Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Heterozygote”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources
PubMed1996

Globin mRNA in beta-thalassemia heterozygotes with different beta-thalassemia alleles and in heterozygotes for hereditary persistence of fetal hemoglobin.

Reverse transcriptase-polymerase chain reaction (RT-PCR) was used to determine the alpha 2/alpha 1-, alpha/beta-, and gamma/beta-mRNA ratios in subjects with beta-thalassemia (beta-thal), hereditary persistence of fetal hemoglobin (HPFH), and normal adults. The alpha- and beta-globin gene mutations were characterized with gene mapping, PCR, and DNA sequencing. The average alpha 2/alpha 1-mRNA ratio was the same in normal adults and beta-thal heterozygotes with four alpha-globin genes (2.61-2.63) or with an alpha-thal-2 trait (1.48-1.55). The average alpha/beta-mRNA ratios were 4.47 and 3.84 in normal adults with four alpha-globin genes and with alpha-thal-2 trait (-alpha/alpha alpha), respectively. There was an increase of approximately 50% in beta-thal heterozygotes with transcriptional mutants [-88 (C-->T) and -29 (A-->G)] with lower values (approximately 25%) in those with alpha-thal-2 trait (-alpha/alpha alpha). High alpha/beta ratios were also observed for heterozygotes for nonsense or frameshift mutants located in exon 1 or exon 2. Increases of approximately 150-165% were seen in subjects with RNA processing defects; an exception was the IVS-1-110 (G-->A) mutation with a normal value in the heterozygote. The increases were also less pronounced in heterozygotes for the codon (CD) 121 (G-->T) mutation and the CDs 134-137 insertion/deletion. Normal alpha/(gamma + beta) values were seen in 3 heterozygotes each with a different deletion involving part of the beta-globin gene. The presence of the silent beta-thal allele, -101 (C-->T), in trans to a CD 8 (-AA) allele has a minor effect on the alpha/beta-mRNA ratio. The alpha/beta-mRNA ratio in HPFH heterozygotes was approximately 145% of normal, but with a gamma-mRNA level of 35.4-44.7% the calculated alpha/(gamma + beta) ratio became as in normal adults. The RT-PCR methodology appears useful in expression studies in beta-thal (and HPFH) and values of mRNA appear to correspond to the type of prevailing mutation(s) and concomitant alpha-thal.

Adolescent↗
PubMed1994

Prevalence of abnormal iron studies in heterozygotes for hereditary hemochromatosis: an analysis of 255 heterozygotes.

Iron studies were compared in 434 patients from 80 hemochromatosis families classified as putative homozygotes, heterozygotes, and normal by HLA typing. There were 28 of 255 (11%) heterozygotes with an elevated serum ferritin and 22 of 255 (8.6%) with an elevated transferrin saturation. Serum ferritin (140 +/- 10.2 micrograms/liter; mean +/- standard error) was greater in heterozygotes than in normal subjects (87 +/- 8.5 micrograms/liter; P < .05, Mann Whitney test). Transferrin saturation was greater in heterozygotes (38% +/- 0.88%) than in normal patients (29% +/- 1.1%; P < .0001). Mean hepatic iron concentration was 54 +/- 6 mumol/g (n = 17), and the hepatic iron index was < 2 in these patients. Most heterozygotes for hemochromatosis have a normal serum ferritin and transferrin saturation. Heterozygotes with minor elevations in serum ferritin or transferrin saturation do not have significant iron overload as assessed by hepatic iron concentration.

Female↗
PubMed2000

A comparison of spermatogenesis in homozygotes, simple Robertsonian heterozygotes and complex heterozygotes of the common shrew (Sorex araneus L.).

Spermatogenesis was studied in 56 shrews (Sorex araneus L.) from two chromosomal hybrid zones in Poland. The hybrid zones were formed between chromosome races that differed in Robertsonian metacentrics. Shrews were compared in four classes: homozygotes, simple Robertsonian heterozygotes, complex heterozygotes forming four-element rings in meiosis I, and complex heterozygotes forming four- or five-element chains. There was a significant effect of karyotype on the level of germ-cell death and chain-forming complex heterozygotes suffered the greatest germ-cell loss. However, the estimated level of germ-cell death is probably insufficient to influence the fertility of these males.

