Mapping quantitative trait loci for carcass and meat quality traits in a wild boar x Large White intercross

An intercross between wild boar and a domestic Large White pig population was used to map quantitative trait loci (QTL) for body proportions, weight of internal organs, carcass composition, and meat quality. The results concerning growth traits and fat deposition traits have been reported elsewhere. In the present study, all 200 F2 animals, their parents, and their grandparents were genotyped for 236 markers. The marker genotypes were used to calculate the additive and dominance coefficients at fixed positions in the genome of each F2 animal, and the trait values were regressed onto these coefficients in intervals of 1 cM. In addition, the effect of proportion of wild boar alleles was tested for each chromosome. Significant QTL effects were found for percentage lean meat and percentage lean meat plus bone in various cuts, proportion of bone in relation to lean meat in ham, muscle area, and carcass length. The significant QTL were located on chromosomes 2, 3, 4, and 8. Each QTL explained 9 to 16% of the residual variance of the traits. Gene action for most QTL was largely additive. For meat quality traits, there were no QTL that reached the significance threshold. However, the average proportion of wild boar alleles across the genome had highly significant effects on reflectance and drip loss. The results show that there are several chromosome regions with a considerable effect on carcass traits in pigs.     

Identification of quantitative trait loci involved in contextual and auditory-cued fear conditioning in BXD recombinant inbred strains.

Fear conditioning shows associations formed between contextual or auditory stimuli with an unconditioned stimulus. Inbred mouse strains differ in their ability to demonstrate fear conditioning, suggesting at least a partial genetic influence. The present study identified the possible chromosomal loci regulating fear conditioning in BXD recombinant inbred strains using quantitative trait loci (QTL) analysis. Estimates of heritability for all 3 measures of conditioning were about .28. Correlational analyses between genetic markers and strain means identified multiple putative QTLs. The strongest associations were on Chromosomes 1 and 17 for freezing to the context, Chromosome 12 for freezing to an altered context, and Chromosome 1 for freezing to the auditory stimulus. Overlapping QTLs may indicate some common genes that underlie aspects of this learning task. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Identification of quantitative trait loci influencing wood specific gravity in an outbred pedigree of loblolly pine

We report the identification of quantitative trait loci (QTL) influencing wood specific gravity (WSG) in an outbred pedigree of loblolly pine (Pinus taeda L.). QTL mapping in an outcrossing species is complicated by the presence of multiple alleles (> 2) at QTL and marker loci. Multiple alleles at QTL allow the examination of interaction among alleles at QTL (deviation from additive gene action). Restriction fragment length polymorphism (RFLP) marker genotypes and wood specific gravity phenotypes were determined for 177 progeny. Two RFLP linkage maps were constructed, representing maternal and paternal parent gamete segregations as inferred from diploid progeny RFLP genotypes. RFLP loci segregating for multiple alleles were vital for aligning the two maps. Each RFLP locus was assayed for cosegregation with WSG QTL using analysis of variance (ANOVA). Five regions of the genome contained one or more RFLP loci showing differences in mean WSG at or below the P = 0.05 level for progeny as grouped by RFLP genotype. One region contained a marker locus (S6a) whose QTL-associated effects were highly significant (P > 0.0002). Marker S6a segregated for multiple alleles, a prerequisite for determining the number of alleles segregating at the linked QTL and analyzing the interactions among QTL alleles. The QTL associated with marker S6a appeared to be segregating for multiple alleles which interacted with each other and with environments. No evidence for digenic epistasis was found among the five QTL.     

Levels of genetic polymorphism: marker loci versus quantitative traits

Species are the units used to measure ecological diversity and alleles are the units of genetic diversity. Genetic variation within and among species has been documented most extensively using allozyme electrophoresis. This reveals wide differences in genetic variability within, and genetic distances among, species, demonstrating that species are not equivalent units of diversity. The extent to which the pattern observed for allozymes can be used to infer patterns of genetic variation in quantitative traits depends on the forces generating and maintaining variability. Allozyme variation is probably not strictly neutral but, nevertheless, heterozygosity is expected to be influenced by population size and genetic distance will be affected by time since divergence. The same is true for quantitative traits influenced by many genes and under weak stabilizing selection. However, the limited data available suggest that allozyme variability is a poor predictor of genetic variation in quantitative traits within populations. It is a better predictor of general phenotypic divergence and of postzygotic isolation between populations or species, but is only weakly correlated with prezygotic isolation. Studies of grasshopper and planthopper mating signal variation and assortative mating illustrate how these characters evolve independently of general genetic and morphological variation. The role of such traits in prezygotic isolation, and hence speciation, means that they will contribute significantly to the diversity of levels of genetic variation within and among species.     

