家族性典型偏头痛：一个基因与Xq24 - 28的显著连锁及定位

Familial typical migraine: significant linkage and localization of a gene to Xq24-28.

作者信息

Nyholt D R, Curtain R P, Griffiths L R

机构信息

Laboratory of Statistical Genetics, Rockefeller University, New York, NY 10021, USA.

出版信息

Hum Genet. 2000 Jul;107(1):18-23. doi: 10.1007/s004390000329.

DOI:10.1007/s004390000329

PMID:10982029

Abstract

In a previous study we found evidence for an X-linked genetic component for familial typical migraine in two large Australian white pedigrees, designated MF7 and MF14. Significant excess allele sharing was indicated by nonparametric linkage (NPL) analysis using GENEHUNTER (P=0.031 and P=0.012, respectively), with a combined analysis of the two pedigrees showing further increased evidence for linkage, producing a maximum NPL score of 2.87 (P=0.011 ) at DXS 1123 on Xq27. The present study was aimed at refining the localization of the migraine X-chromosomal component by typing additional markers, performing haplotype analysis and applying a more powerful technique in the analysis of linkage data from these two pedigrees. Results from the haplotype analyses, coupled with linkage analyses that produced a peak GENEHUNTER-PLUS LOD* score of 2.388 (P=0.0005), provide compelling evidence for the presence of a migraine susceptibility locus on chromosome Xq24-28.

摘要

在之前的一项研究中，我们在两个大型澳大利亚白人系谱（分别命名为MF7和MF14）中发现了家族性典型偏头痛存在X连锁遗传成分的证据。使用GENEHUNTER进行的非参数连锁（NPL）分析表明存在显著的等位基因过度共享（分别为P = 0.031和P = 0.012），对这两个系谱进行联合分析显示连锁证据进一步增加，在Xq27的DXS 1123处产生了最大NPL分数2.87（P = 0.011）。本研究旨在通过对额外的标记进行分型、进行单倍型分析以及在分析这两个系谱的连锁数据时应用更强大的技术，来精确定位偏头痛的X染色体成分。单倍型分析的结果，再加上产生峰值GENEHUNTER-PLUS LOD*分数2.388（P = 0.0005）的连锁分析，为Xq24 - 28染色体上存在偏头痛易感基因座提供了令人信服的证据。