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PubMed2002

Relationship of genetic variation in genes encoding apolipoprotein A-IV, scavenger receptor BI, HMG-CoA reductase, CETP and apolipoprotein E with cholesterol metabolism and the response to plant stanol ester consumption.

BACKGROUND: Differences in genetic constitution may affect cholesterol metabolism and responses to diet. Identification of common variations in genes related to dietary responsiveness is therefore an attractive goal to be able to prescribe individually tailored diets for the treatment of dyslipidaemia. MATERIALS AND METHODS: We have examined relationships between serum lipids and lipoproteins, cholesterol-standardized campesterol and lathosterol concentrations with genetic variation, and the presence of a gene-diet interaction between plant stanol ester consumption. Candidate genes were apolipoprotein A-IV (apoA-IV), scavenger receptor-BI (SR-BI), cholesterol ester transfer protein (CETP), 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, and apolipoprotein E (apoE). These relations were examined in 112 nonhypercholesterolaemic subjects, of whom 70 consumed 3.8-4.0 g plant stanol esters a day for 8 weeks. RESULTS: At baseline, high-density lipoprotein (HDL) concentrations of 1.56 +/- 0.36 mmol L(-1) in SR-BI-2 allele carriers tended to be lower compared to the 1.72 +/- 0.42 mmol L(-1) in SR-BI-1/1 subjects (P = 0.069). Cholesterol standardized lathosterol concentrations were also lower in the SR-BI-2 allele carriers (P = 0.002). Furthermore, low-density lipoprotein (LDL) cholesterol concentrations in apoE2 subjects, were lower compared to the LDL cholesterol concentration in apoE3 group (P = 0.002) and apoE4 subjects (P < 0.001). No significant differences between the polymorphisms and dietary responsiveness to plant stanol ester consumption could be found, which indicates that it is unlikely that one of the single polymorphisms analysed in this study is a major factor in explaining the variation in serum LDL cholesterol responses. CONCLUSION: These findings suggest that all subjects who want to lower their cholesterol concentration, will benefit from plant stanol ester consumption, irrespective of their apoA-IV, SR-BI, HMG-CoA reductase, CETP, or apoE genotype.

Adult↗
PubMedDate not supplied

Genetic variation around the collagen IV 1a gene locus and proliferative retinopathy in type 2 diabetes mellitus.

The development of proliferative retinopathy in type 2 diabetes mellitus may be under genetic control. A well-documented pathological change in the fundal capillaries of patients with diabetic retinopathy is basement membrane thickening, with an increased amount of collagen IV protein. Variation at the collagen 1a IV gene therefore may explain familial susceptibility to this complication. It has been previously reported that genetic variation at the collagen 1a locus, as shown by allelic association with a HindIII restriction site, predisposes to diabetic nephropathy where basement membrane thickening is also prevalent. In order to test the hypothesis that the collagen 1a IV gene locus is important in the development of diabetic retinopathy, a population association study was performed comparing allele frequencies of the HindIII RFLP in diabetic patients with retinopathy and controls. No statistically significant differences were found between allele frequencies or genotypes in the two groups. The future use of similar studies in diabetic retinopathy is discussed.

Aged↗
PubMed2003

Finding and interpreting genetic variations that are important to ophthalmologists.

PURPOSE: To explore two approaches for making the human genome more accessible and useful to practicing ophthalmologists. METHODS: DNA samples were obtained from patients with inherited eye diseases, and these samples were screened for sequence variations in known disease genes with a combination of single-strand conformational polymorphism analysis and automated DNA sequencing. Data from this screening were then used to evaluate strategies for productively narrowing the sample space as well as for estimating the pathogenic potential of variations that were discovered in individual patients. For the latter purpose, a universal nomenclature for pathogenic potential was proposed based upon the segregation of disease alleles and the evolutionary conservation of specific residues as reflected by a substitution matrix known as blosum 62. RESULTS: Sequence variations were found to be unevenly distributed among disease-associated genes, such that screening strategies could be refined to discover more than 50% of clinically important sequence variations with only 10% of the effort. The use of the blosum 62 matrix was more statistically powerful than our previous method of estimating pathogenic probability. CONCLUSIONS: The size of the human genome requires that clinical questions be very carefully focused if they are to be meaningfully answered in a reasonable amount of time and with a reasonable amount of resources. By examining the behavior of known disease genes, one can design strategies for significantly focusing the sample space and for more effectively interpreting the variations that are found.

