Tay-Sachs Disease Carrier Screening Research Articles

Making the case for global carrier screening for Tay-Sachs disease

Making the case for global carrier screening for Tay-Sachs disease

Impact of Pan-Ethnic Expanded Carrier Screening in Improving Population Health Outcomes: Proceedings from a Multi-Stakeholder Virtual Roundtable Summit, June 25, 2020.

Impact of Pan-Ethnic Expanded Carrier Screening in Improving Population Health Outcomes: Proceedings from a Multi-Stakeholder Virtual Roundtable Summit, June 25, 2020.

Neonatal and carrier screening for rare diseases: how innovation challenges screening criteria worldwide

Screening for rare diseases first began more than 50 years ago with neonatal bloodspot screening (NBS) for phenylketonuria, and carrier screening for Tay-Sachs disease, sickle cell anaemia and β-thalassaemia. NBS’s primary aim is health gain for children, while carrier screening enables autonomous reproductive choice. While screening can be beneficial, it also has the potential to cause harm and thus decisions are needed on whether a specific screening is worthwhile. These decisions are usually based on screening principles and criteria. Technological developments, both treatment driven and test driven, have led to expansions in neonatal screening and carrier screening. This article demonstrates how the dynamics and expansions in NBS and carrier screening have challenged four well-known screening criteria (treatment, test, target population and programme evaluation), and the decision-making based on them. We show that shifting perspectives on screening criteria for NBS as well as carrier screening lead to converging debates in these separate fields. For example, the child is traditionally considered to be the beneficiary in NBS, but the family and society can also benefit. Vice versa, carrier screening may be driven by disease prevention, rather than reproductive autonomy, raising cross-disciplinary questions regarding potential beneficiaries and which diseases to include. In addition, the stakeholders from these separate fields vary: Globally NBS is often governed as a public health programme while carrier screening is usually available via medical professionals. The article concludes with a call for an exchange of vision and knowledge among all stakeholders of both fields to attune the dynamics of screening.

The incidence and carrier frequency of Tay-Sachs disease in the French-Canadian population of Quebec based on retrospective data from 24 years, 1992-2015.

Tay-Sachs disease (TSD) is a hereditary neurodegenerative condition inherited through an autosomal recessive pattern. The incidence and carrier frequency of infantile TSD were found to be increased among French Canadians in specific areas of the province of Quebec or calculated from New England populations with French-Canadian heritage. No accurate infantile TSD carrier frequency for the whole French-Canadian population in Quebec has been published. In this study, we estimate the incidence and carrier frequency of infantile TSD in the Quebec French-Canadian population. The number of TSD cases was ascertained during the 1992-2015 period, as well as the number of births to mothers whose language of use is French. Seven cases of TSD have been diagnosed in Quebec during the period of ascertainment. This corresponds to an incidence of 1/218,144, which in turn corresponds to a carrier frequency of 1/234. In the same 24-year period, there are two French-Canadian couples who had a fetus prenatally diagnosed with TSD. If these cases are included, the incidence of TSD in the French-Canadian population of Quebec is 1/169,668 and the carrier frequency 1/206. These findings can be used for genetic counseling and policy decisions regarding carrier screening for TSD in populations of French-Canadian descent.

Tay-Sachs disease carrier screening: Comparative analysis of NGS-based sequencing and enzyme testing results

Tay-Sachs disease carrier screening: Comparative analysis of NGS-based sequencing and enzyme testing results

Reclassification of common variants of unknown significance in the hexosaminidase A gene: Implications for Tay-Sachs disease carrier screening

Reclassification of common variants of unknown significance in the hexosaminidase A gene: Implications for Tay-Sachs disease carrier screening

Testing Fate: Tay-Sachs Disease and the Right to Be Responsible by Shelley Z. Reuter

