Detailed analysis of 15q11–q14 sequence corrects errors and gaps in the public access sequence to fully reveal large segmental duplications at breakpoints for Prader-Willi, Angelman, and inv dup(15) syndromes
Open accessAbstract
BACKGROUND: Chromosome 15 contains many segmental duplications, including some at 15q11-q13 that appear to be responsible for the deletions that cause Prader-Willi and Angelman syndromes and for other genomic disorders. The current version of the human genome sequence is incomplete, with seven gaps in the proximal region of 15q, some of which are flanked by duplicated sequence. We have investigated this region by conducting a detailed examination of the sequenced genomic clones in the public database, focusing on clones from the RP11 library that originates from one individual. RESULTS: Our analysis has revealed assembly errors, including contig NT_078094 being in the wrong orientation, and has enabled most of the gaps between contigs to be closed. We have constructed a map in which segmental duplications are no longer interrupted by gaps and which together reveals a complex region. There are two pairs of large direct repeats that are located in regions consistent with the two classes of deletions associated with Prader-Willi and Angelman syndromes. There are also large inverted repeats that account for the formation of the observed supernumerary marker chromosomes containing two copies of the proximal end of 15q and associated with autism spectrum disorders when involving duplications of maternal origin (inv dup[15] syndrome). CONCLUSION: We have produced a segmental map of 15q11-q14 that reveals several large direct and inverted repeats that are incompletely and inaccurately represented on the current human genome sequence. Some of these repeats are clearly responsible for deletions and duplications in known genomic disorders, whereas some may increase susceptibility to other disorders.
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The ∼1 Mb interval between HERC2 and APBA2 contains a cluster of segmental duplications that serves as a frequent deletion breakpoint (BP3) involved in Prader-Willi and Angelman syndromes.
“the ∼1 Mb interval between HERC2 and APBA2 contains a cluster of segmental duplications that serves as a frequent deletion breakpoint (BP3) involved in Prader-Willi and Angelman syndromes [45].”
From Genetic Architecture of Skin and Eye Color in an African-European Admixed Population (2013) · cites this paper as [45]
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- Authors
- Makoff, A. J., & Flomen, R. H.
- Affiliations
- King's College London (GB)
- Corresponding author
- Makoff, Andrew J
- ORCID
- Flomen, Rachel H
- Venue
- Genome biology
- Published
- 2007-06-15
- Volume
- 8
- Issue
- 6
- Pages
- R114-R114
- ISSN
- 1465-6906 (ISSN-L)
- 1474-760X
- PMC
- PMC2394762
- OpenAlex
- W2101253405
- Cited by
- 87
- References
- 44
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 1 · 2023: 2 · 2022: 4 · 2021: 12 · 2020: 3 · 2019: 4 · 2018: 1 · 2017: 1 · 2016: 4 · 2015: 4 · 2014: 3 · 2013: 3 · 2012: 6
- FWCI
- 4.29
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Genome biology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Research Portal (King's College London) (submittedVersion)
- Funders
- National Alliance for Research on Schizophrenia and Depression
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomic variations and chromosomal abnormalities
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Syndromes and Imprinting
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Chromosomal and Genetic Variations
- Keywords
- segmental duplication, Prader-Willi syndrome, Angelman syndrome, genome assembly errors, direct repeats, inverted repeats, supernumerary marker chromosome, autism spectrum disorder, genomic disorders, chromosome 15, human genome sequence
- MeSH terms
- Chromosome Mapping, Chromosomes, Human, Pair 15, Humans, Prader-Willi Syndrome, Genome, Human, Angelman Syndrome, Chromosome Breakage, Gene Duplication
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