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A H Paterson

Publications and source records attributed to A H Paterson.

At least 73 records · Page 4Linked to original sources
PubMed1996

Genome-wide high-resolution mapping by recurrent intermating using Arabidopsis thaliana as a model.

We demonstrate a method for developing populations suitable for genome-wide high-resolution genetic linkage mapping, by recurrent intermating among F2 individuals derived from crosses between homozygous parents. Comparison of intermated progenies to F2 and "recombinant inbred" (RI) populations from the same pedigree corroborate theoretical expectations that progenies intermated for four generations harbor about threefold more information for estimating recombination fraction between closely linked markers than either RI-selfed or F2 individuals (which are, in fact, equivalent in this regard). Although intermated populations are heterozygous, homozygous "intermated recombinant inbred" (IRI) populations can readily be generated, combining additional information afforded by intermating with the permanence of RI populations. Intermated populations permit fine-mapping of genetic markers throughout a genome, helping to bridge the gap between genetic map resolution and the DNA-carrying capacity of modern cloning vectors, thus facilitating merger of genetic and physical maps. Intermating can also facilitate high-resolution mapping of genes and QTLs, accelerating mapbased cloning. Finally, intermated populations will facilitate investigation of other fundamental genetic questions requiring a genome-wide high-resolution analysis, such as comparative mapping of distantly related species, and the genetic basis of heterosis.

Arabidopsis↗
PubMed1996

Increased thromboembolic complications with concurrent tamoxifen and chemotherapy in a randomized trial of adjuvant therapy for women with breast cancer. National Cancer Institute of Canada Clinical Trials Group Breast Cancer Site Group.

PURPOSE AND METHODS: Associations between thromboembolism and malignancy, usually widespread, and between thromboembolism and hormonal and/or chemotherapy have been previously reported. We performed a randomized trial of tamoxifen 30 mg/d for 2 years (T) versus T plus 6 months of intravenous chemotherapy with cyclophosphamide, methotrexate, and fluorouracil (CMF) for postmenopausal women with involved axillary nodes and positive estrogen receptor (ER) or progesterone receptor (PgR) status following primary therapy for breast cancer. RESULTS: We observed one or more thromboembolic events in 48 of 353 women (13.6%) allocated to receive T plus CMF in comparison to five of 352 women (2.6%) randomized to receive T alone (P < .0001). Six women in the T plus CMF arm, but none randomized to receive T alone, suffered two thromboembolic events while an study therapy. There were also significantly more women who developed severe (grade 3 to 5) thromboembolic events in the T plus CMF arm than in the T arm (34 v five; P < .0001). Most thromboembolic events (39 of 54) occurred while women were actually receiving chemotherapy (P < .0001). Thromboembolic complications resulted in more days in hospital and more deaths than any other complication of therapy, including infection, in this trial. CONCLUSION: Thromboembolism related to the addition of CMF chemotherapy to tamoxifen as adjuvant therapy in this group of women represents a relatively common and serious complication that may outweigh any benefits offered by this additional therapy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1996

High-dose melphalan +/- total body irradiation and autologous hematopoietic stem cell rescue for adult patients with Ewing's sarcoma or peripheral neuroectodermal tumor.