Reviewed by: Testing Fate: Tay-Sachs Disease and the Right to Be Responsible by Shelley Z. Reuter Stephen Pemberton Shelley Z. Reuter. Testing Fate: Tay-Sachs Disease and the Right to Be Responsible. Minneapolis: University of Minnesota Press, 2016. 264 pp. Ill. $27.00 (978-0-8166-9996-4). Between 1880 and 1920, physicians in the United States and Great Britain identified a small but concerning number of infants with severe mental and developmental retardation among Jewish immigrant families. Tay-Sachs disease (TSD), as this hereditary condition is known today, has no cure, but it can be effectively prevented through carrier screening or therapeutic abortion. Fortunately, beginning in the 1980s, aggressive carrier screening coordinated by Jewish communities and their medical partners dramatically reduced TSD’s incidence in North America, Western Europe, and Israel. In 2003–4, for instance, only ten such babies were born in the United States, none Jewish. As the latter example suggests, TSD is not an exclusively Jewish disease. Yet, TSD carrier screening among Jewish communities is often hailed today as an exemplar of successful grassroots public health advocacy within an ethnic group—a kind of self-empowerment with [End Page 212] a presumed genetic basis. Shelley Reuter’s thought-provoking book complicates such genetic disease narratives by showing that TSD has always been tied problematically to race. TSD, she argues, is an instructive case of how much choice, if not “freedom,” the racialized and pathologized “Other” can exercise with regard to one’s genetic fate (p. 2). Testing Fate is a work of critical-historical sociology delivered in three parts and driven by Reuter’s determined argument about how Jewish people have been made socioculturally “responsible” for the genetic diseases that presumably affect them. The book’s first part explains how TSD was configured as a “racialized disease” in an age of rampant anti-immigrant sentiment in the United States (chap. 1) and Great Britain (chap. 2). In the British case, Reuter details how Jews combated stigmatizing portraits of disease—inclusive of TSD—by cultivating a “will to health” in the public consciousness. Representing the interests of the British Jewish community, the Jewish Board of Guardians (JBG) worked resolutely to create the impression among Britons that Anglo-Jews set standards of health, parenthood, and sobriety that native Britons should emulate (p. 63). Part 2 of Testing Fate provides finer textual analysis of the Tay-Sachs experience across the decades. It focuses on how TSD has been visually represented first in the printed medical literature (chap. 3) and later in online representations of the malady (chap. 4). The former chapter highlights how visual imagery accompanying medical case reports and studies of TSD throughout the twentieth century “reified” the malady in racialized terms, making medical practitioners complicit in the “Othering” of Jewish people. The latter chapter highlights how the “Othering” of people affected by TSD shifted in the 1990s and 2000s away from explicitly racial terms to highlight the undesirability of this disease-disability. Whereas the older medical literature was tainted by racialism, for Reuter the contemporary “specularism” constituting TSD as a horrific disease/disability also fails the test of inclusiveness. Part 3 stresses the paradoxical efforts to manage TSD through carrier screening from the 1970s into the 2000s (chap. 5). Here, Reuter focuses squarely on the carrier’s “right to be responsible” relative to the growing and, by most accounts, “effective” sociocultural imperative to prevent TSD lives in the age of medical genetics. The successes were more immediate in the United States, where there was early and aggressive cooperation between medical geneticists and Jewish communities. TSD carrier screening in Great Britain advanced more slowly, in part because British advocates did not initially include JBG or Jewish community leaders. Provocatively, Reuter then turns from the controversies surrounding TSD carrier screening to explore the emergence of wrongful birth and wrongful life suits involving TSD. There were eight such cases in the United States between 1977 and 2003, and Reuter interprets them as instances of “responsible personhood” that expose how autonomy in genetic decision making remains severely limited today. The cultures of TSD, even as they have changed over time, continue to be constituted in exclusive terms, leading Reuter to...

Tay-Sachs Carrier Screening by Enzyme and Molecular Analyses in the New York City Minority Population.

