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At least 145 records · Page 8Linked to original sources

PubMed1999

Association of unstable hemoglobin variants and heterozygous beta-thalassemia: example of a new variant Hb Acharnes or [beta53(D4) Ala --> Thr].

We report here the functional and structural characterization of Hb Acharnes [beta53(D4) Ala --> Thr], an unstable and electrophoretically silent variant, that was found associated in trans with a beta(0)-thalassemic mutation (IVSI-1 G --> A), in a patient with thalassemia intermedia syndrome. This case is discussed in comparison with other sporadic cases that we have previously investigated, resulting from the co-inheritance of a beta(0)-thalassemic mutation (CD39 C --> T) with two other types of unstable hemoglobins, Hb Köln [beta98(FG5) Val --> Met], and Hb Arta [beta45(CD4) Phe --> Cys]. It may be concluded that, in these associated forms, both the degree of instability of the variant and the altered oxygen binding properties (affecting the degree of tissue hypoxia) are major determinants of their clinical expression.

Child↗

PubMed1996

Colon-cancer cell variants producing regressive tumors in syngeneic rats, unlike variants yielding progressive tumors, attach to interstitial collagens through integrin alpha2beta1.

Nine clones of tumor cells, derived from a single rat colon carcinoma, were analyzed for their adhesive properties and in vivo growth patterns. Four clones (denoted REG) gave rise to regressively growing tumors. Cells from the 4 REG clones attached significantly better to collagen types I and III than did cells from the 5 clones (denoted PRO) which grew progressively in vivo. In contrast, REG and PRO clones did not differ in their attachment to collagen type IV, laminin or fibronectin. The attachment of REG cells to collagen was dependent on Mg2+, but not Ca2+. Monospecific rabbit IgG to rat integrin beta 1-chain inhibited REG cell attachment to collagen, demonstrating involvement of a beta 1 integrin in this process. PRO and REG cells expressed an underglycosylated beta 1 chain (Mr approximately 105,000) that was somewhat smaller than beta 1-chains described previously on rat fibroblasts and hepatocytes (Mr approximately 115,000). Monoclonal IgG to rat integrin alpha 2 beta 1, but not to alpha 1 beta 1, readily inhibited REG cell attachment to collagen, demonstrating the involvement of integrin alpha 2 beta 1. However, beta 1 and alpha 2 integrin subunits were found in purified glycoproteins from both PRO and REG cells. This suggests that alpha 2 beta 1 integrin is expressed by both cell variants, but is functional as a collagen receptor on REG cells only. In this system of tumor-cell variants, the clear-cut differences in attachment to interstitial collagens of the 9 clones suggest a possible relationship between this attachment and the capacity to induce progressive or regressive tumors.

Amino Acid Sequence↗

PubMed1994

African-American factor VII-deficient variants in Georgia (FVII variants).

We studied African-American Factor (FVII)-deficient variants and carriers in Georgia by measuring their levels of FVII antigen (FVIIAG) and FVII procoagulant (FVIIC). Factor VIIAG was determined using enzyme-linked immunoassay (ELISA), whereas FVIIC was measured in two ways: 1) by fibrin clotting methods that employed human recombinant (HRFVIIC), human placental (HPFVIIC), rabbit brain (RBFVIIC), and bovine brain (BBFVIIC) thromboplastins; and 2) by an amidolytic method (AMFVIIC). Prothrombin time tests (PT) were also performed by standard methods. These 4 FVII-deficient patients and 3 carriers demonstrated the following results: PT: 18.2 +/- 6.5 sec; FVIIAG: 73.0 +/- 14.9%; HRFVIIC: 30.6 +/- 20.3%; HPFVIIC: 30.5 +/- 21.4%; RBFVIIC: 25.3 +/- 21.4%; BBFVIIC: 30.6 +/- 17.5%; AMFVIIC: 44.1 +/- 18.3%. We conclude that a group of clinically mild African-American FVII-deficient variants exists in Georgia. This group is characterized by the presence of FVIIAG and decreased FVIIC, using a variety of thromboplastins; and excellent correlation was noted for both human thromboplastins.

Antibodies↗

PubMed1995

Genetic evidence that the Lewy body variant is indeed a phenotypic variant of Alzheimer's disease.

