title: Physical and genetic characterization reveals a pseudogene, an evolutionary junction, and unstable loci in distal Xq28.
abstract: A large portion of human Xq28 has been completely characterized but the interval between G6PD and Xqter has remained poorly understood. Because of a lack of stable, high-density clone coverage in this region, we constructed a 1.6-Mb bacterial and P1 artificial chromosome (BAC and PAC, respectively) contig to expedite mapping, structural and evolutionary analysis, and sequencing. The contig helped to reposition previously mismapped genes and to characterize the XAP135 pseudogene near the int22h-2 repeat. BAC clones containing the distal int22h repeats also demonstrated spontaneous rearrangements and sparse coverage, which suggested that they were unstable. Because the int22h repeats are involved in genetic diseases, we examined them in great apes to see if they have always been unstable. Differences in copy number among the apes, due to duplications and deletions, indicated that they have been unstable throughout their evolution. Taking another approach toward understanding the genomic nature of distal Xq28, we examined the homologous mouse region and found an evolutionary junction near the distal int22h loci that separated the human distal Xq28 region into two segments on the mouse X chromosome. Finally, haplotype analysis showed that a segment within Xq28 has resisted excessive interchromosomal exchange through great ape evolution, potentially accounting for the linkage disequilibrium recently reported in this region. Collectively, these data highlight some interesting features of the genomic sequence in Xq28 and will be useful for positional cloning efforts, mouse mutagenesis studies, and further evolutionary analyses.
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza 902E, Houston, TX 77030, USA.
authors.forename: Swaroop
authors.initials: S
authors.lastname: Aradhya
authors.forename: Hayley
authors.initials: H
authors.lastname: Woffendin
authors.forename: Penelope
authors.initials: P
authors.lastname: Bonnen
authors.forename: Nina S
authors.initials: NS
authors.lastname: Heiss
authors.forename: Takanori
authors.initials: T
authors.lastname: Yamagata
authors.forename: Teresa
authors.initials: T
authors.lastname: Esposito
authors.forename: Tiziana
authors.initials: T
authors.lastname: Bardaro
authors.forename: Annemarie
authors.initials: A
authors.lastname: Poustka
authors.forename: Michele
authors.initials: M
authors.lastname: D'Urso
authors.forename: Sue
authors.initials: S
authors.lastname: Kenwrick
authors.forename: David L
authors.initials: DL
authors.lastname: Nelson
mesh_terms: D000818:Animals; D002874:Chromosome Mapping; D019143:Evolution, Molecular; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics; D051379:Mice; D008969:Molecular Sequence Data; D020641:Polymorphism, Single Nucleotide; D011544:Pseudogenes / Q000235:genetics*; D017422:Sequence Analysis, DNA; D017385:Sequence Homology; D014960:X Chromosome / Q000235:genetics* / Q000648:ultrastructure