Background and Aims: Carrier screening for Tay-Sachs disease is performed by sequence analysis of the HEXA gene and/or hexosaminidase A enzymatic activity testing. Enzymatic analysis (EA) has been suggested as the optimal carrier screening method, especially in non-Ashkenazi Jewish (non-AJ) individuals, but its utilization and efficacy have not been fully evaluated in the general population. This study assesses the reliability of EA in comparison with HEXA sequence analysis in non-AJ populations. Methods: Five hundred eight Hispanic and African American patients (516 samples) had EA of their leukocytes performed and 12 of these patients who tested positive by EA (“carriers”) had subsequent HEXA gene sequencing performed. Results: Of the 508 patients, 25 (4.9%) were EA positive and 40 (7.9%) were inconclusive. Of the 12 patients who were sequenced, 11 did not carry a pathogenic variant and one carried a likely deleterious mutation (NM_000520.4(HEXA):c.1510C>T). Conclusions: High inconclusive rates and poor correlation between positive/inconclusive enzyme results and identification of pathogenic mutations suggest that ethnic-specific recalibration of reference ranges for EA may be necessary. Alternatively, HEXA gene sequencing could be performed.

Expanded carrier screening panels-does bigger mean better?

Prenatal carrier screening is offered for some inherited conditions based on recommendations of the American Congress of Obstetricians and Gynecologists (ACOG) and the American College of Medical Genetics and Genomics (ACMG). Currently, ACOG and ACMG recommend that cystic fibrosis carrier screening be offered to all women of reproductive age and that fragile X syndrome (FXS) carrier screening be offered to women with a family history suggestive of FXS or who ask to have testing following genetic counseling (Committee Opinion 469 2010; Committee Opinion 486 2011). For individuals of Eastern European Jewish descent, ACOG recommends carrier screening for Tay-Sachs disease, Canavan disease, cystic fibrosis, and familial dysautonomia (Committee Opinion 442 2009) stating that further testing should be permitted with appropriate counseling if the patient inquires about other conditions that occur more commonly in their ethnic group. ACMG recommends general population screening for spinal muscular atrophy, though this is unsupported by ACOG (Committee Opinion 432 2009; Prior 2008). All of these conditions are inherited in an autosomal recessive fashion except for fragile X syndrome, which is X-linked. People have two copies of each autosomal gene, one inherited from each parent. Recessive conditions manifest when both copies of the same gene have a mutation or do not function normally. Carriers have one abnormal gene copy, as well as one normal copy and are asymptomatic individuals. A 25 % risk for an affected child exists when both parents are carriers, as that poses a one in four risk for a child to receive a gene mutation from both parents. It is estimated that each individual is a carrier of between zero and seven severe childhood recessive conditions, with an average of 2.8 found in one study (Bell et al. 2011). As the first condition for which ethnicity based carrier screening was offered, cystic fibrosis (CF) is the most common lifelimiting autosomal recessive condition in non-Hispanic Caucasians. The debate over general population carrier screening began in 1990 following the discovery of the gene associated with cystic fibrosis (Karem et al. 1989; Beaudet 1990; Caskey et al. 1990; Tatsugawa et al. 1994). The discovery of the gene and the subsequent development of a genetic test were considered breakthroughs in science that would presumably lead to a cure. Questions of when and to who to offer the test presented a new ethical quandary at that time. The first report regarding routine CF carrier screening recommended against offering it to pregnant women stating that it should not yet be considered standard of care (Caskey et al. 1990). With the main benefit being to provide information for reproductive decision making, the potential limitations include anxiety over residual risk, anxiety associated with carrier status, and the cost of testing a large volume of people with very little financial benefit (Beaudet 1990). This debate was largely resolved over the next 10 years by an improvement in testing that increased detection rate, thereby reducing residual risk after negative CF carrier testing. By 2001, prenatal and preconception carrier screening for CF was S. Wienke : C. Strange Division of Pulmonary & Critical Care, Medical University of South Carolina, Charleston, SC, USA

High school Tay-Sachs disease carrier screening: 5 to 11-year follow-up.

