Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “programmed genetic variation”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,225 records · Page 68Linked to original sources

Phylogeography recapitulates topography: very fine-scale local endemism of a saproxylic 'giant' springtail at Tallaganda in the Great Dividing Range of south-east Australia.

Comparative phylogeography can reveal processes and historical events that shape the biodiversity of species and communities. As part of a comparative research program, the phylogeography of a new, endemic Australian genus and species of log-dependent (saproxylic) collembola was investigated using mitochondrial sequences, allozymes and anonymous single-copy nuclear markers. We found the genetic structure of the species corresponds with five a priori microbiogeographical regions, with population subdivision at various depths owing to palaeoclimatic influences. Closely related mtDNA haplotypes are codistributed within a single region or occur in adjacent regions, nuclear allele frequencies are more similar among more proximate populations, and interpopulation migration is rare. Based on mtDNA divergence, a late Miocene-late Pliocene coalescence is likely. The present-day distribution of genetic diversity seems to have been impacted by three major climatic events: Pliocene cooling and drying (2.5-7 million years before present, Mybp), early Pleistocene wet-dry oscillations (c. 1.2 Mybp) and the more recent glacial-interglacial cycles that have characterized the latter part of the Quaternary (<0.4 Mybp).

Animals↗

Genetic parameters for growth rate and backfat in Canadian Yorkshire, Landrace, Duroc, and Hampshire pigs.

Records on 47,360 Yorkshire, 28,762 Landrace, 14,020 Duroc, and 9,983 Hampshire pigs for backfat depth and days to 100 kg made between 1989 and 1992 in herds on the Ontario Swine Improvement Program (OSIP) were used to estimate additive genetic (animal), common environmental (litter), and residual variances and covariances of the two traits. Analysis was by the DFREML program of K. Meyer using a multiple-trait individual animal model with fixed effects of genetic groups and herd-year-season-sex and random effects of animal, litter, and residual. A complete relationship matrix was used. Heritabilities were .51, .53, .55, and .50 for backfat and .31, .30, .26, and .32 for days to 100 kg in Yorkshire, Landrace, Duroc, and Hampshire, respectively. Genetic correlations between backfat and days to 100 kg were -.16, -.06, -.17, and -.10 for Yorkshire, Landrace, Duroc, and Hampshire. Respective phenotypic correlations were -.08, -.04, -.12, and -.09. Litter effects were large, particularly for days to 100 kg. Resulting common environmental (c2) effects were .11, .10, .10, and .11 for backfat and .26, .27, .29, and .22 for days to 100 kg for Yorkshire, Landrace, Duroc, and Hampshire. Estimates were highly consistent across breeds and average heritabilities of backfat and days to 100 kg were .52 and .30. Corresponding average c2 effects were .10 and .26. Average genetic and phenotypic correlations between backfat and days to 100 kg were -.13 and -.08.

Adipose Tissue↗

Genetic parameters for egg number, egg weight, and eggshell color in three Catalan poultry breeds.

Heritabilities for egg number, egg weight, and eggshell color (percentage light absorbance) at 39 wk of age, and the genetic correlations between them were estimated by restricted maximum likelihood in three Catalan poultry breeds: Penedesenca Negra (PN), Prat Lleonada (PL), and Empordanesa Roja (ER). Additive genetic differences between these breeds were also estimated. Data were from the IRTA Poultry Genetic Conservation Program and consisted of records from 1,309 PN, 1,466 PL, and 1,440 ER hens, which were obtained from 80 contemporary batches per breed hatched between 1987 and 1992. Estimates of heritability for egg number, egg weight, and eggshell color were, 0.20, 0.59, and 0.49 for PN, 0.31, 0.48, and 0.53 for PL; and 0.33, 0.50, and 0.27 for ER. Estimated genetic correlations between egg number and egg weight, egg number and shell color, and egg weight and shell color were, for PN, -0.22, -0.03, and 0.00; for PL, -0.21, -0.06, and 0.09; and -0.19, -0.29, and 0.30 for ER. Heritability for eggshell color and genetic correlation between eggshell color and other traits showed a different genetic pattern in ER breed. Significant additive genetic differences (P < 0.05) were found between ER and PN base populations for egg number (3.89), egg weight (0.91), and eggshell color (-3.50); and between ER and PL for egg number (6.69) and eggshell color (35.39). The PN and PL breeds differed significantly (P < 0.05) for eggshell color (38.22), which was darker in PN. These results could be taken as the expected genetic differences for these breeds.

