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Biomedical subjects

L A Rodriguez

Publications and source records attributed to L A Rodriguez.

At least 19 recordsLinked to original sources
PubMed2001

Genome screen for quantitative trait loci underlying normal variation in femoral structure.

Femoral structure contributes to bone strength at the proximal femur and predicts hip fracture risk independently of bone mass. Quantitative components of femoral structure are highly heritable traits. To identify genetic loci underlying variation in these structural phenotypes, we conducted an autosomal genome screen in 309 white sister pairs. Seven structural variables were measured from femoral radiographs and used in multipoint sib-pair linkage analyses. Three chromosomal regions were identified with significant evidence of linkage (log10 of the odds ratio [LOD] > 3.6) to at least one femoral structure phenotype. The maximum LOD score of 4.3 was obtained for femur neck axis length on chromosome 5q. Evidence of linkage to chromosome 4q was found with both femur neck axis length (LOD = 3.9) and midfemur width (LOD = 3.5). Significant evidence of linkage also was found to chromosome 17q, with a LOD score of 3.6 for femur head width. Two additional chromosomal regions 3q and 19p gave suggestive (LOD > 2.2) evidence of linkage with at least two of the structure phenotypes. Chromosome 3 showed evidence of linkage with pelvic axis length (LOD = 3.1), midfemur width (LOD = 2.8), and femur head width (LOD = 2.3), spanning a broad (60 cm) region of chromosome 3q. Linkage to chromosome 19 was supported by two phenotypes, femur neck axis length (LOD = 2.8) and femur head width (LOD = 2.8). This study is the first genome screen for loci underlying variation in femoral structure and represents an important step toward identifying genes contributing to the risk of osteoporotic hip fracture in the general population.

Adult↗
PubMed2000

Long forms of the dopamine receptor (DRD4) gene VNTR are more prevalent in substance abusers: no interaction with functional alleles of the catechol-o-methyltransferase (COMT) gene.

Substance abuse is a complex behavior that is caused by both environmental and genetic factors. Work to understand the genetic factors has focused on genes related to dopamine activity because of its critical role in rewarding and reinforcing behaviors. The DRD3 and other dopamine receptor subtypes are expressed in many areas of the limbic system, and have been the objects of study for their possible roles in several neuropsychiatric disorders. Interest in variants of the D4 gene was heightened by reports that some alleles were more frequent in individuals who score high on Novelty Seeking, an aspect of personality that may be related to drug seeking behavior. We now show that the long form of the DRD4 gene is more frequent in individuals with high quantity/frequency of drug use compared to controls (chi(2) = 5.7, df = 1, P = 0.017, odds ratio = 1.89, CI = 1.1-3.2). There is no difference in DRD3 allele frequencies in these samples, and there is no interaction of DRD4 alleles with those of the catecholamine-o-methyl- transferase gene (COMT) that we previously identified to be more frequent in substance abusers than controls [Vandenbergh, et al.: 1997: Am. J. Med. Gen. 74:439-442].

Alleles↗
PubMed2000

A genetic linkage map of the baboon (Papio hamadryas) genome based on human microsatellite polymorphisms.

A first-generation genetic linkage map of the baboon (Papio hamadryas) genome was developed for use in biomedical and evolutionary genetics. Pedigreed baboons (n = 694) were selected from the breeding colony maintained by the Southwest Foundation for Biomedical Research. To facilitate comparison with the human genome, the baboon linkage map consists primarily of human microsatellite loci amplified using published human PCR primers. Genotypes for 325 human microsatellites and 6 novel baboon microsatellites were used in linkage analyses performed with the MultiMap expert system. The resulting sex-averaged meiotic recombination map covers all 20 baboon autosomes, with average spacing among loci of 7.2 cM. Direct comparison among homologous (orthologous) loci reveals that, for 7 human autosomes, locus order is conserved between humans and baboons. For the other 15 autosomes, one or more rearrangements distinguish the two genomes. The total centimorgan distances among homologous markers are 28.0% longer in the human genome than in the baboon, suggesting that rates of recombination may be higher in humans. This baboon linkage map is the first reported for any nonhuman primate species and creates opportunities for mapping quantitative trait loci in baboons, as well as for comparative evolutionary analyses of genome structure.

