Capçalera

Qgenomics

Genomics for human health

qTrisomy® Plus Test

What is an aneuplody?

An aneuploidy consists in an abnormal number of chromosomes of an individual. There are two main types of aneuplodies: trisomies and monosomies.

A trisomy refers to the presence of an additional chromosome in the genome of an individual. Trisomies affecting chromosomes 13, 18 & 21 are compatible with life and are the genetic cause of Patau, Edwards and Down syndromes, respectively. The combined incidence of these trisomies is about 1 in 700 newborns, and they represent one the main causes of genetic condition. Trisomies in the sex chromosomes also occur with a relatively high frequency (~1/1000 births) but their phenotypic consequences are much milder and are not always diagnosed.

Monosomies occur when one of the copies of a certain chromosome is missing. Turner syndrome (45, X0) is caused by a monosomy of the X chromosome in women. It's incidence is estimated in ~1/2000 female births.

The qTrisomy® Plus Test

The qTrisomy® Plus Test is a laboratory test that allows estimating, through maternal blood, the risk of presence of a trisomy 13, 18 o 21 in the phoetus, as well as aneuplodies of the sex chromosomes. Cell-free fetal DNA present in maternal blood plasma is analyzed by means of massively parallel sequencing and modern bioinformatic algorithms. It exhibits clear advantages over actual methods for screening and diagnosing trisomies, but it should NOT be considered as diagnostic, as it is still considered a research test:

MethodInvasive?GA*To consider:

Biochemical Triple Screening + 
Nuchal translucency

NO11-14False positive rate: 5-10%
Detection rate: 60-80%
Chorion biopsySI10-14Miscarriage risk: 1-2%
AmniocentesisSI16-21Miscarriage risk <1%
qTrisomy® TestNO12-22No miscarriage risk  
False positive rate: <1%
Detection rate: >99%

Why qTrisomy® Plus Test?

+ SAFETY. Since the starting material is maternal venous blood, it is completely harmless for the foetus. 

+ SENSITIVITY & SPECIFICITY. Published data in peer-reviewed international journals report specificity and sensitivity taxes above 99% for trisomy 21.

+ ROBUSTNESS. Since it does not depend on cell culture and can be performed in a wide range of gestation weeks.

 

 SensitivitySpecificityPPVNPV
Trisomy 13 [1]100%98,9%89,3%100%
Trisomy 18 [1]91,9%98,0%87,2%98,8%
Trisomy 21 [2]100%97,9%96,6%100%


How does the qTrisomy® Plus Test work?

4 simple steps:

  1. separation of cell-free DNA present in maternal plasma
  2. massive parallel sequencing of cell-free DNA that contains a small proportion of fetal DNA.
  3. Alignment and determination of chromosome origin of each sequence fragment. Counting of unique sequences from a certain chromosome. 
  4. Bioinformatic and statistical analysis of reads to calculate an statistic (Z-Score) that indicates the risk of fetal trisomy by comparing the number of unique sequences in a certain chromosome in control individuals with that in the index case.

Special situations in which qTrisomy® Plus Test can be used

  • Gestation week 10!!!
  • Multiple pregnancies (only after gestation week 12). In this situation it is not possible to reliably establish fetal sex neither determination of sex chromosome aneuploidies.
  • Pregnancies obtained after egg donation.

Before ordering the test, please take into account that: 

- The test requires 6 to 8mL of maternal peripheral blood, collected either in EDTA tubes or in Streck Cell-Free DNA™ BC Tubes.

- The genetic counseling act and signature of an informed consent document are mandatory before sample processing. We will provide a document prototype that can be used for these purposes. 

- Time between blood draw and processing of plasma is crucial for stability and quality of the fetal DNA preparation, this is why:

  • We advice you to contact the laboratory the day before phlebotomy, so logistics can be properly arranged.
  • If blood is collected in EDTA tubes, sample must be kept refrigerated at 4ºC and has to arrive to qGenomics in no more than 3 hours for further processing. 
  • If you anticipate that it might take longer for the sample to arrive to qGenomics, blood needs to be collected using Streck Cell-Free DNA® BC Tubes. In this case, tubes must be kept, and shipped, at room temperatura (do not refrigerate!!!) and need arrive in place before 36 hours. 

 


Bibliography

1. Chen EZ, et al. (2011) Noninvasive Prenatal Diagnosis of Fetal Trisomy 18 and Trisomy 13 by Maternal Plasma DNA Sequencing. PLoS ONE 6(7): e21791
2. Chiu R.W. et al. (2011). Non-invasive prenatal assessment of trisomy 21 by multiplexed maternal plasma DNA sequencing: large scale validity study. BMJ 2011:342:c7401
3. Canick JA, Kloza EM, Lambert-Messerlian GM, Haddow JE, Ehrich M, van den Boom D, Bombard AT, Deciu C, Palomaki GE. DNA sequencing of maternal plasma to identify Down syndrome and other trisomies in multiple gestations. Prenat Diagn. 2012 Aug;32(8):730-4.
4. Lau TK, Jiang F, Chan MK, Zhang H, Lo PS, Wang W. Non-invasive prenatal screening of fetal Down syndrome by maternal plasma DNA sequencing in twin pregnancies. J Matern Fetal Neonatal Med. 2013 Mar;26(4):434-7