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PubMed1982

The developmental analysis of aldehyde oxidase activity in cin allelic heterozygotes of Drosophila melanogaster.

Aldehyde oxidase (AO) activity has been determined at 11 stages during the development of selected cin allelic homo-, hemi- and heterozygotes in Drosophila melanogaster. The AO activity levels found during development were completely consistent with the levels previously reported for adults, less than 24 h of age (Bentley and Williamson, 1979b). All of the cin homo- and hemizygotes tested exhibited no significant levels of AO activity at any of the 11 stages during development. All cin allelic heterozygotes, which were defined as complementing in adults, less then 24h of age, displayed similar levels of complementation at all stages tested. Conversely, all cin allelic heterozygotes which were defined as noncomplementing in adults, less than 24h of age, were found to lack measurable AO activity at all developmental stages tested.

Aldehyde Oxidase↗
PubMed1997

Decreased production and increased catabolism of apolipoprotein B-100 in apolipoprotein B-67/B-100 heterozygotes.

Apolipoprotein (apo) B-67 is a truncated form of apoB-100 due to deletion of an adenine at cDNA 9327. Heterozygotes have one allele making apoB-100; therefore, plasma apoB levels would be predicted to be at least 50% of normal. However, apoB-67 heterozygotes have total plasma apoB levels that are 24% of normal. To determine the mechanisms responsible for the lower-than-expected levels of apoB, in vivo kinetics of apoB-100 were performed in three apoB-67/apoB-100 heterozygotes and compared with those of six control subjects by using a primed-constant infusion of [5,5,5-2H3]leucine in the fed state. Kinetic parameters were calculated by multicompartmental modeling of the data. The mean total apoB plasma concentration of the apoB-67 subjects was 21.8+/-6.1 mg/dL, or 24% of that of control subjects (89.6+/-24.1 mg/dL, P=.002). ApoB-67 subjects had lower mean VLDL apoB-100 production rates (3.6+/-1.2 versus 13.9+/-3.5 mg x kg(-1) x d(-1), P=.002) and lower mean transport rates of apoB-100 into LDL (3.5+/-1.4 versus 12.6+/-4.1 mg x kg(-1) x d(-1), P=.008) compared with control subjects. The transport rate into IDL was not significantly different (1.2+/-0.5 versus 6.2+/-4.0 mg x kg(-1) x d(-1), P=.07). The fractional catabolic rate of VLDL apoB-100 was significantly higher in apoB-67 subjects than in control subjects (18.1+/-8.6 versus 7.6+/-1.6 mg x kg(-1) x d(-1), P=.017). ApoB-100 IDL and LDL fractional catabolic rates were not significantly different. VLDL apoB-100 pool size in apoB-67 subjects was 11% of that of control subjects (15.8+/-7.7 versus 141.6+/-33.7 mg, P=.0004) due to a 74% lower production rate (26% of control values) and a 2.4-fold higher fractional catabolic rate. LDL apoB-100 pool size in apoB-67 subjects was 22% of that of control subjects (665.3+/-192.4 versus 2968.3+/-765.2 mg, P=.002) due primarily to a lower production rate (27% of control values). Thus, both decreased production of VLDL and LDL apoB-100 and increased catabolism of VLDL apoB-100 are responsible for the low levels of apoB-100 in apoB-67 subjects.

Adult↗
PubMed1975

Globin synthesis in fractionated Normoblasts of beta-thalassemia heterozygotes.

Globin chain synthesis was examined in erythroid cells of increasing maturity, fractionated from the whole bone marrow of beta-thalassemia heterozygotes by a density gradient centrifugation procedure. In experiments using total cell "globin," a gradient of alpha/beta chain ratios was observed, increasing with erythroid cell maturation from unity in the basophilic cells up to 2.0 in reticulocytes. Gel filtration of the lysates from these marrow fractions revealed the presence of free alpha chains even in the most immature cells, the amount of which increased with erythroid cell age; the total alpha/beta ratio derived from gel filtration experiments showed a gradient similar to that observed in the total globin experiments. However, the alpha/beta ratio of the hemoglobin fraction obtained by gel filtration remained constant throughout maturation at an average of 0.65. This latter finding is incompatible with balanced synthesis at any stage of red cell development and excludes the possibility that total beta chain production is higher in the early cells than in the later cells or that alpha chain production in the early cells is reduced to the level of beta chain synthesis. Furthermore, in a Hb S/beta-thalassemia marrow examined, the beta A/beta S ratio remained constant throughout maturation while the alpha/non-alpha ratio showed an increase like that observed in the simple beta-thalassemia heterozygotes. This argues strongly against increased synthesis from either the thalassemic or nonthalassemic beta chain gene being responsible for the balanced synthesis in the immature cells. These findings lead us to suggest that, in beta-thalassemia heterozygotes, a large alpha chain pool is present throughout erythroid cell maturation and that the observed increase in alpha/beta ratios is a function of the ability of those cells to degrade the excess alpha chains.

