Analysis of the DNA sequence and duplication history of human chromosome 15

Abstract

Here we present a finished sequence of human chromosome 15, together with a high-quality gene catalogue. As chromosome 15 is one of seven human chromosomes with a high rate of segmental duplication, we have carried out a detailed analysis of the duplication structure of the chromosome. Segmental duplications in chromosome 15 are largely clustered in two regions, on proximal and distal 15q; the proximal region is notable because recombination among the segmental duplications can result in deletions causing Prader-Willi and Angelman syndromes. Sequence analysis shows that the proximal and distal regions of 15q share extensive ancient similarity. Using a simple approach, we have been able to reconstruct many of the events by which the current duplication structure arose. We find that most of the intrachromosomal duplications seem to share a common ancestry. Finally, we demonstrate that some remaining gaps in the genome sequence are probably due to structural polymorphisms between haplotypes; this may explain a significant fraction of the gaps remaining in the human genome.

The Golgin Coiled-Coil Proteins of the Golgi Apparatus

“…Most are present in the repeats of an element that derived from GOLGA2, the gene encoding GM130 on chromosome 9, but has duplicated on the long arm of chromosome 15. These repeats appear to have been generated by genome rearrangements during primate evolution as similar repeats are found in the genome of the macaque, an old-world (Zody et al 2006). These genes are unlikely to all be pseudogenes as they are predicted to encode proteins and are well represented in EST databases.…”

CNV Concordance in 1,097 MZ Twin Pairs

“…CNVs in 15q11.2 have been associated with Prader-Willi and Angelman syndromes (Donlon, 1988), schizophrenia (Stefansson et al, 2008), behavioral disturbances (Doornbos et al, 2009), developmental and language delay (Burnside et al, 2011), epilepsy (de Kovel et al, 2010, and more recently with decreased fecundity, dyslexia, dyscalculia, and brain structure changes that are associated with schizophrenia and dyslexia (Stefansson et al, 2014). The 15q11.2 region is one of the genomic regions rich in segmental duplications (Zody et al, 2006), which makes CNVs in these regions harder to detect and therefore more likely to contain false positives, but also means this region is enriched for CNVs and more prone to de novo CNV mutations through non-allelic homologous recombination (Redon et al, 2006). MZ twins provide the opportunity for an extra QC step for the relatively noisy microarray CNV data.…”

A Human-Specific α7-Nicotinic Acetylcholine Receptor Gene in Human Leukocytes: Identification, Regulation and the Consequences of CHRFAM7A Expression

“…At the same time, however, they noted the presence of a second, human-specific partially duplicated α7nAChR-like gene that localized 1.6 Mb 5′ upstream from human CHRNA7 (4). With only 386 amino acids of the α7nAChR channel domain, this new human-specific gene was initially called dupα7nAChR and found to encode an amino terminus that originated from a kinase gene on chromosome 3 (5). The ultimate genetic rearrangement, which occurred after the divergence of humans from other primates (6,7), created a new, distinct and human-specific open reading frame (ORF) that produces an exclusively human α7nAChR now called CHRFAM7A (8).…”