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Author: Michael Henri Duyzend Publisher: ISBN: Category : Languages : en Pages : 155
Book Description
Individuals with a diagnosis of a neurocognitive disorder, such as an autism spectrum disorder (ASD), can present with a wide range of phenotypes. Some have severe language and cognitive deficiencies while others are only deficient in social functioning. Sequencing studies have revealed extreme locus heterogeneity underlying the ASDs. Even cases with a known pathogenic variant, such as the 16p11.2 CNV, can be associated with phenotypic heterogeneity. In this thesis, I test the hypothesis that phenotypic heterogeneity observed in populations with a known pathogenic variant, such as the 16p11.2 CNV as well as that associated with the ASDs in general, is due to additional genetic factors. I analyze the phenotypic and genotypic characteristics of over 120 families where at least one individual carries the 16p11.2 CNV, as well as a cohort of over 40 families with high functioning autism and/or intellectual disability. In the 16p11.2 cohort, I assessed variation both internal to and external to the CNV critical region. Among de novo cases, I found a strong maternal bias for the origin of deletions (59/66, 89.4% of cases, p=2.38x10^-11), the strongest such effect so far observed for a CNV associated with a microdeletion syndrome, a significant maternal transmission bias for secondary deletions (32 maternal versus 14 paternal, p=1.14x10^-2), and nine probands carrying additional CNVs disrupting autism-associated genes. In the same cohort, I assessed genome wide exonic variation, including in the 27 16p11.2 CNV critical region genes and the 3 genes that lie in the flanking segmental duplications, BOLA2, SLX1A, and SULT1A3 with the hypothesis that dosage imbalance in these genes could lead to variable phenotypes. I find an absence of variation across the critical region, compared to similarly sized regions genome-wide by average heterozygosity (2nd percentile) and Tajima’s D (3rd percentile) metrics. Among the 27 critical region genes and three duplicated genes, I find no loss of function variants in 16p11.2 CNV carriers. Our genome-wide exome analysis revealed 13 likely-gene disruptive (LGD) variants in 13 probands in autism-associated genes, which is fewer than would be expected by chance (p
Author: Michael Henri Duyzend Publisher: ISBN: Category : Languages : en Pages : 155
Book Description
Individuals with a diagnosis of a neurocognitive disorder, such as an autism spectrum disorder (ASD), can present with a wide range of phenotypes. Some have severe language and cognitive deficiencies while others are only deficient in social functioning. Sequencing studies have revealed extreme locus heterogeneity underlying the ASDs. Even cases with a known pathogenic variant, such as the 16p11.2 CNV, can be associated with phenotypic heterogeneity. In this thesis, I test the hypothesis that phenotypic heterogeneity observed in populations with a known pathogenic variant, such as the 16p11.2 CNV as well as that associated with the ASDs in general, is due to additional genetic factors. I analyze the phenotypic and genotypic characteristics of over 120 families where at least one individual carries the 16p11.2 CNV, as well as a cohort of over 40 families with high functioning autism and/or intellectual disability. In the 16p11.2 cohort, I assessed variation both internal to and external to the CNV critical region. Among de novo cases, I found a strong maternal bias for the origin of deletions (59/66, 89.4% of cases, p=2.38x10^-11), the strongest such effect so far observed for a CNV associated with a microdeletion syndrome, a significant maternal transmission bias for secondary deletions (32 maternal versus 14 paternal, p=1.14x10^-2), and nine probands carrying additional CNVs disrupting autism-associated genes. In the same cohort, I assessed genome wide exonic variation, including in the 27 16p11.2 CNV critical region genes and the 3 genes that lie in the flanking segmental duplications, BOLA2, SLX1A, and SULT1A3 with the hypothesis that dosage imbalance in these genes could lead to variable phenotypes. I find an absence of variation across the critical region, compared to similarly sized regions genome-wide by average heterozygosity (2nd percentile) and Tajima’s D (3rd percentile) metrics. Among the 27 critical region genes and three duplicated genes, I find no loss of function variants in 16p11.2 CNV carriers. Our genome-wide exome analysis revealed 13 likely-gene disruptive (LGD) variants in 13 probands in autism-associated genes, which is fewer than would be expected by chance (p
Author: National Research Council Publisher: National Academies Press ISBN: 0309108675 Category : Social Science Languages : en Pages : 429
Book Description
