Comprehensive whole genome sequence analyses yields novel genetic and structural insights for Intellectual Disability
<h3>Background</h3><p dir="ltr">Intellectual Disability (ID) is among the most common global disorders, yet etiology is unknown in ~30% of patients despite clinical assessment. Whole genome sequencing (WGS) is able to interrogate the entire genome, providing potential to...
محفوظ في:
| المؤلف الرئيسي: | |
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| مؤلفون آخرون: | , , , , , , , , , , , , , , |
| منشور في: |
2017
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إضافة وسم
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| الملخص: | <h3>Background</h3><p dir="ltr">Intellectual Disability (ID) is among the most common global disorders, yet etiology is unknown in ~30% of patients despite clinical assessment. Whole genome sequencing (WGS) is able to interrogate the entire genome, providing potential to diagnose idiopathic patients.</p><h3>Methods</h3><p dir="ltr">We conducted WGS on eight children with idiopathic ID and brain structural defects, and their normal parents; carrying out an extensive data analyses, using standard and discovery approaches.</p><h3>Results</h3><p dir="ltr">We verified <i>de novo</i> pathogenic single nucleotide variants (SNV) in <i>ARID1B c.1595delG</i> and <i>PHF6 c.820C > T</i>, potentially causative <i>de novo</i> two base indels in <i>SQSTM1 c.115_116delinsTA</i> and <i>UPF1 c.1576_1577delinsA,</i> and <i>de novo</i> SNVs in <i>CACNB3 c.1289G > A,</i> and <i>SPRY4 c.508 T > A,</i> of uncertain significance. We report results from a large secondary control study of 2081 exomes probing the pathogenicity of the above genes. We analyzed structural variation by four different algorithms including <i>de novo</i> genome assembly. We confirmed a likely contributory 165 kb <i>de novo</i> heterozygous 1q43 microdeletion missed by clinical microarray. The <i>de novo</i> assembly resulted in unmasking hidden genome instability that was missed by standard re-alignment based algorithms. We also interrogated regulatory sequence variation for known and hypothesized ID genes and present useful strategies for WGS data analyses for non-coding variation.</p><h3>Conclusion</h3><p dir="ltr">This study provides an extensive analysis of WGS in the context of ID, providing genetic and structural insights into ID and yielding diagnoses.</p><h2>Other Information</h2><p dir="ltr">Published in: BMC Genomics<br>License: <a href="https://creativecommons.org/licenses/by/4.0/deed.en" rel="noreferrer noopener" target="_blank">https://creativecommons.org/licenses/by/4.0/</a> <br>See article on publisher's website: <a href="https://dx.doi.org/10.1186/s12864-017-3671-0" target="_blank">https://dx.doi.org/10.1186/s12864-017-3671-0</a></p> |
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