Copy number variation of LINGO1 in familial dystonic tremor

ObjectiveTo elucidate the genetic cause of a large 5 generation South Indian family with multiple individuals with predominantly an upper limb postural tremor and posturing in keeping with another form of tremor, namely, dystonic tremor.MethodsWhole-genome single nucleotide polymorphism (SNP) microarray analysis was undertaken to look for copy number variants in the affected individuals.ResultsWhole-genome SNP microarray studies identified a tandem duplicated genomic segment of chromosome 15q24 present in all affected family members. Whole-genome sequencing demonstrated that it comprised a ∼550-kb tandem duplication encompassing the entire LINGO1 gene.ConclusionsThe identification of a genomic duplication as the likely molecular cause of this condition, resulting in an additional LINGO1 gene copy in affected cases, adds further support for a causal role of this gene in tremor disorders and implicates increased expression levels of LINGO1 as a potential pathogenic mechanism.

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The Role of Copy Number Variation in Psychiatric Disorders

Psychiatric Genetics ◽

10.1093/med/9780190221973.003.0006 ◽

2018 ◽

pp. 84-95

Author(s):

Elliott Rees ◽

George Kirov

Keyword(s):

Autism Spectrum Disorders ◽

Copy Number ◽

Selection Pressure ◽

Copy Number Variants ◽

Autism Spectrum ◽

High Odds ◽

Strong Selection ◽

Increase Risk ◽

Number Variation

Copy number variants (CNVs) are deletions, duplications, inversions, or translocations of large DNA segments. They can play a significant role in human disease. Thirteen CNVs have received strong statistical support for involvement in schizophrenia. They are all rare in cases (<1%), much rarer among controls, and have high odds ratios (ORs) for causing disease. The same CNVs also increase risk for autism spectrum disorders, developmental delay, and medical/physical comorbidities. The penetrance of these CNVs for any disorder is relatively high, ranging from 10% for 15q11.2 deletions to nearly 100% for deletions at 22q11.2. Strong selection pressure operates against carriers of these CNVs. Most of these are formed by non-allelic homologous recombination (NAHR), which leads to high mutation rates, thus maintaining the rates of these CNVs in the general population, despite the strong selection forces.

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Genetics of Schizophrenia and Bipolar Disorder

10.1093/med/9780190681425.003.0013 ◽

2017 ◽

Author(s):

Alexander Charney ◽

Pamela Sklar

Keyword(s):

Bipolar Disorder ◽

Copy Number ◽

Psychotic Disorders ◽

Copy Number Variants ◽

Nucleotide Polymorphisms ◽

Common Variants ◽

Single Nucleotide Variants ◽

Single Nucleotide ◽

Number Variation

Schizophrenia and bipolar disorder are the classic psychotic disorders. Both diseases are strongly familial, but have proven recalcitrant to genetic methodologies for identifying the etiology until recently. There is now convincing genetic evidence that indicates a contribution of many DNA changes to the risk of becoming ill. For schizophrenia, there are large contributions of rare copy number variants and common single nucleotide variants, with an overall highly polygenic genetic architecture. For bipolar disorder, the role of copy number variation appears to be much less pronounced. Specific common single nucleotide polymorphisms are associated, and there is evidence for polygenicity. Several surprises have emerged from the genetic data that indicate there is significantly more molecular overlap in copy number variants between autism and schizophrenia, and in common variants between schizophrenia and bipolar disorder.

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The Role of Cell Growth-Related Gene Copy Number Variation in Autoimmune Thyroid Disease

Biological Trace Element Research ◽

10.1007/s12011-019-01880-7 ◽

2019 ◽

Vol 195 (2) ◽

pp. 409-416 ◽

Cited By ~ 2

Author(s):

Yunfeng Guan ◽

Lixiang Liu ◽

Qingzhen Jia ◽

Xing Jin ◽

Yi Pang ◽

...