The role of high-dose therapy and autologous stem cell transplantation (ASCT) in the treatment of patients with Ewing's sarcoma (EWS) remains uncertain. From November 1985 to September 1994, 13 patients aged 16-30 years (median 20.5) received high-dose melphalan (HDM) 140-200 mg/m2 +/- 500 cGy TBI followed by ASCT for relapsed/refractory (n = 4), metastatic (n = 2), or non-metastatic (n = 6) EWS, or for peripheral neuroectodermal tumor (PNET) (n = 1). This regimen was well tolerated with no transplant-related mortality and no toxicity requiring life sustaining measures. Three of the four patients treated for relapsed/refractory EWS had progression-free survivals (PFS) less than 5 months. The only long-term survivor of these four patients received HDM while in complete remission following pulmonary irradiation. Both patients with pulmonary metastases at presentation died just 5 and 6 months post-ASCT. All four patients with non-metastatic, bulky (> 8 cm) osseous EWS progressed at a median of 11 months (range 7-22 months) while the two patients with non-bulky EWS remain progression-free 25+ and 28+ months post-HDM/TBI + ASCT. The 19-year-old patient with a PNET of the thoracoabdominal wall relapsed 4 months post-ASCT. Overall, only three of these 13 patients remain progression-free at 25+, 28+, and 108+ months following HDM +/- TBI and ASCT. In conclusion, HDM +/- TBI did not obviously improve the outcome of these 13 patients relative to that expected following conventional dose therapy alone.

Adolescent↗
PubMed1995

The weediness of wild plants: molecular analysis of genes influencing dispersal and persistence of johnsongrass, Sorghum halepense (L.) Pers.

Many major weeds rely upon vegetative dispersal by rhizomes and seed dispersal by "shattering" of the mature inflorescence. We report molecular analysis of these traits in a cross between cultivated and wild species of Sorghum that are the probable progenitors of the major weed "johnsongrass." By restriction fragment length polymorphism mapping, variation in the number of rhizomes producing above-ground shoots was associated with three quantitative trait loci (QTLs). Variation in regrowth (ratooning) after overwintering was associated with QTLs accounting for additional rhizomatous growth and with QTLs influencing tillering. Vegetative buds that become rhizomes are similar to those that become tillers--one QTL appears to influence the number of such vegetative buds available, and additional independent genes determine whether individual buds differentiate into tillers or rhizomes. DNA markers described herein facilitate cloning of genes associated with weediness, comparative study of rhizomatousness in other Poaceae, and assessment of gene flow between cultivated and weedy sorghums--a risk that constrains improvement of sorghum through biotechnology. Cloning of "weediness" genes may create opportunities for plant growth regulation, in suppressing propagation of weeds and enhancing productivity of major forage, turf, and "ratoon" crops.

Journal Article↗
PubMed1995

Comparative analysis of QTLs affecting plant height and maturity across the Poaceae, in reference to an interspecific sorghum population.

Correspondence among QTLs affecting height and/or flowering was investigated across the five races of sorghum, an interspecific sorghum F2 population, and 32 previously published sorghum, maize, rice, wheat, and barley populations revealing 185 QTLs or discrete mutants. Among nine QTLs mapped in the interspecific sorghum population (six affecting height and three affecting flowering), at least seven (78%) are associated with "conversion," backcross-introgression of alleles imparting reduced height or earlier flowering from cultivated sorghums into one or more exotic Sorghum bicolor races. One chromosomal region was "converted" in all S. bicolar races--in the interspecific F2, this region explained 54.8% of height variation (putatively the Dw2 gene) and 85.7% of flowering time variation (putatively Ma1). Comparative data suggest that Ma1 and Dw2 orthologs influence height and flowering of other Poaceae taxa and support classical dogma that the sorghum phenotypes attributed to Ma1 and Dw2 (respectively) are due to different genetic loci. Other sorghum QTLs also showed correspondence with those in other Poaceae, more frequently than would be expected by chance. Possible homoeologous QTLs were found within both the maize and sorghum genomes. Comparative QTL mapping provides a means to unify, and thereby simplify, molecular analysis of complex phenotypes.

Chromosome Mapping↗
PubMed1995

Molecular dissection of quantitative traits: progress and prospects.

