Frequent Loss of Genome Gap Region in 4p16.3 Subtelomere in Early-Onset Type 2 Diabetes Mellitus

Kudo, Hirohito; Emi, Mitsuru; Ishigaki, Yasushi; Tsunoda, Uiko; Hinokio, Yoshinori; Ishii, Miho; Sato, Hidenori; Yamada, Tetsuya; Katagiri, Hideki; Oka, Yoshitomo

doi:10.1155/2011/498460

Cited by 10 publications

(17 citation statements)

References 62 publications

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“…This contact may explain why specific subtelomeric regions preferentially associate and share a high degree of sequence identity despite mapping to nonhomologous chromosomes (Hirai et al 2005). The high sequence identity among subtelomeric regions has been an important consideration in understanding changes in the chromatin environment related to some human genomic disorders (Gerber et al 2011;Kudo et al 2011;van der Maarel et al 2011).…”

mentioning

confidence: 99%

The evolution of African great ape subtelomeric heterochromatin and the fusion of human chromosome 2

Ventura¹,

Catacchio²,

Sajjadian³

et al. 2012

Genome Res.

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Chimpanzee and gorilla chromosomes differ from human chromosomes by the presence of large blocks of subterminal heterochromatin thought to be composed primarily of arrays of tandem satellite sequence. We explore their sequence composition and organization and show a complex organization composed of specific sets of segmental duplications that have hyperexpanded in concert with the formation of subterminal satellites. These regions are highly copy number polymorphic between and within species, and copy number differences involving hundreds of copies can be accurately estimated by assaying read-depth of next-generation sequencing data sets. Phylogenetic and comparative genomic analyses suggest that the structures have arisen largely independently in the two lineages with the exception of a few seed sequences present in the common ancestor of humans and African apes. We propose a model where an ancestral humanchimpanzee pericentric inversion and the ancestral chromosome 2 fusion both predisposed and protected the chimpanzee and human genomes, respectively, to the formation of subtelomeric heterochromatin. Our findings highlight the complex interplay between duplicated sequences and chromosomal rearrangements that rapidly alter the cytogenetic landscape in a short period of evolutionary time.

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mentioning

confidence: 99%

The evolution of African great ape subtelomeric heterochromatin and the fusion of human chromosome 2

Ventura¹,

Catacchio²,

Sajjadian³

et al. 2012

Genome Res.

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“…Whole-genome screening with a copy number variation by Kudo et al in T2DM patients revealed that loss of copy number within the 1.3-Mb of chromosome 4p16.3 sub-telomeric region (contains 34 putative genes)was associated with early-onset T2DM. (Kudo et al, 2011).…”

Section: Telomere and Diabetes: Genetic Perspectivementioning

confidence: 99%

Telomere Length and Aging

Muzumdar¹,

Atzmon²

2012

Reviews on Selected Topics of Telomere Biology

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“… 28 , 29 The Agilent high-density custom-made array is a high-resolution array based on the comparative genomic hybridisation method, with 60 mer probes synthesised in situ as oligonucleotide arrays, at a spacing of 100 bp to 500 bp. 8 , 17 , 30 In the present study, the CNV region analysed on 9q22.31 and its flanking region contained the coding regions of the ASPN gene and the extracellular matrix protein 2 ( ECM2 ) gene ( Figs 2 and 3 ). This region contains multiple low-copy repeats in a small region of the genome, such as the ASPN D, which account for the instability of this region and trigger a copy number loss by an unequal crossing-over or end-joining event.…”

Section: Discussionmentioning

confidence: 74%

Copy number loss in the region of the ASPN gene in patients with acetabular dysplasia

Sekimoto

Ishii

Emi

et al. 2017

Bone & Joint Research

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ObjectivesWe have previously investigated an association between the genome copy number variation (CNV) and acetabular dysplasia (AD). Hip osteoarthritis is associated with a genetic polymorphism in the aspartic acid repeat in the N-terminal region of the asporin (ASPN) gene; therefore, the present study aimed to investigate whether the CNV of ASPN is involved in the pathogenesis of AD.MethodsAcetabular coverage of all subjects was evaluated using radiological findings (Sharp angle, centre-edge (CE) angle, acetabular roof obliquity (ARO) angle, and minimum joint space width). Genomic DNA was extracted from peripheral blood leukocytes. Agilent’s region-targeted high-density oligonucleotide tiling microarray was used to analyse 64 female AD patients and 32 female control subjects. All statistical analyses were performed using EZR software (Fisher’s exact probability test, Pearson’s correlation test, and Student’s t-test).ResultsCNV analysis of the ASPN gene revealed a copy number loss in significantly more AD patients (9/64) than control subjects (0/32; p = 0.0212). This loss occurred within a 60 kb region on 9q22.31, which harbours the gene for ASPN. The mean radiological parameters of these AD patients were significantly worse than those of the other subjects (Sharp angle, p = 0.0056; CE angle, p = 0.0076; ARO angle, p = 0.0065), and all nine patients required operative therapy such as total hip arthroplasty or pelvic osteotomy. Moreover, six of these nine patients had a history of operative or conservative therapy for developmental dysplasia of the hip.ConclusionsCopy number loss within the region harbouring the ASPN gene on 9q22.31 is associated with severe AD. A copy number loss in the ASPN gene region may play a role in the aetiology of severe AD.Cite this article: T. Sekimoto, M. Ishii, M. Emi, S. Kurogi, T. Funamoto, Y. Yonezawa, T. Tajima, T. Sakamoto, H. Hamada, E. Chosa. Copy number loss in the region of the ASPN gene in patients with acetabular dysplasia: ASPN CNV in acetabular dysplasia. Bone Joint Res 2017;6:439–445. DOI: 10.1302/2046-3758.67.BJR-2016-0094.R1.

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Frequent Loss of Genome Gap Region in 4p16.3 Subtelomere in Early-Onset Type 2 Diabetes Mellitus

Cited by 10 publications

References 62 publications

The evolution of African great ape subtelomeric heterochromatin and the fusion of human chromosome 2

The evolution of African great ape subtelomeric heterochromatin and the fusion of human chromosome 2

Telomere Length and Aging

Copy number loss in the region of the ASPN gene in patients with acetabular dysplasia

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