Leveraging the T2T assembly to resolve rare and pathogenic inversions in reference genome gaps DOI Creative Commons

Kristine Bilgrav Sæther,

Jesper Eisfeldt,

Jesse D. Bengtsson

et al.

Genome Research, Journal Year: 2024, Volume and Issue: 34(11), P. 1785 - 1797

Published: Nov. 1, 2024

Chromosomal inversions (INVs) are particularly challenging to detect due their copy-number neutral state and association with repetitive regions. Inversions represent about 1/20 of all balanced structural chromosome aberrations can lead disease by gene disruption or altering regulatory regions dosage-sensitive genes in cis . Short-read genome sequencing (srGS) only resolve ∼70% cytogenetically visible referred clinical diagnostic laboratories, likely breakpoints Here, we study 12 long-read (lrGS) ( n = 9) srGS 3) nine them. In four cases, the inversion breakpoint region was missing from at least one human reference genomes (GRCh37, GRCh38, T2T-CHM13) a agnostic analysis needed. One these an INV9 mappable de novo assembled lrGS data using T2T-CHM13 disrupts EHMT1 consistent Mendelian diagnosis (Kleefstra syndrome 1; MIM#610253). Next, pairwise comparison between T2T-CHM13, GRCh37, as well chimpanzee bonobo, show that hundreds megabases sequence reference, highlighting primate contribute genomic diversity. Aligning population indicated variable individuals. Our emphasizes is necessary maximize value for optimal detection diagnostics. These results highlight importance leveraging diverse comprehensive unsolved molecular cases rare diseases.

Language: Английский

Advancing evolutionary medicine with complete primate genomes and advanced biotechnologies DOI
Kaiyue Ma, Xiangyu Yang, Yafei Mao

et al.

Trends in Genetics, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 1, 2024

Language: Английский

Citations

3
Leveraging the T2T assembly to resolve rare and pathogenic inversions in reference genome gaps DOI Creative Commons

Kristine Bilgrav Sæther,

Jesper Eisfeldt,

Jesse D. Bengtsson

et al.

Genome Research, Journal Year: 2024, Volume and Issue: 34(11), P. 1785 - 1797

Published: Nov. 1, 2024

Chromosomal inversions (INVs) are particularly challenging to detect due their copy-number neutral state and association with repetitive regions. Inversions represent about 1/20 of all balanced structural chromosome aberrations can lead disease by gene disruption or altering regulatory regions dosage-sensitive genes in cis . Short-read genome sequencing (srGS) only resolve ∼70% cytogenetically visible referred clinical diagnostic laboratories, likely breakpoints Here, we study 12 long-read (lrGS) ( n = 9) srGS 3) nine them. In four cases, the inversion breakpoint region was missing from at least one human reference genomes (GRCh37, GRCh38, T2T-CHM13) a agnostic analysis needed. One these an INV9 mappable de novo assembled lrGS data using T2T-CHM13 disrupts EHMT1 consistent Mendelian diagnosis (Kleefstra syndrome 1; MIM#610253). Next, pairwise comparison between T2T-CHM13, GRCh37, as well chimpanzee bonobo, show that hundreds megabases sequence reference, highlighting primate contribute genomic diversity. Aligning population indicated variable individuals. Our emphasizes is necessary maximize value for optimal detection diagnostics. These results highlight importance leveraging diverse comprehensive unsolved molecular cases rare diseases.

Language: Английский

Citations

2