A 3-Mb Map of a Large Segmental Duplication Overlapping the α7-Nicotinic Acetylcholine Receptor Gene (CHRNA7) at Human 15q13–q14

Riley, Brien P.; Williamson, Magali; Collier, David; Wilkie, Hazel; Makoff, Andrew

doi:10.1006/geno.2002.6694

Cited by 107 publications

(109 citation statements)

References 24 publications

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“…The gene is transcribed, as mRNA sequences have been detected. 17,68 Two recent studies demonstrated that co-expression of CHRFAM7A with CHRNA7 significantly reduced acetylcholine currents. 69,70 This appeared to be a posttranslational effect, and the presence of the 2-bp deletion in exon 6 of CHRFAM7A further reduced these currents.…”

Section: Discussionmentioning

confidence: 99%

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Association between the 2-bp deletion polymorphism in the duplicated version of the alpha7 nicotinic receptor gene and P50 sensory gating

et al. 2012

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There is considerable evidence implicating the 15q13.3 region in neuropsychiatric disorders, with the a7 nicotinic receptor gene CHRNA7 the most plausible candidate. This region has multiple duplications and many copy number variants (CNVs). A common CNV involves a partial duplication of CHRNA7 (CHRFAM7A), which occurs in either orientation. We examined the distribution of these alternative genomic arrangements in a large cohort of psychiatric patients, their relatives and controls using the 2-bp deletion polymorphism as a marker for the orientation of CHRFAM7A. We investigated three common alleles for association with psychosis and with the P50 sensory gating deficit, which is strongly associated with psychosis and strongly linked to 15q13.3. We found significant within-family association with P50 (empirical P ¼ 0.004), which is robust to population stratification. Most of the effect came from the 2-bp deletion allele, which tags the variant of CHRFAM7A in the same orientation as CHRNA7. This allele is associated with the presence of the P50 sensory gating deficit (empirical P ¼ 0.0006). Tests comparing within-family and between-family components of association suggest considerable population stratification in the sample. We found no evidence for association with psychosis, but this may reflect lower power using this phenotype. Four out of six previous association studies found association of different psychiatric phenotypes with the same 2-bp deletion allele.

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Section: Discussionmentioning

confidence: 99%

“…15,16 However, 15q13.3 is a complex region in the midst of many large segmental duplications. 17,18 These are highly variable, resulting in several different copy number variants (CNVs).…”

Section: Introductionmentioning

confidence: 99%

Association between the 2-bp deletion polymorphism in the duplicated version of the alpha7 nicotinic receptor gene and P50 sensory gating

et al. 2012

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“…The latter model is supported by mouse knockout studies that have established a link between telomere dysfunction, increased epithelial cancers and radically altered cytogenetic profiles typical of those found in human epithelial cancers 3 . Studies of human primary tumors and epithelial cultures have also supported the idea that telomere dysfunction and its associated bridge-fusion-breakage (BFB) cycles are important in shaping the cancer genome [4][5][6] . But it is not yet known at which stage of tumorigenesis telomere-induced chromosomal instability unfolds.…”

Section: Cancer Chromosomes In Crisismentioning

confidence: 92%

“…But the importance of normal copy-number variation involving large segments of DNA has been largely unappreciated, as only a handful of instances have been reported [3][4][5][6][7][8] . Now, using DNA microarrays (array comparative genomic hybridization) to screen the human genome for changes in copy number, two studies 9,10 report a substantial degree of large-scale copynumber variation (LCV) in the human population.…”

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confidence: 99%

As normal as normal can be?

Carter

2004

Nat Genet

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“…Within BP4 is CHRFAM7A, which is a fusion of exons E-A of FAM7A (several copies of which are also in BP4) to exons 5-10 and the 3' untranslated region of CHRNA7, which lies at the distal end of the BP4-BP5 region and extends into BP5. 35 Although the function of FAM7A is unknown, CHRNA7 encodes the a7 subunit of the nicotinic cholinergic receptor that is hypothesized to contribute to the seizures and developmental delay seen in some individuals with 15q13.3 microdeletions extending to BP5. 2,20,36 CHRFAM7A may be deleted in individuals with BP3-BP4 deletions, is likely to be deleted in subject 20 4, and is deleted in individuals with BP3-BP5 deletions.…”

Section: Bp3-bp4 Microdeletions At 15q13mentioning

confidence: 99%

Deletions flanked by breakpoints 3 and 4 on 15q13 may contribute to abnormal phenotypes

et al. 2011

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Non-allelic homologous recombination (NAHR) between segmental duplications in proximal chromosome 15q breakpoint (BP) regions can lead to microdeletions and microduplications. Several individuals with deletions flanked by BP3 and BP4 on 15q13, immediately distal to, and not including the Prader-Willi/Angelman syndrome (PW/AS) critical region and proximal to the BP4-BP5 15q13.3 microdeletion syndrome region, have been reported; however, because the deletion has also been found in normal relatives, the significance of these alterations is unclear. We have identified six individuals with deletions limited to the BP3-BP4 interval and an additional four individuals with deletions of the BP3-BP5 interval from 34 046 samples submitted for clinical testing by microarray-based comparative genomic hybridization (aCGH). Of four individuals with BP3-BP4 deletions for whom parental testing was conducted, two were apparently de novo and two were maternally inherited. A comparison of clinical features, available for five individuals in our study (four with deletions within BP3-BP4 and one with a BP3-BP5 deletion), with those in the literature show common features of short stature and/or failure to thrive, microcephaly, hypotonia, and premature breast development in some individuals. Although the BP3-BP4 deletion does not yet demonstrate statistically significant enrichment in abnormal populations compared with control populations, the presence of common clinical features among probands and the presence of genes with roles in development and nervous system function in the deletion region suggest that this deletion may have a role in abnormal phenotypes in some individuals.

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A 3-Mb Map of a Large Segmental Duplication Overlapping the α7-Nicotinic Acetylcholine Receptor Gene (CHRNA7) at Human 15q13–q14

Cited by 107 publications

References 24 publications

Association between the 2-bp deletion polymorphism in the duplicated version of the alpha7 nicotinic receptor gene and P50 sensory gating

Association between the 2-bp deletion polymorphism in the duplicated version of the alpha7 nicotinic receptor gene and P50 sensory gating

As normal as normal can be?

Deletions flanked by breakpoints 3 and 4 on 15q13 may contribute to abnormal phenotypes

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