Animals↗
PubMed2000

Genome screen for QTLs contributing to normal variation in bone mineral density and osteoporosis.

A major determinant of the risk for osteoporosis is peak bone mineral density (BMD), which is largely determined by genetic factors. We recently reported linkage of peak BMD in a large sample of healthy sister pairs to chromosome 11q12-13. To identify additional loci underlying normal variations in peak BMD, we conducted an autosomal genome screen in 429 Caucasian sister pairs. Multipoint LOD scores were computed for BMD at four skeletal sites. Chromosomal regions with LOD scores above 1.85 were further pursued in an expanded sample of 595 sister pairs (464 Caucasians and 131 African-Americans). The highest LOD score attained in the expanded sample was 3.86 at chromosome 1q21-23 with lumbar spine BMD. Chromosome 5q33-35 gave a LOD score of 2.23 with femoral neck BMD. At chromosome 6p11-12, the 464 Caucasian pairs achieved a LOD score of 2.13 with lumbar spine BMD. Markers within the 11q12-13 region continued to support linkage to femoral neck BMD, although the peak LOD score was decreased to 2.16 in the sample of 595 sibling pairs. Our study is the largest genome screen to date for genes underlying variations in peak BMD and represents an important step toward identifying genes contributing to osteoporosis in the general population.

Adult↗
PubMed1999

Quantitative-trait loci analysis of cocaine-related behaviours and neurochemistry.

We recently conducted a dose-response study of the effects of cocaine on several activity measures in the panel of BxD/Ty recombinant inbred mice. Animals were tested in an automated activity chamber over 2 days with i.p. saline on day 1 and i.p. cocaine on day 2, at one of four doses, 5, 15, 30 or 45 mg kg(-1). The monitor recorded total distance traveled, nosepokes in a holeboard, repeated movements and time spent by an individual in proximity to the centre of the apparatus. Dose-response curves for locomotor activation, i.e. the difference between cocaine and saline scores, showed that for all strains tested, scores increased 5-30 mg kg(-1). With few exceptions, locomotor activity at 45 mg kg(-1) was not significantly higher than that at 30 mg kg(-1). Repeated movement scores showed patterns similar to locomotor activity and nosepokes tended to be progressively inhibited by increasing doses of cocaine. Recombinant inbred strain mean distributions for all behaviours and at all doses exhibited continuous, rather than discrete variation, thus providing evidence of multiple-gene effects on cocaine-related behaviours. Quantitative trait loci (QTL) analysis pointed to several chromosomal locations associated with variations in cocaine-related behaviours and some are either identical or close to QTL reported by others. In separate groups of animals, densities of dopamine D1, and D2 receptors and dopamine uptake transporters were measured in the medial prefrontal cortex, caudate-putamen, nucleus accumbens and ventral midbrain. In all areas, all measures showed distributions consistent with polygenic influence and were associated with QTL. Of particular interest was our finding of a large segment on chromosome 15, which is related to dopamine receptor densities and cocaine-related behaviours.

Animals↗
PubMed1999

Evaluation of the MicroScan system for identification of staphylococci.

Conventional biochemical tests were compared with reactions in a multiple test system, MicroScan Walkaway (Dade Diagnostic Inc. MicroScan Divison, West Sacramento, California) in conjugation with the Combo Pos ID Panels (Dade Diagnostic Inc. MicroScan Divison, West Sacramento, California), in order to evaluate the accuracy for the identification of 99 clinical isolates of Staphylococcus spp. and five reference strains. False-negative or positive reactions were detected from Voges-Proskauer, urease and mannose tests. A good correlation was found among the two identification systems for the fermentation of trehalose, lactose, raffinose, as well as for arginine dyhydrolase, esculin hydrolisis and nitrate reduction. From the results of the present study, it is concluded that the MicroScan Walkaway system is a reliable method for identification of staphylococci (94.23%), although 8.2% could be identified to the species level only after use of additional test.

Bacterial Typing Techniques↗
PubMed1998

Linkage of a QTL contributing to normal variation in bone mineral density to chromosome 11q12-13.

