Molecular genetics of autism spectrum disorders

Shastry, Barkur S.

doi:10.1007/s10038-003-0064-9

Cited by 23 publications

(18 citation statements)

References 120 publications

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“…But they have not come to be conclusive yet [Risch et al, 1999;Jamain et al, 2003;Shastry, 2003;Vincent et al, 2004]. From a number of studies, it appears that specific genetic diseases such as cytogenetic abnormalities and single gene defects (e.g., tuberous sclerosis complex, neurofibromatosis, hypomelanosis of Ito, Williams syndrome, Moebius syndrome, Sotos syndrome, Goldenhar syndrome, CHARGE syndrome, phenylketonuria, metabolic purine disorders, etc.)…”

Section: Discussionmentioning

confidence: 99%

“…In addition, there has been a change in the appreciation of autism from a qualitative to a quantitative disorder, so that it is important to evaluate autistic symptoms quantitatively. Furthermore, recent studies have strongly suggested that autistic traits are continuously distributed in the general population [Constantino and Todd, 2000, 2003Ronald et al, 2005Ronald et al, , 2006b. A quantitative approach with a continuum scale thus complements categorical diagnosis [Baron-Cohen et al, 2006].…”

Section: Introductionmentioning

confidence: 99%

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Genetic influences on the broad spectrum of autism: Study of proband‐ascertained twins

Taniai

Nishiyama

Miyachi

et al. 2008

American J of Med Genetics Pt B

100

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An investigation of genetic structures underlying autistic traits was performed with samples from twins for which at least one proband had been ascertained as having autism spectrum disorders (ASDs) in our catchment area. In order to adjust for recent concepts of autism, we employed criteria for the broad spectrum of disease and the childhood autism rating scale (CARS) for quantitative assessment. The CARS test was performed on 45 twin pairs (19 monozygotic, 26 dizygotic) detected with a regional routine screening system. The obtained CARS scores were subjected to structural equation modeling (SEM), incorporating sex differences for each causal influence ascertainment correction, using the Mx software. A best fitting model of causal influences on autistic traits measured continuously, incorporating additive genetic (A) and non-shared environmental influences (E), was generated. With this AE model, the estimated heritability was 0.73 for males and 0.87 for females, based on the continuous CARS scores. There was no evidence for the existence of sex-specific genetic influences. Autistic traits were highly heritable in twins with even broad spectrum of autism, corresponding to the results of early studies based on classical autism. Additive genetic factors were more influential in females than males.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Genetic influences on the broad spectrum of autism: Study of proband‐ascertained twins

Taniai

Nishiyama

Miyachi

et al. 2008

American J of Med Genetics Pt B

100

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“…Our random sample of cases included males only, and the ascertainment method may thus be biased. The lack of female cases could be due to different clinical presentation 56 or that autism is under-recognized in Faroese females for cultural reasons, or due to early environmental influences. 57 Alternatively, the malefemale ratio could be a chance finding owing to the limited number of cases included.…”

Section: Discussionmentioning

confidence: 99%

A genome-wide search for alleles and haplotypes associated with autism and related pervasive developmental disorders on the Faroe Islands

et al. 2005

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The involvement of genetic factors in the etiology of autism has been clearly established. We undertook a genome-wide search for regions containing susceptibility genes for autism in 12 subjects with childhood autism and related pervasive developmental disorders (PDDs) and 44 controls from the relatively isolated population of the Faroe Islands. In total, 601 microsatellite markers distributed throughout the human genome with an average distance of 5.80 cM were genotyped, including 502 markers in the initial scan. The Faroese population structure and genetic relatedness of cases and controls were also evaluated. Based on a combined approach, including an assumption-free test as implemented in CLUMP, Fisher's exact test for specific alleles and haplotypes, and IBD 0 probability calculations, we found association between autism and microsatellite markers in regions on 2q, 3p, 6q, 15q, 16p, and 18q. The most significant finding was on 3p25.3 (P T1 ¼ 0.00003 and P T4 ¼ 0.00007), which was also supported by other genetic studies. Furthermore, no evidence of population substructure was found, and a higher degree of relatedness among cases could not be detected, decreasing the risk of inflated P-values. Our data suggest that markers in these regions are in linkage disequilibrium with genes involved in the etiology of autism, and we hypothesize susceptibility genes for autism and related PDDs to be localized within these regions.

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“…Autism is a neurodevelopmental disorder with a strong genetic basis [Wassink and Piven, 2000;Folstein and Rosen-Sheidley, 2001;Cook, 2001;Andres, 2002;Shastry, 2003;Yonan et al, 2003;Jamain et al, 2003a,b;Muhle et al, 2004;Wassink, 2004]. The diagnostic criteria for autism spectrum disorders, including Asperger syndrome, continue to be refined, a difficult task given the complexity of the syndrome and the variability in symptoms and severity.…”

Section: How Would You Model Autism In Mice?mentioning

confidence: 99%

Designing mouse behavioral tasks relevant to autistic‐like behaviors

Crawley

2004

Ment. Retard. Dev. Disabil. Res. Rev.

451

357

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The importance of genetic factors in autism has prompted the development of mutant mouse models to advance our understanding of biological mechanisms underlying autistic behaviors. Mouse models of human neuropsychiatric diseases are designed to optimize (1) face validity, i.e., resemblance to the human symptoms; (2) construct validity, i.e., similarity to the underlying causes of the disease; and (3) predictive validity, i.e., expected responses to treatments that are effective in the human disease. There is a growing need for mouse behavioral tasks with all three types of validity for modeling the symptoms of autism. We are in the process of designing a set of tasks with face validity for the defining features of autism: deficits in appropriate reciprocal social interactions, deficits in verbal social communication, and high levels of ritualistic repetitive behaviors. Social approach is tested in an automated three-chambered apparatus that offers the subject a choice between a familiar environment, a novel environment, and a novel environment containing a stranger mouse. Preference for social novelty is tested in the same apparatus, with a choice between the start chamber, the chamber containing a familiar mouse, and the chamber containing a stranger mouse. Social communication is evaluated by measuring the ultrasonic distress vocalizations emitted by infant mouse pups and the parental response of retrieving the pup to the nest. Resistance to change in ritualistic repetitive behaviors is modeled by forcing a change in habit, including reversal of the spatial location of a reinforcer in a T-maze task and in the Morris water maze. Mouse behavioral tasks that may model additional features of autism are discussed, including tasks relevant to anxiety, seizures, sleep disturbances, and sensory hypersensitivity. Applications of these tests include (1) behavioral phenotyping of transgenic and knockout mice with mutations in genes relevant to autism, (2) characterization of mutant mice derived from random chemical mutagenesis, (3) DNA microarray analyses of genes in inbred strains of mice that differ in social interaction, social communication and resistance to change in habit, and (4) evaluation of proposed therapeutics for the treatment of autism.

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Molecular genetics of autism spectrum disorders

Cited by 23 publications

References 120 publications

Genetic influences on the broad spectrum of autism: Study of proband‐ascertained twins

Genetic influences on the broad spectrum of autism: Study of proband‐ascertained twins

A genome-wide search for alleles and haplotypes associated with autism and related pervasive developmental disorders on the Faroe Islands

Designing mouse behavioral tasks relevant to autistic‐like behaviors

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