Linkage of human apolipoproteins A-I and C-III genes

Karathanasis, Sotirios K.; McPherson, Joseph; Zannis, Vassilis I.; Breslow, Jan L.

doi:10.1038/304371a0

Cited by 169 publications

(57 citation statements)

References 20 publications

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“…A genomic clone containing both APOAJ and APOC3 was isolated and characterized, and the results indicated that the genes are oriented 3' to 3' and are separated by about 3 kb of intergenic DNA (56). This contrasts with the tandem (3' to 5') orientation of APOE and APOCJ (Fig.…”

Section: Discussionmentioning

confidence: 74%

Regional mapping of human chromosome 19: organization of genes for plasma lipid transport (APOC1, -C2, and -E and LDLR) and the genes C3, PEPD, and GPI.

Lusis¹,

Heinzmann²,

Sparkes³

et al. 1986

Proc. Natl. Acad. Sci. U.S.A.

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We report the regional mapping of human chromosome 19 genes for three apolipoproteins and a lipoprotein receptor as well as genes for three other markers. The regional mapping was made possible by the use of a reciprocal whole-arm translocation between the long arm of chromosome 19 and the short arm of chromosome 1. Examination of three separate somatic cell hybrids containing the long arm but not the short arm of chromosome 19 indicated that the genes for apolipoproteins CI, CII, and E (APOCI, APOC2, and APOE, respectively) and glucose-6-phosphate isomerase (GPI) reside on the long arm, whereas genes for the low density lipoprotein receptor (LDLR), complement component 3 (C3), and peptidase D (PEPD) reside on the short arm. When taken together with previous studies, our results suggest the following physical gene map: pter-LDLR-C3-pl3.2-PEPD-centromere-(APOE, APOCI, APOC2, GPI)-qter. In addition, we have isolated a single A phage carrying both APOCI and part ofAPOE. These genes are tandemly oriented and are separated by about 6 kilobases of genomic DNA. Since previous family studies indicate tight linkage of APOE and APOC2, the apolipoprotein genes APOCI, APOC2, and APOE form a tight complex on the long arm of chromosome 19, suggesting the possibility of coordinate regulation.

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Section: Discussionmentioning

confidence: 74%

Regional mapping of human chromosome 19: organization of genes for plasma lipid transport (APOC1, -C2, and -E and LDLR) and the genes C3, PEPD, and GPI.

Lusis¹,

Heinzmann²,

Sparkes³

et al. 1986

Proc. Natl. Acad. Sci. U.S.A.

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“…The apo CIII Sst-I polymorphism arises from a C-G transversion in the 3' noncoding region of the apo CIII gene (Karathanasis et al, 1983). The apo AI Msp-I polymorphism arises from the presence or absence of a Msp-I site in the third intron of the apo AI gene (Seilhamer et al, 1984).…”

Section: Discussionmentioning

confidence: 99%

“…The human apo AI and apo CIII genes are tightly linked and form a gene complex together with the apo AIV gene on the long arm of the chromosome 11 (Karathanasis et al, 1983;Law et al, 1984;Cheung et al, 1984;Karathanasis, 1985;Elshourbagy et al, 1986). Restriction fragment length polymorphisms related to the apo AI and apo CIII genes have been reported to be associated with coronary atherosclerosis in Caucasians (Ferns et al, 1985;Rees et aI., 1985;Ferns and Galton, 1986;Ordovas et al, 1986;Buraczynska et al, 1986).…”

Section: Introductionmentioning

confidence: 99%

Apolipoprotein AI-CIII gene polymorphisms in a Japanese population

et al. 1986

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SummaryApolipoprotein (apo) CIII Sst-I genotypes and apo AI Msp-I genotypes were investigated in 82 unrelated healthy Japanese, using genomic hybridization analysis with a 2.2 kb fragment of the human apo AI gene. The frequencies of the $2 and M2 alleles were 0.34 and 0.40, respectively, and much higher than those in Caucasians. The alleles identified by the apo CIII Sst-I and apo AI Msp-I polymorphisms were observed to be in linkage disequilibrium (A=0.206+0.012, p<0.001). Three of the four possible haplotypes were identified: the frequencies of the haplotype were S1-M1=0.604, $2-M2=0.341, and S1-M2=0.055. The data indicate that Japanese are characterized by the common presence of the haplotype $2-M2 as compared with Caucasians and that the haplotypes identified by the apo CIII Sst-I and apo AI Msp-I polymorphisms are useful genetic markers for Japanese.

