Topic: Developmental Genetics
Tan JC, Nocka K, Ray P, Traktman P, Besmer P
The dominant W42 spotting phenotype results from a missense mutation in the c-kit receptor kinase.
Science 247: 209-212, 1990

This is the first class of this year's Developmental Biology course.

While many courses are designed to "provide knowledge" to the participants, the main objective of this course is to "nurture the ability to think critically". The class will be run by using primary literature as course material and discussing on the topic. Lecturers of each session are not necessarily experts in the theme covered by the paper, but have chosen the paper and the topic because they have identified some interesting aspect that they would like to share and discuss with the participants.

The topic for the first class is "Developmental Genetics". The paper that we will be using describes the molecular nature of a mutation in the mouse W locus, which encodes a receptor tyrosine kinase called c-kit. Receptor tyrosine kinases control many cellular events such as proliferation, migration, shape change and fate decision. For example, receptor kinase c-kit is required for the proliferation of mast cells, one type of hematopoietic cells. c-kit also controls the migration of precursor cell of melanocytes; a defect in this migration causes production of hair lacking melanin, resulting in the appearance of "white spotting" in otherwise black coat color.The "panda mouse" is also a mutant allele of c-kit. So, from the view point of developmental biology, results described in this paper help our understanding of coat patterning during development.

However, this week we will look at this paper from the view point of genetics, and discuss the relationship between the molecular nature of of the mutation and the classification of mutation based on their behavior in various genetic situations. Such classification is done by observing the phenotype -- the composite of observable characteristics of the organism. In the case of W[42] allele, the molecular nature of the mutation is a missense mutation (alteration in an amino acid residue), and the mutation exhibits a dominant phenotype (almost white coat color throughout the body). A curious aspect of this allele is that the coat color phenotype that it can produce in heterozygous condition is even stronger than a physical deletion of the gene (null allele). We will discuss how such situation can be achieved.

See you next Monday, either in class or through the remote lecture system!

トピック：発生遺伝学
Tan JC, Nocka K, Ray P, Traktman P, Besmer P
The dominant W42 spotting phenotype results from a missense mutation in the c-kit receptor kinase.
Science 247: 209-212, 1990

多くの授業科目が「知識を授ける」ことを目的にしているのに対し，発生生物学II-IVは「批判的に考える能力を養う」ことを目標にしています．授業は，原著論文をネタにして議論することによって進めます．各セッションの講師は必ずしも論文のトピックの専門家ではありませんが，その論文に何かおもしろい観点を見つけ，皆さんと一緒に議論したいと考えて論文を選んでいます．

最初のセッションのトピックは"Developmental Genetics/発生遺伝学" です．このセッションで用いる論文は，c-kitという受容体型チロシンキナーゼをコードするマウスのW遺伝子のある変異の分子的性質を報告しています．受容体型チロシンキナーゼは，細胞増殖，細胞移動，細胞変形や細胞運命決定など，様々な細胞現象を制御するのに使われています．たとえば，c-kitは肥満細胞（mast cell）と呼ばれる血球系の細胞の増殖に必要です．c-kitは色素細胞の前駆細胞（melanoblast）の細胞移動にも関与しますす．この過程に異常が起こると，メラニンを含まない毛が生じ，本来黒一色の体表の毛に白い斑点（white spotting）が生じます．「パンダマウス 」もc-kit遺伝子の変異系統です．だから「発生生物学」の観点から見れば，この論文で報告されている結果は発生過程での体表の毛のパターン形成の理解につながります．

でも，今回は「遺伝学」の観点からこの論文を読んでみて，変異の分子的性質と遺伝学的性質〔分類）の関係を議論しましょう．変異の分類は表現型（phenotype: 遺伝子型が形質として表現されたもの）を観察することによって行われます．W[42] アリルの場合には，変異の分子的性質はミスセンス変異（アミノ酸の置換）でした．そして，このアリルは優性の表現型（ヘテロ接合体は毛色がほぼ真っ白！）を示します．奇妙なのは，このアリルがヘテロ接合体で作り出せる症状は遺伝子の欠失（null allele）よりも重篤であることです．授業では，どうやってそんな状況が生じえたのか，議論しましょう．