Kim, J.Y.
(Department of Genetic Epidemiology, SNP Genetics, Inc.)
,
Yoon, D.H.
(National Livestock Research Institute, RDA)
,
Park, B.L.
(Department of Genetic Epidemiology, SNP Genetics, Inc.)
,
Kim, L.H.
(Department of Genetic Epidemiology, SNP Genetics, Inc.)
,
Na, K.J.
(National Livestock Research Institute, RDA)
,
Choi, J.G.
(National Livestock Research Institute, RDA)
,
Cho, C.Y.
(National Livestock Research Institute, RDA)
,
Lee, H.K.
(Department of Biotechnology, Hankyong National University)
,
Chung, E.R.
(Department of Biotechnology, Sangi University)
,
Sang, B.C.
(Department of Dairy Science, Graduate School, Chungnam National University)
,
Cheong, I.J.
(National Livestock Research Institute, RDA)
,
Oh, S.J.
(National Livestock Research Institute, RDA)
,
Shin, Hyoung Doo
(Department of Genetic Epidemiology, SNP Genetics, Inc.)
The insulin-like growth factors (IGFs), their receptors, and their binding proteins play key roles in regulating cell proliferation and apoptosis. Insulin-like growth factor binding protein-3 (IGFBP3, OMIM #146732) is one of the proteins that bind to the IGFs. IGFBP3 is a modulator of IGF bioactivit...
The insulin-like growth factors (IGFs), their receptors, and their binding proteins play key roles in regulating cell proliferation and apoptosis. Insulin-like growth factor binding protein-3 (IGFBP3, OMIM #146732) is one of the proteins that bind to the IGFs. IGFBP3 is a modulator of IGF bioactivity, and direct growth inhibitor in the extravascular tissue compartment. We identified twenty-two novel single nucleotide polymorphisms (SNPs) in IGFBP3 gene in Korean cattle (Hanwoo, Bos taurus coreanae) by direct sequencing of full gene including -1,500 bp promoter region. Among the identified SNPs, five common SNPs were screened in 650 Korean cattle; one SNP in promoter (IGFBP3 G-854C), one in 5'UTR region (IGFBP3 G-100A), two in intron 1 (IGFBP3 G+421T, IGFBP3 T+1636A), and one in intron 2 (IGFBP3 C+3863A). The frequencies of each SNP were 0.357 (IGFBP3 G-854C), 0.472 (IGFBP3 G-100A), 0.418 (IGFBP3 G+421T), 0.363 (IGFBP3 T+1636A) and 0.226 (IGFBP3 C+3863A), respectively. Haplotypes and their frequencies were estimated by EM algorithm. Six haplotypes were constructed with five SNPs and linkage disequilibrium coefficients (|D'|) between SNP pairs were also calculated. The information on SNPs and haplotypes in IGFBP3 gene could be useful for genetic studies of this gene.
The insulin-like growth factors (IGFs), their receptors, and their binding proteins play key roles in regulating cell proliferation and apoptosis. Insulin-like growth factor binding protein-3 (IGFBP3, OMIM #146732) is one of the proteins that bind to the IGFs. IGFBP3 is a modulator of IGF bioactivity, and direct growth inhibitor in the extravascular tissue compartment. We identified twenty-two novel single nucleotide polymorphisms (SNPs) in IGFBP3 gene in Korean cattle (Hanwoo, Bos taurus coreanae) by direct sequencing of full gene including -1,500 bp promoter region. Among the identified SNPs, five common SNPs were screened in 650 Korean cattle; one SNP in promoter (IGFBP3 G-854C), one in 5'UTR region (IGFBP3 G-100A), two in intron 1 (IGFBP3 G+421T, IGFBP3 T+1636A), and one in intron 2 (IGFBP3 C+3863A). The frequencies of each SNP were 0.357 (IGFBP3 G-854C), 0.472 (IGFBP3 G-100A), 0.418 (IGFBP3 G+421T), 0.363 (IGFBP3 T+1636A) and 0.226 (IGFBP3 C+3863A), respectively. Haplotypes and their frequencies were estimated by EM algorithm. Six haplotypes were constructed with five SNPs and linkage disequilibrium coefficients (|D'|) between SNP pairs were also calculated. The information on SNPs and haplotypes in IGFBP3 gene could be useful for genetic studies of this gene.
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제안 방법
Among identified SNPs, five SNPs; IGFBP3 G-854C in promoter, IGFBP3 G-100A in 5’UTR, IGFBP3 G+421T, IGFBP3 T+1636A in intron 1 and IGFBP3 C+3863A in intron 2 were selected for large scale screening on the base of the location and frequency.
대상 데이터
Among identified SNPs, five SNPs; IGFBP3 G-854C in promoter, IGFBP3 G-100A in 5’UTR, IGFBP3 G+421T, IGFBP3 T+1636A in intron 1 and IGFBP3 C+3863A in intron 2 were selected for large scale screening on the base of the location and frequency. And then these five common SNPs were screened in 650 Korean cattle (National Livestock Research Institute, Korea).
Among identified SNPs, five SNPs; IGFBP3 G-854C in promoter, IGFBP3 G-100A in 5’UTR, IGFBP3 G+421T, IGFBP3 T+1636A in intron 1 and IGFBP3 C+3863A in intron 2 were selected for large scale screening on the base of the location and frequency. And then these five common SNPs were screened in 650 Korean cattle (National Livestock Research Institute, Korea). The frequencies of those SNPs were 0.
DNA samples for genotyping were isolated from 650 Korean cattle in National Livestock Research Institute, Korea. Primer extension reactions were performed with SNaPSHOT ddNTP Primer Extension Kit (Applied Biosystems, Foster City, CA).
Full gene including -1,500 bp promoter region were PCR-amplified and directly sequenced using ABI PRISM 3700 genetic analyzer (Applied Biosystems, Foster City CA). Seventeen primer sets for the amplification and sequencing analysis were designed based on GenBank sequences (AF_305712) (Table 1). Sequence variants were verified by chromatograms.
성능/효과
As a result, twenty two SNPs were identified; one in promoter, eight in intron 1, three in intron 2, two in intron 3, seven in intron 4 and one in 5’UTR (Figure 1 and Table 2).
Sequence variants were verified by chromatograms. As a result, twenty two SNPs were identified; one in promoter, eight in intron 1, three in intron 2, two in intron 3, seven in intron 4 and one in 5’UTR (Figure 1 and Table 2). The allele frequencies of identified SNPs in twenty four unrelated Korean cattle are shown in Table 2.
후속연구
IGFBP3 possesses both growth inhibitory and potentiating effects on cells that are independent of IGF action and are mediated through specific IGFBP3-binding proteins/receptors located at the cell membrane, cytosol, or nuclear compartments and in the extracellular matrix. Although it would be hard to explain the possible functions of identified SNPs in IGFBP3 without any evidences from further association studies, the potential involvement of this gene and gene polymorphisms in quantitative and/or qualitative traits in cattle might be worth to follow-up in further experiments.
Six haplotypes were reconstructed in IGFBP3 and linkage disequilibrium between all SNP pairs were also calculated (|D’| and d2). The information of SNPs and haplotypes of bovine IGFBP3 gene could be useful for genetic studies of this gene and, therefore, further studies are needed to elucidate the roles of bovine IGFBP3 polymorphisms.
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