Luận văn thạc sĩ identifying rare genetic variation in obsessive compulsive disorder
➤ Gửi thông báo lỗi ⚠️ Báo cáo tài liệu vi phạmNội dung chi tiết: Luận văn thạc sĩ identifying rare genetic variation in obsessive compulsive disorder
Luận văn thạc sĩ identifying rare genetic variation in obsessive compulsive disorder
Yale UniversityEliScholar - A Digital Platform for Scholarly Publishing at YaleYale Medicine Thesis Digital LibrarySchool of Medicine43831Identifying Luận văn thạc sĩ identifying rare genetic variation in obsessive compulsive disorder Rare Genetic Variation In Obsessive-Compulsive DisorderSarah AbdallahFollow this and additional works at: https://elischolar.library.yale.edu/ymtdlRecommended CitationAbdallah, Sarah, "Identifying Rare Genetic Variation In Obsessive-Compulsive Disorder' (2020). Yale Medicine Thesis Digital Library. Luận văn thạc sĩ identifying rare genetic variation in obsessive compulsive disorder 3876https://elischolar.library.yale.edu/ymtdl/3876This Open Access Thesis is brought to you for free and open access by the School of Medicine at EliLuận văn thạc sĩ identifying rare genetic variation in obsessive compulsive disorder
Scholar - A Digital Platform for Scholarly Publishing at Yale. It has been accepted for inclusion in Yale Medicine Thesis Digital Library by an authorYale UniversityEliScholar - A Digital Platform for Scholarly Publishing at YaleYale Medicine Thesis Digital LibrarySchool of Medicine43831Identifying Luận văn thạc sĩ identifying rare genetic variation in obsessive compulsive disorder ifying Rare Genetic Variation in Obsessive-Compulsive DisorderA Thesis Submitted to the Yale University School of Medicine in Partial Fulfillment of the Requirements for the Degr ee of Doctor of MedicinebySarah Barbara Abdallah2020ABSTRACTIDENTIFYING RARE GENETIC VARIATION IN OBSESSIVE-COMPULSIVE DI Luận văn thạc sĩ identifying rare genetic variation in obsessive compulsive disorder SORDERSarah 13. Abdallah, Carolina Cappi. Emily OUsoiL and Thomas V. 1 •cmandcz. Cliild Study Center. Yale University School of Medicine. New Haven. CLuận văn thạc sĩ identifying rare genetic variation in obsessive compulsive disorder
TObsessive-compulsive disorder (OC'D) is a neuropsychiatric developmental disorder with known heritabilily (estimates ranging from 2 7° 0-80%) blit poYale UniversityEliScholar - A Digital Platform for Scholarly Publishing at YaleYale Medicine Thesis Digital LibrarySchool of Medicine43831Identifying Luận văn thạc sĩ identifying rare genetic variation in obsessive compulsive disorder providing an impetus to study the genetic basis of OCD in the hopes of identify ing new therapeutic targets. We previously demonstrated a significant contribution to OC’D risk from likely damaging de novo germline DNA sequence variants, which arise spontaneously in the parental genu cells 01 zygote Luận văn thạc sĩ identifying rare genetic variation in obsessive compulsive disorder instead of being inherited from a parent, and we successfully used these identified variants to implicate new OCD risk genes. Recent studies have demLuận văn thạc sĩ identifying rare genetic variation in obsessive compulsive disorder
onstrated a role tor DNA copy-munber variants (CNVs) in other neuropsychiatric disorders, but CNV studies in OCT) have been limited. Additionally, stuYale UniversityEliScholar - A Digital Platform for Scholarly Publishing at YaleYale Medicine Thesis Digital LibrarySchool of Medicine43831Identifying Luận văn thạc sĩ identifying rare genetic variation in obsessive compulsive disorder lular stages of embryogenesis, suggesting these mosaic variants can be used to study other ncuropsy cliialric disorder’s, hl the studies presented here, we aim to characterize rhe contribution of PTVs and rare CNVs to OCD risk.We examined wholc-cxome sequencing (WES) data from peripheral blood of 18 Luận văn thạc sĩ identifying rare genetic variation in obsessive compulsive disorder 1 OCD trio families (unaffected parents and child with OCD) and 777 control trios that passed quality control measures. We used the biomfoniiatics tooLuận văn thạc sĩ identifying rare genetic variation in obsessive compulsive disorder
