Failure to Find DUP25 in Patients with Anxiety Disorders, in Control Individuals, or in Previously Reported Positive Control Cell Lines

Tabiner, Melody; Youings, Sheila; Dennis, N R; Baldwin, David S.; Buis, C; Mayers, Andrew; Jacobs, Patricia A.; Crolla, John A.

doi:10.1086/367777

Cited by 48 publications

(39 citation statements)

References 5 publications

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“…By broadening the phenotype even more, including comorbid anxiety disorder, childhood anxiety disorders, or continuous anxiety disorder diagnosis since age 13, the authors observed evidence for linkage to chromosome 10q. Finally, a Spanish group detected the presence of a large interstitial duplication of chromosome 15q24-26 in pedigrees segregating PD and joint laxity (Gratacos et al, 2001), a finding that was not replicated in another sample (Tabiner et al, 2003). Oddly, evidence for linkage between this duplication and panic occurred when the phenotype was maximally broadened to comprise PD, AG, joint laxity, and social phobia (lod B5).…”

Section: Discussionmentioning

confidence: 99%

Evidence for Genetic Linkage Between a Polymorphism in the Adenosine 2A Receptor and Panic Disorder

Hamilton

Slager

León

et al. 2003

Neuropsychopharmacol

139

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Data from clinical and behavioral pharmacological studies have implicated adenosine in anxiety behaviors, while genetic studies have suggested that adenosine receptors may be associated with panic disorder. We have undertaken an analysis of several DNA sequence variations in the adenosine 2A receptor (ADORA2A) in a large sample of panic disorder pedigrees. Individuals from 70 panic disorder pedigrees, and 83 child-parent 'trios', were genotyped at five single-nucleotide polymorphisms (SNPs) in and near the ADORA2A gene and were analyzed for genetic linkage and association. Linkage analysis revealed elevated LOD scores for a silent substitution (1083C/T, SNP-4) in the second coding exon. This SNP has been previously reported to be associated with panic disorder. We observed a maximal heterogeneity LOD score of 2.98 (y ¼ 0) under a recessive genetic model and narrow diagnostic model. Other SNPs showed no evidence for linkage. Association tests were not significant for any of the five ADORA2A SNPs. When SNP haplotypes were assessed in the triads with TRANSMIT, one 3-marker haplotype (SNPs 1, 4, 5) was nominally significantly associated with panic disorder (p ¼ 0.029). Pairwise estimations of linkage disequilibrium between the SNPs showed strong patterns of linkage disequilibrium across the ADORA2A locus. Analyses carried out by broadening the panic disorder phenotype to include agoraphobia continued to support linkage to ADORA2A. Our findings provide evidence for a susceptibility locus for panic disorder, and possibly including agoraphobia, either within the ADORA2A gene or in a nearby region of chromosome 22, and serves as the first successful candidate gene replication study in panic disorder.

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Section: Discussionmentioning

confidence: 99%

Evidence for Genetic Linkage Between a Polymorphism in the Adenosine 2A Receptor and Panic Disorder

Hamilton

Slager

León

et al. 2003

Neuropsychopharmacol

139

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“…Moreover interstitial duplications in 15q24-26, engulfing Lingo-1 in its entirety, have been significantly associated with panic, agoraphobia and social phobia in families, and with panic disorder in non-familial cases, with 90% of patients fitting the diagnosis of one or more of the anxiety disorders having the chromosomic duplication (Gratacòs et al, 2001). Despite a number of groups trying to reproduce this finding, none have successfully done so (Henrichsen et al, 2004;Tabiner et al, 2003;Weiland et al, 2003;Zhu et al, 2004), therefore the finding by Gratacòs et. al.…”

Section: Lingo-1 Signaling: a New Role In Psychiatric Disordersmentioning

confidence: 99%

A decade from discovery to therapy: Lingo-1, the dark horse in neurological and psychiatric disorders

