetic background. The mice were fed a semi-purified diet containing 30-mg Zn/kg diet at weaning. Body weights and fat pad weights including epididymal, retroperitoneal, and femoral subcutaneous fat pads were measured at 16weeks of age. We detected two significant QTLs (p<0.05) for body weight and fat deposit. One was in the F2 Znt7 KO population and the other in the F2 WT population. In Znt7 KO mice, the body weight and fat deposit was significantly linked to a locus on chromosome 7 ranging from 64.3 to 78.3Mb. In WT mice, a significant linkage of retroperitoneal fat mass was found on chromosome 8 between 14.5 and 63.5Mb. In addition, several other suggestive QTLs (p<0.63) for body weight and fat accumulation were detected in Znt7 KO and WT mice. In conclusion, the QTLs identified in this study may provide new hints to uncover the genes linking cellular zinc status to growth and body fat accumulation.

Detection of QTL controlling digestive efficiency and anatomy of the digestive tract in chicken fed a wheat-based diet

BackgroundImproving digestive efficiency is a major goal in poultry production, to reduce production costs, make possible the use of alternative feedstuffs and decrease the volume of manure produced. Since measuring digestive efficiency is difficult, identifying molecular markers associated with genes controlling this trait would be a valuable tool for selection. Detection of QTL (quantitative trait loci) was undertaken on 820 meat-type chickens in a F2 cross between D- and D+ lines divergently selected on low or high AMEn (apparent metabolizable energy value of diet corrected to 0 nitrogen balance) measured at three weeks in animals fed a low-quality diet. Birds were measured for 13 traits characterizing digestive efficiency (AMEn, coefficients of digestive utilization of starch, lipids, proteins and dry matter (CDUS, CDUL, CDUP, CDUDM)), anatomy of the digestive tract (relative weights of the proventriculus, gizzard and intestine and proventriculus plus gizzard (RPW, RGW, RIW, RPGW), relative length and density of the intestine (RIL, ID), ratio of proventriculus and gizzard to intestine weight (PG/I); and body weight at 23 days of age. Animals were genotyped for 6000 SNPs (single nucleotide polymorphisms) distributed on 28 autosomes, the Z chromosome and one unassigned linkage group.ResultsNine QTL for digestive efficiency traits, 11 QTL for anatomy-related traits and two QTL for body weight at 23 days of age were detected. On chromosome 20, two significant QTL at the genome level co-localized for CDUS and CDUDM, i.e. two traits that are highly correlated genetically. Moreover, on chromosome 16, chromosome-wide QTL for AMEn, CDUS, CDUDM and CDUP, on chromosomes 23 and 26, chromosome-wide QTL for CDUS, on chromosomes 16 and 26, co-localized QTL for digestive efficiency and the ratio of intestine length to body weight and on chromosome 27 a chromosome-wide QTL for CDUDM were identified.ConclusionsThis study identified several regions of the chicken genome involved in the control of digestive efficiency. Further studies are necessary to identify the underlying genes and to validate these in commercial populations and breeding environments.

Analysis of novel obesity genes with the aid of congenic rats

Background: Obesity is caused by multiple genes and their interaction. Studies in rats have revealed a link between a number of quantitative trait loci (QTLs) with facets of the metabolic syndrome. A QTL for serum cholesterol and body weight was identified on rat chromosome 10.

Genetic map construction and quantitative trait locus (QTL) detection of growth-related traits in Litopenaeus vannamei for selective breeding applications.

Growth is a priority trait from the point of view of genetic improvement. Molecular markers linked to quantitative trait loci (QTL) have been regarded as useful for marker-assisted selection (MAS) in complex traits as growth. Using an intermediate F2 cross of slow and fast growth parents, a genetic linkage map of Pacific whiteleg shrimp, Litopenaeusvannamei , based on amplified fragment length polymorphisms (AFLP) and simple sequence repeats (SSR) markers was constructed. Meanwhile, QTL analysis was performed for growth-related traits. The linkage map consisted of 451 marker loci (429 AFLPs and 22 SSRs) which formed 49 linkage groups with an average marker space of 7.6 cM; they spanned a total length of 3627.6 cM, covering 79.50% of estimated genome size. 14 QTLs were identified for growth-related traits, including three QTLs for body weight (BW), total length (TL) and partial carapace length (PCL), two QTLs for body length (BL), one QTL for first abdominal segment depth (FASD), third abdominal segment depth (TASD) and first abdominal segment width (FASW), which explained 2.62 to 61.42% of phenotypic variation. Moreover, comparison of linkage maps between L . vannamei and Penaeus japonicus was applied, providing a new insight into the genetic base of QTL affecting the growth-related traits. The new results will be useful for conducting MAS breeding schemes in L . vannamei .