DNA↗
PubMed2006

Domestication and the distribution of genetic variation in wild and cultivated populations of the Mesoamerican fruit tree Spondias purpurea L. (Anacardiaceae).

Domestication occurs as humans select and cultivate wild plants in agricultural habitats. The amount and structure of variation in contemporary cultivated populations has been shaped, in part, by how genetic material was transferred from one cultivated generation to the next. In some cultivated tree species, domestication involved a shift from sexually reproducing wild populations to vegetatively propagated cultivated populations; however, little is known about how domestication has impacted variation in these species. We employed AFLP data to explore the amount, structure, and distribution of variation in clonally propagated domesticated populations and sexually reproducing wild populations of the Neotropical fruit tree, Spondias purpurea (Anacardiaceae). Cultivated populations from three different agricultural habitats were included: living fences, backyards, and orchards. AFLP data were analysed using measures of genetic diversity (% polymorphic loci, Shannon's diversity index, Nei's gene diversity, panmictic heterozygosity), population structure (F(ST) analogues), and principal components analyses. Levels of genetic variation in cultivated S. purpurea populations are significantly less than variation found in wild populations, although the amount of diversity varies in different agricultural habitats. Cultivated populations have a greater proportion of their genetic variability distributed among populations than wild populations. The genetic structure of backyard populations resembles that of wild populations, but living fence and orchard populations have 1/3 more variability distributed among populations, most likely a reflection of relative levels of vegetative reproduction. Finally, these results suggest that S. purpurea was domesticated in two distinct regions within Mesoamerica.

Anacardiaceae↗
PubMed1995

Investigation of natural genetic variation in the circadian system of Drosophila melanogaster. II. Biometrical analyses of locomotor activity rhythms recorded in constant darkness.

The locomotor activity rhythms of 24 isochromosomal strains of Drosophila melanogaster were recorded in constant conditions, using an experimental design suitable for the serial screening with so many strains using limited equipment. The data obtained were subjected to biometrical genetic analysis. The results show that four characteristics of the rhythms (period, phase, definition, and waveform) display genetically based variation in expression and that each appears to be affected by a range of genes.

Activity Cycles↗
PubMed1999

Absence of association between genetic variation in the LIPC gene promoter and plasma lipoproteins in three Canadian populations.

The promoter sequence variant -480T in the hepatic lipase gene (LIPC) has been shown to be significantly associated with low post-heparin hepatic lipase activity. Some studies have also found that the -480T variant is associated with elevation in plasma HDL cholesterol. We tested for associations of LIPC -480T with plasma lipoprotein traits in samples taken from three distinct Canadian populations: 657 Alberta Hutterites, 328 Ontario Oji-Cree and 210 Keewatin Inuit. Plasma HL activity was not available for analyses. The LIPC -480T allele frequencies in these three groups, respectively, were 0.219, 0.527 and 0.383, and the prevalence of LIPC -480T/T homozygotes was, respectively, 0.042, 0.274 and 0.167. No significant association was found between LIPC -480T and plasma HDL cholesterol or apolipoprotein AI concentration, after adjusting for covariates including gender and body mass index. There was no consistent relationship between the population mean plasma HDL cholesterol concentration and the population LIPC -480T frequency. Our findings are consistent with the idea that the common promoter variation in LIPC, which has been reported to be associated with variation in post heparin HL activity and HDL triglyceride concentration, is not always associated with variation in plasma HDL cholesterol concentration, possibly due to yet unspecified environmental or genetic factors.

Adolescent↗
PubMed2000

[Allozyme-based genetic variation within an unstable "population" of Chinese Oncomelania hupensis (Gastropoda: Rissoacea: Pomatiopsidae)].

