Analysis of enzymatically amplified β-globin and HLA-DQα DNA with allele-specific oligonucleotide probes

Saiki, Randall K.; Bugawan, Teodorica L.; Horn, Glenn T.; Mullis, Kary B.; Erlich, Henry A.

doi:10.1038/324163a0

Cited by 1,748 publications

(663 citation statements)

References 11 publications

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“…However, this technique was cumbersome and was unsuitable for analyzing bthalassemia, which is generally caused by point mutations. Therefore the development of PCR was truly revolutionary [6]. All of the globin genes are small, just over 2 kilobases, and as such, are all highly amenable to analysis using PCR-based methodology which has been used to great advantage for nearly three decades.…”

Section: Diagnosis: From Protein To Genes To Prenatal Diagnosismentioning

confidence: 99%

Thalassemia 2016: Modern medicine battles an ancient disease

Rund

2015

American J Hematol

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Thalassemia was first clinically described nearly a century ago and treatment of this widespread genetic disease has greatly advanced during this period. DNA‐based diagnosis elucidated the molecular basis of the disease and clarified the variable clinical picture. It also paved the way for modern methods of carrier identification and prevention via DNA‐based prenatal diagnosis. Every aspect of supportive care, including safer blood supply, more regular transfusions, specific monitoring of iron overload, parenteral and oral chelation, and other therapies, has prolonged life and improved the quality of life of these patients. Significant advances have also been made in allogenic bone marrow transplantation, the only curative therapy. Recently, there has been a rejuvenated interest in studying thalassemia at the basic science level, leading to the discovery of previously unknown mechanisms leading to anemia and enabling the development of novel therapies. These will potentially improve the treatment of, and possibly cure the disease. Pathways involving activin receptors, heat shock proteins, JAK2 inhibitors and macrophage targeted therapy, among others, are being studied or are currently in clinical trials for treating thalassemia. Novel types of genetic therapies are in use or under investigation. In addition to the challenges of treating each individual patient, the longer survival of thalassemia patients has raised considerations regarding worldwide control of thalassemia, since prevention is not universally implemented. This review will trace a number of the original medical milestones of thalassemia diagnosis and treatment, as well as some of the most recent developments which may lead to innovative therapeutic modalities. Am. J. Hematol. 91:15–21, 2016. © 2015 Wiley Periodicals, Inc.

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Section: Diagnosis: From Protein To Genes To Prenatal Diagnosismentioning

confidence: 99%

Thalassemia 2016: Modern medicine battles an ancient disease

Rund

2015

American J Hematol

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“…In some cases, samples were also tested with a quantitative real-time PCR assay (Garnett et al, 2002). As a control, PCR with a set of HLA-DQ alpha primers was performed as described (Saiki et al, 1986).…”

Section: Pcr Assaysmentioning

confidence: 99%

Adenovirus DNA is detected at increased frequency in Guthrie cards from children who develop acute lymphoblastic leukaemia

et al. 2007

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“…Sequences of around 100 bp were amplified using primers flanking codons 12/13 and 61 of H, K and NRAS as described previously. [15][16][17] Where sufficient DNA was available, independent confirmation of the results obtained by ONH was obtained using NIH3T3 transformation assays as described. 15,18 Foci were scored 3-4 weeks after transfection, picked, expanded and their DNA extracted for further analysis by Southern blot and SSCP.…”

Section: Cytogenetic Analysismentioning

confidence: 99%

RAS, FMS and p53 mutations and poor clinical outcome in myelodysplasias: a 10-year follow-up

et al. 1998

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The molecular mechanisms underlying the development and evolution of myelodysplastic syndrome (MDS) are largely unknown. The increasing number of blast cells in the bone marrow correlate with poor prognosis and risk of developing acute leukemia. Such progression is frequently associated with increasing chromosomal abnormalities and genetic mutations. A cohort of 75 MDS patients were investigated for RAS, FMS and p53 mutations, and these molecular findings were related to cytogenetics, clinical status, transformation to acute leukemia, prognostic scores and survival. A mutation incidence of 57% (43/75) was found, with 48% (36/75) RAS mutations, 12% (9/75) FMS mutations and 8% (4/50) p53 mutations. The mutation status for RAS and FMS was related to MDS subgroup, increasing with poor-risk disease. The highest incidence was in the chronic myelomonocytic leukemia (CMML) subgroup. The most frequent RAS mutations were of codon 12 and a predominance of FMS codon 969 mutations was observed. A statistically significant increased frequency of transformation to AML was observed in MDS patients harboring RAS or FMS mutations (P Ͻ 0.02). Patients with oncogene mutations had a significantly poorer survival compared with those without mutations at 2 years and at the end of the period of follow-up (P Ͻ 0.02). Multivariate analysis including mutation, age, gender, diagnosis (FAB), cytogenetics and International score shows that the International score and mutation and age is the best predictive model of a poor outcome, (P Ͻ0.0001). When the analysis was undertaken without the International score, mutation and gender was the best predictor of poor survival (P = 0.005). This study shows that oncogene mutation, indicative of genetic instability, is associated with disease progression and poor survival in MDS.

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Analysis of enzymatically amplified β-globin and HLA-DQα DNA with allele-specific oligonucleotide probes

Cited by 1,748 publications

References 11 publications

Thalassemia 2016: Modern medicine battles an ancient disease

Thalassemia 2016: Modern medicine battles an ancient disease

Adenovirus DNA is detected at increased frequency in Guthrie cards from children who develop acute lymphoblastic leukaemia

RAS, FMS and p53 mutations and poor clinical outcome in myelodysplasias: a 10-year follow-up

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