Adult↗
PubMed1978

Genetics of the low density lipoprotein receptor. Diminished receptor activity in lymphocytes from heterozygotes with familial hypercholesterolemia.

Using circulating mononuclear cells as a readily available tissue and using the rate of high affinity degradation of 125-I-labeled low density lipoprotein (LDL) as an index of cell surface LDL receptor activity, we have measured receptor activity in cells from 53 individuals. This group includes 32 healthy subjects, 15 subjects with the heterozygous form of familial hypercholesterolemia, and 6 subjects with hyperlipidemic disorders other than familial hypercholesterolemia. 7 of the healthy subjects and 10 of the heterozygotes were members of a single large kindred with five-generation transmission of the mutant familial hypercholesterolemia gene. LDL receptor activity was assayed in blood mononuclear cells under two sets of conditions. First, 125I-LDL degradation was measured in purified lymphocytes that had been incubated for 3 days in the absence of lipoproteins so as to induce a high level of LDL receptor activity. Phase-contrast autoradiograms of cells incubated with 125I-LDL and electron micrographs of cells incubated with ferritin-labeled LDL confirmed the existence of LDL receptors on lymphocytes. Second, 125I-LDL degradation was measured in mixed mononuclear cells (85-90% lymphocytes and 5-15% monocytes) immediately after their isolation from the bloodstream. This assay represented an attempt to assess the number of receptors actually expressed on the cells when they were in the circulation. Under both sets of conditions, cells from the familial hypercholesterolemia heterozygotes expressed an average of about one-half the normal number of LDL receptors. The current findings are consistent with the conclusion that heterozygotes with familial hypercholesterolemia possess only one functional allele at the LDL receptor locus and that the consequent deficiency of LDL receptors produces the clinical syndrome of heterozygous familial hypercholesterolemia.

Adhesiveness↗
PubMed1991

beta-adrenergic sweat responses in cystic fibrosis heterozygotes with and without the delta F508 allele.

Cystic fibrosis (CF) causes early death for most homozygotes, yet has a carrier frequency among Caucasians of about 4-5%, suggesting a heterozygote advantage. The major defect in the CF gene is a three-base deletion leading to loss of a phenylalanine residue at position 508 (delta F508) that accounts for about 68% of CF alleles in the North American population; the remaining 32% appears to consist of a large assortment of mutations. Sweat secretion in response to beta-adrenergic stimulation is completely lacking in CF homozygotes and is reduced to 1/2 normal in heterozygotes. To determine if this secretory process is affected by different CF alleles, we used the polymerase chain reaction technique with DNA obtained from peripheral leukocytes to determine retrospectively the presence or absence of the delta F508 allele in 20 CF heterozygotes for whom sweat responses to beta-adrenergic stimulation had previously been determined. Twelve of 20 subjects (60%) were positive for the delta F508 mutation. The variance in sweat responses was not reduced in the delta F508 group relative to the non-delta F508 group, but a gender/allele interaction was noted.

Alleles↗
PubMed2005

Heterozygote effects in mice with partial truncations in the growth hormone receptor cytoplasmic domain: assessment of growth parameters and phenotype.

The GH receptor (GHR) is essential for normal postnatal growth and development, and the molecular basis of GHR action has been studied intensively. Clinical case studies and more recently mouse models have revealed the extensive phenotype of impaired GH action. We recently reported two new mouse models, possessing cytoplasmic truncations at position 569 (plus Y539/545-F) and 391, which were created to identify functional subdomains within the cytoplasmic signaling domain. In the homozygous state, these animals show progressively impaired postnatal growth coupled with complex changes in gene expression. We describe here an extended phenotype analysis encompassing the heterozygote state to identify whether single copies of these mutant receptors bring about partial or dominant-negative phenotypes. It appears that the retention of the ubiquitin-dependent endocytosis motif in the N-terminal cytoplasmic domain permits turnover of these mutant receptors because no dominant-negative phenotype is seen. Nonetheless, we do observe partial impairment of postnatal growth in heterozygotes supporting limited haploinsufficiency. Reproductive function is impaired in these models in a progressive manner, in parallel with loss of signal transducer and activator of transcription-5 activation ability. In summary, we describe a more comprehensive phenotypic analysis of these mouse models, encompassing overall and longitudinal body growth, reproductive function, and hormonal status in both the heterozygote and homozygote state. Our results suggest that patients expressing single copies of similarly mutated GHRs would not display an obvious clinical phenotype.

