Department of Neurobiology, Care Sciences and Society, Karolinska Institutet Alzheimer Disease Research Center, KASPAC, Huddinge, Sweden.
J Hum Genet. 2010 Oct;55(10):649-55. doi: 10.1038/jhg.2010.79. Epub 2010 Jul 1.
This study aimed at identifying novel susceptibility genes for a mixed phenotype of Alzheimer's disease and vascular dementia. Results from a genome scan showed strongest linkage to 20p13 in 18 families, and subsequent fine mapping was performed with both microsatellites and single-nucleotide polymorphisms in 18 selected candidate transcripts in an extended sample set of 30 families. The multipoint linkage peak was located at marker rs2144151 in the ANGPT4 gene, which is a strong candidate gene for vascular disease because of its involvement in angiogenesis. Although the significance of the linkage decreased, we find this result intriguing, considering that we included additional families, and thus the reduced linkage signal may be caused by genetic heterogeneity.
本研究旨在鉴定阿尔茨海默病和血管性痴呆混合表型的新易感基因。全基因组扫描结果显示，在 18 个家系中与 20p13 最强连锁，随后在 30 个扩展样本家系的 18 个候选转录本中，使用微卫星和单核苷酸多态性对其进行了精细定位。多点连锁峰定位于 ANGPT4 基因中的标记 rs2144151，该基因是血管疾病的一个强有力候选基因，因为它参与血管生成。尽管连锁的显著性降低，但考虑到我们纳入了更多的家系，因此减少的连锁信号可能是由遗传异质性引起的，我们认为这个结果很有趣。