Osteoporosis is a leading public health problem that is responsible for substantial morbidity and mortality. A major determinant of the risk for osteoporosis in later life is bone mineral density (BMD) attained during early adulthood. BMD is a complex trait that presumably is influenced by multiple genes. Recent linkage of three Mendelian BMD-related phenotypes, autosomal dominant high bone mass, autosomal recessive osteoporosis-pseudoglioma, and autosomal recessive osteopetrosis to chromosome 11q12-13 led us to evaluate this region to determine if the underlying gene(s) could also contribute to variation in BMD in the normal population. We performed a linkage study in a sample of 835 premenopausal Caucasian and African-American sisters to identify genes underlying BMD variation. A maximum multipoint LOD score of 3.50 with femoral neck BMD was obtained near the marker D11S987, in the same chromosomal region as the three Mendelian traits mentioned above. Our results suggest that the gene(s) underlying these Mendelian phenotypes also play a role in determining peak BMD in the normal population and are the first using linkage methods to establish a chromosomal location for a gene important in determining peak BMD. These findings support the hypothesis that a gene responsible for one or more of the rare Mendelian BMD traits linked to chromosome 11q12-13 has an important role in osteoporosis in the general population.

Adult↗
PubMed1998

Confirmation of quantitative trait loci for alcohol preference in mice.

An F2 intercross derived from C57BL/6 and DBA/2 progenitor inbred strains was used to test for replication of quantitative trait loci (QTLs) for alcohol preference nominated by a previous study using BXD recombinant inbred (RI) strains (Rodriguez et al., Alcohol. Clin. Exp. Res. 19:367-379, 1995). Fourteen provisional QTLs were nominated in the original RI study with a p < 0.05 criterion. In the present study, a genome scan (101 microsatellite markers) was conducted on an F2 population (n = 218). Three significant QTLs were detected on chromosomes 1, 4, and 9, and three suggestive QTLs were detected on chromosomes 2, 3, and 10. Of these six QTLs, four were consistent with the previous RI nominations. The replication rate of 28.6% (4 of 14) is in agreement with the results of simulation studies performed by Belknap et al. (Behav. Genet. 26:149-160, 1996) and supports the methodological argument for a multistage research design for nominating and replicating QTLs.

Alcohol Drinking↗
PubMed1997

High-activity catechol-O-methyltransferase allele is more prevalent in polysubstance abusers.

Allelic variants at the catechol-O-methyltransferase (COMT) locus are candidates to contribute to genetic components of interindividual differences in vulnerability to substance abuse. COMT plays a prominent role in dopaminergic circuits important for drug reward, and COMT alleles encode enzymes whose activities vary from three- to four-fold. We compared COMT allele frequencies in control research volunteers reporting insignificant lifetime use of addictive substances with those in volunteers reporting substantial polysubstance use. Homozygosity for the high-activity COMT allele was found in 18% of controls, 31% of volunteers with high lifetime substance use, and 39% meeting DSMIII-R substance abuse criteria [odds ratio (relative risks) 2.0 (control vs. use; 95% confidence interval 1.2-3.5; P < 0.013) and 2.8 (control vs. DSM; 1.3-6.1; P < 0.008)]. Individuals with the high-activity COMT variant may have greater genetic vulnerability to drug abuse.

Alleles↗
PubMed1997

Effect of degradability of dietary protein and fat on ruminal, blood, and milk components of Jersey and Holstein cows.

Twelve Holstein cows and 12 Jersey cows were used in six 4 x 4 Latin squares to investigate the effects of the degradability of dietary protein and supplemental dietary fat on milk components. Dietary dry matter contained 16% crude protein with two concentrations of ruminally undegradable protein (RUP) obtained by substituting blood meal for a portion of the soybean meal. Treatments were 1) 29% RUP, 0% added fat; 2) 29% RUP, 2.7% added fat (Ca soaps of fatty acids); 3) 41% RUP, 0% added fat; and 4) 41% RUP, 2.7% added fat. The dry matter of the total mixed ration fed at 1000 and 1400 h consisted of 30% corn silage, 29% alfalfa haylage, and 41% concentrate. Supplemental dietary fat depressed dry matter intake by 6.2%. Plasma urea N was greater at 0700 and 1600 h for Jerseys fed diets containing added fat and greater at 0700 h for Holsteins fed diets containing 41% RUP than for Holsteins fed 0% added fat and 29% RUP. When averaged across both breeds, milk production increased 7.1%, and production of 4% fat-corrected milk by Jerseys increased 8.4%, in response to added dietary fat. Milk protein was reduced when Holstein diets contained 41% RUP. Milk protein content was reduced 7.1 and 3.9%, and milk urea N was increased 4.9 and 8.5%, by added fat and 41% RUP in both breeds, respectively. Added fat reduced the concentration, but not the yield, of milk components. Substitution of blood meal decreased the concentration and yield of milk protein and casein N.

