Biomedical subjects

James M Cheverud

Publications and source records attributed to James M Cheverud.

44 records · Page 3Linked to original sources

PubMed2003

Helicobacter pylori tissue tropism: mouse-colonizing strains can target different gastric niches.

Studies with the mouse-adapted Helicobacter pylori strain SS1 had supported an idea that infections by this pathogen start in the gastric antrum and spread to the corpus after extensive mucosal damage. This paper shows that the unrelated strain X47 colonizes the corpus preferentially. Differences between strains in preferred gastric region were detected by co-inoculating mice with a mixture of SS1 and X47, and genotyping H. pylori recovered after 2-8 weeks of infection by vacA s allele PCR and RAPD fingerprinting. Mixed infections were found in each of 59 co-inoculated young C57BL/6J mice. On average, however, SS1 was fourfold more abundant than X47 in the antrum and X47 was threefold more abundant than SS1 in the corpus. Similar results were obtained in mice inoculated first with one strain and then the other strain 2 weeks later. SS1 was even more abundant in the antrum of elderly (>1 year old) mice (97 % of isolates). Qualitatively similar SS1 and X47 tissue distributions were seen using unrelated mouse lines (AKR/J, A/J, DBA/2J, BALB/cJ, LG/J, SM/J), but with significantly different SS1 : X47 ratios in some cases. These results suggest the existence of at least two distinct gastric niches whose characteristics may be affected by host genotype and age (physiology), and indicate that strains differ in how effectively they colonize each niche. Differences among gastric regions and the mixed infections that these allow may contribute to H. pylori diversity and genome evolution.

Aging↗

PubMed2003

Perspective: Evolution and detection of genetic robustness.

Robustness is the invariance of phenotypes in the face of perturbation. The robustness of phenotypes appears at various levels of biological organization, including gene expression, protein folding, metabolic flux, physiological homeostasis, development, and even organismal fitness. The mechanisms underlying robustness are diverse, ranging from thermodynamic stability at the RNA and protein level to behavior at the organismal level. Phenotypes can be robust either against heritable perturbations (e.g., mutations) or nonheritable perturbations (e.g., the weather). Here we primarily focus on the first kind of robustness--genetic robustness--and survey three growing avenues of research: (1) measuring genetic robustness in nature and in the laboratory; (2) understanding the evolution of genetic robustness: and (3) exploring the implications of genetic robustness for future evolution.

Adaptation, Biological↗

PubMed2002

Pleiotropy of quantitative trait loci for organ weights and limb bone lengths in mice.

We investigated the genetic basis of several limb bone lengths and weights of organs in mice produced from a cross of the F1 between CAST/Ei (wild strain) and M16i (selected for rapid growth rate) back to M16i. From previous correlation studies, we hypothesized that quantitative trait loci (QTLs) would exhibit greater pleiotropy within than between the limb length and organ weight character sets. Using interval mapping procedures and significance testing at the chromosome-wise level, we discovered 14 putative QTLs affecting weight of the liver, spleen, heart, and/or kidney, 9 of which affected more than one organ; and 12 QTLs for limb lengths, all of which affected the length of two or more of the limb bones in these mice. As was hypothesized, most QTLs affected either organ weights or limb lengths independently of each other, although five QTLs were found that affected both sets of characters. The direction of the effect of these QTLs was almost always consistent within and between characters, with little evidence for antagonistic pleiotropy.

Animals↗

PubMed2002

Discerning evolutionary processes in patterns of tamarin (genus Saguinus) craniofacial variation.

Quantitative genetic theory specifies evolutionary expectations for morphological diversification by genetic drift in a monophyletic clade. If genetic drift is responsible for the evolutionary morphological diversification of a clade, patterns of within- and between-taxon morphological variance/covariance should be proportional. We tested for proportionality of within- and between-species craniofacial morphological variation in 12 species of tamarins (genus Saguinus). We found that within- and between-taxon morphological variations across the entire genus were not proportional, and hence not likely to be due to genetic drift alone. The primary deviation from proportionality is that size and size-related shape in the cranium is more variable relative to other aspects of cranial morphology than expected under genetic drift, suggesting differential size selection between the two major clades, the small-bodied and large-bodied tamarins. Within each of these major clades, most of the interspecific variation is consistent with the pattern expected under genetic drift, although specific contrasts may indicate the involvement of differential selection. Morphological distances among taxa do not correspond very closely to the phylogeny derived from mtDNA. In particular, S. oedipus and S. geoffroyi are very distinct morphologically from the rest of the tamarins, although they are phylogenetically the sister clade to a clade containing S. midas and S. bicolor. Morphological similarity is not a good guide to phylogenetic affinity in the tamarins, especially with regard to deeper nodes in the phylogenetic tree.

Animals↗

PubMed2002

Analysis of quantitative trait locus effects on the size and shape of mandibular molars in mice.