Comparative analysis of quantitative trait loci for body weight, growth rate and growth curve parameters from 3 to 72 weeks of age in female chickens of a broiler–layer cross

BackgroundComparisons of quantitative trait loci (QTL) for growth and parameters of growth curves assist in understanding the genetics and ultimately the physiology of growth. Records of body weight at 3, 6, 12, 24, 48 and 72 weeks of age and growth rate between successive age intervals of about 500 F2 female chickens of the Roslin broiler-layer cross were available for analysis. These data were analysed to detect and compare QTL for body weight, growth rate and parameters of the Gompertz growth function.ResultsOver 50 QTL were identified for body weight at specific ages and most were also detected in the nearest preceding and/or subsequent growth stage. The sum of the significant and suggestive additive effects for bodyweight at specific ages accounted for 23-43% of the phenotypic variation. A single QTL for body weight on chromosome 4 at 48 weeks of age had the largest additive effect (550.4 ± 68.0 g, 11.5% of the phenotypic variation) and a QTL at a similar position accounted 14.5% of the phenotypic variation at 12 weeks of age. Age specific QTL for growth rate were detected suggesting that there are specific genes that affect developmental processes during the different stages of growth. Relatively few QTL influencing Gompertz growth curve parameters were detected and overlapped with loci affecting growth rate. Dominance effects were generally not significant but from 12 weeks of age they exceeded the additive effect in a few cases. No evidence for epistatic QTL pairs was found.ConclusionsThe results confirm the location for body weight and body weight gain during growth that were identified in previous studies and were consistent with QTL for the parameters of the Gompertz growth function. Chromosome 4 explained a relatively large proportion of the observed growth variation across the different ages, and also harboured most of the detected QTL for Gompertz parameters, confirming its importance in controlling growth. Very few QTL were detected for body weight or gain at 48 and 72 weeks of age, probably reflecting the effect of differences in reproduction and random environmental effects.

Quantitative trait locus for body weight identified on rat chromosome 4 in inbred alcohol-preferring and -nonpreferring rats: Potential implications for neuropeptide Y and corticotrophin releasing hormone 2

The alcohol-preferring (P) and -nonpreferring (NP) rat lines were developed using bidirectional selective breeding for alcohol consumption (g/kg/day) and alcohol preference (water:ethanol ratio). During a preliminary study, we detected a difference in body weight between inbred P (iP) and inbred NP (iNP) rats that appeared to be associated with the transfer of the Chromosome 4 quantitative trait locus (QTL) seen in the P.NP and NP.P congenic strains. After the initial confirmation that iP rats displayed lower body weight when compared to iNP rats (data not shown), body weight and growth rates of each chromosome 4 reciprocal congenic rat strain (P.NP and NP.P) were measured, and their body weight was consistent with their respective donor strain phenotype, confirming that a quantitative trait locus for body weight mapped to the chromosome 4 interval. Utilizing the newly developed interval-specific congenic strains (ISCS-A and ISCS-B), the QTL interval was further narrowed identifying the following candidate genes of interest: neuropeptide Y (Npy), juxtaposed with another zinc finger gene 1 (Jazf1), corticotrophin releasing factor receptor 2 (Crfr2) and LanC lantibiotic synthetase component C-like 2 (Lancl2). These findings indicate that a biologically active variant(s) regulates body weight on rat chromosome 4 in iP and iNP rats. This QTL for body weight was successfully captured in the P.NP and NP.P congenic strains, and interval-specific congenic strains (ISCSs) were subsequently employed to fine-map the QTL interval identifying the following candidate genes of interest: Npy, Jazf1, Crfr2 and Lancl2. Both Npy and Crfr2 have been previously identified as candidate genes of interest underlying the chromosome 4 QTL for alcohol consumption in iP and iNP rats.

