Mak Ying T, Hampson Geeta, Beresford Jon N, Spector Tim D
Twin Research and Genetic Epidemiology Unit, St, Thomas' Hospital, London SE1 7EH, United Kingdom.
BMC Genet. 2004 Jun 4;5:14. doi: 10.1186/1471-2156-5-14.
Monozygotic twin pairs who are genetically identical would be potentially useful in gene expression study for specific traits as cases and controls, because there would be much less gene expression variation within pairs compared to two unrelated individuals. However the twin pair has to be discordant for the particular trait or phenotype excluding those resulting from known confounders. Such discordant monozygotic twin pairs are rare and very few studies have explored the potential usefulness of this approach.
We studied genome-wide gene expression in primary osteoblast-like culture from marrow aspirates obtained from three pairs of monozygotic twins. We used the latest Affymetrix microchip contains probe sets for more than 20,000 genes. Two pairs were discordant for bone mineral density at the hip by more than one standard deviation, and the third pair was unrelated concordant and used as control. Only 1.5% on average of genes showed variation in expression within pairs as compared to 5% between pairs or over 15% from the literature. Importantly we identified several groups of genes showing variations within the discordant pairs and not within the concordant pair such as chondroitin beta 1,4 N-acetylgalactosaminyltransferase, inhibin beta A, interleukin 1 beta and colony stimulating factor 1 macrophage. These genes are known to have potential roles in bone physiology relating to bone density, osteoporosis and osteoarthritis.
Using the example of osteoblast-like cells in our monozygotic discordant twins for osteoporosis, we identified genes showing differential expression. Although without further experiment, we cannot confirm or conclude these are genes definitely related to bone physiology, we believe we have shown the potential and cost-effectiveness of further gene expression studies in discordant monozygotic twin pairs. A replication study for confirmation is essential.
基因完全相同的同卵双胞胎有可能作为病例和对照用于特定性状的基因表达研究，因为与两个不相关的个体相比，双胞胎对之间的基因表达差异要小得多。然而，双胞胎对必须在特定性状或表型上不一致，不包括由已知混杂因素导致的情况。这种不一致的同卵双胞胎对很少见，很少有研究探索这种方法的潜在用途。
我们研究了从三对同卵双胞胎的骨髓抽吸物中获得的原代成骨细胞样培养物中的全基因组基因表达。我们使用了最新的Affymetrix微芯片，其包含针对20000多个基因的探针集。两对双胞胎在髋部骨密度上相差超过一个标准差，第三对不相关且情况一致，用作对照。与双胞胎对之间5%或文献中超过15%的基因表达变化相比，平均只有1.5%的基因在双胞胎对内部表现出表达差异。重要的是，我们鉴定出了几组在不一致的双胞胎对中表现出差异而在一致的双胞胎对中未表现出差异的基因，如软骨素β1,4-N-乙酰半乳糖胺基转移酶、抑制素βA、白细胞介素1β和集落刺激因子1巨噬细胞。已知这些基因在与骨密度、骨质疏松症和骨关节炎相关的骨生理学中具有潜在作用。
以我们用于骨质疏松症研究的同卵不一致双胞胎中的成骨细胞样细胞为例，我们鉴定出了表现出差异表达的基因。虽然没有进一步的实验，我们无法确认或得出这些基因肯定与骨生理学相关的结论，但我们相信我们已经展示了在不一致的同卵双胞胎对中进行进一步基因表达研究的潜力和成本效益。进行重复研究以进行确认至关重要。
