Comparison of three selection programs using Tribolium castaneum.
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Analysis of Variance↗
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Genetic variation in body temperature and its response to short-term acute heat stress in broilers.
Genetic variation in body temperature of broilers and its response to short-term acute (43.5 C for 45 min) heat stress was studied. Body temperatures before (T0) and after (T45) heat exposure were recorded and the changes in body temperature (T delta) were calculated for 5-wk-old chicks from 32 broiler sire families. The T0 data were utilized to rank the families as to their relative body temperature and used to conduct a one-generation divergent family selection program for high basal body temperature (H-BT) and low basal body temperature (L-BT). A control (C) line was established by random selection from the nonselected birds. There was little genetic variation in the base broiler population for body temperature, and one generation of selection for divergence in T0 did not result in differences. There were also no differences among lines in T45. Low realized heritability estimates of .09 and .17 were obtained for T0 in the L-BT and H-BT lines. Phenotypic correlations between body temperature and body weight were very low for all groups. Highly significant negative correlations were observed between T0 and T delta after heat exposure. The T0 fluctuated during the course of each day and between days. The adjustment of the data to eliminate this variation did not result in increased heritability estimates.
Animals↗
Genetic variation in trophectoderm function in parthenogenetic mouse embryos.
The developing oocyte constitutes the source of a unique and essential molecular legacy that supports embryo metabolism for a substantial period after fertilization and that also directs important epigenetic events that prepare the embryonic genome for transcription and faithful execution of the developmental program. Parthenogenetically activated embryos provide a useful tool with which to examine how maternally derived factors contribute to early development. They also provide a means for evaluating genetic effects on the maternal genomic imprinting process. We report here that the genetic background of the oocyte affects trophectoderm function at the blastocyst stage. Parthenogenetic embryos obtained from activated (B6D2)F1 oocytes hatch efficiently in culture, whereas parthenogenones from C57BL/6 oocytes hatch less efficiently. Fertilized embryos of both strains hatch efficiently. The (B6D2)F1 parthenogenones also undergo blastocoel re-expansion after treatment with cytoskeletal inhibitors more rapidly than do C57BL/6 parthenogenones and exhibit a moderately greater abundance of the Na+, K(+)-ATPase alpha 1 subunit mRNA. Surprisingly, parthenogenones of both strains undergo blastocoel re-expansion more rapidly than do their normal fertilized counterparts. Parthenogenones of both types are able to attach efficiently in culture after removal of the zona pellucida. These observations indicate that significant genetic effects of maternal genotype on trophectoderm function are revealed in the absence of a paternal genetic contribution and that trophectoderm function also differs between parthenogenetic embryos and fertilized embryos. The differences observed between parthenogenetic and fertilized embryos indicate a likely role for one or more imprinted genes in the development of hatching and blastocoel expansion ability. The effect of maternal genotype on parthenogenetic embryo phenotype is consistent with possible differences in maternal genome imprinting or differences in ooplasm composition that have long-term effects on development. The specific differences in hatching and blastocoel re-expansion between parthenogenones of the two strains may be the result of differences in the activity or expression of a hatching enzyme or other molecules that affect fluid accumulation within the blastocyst, such as components of junctional complexes or proteins that regulate Na+, K(+)-ATPase activity.
Animals↗
Allozyme variation and population genetic structure of Betula alnoides from Guangxi, China.