Fine mapping of quantitative trait loci affecting organ weights by mouse intersubspecific subcongenic strain analysis

The genetic architecture of organ weights is not well understood. In this study, we fine-mapped quantitative trait loci (QTLs) affecting organ weights by characterizing six intersubspecific subcongenic mouse strains with overlapping and non-overlapping genomic regions on chromosome 2 derived from wild Mus musculus castaneus. QTLs for heart, lung, spleen and kidney weights were revealed on a 6.38-Mb genomic region between two microsatellite markers, D2Mit323 and D2Mit472. Effects of the castaneus alleles at the organ weight QTLs were all opposite in direction to a body weight QTL previously mapped to the same genomic region. In addition, new QTLs for lung and kidney weights were revealed on a different 3.57-Mb region between D2Mit205 and D2Mit182. Their effects were dependent on that of another body weight QTL previously mapped to that genomic region. The organ weight QTLs revealed were all duplicated in independent analyses with F2 intercross populations between subcongenic strains carrying these QTLs and their background strain. The findings suggested that organ weights are not exclusively regulated by genetic loci that commonly influence overall body weight and rather that there are loci contributing to the growth of specific organs only.

Genetic Regulation of Life Span, Metabolism, and Body Weight in Pohn, a New Wild-Derived Mouse Strain

Quantitative trait loci (QTL) of longevity identified in human and mouse are significantly colocalized, suggesting that common mechanisms are involved. However, the limited number of strains that have been used in mouse longevity studies undermines the ability to identify longevity genes. We crossed C57BL/6J mice with a new wild-derived strain, Pohn, and identified two life span QTL-Ls1 and Ls2. Interestingly, homologous human longevity QTL colocalize with Ls1. We also defined new QTL for metabolic heat production and body weight. Both phenotypes are significantly correlated with life span. We found that large clone ratio, an in vitro indicator for cellular senescence, is not correlated with life span, suggesting that cell senescence and intrinsic aging are not always associated. Overall, by using Pohn mice, we identified new QTL for longevity-related traits, thus facilitating the exploration of the genetic regulation of aging.

Genetic map construction and quantitative trait locus (QTL) analysis on growth-related traits in common carp (Cyprinus carpio L.)

Common carp (Cyprinus carpio L.) is one of the most widely distributed freshwater species in the world with important values in aquaculture, however, its quantitative trait loci (QTLs) associated to growth-related traits have been rarely identified. In this study, using F2 populations derived from a cross between Purse red common carp (C. carpio var. wuyuanensis) and Xingguo red common carp (C. carpio var.singuonensis), a genetic linkage map of common carp based on amplified fragment length polymorphisms (AFLP) and microsatellite (SSR) markers was constructed, meanwhile QTL analysis were conducted for growth-related traits. A total of 347 AFLP and 22 SSR markers were assembled on the map, which comprised 50 linkage groups and covered 5608.1cM Kosambi. A total of 25 QTLs were identified for growth-related traits, including four QTLs for body weight, one QTL for total length, four QTLs for standard length, six QTLs for body height, eight QTLs for caudal peduncle length and two QTLs for caudal peduncle height, which explained 0.05 to 61.40% of phenotypic variation. Meanwhile, comparison of linkage maps between common carp and zebrafish was also conducted, providing a new insight into the genetic base of the QTL affecting the growth-related traits. This study will be useful for conducting marker-assisted selection (MAS) breeding programs in common carp. Key words: Cyprinus carpio, F2 populations, amplified fragment length polymorphisms, microsatellite, quantitative traits locus.

