Glaser B, Chiu K C, Liu L, Anker R, Nestorowicz A, Cox N J, Landau H, Kaiser N, Thornton P S, Stanley C A
Department of Internal Medicine, Washington University School of Medicine, St Louis, MO 63110, USA.
Hum Mol Genet. 1995 May;4(5):879-86. doi: 10.1093/hmg/4.5.879.
A gene for autosomal recessive familial hyperinsulinism (HI) (OMIM: 256450), a neonatal metabolic disease characterized by inappropriate insulin secretion in the presence of severe hypoglycemia, was recently mapped to a 6.6 cM interval between the markers D11S926 and D11S928 on chromosome 11p in 15 families (1). In the current study we evaluated six additional families and five new markers, and further localized the gene between D11S419 and D11S1310. Using genotype data from CEPH Version 7 and data generated from this study, this region was estimated to be 0.8 cM in length. Significant linkage disequilibrium between markers and the HI gene was observed over a region of 10.3 cM (11 pter-D11S926-D11S1308-11pcen) for Ashkenazi Jewish chromosomes. Haplotype analysis showed that 12 of 36 HI chromosomes, versus one of 36 non-HI chromosomes, bore a specific haplotype for D11S419-D11S902-D11S921 (p < 0.0007), strongly suggesting a founder effect in this ethnic group.
常染色体隐性遗传性家族性高胰岛素血症（HI）（在线人类孟德尔遗传数据库编号：256450）是一种新生儿代谢疾病，其特征是在严重低血糖情况下胰岛素分泌不当。最近，在15个家族中，该疾病相关基因被定位到11号染色体短臂上标记D11S926和D11S928之间6.6厘摩的区间内（1）。在本研究中，我们评估了另外6个家族和5个新标记，并将该基因进一步定位在D11S419和D11S1310之间。利用来自CEPH第7版的基因型数据以及本研究产生的数据，估计该区域长度为0.8厘摩。对于德系犹太人染色体，在10.3厘摩（11号染色体短臂末端 - D11S926 - D11S1308 - 11号染色体短臂着丝粒）的区域内观察到标记与HI基因之间存在显著的连锁不平衡。单倍型分析显示，36条HI染色体中有12条，而36条非HI染色体中有1条，带有D11S419 - D11S902 - D11S921的特定单倍型（p < 0.0007），强烈提示该种族群体存在奠基者效应。
