• Our Objective:
  
  
  • To identify apparently balanced chromosomal rearrangements in patients with multiple congenital anomalies and then to use these chromosomal rearrangements to map and identify genes that are disrupted or dysregulated in critical stages of human development.
  • View a brief slide show that summarizes our project.
    
    
• Project Highlights:
  
  
  
  • DGAP011: Hypogonadotropic hypogonadism and cleft lip and palate caused by a balanced translocation producing haploinsufficiency for FGFR1.  Read the abstract and get the full report at the Journal of Medical Genetics (2005; 42:666-72). 
    
  • DGAP103: Constitutional Rearrangement of the Architectural Factor HMGA2: A Novel Human Phenotype Including Overgrowth and Lipomas.  Read the full report in the American Journal of Human Genetics (2005; 72:340-8).
    
  • DGAP contributes to the Research Article on Human chromosome 7: DNA sequence and biology in Science (2003; 300:767-72) [PDF][Supplemental On-line Material].
    
  • DGAP012: The breakpoint has been mapped to BAC CTD-3193o13 (GenBank AC010336 ) and near cosmid LLNLF-138h2 (GenBank AC008975).  See the FISH image.  This case was reported in Nature's Genome issue on Feb. 15, 2001 [HTML][PDF].
    
  • DGAP151:  SUMO1 haploinsufficiency and loss of post-translational sumoyalation leads to cleft lip and palate [Science, 2006; 313:1751].
    
  • DGAP003:  The translocation in DGAP003 indentifies candidate loci for Zimmermann-Laband syndrome at 3p14.3 [Am J Med Genet A, 2006, 143A:107-111].
    
  • DGAP128: Synaptotagmin (SYT14 ) was associated with cerebral atrophy, seizures and developmental delay in a 12 year-old macrocephalic female [Am J Med Genet A, 2007, 143A:558-563]. 
    
  • DGAP090: Methylthioadenosine Phosphorylase (MTAP) results in impaired hearing [Am J Med Genet A, 2007, in press].
    
  • DGAP107: Disruption of ROBO2 is associated with urinary tract anomalies and confers risk of vesicoureteral reflux [Am J Hum Genet, 2007, 80:616-632].
    
  • DGAP095:  Diacylglycerol kinase delta (DGKD) disruption results in seizures in humans and mice [Am J Hum Genet, 2007, 80:792-799].
    
    
• Progress Summary:

DGAP Cases
	Cases in database	>200
	Cases from the NIGMS Human Genetic Cell Repository	29
	Cases collected by DGAP	136
FISH Mapping
	Breakpoints FISH mapped	170
	DGAP cases FISH mapped	85
	Breakpoints mapped to a single BAC clone	116
	DGAP cases with at least one breakpoint mapped to a single clone	72
Breakpoint Characterization
	Breakpoints mapped to a single BAC clone	116
	Macrodeletions detected (>600 kb)	12
	Breakpoints within non-genic region	19
	Breakpoints within conserverd non-genic region	4
	Genes interrupted by a breakpoint	37
	Breakpoints known to be within an intron	23
	Breakpoints known to be within an exon	1
	Breakpoint within 3' untranslated region	1
	Cases with at least one breakpoint sequenced	14
	Breakpoints sequenced	27
	Microdeletions at the breakpoint (ranging from 1 to 5,115 bp)	15
	Duplications at the breakpoint	4
	Insertions at the breakpoint	11
	No sequence gain or loss from chromosome	5
	Breakpoint within repetitive sequences	15
	Alu	4
	LINE	5
	LTR	2
	SINE	3
Fusion Products
	Cases with predicted fusion proteins	3
Model Organisms
	Mouse	19
	Fly	1