Copy Number Variation in Neuropsychiatric Disorders
Başlık:
Copy Number Variation in Neuropsychiatric Disorders
Yazar:
Huang, Alden Yen-Wen, author.
ISBN:
9780438009844
Yazar Ek Girişi:
Fiziksel Tanımlama:
1 electronic resource (173 pages)
Genel Not:
Source: Dissertation Abstracts International, Volume: 79-10(E), Section: B.
Advisors: Giovanni Coppola Committee members: Eleazar Eskin; Nelson B. Freimer; Bogdan Pasaniuc; Jeremiah M. Schard.
Özet:
In this thesis, I characterize the contribution of rare copy number variation (CNV) to the genetic etiology of Tourette syndrome (TS) and bipolar disorder (BP). I accomplish this using several different study designs and various methods for CNV detection. As array data was widely available for the majority of samples evaluated, I make extensive use of this technology throughout this project and first provide an overview of the technical challenges involved and describe the analytical pipeline I developed to produce reliable CNV calls from such data.
Then, in the largest TS CNV study conducted to date, I report the discovery of the first two genome-wide significant CNVs associated with the disorder, and demonstrate an increased global burden of large, singleton events and CNVs at known, pathogenic loci. Conditioned on this latter observation, I perform an exploratory analysis aimed at gene discovery through the identification of de novo copy number variants from whole-exome sequencing in a sample of affected proband, unaffected parent trios in TS.
I then describe a CNV study of 26 large, multigenerational families with a high incidence of BP from two population isolates, using both microarray and whole-genome sequencing data. While thorough examination of these extended BP pedigrees revealed no segregating variants of large effect, I observe a significant increase in CNV burden across a subset of BP-related genes. Finally, I explore this notion further in a larger North American sample of unrelated individuals ascertained for BP. I demonstrate that although BP cases show no observable differences in the rate or size of rare CNVs, case CNVs affect more highly constrained, brain-expressed genes, and I provide evidence for an increased female CNV burden for BP.
Notlar:
School code: 0031
Tüzel Kişi Ek Girişi:
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Yer Numarası | Demirbaş Numarası | Shelf Location | Lokasyon / Statüsü / İade Tarihi |
---|---|---|---|
XX(682443.1) | 682443-1001 | Proquest E-Tez Koleksiyonu | Arıyor... |
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