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Biomedical subjects

M Frisch

Publications and source records attributed to M Frisch.

At least 19 recordsLinked to original sources

Genetic drift and selection effects of modified recurrent full-sib selection programs in two F2 populations of European flint maize.

Selection response of a modified recurrent full-sib (FS) selection scheme conducted in two European flint F(2) maize (Zea mays L.) populations was re-evaluated. Our objectives were to (1) determine the selection response for per se and testcross performance in both populations and (2) separate genetic effects due to selection from those due to random genetic drift. Modified recurrent FS selection was conducted at three locations using an effective population size N(e) = 32 and a selection rate of 25% for a selection index, based on grain yield and grain moisture. Recombination was performed according to a pseudo-factorial mating scheme. Selection response was assessed using a population diallel including the source population and advanced selection cycles, as well as testcrosses with unrelated inbred line testers and the parental F(1) generation. Selection response per cycle was significant for grain yield and grain moisture in both populations. Effects of random genetic drift caused only a small reduction in the selection response. No significant selection response was observed for testcrosses, suggesting that for heterotic traits, such as grain yield, a high frequency of favorable alleles in the elite tester masked the effects of genes segregating in the populations. We conclude that our modified recurrent FS selection is an alternative to other commonly applied intrapopulation recurrent selection schemes, and some of its features may also be useful for increasing the efficiency of interpopulation recurrent selection programs.

Crosses, Genetic↗

Prediction of single-cross hybrid performance for grain yield and grain dry matter content in maize using AFLP markers associated with QTL.

Prediction methods to identify single-cross hybrids with superior yield performance have the potential to greatly improve the efficiency of commercial maize (Zea mays L.) hybrid breeding programs. Our objectives were to (1) identify marker loci associated with quantitative trait loci for hybrid performance or specific combining ability (SCA) in maize, (2) compare hybrid performance prediction by genotypic value estimates with that based on general combining ability (GCA) estimates, and (3) investigate a newly proposed combination of the GCA model with SCA predictions from genotypic value estimates. A total of 270 hybrids was evaluated for grain yield and grain dry matter content in four Dent x Flint factorial mating experiments, their parental inbred lines were genotyped with 20 AFLP primer-enzyme combinations. Markers associated significantly with hybrid performance and SCA were identified, genotypic values and SCA effects were estimated, and four hybrid performance prediction approaches were evaluated. For grain yield, between 38 and 98 significant markers were identified for hybrid performance and between zero and five for SCA. Estimates of prediction efficiency (R (2)) ranged from 0.46 to 0.86 for grain yield and from 0.59 to 0.96 for grain dry matter content. Models enhancing the GCA approach with SCA estimates resulted in the highest prediction efficiency if the SCA to GCA ratio was high. We conclude that it is advantageous for prediction of single-cross hybrids to enhance a GCA-based model with SCA effects estimated from molecular marker data, if SCA variances are of similar or larger importance as GCA variances.

Biomass↗

Comparison of linkage maps from F2 and three times intermated generations in two populations of European flint maize (Zea mays L.).

Intermated mapping populations are expected to result in high mapping resolution for tightly linked loci. The objectives of our study were to (1) investigate the consequences of constructing linkage maps from intermated populations using mapping methods developed for F(2) populations, (2) compare linkage maps constructed from intermated populations (F(2)Syn3) with maps generated from corresponding F(2) and F(3) base populations, and (3) investigate the advantages of intermated mapping populations for applications in plant breeding programs. We constructed linkage maps for two European flint maize populations (A x B, C x D) by mapping 105 SSR markers in generations F(2) and F(2)Syn3 of population A x B, and 102 SSR markers in generations F(3) and F(2)Syn3 of population C x D. Maps for F(2)Syn3 were constructed with mapping methods for F(2) populations (Map A) as well as with those specifically developed for intermated populations (Map B). Both methods relate map distances to recombination frequencies in a single meiosis and, therefore, did not show a map expansion in F(2)Syn3 compared with maps constructed from the respective F(2) or F(3) base populations. Map A and B differed considerably, presumably because of theoretical shortcomings of Map A. Since loosely linked markers could not unambiguously be mapped in the F(2)Syn3 populations, they may hamper the construction of linkage maps from intermated populations.

Chromosome Mapping↗

Grouping of accessions of Mexican races of maize revisited with SSR markers.

