Rare variants in the genetic background modulate cognitive and developmental phenotypes in individuals carrying disease-associated variants
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Abstract
PURPOSE: To assess the contribution of rare variants in the genetic background toward variability of neurodevelopmental phenotypes in individuals with rare copy-number variants (CNVs) and gene-disruptive variants. METHODS: We analyzed quantitative clinical information, exome sequencing, and microarray data from 757 probands and 233 parents and siblings who carry disease-associated variants. RESULTS: The number of rare likely deleterious variants in functionally intolerant genes ("other hits") correlated with expression of neurodevelopmental phenotypes in probands with 16p12.1 deletion (n=23, p=0.004) and in autism probands carrying gene-disruptive variants (n=184, p=0.03) compared with their carrier family members. Probands with 16p12.1 deletion and a strong family history presented more severe clinical features (p=0.04) and higher burden of other hits compared with those with mild/no family history (p=0.001). The number of other hits also correlated with severity of cognitive impairment in probands carrying pathogenic CNVs (n=53) or de novo pathogenic variants in disease genes (n=290), and negatively correlated with head size among 80 probands with 16p11.2 deletion. These co-occurring hits involved known disease-associated genes such as SETD5, AUTS2, and NRXN1, and were enriched for cellular and developmental processes. CONCLUSION: Accurate genetic diagnosis of complex disorders will require complete evaluation of the genetic background even after a candidate disease-associated variant is identified.
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Pizzo et al. tested RNA knockdown of 16p11.2 genes on more than 20 Drosophila phenotypes and found that combinations of multiple genes elicit varied effects on eye, wing, and nervous system development.
“Pizzo et al, tested the effect of RNA-knockdown of genes on >20 classic phenotypes used to assess development in Drosophila (Pizzo et al., 2018). This study found that combinations of multiple 16p11.2 genes could elicit a variety of effects on development of the eye, wing and nervous system.”
From Getting to the cores of autism (2019) · cites this paper as Pizzo et al., 2018
Similar correlation between clinical severity and secondary rare variant number is observed for ASD subjects carrying gene-disrupting de novo mutations.
“Subsequent studies have shown that the clinical severity of subjects who carry CNVs at 1q21.1, 7q11.23 and 16p11.2 correlates with the number of secondary rare variants, and similar results have been observed for ASD subjects who carry gene disrupting de novo mutations (Pizzo et al., 2018).”
From Getting to the cores of autism (2019) · cites this paper as Pizzo et al., 2018
Transcriptomic analysis of developing brain in transgenic mouse models of SETD5, FOXP1, and TBR1 suggests that mutations in these genes lead to dysregulation of ASD genes in trans.
“Similarly transcriptomic analysis of developing brain in transgenic mouse models of SETD5 (Pizzo et al., 2018), FOXP1 (Araujo et al., 2015), TBR1 (Notwell et al., 2016) suggests that mutations in these genes leads to the dysregulation of ASD genes in trans.”
From Getting to the cores of autism (2019) · cites this paper as Pizzo et al., 2018
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Cites
Analysis of protein-coding genetic variation in 60,706 humans
Exome Aggregation Consortium, Lek, M., Karczewski, K. J., Minikel, E. V., Samocha, K. E., Banks, E., Fennell, T., O’Donnell-Luria, A. H., Ware, J. S., Hill, A. J., et al. (2016) · Nature · doi:10.1038/nature19057 · Cited by 9,587 · see citing works
