Cheung V G, Gregg J P, Gogolin-Ewens K J, Bandong J, Stanley C A, Baker L, Higgins M J, Nowak N J, Shows T B, Ewens W J, Nelson S F, Spielman R S
Department of Pediatrics, The Children's Hospital of Philadelphia, Pennsylvania 19104, USA.
Nat Genet. 1998 Mar;18(3):225-30. doi: 10.1038/ng0398-225.
Genomic mismatch scanning (GMS) is a technique that enriches for regions of identity by descent (IBD) between two individuals without the need for genotyping or sequencing. Regions of IBD selected by GMS are mapped by hybridization to a microarray containing ordered clones of genomic DNA from chromosomes of interest. Here we demonstrate the feasibility and efficacy of this form of linkage-mapping, using congenital hyperinsulinism (HI), an autosomal recessive disease, whose relatively high frequency in Ashkenazi Jews suggests a founder effect. The gene responsible (SUR1) encodes the sulfonylurea receptor, which maps to chromosome 11p15.1. We show that the combination of GMS and hybridization of IBD products to a chromosome-11 microarray correctly maps the HI gene to a 2-Mb region, thereby demonstrating linkage-disequilibrium mapping without genotyping.
基因组错配扫描（GMS）是一种无需基因分型或测序就能富集两个个体间同源性区域（IBD）的技术。通过GMS选择的IBD区域通过与包含来自感兴趣染色体的基因组DNA有序克隆的微阵列杂交进行定位。在这里，我们利用先天性高胰岛素血症（HI）——一种常染色体隐性疾病，在阿什肯纳兹犹太人中相对较高的发病率提示存在奠基者效应，来证明这种连锁图谱绘制形式的可行性和有效性。致病基因（SUR1）编码磺酰脲受体，该基因定位于染色体11p15.1。我们表明，GMS与IBD产物与11号染色体微阵列杂交相结合，可将HI基因正确定位到一个2兆碱基区域，从而证明了无需基因分型的连锁不平衡图谱绘制。