While >50 genes have been found to influence the development of teeth in mice, we still know very little about the genetic basis for the adaptive characteristics of teeth, such as size and shape. We applied interval mapping procedures to Procrustes size and shape data obtained from 10 morphological landmarks on the mandibular molar row of the F(2) progeny from a cross between the LG/J and SM/J strains of mice. This revealed many more QTL for molar shape (18) than for molar centroid size (3), although levels of dominance effects were comparable among QTL for size and shape. Comparisons of patterns of Procrustes additive and dominance shape effects and ordination of QTL effects by principal components analysis suggested that the effects of the shape QTL were dispersed among the three molars and thus that none of these molars represents a genetically distinct developmental structure. The results of an analysis of co-occurrence of QTL for molar shape, mandible shape, and cranial dimensions in these mice suggested that many of the QTL for molar shape may be the same as those affecting these other sets of characters, although in some cases this could be due to effects of closely linked genes.

Animals↗

PubMed2002

Quantitative trait loci for maternal performance for offspring survival in mice.

Maternal performance refers to the effect that the environment provided by mothers has on their offspring's phenotypes, such as offspring survival and growth. Variations in maternal behavior and physiology are responsible for variations in maternal performance, which in turn affects offspring survival. In our study we found females that failed to nurture their offspring and showed abnormal maternal behaviors. The genetic architecture of maternal performance for offspring survival was investigated in 241 females of an F(2) intercross of the SM/J and LG/J inbred mouse strains. Using interval-mapping methods we found two quantitative trait loci (QTL) affecting maternal performance at D2Mit17 + 6 cM and D7Mit21 + 2 cM on chromosomes 2 and 7, respectively. In a two-way genome-wide epistasis scan we found 15 epistatic interactions involving 23 QTL distributed across all chromosomes except 12, 16, and 17. These loci form several small sets of interacting QTL, suggesting a complex set of mechanisms operating to determine maternal performance for offspring survival. Taken all together and correcting for the large number of significant factors, QTL and their interactions explain almost 35% of the phenotypic variation for maternal performance for offspring survival in this cross. This study allowed the identification of many possible candidate genes, as well as the relative size of gene effects and patterns of gene action affecting maternal performance in mice. Detailed behavior observation of mothers from later generations suggests that offspring survival in the first week is related to maternal success in building nests, grooming their pups, providing milk, and/or manifesting aggressive behavior against intruders.

Animals↗

PubMed2002

An epistatic genetic basis for fluctuating asymmetry of mandible size in mice.

The genetic basis of fluctuating asymmetry (FA), or nondirectional variation in the subtle differences between left and right sides of bilateral characters, continues to be of considerable theoretical interest. FA generally has been thought to arise from random noise during development and therefore to have a largely or entirely environmental origin. Whereas additive genetic variation for FA generally has been small and often insignificant, a number of investigators have hypothesized that interactions between loci, or epistasis, significantly influence FA. We tested this hypothesis by conducting a whole-genome scan to detect any epistasis in FA of centroid size in the mandibles of more than 400 mice from an F2 intercross population formed from crossing the Large (LG/J) and Small (SM/J) inbred strains. Genotypic deviations were imputed at each site 2 cM apart on all 19 autosomes, and these and centroid size asymmetry values were used in canonical correlation analyses for each of the 171 possible pairs of 19 autosomes to identify the most probable sites for epistasis. Epistasis for centroid size asymmetry was abundant, occurring far more often than was expected by chance alone (there were 30 separate instances of epistasis at the 0.001 significance level, when only two were expected by chance alone). The contributions of epistasis from 30 pairwise combinations of loci tended to suppress the additive and dominance genetic variance, but greatly increased the epistatic genetic variance for FA in centroid size given the intermediate allele frequencies of an F2 intercross population.

Animals↗

PubMedDate not supplied

The contribution of epistatic pleiotropy to the genetic architecture of covariation among polygenic traits in mice.

The contribution that pleiotropic effects of individual loci make to covariation among traits is well understood theoretically and is becoming well documented empirically. However, little is known about the role of epistasis in determining patterns of covariation among traits. To address this problem we combine a quantitative trait locus (QTL) analysis with a two-locus model to assess the contribution of epistasis to the genetic architecture of variation and covariation of organ weights and limb bone lengths in a backcross population of mice created from the M16i and CAST/Ei strains. Significant epistasis was exhibited by 14 pairwise combinations of QTL for organ weights and 10 combinations of QTL for limb bone lengths, which contributed, on average, about 5% of the variation in organ weights and 8% in limb bone lengths beyond that of single-locus QTL effects. Epistatic pleiotropy was much more common in the limb bones (seven of 10 epistatic combinations affecting limb bone lengths were pleiotropic) than the organs (three of the 14 epistatic combinations affecting organ weights were pleiotropic). In both cases, epistatic pleiotropy was less common than single-locus pleiotropy. Epistatic pleiotropy accounted for an average of 6% of covariation among organ weights and 21% of covariation among limb bone lengths, which represented an average of one-fifth (for organ weights) and one-third (for limb bone lengths) of the total genetic covariance between traits. Thus, although epistatic pleiotropy made a smaller contribution than single-locus pleiotropy, it clearly made a significant contribution to the genetic architecture of variation/covariation.

Animals↗