The Melbourne high school Tay-Sachs disease (TSD) carrier screening program began in 1997. The aim of this study was to assess the outcomes of this screening program among those who had testing more than 5years ago, to evaluate the long-term impact of screening. A questionnaire was used for data collection and consisted of validated scales and purposively designed questions. Questionnaires were sent to all carriers and two non-carriers for each carrier who were screened in the program between 1999 and 2005. Twenty-four out of 69 (34.8%) carriers and 30/138 (21.7%) non-carriers completed the questionnaire. Most participants (82%) retained good knowledge of TSD and there was no evidence of a difference in knowledge between carriers and non-carriers. Most participants (83%) were happy with the timing and setting of screening and thought that education and screening for TSD should be offered during high school. There was no difference between carriers and non-carriers in mean scores for the State Trait Anxiety Inventory and Decision Regret Scale. This evaluation indicated that 5-11years post high school screening, those who were screened are supportive of the program and that negative consequences are rare.

ACOG Committee Opinion No. 442: Preconception and Prenatal Carrier Screening for Genetic Diseases in Individuals of Eastern European Jewish Descent

Certain autosomal recessive disease conditions are more prevalent in individuals of Eastern European Jewish (Ashkenazi) descent. Previously, the American College of Obstetricians and Gynecologists recommended that individuals of Eastern European Jewish ancestry be offered carrier screening for Tay-Sachs disease, Canavan disease, and cystic fibrosis as part of routine obstetric care. Based on the criteria used to justify offering carrier screening for Tay-Sachs disease, Canavan disease, and cystic fibrosis, the American College of Obstetricians and Gynecologists' Committee on Genetics recommends that couples of Ashkenazi Jewish ancestry also should be offered carrier screening for familial dysautonomia. Individuals of Ashkenazi Jewish descent may inquire about the availability of carrier screening for other disorders. Carrier screening is available for mucolipidosis IV, Niemann-Pick disease type A, Fanconi anemia group C, Bloom syndrome, and Gaucher disease.

Heredity and Hope: The Case for Genetic Screening (review)

Reviewed by: Heredity and Hope: The Case for Genetic Screening Stephen Pemberton Ruth Schwartz Cowan. Heredity and Hope: The Case for Genetic Screening. Cambridge, Mass.: Harvard University Press, 2008. 292 pp. Ill. $27.95 (978-0-674-02424-3). Heredity and Hope is an unapologetic polemic against the critics of genetic screening and a must-read for anyone interested in the past and future of genetic medicine. Ruth Schwartz Cowan has crafted a book that uses “historians’ tools” to do the “bioethical work” of buttressing what she describes as the “pronatal” and “anti-eugenic” enterprise of medical genetics (p. 226). Her work is an argument against our acculturated ambivalence about genetic technologies and a defense of medical geneticists and genetic counselors who “are pursuing an ethical vision in their careers, opening up new, moral opportunities for their patients” (p. 245). Cowan advocates for the consumers of genetic screening—even where testing is mandated by communal or government sanction. She boldly champions pronatalist medical practices unburdened by their alleged eugenic past or a universal requirement of informed consent or right of free refusal. There is a glaring absence of well-written histories that detail the evolution of genetic medicine, and Cowan’s work is welcome in that regard. The narrative begins with two measured chapters on the history of the global eugenics movement (ca. 1880–1940) followed by a history of the rise of genetics and medical genetics (ca. 1900–50). Her appraisal is that anyone who thinks that medical genetics was born out of eugenics is simply wrong about the facts. The connections are tenuous, she argues; and those who insist on making them are committing a “genealogical fallacy,” since the pioneers of medical genetics were not motivated by eugenic efforts to rid human populations of the “unfit” (p. 67). Her argument takes full flight where Cowan uses her considerable expertise as a historian of technology to show that genetic tests—namely, amniocentesis, ultrasound, and chorionic villus sampling—are part of a technological system that owes nothing in its social origins to eugenics. Cowan then turns to newborn genetic screening for phenylketonuria and adult carrier screening for Tay-Sachs disease, explaining that successful efforts to reduce the prevalence of these disorders met surprisingly little resistance because they originated within the communities at risk. In counterpoint, she details how sickle cell anemia screening failed because of its [End Page 417] resonance among African Americans as a stigmatizing and “genocidal” practice foisted on them (pp. 167–80). Finally, Cowan ends with a fine-grained tale about universal β-thalassemia carrier screening in the Greek and Turkish republics of Cypress. Here, every sector of Cypriot society allegedly learned to embrace the mandate as a righteous course of action, one that served the original ideal behind eugenics—“beautiful heredity”—without actually being “eugenic” (p. 222). Cowan explains her motives and methods in the book’s opening and conclusion. She also identifies her targets—the “left-wing intellectuals,” “reproductive feminists,” “disability rights activists,” and “adamant pro-lifers” who refuse to endorse genetic screening—as well as those who use genetic testing but are ambivalent about doing so (pp. 7, 227–34). Cowan was once ambivalent herself, but she deftly explains how historical re-education taught her how to stop worrying about genetic screening and learn, like her Cypriots, to embrace it. Heredity and Hope has the potential to engage diverse audiences but is marred by its selective account of eugenics and genetic screening. Cowan has a very restrictive definition of eugenics and completely ignores pertinent historiography that shows that the eugenics movement was thoroughly pronatalist in its promotion of “better breeding.” Her case study of Tay-Sachs wrongly suggests that carrier screening within Jewish communities has escaped controversy, and she focuses entirely on a few single gene defects that are fast becoming the exception rather than the rule. Cowan’s rationale for such selectivity is missing, and readers are left to wonder whether her arguments could withstand the inclusion of more challenging examples—for instance, Gaucher’s, Huntington’s, Alzheimer’s, or cancer. This book may prove useful to boosters of genetic screening, but its origin stories and arguments seem unlikely to convert. Stephen Pemberton New...

