約有15%的新生兒在出生時有體型上偏小或偏大的情形，除了可能造成新生兒發展遲緩外也有可能造成較高的罹病率或是死亡率。對於體型此一受多基因遺傳影響的表型而言，要找出調控的基因事實上非常的困難。就單一罕見遺傳疾病Russell-Silver Syndrome (RSS)來說，此一疾病會造成患者身材矮小、肢體兩側不對稱等症狀，據統計約有10%的RSS患者是屬於第七號染色體的母源單親二體症(maternal uniparental disomy)，提供了一對體型研究的線索。單親二體症最主要會影響鑄記基因的表現而致病。所謂鑄記基因指的是一群會因對偶基因的親源而決定此一對偶基因表現與否的基因。在第七號染色體上一共有三個鑄記基因，其中的兩個與生長發育的調控相關，分別是GRB10及MEST。實驗中對於GRB10及MEST，採用SNP genotyping的方式，對所蒐集的不同的族群做試驗後，以統計方法比較在不同體型大小的族群間以及在所蒐集的RSS疑似病患間，是否有關聯性存在。在結果中發現MEST與體型大小的變化或RSS的發生並沒有相關，而在GRB10方面，經過計算發現點rs1019000與RSS的發生有相關外，在點rs730652也發現與體型大小的變化有正相關，認為GRB10是第七號染色體上扮演調控體型大小角色的基因。後續更針對在點rs1019000所發現的雙核酸重複序列做多型性分析，結果顯示，所發現的雙核酸重複序列在體型上有一相關存在。

There are about 15% newborns with abnormal body size. The abnormal body size may result in growth retardation or higher morbidity and mortality. Body size is a polygenetic phenotype. Most of the genetic causes of abnormal body size are still unknown. At present, it is difficult to find out all of the genes which control this phenotype. The Russell-Silver syndrome (RSS) suffered patients by low-birth-weight dwarfism and lateral asymmetry. Maternal uniparental disomy for chromosome 7 (mUPD7) has found in around 10% Russell-Silver Syndrome patients, which may be shed some light on finding genes for body size control. The major effect of uniparental disomy is it may disturb imprinting gene expression. Genomic imprinting refers to an epigenetic modification in germ line leads to preferential expression of one of two parental alleles in a parental-of-origin-specific manner. And a substantial proportion of imprinting genes are involved in control of fetal growth and placental development. There are three imprinting genes on chromosome 7. Two of these three genes, GRB10 and MEST, were reported to take part in growth or development control. In this study, we try to find out if the GRB10 and MEST genes associate with RSS or abnormal body size by SNP genotyping and association study in different body size population and RSS patients. In this study, we found that the MEST gene is not related to abnormal body size and RSS. The GRB10 gene, in this study, is associated with abnormal body size and RSS. By statistic analysis of four SNP genotyping in different body size population and RSS patients, rs1019000 has a significant contribution to RSS. That is the GRB10 gene, located on chromosome 7p11.2-12, controls fetal development and result in different body size. We also find out a CA di-nucleotide repeat downstream of rs1019000. By genotyping, the microsatellite polymorphism seems to relate to body size difference. The next step for this di-nucleotide repeat is to see if this repeat affects the RNA transcription result in protein higher expressed.

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