Allozyme variation and population genetic structure of Betula alnoides Buch Ham. ex D. Don in 11 natural populations from Guangxi Zhuang Autonomous Region, China, were investigated by starch gel electrophoresis. Variation at 15 loci from 10 enzyme systems was analyzed. Allozyme analysis revealed a high level of genetic variation in this species, with percentage of polymorphic loci (P(p)), the average number of alleles per locus (A(p)), and the expected heterozygosity (H(ep)) being 55.2%, 2.0, and 0.204, respectively, which exceeds the average level among out-crossing wind-pollinated woody species at the population level. At the species level, P(s), A(s), and H(es) were 60.0%, 2.67, and 0.206, respectively. The observed heterozygosity (H(op)) was higher than H(ep), indicating the existence of natural selection against homozygotes. The negative fixation index (F = -0.216) implied a significant excess of heterozygosity at the population level Among-population differentiation (F(ST)) accounted for 4.0% of the total variation. No significant correlation was detected between the genetic distance and geographic distance among populations. Extensive gene flow was inferred, based on the allozyme data (N(m) = 6.000 from F(ST), N(m) = 5.605 from the "private allele" method). The results demonstrated that the fragmentation status of B. alnoides had no remarkable effects on the population genetic structure of this species. Some populations are recommended for both in situ genetic conservation and germplasm collection for breeding programs.
Betula↗
Rare alleles, MHC and captive breeding.
In recent years, more detailed genetic information has become available for individuals of endangered species in captive breeding programs. There have been suggestions that this information be used to identify rare alleles, particularly those at the MHC, that can be subsequently selected for captive breeding programs. First, we summarize the current information on the MHC relevant to conservation genetics, so that such a possible breeding program is seen in a proper perspective. For example, very few specific alleles at the MHC have been identified as selectively advantageous, even though there has been substantial effort to find such alleles in humans and a few other organisms. Further, many of the balancing selection models suggested for MHC variation are based on heterozygotes in general having a higher fitness than homozygotes and not on specific selectively advantageous alleles. Because there is no detailed data on MHC variability in captive populations, we used transferrin data in Przewalski's horses to evaluate a breeding program to select for rare alleles. In this species, one individual, 1060, has been identified to have the transferrin allele J. We determine the effect on founder contribution of multiply mating 1060 to increase the number of copies of this allele. Since there were 485 individuals in the population at this time, this extra mating had little detrimental effect on the distribution of founder contributions and the number of founder equivalents. We then selected 65, an ancestor of 1060, which had a high likelihood of being the individual that passed on the J allele in the lineage of 1060. We examined the effect of increasing the number of copies of alleles of 65 at a time when the population had only 22 other individuals. In this case, even though the founder contributions were changed more, there was also little effect on the founder contributions and the number of founder equivalents. Overall, it appears that selection that results in a limited change in the number of copies of rare alleles may not always have an overall detrimental effect. However, because other pedigrees may have very different properties, it is essential to perform a detailed pedigree analysis of any such selective breeding program to determine its effect before such a selection program is implemented.
Alleles↗
In silico prediction of the deleterious effect of a mutation: proceed with caution in clinical genetics.
When a sequence variation is found in a candidate gene for a disease, it is important to establish whether this change is neutral or responsible for the observed disorders in a patient. To answer this question, in the absence of further experimental investigations, several simulation programs have been proposed to predict whether a nonsynonymous single-nucleotide polymorphism is likely to have or not have a deleterious effect on the phenotype. In this work, we tested two such programs, PolyPhen and SIFT, using two kinds of targets. The first ones concerned the products of the hemoglobin and glucose-6-phosphate dehydrogenase genes, which are abundantly documented. The second concerned two systems for which much less information is available: (a) the TNFRSF1A gene, implicated in tumor necrosis factor receptor-associated periodic syndrome, and (b) the MEFV gene, which is believed to be involved in familial Mediterranean fever. Our data suggest that, from a practical point of view, these programs should not be used to decide, in the absence of other tests or arguments, whether the sequence variation found in a patient is or is not responsible for the disease. The consequence of an erroneous prediction may be disastrous in the perspective of genetic counseling.
Cytoskeletal Proteins↗
Doubled haploids for studying the inheritance of quantitative characters.