Animals↗
PubMed1993

Defects in heart and lung development in compound heterozygotes for two different targeted mutations at the N-myc locus.

Two types of mutant allele, one leaky and one null, have been generated by gene targeting at the N-myc locus in embryonic stem cells and the phenotypes of mice homozygous for these mutations have been described. These mutations have shown that N-myc has a number of functions during development, including a role in branching morphogenesis in the lung, which manifests itself at birth in mice homozygous for the leaky allele, and roles in the development of the mesonephric tubules, the neuroepithelium, the sensory ganglia, the gut and the heart, which become evident at midgestation in embryos homozygous for the null allele. In an attempt to define roles for N-myc at other stages of development, we have combined the two types of N-myc mutant allele in a compound heterozygote that as a result contains approximately 15% of normal levels of N-Myc protein. Compound heterozygotes died during gestation at a time intermediate to the times of death of embryos homozygous for either mutation individually, and their death appeared to result from cardiac failure stemming from hypoplasia of the compact subepicardial layer of the myocardium. Investigation of the expression pattern of N-myc and various markers of differentiation in wild-type and compound heterozygote mutant hearts has suggested that N-myc may function in maintaining the proliferation and/or preventing the differentiation of compact layer myocytes. This study illustrates the importance of generating different mutations at a given locus to elucidate fully the function of a particular gene during development.

Animals↗
PubMed2003

Thermodynamic determination of plasma and leukocyte beta-hexosaminidase isoenzymes in homozygote and heterozygote carriers for the GM2 gangliosidosis B1 variant.

In the GM2 gangliosidosis B1 variant, the mutated isoenzyme A of beta-hexosaminidase (Hex) is incapable of hydrolyzing ganglioside GM2 and negatively charged substrates. Biochemical characterization of this lysosomal disease is carried out using synthetic alpha-subunit-specific sulfated substrates, as heat-inactivation assays are not applicable. The apparent enzyme activation energy of Hex using the chromogenic substrate 3,3'-dichlorophenolsulfonphthaleinyl N-acetyl-beta-D-glucosaminide is related directly to the relative proportions of Hex A and Hex B isoenzymes. This thermodynamic variable was used for the study of Hex enzyme heterogeneity in 3 patients with the GM2 gangliosidosis B1 variant and 6 heterozygote carriers. Hex activity was determined at 25 degrees C, 30 degrees C, 35 degrees C, and 37 degrees C in a Cobas Bio analyzer (Roche Diagnostics, Basel, Switzerland), and Arrhenius plot slopes and apparent activation energies were calculated in plasma samples and mononuclear and polymorphonuclear leukocyte lysates. The determination of the Hex isoenzymes in plasma presented a high discrimination power for B1 variant patients but not for heterozygote carriers, in whom false-negative results may be obtained. However, thermodynamic evaluation of the isoenzyme composition of Hex in leukocyte lysates permits the biochemical identification of patients with the GM2 gangliosidosis B1 variant and of heterozygote carriers.

Female↗
PubMed2003

Amplicon melting analysis with labeled primers: a closed-tube method for differentiating homozygotes and heterozygotes.

BACKGROUND: Common methods for identification of DNA sequence variants use gel electrophoresis or column separation after PCR. METHODS: We developed a method for sequence variant analysis requiring only PCR and amplicon melting analysis. One of the PCR primers was fluorescently labeled. After PCR, the melting transition of the amplicon was monitored by high-resolution melting analysis. Different homozygotes were distinguished by amplicon melting temperature (T(m)). Heterozygotes were identified by low-temperature melting of heteroduplexes, which broadened the overall melting transition. In both cases, melting analysis required approximately 1 min and no sample processing was needed after PCR. RESULTS: Polymorphisms in the HTR2A (T102C), beta-globin [hemoglobin (Hb) S, C, and E], and cystic fibrosis (F508del, F508C, I507del, I506V) genes were analyzed. Heteroduplexes produced by amplification of heterozygous DNA were best detected by rapid cooling (>2 degrees C/s) of denatured products, followed by rapid heating during melting analysis (0.2-0.4 degrees C/s). Heterozygotes were distinguished from homozygotes by a broader melting transition, and each heterozygote had a uniquely shaped fluorescent melting curve. All homozygotes tested were distinguished from each other, including Hb AA and Hb SS, which differed in T(m) by <0.2 degrees C. The amplicons varied in length from 44 to 304 bp. In place of one labeled and one unlabeled primer, a generic fluorescent oligonucleotide could be used if a 5' tail of identical sequence was added to one of the two unlabeled primers. CONCLUSION: High-resolution melting analysis of PCR products amplified with labeled primers can identify both heterozygous and homozygous sequence variants.

