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PubMed1980

Age-related abnormalities of circulating polyamines and diamine oxidase activity in cystic fibrosis heterozygotes and homozygotes.

Serum putrescine (Pu), spermidine (Sd), spermine (Sp), and plasma diamine oxidase ativity (DAO) were determined in cystic fibrosis (CF) homozygotes and heterozygotes plus age-matched controls. Mean (+/- S.E.) levels of Pu (0.51 +/- 0.06 nmoles/ml), Sd (0.63 +/- 0.07 nmoles/ml), and Sp (0.33 +/- 0.08 nmoles/ml) were higher (P < 0.001) in 17 control children versus 16 healthy adults (Pu = 0.15 +/- 0.04; Sd = 0.14 +/- 0.03; Sp = 0 in all). All 4 CF adults tested, but only 3 of 24 CF children, had increased polyamines relative to age-matched controls. Pu (0.33 +/- 0.04), Sd (0.33 +/- 0.05) and Sp (0.16 +/- 0.12) were increased (P < 0.001) in 11 adult heterozygotes; in turn, Pu (0.56 +/- 0.11; P < 0.025) and Sd (0.86 +/- 0.22; P < 0.005) were higher in the adult CF patients than in the heterozygotes. Plasma DAO was higher (P < 0.001) in 45 control children (9.3 +/- 0.7 units/ml) versus 61 healthy adults (5.7 +/- 0.07). Levels greater than or equal to +2 S.D. for controls occurred in 8 (21%) of 39 CF patients. Plasma DAO (19 +/- 4.8) was increased (P < 0.001) in 27 adult heterozygotes; 10 (37%) had values greater than or equal to +2 S.D. for normal adults. One or more polyamines and/or DAO were increased in each of 11 heterozygotes in whom all parameters were measured. These composite abnormalities might be considered as a potential means for identification of asymptomatic CF heterozygotes.

Adolescent↗
PubMed2006

Heterozygote advantage for fecundity.

Heterozygote advantage, or overdominance, remains a popular and persuasive explanation for the maintenance of genetic variation in natural populations in the face of selection. However, despite being first proposed more than 80 years ago, there remain few examples that fit the criteria for heterozygote advantage, all of which are associated with disease resistance and are maintained only in the presence of disease or other gene-by-environment interaction. Here we report five new examples of heterozygote advantage, based around polymorphisms in the BMP15 and GDF9 genes that affect female fecundity in domesticated sheep and are not reliant on disease for their maintenance. Five separate mutations in these members of the transforming growth factor beta (TGFbeta) superfamily give phenotypes with fitness differentials characteristic of heterozygous advantage. In each case, one copy of the mutant allele increases ovulation rate, and ultimately litter size per ewe lambing, relative to the wildtype. However, homozygous ewes inheriting mutant alleles from both parents have impaired oocyte development and maturation, which results in small undeveloped ovaries and infertility. Using data collected over many years on ovulation rates, litter size, and lambing rates, we have calculated the equilibrium solution for each of these polymorphisms using standard population genetic theory. The predicted equilibrium frequencies obtained for these mutant alleles range from 0.11 to 0.23, which are amongst the highest yet reported for a polymorphism maintained by heterozygote advantage. These are amongst the most frequent and compelling examples of heterozygote advantage yet described and the first documented examples of heterozygote advantage that are not reliant on a disease interaction for their maintenance.

Animals↗
PubMed1989

Spermatogenesis in heterozygotes for Robertsonian chromosomal rearrangements from natural populations of the common shrew, Sorex araneus.

Twenty-two adult male common shrews were collected from 5 sites in the vicinity of Oxford (UK) close to the zone of hybridization between two karyotypic races. The shrews were subdivided into 3 karyotypic categories: homozygotes, simple Robertsonian heterozygotes (which form one or more trivalents at prophase I of meiosis) and complex Robertsonian heterozygotes (which form a quadrivalent). The ratio of primary spermatocytes to round spermatids was determined from transverse sections of seminiferous tubules, to provide an indication of germ cell death. In no individual was there severe germ cells loss. Homozygotes had the highest mean spermatocyte: spermatid ratio and complex heterozygotes the lowest, but there was substantial individual variation and the differences were not significant. Complex heterozygotes also had a higher proportion of defective seminiferous tubules and lower testis weights than did other categories and it is reasonable to propose that, as a population, complex heterozygotes had reduced fitness relative to other categories on the basis of spermatogenic performance. However, there is no evidence from studies of spermatogenesis that simple Robertsonian heterozygotes are less fit than homozygotes.

