Human Genetic Screening

Manju Karthikeyan

Copyright 1999


Its no accident that off-spring resemble their parents. Deoxyribonucleic acid or DNA, located within each cell nucleus is a special chemical, that determines our genetic inheritance in a very orderly way. Under the microscope DNA looks like a mass of tangled threads which consist of tiny subunits called genes. Genes carry instructions, sometimes called the blueprint of life, for various characters like hair color, height, eye color. Our genes are received from both mother and father, half from each. Genes instruct our bodies to make proteins - which determines the shape and function of each cell. Each gene controls the production of a particular protein. Genes produce millions of different proteins through different arrangements of just four simple molecules the nucleotides - adenine (A), cytosine (C), thymine (T), and guanine (G). These A,C,T and G's are like letters of the alphabet - their order "spells" out the language of life.

The Human Genome Project (HGP) was proposed in the 1980s and was formally initiated in 1990. Its major aims are to map and determine the chemical sequences of the three billion nucleotide base pairs that comprise the human genome. Completion of the HGP in the projected 15 years will provide a source book for biology and medicine. The Human Genome Diversity Project (HGDP) complements the HGP by examining the genomic variation of the human species, through analysis of DNA from populations, families and individuals worldwide.

There are many different techniques involved in gene screening. With the start of the Human Genome Mapping Project some of these techniques have been altered to speed up the screening process. Examples of these techniques include PCR (polymerize chain reaction), RFLP's (restriction fragment length polymorphism), cloning, and the use of markers for specific genes. One of the biggest inventions that has allowed genetic screening to occur was the invention of PCR (polymerize chain reaction) by Kary Mullis which was patented in 1987. This helps to get large number of copies of a single gene with great speed and ease. RAPD's (Randomly Amplified Polymorphic DNA), GAWTS (Genomic Amplification with Transcript Sequencing) and other techniques are being utilized in the mapping and sequencing of the human genome. GAWTS derived from PCR uses the promoter sequence of a T7 or T3 phage. This is attached to one or both of the PCR primers and is translated into RNA for a single strand template for reverse transcriptase. Advantages of this procedure include amplification of the region of interest thus eliminating the need for purification of the sample after PCR is carried out while compensating for poor quality in the PCR reaction. This along with the ease with which GAWTS lends itself to automation can increase the efficiency at which the screening takes place.

Genetic Screening

Genetic screening is a process to analyze blood or skin for the systematic search for persons with a particular genotype in a defined population. It also serves as an important tool of modern preventive medicine. Such screening has the potential to lessen the devastating impact of genetic disease. The purpose is to identify persons whose genotype places them or their offspring at risk [2]. The human race carries 3,000 - 4,000 diseases in its genes. The faulty gene that causes any of these diseases will be a one in 100,000 and 200,000 healthy gene in each cell. In order to locate this faulty gene, scientists search for variations in larger pieces of DNA called "markers". They are found nearby the DNA and become the basis of genetic screening. With such markers it becomes theoretically possible to screen individuals of every age, from infants to adults, even babies before birth [1].

Markers have already been found for various diseases such as Huntington's disease, cystic fibrosis, Duchenne muscular dystrophy, hemophilia and thalassaemia, and some rare cancers. Scientists are also searching for the genetic connection with more common disorders where environment may play a role - Alzheimer's disease, diabetes, epilepsy, certain cancers and heart disease. The term testing is usually used when seeking to identify individuals or those within a family, screening for analyzing samples from a larger group of people, perhaps within a population. However both these terms are often used to describe the same thing as the process and intent is the same: to discover if someone has disease or is a healthy carrier[3].

Genetic screening is currently available for the following:

Sex, abnormal chromosome number, early onset conditions (e.g. sickle cell, cystic fibrosis), late onset conditions (e.g. Huntington disease, polycystic kidney disease), susceptibility to (e.g. hypercholesterol, alcoholism), carriers of recessive genes (e.g. sickle cell, cystic fibrosis) [4].

The Purpose of Genetic Screening

  1. To confirm the diagnosis in patients with symptoms.
  2. To advise other family members of the diagnosed patient whether they also have the disease (or have genetic markers for the disease even if they don't have symptoms), are carriers or are neither.
  3. When one partner is a sufferer or carrier, to test the other partner in order to advise whether their child will have the disease, be a carrier or will not have the disease.
  4. In the population, screening is carried out to discover undiagnosed sufferers or those with genetic markers for the disease, to discover carriers and to aid research into the prevalence and severity of the disease and the carrier ratio [3].
In Types 2 and 3, the incidence is so rare that discovery usually only takes place once a child has already been born with the disorder. In subsequent pregnancies, the fetus can be tested early in pregnancy. Otherwise if someone is found to be a carrier of Types 2 or 3, the chances of the other partner also being a carrier is extremely rare but screening can be obtained.

