Optical mapping of the 22q11.2DS region reveals complex repeat structures and preferred locations for non-allelic homologous recombination (NAHR).

Scientific Reports
Steven PastorBeverly S Emanuel

Abstract

The most prevalent microdeletion in humans occurs at 22q11.2, a region rich in chromosome-specific low copy repeats (LCR22s). The structure of this region has defied elucidation due to its size, regional complexity, and haplotype diversity, and is not well represented in the human genome reference. Most individuals with 22q11.2 deletion syndrome (22q11.2DS) carry a de novo hemizygous deletion of ~ 3 Mbp occurring by non-allelic homologous recombination (NAHR) mediated by LCR22s. In this study, optical mapping has been used to elucidate LCR22 structure and variation in 88 individuals in thirty 22q11.2DS families to uncover potential risk factors for germline rearrangements leading to 22q11.2DS offspring. Families were optically mapped to characterize LCR22 structures, NAHR locations, and genomic signatures associated with the deletion. Bioinformatics analyses revealed clear delineations between LCR22 structures in normal and deletion-containing haplotypes. Despite no explicit whole-haplotype predisposing configurations being identified, all NAHR events contain a segmental duplication encompassing FAM230 gene members suggesting preferred recombination sequences. Analysis of deletion breakpoints indicates that preferred recombinat...Continue Reading

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Citations

Dec 18, 2020·Nature Reviews. Cancer·Jeffery M Klco, Charles G Mullighan
Jul 8, 2021·Analytical Chemistry·Lahari UppuluriMing Xiao
Aug 3, 2021·Frontiers in Genetics·Lisanne VervoortJoris R Vermeesch

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Datasets Mentioned

BETA
AB261997.1
PRJNA640411

Methods Mentioned

BETA
PCR
chip

Software Mentioned

BLASTn
Bionano Solve
GeneMarker
GENCODE
Bionano Genomics
rpy2
Ensembl
RefAligner
stats
SciPy

Related Concepts

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22q11 Deletion Syndrome

22q11.2 deletion syndrome, also known as DiGeorge syndrome, is a congenital disorder caused by a partial deletion of chromosome 22. Symptoms include heart defects, poor immune system function, a cleft palate, complications related to low levels of calcium in the blood, and delayed development. Discover the latest research on this disease here.