Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “genetic isolates”

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 73 records · Page 4Linked to original sources
PubMed2002

Genetics of population isolates.

Genetic isolates, as shown empirically by the Finnish, Old Order Amish, Hutterites, Sardinian and Jewish communities among others, represent a most important and powerful tool in genetically mapping inherited disorders. The main features associated with that genetic power are the existence of multigenerational pedigrees which are mostly descended from a small number of founders a short number of generations ago, environmental and phenotypic homogeneity, restricted geographical distribution, the presence of exhaustive and detailed records correlating individuals in very well ascertained pedigrees, and inbreeding as a norm. On the other hand, the presence of a multifounder effect or admixture among divergent populations in the founder time (e.g. the Finnish and the Paisa community from Colombia) will theoretically result in increased linkage disequilibrium among adjacent loci. The present review evaluates the historical context and features of some genetic isolates with emphasis on the basic population genetic concepts of inbreeding and genetic drift, and also the state-of-the-art in mapping traits, both Mendelian and complex, on genetic isolates.

Christianity↗
PubMed2000

Screening of microbes, isolation, genetic manipulation, and physiological optimization of Brevibacterium helvolum to produce and excrete thymidine and deoxyuridine in high concentrations.

Analogues of deoxypyrimidines are used in the treatment of a variety of human ailments. Azidothymidine, or AZT, is one such analogue used to treat AIDS. Thymidine is the precursor of AZT, and its cost contributes to the high price of AZT. Attempts are being made to isolate and genetically manipulate microbes that can produce and excrete this compound in high concentrations. To this end, 145 different microbial species from Zeneca and the American Type Culture Collection were screened. Moreover, soil samples were collected from 36 different sites in England, and microbes from these samples were isolated and screened. >From approximately 25,000 isolates screened as single colonies and from 4,000 in liquid cultures, a strain of Brevibacterium helvolum showed the most promising results. Pyrimidine metabolic pathways of this bacterium were worked out, the isolate was genetically manipulated, and physiological conditions were optimized to increase the production of thymidine and deoxyuridine. These mutants of B. helvolum are considered to be of commercial importance.

Journal Article↗
PubMed2001

Genetic isolation of meningococci of the electrophoretic type 37 complex.

Neisseria meningitidis (the meningococcus) is a naturally competent bacterial species in which intra- and interspecific horizontal gene transfer is a major source of genetic diversity. In strains of the electrophoretic type 37 (ET-37) complex and of the A4 cluster, we identified genomic DNA coding for a novel restriction-modification system and for the tail of a previously unidentified prophage. Furthermore, a novel 7.2-kb DNA segment restricted to clones of the ET-37 complex and the A4 cluster was isolated and shown to occur both as a plasmid (pJS-B) and as a chromosomal integration. Neither the genomic loci nor pJS-B was present in ET-5 complex, lineage 3, or serogroup A meningococci. The differential distribution of the DNA segments described herein, as well as of opcA, porB, nmeAI, nmeBI, and nmeDI described previously, supports the concept of genetic isolation of hypervirulent lineages responsible for most cases of serogroup C disease worldwide.

Bacteriophages↗
PubMed1992

Genetic isolation of ADA2: a potential transcriptional adaptor required for function of certain acidic activation domains.

We have devised a genetic strategy to isolate the target of acidic activation domains of transcriptional activators based on toxicity in yeast cells of the chimeric activator, GAL4-VP16. Toxicity required the integrity of both the VP16 acidic activation domain and the GAL4 DNA-binding domain, suggesting that inhibition resulted from trapping of general transcription factors at genomic sites. Mutations that break the interaction between GAL4-VP16 and general factors would alleviate toxicity and identify transcriptional adaptors, if adaptors bridged the interaction between activators and general factors. We thus identified ADA1, ADA2, and ADA3. Mutations in ADA2 reduced the activity of GAL4-VP16 and GCN4 in vivo. ada2 mutant extracts exhibited normal basal transcription, but were defective in responding to GAL4-VP16, GCN4, or the dA:dT activator. Strikingly, the mutant extract responded like wild type to GAL4-HAP4. We conclude that ADA2 potentiates the activity of one class of acidic activation domain but not a second class.