Animals↗
PubMed1984

Hemoglobin constitution of double heterozygotes for alpha or beta-thalassemia and Hb J Sardegna.

In this study, we carried out alpha-globin gene mapping in 12 heterozygotes for Hb J Sardegna and in 5 double heterozygotes for this variant and beta-thalassemia. Then, we correlated the Hb pattern with the alpha and beta-globin genotype. In heterozygotes for Hb J Sardegna with a deletion of a single alpha-globin gene (alpha alpha/-alpha) the amount of the abnormal Hb was significantly (p much less than 0.001) higher than in heterozygotes for this variant with a full complement of 4 alpha-globin structural genes (27.5% versus 20.4%). Double heterozygotes for the abnormal hemoglobin and beta-thalassemia with a full complement of 4 alpha-globin structural genes tended to have lower amount of the abnormal Hb than heterozygotes for this variant who do not have beta-thalassemia.

Chromosome Mapping↗
PubMed2003

Erythroid bone marrow activity and red cell hemoglobinization in iron sufficient beta-thalassemia heterozygotes as reflected by soluble transferrin receptor and reticulocyte hemoglobin in content. Correlation with genotypes and Hb A(2) levels.

BACKGROUND AND OBJECTIVES: Ferrokinetic studies and erythroid cell ultrastructural studies have indicated some degree of ineffective erythropoiesis in heterozygous beta-thalassemia, although a wide case-to-case variation was observed. In this study we applied rapid biochemical and hematologic measurements to assess erythroid marrow activity (sTfR) and reticulocyte hemoglobin content (CHr) in iron-sufficient individuals with heterozygous beta-thalassemia and investigated the correlation with the degree of globin polypeptide chain imbalance by comparing parameters between beta-thalassemia heterozygotes with genotypes of variable severity. DESIGN AND METHODS: We studied 57 iron-sufficient adults with heterozygous beta-thalassemia, divided into groups according to genotype: group A: beta(silent)-thalassemia heterozygotes, group B: beta(+)-thalassemia heterozygotes and group C: beta(0)-thalassemia heterozygotes. Twenty-one hematologically normal individuals served as controls (group D). We measured hematologic parameters including CHr with a Bayer-Advia 120 hematology analyzer. Hemoglobins were analyzed by high performance liquid chromatography, while biochemical parameters of iron status (iron, ferritin, transferrin and sTfR) were measured with chemical, luminometric and nephelometric methods. RESULTS: We found significant positive correlations between sTfR values for all beta-thalassemia heterozygote groups when plotted against Hb A(2) and Hb F levels (r=0.566, p<0.0001 and r=0.283, p<0.03, respectively) and significantly negative correlation between CHr and Hb A(2) values (r=-0.790, p<0.00001). These data reflect the fine association of globin polypeptide chain imbalance with erythron expansion and the greater degree of ineffective erythropoiesis in beta-thalassemia heterozygotes with more severe genotypes. INTERPRETATION AND CONCLUSIONS: This study is the first demonstration that sTfR and CHr are useful parameters for evaluating the relative severity of different genotypes in heterozygous beta-thalassemia.

Adolescent↗
PubMed1976

[Color discrimination in heterozygotes].

By the help of Rabkin polychromatics tables and of the AN-59 anomaloscope it is studied the chromatic eye sight at 33 heterozygots. The used tests have permitted the identification of the different types of heterozygots: heterozygots which transmit and manifest only one chromatic anomaly, double heterozygots which manifest clinical one or both anomalies and unmanifested clinical heterozygots. The study of the chromatic eyesight at men from the same family has confirmed the clinical diagnosis of the heterozygots type in every case.

Color Perception↗
PubMed1988

Variable reduction in beta-adrenergic sweat secretion in cystic fibrosis heterozygotes.