OBJECTIVE: To answer the following questions: 1. For Oncomelania snails collected two years apart from the same locality, has there been genetic divergence? 2. How much experimental error has there been in studying subsets of these populations? 3. As this is an unstable population, what has the net effect been on Hardy-Weinberg equilibrium (HWe)? METHODS: Allozymes were studied using horizontal starch gel electrophoresis. Data collected from numbers of experiments were compiled. Data from each collection were divided into two equal subsets based on chronology of the experiments. Thirty-four loci were studied using 72 to 180 snails per subset. RESULTS: The mean number of alleles per locus ranged from 1.5-1.9. With each consecutive subset, the % polymorphic loci dropped from 38.2 to 17.6. The mean heterozygosity was very low: 0.033 to 0.049 and not significantly different from Hardy-Weinberg expectations. Ten loci and 11 alleles exclusive to the first group were eliminated from the overall study reducing the number of polymorphic loci from 19 to 10. There were significant departures from HWe at five loci having a substantial number of individuals for each allele. Nei's and Wright's D were 0.003 +/- 0.001 and 0.054 +/- 0.006 respectively. CONCLUSION: 1. There were significant errors seen primarily in the results scored in the earliest experiments. 2. These earlier errors involving scoring difficult to resolve loci, and interpretation of rare alleles that were not found in later experiment had no significant effect on overall genetic distance. 3. The use of Wright's D for closely related populations is explained. Results with Nei's D indicated no significant difference among the four subunits; Wright's D yielded significant difference between the collections made two years apart, attributed to the annual flooding of the Yangtze River mixing snails from different localities. 4. Major polymorphic loci were not in Hwe as predicted using the unstable population model. 5. One must study 25 or more individuals to find relatively rare alleles and study population genetics.

Alleles↗
PubMed1989

Intraspecific and interspecific genetic variation in Drosophila.

Utilizing the technique of DNA-DNA hybridization, we have characterized the degree of genetic variability in single-copy DNA both within and between several species of Drosophila. The results of intraspecific variation studies indicate considerable variation both for levels of nucleotide heterozygosity (estimated to be over 2%) as well as for insertions-deletions. Interspecific studies confirm this great deal of variability and further establish an extreme heterogeneity within Drosophila genomes for rates of divergence. This heterogeneity is much more extreme than that seen between exons and introns. The degree of single-copy DNA divergence generally supports phylogenetic affinities deduced from more traditional methods. However, exceptions occur where single-copy DNA divergence is not correlated with other properties such as degree of chromosomal differentiation, morphology, or ability to form interspecific hybrids. We argue that single-copy DNA divergence as measured by DNA-DNA hybridization is an accurate indicator of phylogenetic relationships and therefore sheds light on the evolution of other biological properties. Many, if not most, evolutionary tests require an accurate phylogeny of the group being studied and DNA, because of the high information content inherent within the molecule, offers the best hope of deriving true phylogenies.

Animals↗
PubMed1999

Temporal and spatial genetic variation within and among populations of the mosquito Culex tarsalis (Diptera: Culicidae) from California.

The genetic structure of 11 populations of Culex tarsalis Coquillett from California and 1 population from Nevada was examined at 18 loci using polyacrylamide gel electrophoresis. Six populations from northern and southern California were sampled repeatedly to determine if the genetic structure of Cx. tarsalis changes seasonally. Significant differences in allele frequencies at 13 different loci were seen in 3 populations over time as determined by contingency chi-square tests. Nei's genetic distance coefficients among different sampling dates was consistently < 0.025. The number of alleles per locus in these populations ranged from 1.6 to 2.7, whereas the average heterozygosity ranged from 0.086 to 0.228. No single locus was found to vary in a consistent pattern within all populations that were sampled repeatedly. These results indicate that Cx. tarsalis populations are genetically stable over time and that temporal variation is due to fluctuations in population size or immigration of genetically distinct individuals. In contrast, Cx. tarsalis did exhibit some differences in genetic structure that were related to geographical features including the Sierra Nevada and the Tehachapi Mountains of southern California. Genetically differentiated populations occurred in Nevada, southern and northeastern California, and the Central Valley of California. Little differentiation was observed among populations located in the Central Valley of California and those located at high elevations in the Sierra Nevada. Thus, in the populations examined, mountain ranges or arid conditions that limit the number of larval development sites appeared to be important barriers to the dispersal of Cx. tarsalis.