Aging↗

Variations of the CFTR gene in the Hanoi-Vietnamese.

In order to investigate polymorphic backgrounds of the cystic fibrosis transmembrane conductance regulator gene (CFTR) in the Vietnamese, we analyzed 495 blood samples of randomly selected healthy individuals in Hanoi for the delta F508 mutation and TG-repeats, poly-T, and M470V polymorphisms. We compared their distributions with those of Caucasians and other Asian populations. No delta F508 mutation was found, being consistent with the extremely low incidence of cystic fibrosis (CF) in Vietnam. Allele frequency of the T5 allele promoting exon 9 skipping was 0.037. Greater number of TG-repeats, which is known to facilitate this aberrant splicing, was a predominant trend in the Vietnamese and other Asians. A "T5-TG12-V470" haplotype was most common (29/37) among T5-bearing haplotypes. Three major haplotypes, T7-TG12-M470, T7-TG11-V470, and T7-TG12-V470, estimated by PHASE program, related to 92% of the population. This is the first study of the CFTR gene among the Vietnamese.

Adolescent↗

Decreased chronic lymphocytic leukemia incidence in Asians in Los Angeles County.

Chronic lymphocytic leukemia (CLL) is rare in Asians living in Asia and possibly in US Asians. In contrast, CLL is the most common leukemia in whites. The basis for this ethnic and geographic variation is unknown. We compared average annual age-adjusted incidence rates (AAIR) of CLL diagnosed from 1972 to 1995 among Los Angeles County-resident Asians, non-Spanish-surnamed- and Spanish-surnamed whites (non-Hispanic and Hispanic-whites) and blacks using the University Southern California-Cancer Surveillance Program (USC-CSP), the population-based cancer registry for Los Angeles County. Asian groups studied included Chinese, Japanese, Filipinos and Koreans. Expected numbers of CLL cases were based on the age-adjusted incidence rates in non-Hispanic whites and compared to numbers of cases observed in Chinese, Japanese and Filipinos. Possible association of socioeconomic state (SES) was assessed using AAIRs with SES-specific denominators. In the absence of denominators by birthplace, the association of birthplace and CLL-incidence was evaluated using proportional odds ratios (POR). Los Angeles County Asian males and females had significantly lower AAIRs than non-Hispanic whites (males: AAIR=0.7 per 100000 population, 95% confidence interval (CI), 0.5-1.0 vs. 4.4, 95% CI, 4.3-4.6; and females: AAIR=0.5, 95% CI, 0.3-0.7 vs. 2.3, 95% CI, 2.2-2.4). Fewer Japanese Chinese and Filipinos were diagnosed with CLL than expected (P<0.01). There was no association of birthplace (POR=0.9, 95% CI, 0. 5-1.9) or SES on CLL-risk. CLL-risk was markedly lower in Los Angeles County Asians compared to non-Hispanic whites. Neither birthplace nor socioeconomic state accounted for this difference suggesting a role for genetic or other environmental factors in decreasing CLL-risk.

Adult↗

Peroxisome proliferator--activated receptor alpha gene regulates left ventricular growth in response to exercise and hypertension.

