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Genetic analysis of three loci homologous to human G9a: evidence for linkage of a class III gene with the chicken MHC.

The cDNA clones of two newly discovered genes in the class III region of the human major histocompatibility complex (MHC) were hybridized to chicken DNA. One of these cDNA clones (pG9a-4C7), which detects the single-copy human G9a (BAT8) gene, gave a repeatable restriction pattern. This heterologous cDNA clone was used to detect and map three different PstI restriction fragment length polymorphisms among the two internationally recognized chicken reference populations. Two of the loci were unlinked to previously mapped markers, but one polymorphism cosegregated with the EaB locus in the Compton mapping population. These results provide evidence that some genes of the mammalian class III region, such as G9a, may be linked to the MHC in chickens.

Animals↗

Comprehensive genetic analyses reveal differential expression of spot blotch resistance in four populations of barley.

Spot blotch, caused by Cochliobolus sativus, is an important disease of barley in the Upper Midwest region of the United States. The resistance of six-rowed malting cultivars like Morex has remained effective for over 40 years and is considered durable. Previous research on Steptoe/Morex (S/M), a 6x6-rowed doubled haploid (DH) population, showed that seedling resistance is controlled by a single gene (Rcs5) on chromosome 1(7H) and adult plant resistance by two quantitative trait loci (QTL): one of the major effect on chromosome 5(1H) explaining 62% of the phenotypic variance and a second of minor effect on chromosome 1(7H) explaining 9% of the phenotypic variance. To corroborate these results in a 2x6-rowed DH population, composite interval mapping (CIM) was performed on Harrington/Morex (H/M). As in the S/M population, a single major gene (presumably Rcs5) on chromosome 1(7H) conferred resistance at the seedling stage. However, at the adult plant stage, the results were markedly different as no chromosome 5(1H) effect whatsoever was detected. Instead, a QTL at or near Rcs5 on chromosome 1(7H) explained nearly all of the phenotypic variance (75%) for disease severity. To determine whether this result might be due to the genetic background of the two-rowed susceptible parent Harrington, we analyzed another DH population that included the same resistance donor (Morex) and another six-rowed susceptible cultivar Dicktoo (D/M). Three QTL conferred seedling resistance in the D/M population: one near Rcs5 on chromosome 1(7H) explaining 30%, a second near the centromere of chromosome 1(7H) explaining 9%, and a third on the short arm of chromosome 3(3H) explaining 19% of the phenotypic variation. As in the H/M population, no chromosome 5(1H) QTL was detected for adult plant resistance in the D/M population. Instead, three QTL on other chromosomes explained most of the variation: one on the short arm of chromosome 3(3H) explaining 36%, a second on the long arm of chromosome 3(3H) explaining 11%, and a third at or near Rcs5 on chromosome 1(7H) explaining 20% of the phenotypic variation. These data demonstrate the complexity of expression of spot blotch resistance in different populations and have important implications in breeding for durable resistance.

Ascomycota↗

Chromosomal mapping by means of mutational induction in synchronous populations of Streptococcus faecalis.

Stonehill, E. H. (Sloan-Kettering Institute for Cancer Research, New York, N.Y. and Dorris J. Hutchison. Chromosomal mapping by means of mutational induction in synchronous populations of Streptococcus faecalis. J. Bacteriol. 92:136-143. 1966.-A new method for mapping genetic loci on the bacterial chromosome, based on the linear progression of the deoxyribonucleic acid-replicating enzyme (replicase) in synchronous cultures of Streptococcus faecalis, is described. Ultraviolet irradiation was used to induce mutations to drug and to bacteriophage resistance at various intervals during the progress of the replicase along the chromosome. The time of duplication of the gene in synchronous populations was determined from reductions in the rates of irradiation-induced mutation. After the replication of various genes, the rates fell to half their former values. The resulting data made possible the construction of a 1-hr time-map indicating the sequence of replication of five genes in S. faecalis.

Cell Division↗

Comparative mapping of the chicken genome using the East Lansing reference population.

