Speciality
Spotlight

 




 


Genetics


    

 





 Preimplantation Genetic Diagnosis

      

  • First Unaffected Pregnancy Using Preimplantation Genetic Diagnosis for Sickle Cell Anemia.


    Xu K, Shi ZM, Veeck LL, et al (Cornell Univ., New York; Wayne State Univ., Detroit)

    JAMA 281:1701-1706, 1999

      


    Using FSH and HCG to stimulate multiple ovulation, the authors employed IVF and biopsies 2.7 to 3 days after fertilization. Embryos were then transferred to the uterus on day 4 after fertilization. In the first trial, 1 of 4 embryos proved to be genetically normal but failed implantation. In a second trial, 3 of 7 embroyos, either normal (AA) or showing sickle cell trait (AS), were inserted and resulted in 2 AA normal females. In one of the successful transplants, 2 of 7 embryonic cells were removed for biopsy but after 24 hours, the 5 embryonic cells in the morula had increased to 7 in number and thereafter subsequently developed normally.

       


    This experience helps confirm that much of what is known about PGD in animal species is valid in the human. In particular, the ability to remove nearly 30% of the embryonic cells of an early human embryo without interference with implantation and development is of special importance.

        
  • Prenatal Diagnosis with use of Fetal Cells Isolated from Maternal Blood : Five color fluorescent in Situ Hybridization Analysis on Flowsorted Cells for Chromoscomes X, Y, 13, 18 and 21.


    Bischoff FZ, Lewis DE, Nguyen DD, et al (Bayor College of Medicine, Houston; Univ of Tennesee, Memphis). Am J Obstet Gynecol 179:203-209, 1998

      


    Current prenatal cytogenetic diagnostic methods are invasive and carry a small risk to the fetus. It is known that fetal cells exist in the maternal circulation, albeit at very low levels (1 fetal cell in 1 x 104 to 1 x 107 nucleated maternal cells), and can be detected. A 1 step hybridization reaction for 5 color fluorescent in situ hybridization for simultaneous detection of chromosomes, X, Y, 13, 18 & 21 on flow sorted nuclei from maternal blood samples was described.

      


    Conclusion : The 5 color fluorescent in situ hybridization technique allowed accurate and simultaneous analysis of chromosomes X, Y, 13, 18 & 21 in 97.2% of enriched nuclei isolated from maternal blood samples by flow cytometry. Although this procedure is currently costly, it is hoped that cost will decrease as the procedure is automated. This method has promise for noninvasive prenatal screening.

       


    To separate fetal cells present in concentrations less than 1 in a 100,000 in maternal blood with sufficient cell preservation to allow reactivity in recombinant DNA technology is a wonderful accomplishment.

       
  • Screening of Maternal Serum for Fetal Down’s Syndrome in the First Trimester

    Haddow JE, Palomaki GE, Knight GJ, et al (Found for Blood Research Scarborough, Me: Prenatal Diagnostic Ctr, Lexington, Mass) N Engl J Med 338:955-961, 1998

       


    Nearly all testing of pregnant women for Down syndrome takes place in the second trimester. The finding that maternal serum a- fetoprotien concentrations were relatively low at 9 to 12 weeks of gastation in the presence of Down syndrome led to studies of other potential serum markers a-fetoprotein, unconjugated estriol, human chorionic gonadotropin (hCG), the free beta unit of hCG, and pregnancy associated protein A in screening for Down syndrome in the first trimester was determined.

        


    Study participants were 4,412 women with singleton pregnancies who were referred for chorionic villus sampling or amniocentesis. The women ranged in age from 15 to 51; 82% were or older.Rates of detection of Down syndrome were highest for pregnancy associated protein A(42%), HCG(29%), and the free beta subunit of HcG (25%) and lowest for unconjugated estriol (4%) and a fetoprotein – (17%). When used in combination with the serum concentration of pregnancy associated protein A and maternal age, HCG achieved a 63% detection rate, and its free beta subunit achieved a 60% detection rate for Down syndrome. (at false-positive rates of 5%). 

       


    Conclusion Measurement of pregnancy associated protein A and either HCG or its free beta subunit in maternal serum may allow screening for Down syndrome to be carried out in the first trimester.
     

       
  • GA Harrison, KE Humphrey, N Jones et al (Macquarie Univ, North Ryde, Australia; Univ of New South Wales, Sydney, Australia; Royal Women’s Hosp, Carlton, Australia)

    A Genomewide Linkage Study of Preeclampsia/Eclampsia Reveals Evidence for a Candidate Region on 4q.

    Am J Hum Genet 60:1158-1167, 1997.

       


    A region on the long arm of chromosome 4 has been identified as a strong candidate region for the preeclampsia/eclampsia syndrome. This finding needs to be replicated in other pedigrees before it is accepted as a true linkage.