Biosocial Surveys analyzes the latest research on the increasing number of multipurpose household surveys that collect biological data along with the more familiar interviewerâ€"respondent information. This book serves as a follow-up to the 2003 volume, Cells and Surveys: Should Biological Measures Be Included in Social Science Research? and asks these questions: What have the social sciences, especially demography, learned from those efforts and the greater interdisciplinary communication that has resulted from them? Which biological or genetic information has proven most useful to researchers? How can better models be developed to help integrate biological and social science information in ways that can broaden scientific understanding? This volume contains a collection of 17 papers by distinguished experts in demography, biology, economics, epidemiology, and survey methodology. It is an invaluable sourcebook for social and behavioral science researchers who are working with biosocial data.
Author: Suzanne B. Cassidy Publisher: John Wiley & Sons ISBN: 1118210670 Category : Medical Languages : en Pages : 1678
Book Description
The bestselling guide to the medical management of common genetic syndromes —now fully revised and expanded A review in the American Journal of Medical Genetics heralded the first edition of Management of Genetic Syndromes as an "unparalleled collection of knowledge." Since publication of the first edition, improvements in the molecular diagnostic testing of genetic conditions have greatly facilitated the identification of affected individuals. This thorough revision of the critically acclaimed bestseller offers original insights into the medical management of sixty common genetic syndromes seen in children and adults, and incorporates new research findings and the latest advances in diagnosis and treatment of these disorders. Expanded to cover five new syndromes, this comprehensive new edition also features updates of chapters from the previous editions. Each chapter is written by an expert with extensive direct professional experience with that disorder and incorporates thoroughly updated material on new genetic findings, consensus diagnostic criteria, and management strategies. Edited by two of the field's most highly esteemed experts, this landmark volume provides: A precise reference of the physical manifestations of common genetic syndromes, clearly written for professionals and families Extensive updates, particularly in sections on diagnostic criteria and diagnostic testing, pathogenesis, and management A tried-and-tested, user-friendly format, with each chapter including information on incidence, etiology and pathogenesis, diagnostic criteria and testing, and differential diagnosis Up-to-date and well-written summaries of the manifestations followed by comprehensive management guidelines, with specific advice on evaluation and treatment for each system affected, including references to original studies and reviews A list of family support organizations and resources for professionals and families Management of Genetic Syndromes, Third Edition is a premier source to guide family physicians, pediatricians, internists, medical geneticists, and genetic counselors in the clinical evaluation and treatment of syndromes. It is also the reference of choice for ancillary health professionals, educators, and families of affected individuals looking to understand appropriate guidelines for the management of these disorders. From a review of the first edition: "An unparalleled collection of knowledge . . . unique, offering a gold mine of information." —American Journal of Medical Genetics
Author: Yoshinori Kohwi Publisher: Springer Science & Business Media ISBN: 1592598048 Category : Science Languages : en Pages : 341
Book Description
Trinucleotide repeats are relatively common in the human genome. These simple repeats have received much attention since epoch-making discoveries were made that particular trinucleotide repeats are expanded in the causal genes of human hereditary neurological disorders. For example, the CGG repeat is expanded in fragile X syndrome at the 5' untranslated region (UTR) of its causal gene. In myotonic dystrophy, it is the CTG repeat that is expanded at the 3' UTR of its causal gene. The CAG repeat was also found expanded in coding regions of the genes responsible for X-linked spinal and bulbar muscular atrophy, Huntington’s disease, spinocerebellar ataxia, and other disorders. On the other hand, expansion of the GAA repeat was identified in the intron of the gene responsible for the Friedreich’s ataxia. For these trinucleotide repeat diseases, the longer the trinucleotide expansion, the earlier the age of onset and the more severe the syndrome. Thus, these findings that showed the intriguing link between a particular trinucleotide expansion and its associated neurological disorders have led to a new field of intensive study. Active research addressing the underlying mechanisms for trinucleotide repeat diseases has employed various approaches ranging from DNA biochemistry to animal models for the diseases. In particular, animal models for the triplet repeat diseases have provided excellent resources not only for understanding the mechanisms but also for exploring therapeutic interventions.