Identification of quantitative trait loci governing arthritis severity and humoral responses in the murine model of Lyme disease

A spectrum of disease severity has been observed in patients with Lyme disease, with approximately 60% of untreated individuals developing arthritis. The murine model of Lyme disease has provided strong evidence that the genetic composition of the host influences the severity of arthritis following infection with Borrelia burgdorferi: infected C3H mice develop severe arthritis while infected C57BL/6N mice develop mild arthritis. Regions of the mouse genome controlling arthritis severity and humoral responses during B. burgdorferi infection were identified in the F2 intercross generation of C3H/HeNCr and C57BL/6NCr mice. Rear ankle swelling measurements identified quantitative trait loci (QTL) on chromosomes 4 and 5, while histopathological scoring identified QTL on a unique region of chromosome 5 and on chromosome 11. The identification of QTL unique for ankle swelling or histopathological severity suggests that processes under distinct genetic control are responsible for these two manifestations of Lyme arthritis. Additional QTL that control the levels of circulating Igs induced by B. burgdorferi infection were identified on chromosomes 6, 9, 11, 12, and 17. Interestingly, the magnitude of the humoral response was not correlated with the severity of arthritis in infected F2 mice. This work defines several genetic loci that regulate either the severity of arthritis or the magnitude of humoral responses to B. burgdorferi infection in mice, with implications toward understanding the host-pathogen interactions involved in disease development.     

Prediction of slaughter cow composition using live animal and carcass traits

Slaughter cows (n = 120), representing four genotypes (British, continental, Bos indicus, and dairy) and three body condition classes (thin, moderate, and fat), n = 10 per subclass, were used to identify practical and accurate prediction equations for the yield of boneless manufacturing beef of specific fat percentages. Cows and their carcasses were weighed and evaluated for USDA yield and quality grade factors and for physical muscle and fat indicators. Carcass sides were fabricated; total fat percentage (TFP) was calculated as total fat (trimmed and chemical) divided by side weight, and tissue lean percentage (TLP) was calculated as boneless fat-free lean divided by soft tissue weight. Data were analyzed using maximum R2 multiple regression. The best live trait prediction model for TFP included live preliminary yield grade (LPYG), body condition score (LCOND), visual live muscle score (LMUSC), and live weight (LWT), R2 = .83. The best carcass trait TFP prediction model included adjusted preliminary yield grade (CPYGA); kidney, pelvic, and heart fat adjustment (CKPHADJ); marbling score (CMARB); and hot carcass weight (HCW), R2 = .92. The best live trait TLP prediction model included LPYG, LCOND, LMUSC, and LWT, R2 = .82. The best carcass trait TLP prediction model included CPYGA, CKPHADJ, CMARB, and lean maturity, R2 = .91. These data indicate that TFP and TLP of slaughter cows can be accurately and practically predicted using live animal and carcass traits.     

Estimation of effects of quantitative trait loci in large complex pedigrees

A method was derived to estimate effects of quantitative trait loci (QTL) using incomplete genotype information in large outbreeding populations with complex pedigrees. The method accounts for background genes by estimating polygenic effects. The basic equations used are very similar to the usual linear mixed model equations for polygenic models, and segregation analysis was used to estimate the probabilities of the QTL genotypes for each animal. Method R was used to estimate the polygenic heritability simultaneously with the QTL effects. Also, initial allele frequencies were estimated. The method was tested in a simulated data set of 10,000 animals evenly distributed over 10 generations, where 0, 400 or 10,000 animals were genotyped for a candidate gene. In the absence of selection, the bias of the QTL estimates was < 2%. Selection biased the estimate of the Aa genotype slightly, when zero animals were genotyped. Estimates of the polygenic heritability were 0.251 and 0.257, in absence and presence of selection, respectively, while the simulated value was 0.25. Although not tested in this study, marker information could be accommodated by adjusting the transmission probabilities of the genotypes from parent to offspring according to the marker information. This renders a QTL mapping study in large multi-generation pedigrees possible.     

