Cell-Free DNA and Cell-Free Fetal DNA
Cell-free DNA fragments (cfDNA) are short fragments of DNA which can be found circulating in the blood. During pregnancy, cfDNA fragments originating from both the mother and fetus are present in maternal blood circulation. Cell-free fetal DNA (cfDNA) is present only as a minor component of the total cfDNA in maternal plasma, which poses a significant technical challenge for some NIPT detection methods.
How does NIFTY® work?
The NIFTY test requires taking a small maternal blood sample of 10ml. cfDNA in the maternal blood is then analysed to detect for chromosomal abnormality. If aneuploidy is present, small excesses or deficits in counts of the affected chromosome will be detected.
NIFTY effectively resolves the difficulty in measuring the small increments in the specific chromosome DNA concentration through the use of massively parallel sequencing technology (MPS). This means NIFTY sequences millions of fragments of both fetal and maternal DNA from each sample. Using whole-genome sequencing technology and four different proprietary bioinformatics analysis pipelines, the NIFTY test is able to analyse data across the entire genome and compare chromosomes in the tested sample against optimal reference chromosomes to accurately determine the presence of genetic abnormality.
As opposed to the ‘targeted sequencing’ methods employed by some other NIPT tests, the NIFTY methodology allows for highly accurate results irrespective of the clinical symptoms of the patient, and a broader range of testing options including for trisomy, sex chromosomal aneuploidy and deletion syndromes.
Genetic Conditions Tested by NIFTY
A trisomy is a type of aneuploidy in which there are three chromosomes instead of the usual pair. Trisomy 21 (Down syndrome), Trisomy 18 (Edwards syndrome) and Trisomy 13 (Patau syndrome) are the three most commonly occurring autosomal chromosome aneuploidies in live births. These chromosomal conditions are caused by the presence of an extra copy or partial copy of chromosome 21, 18 or 13 respectively. This additional genetic material can cause dysmorphic features, congenital malformation and different degrees of intellectual disability.
Deletion syndromes are defined as a group of clinically recognisable disorders characterised by a small deletion of a chromosomal segment. The size and position of the deletion determine which clinical features are manifested and how severe they are.
Clinical features of deletions can include developmental delays and intellectual disability, growth differences, behavioural problems, feeding difficulties, low muscle tone, seizures, dysmorphic features and a pattern of varying malformations.
Sex Chromosomal Aneuploidies
Sex chromosome aneuploidy is defined as a numeric abnormality of an X or Y chromosome, with addition or loss of an entire X or Y chromosome. Although most cases of sex chromosome aneuploidies are generally mild without intellectual disability, some have a well-established phenotype that can include physical abnormalities, learning delays and infertility.
List of 60 microdeletion/duplication syndromes included in this test.
|1p36 microdeletion Syndrome||Jacobsen Syndrome|
|Van der Woude Syndrome I (VWS)||1q41-q42 microdeletion Syndrome|
|12q14 microdeletion Syndrome||14q11-q22 deletion Syndrome|
|Feingold Syndrome I||Dandy-Walker Syndrome (DWS)|
|Split-Hand/Foot Malformation type 5 (SHFM5)||Angelman Syndrome/Prader-Willi Syndrome|
|Glass Syndrome||Deafness-infertility Syndrome|
|Holoprosencephaly type 6 (HPE6)||15q26 overgrowth Syndrome|
|Microphthalmia type 6 Syndrome, pituitary hypoplasia||Diaphragmatic hernia, congenital (HCD/DIH1)|
|Rieger Syndrome type 1 (RIEG1)||5q21.1-q31.2 deletion Syndrome|
|Cri du Chat (5p deletion) Syndrome||16p11.2-p12.2 microdeletion Syndrome|
|Cornelia de Lange Syndrome I (CDLS)||16p11.2-p12.2 microduplication Syndrome|
|Alpha Thalassemia, Mental Retardation Syndrome||Potocki-Lupski Syndrome (17p11.2 duplication Syndrome)|
|Saethre-Chotzen Syndrome (SCS)||17q21.31 deletion Syndrome|
|8p23.1 duplication Syndrome||17q21.31 duplication Syndrome|
|8p23.1 deletion Syndrome||Holoprosencephaly type 4 (HPE4)|
|Trichorhinophalangeal type I Syndrome||Chromosome 18p deletion Syndrome|
|Branchlootorenal dysplasia Syndrome I (BOR)/Melnick-Frazer Syndrome||Duchenne/Becker muscular dystrophy (DMD/BMD)|
|Distal Arthrogryposis type 2B (DA2B)||Chromosome 18q deletion Syndrome|
|Langer-Giedion Syndrome (LGS)||Holoprosencephaly type 1 (HPE1)|
|Monosomy 9p Syndrome||Cat-eye syndrome (CES)|
|DiGeorge type 2 Syndrome (DGS2)||Microphthalmia with linear skin defects|
|Split-hand/foot malformation type 3 (SHFM3)||Orofaciodigital Syndrome|
|Chromosome 10q22.3-q23.31 microdeletion Syndrome||Dyggve-Melchior-Clausen Syndrome (DMC)|
|Bannayan-Riley-Ruvalcaba Syndrome (BRRS)||Xp11.22-p11.23 microduplication Syndrome|
|Cowden Syndrome (CD)||Aniridia II & WAGR Syndrome|
|Chromosome 10q deletion Syndrome||Leukodystrophy with 11q14.2-q14.3|
|Androgen insensitivity syndrome (AIS)||X-linked lymphoproliferative syndrome (XLP)|
|Wilms tumour 1 (WT1)||Panhypopituitarism, X-linked|
|11q11-q13.3 duplication Syndrome||Mental retardation X-linked growth hormone. Def (MRGH)|