Amino Acid Sequence↗
PubMed2006

High resolution analysis and phylogenetic network construction using complete mtDNA sequences in sardinian genetic isolates.

For mitochondrial phylogenetic analysis, the best result comes from complete sequences. We therefore decided to sequence the entire mitochondrial DNA (mtDNA) (coding and D-loop regions) of 63 individuals selected in 3 small Ogliastra villages, an isolated area of eastern Sardinia: Talana, Urzulei, and Perdasdefogu. We studied at least one individual for each of the most frequent maternal genealogical lineages belonging to haplogroups H, V, J, K, T, U, and X. We found in our 63 samples, 172 and 69 sequence changes in the coding and in the D-loop region, respectively. Thirteen out of 172 sequence changes in the coding region are novel. It is our hypothesis that some of them are characteristic of the Ogliastra region and/or Sardinia. We reconstructed the phylogenetic network of the 63 complete mtDNA sequences for the 3 villages. We also drew a network including a large number of European sequences and calculated various indices of genetic diversity in Ogliastra. It appears that these small populations remained extremely isolated and genetically differentiated compared with other European populations. We also identified in our samples a never previously described subhaplogroup, U5b3, which seems peculiar to the Ogliastra region.

DNA, Mitochondrial↗
PubMed1996

Genetic and biochemical factors associated with variation in blood pressure in a genetic isolate.

We previously found an association between blood pressure and genetic variation of angiotensinogen in Canadian Hutterites. We hypothesized that variation in other candidate genes would also be associated with variation in blood pressure. We included genotypes of 12 candidate genes, along with clinical features and biochemical variables as covariates in an association analysis. We found that sex and body mass were significantly associated with variation in both systolic and diastolic blood pressures. We found that genotypes of APOB codon 4154 and AGT codon 174 were significantly associated with variation in systolic blood pressure. We found that genotypes of APOB codon 4154, AGT codon 174, and F7 codon 353 were significantly associated with variation in diastolic blood pressure. We found a significant association between age and variation in systolic but not diastolic blood pressure. We found a significant association between plasma apo B concentration and variation in diastolic but not systolic blood pressure. The association of genomic variation with resting blood pressure is consistent with the existence of important structural elements within or proximal to some genes in lipoprotein metabolism, the renin-angiotensin system, and the coagulation cascade. The association between plasma apo B concentration and diastolic blood pressure suggests that these traits may share some determinants.

Angiotensinogen↗
PubMed2003

Identification of a novel gene and a common variant associated with uric acid nephrolithiasis in a Sardinian genetic isolate.

Uric acid nephrolithiasis (UAN) is a common disease with an established genetic component that presents a complex mode of inheritance. While studying an ancient founder population in Talana, a village in Sardinia, we recently identified a susceptibility locus of approximately 2.5 cM for UAN on 10q21-q22 in a relatively small sample that was carefully selected through genealogical information. To refine the critical region and to identify the susceptibility gene, we extended our analysis to severely affected subjects from the same village. We confirm the involvement of this region in UAN through identical-by-descent sharing and autozygosity mapping, and we refine the critical region to an interval of approximately 67 kb associated with UAN by linkage-disequilibrium mapping. After inspecting the genomic sequences available in public databases, we determined that a novel gene overlaps this interval. This gene is divided into 15 exons, spanning a region of approximately 300 kb and generating at least four different proteins (407, 333, 462, and 216 amino acids). Interestingly, the last isoform was completely included in the 67-kb associated interval. Computer-assisted analysis of this isoform revealed at least one membrane-spanning domain and several N- and O-glycosylation consensus sites at N-termini, suggesting that it could be an integral membrane protein. Mutational analysis shows that a coding nucleotide variant (Ala62Thr), causing a missense in exon 12, is in strong association with UAN (P=.0051). Moreover, Ala62Thr modifies predicted protein secondary structure, suggesting that it may have a role in UAN etiology. The present study underscores the value of our small, genealogically well-characterized, isolated population as a model for the identification of susceptibility genes underlying complex diseases. Indeed, using a relatively small sample of affected and unaffected subjects, we identified a candidate gene for multifactorial UAN.

