PMID- 20675683
OWN - NLM
STAT- MEDLINE
DCOM- 20110110
LR  - 20100916
IS  - 1460-2350 (Electronic)
IS  - 0268-1161 (Linking)
VI  - 25
IP  - 10
DP  - 2010 Oct
TI  - Diagnostic accuracy: theoretical models for preimplantation genetic testing of a 
      single nucleus using the fluorescence in situ hybridization technique.
PG  - 2622-8
LID - 10.1093/humrep/deq196 [doi]
AB  - BACKGROUND: The aim of this study was to develop and use theoretical models to 
      investigate the accuracy of the fluorescence in situ hybridization (FISH) 
      technique in testing a single nucleus from a preimplantation embryo without the 
      complicating effect of mosaicism. METHODS: Mathematical models were constructed 
      for three different applications of FISH in preimplantation genetic testing (sex 
      determination for sex-linked diseases, two-way reciprocal translocations and 
      sporadic chromosome aneuploidy). The input values were the degree of aneuploidy 
      (initially set at 3% per chromosome for sporadic aneuploidy) and the accuracy per 
      probe (initially set at 95%), defined as the proportion of normal diploid nuclei 
      with a normal signal pattern. The primary statistic was the predictive value of 
      the test result. RESULTS: Testing two chromosome pairs to determine sex 
      chromosome status or detect unbalanced translocation products had high predictive 
      value: at least 99.5% for a normal test result (95% CI: 99-100%), and 90% for an 
      abnormal test result (95% CI: 88-92%). However, the predictive value of an 
      abnormal test result testing five chromosomes for sporadic chromosome aneuploidy 
      was 41% (95% CI: 36-46%); 90% would be achieved with an aneuploidy rate per 
      chromosome of 20.3% (equivalent to 99.5% prevalence for 23 chromosomes) rather 
      than 3%, or with an accuracy per probe of 99.6% rather than 95%, or when testing 
      23 chromosome pairs, rather than 5 pairs, with either 8.3% aneuploidy (86.4% 
      prevalence) or 99.5% accuracy. CONCLUSIONS: Testing a single cell using the FISH 
      technique has the potential to achieve acceptable analytical performance for sex 
      determination and two-way reciprocal translocations, but is unlikely to achieve 
      adequate performance testing for sporadic chromosome aneuploidy. New techniques 
      for detecting the copy number of every chromosome are emerging, but it remains to 
      be seen if the high accuracy required will be achieved.
FAU - Scriven, P N
AU  - Scriven PN
AD  - Cytogenetics Department, GSTS-Pathology, Guy's Hospital, 5th Floor Tower Wing, 
      Great Maze Pond, London SE1 9RT, UK. paul.scriven@gsts.com
FAU - Bossuyt, P M M
AU  - Bossuyt PM
LA  - eng
PT  - Journal Article
DEP - 20100730
PL  - England
TA  - Hum Reprod
JT  - Human reproduction (Oxford, England)
JID - 8701199
SB  - IM
MH  - *Aneuploidy
MH  - Cell Nucleus/genetics
MH  - Chromosomes, Human, X/genetics
MH  - Chromosomes, Human, Y/genetics
MH  - Female
MH  - Genetic Diseases, X-Linked/*diagnosis/*genetics
MH  - Humans
MH  - *In Situ Hybridization, Fluorescence
MH  - Male
MH  - *Models, Genetic
MH  - Pregnancy
MH  - *Preimplantation Diagnosis
MH  - Sensitivity and Specificity
MH  - Sex Determination Analysis
MH  - Translocation, Genetic
EDAT- 2010/08/03 06:00
MHDA- 2011/01/11 06:00
CRDT- 2010/08/03 06:00
PHST- 2010/08/03 06:00 [entrez]
PHST- 2010/08/03 06:00 [pubmed]
PHST- 2011/01/11 06:00 [medline]
AID - deq196 [pii]
AID - 10.1093/humrep/deq196 [doi]
PST - ppublish
SO  - Hum Reprod. 2010 Oct;25(10):2622-8. doi: 10.1093/humrep/deq196. Epub 2010 Jul 30.