Detection of quantitative trait loci for resistance to gastrointestinal nematode infections in Creole goats

This study aimed to identify regions of the genome affecting resistance to gastrointestinal nematodes in a Creole goat population naturally exposed to a mixed nematode infection (Haemonchus contortus, Trichostrongylus colubriformis and Oesophagostomum columbianum) by grazing on irrigated pasture. A genome-wide quantitative trait loci (QTL) scan was performed on 383 offspring from 12 half-sib families. A total of 101 microsatellite markers were genotyped. Traits analysed were faecal egg count (FEC), packed cell volume (PCV), eosinophil count and bodyweight (BW) at 7 and 11 months of age. Levels of activity of immunoglobulin A (IgA) and activity of immunoglobulin E (IgE) anti-Haemonchus contortus L3 crude extracts and adult excretion/secretion products (ESPs) were also analysed. Using interval mapping, this study identified 13 QTL for parasite resistance. Two QTL linked with FEC were found on chromosomes 22 and 26. Three QTL were detected on chromosomes 7, 8 and 14 for eosinophil counts. Three QTL linked with PCV were identified on chromosomes 5, 9 and 21. A QTL for BW at 7 months of age was found on chromosome 6. Lastly, two QTL detected on chromosomes 3 and 10 were associated with IgE anti-L3, and IgE anti-ESP was linked with two QTL on chromosomes 1 and 26. This study is the first to have identified regions of the genome linked with nematode resistance in a goat population using a genome scan. These results provide useful tools for the understanding of parasite resistance in small ruminants.

Many quantitative trait loci for feather growth in an F2 broiler × layer cross collocate with body weight loci

1. A genome-wide scan of 467 F2 progeny of a broiler x layer cross was conducted to identify quantitative trait loci (QTL) affecting the rate of growth of the tail, wing and back feathers, and the width of the breast feather tract, at three weeks of age. 2. Correlations between the traits ranged from 0·36 to 0·61. Males had longer tail and wing feathers and shorter back feathers than females. Breast feather tract width was greater in females than males. 3. QTL effects were generally additive and accounted for 11 to 45% of sex average feather lengths of the breeds, and 100% of the breast feather tract width. Positive and negative alleles were inherited from both lines, whereas the layer allele was larger than the broiler allele after adjusting for body weight. 4. A total of 4 genome-significant and 4 suggestive QTL were detected. At three or 6 weeks of age, 5 of the QTL were located in similar regions as QTL for body weight. 5. Analysis of a model with body weight at three weeks as a covariate identified 5 genome significant and 6 suggestive QTL, of which only two were coincident with body weight QTL. One QTL for feather length at 148 cM on GGA1 was identified at a similar location in the unadjusted analysis. 6. The results suggest that the rate of feather growth is largely controlled by body weight QTL, and that QTL specific for feather growth also exist.

Quantitative trait loci associated with body weight and abdominal fat traits on chicken chromosomes 3, 5 and 7

Body weight and abdominal fat traits in meat-type chickens are complex and economically important factors. Our objective was to identify quantitative trait loci (QTL) responsible for body weight and abdominal fat traits in broiler chickens. The Northeast Agricultural University Resource Population (NEAURP) is a cross between broiler sires and Baier layer dams. We measured body weight and abdominal fat traits in the F(2) population. A total of 362 F(2) individuals derived from four F(1) families and their parents and F(0) birds were genotyped using 29 fluorescent microsatellite markers located on chromosomes 3, 5 and 7. Linkage maps for the three chromosomes were constructed and interval mapping was performed to identify putative QTLs. Nine QTL for body weight were identified at the 5% genome-wide level, while 15 QTL were identified at the 5% chromosome-wide level. Phenotypic variance explained by these QTL varied from 2.95 to 6.03%. In particular, a QTL region spanning 31 cM, associated with body weight at 1 to 12 weeks of age and carcass weight at 12 weeks of age, was first identified on chromosome 5. Three QTLs for the abdominal fat traits were identified at the 5% chromosome-wide level. These QTLs explained 3.42 to 3.59% of the phenotypic variance. This information will help direct prospective fine mapping studies and can facilitate the identification of underlying genes and causal mutations for body weight and abdominal fat traits.