Lewy Body Variant (LBV) patients present as Alzheimer's disease (AD) clinically; about two-thirds also have mild extrapyramidal features. At autopsy, neocortical and brain stem Lewy bodies are present in addition to changes diagnostic of AD. We have found that the Apolipoprotein E4 allele is a major genetic risk factor for LBV as it is for "pure AD," in contrast to subjects with diffuse Lewy body disease or Parkinson's disease. This genetic evidence supports the concept that LBV--the second most common neurodegenerative form of dementia--is a phenotypic variant of AD.

Aged↗

PubMed1998

Variant in sulfonylurea receptor-1 gene is associated with high insulin concentrations in non-diabetic Mexican Americans: SUR-1 gene variant and hyperinsulinemia.

The high-affinity sulfonylurea receptor (SUR1) gene regulates insulin secretion and may play a role in type 2 diabetes. A silent variant in exon 31 of SUR1 (AGG-->AGA) was detected by single-strand conformational polymorphism and genotypes were determined for 396 Mexican American subjects (289 non-diabetic). The normal and mutant alleles were designated G and A, respectively. Among non-diabetics, those with the AA genotype had higher fasting insulin values than those with the AG and GG genotypes (113.4 pmol/l for AA vs 82.8 pmol/l for AG/GG, P=0.043). Similar results were observed for 2-h insulin (849.6 pmol/l for AA vs 498.6 pmol/l for AG/GG, P=0.0003) and for the proinsulin to specific insulin ratio (0.068 for AA vs 0.056 for AG/GG, P=0.030). Specific insulin levels also differed significantly across the three genotypic classes (P=0.021). No differences in fasting glucose, body mass index, or waist circumference according to genotype were noted. Two-hour glucose was modestly higher in individuals with the AA genotype. Since we have previously reported linkage between SUR1 and hyperglycemia, the present association between a SUR1 variant and hyperinsulinemia in normal individuals from a high diabetes risk ethnic group raises the possibility of primary insulin hypersecretion as an antecedent of type 2 diabetes in at least some individuals from this population.

ATP-Binding Cassette Transporters↗

PubMed1989

Role of variant prealbumin in the pathogenesis of familial amyloidotic polyneuropathy: fate of normal and variant prealbumin in the circulation.

According to recent studies on protein chemistry and genetic engineering, replacement of the Val30 residue of prealbumin by methionine is believed to play a critical role in the formation of amyloid deposit and the pathogenesis of familial amyloidotic polyneuropathy (FAP). However, only limited information is available concerning the behavior of prealbumin in the circulation. To obtain the molecular insight into the mechanism of amyloid deposition, it is indispensable to know the fates of normal and variant prealbumin in vivo. Thus, the fates of prealbumin samples from normal and FAP patients were studied in normal rats as well as in animals that were challenged with acute inflammation induced by turpentine. The effect of in vitro photooxidation of prealbumin samples on their behavior was also examined in vivo. Kinetic analysis revealed no appreciable difference between prealbumin samples from normal and FAP patients. These results suggest that factors other than the rate of transfer of the variant form prealbumin from plasma to an extravascular compartment may play a critical role in the pathogenesis of amyloid deposition in FAP patients.

Amyloidosis↗

PubMed1989

Testis-specific histone H1t is truly a testis-specific variant and not a meiotic-specific variant.

Immunoblotting studies using highly specific polyclonal anti-histone H1t-IgG, which was extensively characterized by us previously, did not produce a signal with any of the histone H1 subtypes of either 1-day-old or adult rat ovarian nuclei. The absence of histone H1t in ovarian nuclei was also confirmed by indirect immunofluorescence studies. It is concluded, therefore, that histone H1t is truly a testis-specific histone variant and not a meiotic-specific variant.

Animals↗

PubMed1989

Comparison of partial amino acid sequences of two protamine 2 variants from stallion sperm. Structural evidence that the variants are products of different genes.

Protamine 1 and two protamine 2 variants were isolated from stallion sperm and separated by acetic acid-urea gel electrophoresis. After electroblotting onto polyvinyldifluoride filters, their amino-terminal amino acid sequences were determined by pulse-liquid peptide sequencing. The sequences of the two protamine 2 variants are homologous but slightly different in length and amino acid composition and indicate for the first time the existence of two different genes for this protamine species.

Amino Acid Sequence↗

PubMed1990

VARIANT: a store and retrieval system for human haemoglobin variants.

VARIANT, a FORTRAN 77 computer system for storing and retrieving the amino acid replacements in human haemoglobin variants on a multicriterion basis, is presented. The system is transportable and user-friendly, can easily be expanded and can also be used to create a database of the amino acid replacements in families of homologous proteins, becoming an efficient tool for evolutionary studies.

