A chromosomal duplication map of malformations: regions of suspected haplo- and triplolethality--and tolerance of segmental aneuploidy--in humans

Abstract

The distribution of simple autosomal duplications associated with congenital malformations has been analyzed by means of data contained in the Human Cytogenetics Database. For each of the 47 malformations, the frequency of duplication of a given chromosome band associated with the malformation was compared with the overall frequency of duplication of that band recorded in the database. In total, there were 143 malformation-associated chromosomal regions (MACR); 21 of these contained at least one band with a highly significant (P<.001) association. The average number of bands per MACR was 3.1. Eight bands, representing 2.1% of haploid autosomal length, were not involved in any duplication, and we suggest that these are potentially triplolethal. This compares with 31 bands, representing 11% of haploid autosomal length, that were identified in the previously reported deletion map and that were not involved in any deletion and are potentially haplolethal. In both cases, approximately half of these bands are pericentromeric. The longest duplication involves 4.3% of haploid autosomal length, and the longest deletion involves 2.7%.