Mexican races of maize (Zea mays L.) represent a valuable genetic resource for breeding and genetic surveys. We applied simple sequence repeat (SSR) markers to characterize 25 accessions of races of maize from Mexico. Our objectives were to (1) study the molecular genetic diversity within and among these accessions and (2) examine their relationships as assumed previously on the basis of morphological data. A total of 497 individuals were fingerprinted with 25 SSR markers. We observed a high total number of alleles (7.84 alleles per locus) and total gene diversity (0.61), confirming the broad genetic base of the maize races from Mexico. In addition, the accessions were grouped into distinct racial complexes on the basis of a model-based clustering approach. The principal coordinate analyses of the four Modern Incipient hybrids corroborated the proposed parental races of Chalqueño, Cónico Norteño, Celaya, and Bolita on the basis of the morphological data. Consequently, for some of the accessions, hybridizations provide a clue that can further be used to explain the associations among the Mexican races of maize.

Alleles↗

Trends in population parameters and best linear unbiased prediction of progeny performance in a European F(2) maize population under modified recurrent full-sib selection.

Recurrent selection is a cyclic breeding procedure designed to improve the mean of a population for the trait(s) under selection. Starting from an F(2) population of European flint maize (Zea mays L.) intermated for three generations, we conducted seven cycles of a modified recurrent full-sib (FS) selection scheme. The objectives of our study were to (1) monitor trends across selection cycles in the estimates of the population mean, additive and dominance variances, (2) compare predicted and realized selection responses, and (3) investigate the usefulness of best linear unbiased prediction (BLUP) of progeny performance under the recurrent FS selection scheme applied. Recurrent FS selection was conducted at three locations using a selection rate of 25% for a selection index, based on grain yield and grain moisture. Recombination was performed according to a pseudo-factorial mating scheme, where the selected FS families were divided into an upper-ranking group of parents mated to the lower-ranking group. Variance components were estimated with restricted maximum likelihood. Average grain yield increased 9.1% per cycle, average grain moisture decreased 1.1% per cycle, and the selection index increased 11.2% per cycle. For the three traits we observed, no significant changes in additive and dominance variances occurred, suggesting future selection response at or near current rates of progress. Predictions of FS family performance in Cn+1 based on mean performance of parental FS families in Cn were of equal or higher precision as those based on the mean additive genetic BLUP of their parents, and corresponding correlations were of moderate size only for grain moisture. The significant increase in grain yield combined with the decrease in grain moisture suggest that the F(2) source population with use of a pseudo-factorial mating scheme is an appealing alternative to other types of source materials and random mating schemes commonly used in recurrent selection.

Breeding↗

Identification of essentially derived varieties with molecular markers: an approach based on statistical test theory and computer simulations.

Genetic similarities (GS) based on molecular markers have been proposed as a tool for identification of essentially derived varieties (EDVs). Nevertheless, scientifically reliable criteria for discrimination of EDVs and independently derived varieties with GS estimates are scanty, and implementation into practical breeding has not yet taken place. Our objectives were to (1) assess the influence of chromosome number and length, marker density, and distribution, as well as the degree of polymorphism between the parental inbreds on the distribution of GS between parental inbreds and their progenies [GS(P1,O)] derived from F2 and different backcross populations and (2) evaluate these factors with regard to the power for distinguishing F2- versus BC1- and BC1- versus BC2-derived lines with molecular markers. We developed an approach based on statistical test theory for the identification of EDVs with molecular markers. Standard deviations and overlaps of distributions of GS(P1,O) of F2-, BC1-, and BC2-derived lines were smaller with (1) increasing chromosome number and length, (2) increasing marker density, and (3) uniformly instead of randomly distributed markers, approaching a lower boundary determined by the genetic parameters. The degree of polymorphism between the parental inbreds influenced the power only if the remaining number of polymorphic markers was low. Furthermore, suggestions are made for (1) determining the number of markers required to ascertain a given power and (2) EDV identification procedures.

Computer Simulation↗

MatInspector and beyond: promoter analysis based on transcription factor binding sites.

MOTIVATION: Promoter analysis is an essential step on the way to identify regulatory networks. A prerequisite for successful promoter analysis is the prediction of potential transcription factor binding sites (TFBS) with reasonable accuracy. The next steps in promoter analysis can be tackled only with reliable predictions, e.g. finding phylogenetically conserved patterns or identifying higher order combinations of sites in promoters of co-regulated genes. RESULTS: We present a new version of the program MatInspector that identifies TFBS in nucleotide sequences using a large library of weight matrices. By introducing a matrix family concept, optimized thresholds, and comparative analysis, the enhanced program produces concise results avoiding redundant and false-positive matches. We describe a number of programs based on MatInspector allowing in-depth promoter analysis (DiAlignTF, FrameWorker) and targeted design of regulatory sequences (SequenceShaper).

