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PubMed1995

Efficient high-resolution genetic mapping of mouse interspersed repetitive sequence PCR products, toward integrated genetic and physical mapping of the mouse genome.

The ability to carry out high-resolution genetic mapping at high throughput in the mouse is a critical rate-limiting step in the generation of genetically anchored contigs in physical mapping projects and the mapping of genetic loci for complex traits. To address this need, we have developed an efficient, high-resolution, large-scale genome mapping system. This system is based on the identification of polymorphic DNA sites between mouse strains by using interspersed repetitive sequence (IRS) PCR. Individual cloned IRS PCR products are hybridized to a DNA array of IRS PCR products derived from the DNA of individual mice segregating DNA sequences from the two parent strains. Since gel electrophoresis is not required, large numbers of samples can be genotyped in parallel. By using this approach, we have mapped > 450 polymorphic probes with filters containing the DNA of up to 517 backcross mice, potentially allowing resolution of 0.14 centimorgan. This approach also carries the potential for a high degree of efficiency in the integration of physical and genetic maps, since pooled DNAs representing libraries of yeast artificial chromosomes or other physical representations of the mouse genome can be addressed by hybridization of filter representations of the IRS PCR products of such libraries.

Animals↗

PubMed1987

Genetic hitchhiking and the evolution of reduced genetic activity of the Y sex chromosome.

A new model for the evolution of reduced genetic activity of the Y sex chromosome is described. The model is based on the process of genetic hitchhiking. It is shown that the Y chromosome can gradually lose its genetic activity due to the fixation of deleterious mutations that are linked with other beneficial genes. Fixation of deleterious Y-linked mutations generates locus-specific selection for dosage tolerance and/or compensation. The hitchhiking effect is most pronounced when operating in combination with an alternative model, Muller's ratchet. It is shown, however, that the genetic hitchhiking mechanism can operate under conditions where Muller's ratchet is ineffective.

Alleles↗

PubMedDate not supplied

Low genetic variation among killer whales (Orcinus orca) in the eastern north Pacific and genetic differentiation between foraging specialists.

Killer whales from the coastal waters off California through Alaska were compared for genetic variation at three nuclear DNA markers and sequenced for a total of 520 bp from the mitochondrial control region. Two putative sympatric populations that range throughout this region were compared. They can be distinguished by social and foraging behavior and are known as "residents" and "transients". We found low levels of variation within populations compared to other cetacean species. Comparisons between fish (resident) versus marine mammal (transient) foraging specialists indicated highly significant genetic differentiation at both nuclear and mitochondrial loci. This differentiation is at a level consistent with intraspecific variation. A comparison between two parapatric resident populations showed a small but fixed mtDNA haplotype difference. Together these data suggest low levels of genetic dispersal between foraging specialists and a pattern of genetic differentiation consistent with matrifocal population structure and small effective population size.

Alleles↗

PubMedDate not supplied

Genetic variation and population genetic structure in Trifolium pratense.

Trifolium pratense (red clover) is a short-lived herbaceous plant native to southeastern Europe and Asia Minor. Widel used in agriculture, T. pratense is cultivated as an annual, winter annual, or biennial. It blooms from mid-spring to early fall and is insect pollinated and self-incompatible. Seeds are mammal and bird dispersed. Naturalized populations of T. pratense occur along roadsides and in old fields as well as native grasslands. Allozyme diversity and population genetic structure were determined for nine populations of T. pratense. Results from 13 allozyme loci indicate that genetic diversity is higher and population divergence is lower than expected based on the life-history characteristics of the species. We conclude that the high levels of genetic diversity found within populations of T. pratense suggest that these are not newly established founder populations, and that the low levels of genetic divergence seen among populations are probably due to high rates of gene flow among populations as a result of seed and pollen movement.

Chi-Square Distribution↗

PubMed2006

The genetic structure of Australasian green turtles (Chelonia mydas): exploring the geographical scale of genetic exchange.

