A putative gene family in 15q11-13 and 16p11.2: possible implications for Prader-Willi and Angelman syndromes.

Abstract

The genetic defects in Prader-Willi syndrome (PWS) and Angelman syndrome (AS) map to 15q11-13. Using microdissection, we have recently isolated several DNA probes for the critical region. Here we report that microclone MN7 detects multiple loci in 15q11-13 and 16p11.2. Eight yeast artificial chromosome (YAC) clones, two genomic phage clones, and two placenta cDNA clones were isolated to analyze these loci in detail. Two of the YAC clones map to 16p. Six YAC clones and two genomic phage clones contain a total of four or five different MN7 copies, which are spread over a large distance within 15q11-13. One cDNA clone is from chromosome 15 and one is from chromosome 16. The chromosome 15 cDNA detects transcripts of 14 and 8 kilobases in various human tissues. The presence of multiple copies of the MN7 gene family in proximal 15q may conceivably be related to the instability of this region and thus to the etiology of associated disorders.

Evaluation of potential models for imprinted and nonimprinted components of human chromosome 15q11-q13 syndromes by fine-structure homology mapping in the mouse.

“…As expected from the data in Fig. 2C, the -14-kb transcript detected by the MN7 probe at the D1SF37SJh locus (17) is not expressed in the brains of p6H/p6H mice.…”

A brief history of human autosomes

“…The large block of constitutive heterochromatin at proximal 16q is polymorphic in size (Verma et al 1978), and proximal 16p has been the integration site for duplicated material from at least four other chromosomes (Eichler 1998): immunoglobulin V H segments from h14 are duplicated at 16p11.2 (Tomlinson et al 1994); sequences are shared by 15q11^q13 and 16p11.2 (Buiting et al 1992); a 26.5 kb segment from Xq28 is duplicated at 16p11.1 (Eichler et al 1996); and 16p11 is polymorphic for material duplicated from 6p25 (Z. . Moreover, chromosome 16-speci¢c repetitive sequences are duplicated on either side of the h16 centromere (Dauwerse et al 1992;Stallings et al 1992).…”

Structure of Chromosomal Duplicons and their Role in Mediating Human Genomic Disorders

“…In addition to the chromosome-specific duplicons described above, a large number of genomic segments have been identified in the last few years that map to multiple non-homologous chromosomes (termed transchromosomal duplicons) (Borden et al 1990;Wong et al 1990;Buiting et al 1992;Bernardi et al 1993;Tomlinson et al 1994;Eichler et al 1996Eichler et al , et al 1997Eichler et al , 1999Frippiat et al 1997;Kehrer-Sawatzki et al 1997;Regnier et al 1997;Zimonjic et al 1997;Eichler, 1998;Trask et al 1998a,b;Brand-Arpon et al 1999;Grewal et al 1999;Horvath et al 2000). Two regions of the human genome that seem unusually enriched for such transchromosomal duplication events are the pericentromeric (defined as the first Giemsa light or dark band flanking the primary constriction) and subtelomeric portions of chromosomes (Eichler 1998;Trask et al 1998a).…”

“…3d; Buiting et al 1992Buiting et al , 1998Amos-Landgraf et al 1999;Ji et al 1999). The END repeats are composed to a large extent of duplications of a huge gene, HERC2, although multiple rearrangements within the derived duplicons have occurred during evolution (Amos-Landgraf et al 1999;Ji et al 1999, Structure 2000).…”