Biomedical subjects

J M Cheverud

Publications and source records attributed to J M Cheverud.

At least 19 recordsLinked to original sources

PubMed2001

Subspecific genetic differences in the saddle-back tamarin (Saguinus fuscicollis) postcranial skeleton.

Saddle-back tamarins (Saguinus fuscicollis) have been differentiated into subspecies based on coat color and facial morphology. Morphology of first-generation genetic hybrids can provide an understanding of population differences and evolution that may otherwise be difficult to obtain. This study compares postcranial morphology in two hybrids of saddle-back tamarins (S. f. illigeri x S. f. lagonotus and S. f. illigeri x S. f. leucogenys) to the purebred subspecies. We examine whether postcranial morphology differs between the purebred subspecies and their hybrids, and whether hybrids exhibit heterosis indicative of genetic differences between the parental subspecies. Fifty postcranial dimensions, or traits, were measured on 287 S. fuscicollis skeletons. Measurements were corrected for sex differences and environmental differences (wild-derived or laboratory-born). Females were larger than males for most postcranial dimensions, especially in the pelvis. Significant environmental differences were found throughout the postcranial skeleton, with wild-derived animals generally larger than animals born in the laboratory. Significant heterosis was found for six postcranial traits in the S. f. illigeri x S. f. leucogenys cross, and heterosis was found for 15 postcranial traits in the S. f. illigeri x S. f. lagonotus cross. These results suggest that subspecies differences in skeletal morphology are generally due to genetic rather than environmental differences. The subspecies appear to represent geographic isolates that differ in gene frequencies and directional dominance for skeletal traits.

Animals↗

PubMed2001

Genetic architecture of adiposity in the cross of LG/J and SM/J inbred mice.

The genetic basis of variation in obesity in human populations is thought to be owing to many genes of relatively small effect and their interactions. The LG/J by SM/J intercross of mouse inbred strains provides an excellent model system in which to investigate multigenic obesity. We previously mapped a large number of quantitative trait loci (QTLs) affecting adult body weight in this cross. We map body composition traits, adiposity, and skeletal size, in a replicate F2 intercross of the same two strains containing 510 individuals. Using interval-mapping methods, we located eight QTLs affecting adiposity (Adip1-8). Two of these adiposity loci also affected tail length (Adip4 and Adip6) along with seven additional tail length QTLs (Skl1-7). A further four QTLs (Wt1-4) affect adult weight but not body composition. These QTLs have relatively small effects, typically about 0.2-0.4 standard deviation units, and account for between 3% and 10% of the variance in individual characters. All QTLs participated in epistatic interactions with other QTLs. Most of these interactions were due to additive-by-additive epistasis, which can nullify the apparent effects of single loci in our population. Adip8 interacts with all the other adiposity QTLs and seems to play a central role in the genetic system affecting obesity in this cross. Only two adiposity QTLs, Adip4 and Adip6, also affect tail length, indicating largely separate genetic control of variation in adiposity and skeletal size. Body size and obesity QTLs in the same locations as those discovered here are commonly found in mapping experiments with other mouse strains.

Adipose Tissue↗

PubMed2001

Genetic architecture of mandible shape in mice: effects of quantitative trait loci analyzed by geometric morphometrics.

This study introduces a new multivariate approach for analyzing the effects of quantitative trait loci (QTL) on shape and demonstrates this method for the mouse mandible. We quantified size and shape with the methods of geometric morphometrics, based on Procrustes superimposition of five morphological landmarks recorded on each mandible. Interval mapping for F(2) mice originating from an intercross of the LG/J and SM/J inbred strains revealed 12 QTL for size, 25 QTL for shape, and 5 QTL for left-right asymmetry. Multivariate ordination of QTL effects by principal component analysis identified two recurrent features of shape variation, which involved the positions of the coronoid and angular processes relative to each other and to the rest of the mandible. These patterns are reminiscent of the knockout phenotypes of a number of genes involved in mandible development, although only a few of these are possible candidates for QTL in our study. The variation of shape effects among the QTL showed no evidence of clustering into distinct groups, as would be expected from theories of morphological integration. Further, for most QTL, additive and dominance effects on shape were markedly different, implying overdominance for specific features of shape. We conclude that geometric morphometrics offers a promising new approach to address problems at the interface of evolutionary and developmental genetics.

