5. SNP? Mutation? Variant?
• (Common) SNP
集団内で同じ変異が1%以上存在している
▫ 多い方 Major allele / 少ない方 Minor allele
• “SNP”ってどうなん?
HGVS(Human Genome Variation Society)によると
Mutation and polymorphism
In some disciplines the term "mutation" is used to indicate "a change" while in other
disciplines it is used to indicate "a disease-causing change". Similarly, the
term "polymorphism" is used both to indicate "a non disease-causing change" or "a
change found at a frequency of 1% or higher in the population". To prevent this
confusion we do not use the terms mutation and polymorphism (including SNP or
Single Nucleotide Polymorphism) but use neutral terms like "sequence
variant","alteration" and "allelic variant". Human Mutation (Vol. 19 ( 1) of 2002)
contains several contributions discussing these issues as well as the fact that the
term"mutation" has developed a negative connotation (see Cotton RGH - p.2, Condit
CM et al. - p.69 and Marshall JH - p.76).
http://www.hgvs.org/mutnomen/recs.html
5
6. SNP? Mutation? Variant?
• (Common) SNP
集団内で同じ変異が1%以上存在している
▫ 多い方 Major allele / 少ない方 Minor allele
• “SNP”ってどうなん?
HGVS(Human Genome Variation Society)によると
Mutation and polymorphism
In some disciplines the term "mutation" is used to indicate "a change" while in other
disciplines it is used to indicate "a disease-causing change". Similarly, the
term "polymorphism" is used both to indicate "a non disease-causing change" or "a
change found at a frequency of 1% or higher in the population". To prevent this
confusion we do not use the terms mutation and polymorphism (including SNP or
Single Nucleotide Polymorphism) but use neutral terms like "sequence
variant","alteration" and "allelic variant". Human Mutation (Vol. 19 ( 1) of 2002)
contains several contributions discussing these issues as well as the fact that the
term"mutation" has developed a negative connotation (see Cotton RGH - p.2, Condit
CM et al. - p.69 and Marshall JH - p.76).
http://www.hgvs.org/mutnomen/recs.html
6
Mutation
変化(change) のときもあれば 病原となる変化(disease-causing change)もある
同様に、
Polymorphism (SNP含む)
病原とならない変化(non disease-causing change)と1%以上の集団にある変化
(change found at a frequency of 1% or higher in the population)どちらにも使う
ややこしいので、”(sequence/allelic) variant”や”alteration”を使いましょう。
7. HWE/HWP(Hardy-Weinberg Equilibrium or Principle)
• ハーディー・ワインバーグの法則
集団内でのSNP解析で基礎となる法則
自由交配である
集団が十分に大きい(理想的には無限大)
他の集団との間で異動がない
突然変異が起こらない
自然選択が働かない
このとき、(2倍体の場合)アレルAとaの頻度p, qにおい
てどの世代でもp + q = 1, AA:Aa:aa = p2:2pq:q2 となる
• HWP(Hardy-Weinberg Probability or Proportion)
HWEに沿っているかの適合度検定
χ二乗検定やMCMCなどを使用する
Wigginton et al., Am J Hum Genet. 2005 May; 76(5): 887–893.
Guo and Thompson, Biometrics. 1992 Jun;48(2): 361-372.
7
32. Random Forestを使用した癌種判定
• The Pan-Cancer Analysis Project (癌種横断的な解析)
▫ Data was retrieved from the Pan-Cancer Analysis repository (synapse accession: syn1710680)
▫ Functional somatic mutations unique to tumours were identified and represented as a samples x
genes mutation matrix (mutated=1, non-mutated=0)
▫ Pairwise Random Forest models were built for the 5 cancer differentiation subtypes
(Adenocarcinoma, Squamous, Urotherial, Brain, Haematological)
• Urotherial(尿路系腫瘍) vs. Haematological(造血器腫瘍)の判
定精度は87.8%、他の組み合わせでも平均で85%
32
http://dx.doi.org/10.6084/m9.figshare.1084404
Russel et. al. (2014)