Using Preimplantation Genetic Diagnosis to Create a Stem Cell Donor: Issues, Guidelines & Limits

2003 ◽  
Vol 31 (3) ◽  
pp. 327-339 ◽  
Author(s):  
Susan M. Wolf ◽  
Jeffrey P. Kahn ◽  
John E. Wagner

Successful preimplantation genetic diagnosis (PGD) to avoid creating a child affected by a genetically-based disorder was reported in 1989. Since then PGD has been used to biopsy and analyze embryos created through in viuo fertilization (IVF) to avoid transferring to the mother’s uterus an embryo affected by a mutation or chromosomal abnormality associated with serious illness. PGD to avoid serious and early-onset illness in the child-to-be is widely accepted. PGD prevents gestation of an affected embryo and reduces the chance that the parents will be faced with a difficult decision of whether to terminate the pregnancy. More controversial have been PGD to select the sex of the child-to-be for “family balancing” (rather than to avoid a sex-linked disorder), PGD for mere susceptibility to disease and for late-onset disorders such as Alzheimer diseas, and most controversially, PGD to create a donor child who is Human Leukocyte Antigen (HLA-matched with a preexisting sibling in need of stem cell transplant.

2015 ◽  
Vol 61 (4) ◽  
pp. 617-626 ◽  
Author(s):  
Yanwen Xu ◽  
Shengpei Chen ◽  
Xuyang Yin ◽  
Xiaoting Shen ◽  
Xiaoyu Pan ◽  
...  

Abstract BACKGROUND The embryonic genome, including genotypes and haplotypes, contains all the information for preimplantation genetic diagnosis, representing great potential for mendelian disorder carriers to conceive healthy babies. METHODS We developed a strategy to obtain the full embryonic genome for a β-thalassemia–carrier couple to have a healthy second baby. We carried out sequencing for single blastomere cells and the family trio and further developed the analysis pipeline, including recovery of the missing alleles, removal of the majority of errors, and phasing of the embryonic genome. RESULTS The final accuracy for homozygous and heterozygous single-nucleotide polymorphisms reached 99.62% and 98.39%, respectively. The aneuploidies of embryos were detected as well. Based on the comprehensive embryonic genome, we effectively performed whole-genome mendelian disorder diagnosis and human leukocyte antigen matching tests. CONCLUSIONS This retrospective study in a β-thalassemia family demonstrates a method for embryo genome recovery through single-cell sequencing, which permits detection of genetic variations in preimplantation genetic diagnosis. It shows the potential of single-cell sequencing technology in preimplantation genetic diagnosis clinical practices.


2008 ◽  
Vol 17 (3) ◽  
pp. 261-269 ◽  
Author(s):  
SVEN OVE HANSSON

Three of the bioethical issues recently discussed in Sweden appear to be particularly interesting also to an international audience. A new law allowing restrictive use of preimplantation genetic diagnosis (PGD)/human leukocyte antigen (HLA) (“savior siblings”) has been implemented, a new recommendation for the cessation of life-sustaining treatment has been issued, and the scope of individual responsibility for medical mistakes has been rather thoroughly discussed.


Blood ◽  
2008 ◽  
Vol 112 (10) ◽  
pp. 4337-4342 ◽  
Author(s):  
Miquel Granell ◽  
Álvaro Urbano-Ispizua ◽  
Aina Pons ◽  
Juan Ignacio Aróstegui ◽  
Bernat Gel ◽  
...  

Abstract The inflammasomes are macromolecular cytosolic complexes involved in the production of interleukin-1β (IL-1β) and IL-18 in response to several pathogen-derived stimuli. Such interleukins have been implicated in the origin of severe allogeneic stem cell transplant (allo-SCT) complications. We analyzed the relationship between the interindividual variability in inflammasome protein-encoding genes in donors and patients and clinical outcome after allo-SCT. Fourteen common genetic variants in 5 genes of the inflammasome, namely, NLRP1, NLRP2, NLRP3, CARD8, and CASP5, were genotyped in 133 human leukocyte antigen-identical sibling pairs undergoing allo-SCT. In the multivariate analysis, donor variants in NLRP2 and NLRP3 were the most important prognostic factors for the clinical outcome after allo-SCT. Thus, donor TT genotype at rs10925027 in NLRP3 was associated with disease relapse (odds ratio (OR) = 6.3, P = 1 × 10−7), and donor GG genotype at rs1043684 in NLRP2 was associated with nonrelapse mortality (OR = 4.4, P = 6 × 10−4) and overall survival (OR = 3.1, P = .001). In addition, patient AA genotype at rs5862 in NLRP1 was associated with nonrelapse mortality (OR = 2.8, P = .005) and overall survival (OR = 2.0, P = .009). These results suggest that inflammasome genetic variants are important prognostic factors for the outcome of allo-SCT. If validated in larger studies, including unrelated allo-SCT, NLRPs genotype would become an important factor in donor selection.


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