Amino Acid Sequence↗
PubMed2000

Genetic isolation by distance among Aedes aegypti populations along the northeastern coast of Mexico.

A population genetic analysis of gene flow was conducted among 10 Aedes aegypti collections from seven cities along the northeastern coast of Mexico. Four collections were made from Monterrey to examine local patterns of gene flow. Markers included 60 random amplified polymorphic DNA (RAPD) loci amplified by the polymerase chain reaction and single strand conformation polymorphism analysis of variation in a 387-basepair region of the NADH dehydrogenase subunit 4 from the mitochondrial DNA (mtDNA). Seven mitochondrial haplotypes were detected and phylogenetic analysis identified two well-supported clades. Regression analysis of geographic distances and pairwise FST estimated from RAPD markers indicated that populations are isolated by distance and that free gene flow occurs among collections within 90-250 km. Isolation by distance was not detected using mtDNA haplotypes. The Nuevo Laredo collection had unique RAPD and mtDNA haplotype frequencies and reduced heterozygosity suggesting that few mosquitoes established this population.

Aedes↗
PubMed2003

From connectivity to isolation: genetic consequences of population fragmentation in capercaillie across Europe.

The capercaillie inhabits a continuous range in large parts of the Palearctic boreal forest, but is patchily distributed in temperate Europe. An ongoing population decline, largely related to human land use changes, has been most pronounced in central and western Europe, where some local populations have become extinct. In this study, we document the genetic differentiation of capercaillie populations at different stages along a gradient of spatial structuring from high connectivity (continuous range in the boreal forest) to a metapopulation systems (Alps) and recent (central Europe) and historic (Pyrenees) isolation. Four hundred and sixty individuals from 14 sample sites were genotyped at 10 polymorphic microsatellite loci to assess genetic structure and variation of capercaillie populations across its European range. As expected, differentiation was least pronounced within the continuous range in the boreal forest. Within the metapopulation system of the Alps, differentiation was less than among the isolated populations of central Europe (Black Forest, Fichtelgebirge, Thuringia, Vosges). In the long-isolated population of the Pyrenees, and the recently isolated populations of central Europe, genetic diversity was significantly reduced compared with the Alps and boreal forest. Our results agree with the concept of a gradual increase in genetic differentiation from connectivity to isolation, and from recent to historic isolation. Anthropogenic habitat deterioration and fragmentation thus not only leads to range contractions and extinctions, but may also have significant genetic and evolutionary consequences for surviving populations. To maintain high levels of genetic variation in species in fragmented habitats, conservation should aim at securing connectivity between spatially distinct populations.

Animals↗
PubMed2002

Resistance gene analogues of chickpea ( Cicer arietinum L.): isolation, genetic mapping and association with a Fusarium resistance gene cluster.

Resistance gene analogues (RGAs) of Cicer were isolated by different PCR approaches and mapped in an inter-specific cross segregating for fusarium wilt by RFLP and CAPS analysis. Initially, two pairs of degenerate primers targeting sequences encoded at nucleotide-binding sites (NBS), which are conserved in plant disease resistance genes such as RPS2, L6 and N, were selected for amplification. Cloning and sequence analysis of amplified products from C. arietinum DNA revealed eight different RGAs. Additionally, five RGAs were identified after characterisation of the presumptive RGA alleles from C. reticulatum. Therefore, a total of 13 different RGAs were isolated from Cicer and classified through pair-wise comparison into nine distinct classes with sequence similarities below a 68% amino acid identity threshold. Sequence comparison of seven RGA alleles of C. arietinum and C. reticulatum revealed polymorphisms in four RGAs with identical numbers of synonymous and non-synonymous substitutions. An NlaIII site, unique in the RGA-A allele of C. arietinum, was exploited for CAPS analysis. Genomic organisation and map position of the NBS-LRR candidate resistance genes was probed by RFLP analysis. Both single-copy as well as multi-copy sequence families were present for the selected RGAs, which represented eight different classes. Five RGAs were mapped in an inter-specific population segregating for three race-specific Fusarium resistances. All RGAs mapped to four of the previously established eight linkage groups for chickpea. Two NBS-LRR clusters were identified that could not be resolved in our mapping population. One of these clusters, which is characterised by RFLP probe CaRGA-D, mapped to the linkage group harbouring two of three Fusarium resistance genes characterised in the inter-specific population. Our study provides a starting point for the characterisation and genetic mapping of candidate resistance genes in Cicer that is useful for marker-assisted selection and as a pool for resistance genes of Cicer.