Base Sequence↗
PubMed2005

Urinary lipid profiling for the identification of fabry hemizygotes and heterozygotes.

BACKGROUND: Fabry disease is an X-linked lysosomal storage disorder resulting from a deficiency of the lysosomal hydrolase, alpha-galactosidase, for which enzyme replacement therapy is now available. In this study, we aimed to identify Fabry heterozygotes not only for genetic counseling of families but because it is becoming increasingly obvious that many heterozygous (carrier) females are symptomatic and should be considered for treatment. METHODS: We measured 29 individual lipid species, including ceramide, glucosylceramide, lactosylceramide, and ceramide trihexoside, in urine samples from Fabry hemizygotes and heterozygotes and from control individuals by electrospray ionization tandem mass spectrometry. Individual analyte species and analyte ratios were analyzed for their ability to differentiate the control and patient groups. RESULTS: The Fabry hemizygotes had increased concentrations of the substrate for the deficient enzyme, ceramide trihexoside, as well as lactosylceramide and ceramide, along with decreased concentrations of both glucosylceramide and sphingomyelin. Ratios of these analytes improved differentiation between the control and Fabry groups, with the Fabry heterozygotes generally falling between the Fabry hemizygotes and the control group. CONCLUSIONS: These lipid profiles hold particular promise for the identification of Fabry individuals, may aid in the prediction of phenotype, and are potentially useful for the monitoring of therapy in patients receiving enzyme replacement.

Fabry Disease↗
PubMed2006

Heterozygotes of NOS3 polymorphisms contribute to reduced nitrogen oxides in high-altitude pulmonary edema.

STUDY OBJECTIVES: High-altitude pulmonary edema (HAPE), which develops on exertion under hypoxic conditions, aggravates due to endothelial dysfunction. Repeat events of the disorder suggests of genetic susceptibility. Endothelial nitric oxide synthase gene (NOS3), a regulator of vasodilation, has emerged as a strong candidate marker. In the present study, we investigated G894T, 27-base-pair 4b/4a (variable number of tandem repeat), -922A/G, and -786T/C polymorphisms of NOS3, individually or in combination, for an association with HAPE. DESIGN: A cross-sectional case control study. SETTINGS: Blood samples of HAPE-resistant lowlanders (HAPE-r) were obtained at sea level, and blood samples of patients with HAPE (HAPE-p) were obtained at Sonam Norboo Memorial Hospital, Leh, at 3,500 m. PARTICIPANTS: The study groups consisted of 60 HAPE-r inducted two to three times to altitudes > 3,600 m; and 72 HAPE-p, who had HAPE on their first visit to high altitude. RESULTS: Nitrogen oxides (NOx) at 77.9 +/- 28.6 micromol/L were significantly elevated in HAPE-r as compared to 42.39 +/- 12.93 micromol/L in HAPE-p (p < 0.0001). Genotype distribution of G894T and 4b/4a polymorphisms was significantly different in the two groups (p = 0.001 and 0.009, respectively). Haplotype analysis revealed -922A/G and -786T/C polymorphisms in complete linkage disequilibrium. The wild-type haplotypes G-b (G894T, 4b/4a), G-A (G894T, -922A/G), and G-b-A (G894T, 4b/4a, -922A/G) were significantly overrepresented in HAPE-r (p < 0.0001, p = 0.03, and p = 0.02, respectively). The heterozygote genotype combination GTba as compared to wild-type combination GGbb was significantly higher in HAPE-p (chi2 = 18.62, p = 0.00009; odds ratio, 7.20; 95% confidence interval, 2.82 to 18.38). The combination of four heterozygotes GTbaAGTC was overrepresented in HAPE-p (p = 0.04), whereas the wild-type genotype combination GGbbAATT was overrepresented in HAPE-r (p = 0.002). Furthermore, the GGbb combination correlated with significantly elevated NOx as compared to remaining combinations as a whole in both HAPE-r and HAPE-p (p = 0.01 and 0.004, respectively). CONCLUSIONS: Reduced NOx and combination of heterozygotes associate with the susceptibility to HAPE. The study impels another step toward application of NOx as a diagnostic marker for HAPE. The NOS3 GTba and GTbaAGTC genotype combinations may find application as genetic markers for predicting the risk for HAPE.