Van der Auwera, G. A., Carneiro, M. O., Hartl, C., Poplin, R., del Angel, G., Levy‐Moonshine, A., Jordan, T., Shakir, K., Roazen, D., Thibault, J., et al. (2013) · Current Protocols in Bioinformatics · doi:10.1002/0471250953.bi1110s43 · Cited by 6,687 · see citing works
A general framework for estimating the relative pathogenicity of human genetic variants
Kircher, M., Witten, D. M., Jain, P., O'Roak, B. J., Cooper, G. M., & Shendure, J. (2014) · Nature Genetics · doi:10.1038/ng.2892 · Cited by 6,183 · see citing works
Goh, K.-I., Cusick, M. E., Valle, D., Childs, B., Vidal, M., & Barabási, A.-L. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0701361104 · Cited by 3,242 · see citing works
The contribution of de novo coding mutations to autism spectrum disorder
Iossifov, I., O’Roak, B. J., Sanders, S. J., Ronemus, M., Krumm, N., Levy, D., Stessman, H. A., Witherspoon, K. T., Vives, L., Patterson, K. E., et al. (2014) · Nature · doi:10.1038/nature13908 · Cited by 2,585 · see citing works
Large-scale gene function analysis with the PANTHER classification system
Mi, H., Muruganujan, A., Casagrande, J. T., & Thomas, P. D. (2013) · Nature Protocols · doi:10.1038/nprot.2013.092 · Cited by 2,422 · see citing works
Enrichment Map: A Network-Based Method for Gene-Set Enrichment Visualization and Interpretation
Merico, D., Isserlin, R., Stueker, O., Emili, A., & Bader, G. D. (2010) · PLoS ONE · doi:10.1371/journal.pone.0013984 · Cited by 2,235 · see citing works
Genome-wide association analysis identifies 13 new risk loci for schizophrenia
Multicenter Genetic Studies of Schizophrenia Consortium, Ripke, S., Psychosis Endophenotypes International Consortium, Wellcome Trust Case Control Consortium 2, O'Dushlaine, C., Chambert, K., Moran, J. L., Kähler, A. K., Akterin, S., Bergen, S. E., et al. (2013) · Nature Genetics · doi:10.1038/ng.2742 · Cited by 1,496 · see citing works
Insights into autism spectrum disorder genomic architecture and biology from 71 risk loci
Sanders, S. J., He, X., Willsey, A. J., Ercan-Sencicek, A. G., Samocha, K. E., Cicek, A. E., Murtha, M. T., Bal, V. H., Bishop, S. L., Dong, S., et al. (2015) · Neuron · doi:10.1016/j.neuron.2015.09.016 · Cited by 1,430 · see citing works
Genic Intolerance to Functional Variation and the Interpretation of Personal Genomes
Petrovski, S., Wang, Q., Heinzen, E. L., Allen, A. S., & Goldstein, D. B. (2013) · PLoS Genetics · doi:10.1371/journal.pgen.1003709 · Cited by 901 · see citing works
Resolution of Disease Phenotypes Resulting from Multilocus Genomic Variation
Posey, J. E., Harel, T., Liu, P., Rosenfeld, J. A., James, R. A., Coban‐Akdemir, Z., Walkiewicz, M. A., Bi, W., Xiao, R., Ding, Y., et al. (2016) · New England Journal of Medicine · doi:10.1056/nejmoa1516767 · Cited by 772 · see citing works
Self-citationAssociation within a family of a balanced autosomal translocation with major mental illness
St Clair, D., Blackwood, D., Muir, W., Walker, M., St Clair, D., Muir, W., Carothers, A., Spowart, G., Gosden, C., & Evans, H. J. (1990) · The Lancet · doi:10.1016/0140-6736(90)91520-k · Cited by 727 · see citing works
CNVs conferring risk of autism or schizophrenia affect cognition in controls
Stefansson, H., Meyer-Lindenberg, A., Steinberg, S., Magnusdottir, B., Morgen, K., Arnarsdottir, S., Bjornsdottir, G., Walters, G. B., Jonsdottir, G. A., Doyle, O. M., et al. (2014) · Nature · doi:10.1038/nature12818 · Cited by 699 · see citing works
A recurrent 16p12.1 microdeletion supports a two-hit model for severe developmental delay
Girirajan, S., Rosenfeld, J. A., Cooper, G. M., Antonacci, F., Siswara, P., Itsara, A., Vives, L., Walsh, T., McCarthy, S. E., Baker, C., et al. (2010) · Nature Genetics · doi:10.1038/ng.534 · Cited by 667 · see citing works