l Mosaic! lunler toidentify low-allele frequency, potentially mosaic siiigle-nucleotide variants (SNVs) 111 probands (OCD cases) and in control childrYale UniversityEliScholar - A Digital Platform for Scholarly Publishing at YaleYale Medicine Thesis Digital LibrarySchool of Medicine43831Identifying Luận văn thạc sĩ identifying rare genetic variation in obsessive compulsive disorder d platform. to identify' CNVs.The rate of all single-nucleotide PZVs per base pair was not significantly different between OCD probands (4.90 X 1O’Ợ) and controls (4.93 X IO’0), rate ratio = 0.994, p = 1. The rate of likely-damaging PZVs (those altering a stop codon or splice site) also is not signi Luận văn thạc sĩ identifying rare genetic variation in obsessive compulsive disorder ficantly different 111 OCD probands (1.45 X 10-i>) than 111 controls (1.09 X 10^). rate ratio = 1.33. p = 0.653.When examining CNVs. the proportion ofLuận văn thạc sĩ identifying rare genetic variation in obsessive compulsive disorder
children with at least one rare duplication 01 deletion is not significantly different between OCD cases (0.869) and controls (0.796). chi-square = 2Yale UniversityEliScholar - A Digital Platform for Scholarly Publishing at YaleYale Medicine Thesis Digital LibrarySchool of Medicine43831Identifying Luận văn thạc sĩ identifying rare genetic variation in obsessive compulsive disorder r 111 OCD trios (0.606) than 111 controls (0.448). chi-square = 8.86. p = 0.00292.Although we did not detect a higher burden of PZVs in blood in individuals with OCD. ftirther studies may benefit from examining a larger sample of families or from looking for PZVs in other tissues. The higher rate of Luận văn thạc sĩ identifying rare genetic variation in obsessive compulsive disorder de novo deletions in cases vs. controls suggests they may contribute to OCD risk, but further work IS needed to experimentally validate the detectedLuận văn thạc sĩ identifying rare genetic variation in obsessive compulsive disorder
CNVs. We hope to eventually use these CNVs to identify- OCD risk genes that could provide jumping-off points for future studies ofmolecular disease meYale UniversityEliScholar - A Digital Platform for Scholarly Publishing at YaleYale Medicine Thesis Digital LibrarySchool of Medicine43831Identifying Luận văn thạc sĩ identifying rare genetic variation in obsessive compulsive disorder tributions to this work They have been lovely, brilliant, and encouraging people to work with. I also have appreciated the encouragement from other members of the Child Study Center and their efforts to create a welcoming work environment. Thanks to my parents and friends for supporting my efforts t Luận văn thạc sĩ identifying rare genetic variation in obsessive compulsive disorder o pursue this sort of work and helping me through the glowing pains. Additional thanks to the Yale office of Student Research for their support.The reLuận văn thạc sĩ identifying rare genetic variation in obsessive compulsive disorder
search included in this thesis was funded by giants from the Allison Family Foundation. Brain and Behavior Research Foundation (NARSAD). and the NatioYale UniversityEliScholar - A Digital Platform for Scholarly Publishing at YaleYale Medicine Thesis Digital LibrarySchool of Medicine43831Identifying Luận văn thạc sĩ identifying rare genetic variation in obsessive compulsive disorder merican Society for Human Genetics, and .American Academy of Child and Adolescent Psychiatry (SB A).Table of ContentsINTRODUCTION................................................................1Features of Obsessive-Compulsive Disorder............................1Approaches to Studying OCD Genetics. Luận văn thạc sĩ identifying rare genetic variation in obsessive compulsive disorder .................................2Association Studies............................................3Yale UniversityEliScholar - A Digital Platform for Scholarly Publishing at YaleYale Medicine Thesis Digital LibrarySchool of Medicine43831Identifying Yale UniversityEliScholar - A Digital Platform for Scholarly Publishing at YaleYale Medicine Thesis Digital LibrarySchool of Medicine43831IdentifyingGọi ngay
Chat zalo
Facebook