Genetic testing of sperm donors: survey of current practices

To determine which genetic tests are being performed on sperm donor applicants in the United States. An electronic survey was distributed to 26 sperm banks to evaluate their genetic testing practices. Sperm banks in the United States. Not applicable. None. Survey of current practices. Survey of current practices. Cystic fibrosis (CF) carrier screening, chromosome analyses, and hemoglobin evaluations are performed on the majority of sperm donor applicants. Tay-Sachs disease carrier screening is performed on most donors with Jewish heritage but there is significant variation in screening for other disorders that occur with increased frequency in this population. Individual sperm banks use different laboratory tests for evaluation of the same conditions, with each test having different carrier detection rates and interpretations. The genetic testing performed on sperm donors varies significantly at sperm banks across the United States. Therefore, recipients should be clearly informed about the specific evaluations performed on their donor of interest. Thus it is important that sperm banks employ genetic professionals to evaluate the donors' and recipients' medical histories and perform a genetic risk assessment. This will allow clients to make informed decisions about use of semen specimens from an anonymous sperm donor.

Carrier Screening for Genetic Disorders in Individuals of Ashkenazi Jewish Descent

ObjectiveTo give recommendations to physicians and midwives providing pre-conception or prenatal care about carrier screening for genetic disorders in individuals of Ashkenazi Jewish descent. OptionsTo offer carrier screening for Tay-Sachs disease (TSD) only or to expand the screening to include other disorders known to occur with increased frequency in the Ashkenazi Jewish population. OutcomesTo offer carrier screening to the Ashkenazi Jewish population for conditions in which the benefits to the couple outweigh the risks, which include psychological distress from screening and diagnostic interventions; to minimize practice variation across Canada with respect to carrier screening in individuals of Ashkenazi Jewish descent. EvidenceThe MEDLINE database was searched for relevant articles published from January 1966 to December 2004 related to carrier screening and genetic disorders in individuals of Ashkenazi Jewish descent. In addition, Canadian maternal-fetal medicine specialists and medical geneticists were surveyed to determine current practices and opinions. ValuesThe results of the survey and evidence collected from the MEDLINE search were reviewed by the Prenatal Diagnosis Committee of the Canadian College of Medical Geneticists (CCMG) and the Genetics Committee of the Society of Obstetricians and Gynaecologists of Canada (SOGC). Recommendations were quantified using the Evaluation of Evidence guidelines developed by the Canadian Task Force on the Periodic Health Examination. Benefits, harms, and costsScreening of couples of Ashkenazi Jewish descent will identify couples who have a 25% risk of having a child with a significant genetic disorder. However, the sensitivity of the tests being offered is not 100% in individuals of Ashkenazi Jewish descent and is significantly less or unknown in non-Ashkenazi Jewish individuals.Screening might identify couples where one member is a carrier and the other member is negative. Given that such a couple would be at low risk but not zero risk of having an affected child, screening might result in psychological distress, unnecessary prenatal diagnostic procedures, and possibly termination of normal pregnancies. This guideline does not include a