QTL mapping is an increasingly useful approach to the study and manipulation of complex traits important in agriculture, evolution, and medicine. The molecular dissection of quantitative phenotypes, supplementing the principles of classical quantitative genetics, is accelerating progress in the manipulation of plant and animal genomes. A growing appreciation of the similarities among different organisms and the usefulness of comparative genetic information is making genome analysis more efficient, and providing new opportunities for using model systems to overcome the limitations of less-favorable systems. The expanding repertoire of techniques and information available for studying heredity is removing obstacles to the cloning of QTLs. Although QTL mapping alone is limited to a resolution of 0.1%-1.0% of a genome, use of QTL mapping in conjunction with a search for mapped candidate genes, with emerging technologies for isolation of genes expressed under conditions likely to account for the quantitative phenotype, and with ever more efficient megabase DNA manipulation and characterization bodes well for the prospect of isolating the genetic determinants of QTLs in the foreseeable future. In the words of Thoday (1961), "An extensive attack on quantitative genetics made from this point of view as well as the biometric approach should be a great help in answering questions concerning the nature of polygenes...."

Animals↗
PubMed1995

Cloning and characterization of the majority of repetitive DNA in cotton (Gossypium L.).

Repetitive DNA elements representing 60-70% of the total repetitive DNA in tetraploid cotton (Gossypium barbadense L.) and comprising 30-36% of the tetraploid cotton genome were isolated from a genomic library of DNA digested with a mixture of four blunt-end cutting restriction enzymes. A total of 313 clones putatively containing nuclear repetitive sequences were classified into 1103 families, based on cross hybridization and Southern blot analysis. The 103 families were characterized in terms of genome organization, methylation pattern, abundance, and DNA variation. As in many other eukaryotic genomes, interspersed repetitive elements are the most abundant class of repetitive DNA in the cotton genome. Paucity of tandem repeat families with high copy numbers (>10(4)) may be a unique feature of the cotton genome as compared with other higher plant genomes. Interspersed repeats tend to be methylated, while tandem repeats seem to be largely unmethylated in the cotton genome. Minimal variation in repertoire and overall copy number of repetitive DNA elements among different tetraploid cotton species is consistent with the hypothesis of a relatively recent origin of tetraploid cottons.

Base Sequence↗
PubMed1995

Role of bisphosphonates in prevention and treatment of bone metastases from breast cancer.

Clinical research over the last decade has confirmed the helpful role of bisphosphonates in the management of patients with bone metastases secondary to breast cancer and other malignancies. This role is also expanding in myeloma and in the management of osteoporosis. Current clinical research in oncology is focusing on their potential for the prevention of skeletal complications of malignant disease and the development of bone metastases while basic researchers are developing compounds of higher potency and, perhaps, higher therapeutic efficacy. One of the earliest agents to be investigated, etidronate, is effective in the management of malignant hypercalcemia and, when used orally and intermittently, results in reduced bone loss in osteoporosis. However, it does not appear to reduce pain in patients with malignant disease. Clodronate has been shown to be an effective agent in the management of hypercalcemia and can be used as a single intravenous infection for this purpose. Clodronate is also effective in some patients in reducing bone pain and improving mobility. When used orally, it can, as can pamidronate, reduce the skeletal complications of breast cancer such as hypercalcemia, bone fractures and bone pain. It may have fewer gastrointestinal side effects than oral pamidronate. There is emerging evidence that bisphosphonates may delay or prevent the clinical appearance of bone metastases as well as reduce other skeletal complications. Trials of adjuvant bisphosphonates such as clodronate and pamidronate in operable breast cancer are currently under way in Europe and North America.

Analgesics, Non-Narcotic↗
PubMed1994

QTL mapping of naturally-occurring variation in flowering time of Arabidopsis thaliana.