Animals↗
PubMed1991

Epidemiologic patterns of wild-type hepatitis A virus determined by genetic variation.

Hepatitis A virus (HAV) isolates from different parts of the world are a single serotype. However, genetic analysis of the VP1 genome region of published HAV sequences suggested that distinct genotypes of HAV could be defined based upon the geographic source of the original isolates. To circumvent the process of cell culture adaptation or animal passage, a 247-bp segment within the VP1 genome region of wild-type HAV was amplified by reverse transcription followed by polymerase chain reaction amplification in the presence of negative- and positive-sense primers. From the sequences obtained from 22 epidemiologically distinct HAV isolates, three genetic groups of HAV could be delineated. Two of the groups differed by 10%, while the third group differed from other isolates by approximately 20%. These investigations indicate that HAV isolates from different parts of the world can be differentiated genetically, which will facilitate studies of epidemiologic transmission.

Animals↗
PubMed1994

Genetic variation in experimental dental caries in four inbred strains of rats.

The relative contribution of the host genetic effect on the susceptibility to dental caries was examined. Four inbred strains of male rats (BN/Sea, F344/Ms, PVG/cSea, and WKA/Sea) were inoculated with Streptococcus mutans and fed a cariogenic diet. The caries scores of the molar teeth were compared among these four strains, and the degree of genetic determination was estimated by analysis of variance. Statistically significant differences in caries scores were found among these strains (F344 > WKA > PVG/c > BN), and a high degree of genetic determination was obtained.

Analysis of Variance↗
PubMedDate not supplied

Genetic variation among natural and laboratory colony populations of Lutzomyia longipalpis (Lutz & Neiva, 1912)(Diptera: Psychodidae) from Colombia.

Genetic diversity among three field populations of Lutzomyia longipalpis in Colombia was studied using isozyme analysis. Study sites were as much as 598 km apart and included populations separated by the eastern Cordillera of the Andes. Genetic variability among populations, estimated by heterozygosity, was within values typical for insects in general (8.1%). Heterozygosity for field populations were compared with a laboratory colony from Colombia (Melgar colony) and were only slightly lower. These results suggest that establishment and long term maintenance of the Melgar colony has had little effect on the level of isozyme variability it carries. Genetic divergences between populations was evaluated using estimates of genetic distance. Genetic divergence among the three field populations was low (D = 0.021), suggesting they represent local populations within a single species. Genetic distance between field populations and the Melgar colony was also low (D = 0.016), suggesting that this colony population does not depart significantly from natural populations. Finally, comparisons were made between Colombian populations and colonies from Brazil and Costa Rica. Genetic distance values were high between Colombian and both Brazil and Costa Rica colony populations (D = 0.199 and 0.098 respectively) providing additional support for our earlier report that populations from the three countries represent distinct species.

Animals↗
PubMed1991

Genetic variation and host-parasite relations: Nematospiroides dubius in mice.

Our work deals with aspects of the genetics and immunology of host-parasite relationships as they influence the development of protective immunity and the phenomenon of coevolution. The aim is to understand parasitism through analyses of host specificity. In earlier studies we examined the inheritance of resistances in mice to infections with Nematospiroides dubius (=Heligmosomoides polygyrus) and established the predominant role played by antibodies in protective immunity. Here we report information concerning the selection of lines of N. dubius that differ in their ability to survive antagonistic immunological reactions from mice. Challenge infections with groups of these mice, immunized and protected by previous repeated infections, show that worms selected to survive the immunity that kills other worms do so by inhibiting the effectiveness of the cellular rather than humoral elements of protective immunity.

Animals↗
PubMed1981

Genetic variation among laboratory strains of the planorbid snail Biomphalaria glabrata.

