A novel quantitative targeted analysis of X-chromosome Inactivation (XCI) using Nanopore sequencing

Johansson, JosefinUppsala universitet,Institutionen för immunologi, genetik och patologi,Science for Life Laboratory, SciLifeLab (author)

X-chromosome inactivation (XCI) analyses often assist in diagnostics of X-linked traits, however accurate assessment remains challenging with current methods. We developed a novel strategy using amplification-free Cas9 enrichment and Oxford nanopore technologies sequencing called XCI-ONT, to investigate and rigorously quantify XCI in human androgen receptor gene (AR) and human X-linked retinitis pigmentosa 2 gene (RP2). XCI-ONT measures methylation over 116 CpGs in AR and 58 CpGs in RP2, and separate parental X-chromosomes without PCR bias. We show the usefulness of the XCI-ONT strategy over the PCR-based golden standard XCI technique that only investigates one or two CpGs per gene. The results highlight the limitations of using the golden standard technique when the XCI pattern is partially skewed and the advantages of XCI-ONT to rigorously quantify XCI. This study provides a universal XCI-method on DNA, which is highly valuable in clinical and research framework of X-linked traits.

MEDICIN OCH HÄLSOVETENSKAP Medicinska och farmaceutiska grundvetenskaper Medicinsk genetik hsv//swe
MEDICAL AND HEALTH SCIENCES Basic Medicine Medical Genetics hsv//eng
X-chromosome inactivation
Cas9 enrichment
Amplification-free
Androgen receptor
HUMARA
X-linked retinitis pigmentosa 2
Oxford Nanopore Technologies
Medicinsk genetik
Medical Genetics

Lidéus, SarahUppsala universitet,Institutionen för immunologi, genetik och patologi,Science for Life Laboratory, SciLifeLab (author)
Höijer, IdaUppsala universitet,Institutionen för immunologi, genetik och patologi,Science for Life Laboratory, SciLifeLab(Swepub:uu)idaho846 (author)
Ameur, AdamUppsala universitet,Institutionen för immunologi, genetik och patologi,Science for Life Laboratory, SciLifeLab(Swepub:uu)adame789 (author)
Gudmundsson, Sanna,1989-Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.; Division of Genetics and Genomics, Boston Children’s Hospital, Harvard Medical School, Boston, MA, USA.(Swepub:uu)sangu463 (author)
Annerén, Göran,1945-Uppsala universitet,Institutionen för immunologi, genetik och patologi,Science for Life Laboratory, SciLifeLab(Swepub:uu)goraanne (author)
Bondeson, Marie-Louise,1960-Uppsala universitet,Institutionen för immunologi, genetik och patologi,Science for Life Laboratory, SciLifeLab(Swepub:uu)malobond (author)
Wilbe, MariaUppsala universitet,Institutionen för immunologi, genetik och patologi,Science for Life Laboratory, SciLifeLab(Swepub:uu)marwi726 (author)
Uppsala universitetInstitutionen för immunologi, genetik och patologi (creator_code:org_t)

By the author/editor: Johansson, Josef ...; Lidéus, Sarah; Höijer, Ida; Ameur, Adam; Gudmundsson, San ...; Annerén, Göran, ...; show more...; Bondeson, Marie- ...; Wilbe, Maria; show less...

About the subject

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Medical Genetics

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