Adult↗
PubMed1985

Postheparin plasma lipoprotein lipase activity in heterozygotes of familial lipoprotein lipase deficiency.

Serum lipoprotein pattern, apoproteins and two postheparin triglyceride lipases were analyzed in a patient with familial lipoprotein lipase (LPL) deficiency and her family. Serum of the patient showed extreme hyperchylomicronemia and her postheparin plasma LPL activity was distinctly decreased. None of heterozygotes had any type of hyperlipoproteinemia. The mother and brother of the patient had moderately decreased LPL activity. There were no consistent changes in hepatic triglyceride lipase (H-TGL) activity among heterozygotes. These results suggest that assay of LPL may be helpful for detection of heterozygotes in familial LPL deficiency.

Adult↗
PubMed1983

HLA genotypic study of insulin-dependent diabetes the excess of DR3/DR4 heterozygotes allows rejection of the recessive hypothesis.

The genetics of insulin-dependent diabetes mellitus (IDDM) is currently an area of controversy, with some investigators proposing heterogeneity within the HLA region and even the existence of non-HLA-linked susceptibility genes, and others maintaining that a simple autosomal recessive gene linked to HLA with reduced penetrance is an adequate explanation. To resolve this latter question, we report here a simple method of testing whether a single HLA-linked susceptibility gene is inherited in a recessive fashion when it is associated with two different HLA alleles, as is the case for IDDM. It is shown that if the number of DR3/DR4 heterozygotes in a diabetic population exceeds the combined sum of DR3/3 and DR4/4 homozygotes in that same diabetic population, then a recessive mode of inheritance can be rejected. The advantages of the method are that it does not depend on ratios, as do relative risk calculations, nor does it depend on control data, but is based only on studies of the diabetics themselves. With data on 193 genotyped IDDM patients, we can clearly reject the recessive mode of inheritance, since the number of heterozygotes is 68 compared with a maximum of 22 homozygotes (P less than 10(-4)). Eight other published studies are in concordance with these results. Therefore, a nonparametric test, independent of the significance of any individual study, rejects equality of heterozygotes and homozygotes (P less than 0.002) and rejects the simple recessive mode of inheritance as a direct consequence. We conclude that more complex modes of inheritance of HLA-linked IDDM susceptibility, such as two different diabetogenic alleles or multiple loci, must be entertained. DIABETES 32:169-174, February 1983.

Alleles↗
PubMed2000

Fabry disease: twenty-two novel mutations in the alpha-galactosidase A gene and genotype/phenotype correlations in severely and mildly affected hemizygotes and heterozygotes.

BACKGROUND: Fabry disease, an inborn error of glycosphingolipid catabolism, results from mutations in the X-chromosomal gene encoding the lysosomal exoglycosidase, alpha-galactosidase A (alpha-Gal A; EC 3.2.1.22). The nature of the molecular lesions in the alpha-Gal A gene in 36 unrelated families was determined in order to provide precise heterozygote detection, prenatal diagnosis, and to define genotype/phenotype correlations. METHODS: Genomic DNA was isolated from affected males and/or carrier females from 36 unrelated families with Fabry disease. The entire alpha-Gal A coding region and flanking intronic sequences were analyzed by PCR amplification and solid-phase or cycle sequencing. Markers closely linked to the alpha-Gal A gene were analyzed to determine if probands with the same mutations were related. RESULTS: Twenty-two novel mutations were identified including 10 missense (P40L, W95S, S148N, C172R, M187V, N224S, W226R, A230T, D266H, N320Y), three nonsense (Y134X, C142X, W204X in two families), three splice-site defects (IVS2(+1), IVS3(+1), IVS4(+1)) and six small deletions or insertions (26delA in two families, 672ins37, 774delAC, 833insA, 1139delC, 1188insT). Of the remaining 12 families (33.3%), each had a previously identified mutation, eight of which occurred at CpG dinucleotides including R112C (two families), R112H, R227Q, R227X (three families), and R301Q. Haplotype analysis of the mutant alleles that occurred in two or three presumably unrelated families revealed that the families with the rare novel alleles (W204X and 26delA) were probably related, whereas those with mutations involving CpG dinucleotides (R112C and R227X) were not, the latter being consistent with their origins as independent mutational events. Genotype/phenotype correlations revealed that certain mutations previously found in mild variant patients also were found in classic patients. In addition, the genotypes and spectrum of phenotypic severity were determined in five heterozygotes with no family history. CONCLUSIONS: These results illustrate the molecular heterogeneity of the lesions causing Fabry disease and emphasize the fact that CpG dinucleotides constitute important hot spots for mutation in the alpha-Gal A gene. These studies also permit precise heterozygote detection and prenatal diagnosis in these families, and delineate phenotype-genotype correlations in this disease.

