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The Search for Molecular Defects in Genetic Disease

Published online by Cambridge University Press:  01 August 2014

H. Galjaard
H. Galjaard*
Affiliation:
Department of Clinical Genetics, Erasmus University, Rotterdam, The Netherlands
*
Department of Clinical Genetics, Erasmus University Rotterdam- P.O. Box 1738, 3000 DR Rotterdam, The Netherlands

Extract

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In most wealthy industrialized countries, socioeconomic circumstances, hygiene and medical care have improved to such an extent that perinatal complications and congenital disorders have become the major causes of infant mortality and of chronic handicap in children [1].

In the past four decades, we have made impressive advances understandig the cytogenetic and molecular basis of congenital disorders. Dozens of syndromes associated with multiple physical handicaps and mental retardation have been related to specific numerical or structural chromosome aberrations. In situ hybridization and the development of a rapidly increasing number of DNA probes enable the detection of chromosomal abnormalities with a resolution down to the level of a single gene. The discovery of tumor-associated chromosomal aberrations, microdeletions, more than a hundred oncogenes, and the cloning of tumor suppressor genes are illustrations of the importance of molecular cytogenetics.

When I started my scientific career at the end of the fifties, some 1,000 syndromes were proven or suspected to be subject to Mendelian inheritance and this number has now increased to more than 6,600 [2]. Progress in elucidating the protein defects responsible for these single gene disorders has been much slower and currently about 400 protein defects have been delineated [3]. This knowledge has been important not only for basic research on biochemical pathways and cell biology, but has also provided new perspectives for early laboratory diagnosis of index patients, carrier detection, genetic counseling and in some instances, such as phenylketonuria, for newborn screening and early treatment [4]. In those instances where a protein defect is also expressed in cultured skin fibroblasts, amniotic cells or chorionic villi, prenatal diagnosis becomes possible for couples at increased risk [5, 6].

Type
Research Article
Information
Acta geneticae medicae et gemellologiae: twin research , Volume 45 , Issue 1-2 , April 1996 , pp. 43 - 52
Copyright
Copyright © The International Society for Twin Studies 1996

References

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