Genetic Screening: Science, Applications, and Ethics

Introduction

Genetic screening is one of the most controversial topics in the scientific arena today. The advent of the Human Genome Project, which maps the complete human genetic code, has brought this issue to the forefront. This paper discusses the basic science that underlies genetic screening, surveys its principal applications, and investigates some of the common misconceptions and ethical questions about its use.

Genetic screening itself is simply "the systematic search within a population for persons possessing particular genotypes, which are either associated with disease, predisposing to disease, or leading to disease in descendants" (Miller). In simpler terms, genetic screening involves testing an individual's genetic material to predict present or future disability or disease, either for oneself or one's offspring (McCarrick). Genetic screening is conducted for several basic reasons: the care of the ill and the prevention of disease, providing reproductive information, determining the incidence of disorders in the general population, and research (Miller).

In recent years, the incidence of genetic screening has increased rapidly. Tests for cystic fibrosis jumped from 9,310 tests in 1991 to 63,000 tests in 1992, according to the U.S. Congress' Office of Technology Assessment. The National Institutes of Health has since recommended routine cystic fibrosis testing for all six million American women who become pregnant each year (McCarrick).

The potential for growth in the application of genetic screening is tremendous. As genes linked to breast cancer are identified, the idea of regular genetic testing for all women is becoming more realistic. Further, as the population ages, interest in genetic testing for age-related diseases such as Alzheimer's disease continues to grow (McCarrick).

Scientific Basis of Genetic Screening

An understanding of genetic screening rests solidly on a basic understanding of genes and DNA. DNA (deoxyribonucleic acid) is a nucleic acid inside a cell's nucleus that contains the basic genetic instructions for the biological development of an organism. DNA is built around a famous double-helix structure that resembles a spiral staircase. Each of the "rails" or sides of the DNA double helix is made of a strand of DNA composed of a sugar, a phosphate, and one of four DNA base nucleotides: adenine (A), thymine (T), cytosine (C), and guanine (G). Each base can only hydrogen-bond to one complementary base (A binds to T, and C binds to G); therefore, the identity of base pairs on one strand determines the identity of bases on the opposing strand. When the double helix is separated, each strand can act as a template to replicate the other (Alberts).

The sequence of nucleotides (bases) on a DNA strand is crucial. That sequence identifies a specific protein, which is the basic building block of the organism. Each series of three nucleotides (a codon) codes for a specific amino acid. Specific combinations of amino acids make up a particular protein. The relationship between the amino acid sequence of a protein and the nucleotide sequence is known as the genetic code.

Genes are pieces of DNA described as the "functional and physical unit of heredity passed from a parent to offspring" (Genetic Science Learning Center). Most genes contain the information needed to make a specific protein. In molecular biology, genes are segments of DNA located within chromosomes (Alberts).

A chromosome is a long, continuous piece of DNA. Humans have 46 chromosomes. Somatic cells (body cells) are diploid, meaning they carry two sets of chromosomes — one from the mother and one from the father. In contrast, gametes (eggs and sperm) are haploid, meaning they contain only one set of chromosomes. When an egg is fertilized by a sperm, the single set of chromosomes from each parent join to form a cell with a complete double set. There are many types of chromosomal aberrations that lead to disease. Perhaps the most commonly recognized is Down syndrome, in which individuals carry an extra chromosome 21, leading to intellectual disability. In Turner syndrome, an individual has only one X chromosome rather than the typical XX (female) or XY (male) configuration, resulting in underdeveloped female sexual characteristics (Alberts).

A mutation is a permanent, transmissible change to the genetic material of an organism. Mutations can occur during cell division or result from exposure to chemicals, radiation, or viruses. Harmful mutations can lead to cancer and often result in cell death or malfunction. Rarely, mutations are favorable and are considered a primary driving force in the theory of natural selection. Neutral mutations do not affect the organism and can accumulate over time. Many mutations do not cause disorders because they are repaired by cellular mechanisms. Because humans have two copies of each chromosome and two copies of each gene, the intact copy can usually compensate for the mutant gene (Genetic Science Learning Center; Alberts).

Mutations can be naturally occurring (spontaneous) or induced by mutagens such as chemicals or radiation. There are three main types: point mutations, insertions, and deletions. Point mutations occur when a single nucleotide is exchanged for another, and are often caused by errors during replication or by chemical exposure. Insertions occur when one or more extra nucleotides are added to the DNA sequence and can cause a shift in the reading frame, profoundly altering the resulting protein. Deletions occur when one or more nucleotides are removed from the DNA sequence, which can similarly alter the reading frame. Insertions and deletions are irreversible (Alberts).