By using a doubled-haploid population derived from F2 plants, additive and additive X additive genetic variances, as well as the number of segregating genes, can be estimated. An F2-derived doubled-haploid population may contain almost 50% more of the best recombinant than an F1-derived population. However, the best recombinant occurs in the same frequency in the two populations when there is no linkage between genes. The difference in the frequency of the best recombinant between F2- and F3-derived populations is small. This implies that the doubled-haploid method using F2 plants provides only slightly less opportunity for recombination than the conventional breeding methods of self-pollinating crops. In the absence of additive epistasis, a weighted mean of recombination values can be estimated using an F2-derived population and its parental lines. When additive epistasis is present, it can be estimated from doubled-haploid populations derived from two backcrosses. Studies on the linkage of quantitative characters are needed for determining whether doubled haploids should be produced from F2 or from F1 plants in a breeding program.
Analysis of Variance↗
Allelopathy, DIMBOA production and genetic variability in accessions of Triticum speltoides.
A screening was conducted to study the allelopathic potential of Australian-held accessions of Triticum speltoides. Of 26 accessions, four were found to inhibit root growth in the indicator species, lettuce (Lactuca sativa). The methanol leaf extracts of these accessions significantly reduced the root length of wild oat (Avena spp.). In all but one case, alellopathic accessions contained higher amounts of DIMBOA than did nonallelopathic accessions. Since some variation in allelopathic response was detected within lines, random amplified polymorphic DNA (RAPD) markers were used to estimate genetic diversity between and within the allelopathic accessions of Triticum speltoides L. The average genetic similarity between all possible pairs of selected accessions was found to be 55% and ranged from 44% to 88%. Comparison of DNA extracted from different single seedlings within the same accession revealed significant intraaccession genetic diversity (4-24%), although this was much less than that observed between accessions tested. This intraaccession diversity has significant implications for the selection of T. speltoides accessions in breeding or screening programs.
Benzoxazines↗
CD44: physiological expression of distinct isoforms as evidence for organ-specific metastasis formation.
Continuous progress has been achieved during recent decades in the therapy of metastasizing malignancies by improving chemotherapeutic strategies and new approaches in radiation therapy. Genetic manipulation of tumor cells and of the tumor fighting immune system is hoped to add significant contributions to curative interventions in disseminated tumors. That we are still far from eradicating death by malignant growth is due ultimately to our limited understanding of the cascade of events resulting in metastasis formation, which until recently was believed to rely on multiple rounds of mutation and selection processes. This implies an individually specific history of each metastatic tumor, which would rule out uniform diagnostic and therapeutic concepts. When it was noted in a rat tumor model that the transfer of cDNA of a single gene, a CD44 variant isoform (CD44v) covering the exons v4-v7, sufficed to initiate metastasis formation of a locally growing tumor, hope was created that a "metastogene" may have been identified. Although the idea of CD44v expression as a unifying concept for tumor progression was not sustained, the discovery of CD44v-initiated metastatic spread allowed a conceptually new hypothesis on tumor progression as a consequence of the reactivation of genetic programs of ontogeny, stem cell differentiation, and/or lymphocyte activation. Since distinct CD44 isoforms play an important role in these processes, unraveling the functions of this family of molecules can indeed provide a cornerstone in the understanding of tumor progression. This article summarizes briefly the present knowledge on known functions of CD44 isoforms with particular focus on parallels between physiological programs and tumor progression.
Animals↗
[Antigenic variation of African trypanosomes].
Although several hundred of different antigen genes exist in the trypanosome genome, only one is usually expressed at a time. This expression occurs in one of several possible telomeric expression sites. Besides being exclusively telomeric, transcription of the antigen gene exhibits other particular characteristics: the RNA polymerase is highly resistant to alpha-amanitin, and the transcription unit comprises several other genes, one of which may encode an adenylate cyclase. Post-transcriptional controls modulate the activity of this transcription unit during the parasite life-cycle. Antigenic variation is achieved through either alternative activation of different expression sites, or gene recombination within a given expression site. These mechanisms ensure a relative programming of antigen expression.