Confirmation of quantitative trait loci for ethanol sensitivity in long-sleep and short-sleep mice

PURPOSE: To determine the efficacy of the combination of cisplatin, fluorouracil, and high-dose l-leucovorin (PFL) as organ-preserving induction therapy followed by radiotherapy in untreated patients with advanced squamous cell carcinoma of the head and neck. PATIENTS AND METHODS: This was a phase II study of PFL in 47 patients with resectable stage III (n = 20) and IV (n = 27) M0 squamous cell carcinoma of the head and neck, including larynx (n = 20), hypopharynx (n = 14), and oropharynx (n = 13). The PFL regimen consisted of cisplatin 25 mg/m2 on days 1 through 5, fluorouracil 800 mg/m2 CI on days 2 through 6, and l-leucovorin 250 mg/m2 on days 1 through 6, all by continuous intravenous infusion every 21 to 28 days for three courses. The primary study endpoint was initial response to and local disease control rate with PFL as induction chemotherapy, with an aim to confirm the previously reported complete response rate of 60% to 70%. RESULTS: Of 47 patients enrolled, 46 were evaluable for response to PFL, 14 (30%) achieved a complete response, and 25 (54%) achieved a partial response, for an overall response rate of 84%. Of 39 patients evaluable for response after radiation therapy, 27 (69%) achieved a complete response and 11 (28%) a partial response. Local disease control was achieved in 37 of 46 (80%). Grade 3 or 4 toxic effects occurred frequently, with neutropenia in 27 (59%) of 46 evaluable patients, thrombocytopenia in 30%, mucositis in 41%, diarrhea in 13%, and nausea/ vomiting in 13%, but there were no treatment-related deaths. With a median follow-up of 35 months there have been nine recurrences (four local/regional and five distant) and 17 deaths (12 in patients with disease progression and five not directly related to the primary tumor). Second primary tumors have developed in six patients. At 3 years 62% of the patients remain alive with no disease progression, and the 3-year survival estimate with preserved organ function is 66%. CONCLUSION: PFL induction chemotherapy produced only a modest complete response rate, possibly due to suboptimal dose intensity, and was associated with substantial, although not life-threatening, toxicity. Newer regimens and treatment modalities are still needed in the management of advanced squamous cell carcinoma of the head and neck.     

Detection of putative loci affecting milk production and composition, health, and type traits in a United States Holstein population

Quantitative trait loci affecting milk yield and composition, health, and type traits were studied for seven large grandsire families of US Holstein using the granddaughter design. The families were genotyped at 20 microsatellite markers on 15 chromosomes, and the effects of the marker alleles were analyzed for 28 traits (21 type traits, 5 milk yield and composition traits, somatic cell score, and productive herd life). Markers BM415 on chromosome 6 and BM6425 on chromosome 14 were associated with effects on protein percentage in a single grandsire family. The latter marker had a lower probability of being associated with changes in milk yield and fat percentage in the same family. Increases in productive herd life were associated with an allele at marker BM719 on chromosome 16 in one grandsire family.     

Detection of quantitative trait loci in outbred populations with incomplete marker data

AcrA protein is a component of the multi-drug efflux complex AcrAB-TolC of Escherichia coli. Judged by the hypersusceptibility phenotype of acrA mutants, the AcrAB-TolC system pumps out an extraordinarily wide variety of antibiotics, chemotherapeutic agents, detergents and dyes. This complex traverses both the inner and outer membranes of E. coli and catalyzes efflux of the drugs directly into the medium. The coordinated operation of the inner membrane transporter AcrB and outer membrane channel TolC is thought to be mediated by AcrA. The latter is a lipoprotein located in the periplasmic space. We show here that a lipid-deficient derivative of AcrA is functionally active as demonstrated by the complementation of the hypersusceptibility phenotype of the acrA mutant. Purified non-lipidated and intact forms of AcrA were able to restore, with similar efficiency, the activity of AcrA-dependent efflux of erythromycin in Ca2+-sucrose-treated E. coli cells. Using analytical ultracentrifugation and dynamic light scattering techniques we determined hydrodynamic properties of the non-lipidated AcrA and found that AcrA exists in solution as a highly asymmetric monomeric molecule with an axial ratio of 8. This elongated shape of AcrA is compatible with the hypothesis that this protein spans the periplasmic space coordinating the concerted operation of inner and outer membrane components of the complex.     

