title: Embryonic left-right separation mechanism allows confinement of mutation-induced phenotypes to one lateral body half of bilaterians.
abstract: A fundamental question in developmental biology is how a chimeric animal such as a bilateral gynandromorphic animal can have different phenotypes confined to different lateral body halves, and how mutation-induced phenotypes, such as genetic diseases, can be confined to one lateral body half in patients. Here, I propose that embryos of many, if not all, bilaterian animals are divided into left and right halves at a very early stage (which may vary among different types of animals), after which the descendants of the left-sided and right-sided cells will almost exclusively remain on their original sides, respectively, throughout the remaining development. This embryonic left-right separation mechanism allows (1) mutations and the mutation-induced phenotypes to be strictly confined to one lateral body half in animals and humans; (2) mothers with bilateral hereditary primary breast cancer to transmit their disease to their offspring at twofold of the rate compared to mothers with unilateral hereditary breast cancer; and (3) a mosaic embryo carrying genetic or epigenetic mutations to develop into either an individual with the mutation-induced phenotype confined unilaterally, or a pair of twins displaying complete, partial, or mirror-image discordance for the phenotype. Further, this left-right separation mechanism predicts that the two lateral halves of a patient carrying a unilateral genetic disease can each serve as a case and an internal control, respectively, for genetic and epigenetic comparative studies to identify the disease causations.
authors.forename: Kun
authors.initials: K
authors.lastname: Ma
mesh_terms: D000818:Animals; D019521:Body Patterning / Q000235:genetics*; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D044127:Epigenesis, Genetic / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental; D030342:Genetic Diseases, Inborn; D006801:Humans; D009154:Mutation; D010641:Phenotype
keywords: CHILD syndrome; bilateral cancer; discordant twins; embryogenesis; embryonic development; embryonic left-right separation mechanism; fluctuation asymmetry; gynandromorph; gynandromorphism; hemiatrophy; left-right asymmetry; unilateral cancer; unilateral diseases