Thesis advisor: Laura Anne Lowery / Thesis advisor: Sarah McMenamin / Development of the central nervous system (CNS) is a complex process that requires the proper function of many genes in order for neurons to proliferate and divide, differentiate, and subsequently migrate long distances to form connections with one another. Abnormalities in any one of these cellular processes can lead to detrimental developmental defects. Growing evidence suggests that genetic mutations caused by rare copy number variants (CNVs) are associated with neurodevelopmental disorders including intellectual disabilities (ID), Autism spectrum disorder (ASD), and schizophrenia. Additionally, these pathogenic CNVs are characterized by extensive phenotypic heterogeneity, as affected individuals often present with microcephaly, craniofacial and heart defects, growth retardation, and seizures. Despite their strong association as risk factors towards neurodevelopmental disorders, the developmental role of individual CNV-affected genes and disrupted cellular mechanisms underlying these mutations remains poorly understood. Moreover, it is unclear as to how the affected genes both individually and combinatorially contribute to the phenotypes associated with pathogenic CNVs. Thus, in this thesis, we explore the functional basis of phenotypic variability of pathogenic CNVs linked to neurodevelopmental disorders. In particular, we focus on the 3q29 deletion and 16p12.1 deletion, to provide insight towards the convergent cellular, molecular, and developmental mechanisms associated with decreased dosage of the affected gene homologs using two complementary model systems, Xenopus laevis and Drosophila melanogaster. First, we examine the role of individual homologs of several CNV-affected genes at chromosome 3q29 and their interactions towards cellular processes underlying the deletion. We find that multiple 3q29-affected genes, including NCBP2, DLG1, FBXO45, PIGZ, and BDH1, contribute to disruptions in apoptosis and cell cycle pathways, leading to neuronal and developmental defects. We then expand further upon this work by discerning the individual contribution of four CNV-affected genes at chromosome 16p12.1, POLR3E, MOSMO, UQCRC2, and CDR2, towards neurodevelopment and craniofacial morphogenesis. We demonstrate that several of these genes affect multiple phenotypic domains during neurodevelopment leading to brain size alterations, abnormal neuronal morphology, and cellular proliferation defects. We then explore their functions during vertebrate craniofacial morphogenesis and demonstrate that some 16p12.1-affected genes are enriched in migratory neural crest, and contribute to early craniofacial patterning and formation of cartilaginous tissue structures. Together, these data are the first to suggest that signature neurodevelopmental phenotypes demonstrated in the 3q29 deletion and 16p12.1 deletion may stem from convergent cellular mechanisms including aberrations in neuronal proliferation, apoptosis and cell cycle regulation, and neural crest cell development. / Thesis (PhD) — Boston College, 2020. / Submitted to: Boston College. Graduate School of Arts and Sciences. / Discipline: Biology.

There are a greater number of inclusive postsecondary education (PSE) programs for students with intellectual disabilities (ID) in the U.S. than ever before. Consequently, there are a greater number of students with ID who now have the opportunity to participate in fully inclusive PSE programs with the intent of improving their transition outcomes related to employment, independent living, and quality of life. For students with ID to get the most out of these expanding PSE opportunities, it is imperative that they develop the personal competencies that will better prepare them to participate in such programs. The current study began the exploratory process of identifying, from a parent perspective, the personal competencies related to inclusive PSE readiness for students with intellectual disabilities in the broad categories of (a) the personal skills, (b) knowledge, and (c) attributes. This purpose was achieved by using a three-round Delphi survey, administered to a sample of parents of students with ID who have participated in one of the 44 federally funded Transition and Postsecondary Programs for Students with Intellectual Disabilities (TPSIDs). The first round of the survey generated 56 items that participants in Round Two then rated on a 7-point scale of importance related to preparing students with ID for participation in inclusive PSE. In the final round of the Delphi survey, participants were provided with the mean, standard deviation, and frequency distribution for each of the 56 items from Round Two and asked to rerate each item based on the additional information provided. In Round Three the expert panel of parents gained consensus on 33 items related to personal skills, knowledge, and attributes they deemed important for students with ID to develop in order to be prepared for an inclusive PSE program. Results of the study were discussed in the context of the literature related to personal competencies for college readiness for students with and without ID. Additionally, implications, limitations, and recommendations for future research were discussed.

Research suggests teaching adults and children with disabilities to follow pictorial cues increases home life skills, vocational skills and on-task behavior. Activity schedules use pictorial cues to prompt individuals to complete behavioral sequences. The purpose of this study was to examine if, after training, adults with intellectual disabilities completed a series of behaviors using an activity schedule. The dependent variable is percent of components completed independently. Three individuals with mild to severe intellectual and physical disabilities receiving services from a private provider day program participated. Each participant used an activity schedule to complete a skill set during training. The results show that, for all participants, an activity schedule increased independently completed steps of the skill set, typing on a computer, as compared to when the activity schedule was not present.

Adult siblings of people with intellectual and developmental disabilities (IDD) are often on the front lines of supporting their brothers and sisters with IDD through caregiving and guardianship roles after their parents pass away. However, these siblings are often uninformed or under informed about ways that they can support their brothers and sisters. This study had the following three purposes: to determine what adult siblings of adults with IDD know about guardianship and its alternatives; to explore how adult siblings view guardianship and its alternatives; and to explore what adult siblings think about their role of being a guardian or supported decision maker for their brother/sister with IDD. Ten adult siblings who had brothers and sisters with IDD were interviewed; their interviews were analyzed using a combination of grounded theory and directed analysis. This study found that siblings had a limited knowledge of guardianship and its alternatives, viewed guardianship as necessary, and desired to be involved in future planning and decision making supports with their brother or sister in adulthood. These findings have several implications for future research, as well as for schools and disability service agencies. For example, siblings’ limited knowledge about guardianship and its alternatives highlights the need for schools, disability agencies, and other disability organizations to better inform families about the full range of options available to support people with IDD in making decisions. Likewise, as the sibling participants were concerned about their brother and sister’s decision-making abilities, there is a need for better training of people with IDD to be able to make and express their choices in a variety of situations. Finally, as this study had a small sample size and the participants’ were all White, future research with more diverse and larger sample sizes is needed.

Students with intellectual disabilities have at times been overlooked and denied effective reading instruction. Teachers tasked with instructing such students are often limited in the training, resources, and support necessary to effectively instruct these students in reading. These problems are further compounded by the fact that students with intellectual disabilities have historically been misperceived, often by the very educators tasked with instructing them, as either being unable to learn to read or that the prospect of teaching them to read is simply too daunting and complicated to be of sufficient worth (Aldridge, 2014; Kluth & Chandler-Olcott, 2008). Such misperception may lead to insufficient and/or misguided instruction of these students limiting their potential learning and growth (Kliewer, Biklen, & Kasa-Hendrickson, 2006). This qualitative case study explored the perceptions and lived experiences of eight special education teachers from five different school districts, who both worked with students with intellectual disabilities and mentored preservice teachers who worked with students with intellectual disabilities in the area of reading. This study focused on the perceptions of these special education teacher/ mentors before, during and after receiving training in the Targeted Reading Intervention (TRI) program, based on five areas of reading: Phonemic Awareness, Phonics, Vocabulary, Fluency, and Vocabulary. Data suggested a universal lack of support and training in reading for these special education teacher/mentors. Changes of perceptions and teaching practices of the special education teacher/mentors relative to explicit reading instruction for students with intellectual abilities are explored. Implications for practice are included.

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