Author: Vinood B. Patel Publisher: Springer ISBN: 9781461447870 Category : Psychology Languages : en Pages : 0
Book Description
Autism is a complex multifaceted disorder affecting neurodevelopment during the early years of life and, for many, throughout the life span. Inherent features include difficulties or deficits in communication, social interaction, cognition, and interpersonal behavioral coordination, to name just a few. Autism profoundly impacts the affected individual, the family, and, in many cases, the localized communities. The increased prevalence of childhood autism has resulted in rapid developments in a wide range of disciplines in recent years. Nevertheless, despite intensive research, the cause(s) remain unresolved and no single treatment strategy is employed. To address these issues, Comprehensive Guide to Autism is an all-embracing reference that offers analyses and discussions of contemporary issues in the field of autism. The work brings together scientific material from leading experts in the field relating to a wide range of important current topics, such as the early identification and treatment of children with autism, pertinent social and behavioral studies, recent developments in genetics and immunology, the influence of diet, models of autism, and future treatment prospects. Comprehensive Guide to Autism contains essential readings for behavioral science researchers, psychologists, physicians, social workers, parents, and caregivers.
Author: Dorothy V.M Bishop Publisher: Psychology Press ISBN: 1317715829 Category : Psychology Languages : en Pages : 320
Book Description
Delayed development of speech and/or language is one of the commonest reasons for parents of preschool children to seek the advice of a paediatrician. Accessible to non-academic Speech and Language Impairments provides an overview of recent research developments in specific speech and language impairments, written by experts in the field. Topics include normal and disordered development of problems , crosslinguistic studies, pragmatic language impairments, early identification, educational and psychiatric outcomes, acquired epileptic aphasia and experimental studies of remediation. The book concludes with a chapter by Michael Rutter that gives guidelines for conducting and evaluating research in this field.
Author: Anthony J. Hannan Publisher: Springer Science & Business Media ISBN: 1461454344 Category : Medical Languages : en Pages : 208
Book Description
This book addresses the role of tandem repeat polymorphisms (TRPs) in genetic plasticity, evolution, development, biological processes, neural diversity, brain function, dysfunction and disease. There are hundreds of thousands of unique tandem repeats in the human genome and their polymorphic distributions have the potential to greatly influence functional diversity and disease susceptibility. Recent discoveries in this expanding field are critically reviewed and discussed in a range of subsequent chapters, with a focus on the role of TRPs and their various gene products in evolution, development, diverse molecular and cellular processes, brain function and disease.
Author: David S. Moore Publisher: Macmillan ISBN: 9780805072808 Category : Science Languages : en Pages : 324
Book Description
This book provides an analysis of the nature vs. nuture debate, arguing for an end to the 'either/or' nature of the discussions in favor of a recognition that environmental and genetic factors interact throughout life to form human traits.
Author: Michael Henri Duyzend
Author: Michael Henri Duyzend
Author: National Research Council
Author: Anthony F. Rotatori
Author: Suzanne B. Cassidy
Author: Yoshinori Kohwi
Author: John O'Keefe
Author: Vinood B. Patel
Author: Dorothy V.M Bishop
Author: Anthony J. Hannan
Author: David S. Moore