The annotation of known genes on linkage maps provides an informative framework for synteny mapping. In comparative gene mapping, conserved synteny is broadly defined as groups of two or more linked markers that are also linked in two or more species. Although many anonymous markers have been placed on the chicken genome map, locating known genes will augment the number of conserved syntenic groups and consolidate linkage groups. In this report, 21 additional genes have been assigned to linkage groups or chromosomes; five syntenic groups were identified. Ultimately, conserved syntenic groups may help to pinpoint important quantitative trait loci.

Animals↗

Linkage disequilibrium: ancient history drives the new genetics.

This brief review provides a summary of the biological causes of genetic association between tightly linked markers--termed linkage disequilibrium--and unlinked markers--termed population structure. We also review the utility of linkage disequilibrium data in gene mapping in isolated populations, in the estimation of recombination rates and in studying the history of particular alleles, including the detection of natural selection. We discuss current understanding of the extent and patterns of linkage disequilibrium in the genome, and its promise for genetic association studies in complex disease. Finally, we highlight the importance of using appropriate statistical procedures, such as the false discovery rate, to maximize the chances of success in large scale association studies.

Chromosome Mapping↗

QTL Express: mapping quantitative trait loci in simple and complex pedigrees.

QTL Express is the first application for Quantitative Trait Locus (QTL) mapping in outbred populations with a web-based user interface. User input of three files containing a marker map, trait data and marker genotypes allows mapping of single or multiple QTL by the regression approach, with the option to perform permutation or bootstrap tests.

Chromosome Mapping↗

A new locus for coeliac disease mapped to chromosome 15 in a population isolate.

Coeliac disease is a common multifactorial disease with a strong genetic component, which is not entirely explained by the HLA association. Four previous whole-genome screens have produced somewhat inconsistent results suggesting genetic heterogeneity. We attempted to overcome this problem by performing a genome-wide scan in a Finnish sub-population, expected to be more homogeneous than the general population of Finland. The families in our study originate from the northeastern part of Finland, the Koilliskaira region, which has been relatively isolated since its founding in the 16th century. Genealogical studies have confirmed that the families share a common ancestor in the 16th century. Nine families with altogether 23 patients were genotyped for 399 microsatellite markers and the data were analysed with parametric linkage analysis using two dominant and one recessive model. A region on chromosome 15q11-q13 was implicated with a LOD score of 3.14 using a highly penetrant dominant model. Addition of more markers and one more sib-pair increased the LOD score to 3.74. This result gives preliminary evidence for existence of a susceptibility factor in this chromosomal region.

Celiac Disease↗

Mixture models and disease mapping.

The analysis and recognition of disease clustering in space and its representation on a map is one of the oldest problems in epidemiology. Some traditional methods of constructing such a map are presented. An alternative approach using mixture models to identify population heterogeneity and map construction within an empirical Bayes framework is described. For hepatitis B data from Berlin in 1989, a map is presented and the different methods are evaluated using a parametric bootstrap approach.

Bayes Theorem↗

Use of body surface maps to identify vessel site of coronary occlusion.

Body surface mapping is more sensitive than conventional electrocardiography for various cardiac regions. In this pilot study, the authors used isoarea maps of early (the first 40 msec), late (the next 40 msec), and total (early and late, or 80 msec) QRS complex to determine the site of coronary occlusion in patients with known coronary artery disease. In the absence of conduction abnormalities or axis deviation in the 12-lead electrocardiogram, isoarea body surface map data of single-vessel disease were unremarkable; however, isoarea departure maps (ie, the average isoarea map of normal population extracted from the study group) were characteristic. Early departure isoarea maps were revealing in all three coronary artery disease groups, with a large negative potential noted over the anterior thorax, midline for the right coronary artery, left anterior in the left anterior descending artery, and further laterally for the left circumflex artery groups. The late isoarea departure map was distinct in the left circumflex artery group with positive potentials leftward, anterolaterally. Discriminant function analysis revealed a high predictive accuracy for the left anterior descending artery group. Thus, isoarea departure maps hold promise for predicting the site of coronary occlusion in this training set of patients.