BACKGROUND: Left ventricular hypertrophy (LVH) occurs as an adaptive response to a physiological (such as exercise) or pathological (valvular disease, hypertension, or obesity) increase in cardiac work. The molecular mechanisms regulating the LVH response are poorly understood. However, inherited defects in fatty acid oxidation are known to cause severe early-onset cardiac hypertrophy. Peroxisome proliferator--activated receptor alpha (PPARalpha) regulates genes responsible for myocardial fatty acid oxidation and is downregulated during cardiac hypertrophy, concomitant with the switch from fatty acid to glucose utilization. METHODS AND RESULTS: The role of PPARalpha in left ventricular growth was investigated in 144 young male British Army recruits undergoing a 10-week physical training program and in 1148 men and women participating in the echocardiographic substudy of the Third Monitoring Trends and Determinants in Cardiovascular Disease (MONICA) Augsburg study. A G/C polymorphism in intron 7 of the PPARalpha gene significantly influenced left ventricular (LV) growth in response to exercise (P=0.009). LV mass increased by 6.7 +/- 1.5 g in G allele homozygotes but was significantly greater in heterozygotes for the C allele (11.8 +/- 1.9 g) and in CC homozygotes (19.4 +/- 4.2 g). Likewise, C allele homozygotes had significantly higher LV mass, which was greater still in hypertensive subjects, and a higher prevalence of LVH in the Third MONICA Augsburg study. CONCLUSIONS: We demonstrate that variation in the PPARalpha gene influences human left ventricular growth in response to exercise and hypertension, indicating that maladaptive cardiac substrate utilization can play a causative role in the pathogenesis of LVH.

Adaptation, Physiological↗

Linkage disequilibrium and haplotype diversity in the genes of the renin-angiotensin system: findings from the family blood pressure program.

Association studies of candidate genes with complex traits have generally used one or a few single nucleotide polymorphisms (SNPs), although variation in the extent of linkage disequilibrium (LD) within genes markedly influences the sensitivity and precision of association studies. The extent of LD and the underlying haplotype structure for most candidate genes are still unavailable. We sampled 193 blacks (African-Americans) and 160 whites (European-Americans) and estimated the intragenic LD and the haplotype structure in four genes of the renin-angiotensin system. We genotyped 25 SNPs, with all but one of the pairs spaced between 1 and 20 kb, thus providing resolution at small scale. The pattern of LD within a gene was very heterogeneous. Using a robust method to define haplotype blocks, blocks of limited haplotype diversity were identified at each locus; between these blocks, LD was lost owing to the history of recombination events. As anticipated, there was less LD among blacks, the number of haplotypes was substantially larger, and shorter haplotype segments were found, compared with whites. These findings have implications for candidate-gene association studies and indicate that variation between populations of European and African origin in haplotype diversity is characteristic of most genes.

Adult↗

Relationship between Y-chromosome length and first-trimester spontaneous abortions.

The hypothesis that variation in Y-chromosome length is associated with repetitive fetal wastage was tested. Chromosome lengths were objectively quantitated by scanning photographic negatives of metaphases with a computer programmed to (1) select boundary thresholds and (2) construct and measure centerlines with a cubic spline-fitting algorithm. Variation in Y length among cells of different individuals was standardized by use of the ratio of the length of the Y to the average of the lengths of the No. 20s (20) in the same cell. Three groups were studied: (1) men whose wives had three or more spontaneous abortions and no live-born infants, (2) men whose wives had both abortions and normal live-born infants, and (3) control men whose wives had normal live-born infants only. Although central tendencies were similar in the three groups, the distributions of Y lengths among the three groups were significantly different (chi 2(6) = 15.33, 0.025 greater than p greater than 0.010). This difference was primarily because more of the subjects with only repetitive loss had Y lengths in the "tails" of the distribution rather than in the center. Our observations suggest the existence of an optimal Y length with respect to reproductive performance.

Abortion, Habitual↗

Diversity of cuticular wax among Salix species and Populus species hybrids.

