Development of a serum enzyme assay test made it feasible to conduct large scale screening for Tay–Sachs in targeted at-risk populations such as Ashkenazi Jews.
[citation needed] Although early testing for human mutations was often conducted by extracting DNA from larger tissue samples, modern testing in human subjects generally employs polymerase chain reaction because small tissue samples can be obtained by minimally invasive techniques, and at very low cost.
Genetic counselors, working with couples that plan to conceive a child, assess risk factors based on ancestry to determine which testing methods are appropriate.
[11] Mutation analysis techniques have declined rapidly in cost since the 1980s, a development that has run parallel with advances in computation and information processing technology.
As the cost of direct mutation analysis declines, medical genetics will confront the fact that full sequencing of the genome identifies polymorphisms that are neutral or harmless.
Czech medical geneticist Eva Machácková writes: "In some cases it is difficult to distinguish if the detected sequence variant is a causal mutation or a neutral (polymorphic) variation without effect on phenotype.
[13] In 2000, Michael Kaback reported that in the United States and Canada, the incidence of TSD in the Jewish population had declined by more than 90% since the advent of genetic screening.
At the time, researchers had only recently uncovered the biochemical basis of TSD as the failure of an enzyme in a critical metabolic pathway.
Every aspect of this landmark study was meticulously planned, including community liaison, blood-draw procedure, laboratory set-up, assay protocol, and follow-up genetic counseling.
On a Sunday in May 1971, more than 1,800 young adults of Ashkenazi Jewish ancestry in the Baltimore and Washington, D.C., areas were voluntarily screened for carrier status.
Within years, these screening programs had been repeated among Ashkenazi Jews throughout the United States, Canada, western Europe, and Israel.
Although the genetic basis of the disease was understood, antenatal testing was not available, and families with a Tay–Sachs infant faced a one in four probability of another devastating outcome with each future pregnancy.
In at-risk families, among couples where both husband and wife were carriers, more than 3000 pregnancies were monitored by amniocentesis or chorionic villus sampling.