Polygenic mutation in Drosophila melanogaster: genetic interactions between selection lines and candidate quantitative trait loci

We have investigated genetic interactions between spontaneous mutations affecting abdominal and sternopleural bristle number that have accumulated in 12 long-term selection lines derived from an inbred strain, and mutations at 14 candidate bristle number quantitative trait loci. The quantitative test for complementation was to cross the selection lines to an inbred wild-type strain (the control cross) and to a derivative of the control strain into which the mutant allele at the candidate locus to be tested was substituted (the tester strain). Genetic interactions between spontaneous mutations affecting bristle number and the candidate locus mutations were common, and in several cases the interaction effects were different in males and females. Analyses of variance of the (tester- control) differences among and within groups of replicate lines selected in the same direction for the same trait showed significant group effects for several candidate loci. Genetically, the interactions could be caused by allelism of, and/ or epistasis between, spontaneous mutations in the selection lines and the candidate locus mutations. It is possible that much of the response to selection was from new mutations at candidate bristle number quantitative trait loci, and that for some of these loci, mutation rates were high.     

Relationship of visual assessments of feeder lamb muscularity to differences in carcass yield traits

We examined the relationship between visual differences in muscle thickness among feeder lambs and subsequent differences in carcass composition. Medium-framed, crossbred feeder lambs (n = 120) were selected at two commercial feedlots to exhibit distinct phenotypic differences in muscularity. The lambs were assigned scores (ranging from 1 to 9; 1 = extremely thin, 5 = average, 9 = extremely thick) for muscle thickness and were sampled serially on d 0, 14, 28, and 42 of the trial. After recording yield grades, one side of each carcass was deboned, and the soft tissues from the entire side were ground, sampled, and analyzed for lipid and moisture content. The opposite side was fabricated into boneless, closely trimmed (.25 cm maximum fat depth) subprimal cuts. When lambs of the same frame size were compared at the same live weight, greater muscle thickness was associated with greater (P < .05) fat-free muscle mass. Correspondingly, thickly muscled lambs produced carcasses of a given weight that had a higher (P < .05) composite yield of lean meat and a lower (P < .05) proportion of trimmable fat compared with carcasses of thinly muscled lambs. When comparisons were made at the same percentage of extractable fat in the carcass, greater muscle thickness was associated with heavier (P < .05) live and carcass weights, increased (P < .05) fat-free muscle mass, and increased (P < .05) weights of trimmed, boneless subprimal cuts. Results suggest that visual assessments of muscle thickness in feeder lambs, as applied in this study, are indicative of commercially important differences in carcass yields of lean meat.     

Common quantitative trait loci for alcohol-related behaviors and CNS neurotensin measures: voluntary ethanol consumption

The alcohol breath test (ABT) is evaluated for variability in response to changes in physiological parameters. The ABT was originally developed in the 1950s, at a time when understanding of pulmonary physiology was quite limited. Over the past decade, physiological studies have shown that alcohol is exchanged entirely within the conducting airways via diffusion from the bronchial circulation. This is in sharp contrast to the old idea that alcohol exchanges in the alveoli in a manner similar to the lower solubility respiratory gases (O2 and CO2). The airway alcohol exchange process is diffusion (airway tissue) and perfusion (bronchial circulation) limited. The dynamics of airway alcohol exchange results in a positively sloped exhaled alveolar plateau that contributes to considerable breathing pattern-dependent variation in measured breath alcohol concentration measurements.     

Spontaneous mutation for a quantitative trait in Drosophila melanogaster. II. Distribution of mutant effects on the trait and fitness

Exposure of the Chinese hamster ovarian AuxB1 cell line in vitro to fractionated X-irradiation generated sublines designated DXR-10, which proved resistant to multiple drugs and overexpressed P-glycoprotein (Pgp), as judged by Western blotting using the C219 monoclonal antibody. Further characterization of these irradiated DXR-10 sublines has provided evidence for: (i) the expression of cross-resistance to gramacidin D, taxol, puromycin and Navelbine, but not to daunomycin or mitoxantrone; (ii) overexpression of the class I Pgp, as judged by Western blotting using the C494 monoclonal antibody; (iii) decreased accumulation of 3H-vincristine, which could be enhanced by verapamil addition; (iv) unaltered accumulation and subcellular distribution of adriamycin; (v) significantly increased rhodamine 123 accumulation in the presence of verapamil; (vi) plasma-membrane ultrastructural modifications resulting in a significantly increased surface area; (vii) numerous clonal karyotypic alterations, with abnormalities involving the long arm of chromosome 1 being consistently identified; (viii) a lack of overexpression of sorcin; (ix) increased total glutathione levels and overexpression of glutathione S-transferase pi. The fact that only certain of these features are considered characteristic of the 'classic' multidrug-resistant CHRC5 cell line supports our earlier proposal that exposure to fractionated X-irradiation results in the expression of a unique drug-resistance phenotype.     