Animals↗
Evolution of H5N1 avian influenza viruses in Asia.
An outbreak of highly pathogenic avian influenza A (H5N1) has recently spread to poultry in 9 Asian countries. H5N1 infections have caused > or =52 human deaths in Vietnam, Thailand, and Cambodia from January 2004 to April 2005. Genomic analyses of H5N1 isolates from birds and humans showed 2 distinct clades with a nonoverlapping geographic distribution. All the viral genes were of avian influenza origin, which indicates absence of reassortment with human influenza viruses. All human H5N1 isolates tested belonged to a single clade and were resistant to the adamantane drugs but sensitive to neuraminidase inhibitors. Most H5N1 isolates from humans were antigenically homogeneous and distinct from avian viruses circulating before the end of 2003. Some 2005 isolates showed evidence of antigenic drift. An updated nonpathogenic H5N1 reference virus, lacking the polybasic cleavage site in the hemagglutinin gene, was produced by reverse genetics in anticipation of the possible need to vaccinate humans.
Animals↗
[Apical hypertrophic myocardiopathy: presentation of 3 cases and review of the literature].
Apical hypertrophic myocardiopathy (AHM) is an entity less frequently reported in our country than in Japan. We studied only three patients between 1980 and 1987. Their age varied from 26 to 40 years. Other studies included vectorcardiograms, Holter monitoring, exercise stress testing, phonocardiograms and cardiac catheterization; only one case had a genetic study, program atrial stimulation and technetium-99m pyrophosphate scintigraphy. All patients underwent echocardiographic study. The clinical features had great variations, from asymptomatic cases to the presence of important left ventricular failure and brain embolism. Electrocardiogram was characteristic in two patients; in one, cardiac catheterization showed an intraventricular pressure gradient of 19 mmHg explained by trapping of the catheter and in the other one, the end-diastole pressure of left ventricle was 22 mmHg; in both, the left ventriculogram showed the characteristic spade image. In all of them the echocardiogram showed segmentary left apical ventricular hypertrophy similar to the angiographic image; one patients had mitral regurgitation. This study demonstrates the usefulness of echocardiogram in this pathology.
Adult↗
Analysis of the genetic structure of endangered bovine breeds from the Western Pyrenees using DNA microsatellite markers.
In the Western Pyrenees, three out of four native cattle breeds are in grave danger of extinction. Genetic variation of all four breeds was assessed by analyzing 478 animals using 11 microsatellite markers. A moderate/high within-breed variability was found, a favorable factor to consider when planning conservation and improvement programs. Interestingly, the only selected commercial breed, the Pirenaica, showed depressed heterozygosity levels and a low average number of alleles, perhaps explainable by intensive human selection exacerbated by a bottleneck effect. The Pirenaica also exhibited pronounced genetic differences and was the largest contributor of diversity among the breeds from the Western Pyrenees. Among endangered cattle breeds from this region, our results highlight the singularity of the Betizu. Geographic isolation among herds may be responsible for the large F(IS) value found in the Betizu breed. Lastly, our study suggests that the use of highly selected breeds may be one of the causes of distortion in phylogenetic analyses.
Alleles↗
Increase in genetic diversity of Haemophilus influenzae serotype b (Hib) strains after introduction of Hib vaccination in The Netherlands.
