合併染病同胞對資料其標識基因之下傳/不下傳訊息與同源全等基因訊息的連鎖分析方法

Combining Transmission-Nontransmission Information and Identical by Descent Information for Test of Linkage in Affected Sib Pairs

曾貞寧(Chen-Ning Tseng)

指導教授 ： 戴政

國立臺灣大學/公共衛生學院/流行病學研究所/碩士(2004年)

https://doi.org/10.6342/NTU.2004.00706

摘要

對於染病同胞對(affected sib pairs)的資料進行遺傳連鎖分析，目前有兩種較常使用的無母數方法，一種是均值檢定(mean test)，用於分析染病同胞對之資料，去測定標識基因下傳到染病同胞對的同源全等基因數目(IBD,identical by decent)；另一種，是針對一個核心家庭具一個染病小孩所發展出來的傳遞不平衡檢定(TDT,transmission/disequilibrium test)，用標識基因與疾病基因一併下傳與否現象，來檢定連鎖不平衡，傳遞不平衡檢定可推廣於染病同胞對的資料，故已有釵h研究比較均值檢定與傳遞不平衡檢定的檢定力。
均值檢定與傳遞不平衡檢定的檢定力在不同連鎖不平衡程度下，會呈現相消長的現象，即若連鎖不平衡程度弱時，均值檢定的檢定力會比傳遞不平衡檢定的檢定力好；連鎖程度強時，傳遞不平衡檢定的檢定力比均值檢定好。本論文目的在嘗試合併兩者訊息，造出一個對連鎖不平衡干擾具有強韌性的新統計量。在這個想法上，先利用均值檢定的IBD值與傳遞不平衡下傳的訊息，找出其聯合機率，並且證明了兩者並不獨立。其後，由聯合機率造出一個新的統計量，並以模擬方法比較新的統計量與均值檢定及傳遞不平衡檢定的檢定力表現。

關鍵字

染病同胞對 ； 傳遞不平衡檢定 ； 均值檢定 ； 同源全等基因數目 ； 連鎖不平衡

並列摘要

There are two major nonparametric methods for the test of linkage.One is the mean test which is applied to affected sib pairs.The other is TDT
(transmission/disequilibrium test)which is applied to case-parent triad families and can be extended to multiple affected children.Therefore,when the data are gathered with affected sib pairs,both methods are applicable for the test of linkage.It has been known that when linkage disequilibrium is weak,the power of mean test is greater than that of TDT,but when linkage disequilibrium is strong,the power of TDT is greater than that of the mean test.In this paper,we propose a new method to combine two tests to construct a new statistic. First,we derived their joint probabilities for the transmission-nontransmission information and identical by descent information in sib pairs.We showed that the two variables representing the two types of information are dependent.Based on this joint probabilities we developed a new statistic for the test of linkage.Finally,we compared the powers of the new statistic,TDT and the mean test.

並列關鍵字

IBD ； TDT ； mean test ； affected sib pairs ； linkage disequilibrium

參考文獻

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McGinnis R.E. (1998). Hidden linkage: a comparison of the affected sib pair (ASP) test and transmission/disequilibrium test (TDT). Ann. Hum. Genet. 62:159-179