Amino Acids↗

PubMed1993

A novel silent variant at codon 711 and a variant at codon 708 of the APP sequence detected in Spanish Alzheimer and control cases.

Pathogenic mutations have been identified in exons 16 and 17 of the beta-amyloid precursor protein (APP) gene in some cases of early onset Alzheimer's disease. Screening of these exons in a number of familial and sporadic cases of Alzheimer's disease in Spain, resulted in the identification of a novel silent variant at codon 711 whose relevance to the AD pathogenesis remains unclear. The 708 variant was also detected in one of normal controls.

Alzheimer Disease↗

PubMed1997

GnRH molecular variants in the brain and pituitary gland of pejerrey, Odontesthes bonariensis (Atheriniformes). Immunological and chromatographic evidence for the presence of a novel molecular variant.

Gonadotropin-releasing hormone (GnRH) molecular variants in the brain and pituitary gland of pejerrey, Odontesthes bonariensis (Atheriniformes), were characterized by gradient reverse phase high performance liquid chromatography (RP-HPLC). Eluted fractions were tested in radioimmunoassays with different antisera. The results show that the brain extract contains three forms of GnRH: one is immunologically and chromatographically similar to cIIGnRH (chicken II), and another is similar to sGnRH (salmon). A third GnRH appears to be chromatographic and immunologically different from the nine other known forms of the vertebrate hormone. This is the only variant present in the pituitary gland.

Animals↗

PubMed2026

Genome-wide annotation of human multi-nucleotide variants reveals widespread functional differences from single nucleotide variants.

Multi-nucleotide variants (MNVs) represent a crucial yet underexplored category of genetic variation. Despite previous studies highlighting the prevalence and potential biological impact of MNVs in populations, comprehensive identification and detailed functional annotation of MNVs remain challenging. Here, we develop MNVAnno, a toolbox for rapid identification and annotation of complex MNVs, and utilize it to identify 3,984,258 MNVs from 700,134 human samples, expanding the human MNV list to 8,199,654. Our analysis reveals that MNVs can not only lead to distinct amino acid changes from their constituent single-nucleotide variants, but also significantly impact the function of non-coding regions. Furthermore, through genome-wide association studies, we identify some MNVs associated with multiple cancers, and establish the Human MNV Database to facilitate MNV research. Our study emphasizes the importance of MNV annotation, broadens the human MNV landscape, and opens avenues for exploring genetic variation in phenotypes and diseases.

Humans↗

PubMed1973

Ganglioside patterns and phenotypic characteristics in a normal variant and a transformed back variant of a simian virus 40-induced hamster tumor cell line.

Ganglioside patterns of a cloned Simian virus 40- (SV40) induced hamster tumor cell (Cl(2)TSV(5)-S), its normal variant (Cl(2)TSV(5)-R) which are Cl(2)TSV(5)-S gradually adapted to grow in the presence of 2 microg/ml actinomycin D and exhibit certain normal phenotypic characteristics, and its back variant (Cl(2)TSV(5)-RR), which are Cl(2)TSV(5)-R cells grown in the absence of actinomycin D for more than 60 passages and which exhibit greater phenotypic similarity to Cl(2)TSV(5)-S cells, have been analyzed. All three cell lines contain N(acetylneuraminyl) galactosylglycosyl ceramide (hematoside, GM(3)), N-acetylgalactosaminyl (N-acetylneuraminyl) galactosylglucosyl ceramide (GM(2)), and a higher ganglioside tentatively identified as disialohematoside. However, Cl(2)TSV(5)-R have more GM(2) than Cl(2)TSV(5)-S whereas Cl(2)TSV(5)-RR contain an intermediate amount of GM(2). The amount of GM(2) is correlative with the activity of UDP-N-acetylgalactosamine: hematoside N-acetylgalactosaminyl transferase in the extract of the three cell lines and with their agglutination by wheat germ agglutinin.

Animals↗

PubMed2001

Disparate response of wild-type and variant forms of LH to GnRH stimulation in individuals heterozygous for the LHbeta variant allele.

