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Kabuki Syndrome Network in Japan Newsletter 歌舞伎ジャーナル  第101号

<<平成22年10月18日>>

  歌舞伎症候群の遺伝子発見

 英語版の歌舞伎ジャーナルで「歌舞伎症候群の責任遺伝子特定」の記事が掲載されました。先ず原文を紹介します。

New Genetic Discovery!

As a result of the research carried out by scientists at the University of Seattle, on August 15, 2010 the National Human Genome Research Institute has announced the discovery of a gene responsible for approximately 70% of individuals with Kabuki Syndrome. The researchers used the newly developed technique of exome sequencing to identify the MLL2 gene mutations. The official press release can be found here.

To help families understand the basics of the discovery, we have included an article, Understanding the Genetics of Kabuki, which appeared in the spring 2010 issue of the Kabuki Journal .

To summarize, scientists at the University of Washington have used a "second generation" technique to examine only the protein-coding gene portion of the human genome, called the exome. Since the exome constitutes only 1 - 2% of the human genome, the cost and time requirement has been greatly reduced, making it more plausible to look for gene mutations.

There are different reasons why a gene may have a mutation. In the case of Kabuki, the MLL2 gene mutations were found to be due to either nonsense or frame-shift mutation which resulted in a shortened, nonfunctional protein.

nonsense A nonsense mutation is a change in one DNA base pair. The altered DNA sequence prematurely signals the cell to stop building a protein. This type of mutation results in a shortened protein that may function improperly or not at all. In the example to the left, you can see how the insertion of the base thymine (T) is now read as TAG instead of the intended CAG. Since TAG is read as a STOP, the resulting protein is shortened. Refer back to the DNA Decoder Wheel in Understanding the Genetics of Kabuki to see how this happens.
frameshift A frameshift mutation occurs when the addition or loss of DNA bases changes a gene痴 reading frame. A reading frame consists of groups of 3 bases that each code for one amino acid. A frameshift mutation shifts the grouping of these bases and changes the code for amino acids. The resulting protein is usually nonfunctional. Insertions, deletions, and duplications can all be frameshift mutations. In the example to the left, you can see how the shift of the first DNA base means that the succeeding bases are all read incorrectly.

It is speculated that Kabuki is a heterogeneous syndrome, meaning that multiple genes could potentially be involved. It is hoped that with continued analysis, other genes will be discovered.

歌舞伎症候群の責任遺伝子特定

 歌舞伎ジャーナル第98号(平成21年11月23日)でお知らせしていましたが、その結果が報告されました。

 米ワシントン大学の研究グループは,エクソンシークエンス法という新しいゲノム解析法を用いて,MLL2を歌舞伎症候群の責任遺伝子として同定したとNational Human Genome Research Institute(米国立ヒトゲノム研究所)に発表した(これに当てはまるのは約70%の確立としています)。

  エクソンシークエンス法とはヒトゲノムの全塩基配列からタンパク質をつくるのに必要なエクソン部分だけ集めたものをエクソームと呼び、これを解析した。今回の研究はエクソームを疾患解明に応用し成功した最初の例だそうです。今後は歌舞伎症候群のような希少で且つ原因不明の疾患の対症療法に応用されると期待されます。

National Human Genome Research Institute(米国立ヒトゲノム研究所)に掲載された記事はこちらからどうぞ。

上の2枚の模式図を理解するためにはビデオブログ(2010.8.1)のDNA DECORDER WHEELをご利用ください。このホィールは4つの塩基(A(アデニン)、T(チミン)、G(グアニン)、C(シトシン))の配列から作られるアミノ酸の種類が判別できます。

 

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