Algorithms↗

Duplicate marker loci can result in incorrect locus orders on linkage maps.

Genetic linkage maps, constructed from multi-locus recombination data, are the basis for many applications of molecular markers. For the successful employment of a linkage map, it is essential that the linear order of loci on a chromosome is correct. The objectives of this theoretical study were to (1) investigate the occurrence of incorrect locus orders caused by duplicate marker loci, (2) develop a statistical test for the detection of duplicate markers, and (3) discuss the implications for practical applications of linkage maps. We derived conditions, under which incorrect locus orders do or do not occur with duplicate marker loci for the general case of n markers on a chromosome in a BC(1) mapping population. We further illustrated these conditions numerically for the special case of four markers. On the basis of the extent of segregation distortion, an exact test for the presence of duplicate marker loci was suggested and its power was investigated numerically. Incorrect locus orders caused by duplicate marker loci can (1) negatively affect the assignment of target genes to chromosome regions in a map-based cloning experiment, (2) hinder indirect selection for a favorable allele at a quantitative trait locus, and (3) decrease the efficiency of reducing the length of the chromosome segment attached to a target gene in marker-assisted backcrossing.

Chromosome Mapping↗

Use of SSRs for establishing heterotic groups in subtropical maize.

Heterotic groups and patterns are of fundamental importance in hybrid breeding. The objectives of our research were to: (1) investigate the relationship of simple sequence repeats (SSR) based genetic distances between populations and panmictic midparent heterosis (PMPH) in a broad range of CIMMYT maize germplasm, (2) evaluate the usefulness of SSR markers for defining heterotic groups and patterns in subtropical germplasm, and (3) examine applications of SSR markers for broadening heterotic groups by systematic introgression of other germplasm. Published data of two diallels and one factorial evaluated for grain yield were re-analyzed to calculate the PMPH in population hybrids. Additionally, 20 pools and populations widely used in CIMMYT's breeding program were assayed with 83 SSR markers covering the entire maize genome. Correlations of squared modified Roger's distance (MRD(2)) and PMPH were mostly positive and significant, but adaption problems caused deviations in some cases. For intermediate- and early-maturity subtropical germplasm, two heterotic groups could be suggested consisting of a flint and dent composite. We concluded that the relationships between the populations obtained by SSR analyses are in excellent agreement with pedigree information. SSR markers are a valuable complementation to field trials for identifying heterotic groups and can be used to introgress exotic germplasm systematically.

Alleles↗

Appendectomy in adulthood and the risk of inflammatory bowel diseases.

BACKGROUND: There is controversy as to whether appendectomy protects against the development of ulcerative colitis, but the possible impact of appendectomies performed in adulthood has not been systematically investigated. METHODS: We conducted a large case-control study based on inpatient records from Veterans Affairs hospitals in the United States for the period 1969-96. We identified 6,172 male patients with ulcerative colitis (age range 19-101 years, mean 57.4 years) and 4,498 male patients with Crohn disease (age range 18-99 years, mean 52.9 years). Each of these case patients was individually age- and race-matched to five other male veterans without recorded history of inflammatory bowel disease. We compared records of prior appendectomies in adulthood for the matched case-control sets using conditional logistic regression. RESULTS: Overall, both ulcerative colitis (odds ratio (OR) = 1.6, 95% confidence interval (CI): 1.3-2.1) and Crohn disease (OR = 2.5, 95% CI: 2.0-3.3) were significantly and positively associated with history of appendectomy in adulthood. However, risks were not increased at intervals of 15 years or more between appendectomy and inflammatory bowel disease (ulcerative colitis: OR = 0.9, 95% CI: 0.4-2.1; Crohn disease: OR = 1.2. 95% CI: 0.5-2.5). CONCLUSIONS: The elevated risk of inflammatory bowel disease, notably Crohn disease, after appendectomy probably reflects differential diagnostic difficulties in patients with abdominal pain. Appendectomy carried out during adulthood seems not to confer protection against ulcerative colitis.

Adolescent↗

Cancers associated with Kaposi's sarcoma (KS) in AIDS: a link between KS herpesvirus and immunoblastic lymphoma.

