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Biomedical subjects

M Band

Publications and source records attributed to M Band.

At least 19 recordsLinked to original sources
PubMed2005

Evolutionary regulation of the blind subterranean mole rat, Spalax, revealed by genome-wide gene expression.

We applied genome-wide gene expression analysis to the evolutionary processes of adaptive speciation of the Israeli blind subterranean mole rats of the Spalax ehrenbergi superspecies. The four Israeli allospecies climatically and adaptively radiated into the cooler, mesic northern domain (N) and warmer, xeric southern domain (S). The kidney and brain mRNAs of two N and two S animals were examined through cross-species hybridizations with two types of Affymetrix arrays (mouse and rat) and muscle mRNA of six N and six S animals with spotted cDNA mouse arrays. The initial microarray analysis was hypothesis-free, i.e., conducted without reference to the origin of animals. Principal component analysis revealed that 20-30% of the expression signal variability could be explained by the differentiation of N-S species. Similar N-S effects were obtained for all tissues and types of arrays: two Affymetrix microarrays using probe oligomer signals and the spotted array. Likewise, ANOVA and t test statistics demonstrated significant N-S ecogeographic divergence and region-tissue specificity in gene expression. Analysis of differential gene expression between species corroborates previous results deduced by allozymes and DNA molecular polymorphisms. Functional categories show significant N-S ecologic putative adaptive divergent up-regulation of genes highlighting a higher metabolism in N, and potential adaptive brain activity and kidney urine cycle pathways in S. The present results confirm ecologic-genomic separation of blind mole rats into N and S. Gene expression regulation appears to be central to the evolution of blind mole rats.

Adaptation, Physiological↗
PubMed2005

Spironolactone reduces brachial pulse wave velocity and PIIINP levels in hypertensive diabetic patients.

AIMS: To assess whether spironolactone has beneficial effects on blood pressure (BP), N-terminal propeptide of type III procollagen (PIIINP) and pulse wave velocity (PWV) in hypertensive, type II diabetics. METHODS: Ten patients with type II diabetes and hypertension were enrolled in a randomized, double-blind crossover study comparing 4 months' treatment with spironolactone and placebo with a 4-week washout phase. BP, PIIINP and carotid-radial PWV were measured at the end of each treatment phase. RESULTS: Compared with placebo, spironolactone reduced systolic BP by 15.6 +/- 46.1 mmHg (P = 0.005, 95% CI 2.7-28.5 mmHg), PIIINP by 0.6 +/- 0.3 microg l(-1) (P = 0.04, 95% CI 0.02-1.1 microg l(-1)) and PWV by 0.6 +/- 0.2 m s(-1) (P = 0.008, 95% CI 0.18-1.02 m s(-1)). CONCLUSIONS: Spironolactone is effective at reducing systolic BP and brachial artery stiffness as indicated by PWV. It also reduces PIIINP in type II diabetic patients with hypertension.

Aged↗
PubMed2004

Spironolactone impairs endothelial function and heart rate variability in patients with type 2 diabetes.

AIMS/HYPOTHESIS: Aldosterone blockade has followed in the footsteps of ACE inhibition in reducing mortality in patients with heart failure. This is associated with its beneficial effects on endothelial function and heart rate variability. Diabetes is another area, where angiotensin II withdrawal has proven to be of particular value. We postulated that aldosterone blockade with spironolactone might also have beneficial effects on the prognostic markers of endothelial function and heart rate variability in diabetic patients. METHODS: We assessed endothelial function by forearm venous occlusion plethysmography in 42 patients with type 2 diabetes mellitus after 1 month of treatment with spironolactone or placebo allocated in a randomised double-blind trial. Of the 42 patients, 20 were on ACE inhibitor therapy. We also assessed heart rate variability, HbA1c and plasma angiotensin II levels at the end of each treatment period. RESULTS: Compared to placebo, spironolactone decreased forearm blood flow response to acetylcholine by 44.56+/-14.56% (p=0.003) in the group as a whole and by 57.61+/-15.56% (p<0.001) in the 20 patients on ACE inhibition. Spironolactone also worsened heart rate variability parameters, with root mean squared standard deviation decreased by 1.99+/-0.93 ms (p=0.03), low-frequency normalised power increased by 2.00+/-0.91 normalised units (nu) (p=0.03), high-frequency normalised power decreased by 1.98+/-0.94 nu (p=0.04) and the low frequency : high frequency ratio increased by 0.40+/-0.19 (p=0.04). HbA1c and angiotensin II increased during treatment with spironolactone by 0.26+/-0.07% (p=0.001) and 8.12+/-1.94 pg/ml (p=0.001) respectively. CONCLUSIONS/INTERPRETATION: Spironolactone worsened endothelial function and heart rate variability in patients with type 2 diabetes. These findings are possibly due to the worsening of glycaemic control and increase in plasma angiotensin II that were seen with spironolactone treatment. Thus the prescription of spironolactone to diabetic patients without heart failure does not seem to be justified.

