Amplification of a pseudogene cassette underlies euchromatic variation of 16p at the cytogenetic level

Euchromatic imbalances at the cytogenetic level are usually associated with phenotypic consequences. Among the exceptions are euchromatic variants of chromosomes 8, 9, 15 and 16, which have each been reported in multiple unre lated families. In this paper. we present a new family and an unrelated ind ividual who have euchromatic variants of 16p. Enhanced hybridisation to the extra material was found by using fluorescence in situ hybridisation with cosmids for both the 16p11.2-specific non-functional immunoglobin heavy cha in segments and the pseudogenetic 16p11.2 creatine transporter region. Comp uterised measurement of the fluorescent signals was consistent with amplifi cation of a pseudogene cassette comprising both these paralogous domains, w hich were originally transposed from 14q32.3 and Xq28, respectively. Amplif ication of pseudogenetic sequences is consistent with the normal phenotype in 36/46 carriers from the 18 families reported to date. Inconsistent pheno typic anomalies in the remaining 10 carriers probably reflect bias of ascer tainment. These results are analogous to the amplification of the 15q11.2-s pecific pseudogene cassette in euchromatic variants of chromosome 15. They also suggest that the majority of established euchromatic variants are asso ciated with variation in the copy number of sequences that have been disper sed between pericentromeric and telomeric loci over recent evolutionary tim e. We propose that constitutional cytogenetic amplification of this kind is part of a more widespread continuum of genomic flux affecting regions in w hich heterochromatin and euchromatin interpose. Euchromatic sequences that vary in a heterochromatic manner might usefully be termed "hemichromatic".