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How to Measure Genetic Heterogeneity

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Presentation on theme: "How to Measure Genetic Heterogeneity"— Presentation transcript:

1 How to Measure Genetic Heterogeneity
International Workshop on Statistical-Mechanical Informatics 2009/09/ /09/16 Unit of Statistical Genetics Center for Genomic Medicine Kyoto University Ryo Yamada

2 What is genetic heterogeneity?

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5 Biological Strategies
Lives cover land. Landcover map by Environmental Research and Teaching at the University of Toronto

6 changes its shape and moves around but uses spores to reproduce.
Wikipedia Slime mold changes its shape and moves around but uses spores to reproduce. 6

7 Food Slime mold is clever enough to find the shortest route in the labyrinth. Its strategy is being investigated as a new model of parallel computing system.

8 Slime mold keeps looking for new (better?) conditions.
Space is too big to be covered completely. Therefore, multiple places are selected and they are bridged without break. Each part seems to act independently. 8

9 Phylogenic tree LIFE keeps looking for new (better?) conditions.
Space is too big to be covered completely. Therefore, multiple places are selected and they are bridged without break. Each part seems to act independently. 9

10 They are bridged without break.
We are here because we are all offspring of “No-break” family sharing the feature of continuous LIFE. 10

11 ?? Features of LIFE ?? Keeps looking for something.
Accepts multiple conditions as GOOD ones. Stays continuous each other. Each acts independently.

12 Slime mold distributes in physical space
Slime mold distributes in physical space. LIFE distributes in genetic space. Distributions ~ Heterogeneity

13 LIFE distributes in genetic space.
What is genetic space? LIFE distributes in genetic space. 13

14 3 x 109 in length (Homo sapience)
DNA molecules 4 letters, {A,T,G,C} 3 x 109 in length (Homo sapience) 14

15 Genetic heterogeneity is consisted of sequence variation
L={1,2,…} 15

16 Biological space is a part of physico-chemical space.
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17 Biological space is far much smaller than chemical space,
But still enormously big.

18 Environments change width of pathways in biological space
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19 遺伝子多型を用いた 集団遺伝学解析 組換え 種の進化系統樹 ヒトの多様性 (種内 遺伝子多型) 19
Nature Reviews Genetics 3, (2002); doi: /nrg795 GENEALOGICAL TREES, COALESCENT THEORY AND THE ANALYSIS OF GENETIC POLYMORPHISMS 種の進化系統樹 Nature Reviews Genetics 3, (2002); doi: /nrg795 GENEALOGICAL TREES, COALESCENT THEORY AND THE ANALYSIS OF GENETIC POLYMORPHISMS ヒトの多様性 (種内 遺伝子多型) 19

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21 私と遺伝統計学と臨床医学と ~みんなちがって、みんないい~
30億塩基対 多型性箇所~1千万? 210,000,000>>>>>65億人 21

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23 Mapping 個々のマーカーについて検定する マーカー間の依存関係に興味がある

24 2マーカーの場合 Pairwise LD index r^2 chi^2(1)=r chi^2(2)

25 連鎖不平衡~マーカー間の非独立性 25

26 Pairwise 2-d plot 2^k types k(k+1)/2 = Combin(k,2) parametersで情報集約

27 Ψ 2^k types 2^k-1 parameters 2^k-1 parametersのまま。ただし、階層化することで情報集約

28 この状態を1つの測度で表して、それが有用たらしめることはできるか?
エントロピー r^k

29 離散的過ぎる・・・ ハミング距離の分布 変異のみ 組み換えも考慮 多型は宝 人口減の影響で多型がなくならないかどうかを指標に

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37 Unit of Statistical Genetic, Center for Genomic Medicine
Graduate School of Medicine, Kyoto University

38 粘菌もがんばる 空間を探索したい。どこかいいところはないか、元の方がよいかも知れないので、戻る道を残しつつ。 覆い尽くせない。
どうしたらよいか、最適な方法は・・・ 粘菌によるコンピューティング

39 イントロ DNA配列 意味


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