Birth Defects: From Molecules to Mechanisms (2024)

PMCID: PMC5401056

Andrew J Copp, MB, BS, DPhil

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Abstract

Birth defects remain a major clinical problem and, although much progress has been made in prenatal diagnosis, few measures are available for primary prevention. This is due, in large part, to our rudimentary understanding of the embryonic mechanisms of birth defects. Until recently it was customary to concentrate on defining teratogenic factors that may be active in humans. Now, with the rapid expansion in molecular biological technology, it has become possible to identify and isolate the genes that determine heritable predisposition to birth defects. The most productive strategy appears to be the genetic analysis of animal, principally mouse, models in which particular classes of birth defects develop owing to known genetic mutations. Gene targeting techniques allow mutations to be induced in previously cloned genes, permitting their potential as birth defect-inducing genes to be evaluated. Gene cloning alone, however, cannot reveal the entire pathogenetic sequence for any birth defect, since the most downstream events can be elucidated only by experimental embryological analysis. Culture methods are now available in which intact mouse and rat embryos undergo normal development for limited periods in vitro. Studies of this type have revealed several steps in the embryonic development of genetically determined spina bifida. The combination of gene centred and embryo centred research promises to advance our understanding of the pathogenesis of major birth defects.

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