Animals↗
PubMed2004

Heterozygote excess in small populations and the heterozygote-excess effective population size.

It has been proposed that effective size could be estimated in small dioecious population by considering the heterozygote excess observed at neutral markers. When the number of breeders is small, allelic frequencies in males and females will slightly differ due to binomial sampling error. However, this excess of heterozygotes is not generated by dioecy but by the absence of individuals produced through selfing. Consequently, the approach can also be applied to self-incompatible monoecious species. Some inaccuracies in earlier equations expressing effective size as function of the heterozygote excess are also corrected in this paper. The approach is then extended to subdivided populations, where time of sampling becomes crucial. When adults are sampled, the effective size of the entire population can be estimated, whereas when juveniles are sampled, the average effective number of breeders per subpopulations can be estimated. The main limitation of the heterozygote excess method is that it will only perform satisfactorily for populations with a small number of reproducing individuals. While this situation is unlikely to happen frequently at the scale of the entire population, structured populations with small subpopulations are likely to be common. The estimation of the average number of breeders per subpopulations is thus expected to be applicable to many natural populations. The approach is straightforward to compute and independent of equilibrium assumptions. Applications to simulated data suggest the estimation of the number of breeders to be robust to mutation and migration rates, and to specificities of the mating system.

Biological Evolution↗
PubMed1997

Alpha-, beta-, and gamma-mRNA levels in beta-thalassemia; transcriptional and translational differences in heterozygotes, homozygotes, and compound heterozygotes.

We have determined the relative levels of alpha-, beta-, and gamma- (G gamma- and A gamma-) mRNAs in the reticulocytes of patients with mild beta-thalassemia intermedia due to combinations of promoter mutations and a classical type of beta-thalassemia, as well as in their relatives. The expected differences in the alpha/beta-mRNA ratio confirmed the mild suppression of beta-mRNA synthesis, particularly in heterozygotes for the -101 (C-->T) promoter mutation and the large increase in the relative gamma-mRNA level in compound heterozygotes. A significant discrepancy between Hb F and gamma-mRNA levels, observed in previously published studies, was confirmed indicating a less efficient gamma-mRNA translation. When the two different gamma-mRNA (G gamma- and A gamma-) levels were determined it was observed that in beta-thalassemia heterozygotes the extra gamma-mRNA was primarily of the G gamma type suggesting a more efficient translation of the A gamma-mRNA. This difference disappeared in homozygotes and compound heterozygotes: both mRNAs (G gamma- and A gamma-) translate with an equal efficiency.

Adult↗
PubMed1979

Intracellular phenylalanine and tyrosine concentrations in 19 heterozygotes for phenylketonuria (PKU) and 26 normals. Do the higher values in heterozygotes explain their lowered intellectual level?

Intracellular phenylalanine and tyrosine was determined in lymphocytes of 10 heterozygotes (parents) for PKU and in 26 randomly collected apparently normal persons. In cells from the heterozygotes the concentrations of both phenylalanine and tyrosine were higher than in those from the normals, the difference being statistically highly significant. It is argued that this could be responsible for the slight, though statistically significant, intellectual inferiority of heterozygotes for PKU.

Female↗
PubMed1990

Levels of multiallelic overdominance fitness, heterozygote excess and heterozygote deficiency.

Concepts and results on selection balance in multiallelic systems are described. These include a multidimensional concept of heterozygote excess and heterozygote deficiency, a hierarchy of means of assessment of heterozygote advantage, comparisons and contrasts of allelic versus gametic polymorphic states, and conditions defining stable equilibria of complementary gametic sets. The concepts are illustrated in the context of viability selection and behavioral models of kin selection and for two major categories of multilocus selection regimes.

Alleles↗
PubMed1979

Occurrence of G gamma Hb F in Greek HPFH: analysis of heterozygotes and compound heterozygotes with beta thalassaemia.

