Hereditary genetic diseases are passed down through families. Until now, the only way to detect whether a baby had inherited the genetic abnormality from its parents was through invasive prenatal testing, such as chorionic villus sampling or amniocentesis. These techniques make it possible not only to reliably diagnose genetic diseases but also chromosomal abnormalities (such as trisomy 21, which is responsible for Down syndrome, among others). But the invasive nature of these techniques can, in some cases, lead to a loss of pregnancy.
Is there any fetal genetic information in maternal blood that can be tested?
From the 9th week of gestation, there is a progressive release into the mother’s blood of fetal genetic material known as free fetal DNA (cffDNA). Using high-performance DNA sequencing techniques, it is possible to detect and analyze these cffDNA molecules from a simple maternal blood draw.
What can be detected in free fetal DNA analysis?
Initially, the test was developed to diagnose chromosomal abnormalities in the baby that affected chromosomes 13, 18, and 21. Normal human cells contain 46 chromosomes or 23 pairs of chromosomes. The characteristics that will determine how our organism works as well as our morphological characteristics are written in the genes. Genes are made up of DNA and are located on the chromosomes. We inherit 23 chromosomes from each parent through their germ cells (sperm or oocytes). As we have pairs of chromosomes, for each gene we will have two copies. One copy of each gene is inherited from the father and the other is inherited from the mother. Any change in the number, size or structure of our chromosomes can mean a change in the amount or reorganization of genetic information. These changes can result in a learning disability, developmental delay, and health problems in the newborn. For example, 3 copies (trisomy) of one of the chromosomes listed above (13, 18, and 21) in the baby can result in severe genetic syndromes (Patau, Edwards, and Down Syndrome’s, respectively). Subsequently, it has been possible to incorporate the study of all the baby’s complementary chromosomes.
Free fetal DNA analysis can detect any genetic disease.
But not only chromosomal anomalies, but also genetic diseases due to the anomalous alteration (mutation) of a gene, can be diagnosed by analyzing the cffDNA. Inicially, it is possible to analyze any genetic disease of which one of the parents is a carrier or affected, and which are due to a pathogenic point change (other types of mutations may not be detected) in the sequence of the gene. In the case of diseases with recessive inheritance, that is, those that require that both copies of the gene, those from the father and mother, are altered, a non-invasive diagnosis could be made by means of a linkage analysis. This analysis consists of determining which of the two chromosomes of the mother and father is the carrier of the alteration and using this information, which we will call haplotype at risk, for the diagnosis in maternal blood. Depending on the presence or absence of these risk haplotypes in the cffDNA, we can determine whether the baby has inherited one of the alterations, both or neither. Usually, if it is determined that the baby has inherited both haplotypes at risk, and would therefore develop the disease, an invasive confirmatory test is recommended.
The non-invasive prenatal analysis is a great advance in prenatal genetic studies, starting from a sample of maternal blood and without risking pregnancy.