A segregating F2 population of Arabidopsis thaliana derived from a cross between the late-flowering ecotype Hannover/Münden (HM) and the early-flowering ectoype Wassilewskija (WS) was analyzed for flowering time and other morphological traits. Two unlinked quantitative trait loci (QTLs) affecting days to first flower (DFF-a and DFF-b) mapped to chromosome 5. QTLs which affect node number (NN), leaf length at flowering (LLF), and lead length at 35 days (LL35) also mapped to chromosome 5; LLF-a, LL35-a, NN-a map to the same region of chromosome 5 as DFF-a; LLF-b and LL35-bmap to the same region of chromosome 5 as DFF-b. Another QTL affecting leaf length at flowering (LLF-c) maps to chromosome 3. The proximity of DFF-a, LLF-a, LL35-a and NN-a, as well as the similarity in gene action among these QTLs (additivity), suggest that they may be pleiotropic consequences of a single gene at this locus. Similarly, LL35-b and LLF-b map near each other and both display recessive gene action, again suggesting the possibility of pleiotropy. DFF-b, which also maps near LL35-b and LLF-b, displays largely additive gene action (although recessive gene action could not be ruled out). This suggests that DFF-b may represent a different gene from LL35-b and/or LLF-b. DFF-a maps near two previously identified mutants: co (which also affects flowering time and displays gene action consistent with additivity) and flc.(ABSTRACT TRUNCATED AT 250 WORDS)

Arabidopsis↗
PubMed1994

Construction and characterization of a bacterial artificial chromosome library of Sorghum bicolor.

The construction of representative large insert DNA libraries is critical for the analysis of complex genomes. The predominant vector system for such work is the yeast artificial chromosome (YAC) system. Despite the success of YACs, many problems have been described including: chimerism, tedious steps in library construction and low yields of YAC insert DNA. Recently a new E.coli based system has been developed, the bacterial artificial chromosome (BAC) system, which offers many potential advantages over YACs. We tested the BAC system in plants by constructing an ordered 13,440 clone sorghum BAC library. The library has a combined average insert size, from single and double size selections, of 157 kb. Sorghum inserts of up to 315 kb were isolated and shown to be stable when grown for over 100 generations in liquid media. No chimeric clones were detected as determined by fluorescence in situ hybridization of ten BAC clones to metaphase and interphase S.bicolor nuclei. The library was screened with six sorghum probes and three maize probes and all but one sorghum probe hybridized to at least one BAC clone in the library. To facilitate chromosome walking with the BAC system, methods were developed to isolate the proximal ends of restriction fragments inserted into the BAC vector and used to isolate both the left and right ends of six randomly selected BAC clones. These results demonstrate that the S. bicolor BAC library will be useful for several physical mapping and map-based cloning applications not only in sorghum but other related cereal genomes, such as maize. Furthermore, we conclude that the BAC system is suitable for most large genome applications, is more 'user friendly' than the YAC system, and will likely lead to rapid progress in cloning biologically significant genes from plants.

Base Sequence↗
PubMed1994

Comparative mapping of Arabidopsis thaliana and Brassica oleracea chromosomes reveals islands of conserved organization.

The chromosomes of Arabidopsis thaliana and Brassica oleracea have been extensively rearranged since the divergence of these species; however, conserved regions are evident. Eleven regions of conserved organization were detected, ranging from 3.7 to 49.6 cM in A. thaliana, spanning 158.2 cM (24.6%) of the A. thaliana genome, and 245 cM (29.9%) of the B. oleracea genome. At least 17 translocations and 9 inversions distinguish the genomes of A. thaliana and B. oleracea. In one case B. oleracea homoeologs show a common marker order, which is distinguished from the A. thaliana order by a rearrangement, indicating that the lineages of A. thaliana and B. oleracea diverged prior to chromosomal duplication in the Brassica lineage (for at least this chromosome). Some chromosomal segments in B. oleracea appear to be triplicated, indicating the need for reevaluation of a classical model for Brassica chromosome evolution by duplication. The distribution of duplicated loci mapped for about 13% of the DNA probes studied in A. thaliana suggests that ancient duplications may also have occurred in Arabidopsis. The degree of chromosomal divergence between A. thaliana and B. oleracea appears greater than that found in other confamilial species for which comparative maps are available.

Arabidopsis↗
PubMed1994

A detailed RFLP map of cotton, Gossypium hirsutum x Gossypium barbadense: chromosome organization and evolution in a disomic polyploid genome.

