Antenatal Diagnosis of Sickle Cell Anaemia by Direct Analysis of the Sickle Mutation

Chang, J.; Kan, YW

doi:10.1016/s0140-6736(81)90584-5

Cited by 80 publications

(26 citation statements)

References 19 publications

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“…The β S allele genotype of all subjects was confirmed by PCR (a fragment of 488 bp amplified by forward primer 5′-TGATGGTATGGGGCCAAGA-3′ and reverse primer 5′-GGGTGGGAAAATAGACCAATA-3′) followed by digestion with Dde I [26]. When the β S allele is present, Dde I cleaves the above mentioned fragment into 4 small fragments and a larger one composed of 381 bp.…”

Section: Methodsmentioning

confidence: 99%

β-Globin Gene Cluster Haplotypes in a Cohort of 221 Children with Sickle Cell Anemia or Sβ⁰-Thalassemia and Their Association with Clinical and Hematological Features

Belisário¹,

Martins

Brito

et al. 2010

Acta Haematol

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Background/Aims: β^S-Haplotype prevalence and its associations with clinical and hematological characteristics were assessed in Brazilian children with sickle cell anemia or Sβ⁰-thalassemia. Methods: A retrospective randomized cohort study was undertaken with 208 SS and 13 Sβ⁰-thalassemia children derived from the Newborn Screening Program of the state of Minas Gerais. β^S-Haplotypes were determined by PCR-RFLP. Results: Thirty-nine percent of the SS subjects had the CAR/CAR genotype, 33% had CAR/Ben, 24% had Ben/Ben, 1% had CAR/Atp, 1% had Ben/Atp, and 1% had Arab-Indian/Ben; 1% could not be characterized. Of the Sβ⁰-thalassemia children, 5 were CAR/undefined, 2 were Ben/undefined, and 1 was CAM/undefined. There was no significant association between β^S-haplotypes and the total Hb, Hb F, MCV, MCH, WBC, and reticulocyte count among the SS children. Likewise, no significant association was detected between β^S-haplotypes and the frequency of acute chest syndrome episodes, blood transfusions, splenic sequestration, or cerebrovascular disease (high-risk/conditional transcranial Doppler ultrasonography or clinical stroke). A limited number of Sβ⁰-thalassemia children precluded valid analyses. Conclusions: The prevalence of β^S-haplotypes in this study is in agreement with the historical records of African slaves brought to the state of Minas Gerais. Furthermore, β^S-haplotypes CAR and Ben were not associated with any analyzed feature of children with sickle cell anemia.

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Section: Methodsmentioning

confidence: 99%

β-Globin Gene Cluster Haplotypes in a Cohort of 221 Children with Sickle Cell Anemia or Sβ⁰-Thalassemia and Their Association with Clinical and Hematological Features

Belisário¹,

Martins

Brito

et al. 2010

Acta Haematol

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“…Indeed, the DNA sequence maintained an open reading frame at this region and the first methionine codon was located at the 5' terminus of the cDNA clone at position -32 (Fig. 2) C 10 20 30 40 50 60 -1 1 8 LEU LEU LEU ILE GLY PHE TRP ASP CYS VAL THR CYS HIS GLY SER PRO VAL ASP ILE CYS T T 70 80 90 100 110 120 28 THR ALA LYS PRO ARG ASP ILE PRO MET ASN PRO MET CYS ILE TYR ARG SER PRO GLU LYS A A G 130 140 150 160 170 180 48 LYS ALA THR GLU ASP GLU GLY SER GLU GLN LYS ILE PRO GLU ALA THR ASH ARG ARG' A C AA A 610 620 630 640 650 660 208 TRP VAL SER ASH LYS THR GLU GLY ARG ILE THR ASP VAL ILE PRO SER GLU ALA ILE ASH T A T 670 6b0 690 700 710 720 229 GLU LEU THR VAL LEU VAL LEU VAL ASH THR ILE TYR PHE LYS GLY LEU TRP LYS SER A A G 730 740 750 760 770 780 248 PHE SER PRO GLU ASH THR ARG LYS GLU LEU PHE TYR LYS ALA ASP GLY GLU SER CYS SER T T A 790 800 810 820 830 840 268 ALA SER MET MET TYR GLN GLU GLY LYS PHE ARG TYR ARG ARG VAL ALA GLU GLY THR GLN 850 860 870 880 890 900 288 VAL LEU GLU LEU PRO PHE LYS GLY ASP ASP ILE THR MET VAL LEU ILE LEU PRO LYS PRO O T 910 920 930 940 950 960 308 GLU LYS SER LEU ALA, LYS VAL GLU LYS GLU LEU THR PRO GLU VAL LEU GLN GLU TRP mutated nucleotide in the /3-globin gene (25,26). In cases such as a1-antitrypsin deficiency, in which the point mutation does not create or destroy a restriction recognition sequence, ...…”

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confidence: 99%

Isolation and sequence characterization of a cDNA clone of human antithrombin III.

Chandra¹,

Stackhouse²,

Kidd³

et al. 1983

Proc. Natl. Acad. Sci. U.S.A.

