Proposed models Heritability of autism

1 proposed models

1.1 single genes
1.2 multigene interactions
1.3 2 family types
1.4 epigenetic
1.5 genomic imprinting
1.6 environmental interactions

proposed models

twin , family studies show autism highly heritable condition, have left many questions researchers, notably

why fraternal twin concordance low considering identical twin concordance high?
why parents of autistic children typically non-autistic?
which factors involved in failure find 100% concordance in identical twins?
is profound intellectual disability characteristic of genotype or totally independent?

clues first 2 questions come studies have shown @ least 30% of individuals autism have spontaneous de novo mutations occurred in father s sperm or mother s egg , disrupt genes important brain development, these spontaneous mutations cause autism in families there no family history. concordance between identical twins isn t quite 100% 2 reasons, because these mutations have variable expressivity , effects manifest differently due chance effects, epigenetic, , environmental factors. spontaneous mutations can potentially occur in 1 twin , not other after conception. likelihood of developing intellectual disability dependent on importance effect gene or mutation has on brain development, , genetic , environmental background upon mutation occurs. recurrence of same mutations in multiple individuals affected autism has led brandler , sebat suggest spectrum of autism breaking quanta of many different genetic disorders.

single genes

the parsimonious explanation cases of autism single child affected , there no family history or affected siblings single spontaneous mutation impacts 1 or multiple genes significant contributing factor. tens of individual genes or mutations have been definitively identified , cataloged simons foundation autism research initiative. examples of autism has arisen rare or de novo mutation in single-gene or locus include neurodevelopmental disorders fragile x syndrome, 22q13 deletion syndrome, , 16p11.2 deletion syndrome.

these mutations characterized considerable variability in clinical outcome , typically subset of mutation carriers meet criteria autism. example, carriers of 16p11.2 deletion have mean iq 32 points lower first-degree relatives not carry deletion, 20% below threshold iq of 70 intellectual disability, , 20% have autism. around 85% have neurobehavioral diagnosis, including autism, adhd, anxiety disorders, mood disorders, gross motor delay, , epilepsy, while 15% have no diagnosis. alongside these neurobehavioral phenotypes, 16p11.2 deletions / duplications have been associated macrocephaly / microcephaly, body weight regulation, , duplication in particular associated schizophrenia. controls carry mutations associated autism or schizophrenia typically present intermediate cognitive phenotypes or fecundity compared neurodevelopmental cases , population controls. therefore, single mutation can have multiple different effects depending on other genetic , environmental factors.

multigene interactions

in model, autism arises combination of common, functional variants of genes. each gene contributes relatively small effect in increasing risk of autism. in model, no single gene directly regulates core symptom of autism such social behavior. instead, each gene encodes protein disrupts cellular process, , combination of these disruptions, possibly environmental influences, affect key developmental processes such synapse formation. example, 1 model many mutations affect met , other receptor tyrosine kinases, in turn converge on disruption of erk , pi3k signaling.

two family types

in model families fall 2 types: in majority, sons have low risk of autism, in small minority risk near 50%. in low-risk families, sporadic autism caused spontaneous mutation poor penetrance in daughters , high penetrance in sons. high-risk families come (mostly female) children carry new causative mutation unaffected , transmit dominant mutation grandchildren.

epigenetic

several epigenetic models of autism have been proposed. these suggested occurrence of autism in individuals fragile x syndrome, arises epigenetic mutations, , rett syndrome, involves epigenetic regulatory factors. epigenetic model explain why standard genetic screening strategies have difficulty autism.

genomic imprinting

genomic imprinting models have been proposed; 1 of strengths explaining high male-to-female ratio in asd. 1 hypothesis autism in sense diametrically opposite schizophrenia , other psychotic-spectrum conditions, alterations of genomic imprinting mediate development of these 2 sets of conditions, , asd involves increased effects of paternally expressed genes, regulate overgrowth in brain, whereas schizophrenia involves maternally expressed genes , undergrowth.

environmental interactions

though autism s genetic factors explain of autism risk, not explain of it. common hypothesis autism caused interaction of genetic predisposition , environmental insult. several theories based on environmental factors have been proposed address remaining risk. of these theories focus on prenatal environmental factors, such agents cause birth defects; others focus on environment after birth, such children s diets. known teratogens (agents cause birth defects) related risk of autism appear act during first 8 weeks conception, strong evidence autism arises in development. although evidence other environmental causes anecdotal , has not been confirmed reliable studies, extensive searches underway.