Animals↗
PubMed1997

Diurnal variation in milk and plasma urea nitrogen in Holstein and Jersey cows in response to degradable dietary protein and added fat.

Four Holstein and four Jersey cows fitted with ruminal and duodenal cannulas were used in two 4 x 4 Latin squares to investigate the effects of varying protein degradability and supplemental fat on diurnal changes in plasma and milk urea N. Dietary dry matter contained 16.2% crude protein with two concentrations of ruminally undegradable protein (RUP) that were obtained by substituting blood meal for a portion of soybean meal. Treatments were 1) 29% RUP and 0% added fat, 2) 29% RUP and 2.7% added fat (Ca soaps of fatty acids), 3) 41% RUP and 0% added fat, and 4) 41% RUP and 2.7% added fat. Dry matter of the total mixed diet fed at 1000 and 1400 h consisted of 30% corn silage, 29% alfalfa haylage, and 41% concentrate. Ruminal ammonia, plasma urea N, and milk urea N were measured every 4 h over a 24-h period. Dry matter intake was depressed 6.7% by added fat. Ruminal ammonia was 25 to 45% lower when the 41% RUP diets were fed. Overall, the concentration of plasma urea N and milk components were not influenced by diet. However, milk urea N was higher in Holsteins than in Jerseys. Both plasma and milk urea N increased within 2 h after the 1000-h feeding followed by a decline at 6 h after the 1400-h feeding. In this short-term study, fat supplementation had no effect on milk production or yields of milk components. The inclusion of blood meal, however, increased the yields of milk components. Plasma and milk urea N did not differ among dietary treatments but varied throughout the day in relation to the time of feeding.

Ammonia↗
PubMed1995

Alcohol acceptance, preference, and sensitivity in mice. II. Quantitative trait loci mapping analysis using BXD recombinant inbred strains.

Quantitative trait loci (QTL) mapping of complex phenotypes has emerged as an important feature of the recombinant inbred (RI) strain methodology. In this second study of our series on alcohol-related behaviors in mice, we examine alcohol acceptance, preference, and hypnotic dose sensitivity (HDS) to a standard dose of alcohol measured in BXD RI strains to identify candidate QTL regions responsible for their heritability. We detected highly significant marker associations for acceptance on chromosome 12 (Eif4e), for preference on chromosome 1 (D1Rti2) and chromosome 7 (D7Mit7), and for HDS on chromosome 7 (Mpmv1). These are the strongest QTL associations that we detected, but several other candidate QTL regions are reported. Given the limited number of BXD RI strains available, the large number of markers used herein, and the consequent chance of identifying false marker associations, these RI QTL mapping results must be seen as tentative, but an important first step toward identifying QTL for alcohol-related behaviors.

Alcohol Drinking↗
PubMed1994

Alcohol acceptance, preference, and sensitivity in mice. I. Quantitative genetic analysis using BXD recombinant inbred strains.

Although the recombinant inbred strain method was designed for molecular genetic analysis of linkage, it also provides powerful quantitative genetic analyses of heritability and genetic correlations. Measures of alcohol acceptance, alcohol preference, and hypnotic dose sensitivity (HDS) were assessed in 21 strains of mice from the BXD RI series. Sex differences were found to be significant at a phenotypic level. However, heritability estimates for acceptance, preference, and HDS are similar in males and females. Heritability estimates for the three measures are approximately 0.20 for acceptance and preference, and 0.10 for HDS. Analyses of genetic correlations reveal that acceptance and preference share some degree of genetic influence, although they mostly operate under different genetically mediated mechanisms. HDS did not show a significant genetic relationship to either acceptance or preference. Strong correlations were obtained when acceptance, preference, and HDS strain means were correlated across male and female recombinant inbreds, suggesting substantial genetic similarity across sexes.

Alcohol Drinking↗
PubMed1993

Effects of the acetylcholinesterase toxin of Aeromonas hydrophila on the central nervous system of fish.

