O'Rahilly S, Patel P, Lehmann O J, Tybjaerg-Hansen A, Nerup J, Turner R C, Wainscoat J S
Diabetes Research Laboratories, Radcliffe Infirmary, Oxford, UK.
Hum Genet. 1992 May;89(2):207-12. doi: 10.1007/BF00217125.
Members of three families with maturity onset diabetes of youth (MODY) and seven with "common" type 2 diabetes were typed for six DNA markers (H-RAS, INS, HBBC, PTH, CALC1, CAT) on the short arm of chromosome 11. Using conventional pairwise linkage analysis, close linkage in the MODY families was excluded for all six markers. By multipoint analysis and a genetic map of the short arm of chromosome 11, MODY was excluded from a region of at least 35 and up to 60 centiMorgans (cM) on the short arm of chromosome 11. Multipoint analysis in the type 2 families also excludes linkage to the INS, H-RAS region of at least 3 and up to 30 cM. This study using multipoint linkage analysis in non-insulin dependent diabetes provides strong evidence against a role for mutations in or around the insulin gene in the causation of MODY or type 2 diabetes in the families studied.
对三个患有青年发病型糖尿病（MODY）的家族成员以及七个患有“普通”2型糖尿病的家族成员，进行了11号染色体短臂上六个DNA标记（H-RAS、胰岛素基因INS、HBBC、甲状旁腺激素基因PTH、钙基因CALC1、过氧化氢酶基因CAT）的分型。采用传统的成对连锁分析，排除了MODY家族中所有六个标记的紧密连锁。通过多点分析和11号染色体短臂的遗传图谱，将MODY排除在11号染色体短臂上至少35厘摩（cM）至60厘摩的区域。2型糖尿病家族的多点分析也排除了与INS、H-RAS区域至少3厘摩至30厘摩的连锁。这项在非胰岛素依赖型糖尿病中使用多点连锁分析的研究，有力地证明在所研究的家族中，胰岛素基因内部或其周围的突变在MODY或2型糖尿病病因中不起作用。
