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- 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.
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Project Highlights:
- Project-wide: DGAP has analyzed the features of 77 breakpoints from 40 apparently balanced chromosomal rearrangements associated with developmental anomalies. In most case, multiple systems are involved. Unsuspected genomic imbalances and cryptic rearrangments were found, but less frequently than has been previously reported. Click the link to read our article in the American Jounral of Human Genetics (2008; 82:712-722).
- DGAP123 and DGAP200: Autism, a neurodevelopmental disorder
of complex etiology, resulted from chromosomal rearrangement involving neurexin
1 (NRXN1) at 2p16.3 in two independent subjects [Am J Hum Genet, 2008;
82:199-207].
- DGAP025: In humans and mice, chromodomain helicase DNA binding protein 2 (CHD2) discruption causes scoliosis [Am J Med Genet A, 2008; 146A:1117-1127].
- DGAP089, DGAP104, DGAP174, and DGAP205: We describe five individuals
who share phenotypically related CNS malformation and in some cases urinary tract
defects, and also haploinsufficience for the NFIA transcription factor gene due
to chromosomal translocation or deletion [PLoS Genet, 2007; 3:830-843].
- DGAP095: Diacylglycerol kinase delta (DGKD) disruption results in seizures in humans and mice [Am J Hum Genet, 2007; 80:792-799].
- DGAP107: Disruption of ROBO2 is associated with urinary tract anomalies and confers risk of vesicoureteral reflux [Am J Hum Genet, 2007; 80:616-632].
- DGAP016: N-myristoyltransferase (NMT2), which is
highly expressed in the testes, was implicated as a cause of testicular hypoplasia
[Am J Med Genet A, 2007; 143A:1796-1798].
- DGAP090: Methylthioadenosine phosphorylase (MTAP) results in impaired hearing [Am J Med Genet A, 2007; 143A:1630-1639].
- 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].
- 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, 2007; 143A:2668-2674 and Am J Med Genet A, 2006; 143A:107-111].
- DGAP011: Hypogonadotropic hypogonadism and cleft lip and palate
can be caused by a balanced translocation producing haploinsufficiency for FGFR1 [Journal of Medical Genetics, 2005; 42:666-72)].
- DGAP103: Constitutional rearrangement of the architectural
factor HMGA2 results in a novel human phenotype including overgrowth and
lipomas [American Journal of Human Genetics, 2005; 72:340-348].
- Project-wide: DGAP contributes to the Research Article on Human chromosome 7: DNA sequence and biology in Science (2003; 300:767-72) [PDF] and its 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].
| DGAP Cases |
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Cases in database |
>200 |
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Cases from the NIGMS Human
Genetic Cell Repository |
29 |
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Cases collected by
DGAP |
136 |
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|
|
| FISH Mapping |
|
|
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Breakpoints FISH mapped |
170 |
|
DGAP cases
FISH mapped |
85 |
|
Breakpoints mapped
to a single BAC clone |
116 |
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DGAP cases with at least one breakpoint
mapped to a single clone |
72 |
|
|
|
| Breakpoint Characterization |
|
|
|
Breakpoints
mapped
to a single BAC clone |
116 |
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Macrodeletions detected (>600 kb) |
12 |
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Breakpoints within
non-genic region |
19 |
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Breakpoints within conserverd
non-genic region |
4 |
|
Genes interrupted by a
breakpoint |
37 |
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Breakpoints known to be within an
intron |
23 |
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Breakpoints known to be
within an exon |
1 |
|
Breakpoint within 3'
untranslated region |
1 |
|
Cases with at least one
breakpoint sequenced |
14 |
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Breakpoints sequenced |
27 |
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Microdeletions at the
breakpoint (ranging from 1
to 5,115 bp) |
15 |
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Duplications at the breakpoint |
4 |
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Insertions at the
breakpoint |
11 |
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No sequence gain or loss from
chromosome |
5 |
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Breakpoint within
repetitive sequences |
15 |
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Alu |
4 |
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LINE |
5 |
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LTR |
2 |
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SINE |
3 |
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| Fusion Products |
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Cases with predicted fusion proteins |
3 |
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| Model Organisms |
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Mouse |
19 |
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Fly |
1 |
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