Comparative mapping of the human 22q11 chromosomal region and the orthologous region in mice reveals complex changes in gene organization

Puech, Anne; Saint-Jore, Bruno; Funke, Birgit; Gilbert, Debra J.; Sirotkin, Howard I.; Copeland, Neal G.; Jenkins, Nancy A.; Kucherlapati, Raju; Morrow, Bernice E.; Skoultchi, Arthur I.

doi:10.1073/pnas.94.26.14608

Cited by 92 publications

(63 citation statements)

References 60 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The correlation observed between human chro- et al (1996) mosomal abnormalities leading to neoplasia with a translocation event and evolutionary breakpoints was suggested previously by previous studies (Carver and Stubbs 1997;Puech et al 1997). However, in most cases, limited chromosomal regions were taken into account, matching generally only humans and mice (Amadou et al 1995;Weterman et al 1996).…”

Section: Comparative Gene Mapping Demonstrates a High Number Of Chromsupporting

confidence: 52%

Comparative Gene Mapping: A Fine-Scale Survey of Chromosome Rearrangements between Ruminants and Humans

Schibler¹,

Vaiman²,

Oustry³

et al. 1998

Genome Res.

159

132

View full text Add to dashboard Cite

A total of 202 genes were cytogenetically mapped to goat chromosomes, multiplying by five the total number of regional gene localizations in domestic ruminants (255). This map encompasses 249 and 173 common anchor loci regularly spaced along human and murine chromosomes, respectively, which makes it possible to perform a genome-wide comparison between three mammalian orders. Twice as many rearrangements as revealed by ZOO-FISH were observed. The average size of conserved fragments could be estimated at 27 and 8 cm with humans and mice, respectively. The position of evolutionary breakpoints often correspond with human chromosome sites known to be vulnerable to rearrangement in neoplasia. Furthermore, 75 microsatellite markers, 30 of which were isolated from gene-containing bacterial artificial chromosomes (BACs), were added to the previous goat genetic map, achieving 88% genome coverage. Finally, 124 microsatellites were cytogenetically mapped, which made it possible to physically anchor and orient all the linkage groups. We believe that this comprehensive map will speed up positional cloning projects in domestic ruminants and clarify some aspects of mammalian chromosomal evolution.[The sequence data described in this paper have been submitted to the GenBank data library under accession nos. G40978–G41020,AF083170–AF083184, AF088286, AF08287, AF083401–AF083406, AF082884, and AF082885.]

show abstract

Section: Comparative Gene Mapping Demonstrates a High Number Of Chromsupporting

confidence: 52%

Comparative Gene Mapping: A Fine-Scale Survey of Chromosome Rearrangements between Ruminants and Humans

Schibler¹,

Vaiman²,

Oustry³

et al. 1998

Genome Res.

159

132

View full text Add to dashboard Cite

show abstract

“…Some reports have indicated that 22q11DS might account for up to 1-2% of subjects diagnosed with SZ (2, 3). All of the genes, except one, in the human 22q11.2 locus exist on mouse chromosome 16, although the organization is different (4). This has facilitated the generation of mouse models of 22q11DS, which carry different-size hemizygous deletions of the 22q11-related region (5)(6)(7)(8).…”

mentioning

confidence: 99%

Deficits in microRNA-mediated Cxcr4/Cxcl12 signaling in neurodevelopmental deficits in a 22q11 deletion syndrome mouse model

Toritsuka

Kimoto

Muraki

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Significance 22q11 deletion syndrome (22q11DS) is a chromosome disorder that frequently accompanies psychiatric conditions such as schizophrenia. However, it remains elusive how the chromosomal microdeletion causes the mental manifestation. Here we show that a 22q11DS mouse model has deficits in the development of interneurons and hippocampal dentate gyrus and that DiGeorge syndrome critical region gene 8 (Dgcr8) , a microprocessor of microRNA and one of the genes in 22q11, underlies these neurodevelopmental abnormalities. Dgcr8 regulates Chemokine receptor 4/Chemokine ligand 12 (Cxcr4/Cxcl12; Sdf1) signaling, which is indispensable for interneuron and dentate gyrus development. Finally, we observe decreased expression of CXCL12 in olfactory neurons from sporadic schizophrenia. Given the increased risk of 22q11DS in schizophrenia, the overall study suggests that CXCR4/CXCL12 signaling may represent a common downstream mediator in the pathophysiology of schizophrenia.

show abstract

“…The mouse deletion (Df1) spans Ϸ1 Mb and encompasses 18 mouse homologs of genes deleted in del22q11 syndrome patients. All the genes within Df1 are represented in the 1.5-Mb deletion (and therefore also in the 3-Mb deletion), although there are some changes in gene order caused by ancestral rearrangements (10,11). Similar to human patients, heterozygously deleted mice (Df1͞ϩ) show reduced penetrance of del22q11 syndrome-like heart defects, namely interrupted aortic arch type-B, right aortic arch, aberrant origin of the right subclavian artery, overriding aorta, pulmonary stenosis, and ventricular septal defects.…”

mentioning

confidence: 99%

Genetic factors are major determinants of phenotypic variability in a mouse model of the DiGeorge/ del22q11 syndromes

Taddei

Morishima

Huynh

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

103

View full text Add to dashboard Cite

The del22q11 syndrome is associated with a highly variable phenotype despite the uniformity of the chromosomal deletion that causes the disease in most patients. Df1͞؉ mice, which model del22q11, present with reduced penetrance of cardiovascular defects similar to those seen in deleted patients but not with other del22q11-like findings. The reduced penetrance of cardiovascular defects is caused by the ability of mutant embryos to recover from a fourth pharyngeal arch artery growth abnormality that is fully penetrant in early embryos. Here we show that genetic background has a major effect on penetrance of cardiovascular defects by affecting this embryonic recovery process. This effect could not be explained by allelic variation at the haploid locus, and it is likely to be caused by genetic modifiers elsewhere in the genome. We also show that genetic factors control extension of the Df1͞؉ phenotype to include thymic and parathyroid anomalies, establishing the Df1 mouse as a model for the genetic analysis of three major features of human del22q11 syndrome. We found that in Df1͞؉ mice, as in human patients, expression of the heart and thymic phenotypes are essentially independent from each other, suggesting that they may be controlled by different genetic modifiers. These data provide a framework for our understanding of phenotypic variability in patients with del22q11 syndrome and the tools for its genetic dissection.

show abstract

Comparative mapping of the human 22q11 chromosomal region and the orthologous region in mice reveals complex changes in gene organization

Cited by 92 publications

References 60 publications

Comparative Gene Mapping: A Fine-Scale Survey of Chromosome Rearrangements between Ruminants and Humans

Comparative Gene Mapping: A Fine-Scale Survey of Chromosome Rearrangements between Ruminants and Humans

Deficits in microRNA-mediated Cxcr4/Cxcl12 signaling in neurodevelopmental deficits in a 22q11 deletion syndrome mouse model

Genetic factors are major determinants of phenotypic variability in a mouse model of the DiGeorge/ del22q11 syndromes

Contact Info

Product

Resources

About