PARENTAL ORIGIN OF TRANSCRIPTION FROM THE HUMAN GNAS1 GENE
PARENTAL ORIGIN OF TRANSCRIPTION FROM THE HUMAN GNAS1 GENE
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DOI：
10.1136/jmg.31.8.607
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发表时间：
1994-08-01
影响因子：
4
通讯作者：
BONTHRON, DT
中科院分区：
文献类型：
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作者：
CAMPBELL, R;GOSDEN, CM;BONTHRON, DT
奥尔布赖特遗传性骨营养不良症（Albright's遗传性骨营养不良症，who）表型表达的变异由传播亲本决定，这表明在who中发生突变的人类Gsa基因（GNAS1）可能受到印迹控制。已知GNAS1也映射到与小鼠印迹区域2E1-2H3具有同源性的染色体区域（20q13.11）。为了确定GNAS1是否确实是印迹的，我们研究了人类胎儿组织中GNAS1转录的亲本来源。在75例胎龄为6 ~ 13周的胎儿中，鉴定出13例GNAS1外显子5 FokI多态性杂合子，其母亲为一个或其他等位基因纯合子。RT-PCR分析了来自每个胎儿多达10个不同组织的RNA。在所有病例中，通过RT-PCR产物的FokI酶切和所得片段的定量分析，均显示亲本等位基因的表达。在这些实验中没有发现组织特异性的表达模式。如果基因组印记调节了人类GNAS1基因的表达，我们的数据表明，这种影响要么是微妙的和定量的，要么局限于目标组织中一小部分专门的激素反应细胞。
Variation in the phenotypic expression of Albright's hereditary osteodystrophy (AHO) determined by the parent of transmission, suggests that the human Gsa gene (GNAS1), in which mutations occur in AHO, may be under imprinted control. GNAS1 is also known to map to a chromosomal region (20q13.11) showing syntenic homology with the imprinted mouse region 2E1-2H3. To establish if GNAS1 is indeed imprinted, we have examined the parental origin of GNAS1 transcription in human fetal tissues. Of 75 fetuses genotyped, at gestational ages ranging from 6 to 13 weeks, 13 heterozygous for a FokI polymorphism in exon 5 of GNAS1 were identified whose mothers were homozygous for one or other allele. RNA from up to 10 different tissues from each fetus was analysed by RT-PCR. In all cases expression from both parental alleles was shown by FokI digestion of RT-PCR products and quantification of the resulting fragments. No tissue specific pattern of expression was discerned in these experiments.If genomic imprinting regulates the expression of the human GNAS1 gene, our data suggest that the effect must either be subtle and quantitative, or be confined to a small subset of specialised hormone responsive cells within the target tissues.