Journal Article↗
PubMedDate not supplied

Genetic isolation of adoptees.

The purpose of this paper is to alert pediatric ophthalmologists to problems of rendering genetic counseling to adoptees at-risk for genetic disease. All states have statutes that provide for secrecy of adoption records. These records are maintained by adoption agencies, county courts, and state registrar. In most cases, the counseling clinician must file a lawsuit to reach the parents of an at-risk adoptee. An administrative procedure is proposed to allow access to certain adoption information for the purposes of genetic counseling and offer of treatment.

Adolescent↗
PubMed1997

Isolation, genetic diversity, and geographic distribution of Bayou virus (Bunyaviridae: hantavirus).

Bayou hantavirus, previously implicated in human hantavirus pulmonary syndrome in Louisiana, was isolated from a rice rat (Oryzomys palustris) captured in Georgia. The presence of antibody among rice rats captured throughout the southeastern United States and the extent of diversity among the genetic variants of Bayou viruses suggest that the rice rat is the most likely natural reservoir of the virus and that both virus and host have probably co-evolved for some years.

Animals↗
PubMed1977

Inbreeding, marital movement, and genetic isolation of a rural Appalachian population.

Genealogical, marital, birthplace and age-at-marriage data were collected on a random sample of 275 reproducing couples from the population of a rural Appalachian county in north-eastern Tennessee. Genealogies covering the three extant generations provided the data for a surname isonymy analysis to determine the amount of inbreeding prevalent, while the marital, birthplace and age at marriage data were used to ascertain the components of marital movement, i.e., marital distance, orientation of marital movement, spatial exogamy, and "diffusion". The effective breeding population and effective immigration rate were calculated for the county population and these in turn were used to compute the coefficient of breeding isolation for the currently reproduction population. Our conclusions agree with those of an earlier genetic and demographic study on one segment of the same population. The more extensive demographic analysis illustrates the value of such studies as this for providing background for interpretations of genetic variation.

Consanguinity↗
PubMed1993

Genetic Isolation, Cloning, and Analysis of a Mutator-Induced, Dominant Antimorph of the Maize amylose extender1 Locus.

We report the genetic identification, molecular cloning, and characterization of a dominant mutant at the amylose extender1 locus, Ae1-5180. The identities of our clones are corroborated by their ability to reveal DNA polymorphisms between seven wild-type revertants from Ae1-5180 relative to the Ae1-5180 mutant allele and between four of five independently derived, Mutator (Mu)-induced recessive ae1 alleles relative to their respective wild-type progenitor alleles. The Ae1-5180 mutation is associated with two Mu1 insertions flanked by complex rearrangements of ae1-related sequences. One of the Mu1 elements is flanked by inverted repeats of ae1-related DNA of at least 5.0 kb in length. This Mu1 element and at least some of this flanking inverted repeat DNA are absent or hypermethylated in six of seven wild-type revertants of Ae1-5180 that were analyzed. The second Mu1 element is flanked on one side by the 5.0-kb ae1-specific repeat and on the other side by a sequence that does not hybridize to the ae1-related repeat sequence. This second Mu1 element is present in revertants to the wild type and does not, therefore, appear to affect ae1 gene function. A 2.7-kb ae1 transcript can be detected in wild-type and homozygous ae1-Ref endosperms 20 days after pollination. This transcript is absent in endosperms containing one, two, or three doses of Ae1-5180. This result is consistent with a suppression model to explain the dominant gene action of Ae1-5180 and establishes Ae1-5180 as an antimorphic allele. Homozygous wild-type seedlings produce no detectable transcript, indicating some degree of tissue specificity for ae1 expression. Sequence analyses establish that ae1 encodes starch branching enzyme II.

Journal Article↗