Because patients with cystic fibrosis (CF) consistently lack sweating response to isoproterenol (ISO) in vivo and in vitro, we studied to what extent beta-adrenergic defect is expressed in CF heterozygotes. To improve the sensitivity and accuracy of determining the sweating response to intradermal ISO (also containing theophylline and atropine), a water vapor analyzer was used, and the peak sweat rates attained after intradermal injection in the forearm of optimal concentrations of ISO and methacholine (MCH) were determined. The peak ISO sweat rate was further normalized by the peak MCH sweat rate in each individual and expressed as the relative ISO sweat ratemax (in percent). The relative ISO sweat ratemax was determined independent of age and sex and was unchanged after brief acclimatization. The mean relative ISO sweat ratemax of CF heterozygotes was significantly lower than that of controls (10.1% vs 19.5%); however, 21 of the 54 CF heterozygotes overlapped with controls, and the remainder of the CF heterozygotes fell below the arbitrary demarcation line drawn at the relative sweat rate of around 10%. Thus, although the ISO sweat test may not be a practical discrimination test for CF heterozygotes, knowledge of the diversity of beta-adrenergic sweating responses in CF heterozygotes will provide a useful data base for further understanding the possible linkage (or its absence) between the abnormal CF gene(s) (which may be identified by molecular biologists in the near future) and the abnormal intracellular process(es) that takes place during beta-adrenergic stimulation of the CF eccrine sweat gland.

Acclimatization↗
PubMed1981

The gamma chain heterogeneity of fetal hemoglobin in black beta-thalassemia and HPFH heterozygotes.

High pressure liquid chromatography (HPLC) was applied to the HbF isolated from blood of numerous black patients with beta-thalassemia trait or homozygosity, G gamma-delta beta-thalassemia trait, G gamma A-gamma HPFH heterozygosity, or the G gamma-[delta+ beta+]-HPFH condition. The method allowed an accurate evaluation of the relative quantities of three types of gamma-chain (G gamma, A gamma I, A gamma T) in the fetal hemoglobins. The results have shown the following. (A) The incidence of the A gamma T-chain in beta-thal heterozygotes and G gamma A gamma-HPFH heterozygotes is about the same as has been observed in black newborn; about one of five blacks are heterozygous for this A gamma-chain variant. The A gamma T-chain was not detected in the nine G gamma-delta beta-thal heterozygotes nor in the eight G gamma-[delta+ beta+]-HPFH heterozygotes. (B) In most cases, the A gamma T-chain was produced by the A gamma gene in trans to the beta-thal or HPFH determinant. The contribution by the gamma-chain genes in trans to the beta-thal or HPFH determinant is about 15% of the total gamma-chain production in both conditions. (C) Three black beta-thal heterozygotes (and five additional relatives) had the A gamma T gene in cis to the beta-thal determinant. Four of these patients had a low levels of G gamma-chain (the "adult" level), and the contribution by the A gamma gene in cis to the beta-thal determinant was about three times that of the A gamma gene in trans. The four additional patients, all members of one family, had a high level of G gamma-chain (the "newborn" level), and the contribution of the A gamma gene in cis was half of that seen in the previously mentioned four patients while that of the A gamma gene in trans was essentially the same. These limited data suggest that the genetic anomaly causing high high G gamma levels in adult beta-thal heterozygotes is linked to the beta-thal determinant and that one of its primary effects is a decreased synthetic expression of the A gamma gene in cis to the beta-thal determinant.

Adolescent↗
PubMed1978

The urinary excretion of radiocopper in presymptomatic and symptomatic Wilson's disease, heterozygotes and controls: its significance in diagnosis and management.

Radiocopper (64Cu, 67CU), given intravenously, has been used to study the pattern of excretion of copper in patients with presymptomatic, symptomatic and treated Wilson's disease, together with heterozygotes for the Wilson's disease gene and a control group of patients with a variety of neurological lesions mimicking Wilson's disease. Urine was collected for three periods after injection, 0 to 8 hours, 8 to 24 hours, at which time a test dose of penicillamine was given, and from 24 to 30 hours. Stable (endogenous) copper was also estimated on these samples and specific activity was determined. This was multiplied by a correction factor to allow for variations in dose and body weight. The findings for stable copper in urine were largely predictable. Controls and heterozygotes had the least copper excretion, the amounts rising in the presymptomatic to a peak in the symptomatic patients. Institution of therapy was associated with a fall in copper excretion pro rata with time. The most important radiochemical findings were as follows. Heterozygotes excreted less of the injected copper than controls both under basal conditions and after penicillamine. Presymptomatic patients excreted less radiocopper than heterozygotes after penicillamine although the excretion during the basal 24 hour period was very much greater. Patients with symptomatic Wilson's disease had by far the highest excretion of radiocopper in all three time periods which fell after treatment, pro rata with time, as had been found for stable copper. These results were subjected to computer analysis. There was no overlap between the various groups with the exception of a single control subject who had combined pyramidal and extrapyramidal system degeneration of obscure aetiology. This patient was classified by the computer study as 'heterozygote'. These findings lend further support to the hypothesis that the loss of a single gene for copper balance can be detected with a high degree of accuracy and also that presymptomatic patients can be selected from a sibship for prophylactic treatment without the risk of subjecting healthy heterozygotes to unnecessary and potentially hazardous long-term therapy.

