Mapping autism risk loci using genetic linkage and chromosomal rearrangements

  title={Mapping autism risk loci using genetic linkage and chromosomal rearrangements},
  author={Peter Szatmari and Andrew D. Paterson and Lonnie Zwaigenbaum and Wendy Roberts and Jessica A. Brian and Xiao-qing Liu and John B. Vincent and Jennifer Skaug and Ann P. Thompson and Lili Senman and Lars Feuk and Cheng Qian and Susan E. Bryson and Marshall B. Jones and Christian R. Marshall and Stephen W. Scherer and Veronica J. Vieland and Christopher Bartlett and La Vonne Mangin and Rhinda J. Goedken and Alberto Maria Segre and Margaret A. Pericak-Vance and Michael L Cuccaro and John R. Gilbert and Harry H. Wright and Ruth K. Abramson and Catalina Betancur and Thomas Bourgeron and Christopher Gillberg and Marion Leboyer and Joseph. D. Buxbaum and Kenneth L. Davis and Eric Hollander and Jeremy M. Silverman and Joachim Hallmayer and Linda J. Lotspeich and James S. Sutcliffe and Jonathan L. Haines and Susan E B Folstein and Joseph Piven and Thomas H. Wassink and Val C. Sheffield and Daniel H. Geschwind and Maja Bucan and W. Ted Brown and Rita M. Cantor and John N. Constantino and T. Conrad Gilliam and Martha Reed Herbert and Clara Lajonchere and David H. Ledbetter and Christa Lese-Martin and Janet Miller and Stan Nelson and Carole A Samango-Sprouse and Sarah J. Spence and Matthew W. State and Rudolph E. Tanzi and Hilary Coon and Geraldine Dawson and Bernie Devlin and Annette M. Estes and Pamela Flodman and Lambertus Klei and William M. McMahon and Nancy J. Minshew and Jeff Munson and Elena Korvatska and Patricia M. Rodier and Gerard D. Schellenberg and Moyra J. Smith and M. Anne Spence and Christopher J. Stodgell and Ping G Tepper and Ellen M. Wijsman and Chang-En Yu and Bernadette Rog{\'e} and Carine Mantoulan and Kerstin Wittemeyer and Annemarie Poustka and B{\"a}rbel Felder and Sabine M. Klauck and Claudia Schuster and Fritz Poustka and Sven B{\"o}lte and Sabine Feineis-Matthews and Evelyn Herbrecht and Gabi Schm{\"o}tzer and John Tsiantis and Katerina Papanikolaou and Elena Maestrini and Elena Bacchelli and Francesca Blasi and Simona Carone and Claudio Toma and Herman van Engeland and Maretha V. de Jonge and Chantal Kemner and F. Bradamante I. Koop and Marjolein Langemeijer and Channa T. Hijmans and Wouter G. Staal and Gillian Baird and Patrick F. Bolton and Michael L. Rutter and Emma J. Weisblatt and Jonathan Green and Catherine Aldred and Julie Anne Wilkinson and Andrew Pickles and Ann Le Couteur and Thomas P. Berney and Helen McConachie and Anthony J. Bailey and Kostas Francis and Gemma Honeyman and A. J. Hutchinson and Jeremy R Parr and Simon Wallace and Anthony P. Monaco and Gabrielle Barnby and Kazuhiro Kobayashi and Janine A. Lamb and In{\^e}s Sousa and Nuala H Sykes and Edwin H. Cook and Stephen J. Guter and Bennett L. Leventhal and Jeff Salt and Catherine Lord and Christina Corsello and Vanessa Hus and Daniel E. Weeks and Fred R. Volkmar and Mait{\'e} Tauber and Eric Fombonne and Andy Shih and Kacie J. Meyer},
  journal={Nature Genetics},
Autism spectrum disorders (ASDs) are common, heritable neurodevelopmental conditions. The genetic architecture of ASDs is complex, requiring large samples to overcome heterogeneity. Here we broaden coverage and sample size relative to other studies of ASDs by using Affymetrix 10K SNP arrays and 1,181 families with at least two affected individuals, performing the largest linkage scan to date while also analyzing copy number variation in these families. Linkage and copy number variation analyses… 

Autism Susceptibility Genes Identification by Linkage Analysis: A Review

The purpose of this review is to evaluate the current status of autism susceptibility gene research and identify a number of suggestive loci.

Genetic architecture in autism spectrum disorder.