Adult↗

Molecular mapping of genes for resistance to the bean pod weevil (Apion godmani Wagner) in common bean.

The bean pod weevil (Apion godmani Wagner) is a serious insect pest of common beans (Phaseolus vulgaris L.) grown in Mexico and Central America that is best controlled by host-plant resistance available in Durango or Jalisco genotypes such as J-117. Given unreliable infestation by the insect, the use of marker-assisted selection is desirable. In the present study, we developed a set of nine molecular markers for Apion resistance and mapped them to loci on chromosomes 2, 3, 4 and 6 (linkage groups b01, b08, b07 and b11, respectively) based on genetic analysis of an F (5:10) susceptible x resistant recombinant inbred line population (Jamapa x J-117) and two reference mapping populations (DOR364 x G19833 and BAT93 x JaloEEP558) for which chromosome and linkage group designations are known. All the markers were derived from randomly amplified polymorphic DNA (RAPD) bands that were identified through bulked segregant analysis and cloned for conversion to sequence tagged site (STS) markers. One of the markers was dominant while four detected polymorphism upon digestion with restriction enzymes. The other markers were mapped as RAPD fragments. Phenotypic data for the population was based on the evaluation of percentage seed damage in replicated trials conducted over four seasons in Mexico. In single point regression analysis, individual markers explained from 3.5 to 22.5% of the variance for the resistance trait with the most significant markers overall being F10-500S, U1-1400R, R20-1200S, W9-1300S and Z4-800S, all markers that mapped to chromosome 2 (b01). Two additional significant markers, B1-1400R and W6-800R, were mapped to chromosome 6 (b11) and explained from 4.3 to 10.2% of variance depending on the season. The latter of these markers was a dominant STS marker that may find immediate utility in marker-assisted selection. The association of these two loci with the Agr and Agm genes is discussed as well as the possibility of additional resistance genes on chromosome 4 (b07) and chromosome 3 (b08). These are among the first specific markers developed for tagging insect resistance in common bean and are expected to be useful for evaluating the mechanism of resistance to A. godmani.

Animals↗

Mapping by admixture linkage disequilibrium in human populations: limits and guidelines.

Certain human hereditary conditions, notably those with low penetrance and those which require an environmental event such as infectious disease exposure, are difficult to localize in pedigree analysis, because of uncertainty in the phenotype of an affected patient's relatives. An approach to locating these genes in human cohort studies would be to use association analysis, which depends on linkage disequilibrium of flanking polymorphic DNA markers. In theory, a high degree of linkage disequilibrium between genes separated by 10-20 cM will be generated and persist in populations that have a history of recent (3-20 generations ago) admixture between genetically differentiated racial groups, such as has occurred in African Americans and Hispanic populations. We have conducted analytic and computer simulations to quantify the effect of genetic, genomic, and population parameters that affect the amount and ascertainment of linkage disequilibrium in populations with a history of genetic admixture. Our goal is to thoroughly explore the ranges of all relevant parameters or factors (e.g., sample size and degree of genetic differentiation between populations) that may be involved in gene localization studies, in hopes of prescribing guidelines for an efficient mapping strategy. The results provide reasonable limits on sample size (200-300 patients), marker number (200-300 in 20-cM intervals), and allele differentiation (loci with allele frequency difference of > or = .3 between admixed parent populations) to produce an efficient approach (> 95% ascertainment) for locating genes not easily tracked in human pedigrees.

Alleles↗

[Quantitative and topographic EEG brain mapping: a study of normal adult population].

We studied the electric brain activity during wakefulness in 20 Brazilian people through digital EEG and spectral analysis in order to propose a standardization for Brazilian adult population. All this group is healthy with laboratory examinations and mini-mental state (scores higher than 27) evaluation normal. After Fourier fast transformation (FFT) calculation, we found a histogram display with monomodal distribution, with higher values in alpha band. Analyzing the average of these results, different standards from the analogical traditional EEG were found, as the distribution of alpha band and delta activity behavior. The beta 2 and beta 3 behavior showed a diffuse distribution, that is not the usual. By the other hand, other findings are congruent to the analogical EEG as the alpha posterior predominance and the bigger presence of theta activity at the central regions.