In Type 1, if both parents have disease, the child must inherit the disease or the genetic markers for the disease. It is possible that one parent has the disease and the other partner also has the genetic markers for it but with no symptoms. Therefore the child may develop the disease or alternatively may not show any symptoms during its lifetime. If one parent has the disease and the other is a carrier, in each pregnancy there is a 50:50 chance of the child inheriting the disease.

If both parents are carriers, there is a one in four chance in each pregnancy that the child will have the disease or the genetic markers for it. Again it partly depends on the genotype of each parent on whether the affected child will have mild or severe disease (or even show any symptoms at all).

In the general population, the screening of undiagnosed people who have the disease, or have genetic markers for it, and those who are carriers, is highly unlikely to occur because of the rarity of the condition.

Types of Screening

There are two classes of genetic screening- i) presymptomatic screening -this is used to test individuals whose health is in danger ii) carrier screening - carried out in healthy individuals where genes are harmful to the health of their future offspring. Other types of genetic screening usually include parental screening, newborn screening, carrier screening, forensic screening and susceptibility screening.

Prenatal screening is done when a fetus is at risk for various identifiable genetic diseases or traits. Prenatal screening began in 1966 [5].

Newborn screening is concerned with the analysis of blood or tissue samples taken in early infancy in order to detect genetic diseases for which early intervention can avert serious health problems or death. This started in 1960 with the ability to test newborns for a rare metabolic disease, phenylketonuria (PKU). Two other examples of newborn screening are the testing of African - American infants for sickle cell anemia and Ashkenazic Jews for Tay-Sachs disease [5].

Carrier screening is related to the analysis of individuals with a gene or a chromosome abnormality that may cause problems either for offspring or the person screened. This can be done by testing of blood or tissue samples and can indicate the existence of a particular genetic trait, changes in chromosomes, or changes in DNA that are associated with inherited diseases in asymptomatic individuals. Examples of carrier screening include sickle cell anemia, Tay-Sachs disease, duchenne muscular dystrophy, hemophilia, Huntington's disease, and neurofibromatosis [5].

Forensic screening seeks to discover a genetic linkage between suspects and evidence discovered in criminal investigations. This is a very powerful tool to clear the innocent and convict the guilt. Since DNA is unique, many people are reluctant to see such information become part of any national database, which might include information not only about identity but also about proclivity toward disease or behavior [5].

Susceptibility screening involves the screening of selected populations for genetic susceptibility to environmental hazards. Helps to identify workers who may be susceptible to toxic substances that are found in their workplace and may cause future disabilities [5].

There are different times throughout the life span of a human in which genetic tests, both screening and diagnostic can be preformed. The most popular and recognizable are the prenatal tests and testing of newborns. The genetic screening tests currently available for pregnant women are maternal serum alpha-fetoprotein (MSAFP) screening, enhanced MSAFP, amniocentesis,chorionic villus sampling (CVS), percutaneous umbilical blood sampling (PUBS),fetal biopsy and fetal cell sorting [8].

MSAFP is a blood-screening test performed at the 16-18 week gestation date and tests for spina bifida. Enhanced MSAFP is also a blood-screening test that measures levels of certain biochemical markers to test for the presence of Down's syndrome. However, this test only has an accuracy of 60-65%. Amniocentesis performed at the 16-18 week of gestation uses amniotic fluid to test for chromosomal abnormalities. It can also be used to find biochemical abnormalities at the genetic level, detecting up to 180 genetic disorders. CVS is performed 10-12 weeks into gestation and uses chorion tissue for chromosomal analysis in biochemical and DNA studies. This test is not widely used because of correlation to producing newborns with limb abnormalities. PUBS can be performed after week 18 and is used only as a confirmation test based on results from previous tests. Fetal biopsy involves taking fetal tissue for DNA testing. Fetal cell sorting is an experimental procedure that takes blood from the mother and tests the fetal cells in the mother's blood [8].

