The evolution and practical application of genetic testing

Genetic testing began in the 1950s when scientists discovered that an extra copy of chromosome 21 caused trisomy 21, also known as Down syndrome. Chromosome staining methods have been used to sort and count chromosomes, a process called karyotyping. This process, combined with the ability to collect fetal cells from the amniotic fluid of a pregnant woman, has enabled scientists to perform genetic prenatal screening. These tests revealed DNA-based diagnoses of genetic disorders caused by biological irregularities such as too many chromosomes, too few, or clumps of chromosomes in the wrong places. As genetic testing became more widespread, scientists began to search for the substance of DNA, the chemical structure deciphered in 1953 by Rosalind Franklin, James Watson, and Francis Crick. Over the following decades, it was discovered that helix-shaped models of paired chemical bases – adenine, thymine, cytosine, and guanine – provided a code that cells would decode into amino acids, the building blocks of proteins. Scientists have also found, through research on the human genome, that approximately 98% of DNA does not actually code for proteins and is considered “unwanted DNA”.


As the science around genetics has developed, the application and use in obstetric medicine has also expanded. Many diseases that affect humans have a genetic component. Some disorders are passed on from parents to their children during conception. A change in the DNA sequence from the normal sequence can lead to a genetic disorder. These genetic disorders can result from a mutation in one gene (monogenic disorder), mutations in several genes (inherited multifactorial disorder), a combination of genetic mutations and environmental factors, or damage to chromosomes (changes in the number or the structure of whole chromosomes, the structures that carry genes).

Advances in genetic mapping and technology have increased the accessibility and affordability of pre-conception carrier screening for couples considering pregnancy. With advanced reproductive technologies now available, carrier screening before conception enables a woman and her reproductive partner to make informed reproductive decisions.

Systemic genetic testing has been available in the United States since the 1960s, when Dr. Robert Guthrie developed the newborn screening test for phenylketonuria, a metabolic disorder also known as PKU. Since 1964, the Minnesota Department of Health has coordinated the screening of all newborns for more than 50 inherited or congenital disorders through a blood test between 24 and 48 hours after birth. In 2010, the Uniform Recommended Screening Committee (RUSP) was adopted as the national standard for newborn screening, comprising five main categories: (1) hemoglobinopathies, (2) organic acid disorders, (3) acid disorders amino, (4) acid oxidation disorders, and (5) miscellaneous disorders, such as cystic fibrosis and hypothyroidism. The newborn screening program is the world’s largest genetic screening program, with approximately 4 million infants tested each year. Although advances in newborn genetic screening programs have improved detection and early intervention for treatable genetic diseases, newborn testing cannot replace preconception or early prenatal screening of carriers in parents.

From 2017, obstetricians were advised to extend the offer of genetic screening to their patients. Two committee opinions from the American College of Obstetricians and Gynecologists (ACOG), published in the March 2017 issue of Obstetrics & Gynecology, expanded the guidelines for screening for carriers of genetic disorders. These committee opinions were issued in response to the availability and affordability of extensive genetic testing that could screen for hundreds of conditions in a single test, as well as in response to the dilution of ethnic population concentrations that had previously guided genetic screening recommendations. ACOG Opinion 690, “Carrier Screening in the Age of Genomic Medicine,” includes general guidelines; and Committee Opinion 691, “Screening for carriers of genetic diseases”, deals with testing for specific diseases.

The opinions of the committee distinguish three fields of application of genetic screening:

  • ethnically specific, such as Tay-Sachs disease in people of Ashkenazi Jewish descent;
  • panethnic (for everyone), such as a test for cystic fibrosis, spinal muscular atrophy and fragile X syndrome offered to all patients; and
  • extensive carrier screening, which analyzes up to hundreds of conditions.

The general recommendation advises healthcare providers to “establish a one-size-fits-all approach” that they routinely offer to patients, including counseling and informed consent. The advice should include a discussion of the “residual risk” resulting from de novo mutations and mutations not included in test panels. At a minimum, the committee’s opinions advised that all patients should be offered screening for cystic fibrosis, spinal muscular atrophy and hemoglobinopathies, as these are the most common inherited recessive conditions.

Advances in genetic science have led to the availability of preconception screening, offering couples seeking to become pregnant the opportunity to test for genetic changes that have little or no impact on their own health but can cause significant health problems for them. their children. ACOG defines carrier testing as “a genetic test performed on an asymptomatic person to determine whether that person has a mutation or abnormal allele in a gene associated with a particular disorder.” Genetic changes carried by both partners can cause a health problem if both copies of the genetic change are inherited by a child. These are known as autosomal recessive conditions. The genetic changes which are carried by the female partner and cause a health problem when a male child inherits the genetic change are known as X-linked conditions.

Carrier testing is particularly useful for consanguineous couples, whose offspring are at high risk of inheriting recessive mutations from common ancestors. Prenatal carrier screening provides information for diagnostic tests of the fetus or newborn, for termination of pregnancy or for the organization of care.

Ideally, carrier screening should take place before pregnancy. If both partners are carriers of the same genetic disease, genetic counseling is recommended to help couples understand the meaning of test results and the reproductive options available, such as in vitro fertilization (IVF) with prenatal diagnosis and testing. preimplantation genetics of embryos, or the use of donor gametes.

ACOG’s current guidelines are that women’s health care providers offer carrier testing to all people who express an interest in becoming pregnant, regardless of ethnicity or family history. Recent advances in genetic testing technology with next-generation sequencing make expanded carrier screening readily available to most couples. When couples present for pre-conception health assessments, a provider has a duty to notify availability and offer carrier screening. When genetic testing is not offered to people who request a preconception assessment, it is a deviation from accepted standards of care and could result in a claim for misconception in certain circumstances.

With the additional scientific knowledge gained through the National Institutes of Health Human Genome Project and derivative research, we can expect continued expansion of the applications of genetic science.

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