The purified acetylcholinesterase (AcChE) toxin, crude extracellular products (ECP) or viable virulent Aeromonas hydrophila were injected intraperitoneally into rainbow trout in different sublethal and lethal doses. When fish showed signs of morbidity, brain tissue was excised and assayed for acetylcholinesterase activity. In all cases there was a large increase in AcChE activity (about 40-fold for purified AcChE-toxin). This was shown to be due to an accumulation of the fish's own AcChE and not the bacterial toxin. Nevertheless, the latter was detected in brain homogenates from fish in all treatment groups using a rabbit antiserum to the purified toxin to probe Western blots of brain homogenates, demonstrating that the toxin does gain access to brain tissue and is produced during in vivo infection. The results strongly suggest that this toxin plays a central role in the pathogenesis of A. hydrophila infection.

Acetylcholinesterase↗
PubMed1993

A maximum-likelihood model-fitting approach to conducting a Hayman analysis of diallel tables with complete or missing data.

A method is presented for conducting a Hayman analysis of non-replicated diallel tables using a maximum-likelihood (ML) model-fitting approach, rather than a traditional analysis of variance (ANOVA) approach. Hayman's linear model for a diallel analysis is used to generate a table of expected cell means. This table of expected cell means is fit to a table of observed cell means, and the fit is assessed using a chi-square value. Often data collected from diallel crosses fail to meet the underlying assumptions of ANOVA. The ML method makes no assumptions about equal cell sizes or homogeneity of variance. Thus, the ML method for diallel analysis provides some statistical advantages over ANOVA methods. The ML method also offers the advantage of having the ability to analyze diallels with missing cells. Using the ML method, incomplete diallel tables can be analyzed, and the partitioning of all the sources of variation in a diallel table is still accomplished from the remaining crosses. These advantages make the ML method an attractive approach for extracting the maximum amount of information from a diallel table.

Alleles↗
PubMed1993

Does psychomotor sensitivity to alcohol predict subsequent alcohol use?

Data from 42 male and 58 female subjects who participated in the Colorado Alcohol Research on Twins and Adoptees (CARTA) project were subjected to model-fitting analyses. The aim of the present study was to use linear structural equation models to determine whether differences in previously measured psychomotor sensitivity to alcohol predict differences in self-reported alcohol consumption over a 4-year period. LISREL model-fitting results indicate that, for male subjects, only rail walking insensitivity is predictive of alcohol use reported 2 years after their initial CARTA testing. For females, only hand steadiness sensitivity is predictive of alcohol use reported 2 years after their initial CARTA testing. The results for males support a hypothesis that would consider alcohol insensitive individuals at greater risk for alcohol abuse. The female results, however, would argue against such a hypothesis. With only one measure of sensitivity predicting alcohol use at only one out of four time points, in both men and women, the overall results suggest that our three measures of psychomotor sensitivity to alcohol are, in general, poor predictors of alcohol consumption in this sample.

Adult↗
PubMed1992

Purification and characterisation of an extracellular metalloprotease, serine protease and haemolysin of Aeromonas hydrophila strain B32: all are lethal for fish.

Three different lethal (for rainbow trout, Salmo gairdneri) extracellular toxins were purified by HPLC from the culture supernatants of Aeromonas hydrophila strain B32 which had been isolated from rainbow trout. A metalloprotease, MW 38 kDa, was stable at 56 degrees C for 10 min, had no cytotoxic activity and and LD50 of 150 ng/g fish. In narrow range isoelectric-focusing (IEF) the enzyme had 11 isomers with (pls) between 4.12 and 4.8. A serine protease (22 kDa) was stable at 56 degrees C for 10 min, possessed cytotoxic activity and had an LD50 of 150 ng/g fish. In IEF, multiple isomers possessed pls between 4.5-5.2. The haemolysin had alpha-haemolytic activity (68 kDa) multiple isomers in IEF with pl range 4.5-5.1 and an LD50 of 2 micrograms/g fish. It was stable after heating to 56 degrees C for 20 min, 60 degrees C for 10 min and possessed esterase activity on beta-naphthyl acetate. These latter properties suggest it may be a novel haemolysin distinct from alpha- and beta-haemolysin.

Acetylcholinesterase↗