Keyword(s):

Cell Growth ◽

Copy Number ◽

Autoimmune Thyroid Disease ◽

Gene Copy Number ◽

Gene Copy ◽

Related Gene ◽

Autoimmune Thyroid ◽

Gene Copy Number Variation ◽

Number Variation

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Association of copy number variation in the AHI1 gene with risk of obesity in the Chinese population

Acta Endocrinologica ◽

10.1530/eje-11-0999 ◽

2012 ◽

Vol 166 (4) ◽

pp. 727-734 ◽

Cited By ~ 11

Author(s):

Liansha Huang ◽

Dacai Teng ◽

Hao Wang ◽

Guoqing Sheng ◽

Tonghua Liu

Keyword(s):

Copy Number ◽

Integration Site ◽

Linear Trend ◽

Copy Number Variants ◽

Gene Copy Number ◽

Copy Number Gain ◽

Gene Copy ◽

Significant Linear Trend ◽

Number Variation ◽

Dna Copy Number Change

ObjectiveThe prevalence of obesity has increased dramatically over the past decade. Gene copy number variants (CNVs) have been recognized as a hereditable source of susceptibility in human complex diseases including obesity. Recent studies have shown that Abelson helper integration site 1 (Ahi1) gene has a significant contribution in the homeostasis regulation in mouse models of obesity. A study was therefore carried out to investigate whether CNVs inAHI1gene contribute to human obesity.Subjects and methodsWe analyzed samples from 70 Chinese overweight adults and 74 healthy controls for DNA copy number change using the Affymetrix single-nucleotide polymorphism (SNP) 6.0 array. Validation of CNVs ofAHI1was achieved by real-time PCR using the ΔΔCtmethod.ResultsCopy number gain analysis revealed significant gains (P=0.0017) ofAHI1gene copy number in 17 of 70 (24.3%) samples but only four of 74 (5.4%) controls overall. Then we studied the frequency distribution of CNVs inAHI1gene according to body mass index (BMI) grade. Five out of 28 (18.5%) at-risk obese, six out of 26 (26.9%) moderate obese, and six out of 17 (29.4%) severe obese subjects studied showed increasedAHI1gene copy number.ConclusionsThe result suggested that there was a significant linear trend for increasingAHI1gene copy number frequencies with increasing BMI.

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Gene copy-number polymorphism in nature

Proceedings of The Royal Society B Biological Sciences ◽

10.1098/rspb.2010.1180 ◽

2010 ◽

Vol 277 (1698) ◽

pp. 3213-3221 ◽

Cited By ~ 97

Author(s):

Daniel R. Schrider ◽

Matthew W. Hahn

Keyword(s):

Natural Selection ◽

Copy Number Variation ◽

Copy Number ◽

Molecular Mechanisms ◽

Copy Number Variants ◽

Gene Copy Number ◽

Gene Copy ◽

Phenotypic Differences ◽

Sequencing Technologies ◽

Number Variation

Differences between individuals in the copy-number of whole genes have been found in every multicellular species examined thus far. Such differences result in unique complements of protein-coding genes in all individuals, and have been shown to underlie adaptive phenotypic differences. Here, we review the evidence for copy-number variants (CNVs), focusing on the methods used to detect them and the molecular mechanisms responsible for generating this type of variation. Although there are multiple technical and computational challenges inherent to these experimental methods, next-generation sequencing technologies are making such experiments accessible in any system with a sequenced genome. We further discuss the connection between copy-number variation within species and copy-number divergence between species, showing that these values are exactly what one would expect from similar comparisons of nucleotide polymorphism and divergence. We conclude by reviewing the growing body of evidence for natural selection on copy-number variants. While it appears that most genic CNVs—especially deletions—are quickly eliminated by selection, there are now multiple studies demonstrating a strong link between copy-number differences at specific genes and phenotypic differences in adaptive traits. We argue that a complete understanding of the molecular basis for adaptive natural selection necessarily includes the study of copy-number variation.

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