The leaf cuticular waxes of three Salix species and two Populus species hybrids, selected for their ability to produce high amounts of biomass, were characterized. Samples were extracted in CH(2)Cl(2) three times over the growing season. Low kV SEM was utilized to observe differences in the ultrastructure of leaf surfaces from each clone. Homologous series of wax components were classified into organic groups, and the variation in wax components due to clone, sample time, and their interaction was identified. All Salix species and Populus species hybrids showed differences in total wax load at each sampling period, whereas the pattern of wax deposition over time differed only between the Salix species. A strong positive relationship was identified between the entire homologous series of alcohols and total wax load in all clones. Similarly strong relationships were observed between fatty acids and total wax load as well as fatty acids and alcohols in two Salix species and one Populus species hybrid. One Salix species, S. dasyclados, also displayed a strong positive relationship between alcohols and alkanes. These data indicate that species grown under the same environmental conditions produce measurably different cuticular waxes and that regulation of wax production appears to be different in each species. The important roles cuticular waxes play in drought tolerance, pest, and pathogen resistance, as well as the ease of wax extraction and analysis, strongly suggest that the characteristics of the cuticular wax may prove to be useful selectable traits in a breeding program.

Hybridization, Genetic↗

Long terminal repeat retrotransposons of Oryza sativa.

BACKGROUND: Long terminal repeat (LTR) retrotransposons constitute a major fraction of the genomes of higher plants. For example, retrotransposons comprise more than 50% of the maize genome and more than 90% of the wheat genome. LTR retrotransposons are believed to have contributed significantly to the evolution of genome structure and function. The genome sequencing of selected experimental and agriculturally important species is providing an unprecedented opportunity to view the patterns of variation existing among the entire complement of retrotransposons in complete genomes. RESULTS: Using a new data-mining program, LTR_STRUC, (LTR retrotransposon structure program), we have mined the GenBank rice (Oryza sativa) database as well as the more extensive (259 Mb) Monsanto rice dataset for LTR retrotransposons. Almost two-thirds (37) of the 59 families identified consist of copia-like elements, but gypsy-like elements outnumber copia-like elements by a ratio of approximately 2:1. At least 17% of the rice genome consists of LTR retrotransposons. In addition to the ubiquitous gypsy- and copia-like classes of LTR retrotransposons, the rice genome contains at least two novel families of unusually small, non-coding (non-autonomous) LTR retrotransposons. CONCLUSIONS: Each of the major clades of rice LTR retrotransposons is more closely related to elements present in other species than to the other clades of rice elements, suggesting that horizontal transfer may have occurred over the evolutionary history of rice LTR retrotransposons. Like LTR retrotransposons in other species with relatively small genomes, many rice LTR retrotransposons are relatively young, indicating a high rate of turnover.

Animals↗

Pharmacokinetic variability of routinely administered bisoprolol in middle-aged and elderly Japanese patients.

The nonlinear mixed effects model (NONMEM) was used to analyze the pharmacokinetics of routinely administered bisoprolol in middle-aged and elderly Japanese patients. The subjects consisted of 29 males and 11 females with a mean age of 63.5+/-10.1. Data on the plasma concentration of bisoprolol from 94 blood samples obtained at steady-state following repetitive oral administration were analyzed using the NONMEM program, where a one-compartment model with repetitive bolus dosing was parameterized in terms of oral clearance (CL/F) and apparent volume of distribution (V/F). Individual CL/F values were correlated with body weight (WT) and creatinine clearance (CLcr). The relation between CLcr and the CL/F of bisoprolol was not altered by the CYP2D6 and CYP2C19 genotypes, gender, or age. The mean CL/F value estimated with NONMEM was 0.0612.WT+1.15.CLcr (l/h), and the mean V/F value was 2.61.WT (l). The residual interindividual variability of CL/F and V/F were 22.0% and 12.6%, respectively. The pharmacokinetic variability of bisoprolol is small even in routinely treated Japanese patients, provided that both body weight and renal function are taken into account for the prediction of oral clearance of the drug.

Adult↗

DNA methylation and epigenotypes.