Animals↗

PubMed2000

Phenotypic covariance structure in tamarins (genus Saguinus): a comparison of variation patterns using matrix correlation and common principal component analysis.

Constancy of variation/covariation structure among populations is frequently assumed in order to measure the differential selective forces which have caused population differentiation through evolutionary time. Following Steppan ([1997] Evolution 51:571-594), this assumption is examined among closely related tamarin species (genus Saguinus), using two distinct approaches applied to the task of evaluating similarity in patterns of morphological variation: common principal component analysis and matrix correlations. While the results of these analyses may appear contradictory, closer examination reveals them as complementary, highlighting the wisdom of combined methodologies. Overall, the results reveal a close relationship among the morphologically based variance structures of the tamarin species a relationship whose pattern is consistent with the pattern of phylogenetic relatedness as found via a molecular genetic study. More specifically, both methodological approaches provide some support for divergence of S. geoffroyi and S. oedipus (with regards to their patterns of morphological variation) from other tamarin species. This suggests that variance/covariance structure may have diverged through evolutionary time in the tamarin lineage, placing assumptions of constancy in doubt.

Analysis of Variance↗

PubMed2000

Quantitative trait loci for directional but not fluctuating asymmetry of mandible characters in mice.

Non-directional variation in right minus left differences in bilateral characters, referred to as fluctuating asymmetry (FA), often has been assumed to be largely or entirely environmental in origin. FA increasingly has been used as a measure of developmental stability, and its presumed environmental origin has facilitated the comparisons of populations believed to differ in their levels of stability. Directional asymmetry (DA), in which one side is consistently larger than the other, has been assumed to be at least partially heritable. Both these assumptions were tested with interval mapping techniques designed to detect any quantitative trait loci (QTLs) affecting FA or DA in 15 bilateral mandible characters in house mice resulting from a cross of the F1 between CAST/Ei (wild strain) and M16i (selected for rapid growth rate) back to M16i. For purposes of the analysis, all mandibles were triply measured and 92 microsatellite markers were scored in a total of 350 mice. No significant QTLs were found for FA, but three QTLs significantly affected DA in several characters, confirming both assumptions. The QTLs for DA were similar in location to those affecting the size of several of the mandible characters, although they accounted for an average of only 1% of the total phenotypic variation in DA.

Analysis of Variance↗

PubMed2000

Is the genotype-phenotype map modular? A statistical approach using mouse quantitative trait loci data.

Various theories about the evolution of complex characters make predictions about the statistical distribution of genetic effects on phenotypic characters, also called the genotype-phenotype map. With the advent of QTL technology, data about these distributions are becoming available. In this article, we propose simple tests for the prediction that functionally integrated characters have a modular genotype-phenotype map. The test is applied to QTL data on the mouse mandible. The results provide statistical support for the notion that the ascending ramus region of the mandible is modularized. A data set comprising the effects of QTL on a more extensive portion of the phenotype is required to determine if the alveolar region of the mandible is also modularized.

Alleles↗

PubMed1999

Differential response to dietary fat in large (LG/J) and small (SM/J) inbred mouse strains.

The "large" (LG/J) and "small" (SM/J) inbred mouse strains differ for a wide variety of traits related to body size and obesity. Ninety-three LG/J and SM/J mice were divided into two treatment categories and fed a moderately high-fat diet (21% kcal fat) or a low-fat diet (12% kcal fat) from weaning to necropsy. Strain differences in obesity-related traits and differential response to dietary fat increases were analyzed using ANOVA. LG/J animals grow faster from 3 to 10 wk, have longer tails, and have heavier body weight, liver weight, and fat pad weight than SM/J animals. SM/J animals grow faster after 10 wk of age and have higher fasting glucose levels than LG/J animals. SM/J mice were more responsive to increased dietary fat than LG/J mice for growth after 10 wk, necropsy weight, liver weight, fat pad weights, and fasting glucose levels (in males). The growth from 3 to 10 wk had a much greater response in the LG/J strain, whereas tail length had no response. This pattern of dietary response is similar to that expected under the "thrifty" phenotype hypothesis. Genes affecting strain differences and the differential response of the strains to dietary fat can be successfully mapped in the intercross of the LG/J and SM/J strains. This intercross provides an excellent multigenic model for the genetic basis of complex traits and diseases related to body size and obesity.