cost analysis. Recommendations1.Carrier screening for Tay-Sachs disease (II-2A), Canavan disease, and familial dysautonomia should be offered to Ashkenazi Jewish couples. (III-A)2.2Carrier screening for other disorders seen with increased frequency in Ashkenazi Jewish individuals (e.g., Bloom syndrome, Fanconi anemia, Gaucher disease, glycogen storage disease type 1a,mucolipidosis type IV, Niemann-Pick disease type 1A, cystic fibrosis) should be offered when there is a positive familyhistory. (III–A)3.When only one member of a couple is of Ashkenazi Jewish ancestry, screening should be offered for TSD only. (II-2A)4.When only one member of a couple is of Ashkenazi Jewish ancestry, screening should not be offered for Canavan disease or familial dysautonomia (FD) because of a low carrier frequency and limitations of carrier screening (low detection rate in individuals of non-Ashkenazi Jewish ancestry). (III-D)5.When both partners are carriers of the same autosomal recessive condition, they have a 25% risk of having an affected child. They should be referred for genetic counselling, either before conception or prenatally. Prenatal diagnosis would be offered and performed according to the patient’s informed decision. Prenatal diagnosis would consist of DNA analysis done on cells obtained by chorionic villus sampling or amniocentesis. (II-3A) ValidationThis guideline has been prepared by the Prenatal Diagnosis Committee of the CCMG and the Genetics Committee of the SOGC and approved by the Board of Directors of the CCMG and Executive Council of the SOGC.

It's ‘back to school’ for genetic screening

Implementation of population genetic screening programmes requires consideration of strategies for reaching the greatest proportion of the target population in order to achieve maximum awareness. This article reviews the current strategy of school-based population genetic screening programmes. The school environment is an ideal setting for offering relevant genetic screening programmes as it provides an opportunity to engage people at a time when they are exposed to a range of educational experiences and are sufficiently mature to be involved in decision-making processes. Such programmes allow all students, not only those studying biology, an opportunity to be educated and experience genetic screening in a supportive environment, ultimately increasing understanding and empowering students. While the major form of genetic screening in schools has been for reproductive health information (eg carrier screening for TaySachs disease and cystic fibrosis), genetic screening in schools for other conditions may be a timely proposition.

Multiplexed fluorescence analysis for mutations causing Tay-Sachs disease.

AbstractTay-Sachs disease is a severe, neurodegenerative disease fatal in childhood that is caused by deficiency of the enzyme β-hexosaminidase A (Hex A) (1). Tay-Sachs is most common in the Ashkenazi Jewish population, with an incidence of 1/3600 affected individuals and a carrier rate of approx 1 in 30 (1). Owing to the severity of the disease and the high incidence, carrier screening for Tay-Sachs disease has been available to Ashkenazi Jewish individuals since the 1970s, which has greatly reduced the number of affected children in this population. The standard method of carrier testing is by biochemical analysis for reduced Hex A activity in serum (2).KeywordsMutant AlleleCarrier ScreeningCarrier TestingAshkenazi Jewish PopulationResultant Polymerase Chain Reaction ProductThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

The frequency of Tay-Sachs disease causing mutations in the Brazilian Jewish population justifies a carrier screening program.

