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miRNA and miRNA target genes in copy number variations occurring in individuals with intellectual disability.

Qiao Y, Badduke C, Mercier E, Lewis SM, Pavlidis P, Rajcan-Separovic E - BMC Genomics (2013)

Bottom Line: Our results show that 1).The number of miRNAs is significantly higher in de novo or DECIPHER CNVs than in familial or common CNV subgroups (P < 0.01). 2). miRNAs with brain related functions are more prevalent in de novo CNV groups compared to common CNV groups. 3).Systematic analysis of expression/function of miRNAs in addition to coding genes integral to CNVs could uncover new causes of ID.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Pathology and Lab Medicine, BC Child and Family Research Institute, University of British Columbia, Vancouver, BC V5Z 4H4, Canada.

ABSTRACT

Background: MicroRNAs (miRNAs) are a family of short, non-coding RNAs modulating expression of human protein coding genes (miRNA target genes). Their dysfunction is associated with many human diseases, including neurodevelopmental disorders. It has been recently shown that genomic copy number variations (CNVs) can cause aberrant expression of integral miRNAs and their target genes, and contribute to intellectual disability (ID).

Results: To better understand the CNV-miRNA relationship in ID, we investigated the prevalence and function of miRNAs and miRNA target genes in five groups of CNVs. Three groups of CNVs were from 213 probands with ID (24 de novo CNVs, 46 familial and 216 common CNVs), one group of CNVs was from a cohort of 32 cognitively normal subjects (67 CNVs) and one group of CNVs represented 40 ID related syndromic regions listed in DECIPHER (30 CNVs) which served as positive controls for CNVs causing or predisposing to ID. Our results show that 1). The number of miRNAs is significantly higher in de novo or DECIPHER CNVs than in familial or common CNV subgroups (P < 0.01). 2). miRNAs with brain related functions are more prevalent in de novo CNV groups compared to common CNV groups. 3). More miRNA target genes are found in de novo, familial and DECIPHER CNVs than in the common CNV subgroup (P < 0.05). 4). The MAPK signaling cascade is found to be enriched among the miRNA target genes from de novo and DECIPHER CNV subgroups.

Conclusions: Our findings reveal an increase in miRNA and miRNA target gene content in de novo versus common CNVs in subjects with ID. Their expression profile and participation in pathways support a possible role of miRNA copy number change in cognition and/or CNV-mediated developmental delay. Systematic analysis of expression/function of miRNAs in addition to coding genes integral to CNVs could uncover new causes of ID.

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Comparison of weighted median number of miRNAs/Mb in different CNV subgroups.
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Figure 1: Comparison of weighted median number of miRNAs/Mb in different CNV subgroups.

Mentions: The number and loci of miRNAs in different CNV subgroups were obtained using Galaxy (https://main.g2.bx.psu.edu/) and miRBase (http://www.mirbase.org/). To avoid bias caused by varying CNV size, the number of miRNA in each CNV region was weighted by the size of the CNV, and expressed as miRNA/Mb. The weighted median number of miRNAs/Mb in each CNV subgroup is shown in Table 1 and was compared among different pairs of CNV subgroups using the Wilcoxon rank-sum test. We found the median number of miRNAs/Mb is significantly higher in de novo and DECIPHER CNVs than familial or common CNVs from cases, and common CNVs from controls (P < 0.01) (Table 1 and Figure 1). However, the average miRNA/Mb between the common and pathogenic subgroups is comparable which is likely due to the presence of few very small common CNVs with high miRNA density (for example, 8 miRNAs within one common CNV at 16p13 (16,322,499-16,682,499).


miRNA and miRNA target genes in copy number variations occurring in individuals with intellectual disability.

Qiao Y, Badduke C, Mercier E, Lewis SM, Pavlidis P, Rajcan-Separovic E - BMC Genomics (2013)

Comparison of weighted median number of miRNAs/Mb in different CNV subgroups.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3750877&req=5

Figure 1: Comparison of weighted median number of miRNAs/Mb in different CNV subgroups.
Mentions: The number and loci of miRNAs in different CNV subgroups were obtained using Galaxy (https://main.g2.bx.psu.edu/) and miRBase (http://www.mirbase.org/). To avoid bias caused by varying CNV size, the number of miRNA in each CNV region was weighted by the size of the CNV, and expressed as miRNA/Mb. The weighted median number of miRNAs/Mb in each CNV subgroup is shown in Table 1 and was compared among different pairs of CNV subgroups using the Wilcoxon rank-sum test. We found the median number of miRNAs/Mb is significantly higher in de novo and DECIPHER CNVs than familial or common CNVs from cases, and common CNVs from controls (P < 0.01) (Table 1 and Figure 1). However, the average miRNA/Mb between the common and pathogenic subgroups is comparable which is likely due to the presence of few very small common CNVs with high miRNA density (for example, 8 miRNAs within one common CNV at 16p13 (16,322,499-16,682,499).

Bottom Line: Our results show that 1).The number of miRNAs is significantly higher in de novo or DECIPHER CNVs than in familial or common CNV subgroups (P < 0.01). 2). miRNAs with brain related functions are more prevalent in de novo CNV groups compared to common CNV groups. 3).Systematic analysis of expression/function of miRNAs in addition to coding genes integral to CNVs could uncover new causes of ID.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Pathology and Lab Medicine, BC Child and Family Research Institute, University of British Columbia, Vancouver, BC V5Z 4H4, Canada.

ABSTRACT

Background: MicroRNAs (miRNAs) are a family of short, non-coding RNAs modulating expression of human protein coding genes (miRNA target genes). Their dysfunction is associated with many human diseases, including neurodevelopmental disorders. It has been recently shown that genomic copy number variations (CNVs) can cause aberrant expression of integral miRNAs and their target genes, and contribute to intellectual disability (ID).

Results: To better understand the CNV-miRNA relationship in ID, we investigated the prevalence and function of miRNAs and miRNA target genes in five groups of CNVs. Three groups of CNVs were from 213 probands with ID (24 de novo CNVs, 46 familial and 216 common CNVs), one group of CNVs was from a cohort of 32 cognitively normal subjects (67 CNVs) and one group of CNVs represented 40 ID related syndromic regions listed in DECIPHER (30 CNVs) which served as positive controls for CNVs causing or predisposing to ID. Our results show that 1). The number of miRNAs is significantly higher in de novo or DECIPHER CNVs than in familial or common CNV subgroups (P < 0.01). 2). miRNAs with brain related functions are more prevalent in de novo CNV groups compared to common CNV groups. 3). More miRNA target genes are found in de novo, familial and DECIPHER CNVs than in the common CNV subgroup (P < 0.05). 4). The MAPK signaling cascade is found to be enriched among the miRNA target genes from de novo and DECIPHER CNV subgroups.

Conclusions: Our findings reveal an increase in miRNA and miRNA target gene content in de novo versus common CNVs in subjects with ID. Their expression profile and participation in pathways support a possible role of miRNA copy number change in cognition and/or CNV-mediated developmental delay. Systematic analysis of expression/function of miRNAs in addition to coding genes integral to CNVs could uncover new causes of ID.

Show MeSH
Related in: MedlinePlus