Silage or limit-fed grain growing diets for steers: II. Empty body and carcass composition

The influence of energy source (silage- or grain-based) on empty body and carcass composition and adipocyte cellularity independent of rate of gain was tested. Sixty-four Angus steers were allotted to either a forage (ad libitum) or grain (limit-fed) diet for a growing phase (145 d) followed by 45, 75, or 105 d of ad libitum access to a grain-based diet. Eight steers were slaughtered initially and eight from each treatment were slaughtered at the end of the growing phase, and at each of the termination dates. The silage growing diet consisted (DM basis) of 55% sorghum silage (approximately 24% dry matter), 22% alfalfa hay, 11% ground shelled corn, and 11% soybean meal. The grain-based growing diet was composed of 77% ground shelled corn, 5% soybean meal, 14% cottonseed hulls, 3% molasses, and 1% salt and mineral; it was limit-fed to produce the same rate of gain as the silage diet. No implants or ionophores were used. At the end of the growing phase, the steers fed grain were heavier and had a higher percentage of fat in the empty body (24 vs 19% fat) and the carcass (26 vs 21% fat) than did steers fed forage. Rate of gain during the growth phase was related positively to percentage of carcass fat; when corrected for fill, data for both diets fit one regression line for fat vs rate of gain. When adjusted for gain during the growing phase, fat content was not different in empty body or carcass, but internal fat was higher (P < .10) for steers fed grain. After 45 d on the finishing diet, carcass fat remained low (23%), but after 75 and 105 d, fat content reached 27%. Source of energy did not detectably affect carcass composition independent of rate of gain. Cell size of adipocytes from four adipose depots increased with time on feed but were not affected by diet during the growing phase. Lean Choice beef can be produced in only 45 d in the feedlot with medium-framed Angus cattle.     

A nonparametric bootstrap method for testing close linkage vs. pleiotropy of coincident quantitative trait loci

A novel method using the nonparametric bootstrap is proposed for testing whether a quantitative trait locus (QTL) at one chromosomal position could explain effects on two separate traits. If the single-QTL hypothesis is accepted, pleiotropy could explain the effect on two traits. If it is rejected, then the effects on two traits are due to linked QTLs. The method can be used in conjunction with several QTL mapping methods as long as they provide a straightforward estimate of the number of QTLs detectable from the data set. A selection step was introduced in the bootstrap procedure to reduce the conservativeness of the test of close linkage vs. pleiotropy, so that the erroneous rejection of the null hypothesis of pleiotropy only happens at a frequency equal to the nominal type I error risk specified by the user. The approach was assessed using computer simulations and proved to be relatively unbiased and robust over the range of genetic situations tested. An example of its application on a real data set from a saline stress experiment performed on a recombinant population of wheat (Triticum aestivum L. ) doubled haploid lines is also provided.     

Common quantitative trait loci for alcohol-related behaviors and central nervous system neurotensin measures: locomotor activation

We have analyzed LSXSS recumbinant inbred for ethanol-induced activity using 2.0 g/kg ethanol and a new method we call ethanol activation slope. The ethanol activation slope provides a robust dose-response measure of ethanol activation, independent of both activity after saline and the inhibitory effects of ethanol on locomotor activity. These behavioral data were used in a quantitative trait locus analysis to map chromosomal loci involved in ethanol-induced locomotor activity. We tentatively identified seven loci that mediate the low-dose stimulatory effect of ethanol and six loci involved in locomotion after 2.0 g/kg ethanol. Only one of the loci are in common between the two behaviors. We also compared the behavioral quantitative trait locus to those previously identified that are involved in regulating central nervous system neurotensin levels and neurotensin receptor densities. Six chromosomal regions were identified that regulate at least one central nervous system neurotensin measure and an ethanol-induced locomotor behavior. The identification of loci controlling both central nervous system neurotensin levels or neurotensin receptor densities and ethanol-induced locomotor activity strengthens the proposal that neurotensin regulates, in part, ethanol-induced behaviors and central nervous system sensitivity to ethanol.     