Self-citationPhenotypic Heterogeneity of Genomic Disorders and Rare Copy-Number Variants
Girirajan, S., Rosenfeld, J. A., Coe, B. P., Parikh, S., Friedman, N., Goldstein, A., Filipink, R. A., McConnell, J. S., Angle, B., Meschino, W. S., et al. (2012) · New England Journal of Medicine · doi:10.1056/nejmoa1200395 · Cited by 621 · see citing works
Self-citationJacquemont, S., Coe, B. P., Hersch, M., Duyzend, M. H., Krumm, N., Bergmann, S., Beckmann, J. S., Rosenfeld, J. A., & Eichler, E. E. (2014) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2014.02.001 · Cited by 605 · see citing works
Self-citationExcess of rare, inherited truncating mutations in autism
Krumm, N., Turner, T. N., Baker, C., Vives, L., Mohajeri, K., Witherspoon, K., Raja, A., Coe, B. P., Stessman, H. A., He, Z.-X., et al. (2015) · Nature Genetics · doi:10.1038/ng.3303 · Cited by 587 · see citing works
Autism genetics: opportunities and challenges for clinical translation
Vorstman, J. A. S., Parr, J. R., Moreno‐De‐Luca, D., Anney, R., Nürnberger, J. I., & Hallmayer, J. F. (2017) · Nature Reviews Genetics · doi:10.1038/nrg.2017.4 · Cited by 466 · see citing works
Mirror extreme BMI phenotypes associated with gene dosage at the chromosome 16p11.2 locus
Jacquemont, S., Reymond, A., Zufferey, F., Harewood, L., Walters, R. G., Kutalik, Z., Martinet, D., Shen, Y., Valsesia, A., Beckmann, N. D., et al. (2011) · Nature · doi:10.1038/nature10406 · Cited by 462 · see citing works
Self-citationDevelopmental brain dysfunction: revival and expansion of old concepts based on new genetic evidence
Moreno-De-Luca, A., Myers, S. M., Challman, T. D., Moreno-De-Luca, D., Evans, D. W., & Ledbetter, D. H. (2013) · The Lancet Neurology · doi:10.1016/s1474-4422(13)70011-5 · Cited by 330 · see citing works
Genomic Patterns of De Novo Mutation in Simplex Autism
Turner, T. N., Coe, B. P., Dickel, D. E., Hoekzema, K., Nelson, B. J., Zody, M. C., Kronenberg, Z. N., Hormozdiari, F., Raja, A. N., Pennacchio, L. A., et al. (2017) · Cell · doi:10.1016/j.cell.2017.08.047 · Cited by 330 · see citing works
Bijlsma, E. K., Gijsbers, A. C. J., Schuurs-Hoeijmakers, J. H. M., van Haeringen, A., Fransen van de Putte, D. E., Anderlid, B.-M., Lundin, J., Lapunzina, P., Pérez Jurado, L. A., Delle Chiaie, B., et al. (2009) · European Journal of Medical Genetics · doi:10.1016/j.ejmg.2009.03.006 · Cited by 282 · see citing works
Self-citationDefining the effect of the 16p11.2 duplication on cognition, behavior, and medical comorbidities
D’Angelo, D., Lebon, S., Chen, Q., Martin-Brevet, S., Snyder, L. G., Hippolyte, L., Hanson, E., Maillard, A. M., Faucett, W. A., Macé, A., et al. (2016) · JAMA Psychiatry · doi:10.1001/jamapsychiatry.2015.2123 · Cited by 277 · see citing works
Self-citationClinical studies on submicroscopic subtelomeric rearrangements: a checklist
Vries, B. B. A. D., White, S. M., Knight, S. J. L., Regan, R., Homfray, T., Young, I. D., Super, M., McKeown, C., Splitt, M., Quarrell, O. W. J., et al. (2001) · Journal of Medical Genetics · doi:10.1136/jmg.38.3.145 · Cited by 268 · see citing works
The Genotype-Tissue Expression (GTEx) project
Lonsdale, J., Thomas, J., Salvatore, M., Phillips, R., Lo, E., Shad, S., Hasz, R., Walters, G., Garcia, F., Young, N., et al. (2013) · Nature Genetics · doi:10.1038/ng.2653 · Cited by 263 · see citing works
Singh, T., Walters, J. T. R., Johnstone, M., Curtis, D., Suvisaari, J., Torniainen, M., Rees, E., Iyegbe, C., Blackwood, D., McIntosh, A. M., et al. (2017) · Nature Genetics · doi:10.1038/ng.3903 · Cited by 231 · see citing works
Paternally inherited cis-regulatory structural variants are associated with autism