Haplotype structure enables prioritization of common markers and candidate genes in autism spectrum disorder

The rich multimodal genomic information collected on AGRE families is leveraged to present an efficient integrative strategy for prioritizing autism candidates and improving the understanding of the relationships among the vast collection of past genetic studies.

Autism genome-wide copy number variation reveals ubiquitin and neuronal genes

Several new susceptibility genes encoding neuronal cell-adhesion molecules, including NLGN1 and ASTN2, were enriched with CNVs in ASD cases compared to controls, and duplications 55 kilobases upstream of complementary DNA AK123120 indicate that these two important gene networks expressed within the central nervous system may contribute to the genetic susceptibility of ASD.

Segregating patterns of copy number variations in extended autism spectrum disorder (ASD) pedigrees

  • M. Woodbury-SmithM. Zarrei P. Szatmari
  • Psychology, Biology
    American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics
  • 2020
The heritable nature of ASD in the families studied remains poorly understood; only one CNV was identified that segregated with ASD phenotype; namely, a duplication overlapping DLGAP2 in three male offspring each with an ASD diagnosis.

Linkage and candidate gene studies of autism spectrum disorders in European populations

The case for a more detailed study of the role of RELN and GRIK2 in autism susceptibility is strengthened, as well as identifying two new potential candidate genes, MKL2 and SND1.

Copy number variation in the autism genome.

  • L. Feuk
  • Medicine, Biology
    Expert opinion on medical diagnostics
  • 2008
It has been shown that chromosomal rearrangements play an important role in ASDs and screening for copy number variation is an important approach in ASD research.

Towards understanding the genetics of Autism.

Next generation sequencing approaches have recently identified novel candidate genes and several point mutations in sporadic ASDs, thus increasing knowledge of ASD etiology.

Copy-number variations associated with autism spectrum disorder.

Current advances in array-based technology have increased the resolution in detecting submicroscopic deletions and duplications, referred to as copy-number variations, which will provide an opportunity to search for genes causing or contributing to ASDs but also to understand the genetics of ASD.

Molecular Cytogenetics of Autism

It is hypothesized that there might be at least three types of autism susceptibility genes/mutations that can be specific to an individual patient or family, in a genetically isolated sub-population and a common factor shared amongst different populations.

Analysis of IMGSAC autism susceptibility loci: evidence for sex limited and parent of origin specific effects

Analysis of an expanded sample of 219 affected sibling pairs suggests the possibility of two discrete loci underlying linkage of autism to chromosome 7, and implicate possible parent of origin specific effects in the aetiology of autism.

Evidence for sex-specific risk alleles in autism spectrum disorder.

The results suggest that sexual dichotomy is an important factor in the genetics of autism; the same strategy can be used to explore this possibility in other complex disorders that exhibit significant sex biases.

Autism as a paradigmatic complex genetic disorder.

It is essential that the restricted interests of patients with autism not be reflected in overly restrictive genetic approaches if the authors are to better understand the genetics of autism in the most expeditious and thorough manner.

Fragile X syndrome and autism at the intersection of genetic and neural networks

Understanding how the single-gene alteration in FXS plays out within complex genetic and neural network processes may suggest targets for autism research and illustrate strategies for relating autism to more singular genetic syndromes.

The broad autism phenotype: a complementary strategy for molecular genetic studies of autism.

  • J. Piven
  • Biology, Psychology
    American journal of medical genetics
  • 2001
Inclusion of information on the broad autism phenotype in relatives, in linkage studies of autism, may provide a potentially important, complementary approach for detecting the genes causing this condition.

Mutations of the X-linked genes encoding neuroligins NLGN3 and NLGN4 are associated with autism

Many studies have supported a genetic etiology for autism. Here we report mutations in two X-linked genes encoding neuroligins NLGN3 and NLGN4 in siblings with autism-spectrum disorders. These

Mutations in the gene encoding the synaptic scaffolding protein SHANK3 are associated with autism spectrum disorders

It is reported that a mutation of a single copy of SHANK3 on chromosome 22q13 can result in language and/or social communication disorders.

On the twin risk in autism.

The data clearly do not support twinning as a substantial risk factor in the etiology of autism, and it is demonstrated that the high proportion of twins found in affected-sib-pair studies can be adequately explained by the high ratio of concordance rates in monozygotic twins versus siblings and the distribution of family size in the population studied.

A genomic screen of autism: evidence for a multilocus etiology.

The results suggest that positional cloning of susceptibility loci by linkage analysis may be a formidable task and that other approaches may be necessary.