Evaluation of the ovine callipyge locus: II. Genotypic effects on growth, slaughter, and carcass traits

A resource flock of 362 F2 lambs provided phenotypic and genotypic data to estimate effects of callipyge (CLPG) genotypes on growth, slaughter, and carcass traits. Lambs were serially slaughtered in six groups at 3-wk intervals starting at 23 wk of age to allow comparisons at different end points. Probabilities of CLPG genotypes were calculated at a position 86 cM from the most centromeric marker of chromosome 18. A contrast of CLPG genotypic effects, based on the paternal polar overdominance model, was used to evaluate callipyge and normal phenotypes. Relationships of traits with slaughter age, carcass weight, or 12th-rib fat depth for callipyge and normal phenotypic groups were estimated by regression. Callipyge and normal lambs did not differ for growth traits measured from birth to slaughter. Callipyge lambs produced 55.9% of live weight as chilled carcass weight compared with 51.7% for normal lambs at the same mean live weight of 48.32 kg. Lighter pelt, kidney-pelvic fat, and liver weights contributed to this advantage of callipyge lambs for dressing percentage (P < .001). Estimated accretion rates of carcass protein at the mean slaughter age were 12.5 and 10.2 g/d for callipyge and normal carcasses, respectively. Corresponding values for carcass fat were 35.2 and 42.1 g/d. Compositional differences in favor of callipyge carcasses were detected at constant values of slaughter age, carcass weight, and 12th-rib fat depth. Callipyge carcasses had 2.56 kg greater fat-free lean and 1.39 kg less fat than normal carcasses at the same mean age of 214.9 d (P < .001). The majority of these differences were established before the initial group was slaughtered and were maintained as age increased. Callipyge carcasses consisted of 24.3% fat and 71.3% fat-free lean, compared with 31.5 and 64.0% for normal carcasses at 25.6 kg of carcass weight. When evaluated at .49 cm of 12th-rib fat depth, callipyge lambs were 15.4 d older and produced 4.1 kg heavier carcasses with 4.3% less fat (P < .001). Effects of CLPG genotypic groups on carcass composition were greater than virtually all reported breed substitution effects. Use of the CLPG mutant allele in structured mating systems can dramatically increase production of lean lamb.     

Quantitative trait loci affecting differences in floral morphology between two species of monkeyflower (Mimulus)

Conspicuous differences in floral morphology are partly responsible for reproductive isolation between two sympatric species of monkeyflower because of their effect on visitation of the flowers by different pollinators. Mimulus lewisii flowers are visited primarily by bumblebees, whereas M. cardinalis flowers are visited mostly by hummingbirds. The genetic control of 12 morphological differences between the flowers of M. lewisii and M. cardinalis was explored in a large linkage mapping population of F2 plants n = 465 to provide an accurate estimate of the number and magnitude of effect of quantitative trait loci (QTLs) governing each character. Between one and six QTLs were identified for each trait. Most (9/12) traits appear to be controlled in part by at least one major QTL explaining >/=25% of the total phenotypic variance. This implies that either single genes of individually large effect or linked clusters of genes with a large cumulative effect can play a role in the evolution of reproductive isolation and speciation.     

Mapping quantitative trait loci with dominant and missing markers in various crosses from two inbred lines

Bacterial resistance to beta-lactam antibiotics, a clinically worrying and recurrent problem, is often due to the production of beta-lactamases, enzymes that efficiently hydrolyze the amide bond of the beta-lactam nucleus. Imipenem and other carbapenems escape the activity of most active site serine beta-lactamases and have therefore become very popular drugs for antibacterial chemotherapy in the hospital environment. Their usefulness is, however, threatened by the appearance of new beta-lactamases that efficiently hydrolyze them. This study is focused on the structure and properties of two recently described class A carbapenemases, produced by Serratia marcescens and Enterobacter cloacae strains and leads to a better understanding of the specificity of beta-lactamases. In turn, this will contribute to the design of better antibacterial drugs. Three-dimensional models of the two class A carbapenemases were constructed by homology modeling. They suggested the presence, near the active site of the enzymes, of a disulfide bridge (C69-C238) whose existence was experimentally confirmed. Kinetic parameters were measured with the purified Sme-1 carbapenemase, and an attempt was made to explain its specific substrate profile by analyzing the structures of minimized Henri-Michaelis complexes and comparing them to those obtained for the "classical" TEM-1 beta-lactamase. The peculiar substrate profile of the carbapenemases appears to be strongly correlated with the presence of the disulfide bridge between C69 and C238.