138

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A human liver cDNA library was constructed by using poly(A)-containing RNA isolated from a human liver biopsy specimen. This library is comprised of 40,000 independent transformants with an average inserted DNA length of 1,200 base pairs. By using the previously cloned baboon antithrombin III cDNA as a specific hybridization probe, >30 human antithrombin mII cDNA clones were identified from this library. The Antithrombin III is a plasma protease inhibitor synthesized in the liver. The glycoprotein has a molecular weight of 55,000 and its entire amino acid sequence has almost been completed (1). It is a natural anticoagulant in that it specifically inhibits a number of serine proteases that participate in the blood coagulation cascade, including thrombin, factors IXa, Xa, XIa, and XIIa (2-5). The mechanism of inhibition involves the stoichiometric formation of protease-antiprotease complexes and the rate of complex formation is greatly enhanced in the presence of heparin, which is a well-known anticoagulant used clinically in myocardial infarction and surgery (6, 7). Deficiency of antithrombin III is a hereditary disorder that is associated with recurrent thrombophlebitis, acute aortic thrombosis, and thromboembolism (8-10). Heterogeneity of the classical antithrombin III deficiency has been observed (11). Abnormal antithrombin III also has been isolated from deficient patients and partially characterized (12), suggesting that the deficiency could be the result of mutations in the antithrombin III gene itself. Therefore, the genetic deficiency can be analyzed in molecular detail if the human antithrombin III gene can be isolated and characterized. We recently have reported the purification of antithrombin III mRNA from a baboon liver by polysome immunoprecipitation and the cloning of its cDNA (13). In this paper, we report the construction of a human liver cDNA library and the identification and sequence of a full-length human antithrombin III cDNA clone. MATERIALS AND METHODSConstruction of a Human Liver cDNA Library. A human liver biopsy specimen was kindly provided by Bill Williams (University of Texas Medical School in Houston). Total nucleic acid was extracted from the frozen tissue with phenol (14), and poly(A)-containing RNA was prepared by oligo(dT)-cellulose column chromatography (15). The RNA preparation was used for cDNA synthesis under conditions that favored full-length cDNA production (16). The cDNA preparation was sedimented through an alkaline sucrose gradient (16) and only fractions containing cDNA species of 1,000 nucleotides or more were pooled. The single-stranded cDNA was subsequently made double-stranded with reverse transcriptase (17). After nuclease S1 treatment, tracts of poly(dC) were added to the 3' termini of the DNA molecules by using terminal transferase (18). The enzymatically synthesized cDNA was rehybridized with Pst I-linearized pBR322 DNA that had been tailed with poly(dG) and the DNA was used for transformation of Escherichia coli RR1 (18). Bacterial transformants we...

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“…The best known such mutation is the sickle cell gene in which, by means of a single A→T transversion, the codon for a glutamic acid residue in the sixth position of the β-chain globin gene is converted to a codon for valine [3]. This can be considered a GOF mutation, because the hemoglobin gains a self-association site on its surface, allowing the individual proteins upon deoxygenation to aggregate into microtubular-like structures [4].…”

Section: The Modelmentioning

confidence: 99%

Getting There First: An Evolutionary Rate Advantage for Adaptive Loss-of-Function Mutations

Behe

2013

Biological Information

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Over the course of evolution organisms have adapted to their environments by mutating to gain new functions or to lose pre-existing ones. Because adaptation can occur by either of these modes, it is of basic interest to assess under what, if any, evolutionary circumstances one of them may predominate. Since mutation occurs at the molecular level, one must look there to discern if an adaptation involves gain-or loss-of-function. Here I present a simple, deterministic model for the occurrence and spread of adaptive gain-of-function versus loss-of-function mutations, and compare the results to laboratory evolution experiments and studies of evolution in nature. The results demonstrate that loss-of-function mutations generally have an intrinsic evolutionary rate advantage over gain-offunction mutations, but that the advantage depends radically on population size, ratio of selection coefficients of competing adaptive mutations, and ratio of the mutation rates to the adaptive states.

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Antenatal Diagnosis of Sickle Cell Anaemia by Direct Analysis of the Sickle Mutation

Cited by 80 publications

References 19 publications

β-Globin Gene Cluster Haplotypes in a Cohort of 221 Children with Sickle Cell Anemia or Sβ⁰-Thalassemia and Their Association with Clinical and Hematological Features

β-Globin Gene Cluster Haplotypes in a Cohort of 221 Children with Sickle Cell Anemia or Sβ⁰-Thalassemia and Their Association with Clinical and Hematological Features

Isolation and sequence characterization of a cDNA clone of human antithrombin III.

Getting There First: An Evolutionary Rate Advantage for Adaptive Loss-of-Function Mutations

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Antenatal Diagnosis of Sickle Cell Anaemia by Direct Analysis of the Sickle Mutation

Cited by 80 publications

References 19 publications

β-Globin Gene Cluster Haplotypes in a Cohort of 221 Children with Sickle Cell Anemia or Sβ&#8304;-Thalassemia and Their Association with Clinical and Hematological Features

β-Globin Gene Cluster Haplotypes in a Cohort of 221 Children with Sickle Cell Anemia or Sβ&#8304;-Thalassemia and Their Association with Clinical and Hematological Features

Isolation and sequence characterization of a cDNA clone of human antithrombin III.

Getting There First: An Evolutionary Rate Advantage for Adaptive Loss-of-Function Mutations

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Product

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β-Globin Gene Cluster Haplotypes in a Cohort of 221 Children with Sickle Cell Anemia or Sβ⁰-Thalassemia and Their Association with Clinical and Hematological Features

β-Globin Gene Cluster Haplotypes in a Cohort of 221 Children with Sickle Cell Anemia or Sβ⁰-Thalassemia and Their Association with Clinical and Hematological Features