Adipose Tissue↗

PubMed1999

Historical biogeography of tamarins, genus Saguinus: the molecular phylogenetic evidence.

Hypotheses of the historical biogeography of tamarins (genus Saguinus) based on variation in coat colors and body size are tested using phylogenetic relationships inferred from mitochondrial DNA (mtDNA) sequence data. Samples from all 12 species of Saguinus and several subspecies are included in the analysis. Approximately 1,200 bases of mtDNA sequence from the cytochrome b and D-loop regions are reported for the tamarins and several outgroup taxa. Parsimony analysis of the mtDNA sequence data reveals Saguinus to be a monophyletic taxon composed of two major clades: one, the Small-bodied clade, contains S. nigricollis, S. tripartitus, and S. fuscicollis, and the other, the Large-bodied clade, contains the other nine species. The phylogenetic relationships among tamarins inferred from the mtDNA sequence data reject previous hypotheses for the historical biogeography of tamarins and suggest different dispersal routes for this group of New World monkeys. The molecular data suggest that tamarins dispersed across South America in two major waves from an origin somewhere south of the Amazon. One wave moved in a westerly direction, whereas the other moved in a northeastern direction toward the Amazon delta and then west along the northern portion of the continent into northern Colombia and Panama.

Animals↗

PubMed1999

Mapping quantitative trait loci for murine growth: a closer look at genetic architecture.

Over 20 years ago, D. S. Falconer and others launched an important avenue of research into the quantitative of body size growth in mice. This study continues in that tradition by locating quantitative trait loci (QTLs) responsible for murine growth, such as age-specific weights and growth periods, and examining the genetic architecture for body weight. We identified a large number of potential QTLs in an earlier F2 intercross (Intercross I) of the SM/J and LG/J inbred mouse strains. Many of these QTLs are replicated in a second F2 intercross (Intercross II) between the same two strains. These replicated regions provide candidate regions for future fine-mapping studies. We also examined body size and growth QTLs using the combined data set from these two intercrosses, resulting in 96 microsatellite markers being scored for 1045 individuals. An examination of the genetic architecture for age-specific weight and growth periods resulted in locating 20 separate QTLs, which were mainly additive in nature, although dominance was found to affect early growth and body size. QTLs affecting early and late growth were generally distinct, mapping to separate chromosome locations. This QTL pattern indicates largely separate genetic and physiological systems for early and later murine growth, as Falconer suggested. We also found sex-specific QTLs for body size with implications for the evolution of sexual dimorphism.

Aging↗

PubMed1998

Quantitative trait loci for fluctuating asymmetry of discrete skeletal characters in mice.

Levels of fluctuating asymmetry (FA) are often taken as indicators of the degree to which genotypes differ in their ability to buffer genetic and environmental sources of variation. Interval mapping techniques were used to search for quantitative trait loci (QTLs) affecting directional asymmetry (DA) and fluctuating asymmetry (FA) in six bilateral discrete skeletal traits in house mice. These six characters as well as 76 microsatellite markers were scored in over 500 mice that resulted from crosses of F1 mice originally produced from matings of the Large (LG/J) and Small (SM/J) inbred strains. The number of QTLs affecting DA in each of the characters was no more than expected by chance alone so it was concluded that there was little evidence for individual genes affecting DA. There appeared to be a genetical basis for FA in these characters, however, because the number of QTLs significantly affecting FA (10 at the 5% level, three at the 1% level) was greater than expected by chance alone. The 10 QTLs significantly affecting FA in any given character were located on eight different chromosomes, mostly at locations for QTLs affecting other characters or DA in other characters. Their cumulative contribution to the total phenotypic variance was small, averaging only 3.9% per locus. Dominance genotypic values for these QTLs were more extreme than additive genotypic values, suggesting that heterozygotes at many loci are better buffered than homozygotes and that allelic interactions (dominance) may play an important role in the production of FA.

