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Characterization of the past and current duplication activities in the human 22q11.2 region.

Guo X, Freyer L, Morrow B, Zheng D - BMC Genomics (2011)

Bottom Line: Segmental duplications (SDs) on 22q11.2 (LCR22), serve as substrates for meiotic non-allelic homologous recombination (NAHR) events resulting in several clinically significant genomic disorders.Some subunits have expanded more actively than others, and young Alu SINEs, are associated much more frequently with duplicated sequences that have undergone active expansion, confirming their role in mediating recombination events.Our study indicates that AluYs are implicated in the past and current duplication events, and moreover suggests that DNA rearrangements in 22q11.2 genomic disorders perhaps do not occur randomly but involve both actively expanded duplication subunits and Alu elements.

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Affiliation: Department of Neurology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.

ABSTRACT

Background: Segmental duplications (SDs) on 22q11.2 (LCR22), serve as substrates for meiotic non-allelic homologous recombination (NAHR) events resulting in several clinically significant genomic disorders.

Results: To understand the duplication activity leading to the complicated SD structure of this region, we have applied the A-Bruijn graph algorithm to decompose the 22q11.2 SDs to 523 fundamental duplication sequences, termed subunits. Cross-species syntenic analysis of primate genomes demonstrates that many of these LCR22 subunits emerged very recently, especially those implicated in human genomic disorders. Some subunits have expanded more actively than others, and young Alu SINEs, are associated much more frequently with duplicated sequences that have undergone active expansion, confirming their role in mediating recombination events. Many copy number variations (CNVs) exist on 22q11.2, some flanked by SDs. Interestingly, two chromosome breakpoints for 13 CNVs (mean length 65 kb) are located in paralogous subunits, providing direct evidence that SD subunits could contribute to CNV formation. Sequence analysis of PACs or BACs identified extra CNVs, specifically, 10 insertions and 18 deletions within 22q11.2; four were more than 10 kb in size and most contained young AluYs at their breakpoints.

Conclusions: Our study indicates that AluYs are implicated in the past and current duplication events, and moreover suggests that DNA rearrangements in 22q11.2 genomic disorders perhaps do not occur randomly but involve both actively expanded duplication subunits and Alu elements.

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Many CNVs are flanked by paralogous subunits and/or Alu SINES. (A) A total of 13 previously detected CNVs have their endpoints located to paralogous subunits. All subunits are colored as Figure 2, in addition, with blue color for gain CNVs and red for loss CNVs. One CNV marked with a "*" is found by our clone mapping (Figure 6). Sequence features around (± 1 kb) the insertion sites of ten gain CNVs (B) or the two breakpoints of 18 loss CNVs (C) from current clone mapping analysis. In (B) and (C) arrows point to the breakpoints and coordinates and other detailed information is in Table 3.
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Figure 7: Many CNVs are flanked by paralogous subunits and/or Alu SINES. (A) A total of 13 previously detected CNVs have their endpoints located to paralogous subunits. All subunits are colored as Figure 2, in addition, with blue color for gain CNVs and red for loss CNVs. One CNV marked with a "*" is found by our clone mapping (Figure 6). Sequence features around (± 1 kb) the insertion sites of ten gain CNVs (B) or the two breakpoints of 18 loss CNVs (C) from current clone mapping analysis. In (B) and (C) arrows point to the breakpoints and coordinates and other detailed information is in Table 3.

Mentions: Total of 13 previously detected CNVs (from the Database of Genomic Variants) with breakpoints located to the paralogous subunits (see Figure 7A)


Characterization of the past and current duplication activities in the human 22q11.2 region.

Guo X, Freyer L, Morrow B, Zheng D - BMC Genomics (2011)

Many CNVs are flanked by paralogous subunits and/or Alu SINES. (A) A total of 13 previously detected CNVs have their endpoints located to paralogous subunits. All subunits are colored as Figure 2, in addition, with blue color for gain CNVs and red for loss CNVs. One CNV marked with a "*" is found by our clone mapping (Figure 6). Sequence features around (± 1 kb) the insertion sites of ten gain CNVs (B) or the two breakpoints of 18 loss CNVs (C) from current clone mapping analysis. In (B) and (C) arrows point to the breakpoints and coordinates and other detailed information is in Table 3.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3040729&req=5

Figure 7: Many CNVs are flanked by paralogous subunits and/or Alu SINES. (A) A total of 13 previously detected CNVs have their endpoints located to paralogous subunits. All subunits are colored as Figure 2, in addition, with blue color for gain CNVs and red for loss CNVs. One CNV marked with a "*" is found by our clone mapping (Figure 6). Sequence features around (± 1 kb) the insertion sites of ten gain CNVs (B) or the two breakpoints of 18 loss CNVs (C) from current clone mapping analysis. In (B) and (C) arrows point to the breakpoints and coordinates and other detailed information is in Table 3.
Mentions: Total of 13 previously detected CNVs (from the Database of Genomic Variants) with breakpoints located to the paralogous subunits (see Figure 7A)

Bottom Line: Segmental duplications (SDs) on 22q11.2 (LCR22), serve as substrates for meiotic non-allelic homologous recombination (NAHR) events resulting in several clinically significant genomic disorders.Some subunits have expanded more actively than others, and young Alu SINEs, are associated much more frequently with duplicated sequences that have undergone active expansion, confirming their role in mediating recombination events.Our study indicates that AluYs are implicated in the past and current duplication events, and moreover suggests that DNA rearrangements in 22q11.2 genomic disorders perhaps do not occur randomly but involve both actively expanded duplication subunits and Alu elements.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Neurology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.

ABSTRACT

Background: Segmental duplications (SDs) on 22q11.2 (LCR22), serve as substrates for meiotic non-allelic homologous recombination (NAHR) events resulting in several clinically significant genomic disorders.

Results: To understand the duplication activity leading to the complicated SD structure of this region, we have applied the A-Bruijn graph algorithm to decompose the 22q11.2 SDs to 523 fundamental duplication sequences, termed subunits. Cross-species syntenic analysis of primate genomes demonstrates that many of these LCR22 subunits emerged very recently, especially those implicated in human genomic disorders. Some subunits have expanded more actively than others, and young Alu SINEs, are associated much more frequently with duplicated sequences that have undergone active expansion, confirming their role in mediating recombination events. Many copy number variations (CNVs) exist on 22q11.2, some flanked by SDs. Interestingly, two chromosome breakpoints for 13 CNVs (mean length 65 kb) are located in paralogous subunits, providing direct evidence that SD subunits could contribute to CNV formation. Sequence analysis of PACs or BACs identified extra CNVs, specifically, 10 insertions and 18 deletions within 22q11.2; four were more than 10 kb in size and most contained young AluYs at their breakpoints.

Conclusions: Our study indicates that AluYs are implicated in the past and current duplication events, and moreover suggests that DNA rearrangements in 22q11.2 genomic disorders perhaps do not occur randomly but involve both actively expanded duplication subunits and Alu elements.

Show MeSH
Related in: MedlinePlus