A novel approach for simultaneous detection of structural and single-nucleotide variants based on a combination of chromosome conformation capture and exome sequencing

Gridina, M.; Lagunov, T.; Belokopytova, P.; Torgunakov, N.; Nuriddinov, M.; Nurislamov, A.; Nazarenko, L.; Kashevarova, A.; Lopatkina, M.; Belyaeva, E.; Salyukova, O.; Cheremnykh, A.; Suhanova, N.; Minzhenkova, M.; Markova, Z.; Demina, N.; Stepanchuk, Y.; Khabarova, A.; Yan, A.; Valeev, E.; Koksharova, G.; Grigoreva, E.; Kokh, N.; Lukjanova, T.; Maximova, Y.; Musatova, E.; Shabanova, E.; Kechin, A.; Khrapov, E.; Boyarskih, U.; Ryzhkova, O.; Suntsova, M.; Matrosova, A.; Karoli, M.; Manakhov, A.; Filipenko, M.; Rogaev, E.; Shilova, N.; Lebedev, I.; Fishman, V.

doi:10.1101/2024.01.26.577292

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bioRxiv · 10.1101/2024.01.26.577292

A novel approach for simultaneous detection of structural and single-nucleotide variants based on a combination of chromosome conformation capture and exome sequencing

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Abstract

Effective molecular diagnosis of congenital diseases hinges on comprehensive genomic analysis, traditionally reliant on various methodologies specific to each variant type--whole exome or genome sequencing for single nucleotide variants (SNVs), array CGH for copy-number variants (CNVs), and microscopy for structural variants (SVs). We introduce a novel, integrative approach combining exome sequencing with chromosome conformation capture, termed Exo-C. This method enables the concurrent identification of SNVs in clinically relevant genes and SVs across the genome and allows analysis of heterozygous and mosaic carriers. Enhanced with targeted long-read sequencing, Exo-C evolves into a cost-efficient solution capable of resolving complex SVs at base-pair accuracy. Through several case studies, we demonstrate how Exo-Cs multifaceted application can effectively uncover diverse causative variants and elucidate disease mechanisms in patients with rare disorders.

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Gridina, M., Lagunov, T., Belokopytova, P., Torgunakov, N., Nuriddinov, M., Nurislamov, A., Nazarenko, L., Kashevarova, A., Lopatkina, M., Belyaeva, E., Salyukova, O., Cheremnykh, A., Suhanova, N., Minzhenkova, M., Markova, Z., Demina, N., Stepanchuk, Y., Khabarova, A., Yan, A., Valeev, E., Koksharova, G., Grigoreva, E., Kokh, N., Lukjanova, T., Maximova, Y., Musatova, E., Shabanova, E., Kechin, A., Khrapov, E., Boyarskih, U., Ryzhkova, O., Suntsova, M., Matrosova, A., Karoli, M., Manakhov, A., Filipenko, M., Rogaev, E., Shilova, N., Lebedev, I., Fishman, V.. 2024-01-29. A novel approach for simultaneous detection of structural and single-nucleotide variants based on a combination of chromosome conformation capture and exome sequencing. https://doi.org/10.1101/2024.01.26.577292

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