Amino Acid Sequence↗
PubMed1998

[Gene identification and pedigree analysis of the double mutation heterozygote of beta-thalassemia[-28(A-->G).CD17(A-->T)/N]].

OBJECTIVE: To report the result of gene identification and pedigree analysis of the double mutation heterozygote of beta-thalassemia[-28(A-->G).CD17(A-->T)/N]. METHODS: Polymerase chain reaction in combination with dot-blot hybridization of allele-specific oligonucleotide(PCR/ASO) probes was used. RESULTS: Gene identification was carried out in four probands and 35 other family members. There were 22 patients with beta-thalassemia -28(A-->G) and CD17(A-->T) mutant gene. Based on the clinical features, the results of hematological and biochemical examinations and pedigree analysis, they proved to be the double mutation heterozygote of beta-thalassemia[-28(A-->G).CD17(A-->T)/N], i.e., double point mutations on the same chromosome. CONCLUSION: Double mutation heterozygote[-28(A-->G).CD17(A-->T)/N] is a new type of beta-thalassemia.

Adolescent↗
PubMed2001

[The prevalence of beta-thalassemia heterozygotes compound alpha-thalassemia in Guangdong district].

OBJECTIVE: To investigate the prevalence of beta-thalassemia (beta-thal) heterozygotes compound alpha-thal in Guangdong area. METHODS: alpha-thal 1 genes were amplified in 500 beta-thal carriers diagnosed by reverse dot blotting (RDB) using gap-PCR method, alpha-thal 2 genes were detected in 400 of the 500 beta-thal carriers using Southern blotting with alpha-globin DNA probe and restrict endonuclease zymogram analytical method. RESULTS: Forty three alpha-thal-1(alpha alpha/- -SEA) cases were identified in the 500 beta-thal traits, and 26 alpha-thal 2 including 17 rightward deletion (alpha alpha/- alpha 3.7) and 9 leftward deletion(alpha alpha/-alpha 4.2) cases were identified in the 400 beta-thal traits. CONCLUSION: The prevalence of beta-thal heterozygote carrying alpha-thal-1 gene was 8.6% and that of beta-thal heterozygote carrying alpha-thal-2 gene was 6.5% (4.2% rightward deletion and 2.2% leftward deletion).

Adult↗
PubMed1965

SWEAT CHLORIDES IN SALT-DEPRIVED CYSTIC FIBROSIS HETEROZYGOTES.

Sweat chlorides of 10 sets of parents of children with cystic fibrosis and 11 controls were studied in an attempt to develop a test for the diagnosis of cystic fibrosis heterozygotes by subjecting both the parents and controls to a low sodium diet and comparing sweat chloride values as the diet progressed. It was hoped that the sweat chloride levels of the parents, the heterozygotes, would remain stationary throughout the diet, since their children, the homozygotes, reveal this finding under similar conditions of salt deprivation. The sweat chloride levels of the controls, because of effects of aldosterone, were expected to decrease steadily from the commencement of the diet to its termination.A decrease in sweat chloride values of similar magnitude was found in both parents and controls as the diet continued. It is concluded that the study of sweat electrolyte levels in salt-deprived subjects is of no value in the diagnosis of cystic fibrosis heterozygotes.

Aldosterone↗
PubMed1977

Detection of heterozygotes for tyrosinase-negative oculocutaneous albinism by hairbulb tyrosinase assay.

Five heterozygotes for ty-neg OCA had absent or markedly reduced hairbulb tyrosinase activity, when compared to normally pigmented control subjects. Clinically, all five were fully pigmented and could not be distinguished from the normal control subjects. It is proposed that the quantitative hairbulb tyrosinase assay can be used to detect heterozygotes for ty-neg OCA. A mechanism to explain the low levels of activity in the hairbulbs from heterozygotes is discussed.

Albinism↗