Haemoglobin F has been isolated from the red cells of individuals with the Greek form of hereditary persistence of fetal haemoglobin (HPFH), and the glycine/alanine composition of the gamma CB3 peptides determined. In contrast to previous reports we have shown that the Hb F of the Greek HPFH heterozygotes contains significant amounts of G gamma chains and circumstantial evidence indicates that these are the products of the same chromosome that carries the Greek HPFH determinant. Hence this chromosome must be directing the synthesis of G gamma, A gamma and (probably) beta and delta chains, thus implying that the Greek form of HPFH does not result from a deletion involving the globin chain structural genes. Analysis of the levels and structure of Hb F from the Greek HPFH heterozygotes and from separated cell populations from the Greek HPFH/beta thalassaemia compound heterozygotes indicate that the Greek HPFH determinant, while allowing an overall increase in gamma chain synthesis, is not the sole factor determining the absolute amount of Hb F production on a cellular basis.

Adult↗
PubMed1976

Studies of the proporation and synthesis of haemoblogin C Philadelphia in red cells of heterozygotes, a homozygote, and a heterozygote for both haemoglobin G and alpha thalassaemia.

The proportion of Hb G Philadelphia (alpha68-Asn leads to Lys) in heterozygotes has been found to have a well-defined bimodal distribution around means of 33% and 46% Hb G. microcytosis and hypochromia are consistently associated with the latter group, who also have a decreased ratio of alpha/beta-chain synthesis in the peripheral blood, but these characters are not linked to the Hb-Galpha gene, because a parent with microcytosis and 46% Hb Galpha may have offspring with 33% Hb G without significant microcytosis. In one family a subject with Hb G and Hb G2 but no Hb A or Hb A2 is presumably a homozygote for alphaG. This subject has microcytosis and a decreased ratio of alpha/beta chain synthesis. In another family a subject with Hbs H, G and G2 but without Hbs A or A2 is heterozygous for both Hb G and alpha thalassaemia I. These findings are compatible with the hypothesis that the alphaG mutation occurs on a chromosome with only a single alpha-chain locus and that the expression in heterozygotes as 46% or 33% Hb G is determined by the homologous chromosome in trans having either one or two normal alphaA genes respectively. The significance of this polymorphism for chromosomes carrying alpha-chain genes is discussed.

Chromosomes, Human, 21-22 and Y↗
PubMed1992

[A computer simulated test for the long-time change of heterozygote. Analysis of possibility on preserving the heterozygote for long-time in population].

Under the conditions of random mating and selecting. The research by computer simulation analysed the possibility of long-time conserving heterozygote in colong. An important conclusion was obtained. It was impossible to conserve heterozygote for a long time in colong. Therefore it is not necessary to control inbreeding for conserving all genes of colong by reducing gene purity in the work of conserving breeds for farm animal and poultry.

Animals↗
PubMed1988

A frequent A gamma-hereditary persistence of fetal hemoglobin in northern Sardinia: its molecular basis and hematologic phenotype in heterozygotes and compound heterozygotes with beta-thalassemia.

A survey of hemoglobinopathies in northern Sardinia revealed a high frequency (0.3%) of carriers of a hematologic condition characterized by increased expression of fetal hemoglobin during adult life (hereditary persistence of fetal hemoglobin or HPFH). In spite of a normal hematologic phenotype, the heterozygous carriers for this condition display about 12% HbF, almost exclusively of the A gamma type; compound heterozygotes with beta-thalassemia have 20%-26% HbF and run a very mild clinical course. The sequence analysis of the cloned A gamma gene linked to the HPFH determinant revealed the presence of a G----A substitution at position -117 of the A gamma-globin gene promoter; the same mutation occurs also in Greek HPFH, although associated with different restriction polymorphisms. Another hereditary condition characterized by increased HbF (alpha 2 A gamma 2) level and a mild thalassemia phenotype in Sardinia is associated with the -196C----T substitution in the A gamma-globin gene promoter (Sardinian delta beta-thalassemia). Population studies using oligonucleotides complementary both to the -117 G----A and -196C----T mutations and the corresponding normal sequences confirm the presence of these mutations only in HPFH and delta beta-thalassemia chromosomes and exclude these changes being common DNA polymorphisms.

Female↗
PubMed1986

Studies of erythropoietic cells in heterozygotes and homozygotes for haemoglobin Constant Spring and in heterozygotes for both haemoglobin Constant Spring and alpha-thalassaemia 1 trait: extent of globin chain precipitation and cell cycle distribution.