Adolescent↗
PubMed1980

Reduced capacity to repair irradiated adenovirus in fibroblasts from xeroderma pigmentosum heterozygotes.

Xeroderma pigmentosum (XP) is one of a number of autosomal recessive syndromes in humans characterized by a marked predisposition to cancer. Fibroblasts from these patients show a defect in DNA repair. The XP heterozygotes also show elevated skin cancer incidence, but reports concerning their DNA repair capacity are conflicting. In this study, the DNA repair capacity of four XP heterozygotes was examined using a sensitive host cell reactivation technique. Unirradiated and irradiated suspensions of adenovirus type 2 (Ad 2) were assayed for their ability to form viral structural antigens in fibroblasts from XP heterozygotes, XP homozygotes, and normals. A reduced host cell reactivation (of viral structural antigen production) for both ultraviolet- and gamma-irradiated Ad 2 was detected in four XP heterozygotes representing three different complementation groups as well as their XP homozygous children. The doses necessary to reduce the survival of viral structural antigen production by irradiated AD 2 to 37% in the XP heterozygous strains were expressed as a percentage of that obtained in normal strains and ranged from 55 to 82% for ultraviolet-irradiated Ad 2 and 71 to 79% for gamma-irradiated Ad 2. These results add further support to a direct relationship between cancer proneness and DNA repair defects and show the merits of this host cell reactivation technique in identifying XP heterozygotes. Identification of XP heterozygotes is of considerable public health interest not only in genetic counseling but also in the prevention of cancer.

Adenoviruses, Human↗
PubMed1990

Detection of heterozygotes for recessive alleles. Homocyst(e)inemia: paradigm of pitfalls in phenotypes.

Excess homocysteine in body fluids has been implicated as a factor in the pathogenesis of occlusive vascular disease (peripheral and cerebrovascular arterial disease, and perhaps coronary artery disease). Heterozygotes for inborn errors of homocysteine metabolism (transsulfuration or remethylation pathways) are much more frequent than are homozygotes/compounds. If heterozygotes are at increased risk (a question not addressed here), it is of interest to know whether they can be identified consistently by a "screening" measurement of blood homocyst(e)ine. We used hyperhomocyst(e)inemia (cystathioninemia beta-synthase deficiency) as a test case. From reviews of metabolite values in blood samples either fasting (11 articles) or after a methionine load (8 articles), and of measures of enzyme activity (12 articles), it is apparent that (1) The heterozygous phenotype cannot be identified consistently by any single measure (there is overlap with normal values); and (2) the exaggerated gene dosage effect (negative allelic complementation) present in most heterozygotes does not assist their classification. The failure of enzyme assay to distinguish heterozygotes consistently (relative to normal values) may reflect allelic heterogeneity. The failure of metabolic values to identify heterozygotes consistently reflects the local and global properties of the homeostatic system controlling the homocysteine pool size. The problem described here is a particular example of a general one in physiological and medical genetics, namely detection of heterozygotes for recessive alleles, affecting metabolic homeostasis, for purposes of medical intervention and for genetic counselling.

Alleles↗
PubMed1985

Improved identification of heterozygotes for homocystinuria due to cystathionine synthase deficiency by the combination of methionine loading and enzyme determination in cultured fibroblasts.