Ecological and genetic studies of marine turtles generally support the hypothesis of natal homing, but leave open the question of the geographical scale of genetic exchange and the capacity of turtles to shift breeding sites. Here we combine analyses of mitochondrial DNA (mtDNA) variation and recapture data to assess the geographical scale of individual breeding populations and the distribution of such populations through Australasia. We conducted multiscale assessments of mtDNA variation among 714 samples from 27 green turtle rookeries and of adult female dispersal among nesting sites in eastern Australia. Many of these rookeries are on shelves that were flooded by rising sea levels less than 10 000 years (c. 450 generations) ago. Analyses of sequence variation among the mtDNA control region revealed 25 haplotypes, and their frequency distributions indicated 17 genetically distinct breeding stocks (Management Units) consisting either of individual rookeries or groups of rookeries in general that are separated by more than 500 km. The population structure inferred from mtDNA was consistent with the scale of movements observed in long-term mark-recapture studies of east Australian rookeries. Phylogenetic analysis of the haplotypes revealed five clades with significant partitioning of sequence diversity (Phi = 68.4) between Pacific Ocean and Southeast Asian/Indian Ocean rookeries. Isolation by distance was indicated for rookeries separated by up to 2000 km but explained only 12% of the genetic structure. The emerging general picture is one of dynamic population structure influenced by the capacity of females to relocate among proximal breeding sites, although this may be conditional on large population sizes as existed historically across this region.

Animal Migration↗

PubMed2005

Assessment of the genetic causes of recessive childhood non-syndromic deafness in the UK - implications for genetic testing.

Approximately one in 2000 children is born with a genetic hearing impairment, mostly inherited as a non-syndromic, autosomal recessive trait, for which more than 30 different genes have been identified. Previous studies have shown that one of these genes, connexin 26 (GJB2), accounts for 30-60% of such deafness, but the relative contribution of the many other genes is not known, especially in the outbred UK population. This lack of knowledge hampers the development of diagnostic genetic services for deafness. In an effort to determine the molecular aetiology of deafness in the population, 142 sib pairs with early-onset, non-syndromic hearing impairment were recruited. Those in whom deafness could not be attributed to GJB2 mutations were investigated further for other mapped genes. The genetic basis of 55 cases (38.7%) was established, 33.1% being due to mutations in the GJB2 gene and 3.5% due to mutations in SLC26A4. None of the remaining 26 loci investigated made a significant contribution to deafness in a Caucasian population. We suggest that screening the GJB2 and SLC26A4 genes should form the basis of any genetic testing programme for childhood deafness and highlight a number of important issues for consideration and future work.

Cadherin Related Proteins↗

PubMed2006

Sharing the benefits of genetic resources: from biodiversity to human genetics.

Benefit sharing aims to achieve an equitable exchange between the granting of access to a genetic resource and the provision of compensation. The Convention on Biological Diversity (CBD), adopted at the 1992 Earth Summit in Rio de Janeiro, is the only international legal instrument setting out obligations for sharing the benefits derived from the use of biodiversity. The CBD excludes human genetic resources from its scope, however, this article considers whether it should be expanded to include those resources, so as to enable research subjects to claim a share of the benefits to be negotiated on a case-by-case basis. Our conclusion on this question is: 'No, the CBD should not be expanded to include human genetic resources.' There are essential differences between human and non-human genetic resources, and, in the context of research on humans, an essentially fair exchange model is already available between the health care industry and research subjects. Those who contribute to research should receive benefits in the form of accessible new health care products and services, suitable for local health needs and linked to economic prosperity (e.g. jobs). When this exchange model does not apply, as is often the case in developing countries, individually negotiated benefit sharing agreements between researchers and research subjects should not be used as 'window dressing'. Instead, national governments should focus their finances on the best economic investment they could make; the investment in population health and health research as outlined by the World Health Organization's Commission on Macroeconomics and Health; whilst international barriers to such spending need to be removed.

AIDS Vaccines↗

PubMed2006

Host genetics of Bordetella pertussis infection in mice: significance of Toll-like receptor 4 in genetic susceptibility and pathobiology.

The susceptibility to and the severity of Bordetella pertussis infections in infants and children varies widely, suggesting that genetic differences between individuals influence the course of infection. We have previously identified three novel loci that influence the severity of whooping cough by using recombinant congenic strains of mice: Bordetella pertussis susceptibility loci 1, 2, and 3 (Bps1, -2, and -3). Because these loci could not account for all genetic differences between mice, we extended our search for additional susceptibility loci. We therefore screened 11 inbred strains of mice for susceptibility to a pertussis infection after intranasal infection. Susceptibility was defined by the number of bacteria in the lungs, being indicative of the effect between the clearance and replication of bacteria. The most resistant (A/J) and the most susceptible (C3H/HeJ) strains were selected for further genetic and phenotypic characterization. The link between bacterial clearance and chromosomal location was investigated with 300 F2 mice, generated by crossing A/J and C3H/HeJ mice. We found a link between the delayed clearance of bacteria from the lung and a large part of chromosome 4 in F2 mice with a maximum log of the odds score of 33.6 at 65.4 Mb, which is the location of Tlr4. C3H/HeJ mice carry a functional mutation in the intracellular domain of Tlr4. This locus accounted for all detectable genetic differences between these strains. Compared to A/J mice, C3H/HeJ mice showed a delayed clearance of bacteria from the lung, a higher relative lung weight, and increased body weight loss. Splenocytes from infected C3H/HeJ mice produced almost no interleukin-1beta (IL-1beta) and tumor necrosis factor alpha (TNF-alpha) upon ex vivo restimulation with B. pertussis compared to A/J mice and also showed a delayed gamma interferon (IFN-gamma) production. TNF-alpha expression in the lungs 3 days after infection was increased fivefold compared to uninfected controls in A/J mice and was not affected in C3H/HeJ mice. In conclusion, Tlr4 is a major host factor explaining the differences in the course of infection between these inbred strains of mice. Functional Tlr4 is essential for an efficient IL-1-beta, TNF-alpha, and IFN-gamma response; efficient clearance of bacteria from the lung; and reduced lung pathology.