Electron microscope studies revealed that the average value for the percentage of erythropoietic cell profiles containing globin chain precipitates in heterozygotes for haemoglobin Constant Spring (HbCS) was similar to that in subjects with alpha-thalassaemia 2 trait and that the average values for this parameter in homozygotes for HbCS and patients with HbCS-H disease were similar to that in individuals with HbH disease. The explanation for the finding that the presence of two alpha cs genes (in homozygotes for HbCS) caused a degree of precipitation corresponding to that seen in patients with HbH disease, who have three deleted alpha genes, rather than to that seen in individuals with alpha-thalassaemia 1 trait, who have two deleted alpha genes, is uncertain. In all the patients with HbCS studied, the majority of the inclusions of precipitated globin chains had a stellate or branching appearance and were considered to consist of beta-chains. However, in the homozygotes for HbCS and to a lesser extent in the patients with HbCS-H disease there were small but significant numbers of erythropoietic cell profiles containing multiple rounded inclusions of the type seen in the beta-thalassaemia syndromes, or both branching and multiple rounded inclusions. It is argued that these rounded inclusions probably consisted either of precipitated HbCS or beta-chains rather than alpha-chains. The distribution of erythroblasts in the different stages of the cell cycle was normal in two homozygotes for HbCS and two patients with HbCS-H disease, indicating that there was little or no cell death during the proliferative phase of erythropoiesis in either of these conditions.

Adult↗
PubMed1975

Heterozygote detection in phenylketonuria. Measurement of discriminatory ability and interpretation of the phenylalanine loading test by determination of the heterozygote likelihood ratio.

Two tests of heterozygosity for phenylketonuria, the phenylalanine/tyrosine ratio in the plasma after a fast and the response to an oral load of phenylalanine, have been compared in obligate heterozygotes for phenylketonuria and apparent normal homozygotes. The discriminatory ability of the tests is measured using both parametric and non-parametric methods, the correlation between them is determined, and the reproducibility of the loading test is examined. Because complete separation between the genotypes cannot be achieved by these tests, a method of interpretation which avoids possibly erroneous categoric statements and which enables the family history of a subject and his test result to be combined in a quantitative and meaningful way is described.

Heterozygote↗
PubMed1996

Cystic fibrosis heterozygote screening in the Orthodox Community of Ashkenazi Jews: the Dor Yesharim approach and heterozygote frequency.

In the community of the Orthodox Jews most of the marriages are arranged a screening program that is aimed at preventing the marriage of two carriers of autosomal recessive disorders is conducted by the Dor Yesharim organization. A random sample of 6,076 individuals of the Orthodox Jewish Ashkenazi community, were screened for the five mutations common in Ashkenazi patients (delta F508, W1282X, G542X, N1303K, 3849 + 10Kb C-->T). Two hundred thirty-two carriers were identified, giving a heterozygote frequency of 1:26. The relative frequencies of the individual mutations in the general population were comparable to those in the patients.

Adolescent↗
PubMed1985

Neuropathologic study in the heterozygotes of X-linked brindled mutant mouse.

The clinical and morphological features were studied in female heterozygotes of the sex-linked brindled mutant mice, which are an appropriate animal model for human Menkes' kinky hair disease (MKHD). Clinically, female heterozygotes presented phenotypical variety. In these heterozygotes, we distinguished the unique group of mice, which showed mottled white and dark brown fur and curly whiskers. We designated this unique group "heterozygote, variant type", in contrast to the remaining group--"heterozygote, usual type"--, of which the fur was mottled dark and light brown, and the whiskers were straight. Ultrastructurally, various degrees of mitochondrial changes, from an almost normal appearance of the mitochondria to similar to those of the hemizygotes, were observed. Furthermore we noticed that, in the heterozygotes, there were positive correlations between this morphological spectrum and those phenotypical varieties. These findings were interpreted as a possible subclinical copper deficiency in the heterozygotes, and the morphological alterations in heterozygotes were probably due to X-chromosome inactivation according to Lyon's hypothesis. The presence, however, of clinical and morphological varieties in the heterozygotes leads us to the hypothesis that the inactivation rate is not necessarily the same for all carriers. Moreover, it can be speculated that pathologic changes similar to those in heterozygotes may be present in the female carriers of human MKHD.

Animals↗