Previous data on tentative identification of the carrier state for homocystinuria due to cystathionine synthase deficiency using methionine loading or measurement of cystathionine synthase activity in tissue extracts are conflicting. We studied the results of standardized oral methionine loading in 20 obligate heterozygotes and compared them with those of determination of cystathionine synthase activity in cultured fibroblasts. Special attention was devoted to our recently reported observation on the small but striking differences in methionine metabolism between healthy pre- and postmenopausal women and men. Fasting and after load peak levels of methionine in serum did not discriminate the carriers from the control subjects. The mean fasting level of total homocysteine was only significantly higher in the group of premenopausal heterozygotes than in the corresponding control group. Nevertheless, the individual values overlapped with the normal range in 4 of 12 premenopausal heterozygotes. After loading peak levels of total homocysteine in 18 out of the 20 obligate heterozygotes exceeded the upper limit of the ranges in the three control groups. Thus, this parameter discriminated 90% of the obligate carriers. Measurement of cystathionine synthase activity in cultured fibroblasts from a skin biopsy identified the obligate heterozygotes to a similar degree (85%). No significant correlation between the measurements of cystathionine synthase activity and the after load peak levels of total homocysteine in the individual heterozygotes was established. Combination of both methionine loading and determination of cystathionine synthase activity in cultured fibroblasts identified all of these carriers.

Adolescent↗
PubMed1998

Usefulness of cyanide-nitroprusside test in detecting incomplete recessive heterozygotes for cystinuria: a standardized dilution procedure.

We present the results of a cyanide-nitroprusside test (CNT) after a standardized dilution procedure of urine samples and report the efficiency of this method in detecting heterozygotes for cystinuria when applied on an open pediatric population. In the preliminary study we assayed by quantitative determination of amino acids 162 urine samples from a hospital population identifying 24 type III heterozygotes and 2 type II heterozygotes for cystinuria. The classic CNT gave 38 false positive results and 5 false negative results showing a sensitivity and specificity of 0.808 and 0.721, respectively. When progressively diluted, all samples of heterozygotes remained CNT positive up to a creatinine concentration of 90 mg/dl. At this level of dilution 31 out of 38 false positive turned to negative, thus obtaining a specificity of 0.922 without a lowering of the sensitivity in detecting heterozygotes. The standardized dilution at 90 mg/dl of creatinine concentration was applied to 74.7% of a population of 1024 schoolchildren. In this way 163 out of 210 positive results were eliminated and thus the specificity of CNT rose from 0.789 to 0.953. On the basis of these results, the method proposed can be regarded as reliable and useful for a screening program in detecting heterozygotes for cystinuria.

Adolescent↗
PubMedDate not supplied

Detection of mucopolysaccharidosis type I heterozygotes based on the biochemical characteristics of leukocyte alpha-L-iduronidase.

BACKGROUND: In the present study, we biochemically characterized the enzyme alpha-L-iduronidase (IDUA) of leukocytes from normal individuals and from mucopolysaccharidosis I (MPS I) heterozygotes, and compared these characteristics to discriminate for inclusion into two different groups. METHODS: We fluorimetrically measured IDUA activity in leukocytes using 4-methylumbelliferyl-alpha-L-iduronide as an artificial substrate. Optimum pH, Km, Vmax, and thermostability of the enzyme at 50 degrees C were determined. RESULTS: Based on leukocyte IDUA activity, we divided the heterozygotes into two groups, one (group 1) with activity below that detected in controls, and the other with activity similar to that of normal individuals (group 2). The optimum pH for IDUA was 2.7 for normal individuals and 2.6-2.8 for heterozygotes. With respect to Km, there was a difference only between the value for normal IDUA (0.60 mM) and the value for group 2 (0.38 mM), while group 1 showed a statistically similar value (0.49 mM). The Vmax of the reaction was discriminated in the three groups in a highly effective manner. The IDUA of normal individuals had a higher Vmax (60.98 nmoL/h x mg protein) than the enzyme of group 1 heterozygotes (28.66 nmoL/h x mg protein) and the enzyme of group 2 (31.78 nmoL/h x mg protein). When the IDUA from the three groups was pre-incubated at 50 degrees C, we observed that the IDUA of both group 1 and group 2 was significantly more thermostable than the IDUA of normal individuals. CONCLUSIONS: Determination of IDUA activity alone is not sufficient to discriminate between MPS I heterozygotes and normal individuals because a considerable overlap occurs between them. Our study showed that leukocyte IDUA from MPS I heterozygotes differed from the normal enzyme in terms of optimum pH, Km, and Vmax of the reaction and thermostability at 50 degrees C. These parameters provide a simple and reliable tool for the detection of carriers for MPS I.

Child↗
PubMed2002

Genetic testing for HFE hemochromatosis in Australia: the value of testing relatives of simple heterozygotes.

