New genes? Possibly, MABy...

Abstract

Congenital malformations account for a very substantial proportion of pediatric morbidity in the human population. Cytogenetic deletions have a live birth incidence of approximately 1 in 7000, and such deletions have often been utilized in human genetics for the mapping of genes involved in rare mendelian traits. To date, however, a relatively small proportion of the genetic defects responsible for congenital malformations have been identified. Somewhat surprisingly, no systematic approach has yet been taken to correlate cytogenetic deletions with phenotype in humans. Here, Brewer et al.1 Brewer C. et al. A chromosomal deletion map of human malformations. Am. J. Hum. Genet. 1998; 63: 1153-1159 Abstract Full Text Full Text PDF PubMed Scopus (132) Google Scholar report the first attempt to do so. They have analyzed the distribution of 289 whole or partial deletion bands in 47 common congenital malformations covering a wide spectrum of developmental processes, and thereby identified 199 statistically significant malformation-associated bands (MABs). The average number of significant MABs detected per malformation was 4.3. Only 6% of the MABs identified contain previously identified mendelian loci associated with the malformation, and a further 6% overlap with known aneuploid syndrome regions. Thus, assuming that haploinsufficiency for one or more genes in the deleted regions plays a causative role in the associated malformations (already proven in the cases of several well known deletion syndromes), this analysis should provide rich hunting grounds for the identification of human developmental genes.