Detection of quantitative trait loci for growth‐ and fatness‐related traits in a large‐scale White Duroc × Erhualian intercross pig population

Growth and fatness are economically important traits in pigs. In this study, a genome scan was performed to detect quantitative trait loci (QTL) for 14 growth and fatness traits related to body weight, backfat thickness and fat weight in a large-scale White Duroc × Erhualian F(2) intercross. A total of 76 genome-wide significant QTL were mapped to 16 chromosomes. The most significant QTL was found on pig chromosome (SSC) 7 for fatness with unexpectedly small confidence intervals of ∼2 cM, providing an excellent starting point to identify causal variants. Common QTL for both fatness and growth traits were found on SSC4, 5, 7 and 8, and shared QTL for fat deposition were detected on SSC1, 2 and X. Time-series analysis of QTL for body weight at six growth stages revealed the continuously significant effects of the QTL on SSC4 at the fattening period and the temporal-specific expression of the QTL on SSC7 at the foetus and fattening stages. For fatness traits, Chinese Erhualian alleles were associated with increased fat deposition except that at the major QTL on SSC7. For growth traits, most of White Duroc alleles enhanced growth rates except for those at three significant QTL on SSC6, 7 and 9. The results confirmed many previously reported QTL and also detected novel QTL, revealing the complexity of the genetic basis of growth and fatness in pigs.

Mapping of Quantitative Trait Loci Affecting Growth Traits in a Japanese Native Chicken Cross

The Hinai-dori is a breed of chicken native to Akita Prefecture, Japan. An resource population produced by crossing low- and high-growth lines of the Hinai-dori breed was analyzed to detect quantitative trait loci (QTL) for growth traits. Highly significant QTLs for body weight at 10 and 14 weeks of age and average daily gain between 4 and 10 weeks and between 10 and 14 weeks of age were accordingly mapped in a common region between ADL0198 and ABR0287 on chromosome 1 and between MCW0240 and ABR0622 on chromosome 4, respectively. A significant QTL for body weight at 4 weeks of age and a significant QTL for average daily gain between 0 and 4 weeks of age were mapped for the first time to the same region flanking ABR0204 and ABR0284 on chromosome 1. These QTLs are good candidates for application in the development of marker-assisted selection strategies for increasing growth efficiencies in the Hinai-dori breed and native breeds of chickens in Asia.

Fine-mapping of quantitative trait loci for body weight and bone traits and positional cloning of the RB1 gene in chicken

Previously, a quantitative trait locus (QTL) that affects body weight (BW) at 4-12 weeks of age and carcass weight at 12 weeks of age had been mapped on chicken chromosome 1. After including more markers and individuals, the confidence interval was narrowed down to approximately 5.5 Mbps and located this QTL near a microsatellite marker (ADL328). This QTL is the same as the QTL for 12 bone traits, including metatarsus length and metatarsus circumference at 4, 6, 8, 10 and 12 weeks of age and keel length and metatarsus claw weight at 12 weeks of age, that was identified using the same population. In the current study, 1010 individuals from the Northeast Agricultural University F(2) resource population were used and 14 single-nucleotide polymorphism (SNPs) around ADL328 were developed to construct haplotypes, and an association analysis was performed to fine-map the QTL. The haplotypes were constructed on the basis of a sliding 'window', with three SNP markers included in each 'window'. The association analysis results indicated that the haplotypes in 'windows' 6-12 were significantly associated with BW and bone traits and suggested that the QTL for BW and bone traits was located between SNP8 and SNP14 or was in linkage disequilibrium with this region. The interval from SNP8 to SNP14 was approximately 400 kbps. This region contained five RefSeq genes (RB1, P2RY5, FNDC3A, MLNR and CAB39L) on the University of California Santa Cruz website. The RB1 gene was selected as a candidate gene and five SNPs were identified in the gene. The association results indicated that the RB1 gene was a major gene for BW and bone traits. The SNPs g.39692 G>A and g.77260 A>G in RB1 gene might be two quantitative trait nucleotides for BW and bone traits.