The science of epigenetics is the study of all those mechanisms that control the unfolding of the genetic program for development and determine the phenotypes of differentiated cells. The pattern of gene expression in each of these cells is called the epigenotype. The best known and most thoroughly studied epigenetic mechanism is DNA methylation, which provides a basis both for the switching of gene activities, and the maintenance of stable phenotypes. The human epigenome project is the determination of the pattern of DNA methylation in multiple cell types. Some methylation sites, such as those in repeated genetic elements, are likely to be the same in all cell types, but genes with specialized functions will have distinct patterns of DNA methylation. Another project for the future is the study of the reprogramming of the genome in gametogenesis and early development. Much is already known about the de novo methylation of tumor suppressor genes in cancer cells, but the significance of epigenetic defects during ageing and in some familial diseases remains to be determined.

Aging↗

Genome-wide prediction of human VNTRs.

Polymorphic minisatellites, also known as variable number of tandem repeats (VNTRs), are tandem repeat regions that show variation in the number of repeat units among chromosomes in a population. Currently, there are no general methods for predicting which minisatellites have a high probability of being polymorphic, given their sequence characteristics. An earlier approach has focused on potentially highly polymorphic and hypervariable minisatellites, which make up only a small fraction of all minisatellites in the human genome. We have developed a model, based on available minisatellite and VNTR sequence data, that predicts the probability that a minisatellite (unit size > or = 6 bp) identified by the computer program Tandem Repeats Finder is polymorphic (VNTR). According to the model, minisatellites with high copy number and high degree of sequence similarity are most likely to be VNTRs. This approach was used to scan the draft sequence of the human genome for VNTRs. A total of 157,549 minisatellite repeats were found, of which 29,224 are predicted to be VNTRs. Contrary to previous results, VNTRs appear to be widespread and abundant throughout the human genome, with an estimated density of 9.1 VNTRs/Mb.

Genome, Human↗

Mosaic nature of the wolbachia surface protein.

Lateral gene transfer and recombination play important roles in the evolution of many parasitic bacteria. Here we investigate intragenic recombination in Wolbachia bacteria, considered among the most abundant intracellular bacteria on earth. We conduct a detailed analysis of the patterns of variation and recombination within the Wolbachia surface protein, utilizing an extensive set of published and new sequences from five main supergroups of Wolbachia. Analysis of nucleotide and amino acid sequence variations confirms four hypervariable regions (HVRs), separated by regions under strong conservation. Comparison of shared polymorphisms reveals a complex mosaic structure of the gene, characterized by a clear intragenic recombining of segments among several distinct strains, whose major recombination effect is shuffling of a relatively conserved set of amino acid motifs within each of the four HVRs. Exchanges occurred both within and between the arthropod supergroups. Analyses based on phylogenetic methods and a specific recombination detection program (MAXCHI) significantly support this complex partitioning of the gene, indicating a chimeric origin of wsp. Although wsp has been widely used to define macro- and microtaxonomy among Wolbachia strains, these results clearly show that it is not suitable for this purpose. The role of wsp in bacterium-host interactions is currently unknown, but results presented here indicate that exchanges of HVR motifs are favored by natural selection. Identifying host proteins that interact with wsp variants should help reveal how these widespread bacterial parasites affect and evolve in response to the cellular environments of their invertebrate hosts.

Amino Acid Sequence↗

Identification of genetically diverse sequences (ORF 5) of porcine reproductive and respiratory syndrome virus in a swine herd.

The ability of genetically diverse strains of porcine reproductive and respiratory syndrome virus (PRRSV) to coexist in a 1750-sow farm was assessed through the case study describing a chronically infected farm, and also by an animal experiment involving the use of swine bioassay. The case study employed a program of monitoring sera from suckling, nursery, and finishing pigs for the presence of PRRSV by polymerase chain reaction (PCR) and virus isolation (VI). The swine bioassay tested homogenates, consisting of lymphoid and pulmonary tissues, collected from 60 breeding animals from the same farm. The open reading frame (ORF) 5 portion of selected positive PRRSV detected from sera or tissues were nucleic acid sequenced and their phylogenies compared. The results indicated the presence of 3 genetically diverse groups, designated PRRSV-A, -B, and -C. Sequence heterology ranged from 5.8 to 11% between groups. Sequence homology ranged from 98.7 to 99.8% within groups. Swine bioassay verified the presence of PRRSV-A in 1 of 60 animals, and no evidence of strains B or C were detected. This paper indicates that based on the evaluation of ORF 5, genetically diverse strains of PRRSV appear to coexist, although the frequency and significance of this observation is not understood.