Adult↗
PubMed2004

Cardiovascular autonomic function in patients with hemodynamic instability at induction of capnoperitoneum: a case-control study.

BACKGROUND: This study hypothesized that patients in whom bradycardia and hypotension develop with induction of positive-pressure capnoperitoneum have an underlying autonomic cardiovascular dysfunction. METHODS: A case-control study was conducted to examine the baseline autonomic function of patients in whom bradycardia and hypotension develop with induction of positive-pressure capnoperitoneum. The control group consisted of patients who maintained normal cardiac rhythm and blood pressure during the same procedure. Two groups of tests were performed: bedside stress tests of cardiovascular autonomic function (response graded 1 (normal) to 4 (severely abnormal) and heart rate variability analysis (spectral and time domain components). RESULTS: The study evaluated 6 patients in the bradycardia group and 10 in the control group. The group in whom bradycardia had developed scored significantly worse on the bedside stress tests than the control group (for grades I to IV: chi2 = 6.5, p = 0.022; for trend: chi2 = 5.6, p = 0.018). In contrast, both groups had similar baseline autonomic tone, as measured by heart rate variability. CONCLUSIONS: Patients in whom bradycardia and hypotension develop with induction of positive-pressure capnoperitoneum have cardiovascular autonomic dysfunction, which is identifiable by bedside stress tests of autonomic function.

Autonomic Nervous System↗
PubMed1999

A genome scan for QTL influencing milk production and health traits in dairy cattle.

A genome scan was conducted in the North American Holstein-Friesian population for quantitative trait loci (QTL) affecting production and health traits using the granddaughter design. Resource families consisted of 1,068 sons of eight elite sires. Genome coverage was estimated to be 2,551 cM (85%) for 174 genotyped markers. Each marker was tested for effects on milk yield, fat yield, protein yield, fat percentage, protein percentage, somatic cell score, and productive herd life using analysis of variance. Joint analysis of all families identified marker effects on 11 chromosomes that exceeded the genomewide, suggestive, or nominal significance threshold for QTL effects. Large marker effects on fat percentage were found on chromosomes 3 and 14, and multimarker regression analysis was used to refine the position of these QTL. Half-sibling families from Israeli Holstein dairy herds were used in a daughter design to confirm the presence of the QTL for fat percentage on chromosome 14. The QTL identified in this study may be useful for marker-assisted selection and for selection of a refined set of candidate genes affecting these traits.

Animals↗
PubMed1998

A radiation hybrid map of BTA23: identification of a chromosomal rearrangement leading to separation of the cattle MHC class II subregions.

Bovine chromosome 23 (BTA23) contains the bovine major histocompatibility complex (MHC) and is thus of particular interest because of the role of MHC genes in immunity. Previous studies have shown cattle MHC class II genes to be subdivided into two distinct subregions separated by a variable genetic distance of 15-30 cM. To elucidate the genetic events that resulted in the present organization of the class II and other MHC genes, a framework radiation hybrid (RH) map of BTA23 was developed by testing DNA samples from a 5000 rad whole genome RH panel. Twenty-six markers were screened with an average retention frequency of 0.27, ranging from 0.14 to 0.42. Total length of the chromosome was 220 cR5000, with 4.1 cR5000/cM when compared to linkage data. Gene orders for the markers common to both the RH framework map and the consensus framework linkage map are identical. Large centiray intervals, D23S23-D23S7, DYA-D23S24 and CYP21-D23S31, were observed compared to linkage distances. These data may indicate a much larger physical distance or suppression of recombination in the interval separating the class II subregions and also within the class I region than previously estimated. Comparison of 13 Type I genes conserved between BTA23 and the human homolog HSA6p suggests the occurrence of an inversion encompassing the centromeric half of the bovine chromosome, thus explaining the large distance between the bovine class IIa and IIb clusters. These results exemplify the power of RH mapping in solving problems in comparative genomics and evolution. Furthermore, noncongruence of the genetic and physical RH map distances indicates that caution must be observed in using either resource alone in searching for candidate genes controlling traits of economic importance.

