摘要:

Prenatal diagnosis is available for pregnancies at risk for virtually all inherited disorders of hemoglobin production. The field of reproductive genetics must confront many ethical, legal, and social concerns regarding its use, many of which derive from a woman's desire to bear children but legal right to abortion. The goal of more widespread utilization of prenatal diagnosis is sought in the context of questioning the ethical control to be exerted over the biological makeup of future generations. Its appropriate application would be facilitated greatly by the availability of reliable DNA markers of disease severity. Advances in fetal sampling and in detecting mutant globin genes have provided the safe, accurate methodology required for prenatal diagnosis. Chorionic villus sampling in the first trimester has become standard practice, but second trimester amniocentesis also is used for sampling fetal DNA. The use of preimplantation diagnosis and testing fetal cells from the maternal circulation will soon be practical. DNA-based detection of globin gene mutations has been facilitated greatly by the polymerase chain reaction revolution, and several reliable diagnostic methods are available. Polymerase chain reaction-based methods rely on restriction analysis, allele-specific hybridization or amplification, DNA sequence analysis, and new non-polymerase chain reaction methods for DNA amplificationin vitro.These methods are available for detecting hemoglobinopathy, thalassemia, and thalassemic-hemoglobinopathy genes that affectα- orβ-globin loci.

ISSN:0363-0269    

DOI:10.3109/03630269509005812

出版商:Taylor&Francis    

年代:1995

数据来源: Taylor

摘要:

Erythropoiesis is increased in cultures of human blood progenitors when oxygen tension is reduced from 20% (room air) to 5% (low oxygen, closer to physiological bone marrow levels). The effects of low oxygen onγ-globin synthesis and colony growth in methyl cellulose cultures of blood mononuclear cells from normal individuals and patients with sickle cell diseases were examined. Low oxygen increased colony numbers by 1.5- to 2-fold and erythropoietin sensitivity by almost 2-fold. The interval required for maximal colony growth in cultures from patients with sickle cell disease (sickle colonies) was reduced from 17 days in 20% oxygen to 13 days in 5% oxygen. Relative synthesis ofγ-globin was examined by labeling with -3H-leucine and electrophoresis on Triton acid urea poly-acrylamide gels. The %γwas 1.7-fold higher in normal and 1.4-fold higher in sickle cultures on day 13 in low oxygen. On day 16 the expected temporal decline was not seen in low oxygen, and the %γwas 2-fold higher in normal and 1.8-fold higher in the sickle studies. Hemin increased colony growth andγ-globin synthesis in normal cultures in air, and the effects of hemin and low oxygen were additive. In sickle cultures, hemin and low oxygen had additive effects on colony growth, but only low oxygen increasedγ-globin synthesis. Interleukin-3 increased colony numbers on day 13, primarily by acceleration of peak growth. Interleukin-3 also increasedγ-globin synthesis in low oxygen in normal but not sickle cultures. Thus, low oxygen increasesin vitrosensitivity to erythropoietin, colony numbers, and relativeγ-globin synthesis in normal and sickle cultures.

ISSN:0363-0269    

DOI:10.3109/03630269509005813

出版商:Taylor&Francis    

年代:1995

数据来源: Taylor

ISSN:0363-0269    

DOI:10.3109/03630269509005814

出版商:Taylor&Francis    

年代:1995

数据来源: Taylor

ISSN:0363-0269    

DOI:10.3109/03630269509005815

出版商:Taylor&Francis    

年代:1995

数据来源: Taylor

ISSN:0363-0269    

DOI:10.3109/03630269509005816

出版商:Taylor&Francis    

年代:1995

数据来源: Taylor

ISSN:0363-0269    

DOI:10.3109/03630269509005817

出版商:Taylor&Francis    

年代:1995

数据来源: Taylor

ISSN:0363-0269    

DOI:10.3109/03630269509005818

出版商:Taylor&Francis    

年代:1995

数据来源: Taylor

ISSN:0363-0269    

DOI:10.3109/03630269509005819

出版商:Taylor&Francis    

年代:1995

数据来源: Taylor

ISSN:0363-0269    

DOI:10.3109/03630269509005820

出版商:Taylor&Francis    

年代:1995

数据来源: Taylor

ISSN:0363-0269    

DOI:10.3109/03630269509005821

出版商:Taylor&Francis    

年代:1995

数据来源: Taylor