Andrews

Fernandez

2015

Neuroscience & Biobehavioral Reviews

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Leucine-rich repeat and immunoglobulin domain-containing protein (Lingo-1) is a potent negative regulator of neuron and oligodendrocyte survival, neurite extension, axon regeneration, oligodendrocyte differentiation, axonal myelination and functional recovery; all processes highly implicated in numerous brain-related functions. Although playing a major role in developmental brain functions, the potential application of Lingo-1 as a therapeutic target for the treatment of neurological disorders has so far been underestimated. A number of preclinical studies have shown that various methods of antagonizing Lingo-1 results in neuronal and oligodendroglial survival, axonal growth and remyelination; however to date literature has only detailed applications of Lingo-1 targeted therapeutics with a focus primarily on myelination disorders such as multiple sclerosis and spinal cord injury; omitting important information regarding Lingo-1 signaling cofactors. Here, we provide for the first time a complete and thorough review of the implications of Lingo-1 signaling in a wide range of neurological and psychiatric disorders, and critically examine its potential as a novel therapeutic target for these disorders. Disciplines Medicine and Health Sciences | Social and Behavioral Sciences AbstractLeucine-rich repeat and immunoglobulin domain-containing protein (Lingo-1) is a potent negative regulator of neuron and oligodendrocyte survival, neurite extension, axon regeneration, oligodendrocyte differentiation, axonal myelination and functional recovery; all processes highly implicated in numerous brain-related functions. Although playing a major role in developmental brain functions, the potential application of Lingo-1 as a therapeutic target for the treatment of neurological disorders has so far been under-estimated. A number of preclinical studies have shown that various methods of antagonizing Lingo-1 results in neuronal and oligodendroglial survival, axonal growth and remyelination; however to date literature has only detailed applications of Lingo-1 targeted therapeutics with a focus primarily on myelination disorders such as multiple sclerosis and spinal cord injury; omitting important information regarding Lingo-1 signaling co-factors. Here, we provide for the first time a complete and thorough review of the implications of Lingo-1 signaling in a wide range of neurological and psychiatric disorders, and critically examine its potential as a novel therapeutic target for these disorders.

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“…The observation both here and elsewhere (Depinet et al 1997) that rearrangements which lead to neocentromere emergence on chromosome 15 are mitotic in origin is interesting in this respect, as mitotic instability of the DUP25 duplicons has already been reported within a clinical context . However, the latter data were recently questioned by Tabiner et al (2003).…”

Section: Duplicons and Neocentromere Emergence On 15qmentioning

confidence: 99%

Neocentromeres in 15q24-26 Map to Duplicons Which Flanked an Ancestral Centromere in 15q25

Ventura¹,

Mudge²,

Palumbo³

et al. 2003

Genome Res.

115

111

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The existence of latent centromeres has been proposed as a possible explanation for the ectopic emergence of neocentromeres in humans. This hypothesis predicts an association between the position of neocentromeres and the position of ancient centromeres inactivated during karyotypic evolution. Human chromosomal region 15q24-26 is one of several hotspots where multiple cases of neocentromere emergence have been reported, and it harbors a high density of chromosome-specific duplicons, rearrangements of which have been implicated as a susceptibility factor for panic and phobic disorders with joint laxity. We investigated the evolutionary history of this region in primates and found that it contains the site of an ancestral centromere which became inactivated about 25 million years ago, after great apes/Old World monkeys diverged. This inactivation has followed a noncentromeric chromosomal fission of an ancestral chromosome which gave rise to phylogenetic chromosomes XIV and XV in human and great apes. Detailed mapping of the ancient centromere and two neocentromeres in 15q24-26 has established that the neocentromere domains map approximately 8 Mb proximal and 1.5 Mb distal of the ancestral centromeric region, but that all three map within 500 kb of duplicons, copies of which flank the centromere in Old World Monkey species. This suggests that the association between neocentromere and ancestral centromere position on this chromosome may be due to the persistence of recombinogenic duplications accrued within the ancient pericentromere, rather than the retention of “centromere-competent” sequences per se. The high frequency of neocentromere emergence in the 15q24-26 region and the high density of clinically important duplicons are, therefore, understandable in the light of the evolutionary history of this region.

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Failure to Find DUP25 in Patients with Anxiety Disorders, in Control Individuals, or in Previously Reported Positive Control Cell Lines

Cited by 48 publications

References 5 publications

Evidence for Genetic Linkage Between a Polymorphism in the Adenosine 2A Receptor and Panic Disorder

Evidence for Genetic Linkage Between a Polymorphism in the Adenosine 2A Receptor and Panic Disorder

A decade from discovery to therapy: Lingo-1, the dark horse in neurological and psychiatric disorders

Neocentromeres in 15q24-26 Map to Duplicons Which Flanked an Ancestral Centromere in 15q25

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