       

 



 

 

Speciality Spotlight

 

 
Genetics
    

 

 Preimplantation Genetic Diagnosis
      

  • First Unaffected Pregnancy Using Preimplantation Genetic Diagnosis for Sickle Cell Anemia.
    Xu K, Shi ZM, Veeck LL, et al (Cornell Univ., New York; Wayne State Univ., Detroit)
    JAMA 281:1701-1706, 1999
      
    Using FSH and HCG to stimulate multiple ovulation, the authors employed IVF and biopsies 2.7 to 3 days after fertilization. Embryos were then transferred to the uterus on day 4 after fertilization. In the first trial, 1 of 4 embryos proved to be genetically normal but failed implantation. In a second trial, 3 of 7 embroyos, either normal (AA) or showing sickle cell trait (AS), were inserted and resulted in 2 AA normal females. In one of the successful transplants, 2 of 7 embryonic cells were removed for biopsy but after 24 hours, the 5 embryonic cells in the morula had increased to 7 in number and thereafter subsequently developed normally.
       
    This experience helps confirm that much of what is known about PGD in animal species is valid in the human. In particular, the ability to remove nearly 30% of the embryonic cells of an early human embryo without interference with implantation and development is of special importance.
        
  • Prenatal Diagnosis with use of Fetal Cells Isolated from Maternal Blood : Five color fluorescent in Situ Hybridization Analysis on Flowsorted Cells for Chromoscomes X, Y, 13, 18 and 21.
    Bischoff FZ, Lewis DE, Nguyen DD, et al (Bayor College of Medicine, Houston; Univ of Tennesee, Memphis). Am J Obstet Gynecol 179:203-209, 1998
      
    Current prenatal cytogenetic diagnostic methods are invasive and carry a small risk to the fetus. It is known that fetal cells exist in the maternal circulation, albeit at very low levels (1 fetal cell in 1 x 104 to 1 x 107 nucleated maternal cells), and can be detected. A 1 step hybridization reaction for 5 color fluorescent in situ hybridization for simultaneous detection of chromosomes, X, Y, 13, 18 & 21 on flow sorted nuclei from maternal blood samples was described.
      
    Conclusion : The 5 color fluorescent in situ hybridization technique allowed accurate and simultaneous analysis of chromosomes X, Y, 13, 18 & 21 in 97.2% of enriched nuclei isolated from maternal blood samples by flow cytometry. Although this procedure is currently costly, it is hoped that cost will decrease as the procedure is automated. This method has promise for noninvasive prenatal screening.
       
    To separate fetal cells present in concentrations less than 1 in a 100,000 in maternal blood with sufficient cell preservation to allow reactivity in recombinant DNA technology is a wonderful accomplishment.
       
  • Screening of Maternal Serum for Fetal Down’s Syndrome in the First Trimester Haddow JE, Palomaki GE, Knight GJ, et al (Found for Blood Research Scarborough, Me: Prenatal Diagnostic Ctr, Lexington, Mass) N Engl J Med 338:955-961, 1998
       
    Nearly all testing of pregnant women for Down syndrome takes place in the second trimester. The finding that maternal serum a- fetoprotien concentrations were relatively low at 9 to 12 weeks of gastation in the presence of Down syndrome led to studies of other potential serum markers a-fetoprotein, unconjugated estriol, human chorionic gonadotropin (hCG), the free beta unit of hCG, and pregnancy associated protein A in screening for Down syndrome in the first trimester was determined.
        
    Study participants were 4,412 women with singleton pregnancies who were referred for chorionic villus sampling or amniocentesis. The women ranged in age from 15 to 51; 82% were or older.Rates of detection of Down syndrome were highest for pregnancy associated protein A(42%), HCG(29%), and the free beta subunit of HcG (25%) and lowest for unconjugated estriol (4%) and a fetoprotein – (17%). When used in combination with the serum concentration of pregnancy associated protein A and maternal age, HCG achieved a 63% detection rate, and its free beta subunit achieved a 60% detection rate for Down syndrome. (at false-positive rates of 5%). 
       
    Conclusion Measurement of pregnancy associated protein A and either HCG or its free beta subunit in maternal serum may allow screening for Down syndrome to be carried out in the first trimester.
     
       
  • GA Harrison, KE Humphrey, N Jones et al (Macquarie Univ, North Ryde, Australia; Univ of New South Wales, Sydney, Australia; Royal Women’s Hosp, Carlton, Australia)
    A Genomewide Linkage Study of Preeclampsia/Eclampsia Reveals Evidence for a Candidate Region on 4q.
    Am J Hum Genet 60:1158-1167, 1997.
       
    A region on the long arm of chromosome 4 has been identified as a strong candidate region for the preeclampsia/eclampsia syndrome. This finding needs to be replicated in other pedigrees before it is accepted as a true linkage.
       

 

 

By |2022-07-20T16:41:55+00:00July 20, 2022|Uncategorized|Comments Off on Genetic Diagnosis

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