Debate on Genetic Screening

Developments in genetic screening and the social response to these developments vary widely. General international opinion about programs of genetic testing and screening is represented by the recommendations of the UK Nuffield Council on Bioethics. These include the requirement for informed consent and that all written information should be s supplemented with counseling, individuals and parents of unborn or young children, should be fully informed of the results of genetic screening and their implications for the family, genetic screening of employees should only be contemplated when either there is a clear connection between the working environment and the development of the condition screened for, or where the condition seriously endangers the health of the employee or third parties. Insurance companies should not require genetic tests as a prerequisite of insurance and central coordinating bodies should be established to review genetic screening and testing programs and monitor their implementation and outcome [6].

The National Academy of Sciences says screening can be used for medical intervention and research; for reproductive information; for enumeration, monitoring, and surveillance; and for registries of genetic disease and disability [5].

The Committee of Ministers of the Council of Europe thinks that the public generally recognizes the benefits and the potential usefulness of genetic testing and screening for individuals, for families, and for the population as a whole, but it says that there is an accompanying anxiety that genetic testing and screening arouses. Its recommendations to allay any future unease include: informing the public in advance; educating professionals to provide quality services (genetic tests would only be carried out by physicians); offering appropriate, non-directive, counseling; providing equality of access; respecting the self-determination of those tested; making testing or screening non-compulsory; and denying insurers the right to require testing or to seek the results of previous tests.

The Danish Council of Ethics views genetic information as different from other private information since it reveals knowledge not only about an individual, but also the individual's relatives, and because analyses will provide comprehensive information about both individuals and population groups. The Council says that screening provides information useful either to the individual or to public health officials, but this information is not concerned with treatment. From a public health point of view, testing may prevent costly treatment of a disease, protect third parties, and give the person the option of treatment. However, from the individual's point of view, there may be ambivalence about the possibility of a relative's potential disease [5].

Issues of confidentiality loom large in discussions of genetic testing and screening. According to the Privacy Commission of Canada, genetic privacy has two dimensions: protection from the intrusions of others and protection from one's own secrets. It concludes that privacy is an explicit constitutional right that includes respect for genetic privacy and is protected by legislation. Consequently, employers, in general, should be prohibited from collecting genetic information; services and benefits should not be denied on the basis of genetic testing; and information should be used only to inform a person's own decisions [5].

The President's Commission, in a 1983 study, states that the results of the screening is not be given to any other source without the consent of the person screened. The Commission recommends that information stored in computers be coded and also compulsory genetic screening not to be justified to create a health gene pool or to reduce health. The NIH/DOE Working Group on the Ethical, Legal and Social Implications of Human Genome Research recommends that health insurers should consider a moratorium on the use of genetic tests in underwriting [5].


There are both pros and cons to genetic screening and the underlying question is. Is genetic screening an ethical solution to human life? A person who is having, carrying, or is at risk of a disorder is subject to genetic testing. Pre-natal diagnosis for a genetic condition is available in the case of diseases like Down's syndrome. The increasing range of genetic tests for an increasing range of disorders made possible by human genome research offers parents much greater informed choice of whether or not to continue with a pregnancy. Pre-natal diagnosis have a major effect on individuals and their families with a history of a genetic disorder. Known genetic traits or conditions (such as colour blindness) have been screened for many years.

Concern, however, has been raised about the possible (mis)use of such genetic profiles with calls for restricting the accessibility of this information and ensuring confidentiality. New born screening for treatable diseases such as Phenylketonuria and Congenital hypothyroidism should certainly be done. People with a family history of a heritable disease should consider genetic testing as a precautionary measure. Early testing for such disease can bring the disease close to cure and minimizing many discomforts. There are many issues to be solved before genetic screening is made universal. This can be clearly depicted by one of the recent incidents published in Science [7]. As per the article the information from genetic screening has been used to create discrimination in work place. Various organizations like working group on ELSI (Ethical, Leagal and Social Implications) of HGR ( Human Genome Research), NIH (National Institute of Health) with DOE (department of Energy), monitor the misuse of genetic screening. The potentials for genetic screening are rapidly increasing as scientists further elucidate the human genome.


1. Genetic Screening for Disease; Toronto Biotechnology Initiative. Obtained from WWW:
2. Encyclopaedia Britannica. Obtained from WWW :
3. Genetic Screening and Counseling. Obtained from WWW :
4. Genetic Screening and Ethics an Overview Obtained from WWW :
5. Genetic Testing and Genetic Screening. Obtained from WWW :
6. The Application of Human Genetic Research. Obtained from WWW :
7. Marshall, Eliot. 1999. Beryllium Screening Raises Ethical Issues. Science. 285(5425): pp178-179.
8. Blatt, Robin JR."An Overview of genetic screening and diagnostic Tests in Health Care". Obtained from the WWW:

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