BACKGROUND: It is unclear whether screening of relatives of C282Y and H63D heterozygotes (other than compound heterozygotes) for hemochromatosis will detect sufficient numbers of cases to justify introduction of this screening strategy. METHODS: Conditional probabilities were determined using published Australian allele frequencies and penetrance data to determine the detection rate of hemochromatosis by testing the siblings and offspring of heterozygotes (subjects with only one HFE mutation). RESULTS: The number of individuals who are at risk of developing increased body iron stores because of HFE mutations is substantially higher (1 in 80) than previously estimated. In addition, 33% of the Australian population are heterozygous for either C282Y or H63D. Based on population estimates, the relative risk to the offspring of C282Y and H63D heterozygotes of developing increased iron stores is 4.1 and 1.5, respectively, while the relative risk to each sibling is 2.3 and 1, respectively. The risk of developing clinical features of hemochromatosis or hepatic fibrosis is likely to be substantially lower. CONCLUSIONS: Although the detection rate from testing the families of unaffected heterozygotes is low, this can be justified as a clinically useful screening strategy. At the present time this strategy should be restricted to first-degree relatives of heterozygotes. Further studies are recommended to determine if cascade genetic screening is a cost-effective alternative to general population screening.

Australia↗
PubMed2001

[A study of phenylketonuria heterozygotes screening in married population of Tianjin area].

OBJECTIVE: To find out a method that is simple and reliable for screening phenylketonuria(PKU) heterozygotes. METHODS: Detecting and analyzing plasma phenylalanine(Phe) and tyrosine(Tyr) from 101 known-PKU heterozygotes and 2023 married people by means of a high performance liquid chromatograph. RESULTS: Significant differences were observed between known- PKU heterozygotes and screening population in plasma Phe, Phe/Tyr and Phe(2)/Tyr. The values of plasma Phe, Phe/Tyr and Phe(2)/ Tyr from 94.1% known-PKU heterozygotes were higher than mean+2s of those values from screening population. According to the limits of mean+2s, 81 cases were screened out from the 2023 married people. It was the first time to get the actual heterozygote frequency of 4% from population. CONCLUSION: The biochemical method mentioned above is available for use in screening PKU heterozygotes.

Adult↗
PubMed1985

An assessment of the radiosensitivity of ataxia-telangiectasia heterozygotes.

Heterozygotes of ataxia-telangiectasia (AT) can, in certain parts of the world, represent a significant proportion of the population. Epidemiological studies suggest that they are more cancer prone than normal individuals. Fibroblasts of five AT heterozygotes are significantly more sensitive to gamma irradiation (mean D0 = 1.18 Gy) than five normals (mean D0 = 1.49 Gy) although some overlap in response is observed. Experiments designed to maximize differences in survival by allowing a period for the repair of potentially lethal damage (PLD) showed that only one out of five AT heterozygotes was defective in the repair of PLD. This technique does not, therefore, permit an improved discrimination of AT heterozygotes. Two AT heterozygotes were tested for their ability to repair lesions that give rise to micronuclei. Both, like the homozygote, were seen to be defective in this capacity. Defects in the repair of chromosome damage may permit a cellular discrimination of the heterozygotes.

Ataxia Telangiectasia↗
PubMed1985

Sandhoff disease heterozygote detection: a component of population screening for Tay-Sachs disease carriers. I. Statistical methods.

Serum and leukocyte hexosaminidase profiles (total activity and percent heat-labile activity levels) in obligate Sandhoff disease (SHD) heterozygotes differ from those of obligate Tay-Sachs disease (TSD) heterozygotes and noncarrier individuals. We have developed a procedure to identify, with 95% sensitivity, carriers of the allele(s) for SHD among individuals screened in a TSD heterozygote identification program. Using multivariate statistical methods of cluster analysis and discriminant analysis on serum and leukocyte hexosaminidase profiles from 102 potential SHD carriers, a linear discriminant function to classify individuals as SHD carriers or SHD noncarriers was constructed. This function classifies the serum and leukocyte profiles from all 15 obligate SHD heterozygotes studied, as those of SHD carriers. A 95% isodensity ellipse derived from only the serum hexosaminidase profiles of the 15 SHD obligate carriers has been applied to a TSD screened sample of 37,843 Jewish and non-Jewish individuals. A potential recall rate of screened individuals for serum retests and leukocyte assays of 2.01% has been estimated. These statistical methods enhance the TSD heterozygote screening program by permitting one to detect SHD heterozygotes within the screened population.

Genetic Carrier Screening↗