识别三核苷酸repeat-containing人类胰岛细胞基因。
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青木M, Koranyi L,里格斯AC, Wasson J,赵KC, Vaxillaire M, Froguel P,高夫年代,刘L, Donis-Keller H,等。
识别三核苷酸repeat-containing人类胰岛细胞基因。
糖尿病。1996年2月,45 (2):157 - 64。
- PubMed ID
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8549859 (在PubMed]
- 文摘
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在寻找糖尿病基必威国际app因定位克隆的方法与随机标记和后续评估候选基因映射到感兴趣的领域将越来越多地使用。未知函数的胰岛候选基因表达三核苷酸(三联体)序列代表一种独特的子集。不太可能的异常扩张表达胰岛三合重复是糖尿病的主要原因,然而,三个一组重复经常多态,因此可以用于地图基因在人类基因组中。在这项研究中,一个人类胰岛cDNA库筛选(CGG) 7和(CAG) 7日和23个三个一组重复被孤立。基因测序显示四个已知和六个小说胰岛包含4-15三合重复。四个已知的互补包括铁蛋白,主要铁扎在细胞蛋白质;HSGSA2R,全长的克隆的alpha-subunit g调整蛋白质;HUMSATB1A dna结合蛋白主要表达在胸腺;和HUMPPA-PRO核糖体蛋白质。铁蛋白的三联体重复和HUMPPAPRO单型的被发现。 Characterization of the six unique novel expressed islet triplet cDNAs revealed that they were 0.6-1.5 kb in size, contained 4-15 triplet repeats, and were expressed in islets and all other tissues examined. Four of the novel clones, CGG-isl 10, CGG-isl 11, CAG-isl 6, and CAG-isl 7, were mapped to human chromosomes 19, 16, 12, and 3, respectively, via somatic cell hybrids. One islet cDNA, CAG-isl 7, contained a repeat that was highly polymorphic, with 14 alleles (4-18 triplets) in African-Americans (heterozygosity = 0.86) and 6 alleles (heterozygosity = 0.77) in whites. Northern analysis indicated that the mRNA was abundant in pancreatic islets. A putative full-length clone contained an open reading frame encoding 213 amino acids with a variable number of alanines (4-18) within the COOH-terminal. The gene was uniquely mapped with odds > 1,000:1 on chromosome 3p in Centre d'Etude du Polymorphisme Humain pedigrees. There were no differences in CAG-isl 7 allele frequencies between African-American patients with NIDDM (n = 108) and control subjects (n = 116), nor was expansion above 18 repeats noted. Linkage analysis in 14 nonglucokinase maturity-onset diabetes of the young pedigrees showed a cumulative logarithm of odds score of -33.19 at theta = 0.00. Abnormal expansion was not observed in 20 IDDM patients with one NIDDM parent. While these data suggest no major role for CAG-isl 7 in diabetes, at least four of the six novel islet triplet genes are coexpressed in pancreatic islets and neural tissue, and these genes can now be considered as candidates for diabetes and/or neuropsychiatric diseases.