Genetic disorders can be separated into four main categories: chromosome abnormalities, single-gene disorders, multifactorial disorders, and mitochondrial disorders (Genetic Science Learning Center).

Chromosome abnormalities occur when entire chromosomes or large segments are altered, duplicated, or missing. Turner syndrome and Down syndrome are examples. In individuals with chromosome abnormalities, the karyotype (a visual display of chromosomes within a single cell) is altered. Other examples include Klinefelter syndrome, Cri du chat syndrome, Williams syndrome, Reciprocal Translocation (Philadelphia Chromosome), and Robertsonian Translocation (Genetic Science Learning Center).

Single-gene disorders occur when a mutation results in the alteration or loss of a protein produced by a single gene. Sickle cell anemia is a well-known example (Genetic Science Learning Center).

Multifactorial disorders arise when multiple genes are mutated and are often associated with environmental factors. These disorders are difficult to treat and study, and include diabetes, cancer, and heart disease (Genetic Science Learning Center).

Mitochondrial disorders are rare and are caused by mutations in the non-chromosomal DNA found within mitochondria. Mitochondria — often called the cell's powerhouse — are organelles that use sugar and oxygen to produce energy. Each cell contains many mitochondria, and each mitochondrion carries its own DNA. Mitochondrial DNA is inherited exclusively from the mother (Genetic Science Learning Center).

Application of Genetic Testing

There are five main areas of focus within genetic testing: prenatal diagnosis, newborn screening, carrier screening, forensic screening, and susceptibility screening (McCarrick).

In prenatal diagnosis, a fetus is assessed for risk of a range of genetic traits or diseases. Amniotic fluid, fetal cells, and maternal or fetal blood cells are obtained through alpha-fetoprotein assays, chorionic villus sampling, amniocentesis, or, less invasively, ultrasound. In the United States, prenatal screening began in 1966, and the number of identifiable disorders and metabolic defects continues to grow. Testing of embryos prior to implantation in the uterus represents one potential application of this technology, enabling selection of embryos free of specific genetic diseases (McCarrick).

Newborn screening takes place in early infancy and involves testing blood or tissue for genetic diseases. The hope is that early intervention can help avert serious health problems or even mortality. Newborn screening is well established in the United States; the first instance was the screening of newborns for phenylketonuria (PKU), a disorder that can be managed through a strict diet. Since then, testing of African-American babies for sickle cell anemia and Ashkenazic Jewish babies for Tay-Sachs disease has also become common (McCarrick).

Carrier screening identifies individuals who carry a chromosomal or genetic abnormality that may affect them or their children. Blood or tissue samples are tested for changes in DNA or chromosomes, or for the presence of a genetic trait associated with inherited disease. Tests for sickle cell anemia and Tay-Sachs disease are common, but tests for Huntington's disease, Duchenne muscular dystrophy, cystic fibrosis, hemophilia, and neurofibromatosis have also become more prevalent. Often, carrier screening is conducted across large cross-sections of the general population, with results stored in a central database to determine the prevalence of a disorder (McCarrick).

In forensic testing, individuals are screened to determine a genetic link between suspects and evidence from police investigations. Results of these tests are admissible in courts and have been used to conclusively establish guilt or innocence (McCarrick).

Susceptibility testing is used to identify individuals most at risk for certain disorders. For example, workers can be screened for susceptibility to toxic substances in the workplace that can cause specific conditions. It is estimated that approximately 390,000 susceptible workers are disabled by occupational illnesses each year, while many of their non-susceptible co-workers remain unaffected (McCarrick).

Conclusion

While the scientific basis of genetic screening is relatively straightforward, the social and ethical issues surrounding it are far more difficult to resolve. Common misconceptions about genetic screening add fuel to these controversies, and meaningful solutions will require sustained public debate, careful policy consideration, and patience.

Works Cited

Alberts, Bruce. Molecular Biology of the Cell, 4th ed. New York: Garland Science, 2002.

Genetic Science Learning Center. "Genetic Disorder Corner." University of Utah, 2004. http://gslc.genetics.utah.edu/units/disorders/

McCarrick, Pat Milmoe. "Genetic Testing and Genetic Screening." Scope Note 22. National Reference Center for Bioethics Literature, Georgetown University, 1993. Kennedy Institute of Ethics Journal. Reprinted September 1993. Last updated February 2002.

Miller, Kelly. "Genetic Screening." Intermediate Genetics course paper. North Dakota State University, 1999.