Kaposi's sarcoma (KS), common among persons with acquired immunodeficiency syndrome (AIDS), is caused by KS herpesvirus (KSHV) but whether KSHV causes other malignancies is uncertain. Using linked United States AIDS and cancer registries, we measured the incidence of specific malignancies in persons with AIDS (4-27 months after AIDS onset). We identified associations with KSHV by calculating a relative risk: cancer incidence in persons with KS (all were KSHV-infected) divided by incidence in persons without KS. Using Poisson regression, relative risks were adjusted for human immunodeficiency virus risk group, gender, age, race, and calendar year. We included 189 159 subjects (26 972 with KS). Immunoblastic lymphoma was significantly associated with KS (506 cases; relative risks: unadjusted 2.44, 95%CI 2.00-2.96, adjusted 1.58, 95%CI 1.29-1.93). Only one immunoblastic lymphoma had pleura as primary site. None of 37 other specified malignancies (other non-Hodgkin lymphomas, haematological malignancies, solid tumours) was significantly associated with KS. In summary, the association of immunoblastic lymphoma with KS was specific among examined malignancies and remained significant after statistical adjustment. Our findings, and the previously demonstrated presence of KSHV in the histologically related primary effusion lymphoma, suggest that KSHV is involved in the pathogenesis of some immunoblastic lymphomas.

Acquired Immunodeficiency Syndrome↗

Incidence of Hodgkin's disease in Nordic countries.

We analysed age and sex-specific trends in the incidence of Hodgkin's lymphoma in Denmark, Sweden, Norway, and Finland during 1978-97. The incidence of Hodgkin's lymphoma decreased significantly in all age groups above 40 years; there was a significant increase in incidence among adolescents and young adults. This increase occurred primarily for Hodgkin's lymphoma of the nodular sclerosis subtype. These observations emphasise the need to identify risk factors for Hodgkin's lymphoma in the young.

Adolescent↗

Association of cancer with AIDS-related immunosuppression in adults.

CONTEXT: Large-scale studies are needed to determine if cancers other than Kaposi sarcoma, non-Hodgkin lymphoma, and cervical cancer occur in excess in persons with human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS). OBJECTIVES: To examine the general cancer pattern among adults with HIV/AIDS and to distinguish immunosuppression-associated cancers from other cancers that may occur in excess among persons with HIV/AIDS. DESIGN, SETTING, AND SUBJECTS: Analysis of linked population-based AIDS and cancer registry data from 11 geographically diverse areas in the United States, including 302 834 adults aged 15 to 69 years with HIV/AIDS. The period of study varied by registry between 1978 and 1996. MAIN OUTCOME MEASURE: Relative risks (RRs) of cancers, calculated by dividing the number of observed cancer cases by the number expected based on contemporaneous population-based incidence rates. We defined cancers potentially influenced by immunosuppression by 3 criteria: (1) elevated overall RR in the period from 60 months before to 27 months after AIDS; (2) elevated RR in the 4- to 27-month post-AIDS period; and (3) increasing trend in RR from before to after AIDS onset. RESULTS: Expected excesses were observed for the AIDS-defining cancers, but non-AIDS-defining cancers also occurred in statistically significant excess (n = 4422; overall RR, 2.7; 95% confidence interval [CI], 2.7-2.8). Of individual cancers, only Hodgkin disease (n = 612; RR, 11.5; 95% CI, 10.6-12.5), particularly of the mixed cellularity (n = 217; RR, 18.3; 95% CI, 15.9-20.9) and lymphocytic depletion (n = 36; RR, 35.3; 95% CI, 24.7-48.8) subtypes; lung cancer (n = 808; RR, 4.5; 95% CI, 4.2-4.8); penile cancer (n = 14; RR, 3.9; 95% CI, 2.1-6.5); soft tissue malignancies (n = 78; RR, 3.3; 95% CI, 2.6-4.1); lip cancer (n = 20; RR, 3.1; 95% CI, 1.9-4.8); and testicular seminoma (n = 115; RR, 2.0; 95% CI, 1.7-2.4) met all 3 criteria for potential association with immunosuppression. CONCLUSION: Although occurring in overall excess, most non-AIDS-defining cancers do not appear to be influenced by the advancing immunosuppression associated with HIV disease progression. Some cancers that met our criteria for potential association with immunosuppression may have occurred in excess in persons with HIV/AIDS because of heavy smoking (lung cancer), frequent exposure to human papillomavirus (penile cancer), or inaccurately recorded cases of Kaposi sarcoma (soft tissue malignancies) in these persons. However, Hodgkin disease, notably of the mixed cellularity and lymphocytic depletion subtypes, and possibly lip cancer and testicular seminoma may be genuinely influenced by immunosuppression.

Adolescent↗

Risk of T-cell lymphomas in persons with AIDS.