Adult↗

Genomic tools to improve parasite resistance.

The natural genetic variability of the ruminant immune system provides a feasible means to control gastrointestinal (GI) parasite infection without anthelmintics. However, the paradigm of traditional selection has not been effectively applied to the moderately heritable traits of parasite resistance (h approximately equal to 0.3) due to the difficulty and expense of gathering accurate phenotypes in a commercial production setting. These characteristics make host traits related to GI nematode infection ideal candidates for genomics-based research. To initiate explanation of important allelic differences, economic trait loci (ETL) are being identified and mapped using a resource population of Angus cattle segregating for GI nematode resistance and susceptibility to the two most common nematode parasites of US cattle, Ostertagia ostertagi and Cooperia oncophora. The population is composed of five generations of half-sib progeny with complete phenotypic records produced from controlled infections. To detect the genomic locations of the three distinct phenotypic traits being expressed (innately immune, acquired immune, and immunologically non-responsive), genotypes have been generated for DNA markers (N=199) spaced at regular intervals (approximately 20cm intervals) throughout the entire genome (3000cm). Although initial ETL detection may be limited by half-sib family size, the unique structure of this population provides additional statistical power for refining map position of potential ETL. After allele frequency and contribution to phenotype are determined in this population, marker tests associated with ETL most beneficial for controlling parasite infection can be accurately used for selection. Comparative map and functional genomic information from humans and other species of biomedical importance will be utilized in further investigations to elucidate the genes underlying ETL.

Animals↗

QTLs influencing panicle size detected in two reciprocal introgressive line (IL) populations in rice (Oryza sativa L.).

Two sets of reciprocal introgression line (IL) populations, i.e., ILs with Lemont as recurrent parent (IL_LT) and ILs with Teqing as recurrent parent (IL_TQ), were developed and evaluated for traits representing panicle size, including primary branch number (PBN), secondary branch number (SBN), and spikelet number per panicle (SNP). Together with the regression to recurrent parent by advanced backcross, transgressive segregations were observed for all traits. Correlation and regression analysis showed that SBN had much higher contribution to SNP than PBN. It was confirmed by the QTL analysis that many common loci were detected between SBN and SNP, in comparison with single common locus between PBN and SNP. One and three main effect QTLs (M-QTLs) were detected for PBN in IL_LT and IL_TQ, respectively. Six M-QTLs per trait per populations were associated with SBN and SNP. Less number and lower contribution of epistasis were detected in IL populations in comparison with mapping result from F2 or RI population. There were only four QTLs in fourteen loci (near 30%) commonly detected in both reciprocal IL populations implying the large impact of genetic background on QTLs expression.

Chromosome Mapping↗

Identification and mapping of cleistogamy genes in barley.

Cleistogamy is a closed type of flowering with ensured self-pollination and an important trait to study evolutionary development in flower organs, reproduction systems, gene flow, and disease control. Still, very limited information is available about the genetic control and regulatory mechanism of this trait in barley. In this work, from the eight crosses between cleistogamous and chasmogamous accessions, five crosses generated chasmogamous F1 plants and their F2 plants segregated as 3 chasmogamous:1 cleistogamous, whereas three crosses generated cleistogamous F1 plants, and their F2 plants segregated as 1 chasmogamous:3 cleistogamous. Although a single gene was responsible for the control of cleistogamy in these two groups of crosses, the direction of dominance was opposite, suggesting two genes, cly1 and Cly2, for the genetic control of cleistogamy in barley. Epistatic type of gene interaction between the two loci was detected. In the analysis of 99 recombinant inbred lines of 'Azumamugi' x 'Kanto Nakate Gold' and doubled haploid lines of 'Harrington' x 'Mikamo Golden', where in both crosses F1 was chasmogamous, the cly1 locus has been mapped on chromosome 2HL. Using the analysis of the F2 population of 'Misato Golden' and 'Satsuki Nijo' where F1 was cleistogamous, the Cly2 locus was mapped in the same region of chromosome 2HL. Because the cly1 and Cly2 loci were mapped in the same region in these three different mapping populations, it was concluded that the expression of cleistogamy is under the control of two tightly linked genes or different alleles of the same gene.