Amino Acid Sequence↗

Comprehensive screening of the human KRAS2 gene for sequence variants.

To search for mutations in the human KRAS2 oncogene, we have analyzed polymerase chain reaction (PCR) fragments by denaturing gradient gel electrophoresis. We used six different PCR fragments to screen the five coding exons of this gene as well as the splice sites. GC clamps were added to each fragment by means of heteroduplex extension. We infer, from a theoretical analysis in which we employed the computer programs MELT and SQHTX, that virtually any mutation affecting one or a few base pairs in the coding exons or splice sites will be detectable. Thus the system that we describe should allow comprehensive detection of mutations throughout the coding exons and splice sites of the KRAS2 gene. As an example, we show that missense mutations at codons 12, 13, and 61 can be detected; mutant KRAS2 gene isolated from human tumors have been found to contain mutations only at these codons. We also report the discovery of three new polymorphic loci in the KRAS2 gene. We show that PCR reactions containing two or three fragments can be screened in a single lane of a denaturing gradient gel; this dramatically increases the number of base pairs that can be screened per gel.

Base Sequence↗

A combined computational and experimental analysis of two families of snoRNA genes from Caenorhabditis elegans, revealing the expression and evolution pattern of snoRNAs in nematodes.

Small nucleolar RNAs (snoRNAs) are an abundant group of noncoding RNAs mainly involved in the posttranscriptional modifications of rRNAs in eukaryotes. Prior to this study, only 28 snoRNA genes had been identified from Caenorhabditis elegans, indicating that most snoRNA genes are hidden in the worm genome, which represents a simple multicellular metazoan. In this study, a genome-wide analysis of the two major families of snoRNA genes in C. elegans was performed using the snoscan and snoGPS programs incorporating comparative genome analyses. Seventy gene variants, including 36 box C/D and 34 box H/ACA snoRNA genes, were identified, of which 50 are novel. Two families of snoRNAs showed a characteristic genomic organization. Notably, 6 box C/D snoRNA genes were located in the antisense orientation of introns. In contrast to insect and mammal, the distances between many intronic snoRNAs and 3' splice sites of introns were less than 50 nt in the worm, an unexpected finding as intron-encoded snoRNAs in C. elegans are supposed to be expressed in a splicing-dependent pathway. Interestingly, a canonical H/ACA snoRNA, PsiCeU5-48, was revealed to be partially homologous to small Cajal body-specific RNA (scaRNA) U85 and U89 in fly and human, indicating a possible evolutionary relationship between snoRNAs and scaRNAs.

Animals↗

Update of the Human MitBASE database.

Human MitBASE is a database collecting human mtDNA variants. This database is part of a greater mitochondrial genome database (MitBASE) funded within the EU Biotech Program. The present paper reports the recent improvements in data structure, data quality and data quantity. As far as the database structure is concerned it is now fully designed and implemented. Based on the previously described structure some changes have been made to optimise both data input and data quality. Cross-references with other bio-databases (EMBL, OMIM, MEDLINE) have been implemented. Human MitBASE data can be queried with the MitBASE Simple Query System (http://www.ebi.ac.uk/htbin/Mitbase/mit base.pl) and with SRS at the EBI under the 'Mutation' section (http://srs.ebi.ac.uk/srs5/). At present the HumanMitBASE node contains approximately 5000 variants related to studies investigating population polymorphisms and pathologies.

Animals↗