There is a common genetic variant of LH due to two amino acid changes in the LHbeta subunit, Trp(8)Arg and Ile(15)Thr. In order to compare the relative activities of wild type (wt-LH) and variant LHbeta (v-LHbeta) genes in LH production and secretion, we performed gonadotrophin-releasing hormone (GnRH) stimulation tests for healthy females (n = 7) and males (n = 10) heterozygous for the v-LHbeta allele. Blood samples were drawn up to 180 min after injection of GnRH. The serum samples were subjected to two immunofluorometric assays, one detecting wt hormone, the other detecting equally both LH types. The wt/total ratio increased significantly (P < or = 0.016) after GnRH injection in males. This indicates that the proportion of wt-LH increases in the circulation in men but not in women, and that women consequently secrete relatively more v-LH. An in-vitro bioassay was performed on 0 and 60 min samples, and the bio/immunoreactivity (B/I) ratio decreased in both sexes (P = 0.010-0.012). This supports the previously reported lower B/I ratio of wt. than v-LH, since wt-LH is expected to accumulate in circulation because of its longer half-life. In conclusion, these findings demonstrate that wt.- and v-LH respond differently to GnRH stimulation in men and women heterozygous for v-LHbeta. These results are in agreement with previously documented differences of the two forms in circulation, as well as with different promoter activities of the two LHbeta alleles.

Adolescent↗

PubMed1979

Thymidine kinase enzyme variants in Physarum polycephalum. Kinetics and properties of the enzyme variants.

Thymidine kinase variants of Physarum polycephalum separated by repeated DEAE-cellulose chromatography have been characterized. The enzyme variants show similar catalytic properties (e.g., substrate specificity, pH optimum) and molecular weights, as judges by their sedimentation in sucrose gradients. However, they differ significantly with respect to pI, inhibition by dTTP and thermostability, and they have slightly different Km values for deoxythymidine as a substrate.

Deoxyribonucleotides↗

PubMed1994

Isolation and characterization of human immunodeficiency virus type 1 variants infectious to brain-derived cells: detection of common point mutations in the V3 region of the env gene of the variants.

T-cell-line-tropic human immunodeficiency virus type 1 cannot infect CD4-positive, brain-derived cells. We isolated several new variants that readily infected brain-derived cells. Mutation of proline to serine, to alanine, or to threonine in the well-conserved GPGR sequence in the V3 region of the envelope glycoprotein was found in all these variants. This indicates the importance of amino acid sequences at the tip of the V3 region for brain cell tropism of human immunodeficiency virus type 1.

Amino Acid Sequence↗

PubMed1998

The 30-base-pair deletion in Chinese variants of the Epstein-Barr virus LMP1 gene is not the major effector of functional differences between variant LMP1 genes in human lymphocytes.

One group of sequence variants of Epstein-Barr virus is characterized by a 10-amino-acid deletion within the CTAR-2 functional domain of the latent membrane protein, LMP1. A role for this deletion in enhancing the tumorigenicity of the viral oncogene in rodent fibroblasts was recently demonstrated. We examined the effect of this deletion upon LMP1 function in four human lymphoid cell lines by using three natural variants of LMP1: the prototype B95.8 gene and the CAO and AG876 genes, both of which have codons 343 to 352 of the B95.8-LMP1 deleted. These experiments revealed that LMP1-mediated upregulation of CD40 and CD54 was markedly impaired (by 60 to 90%) with CAO-LMP1 compared with B95.8-LMP1. In contrast, the function of AG876-LMP1 was indistinguishable from that of B95.8-LMP1 in two lines and was only slightly impaired in the other two lines. Activation of NF-kappaB by CAO-LMP1 was not impaired in any of the lines; rather, activation of an NF-kappaB reporter by CAO-LMP1 was consistently about twofold greater than the activation with B95.8- or AG876-LMP1. Therefore, while the CAO-LMP1 is functionally distinct from the prototype B95.8-LMP1 in human lymphocytes, the 10-amino-acid deletion appears not to be directly responsible. This conclusion was confirmed by using a B95.8-LMP1 mutant with codons 343 to 352 deleted and chimerae of CAO- and B95.8-LMP1 in which the CTAR-2 domains of these genes were exchanged. Sequences outside the CTAR-2 domain were implicated in the distinct functional characteristics of CAO-LMP1 in human lymphoid cells.

Amino Acid Sequence↗

PubMed1987

Transferrin variants in Japan and New Zealand. Report of an unusually sialyzed TF variant.

The genetic polymorphism of transferrin (TF) was studied in 2,167 Japanese individuals and in 448 New Zealanders. The three TF C subtypes were identified, but TF C3 was absent from Japanese populations. In addition, three TF B and six TF D variants were observed, each of which occurred either in Japanese or in New Zealanders. Stepwise removal of N-acetyl-neuraminic acid (NANA) with neuraminidase revealed that the most cathodal variant TF DShinnanyo found in a Japanese family was characterized by having only two NANA residues.

Gene Frequency↗