Animals↗

PubMedDate not supplied

Transient phenomena in learning and evolution: genetic assimilation and genetic redistribution.

Deacon has recently proposed that complexes of genes can be integrated into functional groups as a result of environmental changes that mask and unmask selection pressures. For example, many animals endogenously synthesize ascorbic acid (vitamin C), but anthropoid primates have only a nonfunctional version of the crucial gene for this pathway. It is hypothesized that the loss of functionality occurred in the evolutionary past when a diet rich in vitamin C masked the effect of the gene, and its loss effectively trapped the animals in a fruit-eating lifestyle. As a result, the complex of abilities that support this lifestyle were evolutionarily bound together, forming a multilocus complex. In this study we use evolutionary computation simulations to explore the thesis that masking and unmasking can transfer dependence from one set of genes to many sets, and thereby integrate the whole complex of genes. We used a framework based on Hinton and Nowlan's 1987 simulation of the Baldwin effect. Additional gene complexes and an environmental parameter were added to their basic model, and the fitness function extended. The simulation clearly demonstrates that the genetic redistribution effect can occur in silico, showing an initial advantage of endogenously synthesized vitamin C, followed by transfer of the fitness contribution to the complex of genes that together allow the acquisition of vitamin C from the environment. As is well known in the modeling community, the Baldwin effect only occurs in simulations when the population of agents is ''poised on the brink'' of discovering the genetically specified solution. Similarly, the redistribution effect occurs in simulations under specific initial conditions: too little vitamin C in the environment, and its synthesis it is never fully masked; too much vitamin C, and the abilities required to acquire it are not tightly integrated. The Baldwin effect has been hypothesized as a potential mechanism for developing language-specific adaptations like innate universal grammar and other highly modular capacities. We conclude with a discussion of the relevance of genetic assimilation and genetic redistribution to the evolution of language and other cognitive adaptations.

Biological Evolution↗

PubMed2003

In vivo studies on possible health consequences of genetically modified food and feed--with particular regard to ingredients consisting of genetically modified plant materials.

This synopsis reviews published in vivo studies on possible health consequences of genetically modified food and feed where the ingredients in question have consisted of genetically modified plant materials. The following, however, have not been taken into consideration:--ingredients consisting of genetically modified microorganisms or parts of animals/fish--ingredients produced by/from genetically modified organisms but without any DNA present--studies on consequences for the environment or biodiversity--in vitro studies or computer simulations. According to a Norwegian report "Gen-mat" (NOU 2000:29), and a more recent search in Medline and Citations Index, to our knowledge a total of ten studies have been published on the health effects of GM-foods and feeds. In this minireview the data made available in these published studies is discussed.

Animal Feed↗

PubMed2005

Mouse models and the genetics of diabetes: is there evidence for genetic overlap between type 1 and type 2 diabetes?

In humans, both type 1 and type 2 diabetes exemplify genetically heterogeneous complex diseases in which epigenetic factors contribute to underlying genetic susceptibility. Extended human pedigrees often show inheritance of both diabetes types. A common pathophysiological denominator in both disease forms is pancreatic beta-cell exposure to proinflammatory cytokines. Hence, it is intuitive that systemically expressed genes regulating beta-cell ability to withstand chronic diabetogenic stress may represent a component of shared susceptibility to both major disease forms. In this review, the authors assemble evidence from genetic experiments using animal models developing clearly distinct diabetes syndromes to inquire whether some degree of overlap in genes contributing susceptibility can be demonstrated. The conclusion is that although overlap exists in the pathophysiological insults leading to beta-cell destruction in the currently studied rodent models, the genetic bases seem quite distinct.