Animals↗

PubMed1997

Age of epiphyseal closure in tamarins and marmosets.

Estimates of the chronological age for animals of unknown age provide useful information for medical, demographic, and evolutionary studies. Skeletal development, as indicated by epiphyseal closure, can be used to estimate an animal's chronological age or specify its stage of development. Many studies of Primate skeletal development have used animals of unknown age, with the order of epiphyseal closure providing a relative age for each animal. This study examines the age of epiphyseal closure at 22 epiphyseal sites using animals of known age at death in three calitrichid species (Saguinus fuscicollis, Saguinus oedipus, and Callithrix jacchus). The observed average age of epiphyseal closure is similar in these tamarins and marmosets. There is a significant difference in rate of development between the species. Regression equations can predict the age of unknown animals to within 4.8 months for S. fuscicollis, 8.6 months for S. oedipus, and 7.6 months for C. jacchus (twice the standard error of the estimate). These age estimates allow us to determine if an animal is relatively mature or immature, but are largely unacceptable for studies in which precise age estimates are necessary. The order of epiphyseal closure is similar across 11 monkey species (using additional data from published literature) and supports the suggestion of a general pattern in Primate skeletal development.

Age Determination by Skeleton↗

PubMed1997

Interactions between infant growth and survival: evidence for selection on age-specific body weight in captive common marmosets (Callithrix jacchus).

The objective of this study is to investigate factors influencing infant survival in captive common marmosets. We investigated the influence of age-specific weight, litter size, caging, and the presence of helpers on survival to 6 months of age in 189 Callithrix jacchus infants. Infant survival was analyzed using Cox Proportional Hazards regression, and fitness functions were plotted to explore the relationship between survival and growth. Results indicate that weights at birth and 120 days significantly affect future survival probability. Litter size significantly influences survival prior to 60 days of age with larger litters having poorer survival. Males and females did not have significantly different survival and the presence of helpers in the group did not influence survival probability. Patterns of survival with respect to age-specific weights suggest stabilizing selection on birth weight and directional selection on weight at 120 days of age.

Age Factors↗

PubMed1996

Precision of surface measurements for below-knee residua.

OBJECTIVE: To determine the absolute and relative precision of geometric measurements made of below knee (BK) residua and their BK plaster positive casts using calipers, electromagnetic digitizer, optical surface scanner (OSS), and spiral x-ray computed tomography (SXCT). DESIGN: The experimental measurement protocol for a single measurement session was as follows: Dot markers were placed on the residuum, and volume and distances were measured using water displacement and calipers; residuum was measured using electromagnetic digitizer; residuum was scanned using three-dimensional (3D) OSS; a negative plaster cast of subject's residuum was made; the residuum was scanned using SXCT scanner. These steps were repeated at a second measurement session. Plaster positive casts were constructed and subsequently measured using the same protocol. PARTICIPANTS: Thirteen adult below-knee amputee volunteers (subjects) participated in the study, and nine subjects returned for a second measurement session. The study group consisted of 9 men and 4 women; 10 Caucasians and 3 African Americans. RESULTS: Distance measurements for all measurement devices were repeatable within 1% in vivo and within 0.5% on plaster casts; and volumes were within 1% in vivo and within 0.1% on plaster casts. Distance measurements for each device were precise within 3% in vivo and within 1% on plaster casts; and volumes were within 5% in vivo and within 6% on plaster casts when compared with caliper and water displacement measures. CONCLUSION: These measurement systems were found to be substantially equivalent in terms of repeatability and precision for measurement of lower extremity residua.

Adult↗

PubMed1996

Quantitative trait loci for murine growth.

Body size is an archetypal quantitative trait with variation due to the segregation of many gene loci, each of relatively minor effect, and the environment. We examine the effects of quantitative trait loci (QTLs) on age-specific body weights and growth in the F2 intercross of the LG/J and SM/J strains of inbred mice. Weekly weights (1-10 wk) and 75 microsatellite genotypes were obtained for 535 mice. Interval mapping was used to locate and measure the genotypic effects of QTLs on body weight and growth. QTL effects were detected on 16 of the 19 autosomes with several chromosomes carrying more than one QTL. The number of QTLs for age-specific weights varied from seven at 1 week to 17 at 10 wk. The QTLs were each of relatively minor, subequal effect. QTLs affecting early and late growth were generally distinct, mapping to different chromosomal locations indicating separate genetic and physiological systems for early and later murine growth.

