VI. Genome structure and cognitive map of Williams syndrome
Abstract
Williams syndrome (WMS) is a most compelling model of human cognition, of human genome organization, and of evolution. Due to a deletion in chromosome band 7q11.23, subjects have cardiovascular, connective tissue, and neurodevelopmental deficits. Given the striking peaks and valleys in neurocognition including deficits in visual-spatial and global processing, preserved language and face processing, hypersociability, and heightened affect, the goal of this work has been to identify the genes that are responsible, the cause of the deletion, and its origin in primate evolution. To do this, we have generated an integrated physical, genetic, and transcriptional map of the WMS and flanking regions using multicolor metaphase and interphase fluorescence in situ hybridization (FISH) of bacterial artificial chromosomes (BACs) and P1 artificial chromosomes (PACs), BAC end sequencing, PCR gene marker and microsatellite, large-scale sequencing, cDNA library, and database analyses. The results indicate the genomic organization of the WMS region as two nested duplicated regions flanking a largely single-copy region. There are at least two common deletion breakpoints, one in the centromeric and at least two in the telomeric repeated regions. Clones anchoring the unique to the repeated regions are defined along with three new pseudogene families. Primate studies indicate an evolutionary hot spot for chromosomal inversion in the WMS region. A cognitive phenotypic map of WMS is presented, which combines previous data with five further WMS subjects and three atypical WMS subjects with deletions; two larger (deleted for D7S489L) and one smaller, deleted for genes telomeric to FZD9, through LIMK1, but not WSCR1 or telomeric. The results establish regions and consequent gene candidates for WMS features including mental retardation, hypersociability, and facial features. The approach provides the basis for defining pathways linking genetic underpinnings with the neuroanatomical, functional, and behavioral consequences that result in human cognition.
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Williams syndrome is caused by a deletion of 25-30 genes in the q11.23 region of chromosome 7 that spans approximately 1.5 megabases.
“The cause of this disorder has been determined to be a deletion of 25–30 genes in the q11.23 region of either maternal or paternal chromosome 7 that spans approximately 1.5 megabases (Ewart et al., 1993; Korenberg et al., 2000; Lowery et al., 1995; Schubert, 2009).”
From Oxytocin and vasopressin systems in genetic syndromes and neurodevelopmental disorders (2014) · cites this paper as Korenberg et al., 2000
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- Authors
- Korenberg, J. R., Chen, X.-N., Hirota, H., Lai, Z., Bellugi, U., Burian, D., Roe, B., & Matsuoka, R.
- Affiliations
- Cedars-Sinai Medical Center (US)
- Salk Institute for Biological Studies (US)
- University of Oklahoma (US)
- Tokyo Women's Medical University (JP)
- Venue
- Journal of Cognitive Neuroscience
- Publisher
- MIT Press - Journals
- Published
- 2000-03-01
- Volume
- 12
- Issue
- Supplement 1
- Pages
- 89-107
- ISSN
- 0898-929X (ISSN-L)
- 1530-8898
- OpenAlex
- W2154826895
- Cited by
- 285
- References
- 54
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 4 · 2023: 6 · 2022: 6 · 2021: 7 · 2020: 6 · 2019: 8 · 2018: 3 · 2017: 6 · 2016: 9 · 2015: 13 · 2014: 10 · 2013: 11 · 2012: 9
- FWCI
- 3.49
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Cognitive Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r01hg000313-09)
- National Human Genome Research Institute (HG00313)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD33113, P01HD033113)
- Topics
- Life Sciences › Neuroscience › Developmental Neuroscience › Williams Syndrome Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomic variations and chromosomal abnormalities
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Keywords
- Williams syndrome, chromosome 7q11.23 deletion, genome organization, chromosomal inversions, pseudogenes, deletion breakpoints, neurocognitive phenotype, hypersociability, intellectual disability, facial dysmorphism, candidate genes, primate evolution
- MeSH terms
- Adolescent, Adult, Brain, Brain Mapping, Child, Child, Preschool, Chromosome Mapping, Chromosomes, Cognition, DNA, Female, Genetic Markers, Humans, Male, Phenotype, Polymorphism, Genetic, Blotting, Southern, Genome, Human, In Situ Hybridization, Fluorescence, Williams Syndrome, Reverse Transcriptase Polymerase Chain Reaction
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