遺傳連鎖分析之可調適全基因組掃描策略

做基因全體逐點搜尋 (genomewide scan) 時，需事先針對所有的標識基因做完基因型判定 (genotyping)，再針對每一個標識基因逐點作連鎖分析，觀察標識基因和疾病間的相關以推測疾病基因座可能的位置。由於基因全體逐點搜尋需要大量的標識基因，若每一標識基因都做基因型定位，會耗費許多時間與金錢成本，使眾多研究者卻步。本研究目的在於提出一個搜尋策略，期望只需做一部份的基因型分析就可發現疾病基因座的可能位置，以節省研究經費與成本。本搜尋策略是以可調適方法並利用傳遞不平衡檢定 (TDT) 來找尋疾病基因座位置。可調適方法是指將所有標識基因分成數個步驟分批以TDT檢定，於前一步驟中已達門檻顯著水準 (SLST) 之標識基因附近再多選取幾個標識基因續做分析，若達更嚴格的停止標準顯著水準 (SLSS) 則可停止搜尋策略。透過模擬結果，本搜尋策略平均約可節省一半的標識基因，即可正確發現和疾病基因有連鎖的標識基因座，顯示本策略是一個有效的基因全體逐點搜尋方法。

關鍵字

傳遞不平衡檢定；基因定位；效率；基因型判定；連鎖分析

並列摘要

Linkage analysis has been considered as a major instrument for gene mapping. When performing a genomewide scan, there requires a large number of markers being genotyped in advance and then being analyzed to find the candidate markers linked with the disease gene. To save the cost in labor and time, here we propose an adaptive stepwise selection strategy with the use of transmission/disequilibrium test that may only need to analyze a part of the whole markers to catch the disease gene. We have used computer simulation to investigate the efficiency of the adaptive genomewide scan strategy. In general, the results show that the strategy does not need to genotype all the markers and can still efficiently locate the gene.

並列關鍵字

transmission/disequilibrium test ； gene mapping ； efficiency ； linkage analysis ； genotyping

參考文獻

Camp NJ. Genomwide transmission/disequilibrium testing- consideration of the genotypic relative risks at disease loci. Am J Hum Genet. 1997, 61:1424-1430.

Elston RC, Guo X, Williams LV. Two-stage global search designs for linkage analysis using pairs of affected relatives. Genet Epidemiol. 1996;13(6):535-558.

Guo X, Elston RC. Two-stage global search designs for linkage analysis I: use of the mean statistic for affected sib pairs. Genet Epidemiol. 2000;18(2):97-110.

Guo X, Elston RC. Two-stage global search designs for linkage analysis II: including discordant relative pairs in the study. Genet Epidemiol. 2000;18(2):111-127.

Guo X, Elston RC. One-stage versus two-stage strategies for genome scans. Adv Genet. 2001;42:459-471.

國際替代計量

遺傳連鎖分析之可調適全基因組掃描策略

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