Chromosome Mapping↗

Methamphetamine abuse and emergency department utilization.

Methamphetamine (MAP) abuse continues to increase worldwide, based on morbidity, mortality, drug treatment, and epidemiologic studies and surveys. MAP abuse has become a significant health care, environmental, and law enforcement problem. Acute intoxication often results in agitation, violence, and death. Chronic use may lead to infection, heart failure, malnutrition, and permanent psychiatric illness. MAP users frequently use the emergency department (ED) for their medical care. Over a 6-month period we studied the demographics, type, and frequency of medical and traumatic problems in 461 MAP patients presenting to our ED, which serves an area noted for high levels of MAP production and consumption. Comparison was made to the general ED population to assess use patterns. MAP patients were most commonly Caucasian males who lacked health insurance. Compared to other ED patients during this time, MAP patients used ambulance transport more and were more likely to be admitted to the hospital. There was a significant association between trauma and MAP use in this patient population. Our data suggest MAP users utilize prehospital and hospital resources at levels higher than the average ED population. Based on current trends, we can expect more ED visits by MAP users in the future.

Adult↗

Mapping quantitative trait loci using the experimental designs of recombinant inbred populations.

In the data collection of the QTL experiments using recombinant inbred (RI) populations, when individuals are genotyped for markers in a population, the trait values (phenotypes) can be obtained from the genotyped individuals (from the same population) or from some progeny of the genotyped individuals (from the different populations). Let Fu be the genotyped population and Fv (v>or=u) be the phenotyped population. The experimental designs that both marker genotypes and phenotypes are recorded on the same populations can be denoted as (Fu/Fv, u=v) designs and that genotypes and phenotypes are obtained from the different populations can be denoted as (Fu/Fv, v>u) designs. Although most of the QTL mapping experiments have been conducted on the backcross and F2(F2/F2) designs, the other (Fu/Fv, v>or=u) designs are also very popular. The great benefits of using the other (Fu/Fv, v>or=u) designs in QTL mapping include reducing cost and environmental variance by phenotyping several progeny for the genotyped individuals and taking advantages of the changes in population structures of other RI populations. Current QTL mapping methods including those for the (Fu/Fv, u=v) designs, mostly for the backcross or F2/F2 design, and for the F2/F3 design based on a one-QTL model are inadequate for the investigation of the mapping properties in the (Fu/Fv, u or=u) designs. In addition, the QTL mapping properties of the proposed and approximate methods in different designs are discussed. Simulations were performed to evaluate the performance of the proposed and approximate methods. The proposed method is proven to be able to correct the problems of the approximate and current methods for improving the resolution of genetic architecture of quantitative traits and can serve as an effective tool to explore the QTL mapping study in the system of RI populations.

Algorithms↗

Use of linkage disequilibrium approaches to map genes for bipolar disorder in the Costa Rican population.

Linkage disequilibrium (LD) analysis provides a powerful means for screening the genome to map the location of disease genes, such as those for bipolar disorder (BP). As described in this paper, the population of the Central Valley of Costa Rica, which is descended from a small number of founders, should be suitable for LD mapping; this assertion is supported by reconstruction of extended haplotypes shared by distantly related individuals in this population suffering low-frequency hearing loss (LFHL1), which has previously been mapped by linkage analysis. A sampling strategy is described for applying LD methods to map genes for BP, and clinical and demographic characteristics of an initially collected sample are discussed. This sample will provide a complement to a previously collected set of Costa Rican BP families which is under investigation using standard linkage analysis.

Adult↗