Animals↗

PubMed2005

Genetic evaluation using parentage information from genetic markers.

Genetic evaluation relies on pedigree information to account for the trait information on individuals and their relatives. Recording pedigrees may place unfavorable restrictions on the management of breeding populations, such as the use of single-sire mating groups and the observation of parturition. The use of DNA marker information is an alternative method to identify parents, but it is difficult to assign the parents unambiguously for all progeny in extensively farmed livestock without the use of very many markers. We present methods that use DNA information on parentage within a genetic evaluation system that allow for genotyping errors and for the parentage information to be incomplete, with probabilities assigned to possible parent pairs (i.e., fractional parentage assignment). Two of these methods use a computing strategy that circumvents the high memory requirements associated with the application of previous methods designed for use with fractional parentage assignment. This strategy has an additional advantage of allowing the same statistical models to be used in the evaluation as with recorded pedigrees. The use of DNA marker-based parentage for genetic evaluation is associated with lower genetic gain (at the same survival levels) than by using the true pedigree. This decrease in gain depends on a number of factors, including trait heritability and the DNA markers used. The methods we have described show how DNA marker information could be used to replace traditional pedigree recording.

Animals↗

PubMed2004

Genetic selection for health traits using producer-recorded data. II. Genetic correlations, disease probabilities, and relationships with existing traits.

The objectives of this study were to calculate genetic correlations between health traits that were recorded in on-farm herd management software programs and to assess relationships between these traits and other traits that are routinely evaluated in US dairy sires. Data consisted of 272,576 lactation incidence records for displaced abomasum (DA), ketosis (KET), mastitis (MAST), lameness (LAME), cystic ovaries (CYST), and metritis (MET) from 161,622 cows in 646 herds. These data were collected between January 1, 2001 and December 31, 2003 in herds using the Dairy Comp 305, DHI-Plus, or PCDART herd management software programs. Binary incidence data for all disorders were analyzed simultaneously using a multiple-trait threshold sire model that included random sire and herd-year-season of calving effects. Although data from multiple lactations were available for some animals, our genetic analysis included only first parity records due to concerns about selection bias and improper modeling of the covariance structure. Heritability estimates for the presence or absence of each disorder during first lactation were 0.14 for DA, 0.06 for KET, 0.09 for MAST, 0.03 for LAME, 0.04 for CYST, and 0.06 for MET. Estimated genetic correlations were 0.45 between DA and KET, 0.42 between KET and CYST, 0.20 between MAST and LAME, 0.19 between KET and LAME, 0.17 between DA and CYST, 0.17 between KET and LAME, 0.17 between KET and MET, and 0.16 between LAME and CYST. All other correlations were negligible. Correlations between predicted transmitting abilities for the aforementioned health traits and existing production, type, and fitness traits were low, though it must be noted that these estimates may have been biased by low reliability of the health trait evaluations. Based on results of this study, it appears that genetic selection for health disorders recorded in on-farm software programs can be effective. These traits can be incorporated into selection indices directly, or they can be combined into composite traits, such as "reproductive disorders", "metabolic disorders", or "early lactation disorders".

Abomasum↗

PubMed2000

Genetic syndromes and genetic tests in colorectal cancer.

Our understanding of the biology of colon cancer has matured to the point that it is a useful general paradigm for understanding solid tumor development. Recent advances provide insight into the genetic alterations underlying the development of colon cancer. These insights provide unique opportunities for genetic testing in predisposed, asymptomatic patients that can direct screening efforts and their clinical management. This review examines several inherited colon cancer predispositions, well described clinically for a century, that are now amenable to genetic testing. Additional discussion focuses on colon cancer predisposition traits that occur with high frequency but low penetrance characteristics. Finally, genetic tests for tumor markers that potentially have prognostic or therapeutic implications are reviewed.

Adenomatous Polyposis Coli↗

PubMed1998

Genetic studies of spondylarthropathies. French Spondylarthropathy Genetic Study Group.

