Hiltunen M, Mannermaa A, Thompson D, Easton D, Pirskanen M, Helisalmi S, Koivisto A M, Lehtovirta M, Ryynänen M, Soininen H
Department of Neurology, University Hospital and University of Kuopio, Finland.
Neurology. 2001 Nov 13;57(9):1663-8. doi: 10.1212/wnl.57.9.1663.
AD is a complex neurodegenerative disorder comprising several disease-associated chromosome loci. To find novel susceptibility genes for late-onset AD, a population-based genome-wide search using linkage disequilibrium (LD) mapping approach has been performed.
Forty-seven patients with late-onset AD and 51 age-matched control subjects were carefully chosen from the same geographic area in eastern Finland, where the population is descended mainly from a small group of original founders. These subjects were initially genotyped with 366 polymorphic microsatellite markers, and a follow-up analysis was performed with additional microsatellite markers for those chromosome loci found to be associated with AD.
Initial genome-wide screening revealed 21 chromosomal loci significantly associated with AD in addition to the 13q12 locus described previously. Subsequent comparison of single-allele frequencies of the microsatellite markers in the AD and control groups indicated the presence both of possible risk alleles (odds ratio [OR] > 1) and of possible protective alleles (OR < 1). Screening of the LD regions with additional microsatellite markers revealed seven chromosomal loci where more than one microsatellite marker was associated with AD (1p36.12, 2p22.2, 3q28, 4p13, 10p13, 18q12.1, and 19p13.3) in addition to the 13q12 locus.
These genome-wide LD screening data suggest that several AD-associated chromosomal loci exist, which may encompass novel susceptibility genes for late-onset AD. Therefore, extensive screening of the genes located in the vicinity of these LD regions is necessary to elucidate their role in AD.
阿尔茨海默病（AD）是一种复杂的神经退行性疾病，涉及多个与疾病相关的染色体位点。为了寻找晚发型AD的新的易感基因，已经采用连锁不平衡（LD）图谱方法进行了基于人群的全基因组搜索。
从芬兰东部同一地理区域精心挑选了47例晚发型AD患者和51例年龄匹配的对照受试者，该地区人群主要源自一小群原始创始人。这些受试者最初用366个多态性微卫星标记进行基因分型，对于那些发现与AD相关的染色体位点，用额外的微卫星标记进行了后续分析。
最初的全基因组筛查除了先前描述的13q12位点外，还发现了21个与AD显著相关的染色体位点。随后对AD组和对照组中微卫星标记的单等位基因频率进行比较，发现既有可能的风险等位基因（优势比[OR]>1），也有可能的保护等位基因（OR<1）。用额外的微卫星标记对LD区域进行筛查，除了13q12位点外，还发现了7个染色体位点，其中不止一个微卫星标记与AD相关（1p36.12、2p22.2、3q28、4p13、10p13、18q12.1和19p13.3）。
这些全基因组LD筛查数据表明存在几个与AD相关的染色体位点，可能包含晚发型AD的新的易感基因。因此，有必要对位于这些LD区域附近的基因进行广泛筛查，以阐明它们在AD中的作用。