We employ a detailed restriction fragment length polymorphism (RFLP) map to investigate chromosome organization and evolution in cotton, a disomic polyploid. About 46.2% of nuclear DNA probes detect RFLPs distinguishing Gossypium hirsutum and Gossypium barbadense; and 705 RFLP loci are assembled into 41 linkage groups and 4675 cM. The subgenomic origin (A vs. D) of most, and chromosomal identity of 14 (of 26), linkage groups is shown. The A and D subgenomes show similar recombinational length, suggesting that repetitive DNA in the physically larger A subgenome is recombinationally inert. RFLPs are somewhat more abundant in the D subgenome. Linkage among duplicated RFLPs reveals 11 pairs of homoelogous chromosomal regions-two appear homosequential, most differ by inversions, and at least one differs by a translocation. Most homoeologies involve chromosomes from different subgenomes, putatively reflecting the n = 13 to n = 26 polyploidization event of 1.1-1.9 million years ago. Several observations suggest that another, earlier, polyploidization event spawned n = 13 cottons, at least 25 million years ago. The cotton genome contains about 400-kb DNA per cM, hence map-based gene cloning is feasible. The cotton map affords new opportunities to study chromosome evolution, and to exploit Gossypium genetic resources for improvement of the world's leading natural fiber.

Biological Evolution↗
PubMed1993

An improved method of plant megabase DNA isolation in agarose microbeads suitable for physical mapping and YAC cloning.

The isolation of high quality megabase DNA from plant cells that is susceptible to a variety of molecular reagents is a critical first step in the physical analysis of complex genomes. A method for the isolation of such DNA by encapsulating plant protoplasts in agarose microbeads is presented. In comparison with the conventional agarose plug method, microbeads provide a dramatic increase in the surface area yielding megabase DNA that can be treated essentially as an aqueous DNA solution. Examples of the utility of DNA prepared by this technique for physical mapping, partial restriction enzyme digestion and cloning of large inserts as YACs are presented.

Chromosomes, Artificial, Yeast↗
PubMed1993

Double-blind controlled trial of oral clodronate in patients with bone metastases from breast cancer.

PURPOSE: Osteolytic metastases often give rise to hypercalcemia, fracture, and bone pain, and occur commonly in patients with recurrent breast cancer. We assessed the bisphosphonate, clodronate, which has proven to be a useful treatment for hypercalcemia and may be a potent inhibitor of tumor-induced osteolysis, for its effect on reducing the osseous complications of metastatic breast cancer. PATIENTS AND METHODS: We studied 173 patients with bone metastases due to breast cancer in a randomized, double-blind, placebo-controlled trial of oral clodronate 1,600 mg/d (85 patients) compared with an identical placebo (88 patients). RESULTS: The patients in each wing were comparable in their clinical, radiologic, and biochemical characteristics at trial entry. In patients who received clodronate, there was a significant reduction compared with placebo in the total number of hypercalcemic episodes (28 v 52; P < .01), in the number of terminal hypercalcemic episodes (seven v 17; P < .05), in the incidence of vertebral fractures (84 v 124 per 100 patient-years; P < .025), and in the rate of vertebral deformity (168 v 252 per 100 patient-years; P < .001). The combined rate of all morbid skeletal events was significantly reduced (218.6 v 304.8 per 100 patient-years; P < .001). Trends were seen in favor of clodronate for nonvertebral fracture rates and radiotherapy requirements for bone pain (particularly spinal pain). No significant survival differences and no significant differences in side effects were observed between the two groups. CONCLUSIONS: These findings indicate that oral clodronate has a beneficial effect on the skeletal morbidity associated with breast cancer and should be considered as antiosteolytic therapy in affected patients. It deserves further investigation as an adjuvant therapy in operable breast cancer and in patients with nonosseous recurrence who are at high risk for bone metastases.

Administration, Oral↗