Lymphomas in persons with AIDS are mostly B-cell types, but T-cell lymphomas have also been reported. We examined T-cell lymphoma risk in the 2-year period after AIDS onset by linking 302,834 adults with AIDS to cancer registry data. Of 6,788 cases of non-Hodgkin's lymphoma (NHL) with specified histologies, 96 (1.4%) were T-cell lymphomas. Assessment was based on clinical diagnosis and histology because T-cell marker data were inadequate, but when present, marker data supported the T-cell diagnosis. The relative risk of T-cell lymphoma, estimated by standardized incidence ratio, was 15.0 (95% confidence interval: 10.0--21.7). Risks were increased for all subtypes, including mycosis fungoides, peripheral lymphomas, cutaneous lymphomas, and adult T-cell leukemia/lymphoma (ATLL). HIV-related immunodeficiency could be important, but differences between the population developing AIDS and the general population (e. g., immigration from the Caribbean region for ATLL) might independently increase T-cell lymphoma risk.

Acquired Immunodeficiency Syndrome↗

Central activation by histamine-induced itch: analogies to pain processing: a correlational analysis of O-15 H2O positron emission tomography studies.

The aim of this study was to identify the functional cerebral network involved in the central processing of itch and to detect analogies and differences to previously identified cerebral activation patterns triggered by painful noxious stimuli. Repeated positron emission tomography regional cerebral blood flow (rCBF) measurements using O15-labeled water were performed in six healthy right-handed male subjects (mean age 32 +/- 2 years). Each subject underwent 12 sequential rCBF measurements. In all subjects a standardized skin prick test was performed on the right forearm 2 min before each rCBF measurement. For activation, histamine was applied in nine tests in logarithmically increasing concentrations from 0.03 to 8%. Three tests were performed with isotonic saline solution serving as a control condition. Itch intensity and unpleasantness were registered with a visual analogue scale during each test. Subtraction analysis between activation and control conditions as well as correlation analysis with covariates were performed. Itch induced a significant activation in the predominantly contralateral somatosensory cortex and in the ipsilateral and contralateral motor areas (supplementary motor area (SMA), premotor cortex, primary motor cortex). Additional significant activations were found in the prefrontal cortex and the cingulate gyrus, but not in subcortical structures nor in the secondary somatosensory cortex. In correlation analyses, several cortical areas showed a graded increase in rCBF with the logarithm of the histamine concentration (bilateral sensorimotor areas and cingulate cortex; contralateral insula, superior temporal cortex and prefrontal cortex) and with itch unpleasantness (contralateral sensorimotor cortex, prefrontal cortex and posterior insula; ipsilateral SMA). Induction of itch results in the activation of a distributed cerebral network. Itch and pain seem to share common pathways (a medial and a lateral processing pathway and a strong projection to the motor system). In contrast to pain activation studies, no subcortical (i.e. thalamic) activations were detected and correlation analyses suggest differences in subjective processing of the two sensations.

Adult↗

Associations between smoking and adenocarcinomas and squamous cell carcinomas of the uterine cervix (United States).

OBJECTIVES: Few studies of smoking and cervical carcinoma have addressed the rare cervical adenocarcinomas or used DNA-based tests to control for human papillomavirus (HPV) infection. METHODS: This multicenter case-control study included 124 adenocarcinoma cases, 307 community controls (matched on age, race, and residence to adenocarcinoma cases), and 139 squamous carcinoma cases (matched on age, diagnosis date, clinic, and disease stage to adenocarcinoma cases). Participants completed risk-factor interviews and volunteered cervical samples for PCR-based HPV testing. Polychotomous logistic regression generated adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for both histologic types. RESULTS: Eighteen percent of adenocarcinoma cases, 43% of squamous carcinoma cases, and 22% of controls were current smokers. After control for HPV and other questionnaire data, adenocarcinomas were consistently inversely associated with smoking (e.g. current: OR = 0.6, 95% CI 0.3-1.1; > or = 1 pack per day: OR = 0.7, 95% CI 0.4-1.3), while squamous carcinomas were positively associated with smoking (e.g. current: OR = 1.6, 95% CI 0.9-2.9; > or = 1 pack per day: OR = 1.8, 95% CI 1.0-3.3). Results in analyses restricted to HPV-positive controls were similar. CONCLUSION: Smoking has opposite associations with cervical adenocarcinomas and squamous carcinomas. Although both histologic types are caused by HPV and arise in the cervix, etiologic co-factors for these tumors may differ.

Adenocarcinoma↗