Deep congenic analysis identifies many strong, context-dependent QTLs, one of which, Slc35b4, regulates obesity and glucose homeostasis

Although central to many studies of phenotypic variation and disease susceptibility, characterizing the genetic architecture of complex traits has been unexpectedly difficult. For example, most of the susceptibility genes that contribute to highly heritable conditions such as obesity and type 2 diabetes (T2D) remain to be identified despite intensive study. We took advantage of mouse models of diet-induced metabolic disease in chromosome substitution strains (CSSs) both to characterize the genetic architecture of diet-induced obesity and glucose homeostasis and to test the feasibility of gene discovery. Beginning with a survey of CSSs, followed with genetic and phenotypic analysis of congenic, subcongenic, and subsubcongenic strains, we identified a remarkable number of closely linked, phenotypically heterogeneous quantitative trait loci (QTLs) on mouse chromosome 6 that have unexpectedly large phenotypic effects. Although fine-mapping reduced the genomic intervals and gene content of these QTLs over 3000-fold, the average phenotypic effect on body weight was reduced less than threefold, highlighting the "fractal" nature of genetic architecture in mice. Despite this genetic complexity, we found evidence for 14 QTLs in only 32 recombination events in less than 3000 mice, and with an average of four genes located within the three body weight QTLs in the subsubcongenic strains. For Obrq2a1, genetic and functional studies collectively identified the solute receptor Slc35b4 as a regulator of obesity, insulin resistance, and gluconeogenesis. This work demonstrated the unique power of CSSs as a platform for studying complex genetic traits and identifying QTLs.

Architecture of energy balance traits in emerging lines of the Collaborative Cross

The potential utility of the Collaborative Cross (CC) mouse resource was evaluated to better understand complex traits related to energy balance. A primary focus was to examine if genetic diversity in emerging CC lines (pre-CC) would translate into equivalent phenotypic diversity. Second, we mapped quantitative trait loci (QTL) for 15 metabolism- and exercise-related phenotypes in this population. We evaluated metabolic and voluntary exercise traits in 176 pre-CC lines, revealing phenotypic variation often exceeding that seen across the eight founder strains from which the pre-CC was derived. Many phenotypic correlations existing within the founder strains were no longer significant in the pre-CC population, potentially representing reduced linkage disequilibrium (LD) of regions harboring multiple genes with effects on energy balance or disruption of genetic structure of extant inbred strains with substantial shared ancestry. QTL mapping revealed five significant and eight suggestive QTL for body weight (Chr 4, 7.54 Mb; CI 3.32-10.34 Mb; Bwq14), body composition, wheel running (Chr 16, 33.2 Mb; CI 32.5-38.3 Mb), body weight change in response to exercise (1: Chr 6, 77.7Mb; CI 72.2-83.4 Mb and 2: Chr 6, 42.8 Mb; CI 39.4-48.1 Mb), and food intake during exercise (Chr 12, 85.1 Mb; CI 82.9-89.0 Mb). Some QTL overlapped with previously mapped QTL for similar traits, whereas other QTL appear to represent novel loci. These results suggest that the CC will be a powerful, high-precision tool for examining the genetic architecture of complex traits such as those involved in regulation of energy balance.

A proximal genomic region of mouse chromosome 10 contains quantitative trait loci affecting fatness

Body weight and fatness are quantitative traits of agricultural and medical importance. In previous genome-wide quantitative trait locus (QTL) analyses, two QTLs for body weight and weight gain at an early postnatal growth period were discovered on mouse chromosome 10 from a gene pool of wild subspecies mice, Mus musculus castaneus. In this study, we developed a congenic strain with an approximately 63-Mb wild-derived genomic region on which the two growth QTLs could be located, by recurrent backcrossing to the common inbred strain C57BL/6J. We compared body weights at 1-10 weeks of age, body weight gains at 1-3, 3-6 and 6-10 weeks, internal organ weights and body lengths between the congenic strain developed and C57BL/6J. Unfortunately, no effects of the two growth QTLs on body weights and weight gains were confirmed. However, at least two new QTLs affecting fatness traits were discovered within the introgressed congenic region. The wild-derived allele at one QTL increased body mass index, whereas at another one it decreased white fat pad weight and adiposity index. Thus, the congenic mouse strain developed here is a useful model animal for understanding the genetic and molecular basis of fat deposition in livestock as well as humans.