Isozymes of laboratory strains of Biomphalaria glabrata have been studied by starch gel electrophoresis. Methods are outlined for adaptation of this technique to the genetic study of these snails. Twenty-eight presumptive gene loci have been identified. Twelve invariant enzymes were observed. Sixteen loci displayed some polymorphism within or among the strains. These polymorphisms were generally widespread among strains from Brazil, Puerto Rico, St. Lucia, and the Dominican Republic. A high degree of intrastrain polymorphism was noted even in some presumably inbred laboratory strains. Crosses between strains were used to demonstrate the genetic basis for the patterns observed at 9 of the 16 polymorphic loci.

Animals↗
PubMed2026

Peripheral pain threshold, glycaemic status, and LAMP3 genetic variation: A community-based analysis.

Diabetic polyneuropathy is a common complication of diabetes, yet substantial inter-individual variation in peripheral pain perception suggests underlying genetic influences. This population-based study investigated clinical, metabolic, and genetic determinants of pain threshold using intraepidermal electrical stimulation in 906 participants from the Iwaki Health Promotion Project 2017. Genome-wide association analysis identified 12 loci showing suggestive associations, among which a missense variant in LAMP3 (rs482912) was prioritized as a biologically plausible candidate. Phenotype-stratified analyses showed that individuals carrying the CT or CC genotypes had lower PINT indices than those with the TT genotype, indicating reduced pain thresholds. Notably, the CC genotype retained an association with lower pain threshold using intraepidermal electrical stimulation under conditions of metabolic stress, including impaired glucose tolerance, elevated HbA1c, and obesity, whereas this association was attenuated in the presence of hypertension. Single-cell RNA sequencing analysis of human skin revealed that LAMP3-positive mature dendritic cells, enriched in immunoregulatory molecules, exhibited transcriptional enrichment of inflammatory, antigen-presenting, and nociception-related pathways, including NF-&#x3ba;B, JAK-STAT, cytokine signaling, and neuroimmune sensitization cascades. Autopsy-based skin analysis further demonstrated genotype-associated differences in dermal LAMP3-positive cell infiltration and CD8-positive T-cell abundance, while CD4-positive T-cell abundance and intraepidermal nerve fiber density remained unchanged across genotypes. Taken together, these findings suggest a potential association between LAMP3 variation and individual differences in peripheral pain threshold and provide biological context supporting a role for neuroimmune interactions in early sensory modulation under metabolic stress. Given the suggestive genetic evidence and indirect mechanistic data, these observations should be interpreted as exploratory and hypothesis-generating.

Humans↗
PubMed2004

Phenotypic consequences of genetic variation in a gynogenetic complex of Phoxinus eos-neogaeus clonal fish (Pisces: Cyprinidae) inhabiting a heterogeneous environment.

We examined the genetic composition, habitat use, and morphological variation of a Phoxinus eos-neogaeus unisexual hybrid complex and its sexually reproducing progenitor species inhabiting beaver-modified drainages of Voyageurs National Park, Minnesota. In addition to the single diploid P. eos-neogaeus gynogenetic clone, triploid and diploid-triploid mosaic biotypes were present at our study sites. Both P. eos and P. neogaeus, and all three hybrid biotypes were ubiquitous throughout one intensively surveyed drainage, but abundances and relative frequencies of the parental species and hybrids varied considerably within and among successional environments. Data from a large number of additional sites indicated that the proportion of polyploid hybrids within an environment was negatively related to hybrid relative frequency, implying that the genomic constitution of hybrids is an important determinant of clonal fitness among successional environments. Statistical comparisons of variation along size-free multivariate body shape axes indicated that despite its genetic uniformity, the P. eos-neogaeus clone is no less variable than its sexual progenitors, suggesting that a single genotype may actually respond to environmental variation with as much phenotypic variation as a genetically variable sexual population. The incorporation and expression of a third genome in triploid and diploid-triploid mosaic biotypes derived from the gynogenetic clone significantly expanded phenotypic variation of the clone. This additional variation results in greater similarities in habitat use and morphological overlap with the parental species, primarily P. eos, the predominant sperm donor for gynogenetic hybrid females in this complex. Polyploid augmentation of a diploid gynogenetic clone appears to be typical in the P. eos-neogaeus complex, and the additional genetic and phenotypic variation that it generates has potentially significant ecological and evolutionary consequences for the success and persistence of a single genotype in highly variable environments.

Animals↗