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“…It is thought that apo A-I, together with lecithin -cholesterol acyltransferase, facilitates the removal of cholesterol from peripheral tissues and transports it to the liver for catabolism [2]. Patients with a defective apo A-I gene show low levels of plasma high-density lipoprotein and apo A-I and accelerated atherosclerosis [3]. Several epidemiological studies have established that plasma levels of high-density lipoprotein and apo A-I are negatively correlated with the incidence of coronary heart diseases [4 -61.…”

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confidence: 99%

Binding of nuclear proteins to the enhancer elements of the rat apolipoprotein A‐I gene

Dai

Lan

Ding

et al. 1990

European Journal of Biochemistry

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To determine the cis-and trans-regulatory elements which control the expression of the apolipoprotein (apo) A-I gene, several DNA-protein binding assays, namely, gel mobility shift, exonuclease 111 protection, and exonuclease 111 footprinting assays, were employed to identify these elements. It is demonstrated that nuclear proteins of Hep G2 cells bind to five regions of DNA sequences between 252 and 149 base pairs upstream from the transcription initiation site of the rat apo A-I gene. Using South-Western blot analysis, it is determined that DNA-binding protein has a molecular mass of approximately 90 kDa. It is also shown that the DNA-binding protein was present in Hep G2 cells and rat livers but absent in rabbit livers. The results suggest that the lack of expression of the apo A-I gene in rabbit livers is due to the absence of this DNA-binding protein.Apolipoprotein (apo) A-I is an important plasma protein.It is a major constituent of plasma high-density lipoproteins and a cofactor of plasma lecithin -cholesterol acyltransferase [l] which catalyzes the formation of most of the cholesteryl esters in plasma. It is thought that apo A-I, together with lecithin -cholesterol acyltransferase, facilitates the removal of cholesterol from peripheral tissues and transports it to the liver for catabolism [2]. Patients with a defective apo A-I gene show low levels of plasma high-density lipoprotein and apo A-I and accelerated atherosclerosis [3]. Several epidemiological studies have established that plasma levels of high-density lipoprotein and apo A-I are negatively correlated with the incidence of coronary heart diseases [4 -61. Hence it is beneficial to raise plasma levels of both high-density lipoproteinThe expression of apo A-I can be induced at transcriptional levels by several pharmacological agents: phenobarbital, estrogen, insulin and dexamethasone [7 -91. Usually, the expression of eukaryotic genes is regulated by the 5'-flanking promoter and enhancer elements of the genes. These elements interact with and bind to specific trans-acting nuclear proteins [lo -121. Thus, the identification of the trans-acting elements which bind to and interact with the enhancer elements of the apo A-S gene becomes crucial for designing therapeutic agents which intervene in the expression of this gene. The nucleotide sequences of the rat and human apo A-I genes have been reported [13, 141. Recently, we have identified a 45-base-pair nucleotide element, located between 235 and 190 nucleotides upstream from the transcription initiation site of the rat apo A-I gene, which is essential for the expression of this gene in Hep G2 cells and that this element exerts its function with an enhancerlike activity [l 51. In the current research we studied the binding of nuclear proteins from Hep G2 cells and rat livers to the enhancer element of the rat apo A-I gene; our data suggest and apo A-S. that the lack of expression of the apo A-I gene in rabbit livers is due to decreased levels of this binding protein in rabbit livers. MATERIALS AND ...

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Linkage of human apolipoproteins A-I and C-III genes

Cited by 169 publications

References 20 publications

Regional mapping of human chromosome 19: organization of genes for plasma lipid transport (APOC1, -C2, and -E and LDLR) and the genes C3, PEPD, and GPI.

Regional mapping of human chromosome 19: organization of genes for plasma lipid transport (APOC1, -C2, and -E and LDLR) and the genes C3, PEPD, and GPI.

Apolipoprotein AI-CIII gene polymorphisms in a Japanese population

Binding of nuclear proteins to the enhancer elements of the rat apolipoprotein A‐I gene

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