Influence of genetic factors in the spondylarthropathies has been clearly established. The goal of familial studies is to determine the respective weight of genetic factors and to discover new genes involved in the pathogenesis of spondylarthropathies. Among these factors, the HLA region appears to be of most importance. We are currently conducting a prospective multicenter French study aimed at collecting multiplex families of spondylarthropathies. We present preliminary results obtained from nearly 300 individuals corresponding to the first 20 collected families. Through the screening procedure, we have identified 57 patients of an average age of 42 and a mean age at onset of 23. The relative risk of spondylarthropathy in males as compared with females is 1.03. HLA typing revealed the presence of HLA-B27 in all affected patients from 19 of the 20 families, whereas in the last family, the two affected individuals shared the HLA-B14 allele. Study of HLA class I allelic transmission confirmed a strong association of spondylarthropathy with HLA-B27 (p < 10(-9)). A weaker association was found with HLA-A28, HLA-C1 and HLA-C2, probably secondary to linkage disequilibrium between these alleles and HLA-B27. Study of HLA class II region indicated a possible protective effect of HLA-DR2 and an influence due to the presence of HLA-DR14. The risk to develop spondylarthropathy in HLA-B27+ relatives of patients decreased very rapidly in respect to the genetic distance, suggesting the genetic contribution of at least one other important gene distinct from the HLA region. These data encourage us to carry on a systematic screening of the whole human genome to discover implicated genes.

Adult↗

PubMed2001

[Genetic structure and intraspecific genetic polymorphisms in natural populations of Psathyrostachys huashanica].

Psathyrostachys huashanica Keng, which is endemic to China, only distributes in Mt. Hua of Shaanxi Province. 5 enzyme systems coding 13 loci were analyzed in 13 subpopulations of P. huashanica from Mt. Hua. Allozyme analysis showed that high genetic variability and clonal diversity existed in the species. Mean proportions of polymorphic loci (95% criterion), average number of alleles per locus, and mean expected heterozygosity were 69.2%, 1.8 and 0.344, respectively. Simpson index was 0.998. A negative species mean fixation indice (-0.252) indicates that there is a considerable excess of heterozygotes compared to the expected proportions of heterozygote loci. Mean genetic distance among populations was 0.049 (range: 0-0.139), and 91% of the genetic variation resided within populations. Gene flow estimated by indirect methods was 2.77, which was much lower than the Nm value (5.24) of anemophytes. This suggested that gene flow of P. huashanica might be in a critical level, and genetic differentiation might occur in natural population of this species.

Genetic Variation↗

PubMed2001

RAPD and ISSR fingerprints as useful genetic markers for analysis of genetic diversity, varietal identification, and phylogenetic relationships in peanut (Arachis hypogaea) cultivars and wild species.

Abstract: Twenty-one random and 29 SSR primers were used to assess genetic variation and interrelationships among subspecies and botanical varieties of cultivated peanut, Arachis hypogaea (2n = 4x = 40), and phylogenetic relationships among cultivated peanut and wild species of the genus Arachis. In contrast with the previous generalization that peanut accessions lack genetic variation, both random and SSR primers revealed 42.7 and 54.4% polymorphism, respectively, among 220 and 124 genetic loci amplified from 13 accessions. Moreover, the dendrograms based on RAPD, ISSR, and RAPD + ISSR data precisely organized the five botanical varieties of the two subspecies into five clusters. One SSR primer was identified that could distinguish all the accessions analysed within a variety. Although the polymorphic index content varied from 0.1 to 0.5 for both ISSR and RAPD markers, primer index values were substantially higher for RAPD primers (0.35-4.65) than for SSR primers (0.35-1.73). It was possible to identify accessions, particularly those of divergent origins, by RAPD and (or) ISSR fingerprints. Based on these results, marker-based genetic improvement in A. hypogaea appears possible. None of the 486 RAPD and 330 ISSR amplification products were found to be commonly shared among 13 species of section Arachis and one species each of sections Heteranthae, Rhizomatosae, and Procumbentes. Dendrograms constructed from RAPD, ISSR, and RAPD + ISSR data showed overall similar topologies. They could be resolved into four groups corresponding to the species grouped in four taxonomic sections. The present results strongly support the view that Arachis monticola (2n = 4x = 40) and A. hypogaea are very closely related, and indicate that A. villosa and A. ipaensis are the diploid wild progenitors of these tetraploid species.

Arachis↗

PubMed2001

Protecting genetic materials and genetic information: a case study of Guthrie Cards in Victoria.

The authors are privileged to have been provided with correspondence about a dispute over the ongoing storage of genetic material (as Guthrie Cards) in Victoria. The correspondence details confusion over the roles of government and the private sector service provider in accounting for the storage, use and destruction of these stored genetic materials collected as part of a government public health program. The purpose in publishing this account is to highlight the present inadequacies in current practices and the ongoing potential for a crisis in the management of collected genetic materials through a lack of appropriate regulation, transparency and accountability. The article suggests measures to remedy some of the existing inadequacies in contractual arrangements and recommends that the government retain ownership and control of both the genetic materials and the derived information to ensure some accountability in the present legal environment.

Contract Services↗