PMID- 10953236
OWN - NLM
STAT- MEDLINE
DCOM- 20001011
LR  - 20191104
IS  - 0898-929X (Print)
IS  - 0898-929X (Linking)
VI  - 12 Suppl 1
DP  - 2000
TI  - VI. Genome structure and cognitive map of Williams syndrome.
PG  - 89-107
AB  - 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.
FAU - Korenberg, J R
AU  - Korenberg JR
AD  - Cedars-Sinai Medical Center and University of California, Los Angeles, USA.
FAU - Chen, X N
AU  - Chen XN
FAU - Hirota, H
AU  - Hirota H
FAU - Lai, Z
AU  - Lai Z
FAU - Bellugi, U
AU  - Bellugi U
FAU - Burian, D
AU  - Burian D
FAU - Roe, B
AU  - Roe B
FAU - Matsuoka, R
AU  - Matsuoka R
LA  - eng
GR  - HD33113/HD/NICHD NIH HHS/United States
GR  - HG00313/HG/NHGRI NIH HHS/United States
PT  - Clinical Trial
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Cogn Neurosci
JT  - Journal of cognitive neuroscience
JID - 8910747
RN  - 0 (Genetic Markers)
RN  - 9007-49-2 (DNA)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Blotting, Southern
MH  - Brain/growth & development
MH  - Brain Mapping
MH  - Child
MH  - Child, Preschool
MH  - Chromosome Mapping
MH  - Chromosomes/genetics/ultrastructure
MH  - Cognition/*physiology
MH  - DNA/chemistry/genetics
MH  - Female
MH  - Genetic Markers
MH  - *Genome, Human
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Male
MH  - Phenotype
MH  - Polymorphism, Genetic/genetics
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Williams Syndrome/*genetics/*psychology
EDAT- 2000/08/23 11:00
MHDA- 2000/10/14 11:01
CRDT- 2000/08/23 11:00
PHST- 2000/08/23 11:00 [pubmed]
PHST- 2000/10/14 11:01 [medline]
PHST- 2000/08/23 11:00 [entrez]
AID - 10.1162/089892900562002 [doi]
PST - ppublish
SO  - J Cogn Neurosci. 2000;12 Suppl 1:89-107. doi: 10.1162/089892900562002.