Animals↗
PubMed1998

Determination of allele frequency from DNA pools using bovine trinucleotide microsatellites.

Three sets of fluorescent labelled primers were used to amplify bovine trinucleotide microsatellites from DNA pools. DNA from 20 individuals were collected to create 3 pools differing in allele frequencies. Replicate mixes from each pool were used as template for PCR reactions. PCR products were separated and quantified on an automated DNA sequencer. Allele frequency estimates from pooled samples corrected for overlapping shadow peaks were calculated. Rare alleles representing only 2.5% of the total pool were accurately detected. Standard error of allele frequency estimates expressed as percent of the total 40 chromosomes per pool ranged between 0.8%-4.6% for different microsatellite-pool combinations as compared to 8.0% binomial sampling error. Regression coefficients of actual allele frequencies, determined by individual genotyping, on estimated frequencies ranged from 0.96-1.06. As regression slopes were close to unity it can be deduced that corrected peak height values from a DNA pool are unbiased estimates of actual allele frequencies. With standard error of the y-intercept of 0.21, the 95% confidence interval of allele frequency is 0.42 alleles or 1% in a pool of 40 chromosomes. Thus, it would be possible to detect an allele with a frequency of greater than 1% within the pool.

Alleles↗
PubMed1997

A medium-density genetic linkage map of the bovine genome.

A cattle genetic linkage map was constructed which covers more than 95 percent of the bovine genome at medium density. Seven hundred and forty six DNA polymorphisms were genotyped in cattle families which comprise 347 individuals in full sibling pedigrees. Seven hundred and three of the loci are linked to at least one other locus. All linkage groups are assigned to chromosomes, and all are orientated with regards to the centromere. There is little overall difference in the lengths of the bull and cow linkage maps although there are individual differences between maps of chromosomes. One hundred and sixty polymorphisms are in or near genes, and the resultant genome-wide comparative analyses indicate that while there is greater conservation of synteny between cattle and humans compared with mice, the conservation of gene order between cattle and humans is much less than would be expected from the conservation of synteny. This map provides a basis for high-resolution mapping of the bovine genome with physical resources such as Yeast and Bacterial Artificial Chromosomes as well as providing the underpinning for the interpolation of information from the Human Genome Project.

Animals↗
PubMed1997

Isolation of microsatellites from a bovine YAC clone harbouring the SOD1 gene.

A bovine yeast artificial chromosome (YAC) clone containing the superoxide dismutase 1 (SOD1) gene was used as a template for polymerase chain reaction (PCR) amplification using a conserved short interspersed nuclear element (SINE) primer. Two highly polymorphic microsatellites with nine and eight alleles were isolated and mapped by linkage analysis to the centromeric region of BTA1. These microsatellites will be used in the construction of a genetic and physical map of the SOD1 region towards positional cloning of the polled gene.

Animals↗
PubMed1996

Creation of a SINE enriched library for the isolation of polymorphic (AGC)n microsatellite markers in the bovine genome.

Trinucleotide (AGC)n microsatellites are found as 3' tails of the artiodactyl short insterspersed nuclear element (SINE) A-dimer. We describe a polymerase chain reaction (PCR)-based method for the construction of a plasmid library enriched for SINE (AGC)n microsatellites. By amplifying Sau3AI inserts with a conserved SINE primer and a flanking vector primer, a 35-fold enrichment of (AGC)n microsatellites over a conventional genomic library was obtained. The SINE primer was used for both sequencing of AGC-containing inserts and analysis of polymorphism. Twenty-three unique reverse primers were synthesized and used on bovine genomic DNA, 21 producing PCR products of expected size. Five polymorphic (AGC)n microsatellites with 2-4 alleles each were characterized. Allele sizes differed by a 3 bp motif and lacked the stutter bands associated with dinucleotide repeats. A tendency of increased polymorphism for longer AGC repeat arrays was observed. High stringency selection for positive clones containing eight or more AGC repeats can thus facilitate the isolation of polymorphic (AGC)n microsatellites. Enrichment for (AGC)n microsatellites by SINE-vector PCR can be applied to other bovidae species, such as sheep or goat, containing the artiodactyl SINE elements.

Animals↗
PubMed1996

Misidentification rate in the Israeli dairy cattle population and its implications for genetic improvement.

