Analysis of the Cat Eye Syndrome Critical Region in Humans and the Region of Conserved Synteny in Mice: A Search for Candidate Genes at or near the Human Chromosome 22 Pericentromere

Abstract

We have sequenced a 1.1-Mb region of human chromosome 22q containing the dosage-sensitive gene(s) responsible for cat eye syndrome (CES) as well as the 450-kb homologous region on mouse chromosome 6. Fourteen putative genes were identified within or adjacent to the human CES critical region (CESCR), including three known genes (IL-17R,ATP6E, and BID) and nine novel genes, based on EST identity. Two putative genes (CECR3 and CECR9) were identified, in the absence of EST hits, by comparing segments of human and mouse genomic sequence around two solitary amplified exons, thus showing the utility of comparative genomic sequence analysis in identifying transcripts. Of the 14 genes, 10 were confirmed to be present in the mouse genomic sequence in the same order and orientation as in human. Absent from the mouse region of conserved synteny areCECR1, a promising CES candidate gene from the center of the contig, neighboring CECR4, and CECR7 andCECR8, which are located in the gene-poor proximal 400 kb of the contig. This latter proximal region, located ∼1 Mb from the centromere, shows abundant duplicated gene fragments typical of pericentromeric DNA. The margin of this region also delineates the boundary of conserved synteny between the CESCR and mouse chromosome 6. Because the proximal CESCR appears abundant in duplicated segments and, therefore, is likely to be gene poor, we consider the putative genes identified in the distal CESCR to represent the majority of candidate genes for involvement in CES.

A 600 kb triplication in the cat eye syndrome critical region causes anorectal, renal and preauricular anomalies in a three-generation family

“…As the original patient described by Mears et al 13 died at 17 days of life, a contribution to physical and mental development of these distally located genes BCL2L13, BID and MICAL3 cannot be ruled out. 12 In the amplification found in the current family, six genes, CECR2, SLC25A18, ATP6V1E1, BCL2L13, BID and MICAL3 (latter only partially amplified), are involved. The family members carrying the intrachromosomal amplification have anal atresia (3 out of 4) and/or preauricular pits or tags (4 out of 4).…”

“…FISH analysis of the CES region was performed in the index patient with BAC clones RP11-155N18 and RP11-958H20, located in 22q11.1 and 22q11.1q11.21, respectively, and together covering about 470 kb of the CES critical region, 12,13 including the genes CECR1, CECR2, CECR4, CECR5, CECR6 and IL17RA. FISH experiments were performed using standard procedures 14 with alphoid probe p190.22 as a control probe for centromere 22.…”

Sequence Analysis of LRPPRC and Its SEC1 Domain Interaction Partners Suggests Roles in Cytoskeletal Organization, Vesicular Trafficking, Nucleocytosolic Shuttling, and Chromosome Activity

“…CECR2 is one of the few expressed sequences that maps within the region near the human chromosome 22 pericentromere that is linked to the multi-phenotype cat eye syndrome [38]. Combined HMM and 3D-PSSM searches suggested a homology domain structure for CECR2 summarized in Fig.…”

Molecular cloning of chicken Cecr2 and its expression during chicken embryo development

“…Cecr2 was first identified in the region q11.2 of human chromosome 22 (Footz et al, 2001). The full length of the coding region is 4392bp, containing an AT hook and a bromodomain that are present in many chromatin remodeling proteins.…”