Cited by 93Genomic variations and chromosomal abnormalitiesGenetic Syndromes and ImprintingChromosomal and Genetic Variations

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

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Makoff, Andrew J, Flomen, Rachel H·2007·Genome biology

Abstract

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].”

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  1. Leonard S Gault J Moore T Hopkins J Robinson M Olincy A Adler LE Cloninger CR Kaufmann CA Tsuang MT Further investigation of a chromosome 15 locus in schizophrenia: analysis of affected sibpairs from the NIMH Genetics Initiative. Am J Med Genet 1998 81 308 312 9674976 10.1002/(SICI)1096-8628(19980710)81:4<308::AID-AJMG6>3.0.CO;2-P · DOI
  2. Stassen HH Bridler R Hagele S Hergersberg M Mehmann B Schinzel A Weisbrod M Scharfetter C Schizophrenia and smoking: evidence for a common neurobiological basis? Am J Med Genet 2000 96 173 177 10893492 10.1002/(SICI)1096-8628(20000403)96:2<173::AID-AJMG10>3.0.CO;2-U · DOI

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Authors
Makoff, A. J., & Flomen, R. H.
Affiliations
King's College London (GB)
Corresponding author
Makoff, Andrew J
Venue
Genome biology
Published
2007-06-15
Volume
8
Issue
6
Pages
R114-R114
ISSN
  • 1465-6906 (ISSN-L)
  • 1474-760X
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
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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