DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage

Abstract

Chromosome 17 is unusual among the human chromosomes in many respects. It is the largest human autosome with orthology to only a single mouse chromosome1, mapping entirely to the distal half of mouse chromosome 11. Chromosome 17 is rich in protein-coding genes, having the second highest gene density in the genome2,3. It is also enriched in segmental duplications, ranking third in density among the autosomes4. Here we report a finished sequence for human chromosome 17, as well as a structural comparison with the finished sequence for mouse chromosome 11, the first finished mouse chromosome. Comparison of the orthologous regions reveals striking differences. In contrast to the typical pattern seen in mammalian evolution5,6, the human sequence has undergone extensive intrachromosomal rearrangement, whereas the mouse sequence has been remarkably stable. Moreover, although the human sequence has a high density of segmental duplication, the mouse sequence has a very low density. Notably, these segmental duplications correspond closely to the sites of structural rearrangement, demonstrating a link between duplication and rearrangement. Examination of the main classes of duplicated segments provides insight into the dynamics underlying expansion of chromosome-specific, low-copy repeats in the human genome.

Testing Chromosomal Phylogenies and Inversion Breakpoint Reuse in Drosophila

“…Segmental duplications represent 5% of the human genome (Bailey et al 2002) and 2% of the mouse genome (Bailey et al 2004a). They induce rearrangements by unequal crossing over (Shaffer and Lupski 2000) and are hotspots for mammalian chromosomal evolution (Bailey et al 2004b;Zody et al 2006). The Drosophila genome is quite different from that of mammals: the amount of repetitive DNA is much lower (5 vs. 44%) and the fraction of segmental duplications is negligible (Lander et al 2001;Celniker and Rubin 2003).…”

17q24.2 microdeletions: a new syndromal entity with intellectual disability, truncal obesity, mood swings and hallucinations

“…1 Hence, various microdeletion and duplication syndromes on chromosome 17 have been reported. [2][3][4][5][6][7] Deletions of chromosome band 17q24.2 are, however, rare.…”

A functional analysis of GABARAP on 17p13.1 by knockdown zebrafish

“…For these reasons, human chromosome 17 has been implicated in a wide range of human diseases. 16 The proximal chromosome 17p arm, in which 423% of the genomic sequence consists of low-copy repeats, is associated with a wide variety of recurrent chromosomal aberrations resulting from nonallelic homologous recombination between low-copy repeats, including four wellknown genomic disorders: Charcot-Marie-Tooth type1A disease; hereditary neuropathy with liability to pressure palsies, which results from reciprocal duplication or deletion of 17p12; 17 Smith-Magenis syndrome and the Potocki-Lupski syndrome, which is associated with deletion or duplication of 17p11.2. [18][19][20][21] Miller-Dieker syndrome characterized by lissencephaly and characteristic facial features is caused by subtelomeric deletion of 17p, in which PAFAH1B/LIS1 is included, 22 and heterozygous duplication of PAFAH1B/LIS1 has been reported to cause neurodevelopmental delays.…”