Tay-Sachs disease is an autosomal recessive disease characterized by progressive neurologic degeneration, fatal in early childhood. In the Ashkenazi Jewish population the disease incidence is about 1 in every 3,500 newborns and the carrier frequency is 1 in every 29 individuals. Carrier screening programs for Tay-Sachs disease have reduced disease incidence by 90% in high-risk populations in several countries. The Brazilian Jewish population is estimated at 90,000 individuals. Currently, there is no screening program for Tay-Sachs disease in this population. To evaluate the importance of a Tay-Sachs disease carrier screening program in the Brazilian Jewish population by determining the frequency of heterozygotes and the acceptance of the program by the community. Laboratory of Molecular Genetics--Institute of Biosciences--Universidade de São Paulo. 581 senior students from selected Jewish high schools. Molecular analysis of Tay-Sachs disease causing mutations by PCR amplification of genomic DNA, followed by restriction enzyme digestion. Among 581 students that attended educational classes, 404 (70%) elected to be tested for Tay-Sachs disease mutations. Of these, approximately 65% were of Ashkenazi Jewish origin. Eight carriers were detected corresponding to a carrier frequency of 1 in every 33 individuals in the Ashkenazi Jewish fraction of the sample. The frequency of Tay-Sachs disease carriers among the Ashkenazi Jewish population of Brazil is similar to that of other countries where carrier screening programs have led to a significant decrease in disease incidence. Therefore, it is justifiable to implement a Tay-Sachs disease carrier screening program for the Brazilian Jewish population.

23. The Dor Yeshorim story: Community-based carrier screening for Tay-Sachs disease

This chapter describes the community characteristics and dynamics, which are the context for the Dor Yeshorim program, along with the mechanics of the program. The 17-year history, its findings and accomplishments are summarized with interesting and surprising results. Genetics is fraught with difficult issues in terms of how and when to use its powerful capabilities. It is likely that the society will accept if it remains open to a wide diversity of ideas. Dor Yeshorim, the Committee for Prevention of Jewish Genetic Diseases, began within the context of the Hasidic Jewish community, then expanded to the broader Orthodox Jewish communities of the metropolitan New York area, Dor Yeshorim program contributes to solution building. This program also serves as a successful model of “genetic compatibility” testing and is designed to meet the special needs of the Orthodox Jewish community. The Orthodox and Hasidic Jewish communities adhere to strict religious practices. They are health conscious, have strong beliefs about family and any program directed at serving these communities must accommodate these principles and practices.

Tay-Sachs disease carrier screening: a 21-year experience.

This paper presents the findings of a community-based carrier screening program for Tay-Sachs disease, initiated on the University of Wisconsin-Madison campus in 1978. The Madison Community Tay-Sachs Screening Program (MCTSSP) is a collaborative, interdisciplinary program that organizes and conducts periodic screening for Tay-Sachs disease (TSD) for the purpose of identifying Tay-Sachs carriers. We present and analyze data on carrier detection with regard to various demographics, including family history of TSD, ancestry, gender, medication exposure, and illness. Individuals participating in the MCTSSP between 1978 and 1999 were primarily of the target population, and the carrier rate was within the expected range (1/25). Despite aggressive publicity efforts and a well-established program, attendance at the screens has declined. A recent survey of Jewish undergraduate students at the University of Wisconsin-Madison showed poor recall of family screen history and carrier status and reinforced the perception that utilization of the Madison screening program has been low. Ways to increase awareness of and interest in carrier screening for TSD are explored.

Tay-Sachs disease carrier screening: a model for prevention of genetic disease.

Tay-Sachs disease (TSD) is an autosomal-recessive, progressive, and ultimately fatal neurodegenerative disorder. Within the last 30 years, the discovery of the enzymatic basis of the disease, namely deficiency of the enzyme hexosaminidase A, made possible both enzymatic diagnosis of TSD and heterozygote identification. In the last decade, the cloning of the HEXA gene and the identification of more than 80 associated TSD-causing mutations has permitted molecular diagnosis in many instances. TSD was the first genetic condition for which community-based screening for carrier detection was implemented. As such, the TSD experience can be viewed as a prototypic effort for public education, carrier testing, and reproductive counseling for avoiding fatal childhood disease. More importantly, the outcome of TSD screening over the last 28 years offers convincing evidence that such an effort can dramatically reduce incidence of the disease.