The DNA microsatellites can be efficiently used to determine incorrect paternity attribution of cattle without genotyping of dams. Allelic frequencies of the population were determined for 12 microsatellites using the maternal alleles of 102 AI sires. The frequency of the most common microsatellite allele ranged from 0.27 to 0.58. Most loci had at least one allele that was present in only a single individual. Paternity of 9 of 173 cows (5.2%) and 3 of 102 bulls (2.9%) was excluded because putative paternal alleles were not present in progeny for at least one locus. For 4 of the 9 cows and all 3 bulls, exclusion was based on at least two loci. Mean probability of exclusion was 0.85 for cows and 0.99 for bulls. With an assumed cost of US $5 per genotype, a misidentification rate of 5%, and a discount rate of 0.05, additional profit for the Israeli-Holstein breeding program from genotyping 100 test daughters of each young sire becomes positive within 10 yr and reaches nearly US $2.4 million after 20 yr.

Alleles↗
PubMed1995

Prediction of informativeness for microsatellite markers among progeny of sires used for detection of economic trait loci in dairy cattle.

Individual loci affecting economic traits can be located using genetic linkage. Application of either daughter or granddaughter design requires determination of allele origin in the progeny. If only the sires and their progeny are genotyped, the paternal allele origin of progeny having the same genotype as the sire cannot be determined. The expected frequency of informative sons can be predicted for each sire and genetic marker from the allele frequencies in the population. The accuracy of a predictor of the frequency of informative progeny was tested on 103 grandsire x microsatellite combinations. Number of sons per grandsire varied from 24 to 129. Allele frequencies in the population were estimated by genotyping seven sires. The regression of the frequency of informative sons on the predicted frequency was 1.04 with a zero intercept model. Thus, considering the large number of genetic markers available for analysis, predicted informative frequency is a useful criterion for selection of genetic markers.

Animals↗
PubMed1994

Mapping quantitative trait loci with DNA microsatellites in a commercial dairy cattle population.

Individual loci affecting economically important traits can be located using genetic linkage between quantitative trait loci and genetic markers. In the 'granddaughter' experimental design, heterozygous grandsires and their sons are genotyped for the genetic marker, while the quantitative trait records of the granddaughters are used for statistical analysis. Ten DNA microsatellite markers were used to look for associations with quantitative trait loci affecting milk production traits in seven Israeli Holstein grandsire families. At least 60% more grandsires were heterozygous, and 40% fewer individuals were discarded because of unknown paternal allele origin, as compared with diallelic markers. The effects of paternal alleles for locus D21S4 on kg milk and protein were significant (P < 0.025). The allele substitution effects for sire 783 were 283 kg milk and 5.7 kg protein. For both traits, progeny of sire 783 that inherited allele '18' had higher evaluations than progeny that inherited allele '21'. These results were verified by genotyping 151 of his daughters. Thus, the rate of genetic gain for protein production can be increased by selecting progeny of sire 783 carrying allele '18' at this locus.

Animals↗
PubMed1994

Isolation of polymorphic AGC repeats located 3' to bovine SINEs.

A bovine genomic library was screened for the presence of (AGC)n repeats. All isolated AGC repeats were located adjacent to the 3' end of bovine short interspersed nuclear elements (SINE). Polymerase chain reactions (PCR) using either two unique primers or one unique and one SINE primer produced high-resolution products without the secondary artifact ladders typical of dinucleotide microsatellites. Four AGC microsatellites were found to be polymorphic with 2-4 alleles each and polymorphism information context (PIC) values ranging between 0.26 and 0.49. One microsatellite, ARO25, was mapped to chromosome 26 with the CSIRO reference families. Because of their strong association with AGC repeats and high frequency in the genome, SINE-3' PCR may prove to be a novel source of polymorphic trinucleotide markers in the bovine genome.

Animals↗
PubMed1993

Unequivocal determination of sire allele origin for multiallelic microsatellites when only the sire and progeny are genotyped.

The effect of a segregating economic trait locus (ETL) can be detected with the aid of a linked genetic marker, if specific alleles of each locus are in association among the individuals genotyped for the genetic marker. For dairy cattle this can be achieved by application of the 'granddaughter design'. If only the sires and their sons are genotyped for the genetic markers, then the allele origin of sons having the same genotypes as their sires cannot be determined. Seven sires and 101 sons were genotyped for five microsatellites. The mean frequency of heterozygous sires was 77%. The mean number of alleles per locus was 8.2. Frequency of informative sons per locus ranged from 60% to 80% with a mean of 72%. With highly polymorphic microsatellites, at least 60% more grandsire families can be included in the analysis, and the number of sons assayed can be reduced by 40%, as compared to diallelic markers.

Alleles↗