Age Factors↗

PubMed1995

Asymmetric vault modification in Hopi crania.

Cradleboarding was practiced by numerous prehistoric and historic populations, including the Hopi. In this group, one result of cradleboarding was bilateral or asymmetric flattening of the posterior occipital. We test whether cradleboarding had significant effects on the morphology of the cranial vault, cranial base, and face. Additionally, we examine associations between direction of flattening and asymmetric craniofacial growth. A skeletal sample of Hopi from the Old Walpi site includes both nonmodified (N = 43) and modified individuals (N = 39). Three-dimensional coordinates of 53 landmarks were obtained using a diagraph. Thirty-six landmarks were used to define nine finite elements in the cranial vault, cranial base, and face. Finite element scaling was used to compare average nonmodified individuals, with averages of bilaterally, right, and left modified individuals. The significance of variation among "treatment" groups was evaluated using a bootstrap test. Pearson product-moment correlations test the association of asymmetry with direction of modification. Hopi cradleboarding has a significant effect on growth of the cranial vault, but does not affect morphology of the cranial base or face. Bilateral flattening of the cranial vault leads to decreased length and increased width of the cranial vault. Flattening of the right or left cranial vault results in ipsilaterally decreased length and width coupled with a corresponding increased length and width on the contralateral side of the cranial vault. There is a significant correlation of size asymmetry with direction of modification in the cranial vault, but not with size or shape change in the cranial base or face.

Adult↗

PubMed1995

Polymorphism for PCR-analyzed microsatellites between the inbred mouse strains LG and SM.

Using agarose gel electrophoresis, we surveyed four strains of inbred mice (AKR/J, C57BL/J, LG/J, and SM/J) for 472 microsatellite loci. Agarose electrophoresis proved to be extremely efficient in separating alleles differing by six or more base pairs and detected a majority of allelic differences of between two and six base pairs. Overall, 64.4% of loci showed polymorphism among the four strains, and pairwise comparisons ranged from 42.1% to 48.1%. Microsatellite polymorphism for strains LG/J and SM/J has not been previously described and was sufficiently high (47.1%) to make these size-divergent strains excellent candidates for quantitative trait loci (QTL) analysis of normal growth.

Alleles↗

PubMed1995

Epistasis and its contribution to genetic variance components.

We present a new parameterization of physiological epistasis that allows the measurement of epistasis separate from its effects on the interaction (epistatic) genetic variance component. Epistasis is the deviation of two-locus genotypic values from the sum of the contributing single-locus genotypic values. This parameterization leads to statistical tests for epistasis given estimates of two-locus genotypic values such as can be obtained from quantitative trait locus studies. The contributions of epistasis to the additive, dominance and interaction genetic variances are specified. Epistasis can make substantial contributions to each of these variance components. This parameterization of epistasis allows general consideration of the role of epistasis in evolution by defining its contribution to the additive genetic variance.

Animals↗

PubMed1995

Anthropometric optical surface imaging system repeatability, precision, and validation.

Disciplines using human body surface dimensions require accurate, repeatable measurements. This study presents a design for the analysis of repeatability, precision, and validation of a new anthropometric device. This model enables estimation of the proportion of the total variation attributable to each level of data collection. This model is applied to an analysis of repeatability, precision, and validation of the Cencit Imaging System, a new optical surface scanner. Twenty-seven facial landmarks were marked on 10 men and 10 women at two measurement sessions. Two images were scanned during each session, and each image was digitized twice. The Cencit Imaging System results were compared with a previously validated digitizer. The Cencit Imaging System was found to produce accurate, highly repeatable images. Much of the error in this study is attributable to human error in marking landmarks on the subjects. The new imaging system will prove useful in a variety of anthropometric applications.

Anthropometry↗