Recently, there has been an increase in The Netherlands in the number of cases of invasive disease caused by Haemophilus influenzae serotype b (Hib). To study a possible change in the Hib population that could explain the rise in incidence, a multiple-locus variable number tandem repeats analysis (MLVA) was developed to genotype H. influenzae isolates. The MLVA enabled the differentiation of H. influenzae serotype b strains with higher discriminatory power than multilocus sequence typing (MLST). MLVA profiles of noncapsulated H. influenzae and H. influenzae serotype f strains were more heterogeneous than serotype b strains and were distinct from Hib, although some overlap occurred. The MLVA was used to genotype a collection of 520 H. influenzae serotype b strains isolated from patients in The Netherlands with invasive disease. The strains were collected from 1983 from 2002, covering a time period of 10 years before and 9 years after the introduction of the Hib vaccine in the Dutch national vaccination program. MLVA revealed a sharp increase in genetic diversity of Hib strains isolated from neonates to 4-year-old patients after 1993, when the Hib vaccine was introduced. Hib strains isolated from patients older than 4 years in age were genetically diverse, and no significant change in diversity was seen after the introduction of the vaccine. These observations suggest that after the introduction of the Hib vaccine young children no longer constitute the reservoir for Hib and that they are infected by adults carrying genetically diverse Hib strains.
Adult↗
Use of stored newborn blood spots in research on birth defects: variation in retrieval rates by type of defect and infant characteristics.
Stored blood spots from state newborn screening programs represent a potential source of DNA for molecular genetics research on birth defects. The stored blood spots of cases and controls from an epidemiologic database on congenital heart defects were sought in the present study, which aimed to establish the feasibility of linking the data sources and to examine blood spot retrieval rates for selected cardiac defects. Blood spots were located on 341 of 522 infants (65%) with congenital heart defects and for 1,484 of 1,645 infants without birth defects (84%) born in Maryland during 1981-1989. Retrieval rates were low among infants with clinically severe lesions such as truncus arteriosus (26%) but were considerably higher in infants with coarctation of the aorta (62%), pulmonic valve stenosis (71%), and atrial septal defect (76%). Retrieval rates were significantly lower for premature and low-birth-weight infants than among full-term, normal-birth-weight infants. Retrieval rates did not vary significantly by gender, race, county of residence, or parental socioeconomic characteristics. These results demonstrate the feasibility of linking epidemiologic databases with stored newborn blood specimens, especially for normal infants and even for infants with certain congenital heart defects, but raise concerns about the adequacy of such methods to obtain stored specimens from premature infants and from those with severe heart defects.
Female↗
[Genetic program and environmental imprinting: the critical perinatal period].
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Animals↗
Use of dose-response relationships to discriminate between the mechanisms of cleft-palate induction by different teratogens: an argument for discussion.
The examples of 6-AN- and cortisone-induced cleft palate in the mouse suggest that dose-response studies can be used to discriminate whether mechanisms of action are different for different teratogens. Evidence for differences in the mechanisms of teratogenic action can be found in terms of the parameters of the response without reliance on other consequences of teratogen treatment. It is argued that the application of established biometrical models or, possibly, the development of new ones is critical to consolidate enumerative data. With practical methods, genetic variation can be sought, interpreted and put to experimental use, structure-function studies can be made intelligible, and safety evaluation programs might begin to make sense.
6-Aminonicotinamide↗
Isozyme evidence for three sibling species in the Anopheles sundaicus complex from Indonesia.
Electrophoretic studies of isoenzymes in three chromosomally distinct forms (A, B and C) of the mosquito Anopheles sundaicus Theobald (Diptera: Culiciae) were undertaken on wild samples collected from six geographically isolated populations in Indonesia. Analyses of 12 enzyme systems comprising 15 loci revealed significant allelic variations, genetic polymorphism, within and among the populations of the An. sundaicus complex. Phylogenetic dendrograms produced by analysis using the Biosys-1 program based on UPGMA methods show that all the populations of form A fall into one cluster, which is closely related to the form C cluster, whereas the populations of form B belong to a more distinct cluster. Allelic frequency and Wright's F statistics of Mpi (mannose phosphate isomerase) are sufficient to identify individuals of each cytological form. This isozyme data correlates with our previous cytological evidence for the existence of three isomorphic species within the taxon An. sundaicus in Indonesia. These three species of the An. sundaicus complex were found together sympatrically at one locality, Asahan in North Sumatra.
Animals↗