Brandler, W. M., Antaki, D., Gujral, M., Kleiber, M. L., Whitney, J., Maile, M. S., Hong, O., Chapman, T. R., Tan, S., Tandon, P., et al. (2018) · Science · doi:10.1126/science.aan2261 · Cited by 209 · see citing works
Rosenfeld, J. A., Coppinger, J., Bejjani, B. A., Girirajan, S., Eichler, E. E., Shaffer, L. G., & Ballif, B. C. (2010) · Journal of Neurodevelopmental Disorders · doi:10.1007/s11689-009-9037-4 · Cited by 207 · see citing works
Self-citationCopy Number Variations and Cognitive Phenotypes in Unselected Populations
Männik, K., Mägi, R., Macé, A., Cole, B., Guyatt, A. L., Shihab, H. A., Maillard, A. M., Alavere, H., Kolk, A., Reigo, A., et al. (2015) · JAMA · doi:10.1001/jama.2015.4845 · Cited by 201 · see citing works
Self-citationOligogenic heterozygosity in individuals with high-functioning autism spectrum disorders
Schaaf, C. P., Sabo, A., Sakai, Y., Crosby, J., Muzny, D., Hawes, A., Lewis, L., Akbar, H., Varghese, R., Boerwinkle, E., et al. (2011) · Human Molecular Genetics · doi:10.1093/hmg/ddr243 · Cited by 175 · see citing works
The Simons VIP Consortium (2012) · Neuron · doi:10.1016/j.neuron.2012.02.014 · Cited by 165 · see citing works
Low load for disruptive mutations in autism genes and their biased transmission
Iossifov, I., Levy, D., Allen, J., Ye, K., Ronemus, M., Lee, Y.-H., Yamrom, B., & Wigler, M. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1516376112 · Cited by 156 · see citing works
Phenotypic expansion illuminates multilocus pathogenic variation
Karaca, E., Posey, J. E., Coban‐Akdemir, Z., Pehli̇van, D., Harel, T., Jhangiani, S. N., Bayram, Y., Song, X., Bahrambeigi, V., Yüreğir, Ö. Ö., et al. (2018) · Genetics in Medicine · doi:10.1038/gim.2018.33 · Cited by 150 · see citing works
A Cross-Disorder Method to Identify Novel Candidate Genes for Developmental Brain Disorders
Gonzalez-Mantilla, A. J., Moreno-De-Luca, A., Ledbetter, D. H., & Martin, C. L. (2016) · JAMA Psychiatry · doi:10.1001/jamapsychiatry.2015.2692 · Cited by 139 · see citing works
Moreno-De-Luca, A., Evans, D. W., Boomer, K. B., Hanson, E., Bernier, R., Goin-Kochel, R. P., Myers, S. M., Challman, T. D., Moreno-De-Luca, D., Slane, M. M., et al. (2015) · JAMA Psychiatry · doi:10.1001/jamapsychiatry.2014.2147 · Cited by 137 · see citing works
Schuurs-Hoeijmakers, J. H. M., Oh, E. C. T., Vissers, L. E. L. M., Swinkels, M. E. M., Gilissen, C., Willemsen, M. A. A. P., Holvoet, M., Steehouwer, M., Veltman, J. A., Vries, B. B. A. D., et al. (2012) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2012.10.013 · Cited by 131 · see citing works
An assessment of sex bias in neurodevelopmental disorders
Polyak, A., Rosenfeld, J. A., & Girirajan, S. (2015) · Genome Medicine · doi:10.1186/s13073-015-0216-5 · Cited by 129 · see citing works
Self-citationRees, E., Walters, J., Chambert, K., O'Dushlaine, C., Szatkiewicz, J., Richards, A. L., Georgieva, L., Mahoney‐Davies, G., Legge, S. E., Moran, J. L., et al. (2013) · Human Molecular Genetics · doi:10.1093/hmg/ddt540 · Cited by 129 · see citing works
Variable epilepsy phenotypes associated with a familial intragenic deletion of the SCN1A gene
Guerrini, R., Cellini, E., Mei, D., Metitieri, T. T., Petrelli, C., Pucatti, D., Marini, C., & Zamponi, N. (2010) · Epilepsia · doi:10.1111/j.1528-1167.2010.02790.x · Cited by 65 · see citing works
Histone Modifier Genes Alter Conotruncal Heart Phenotypes in 22q11.2 Deletion Syndrome
Guo, T., Chung, J. H., Wang, T., McDonald‐McGinn, D. M., Kates, W. R., Hawuła, W., Coleman, K. B., Zackai, E. H., Emanuel, B. S., & Morrow, B. E. (2015) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2015.10.013 · Cited by 60 · see citing works
Revealing the Complexity of a Monogenic Disease: Rett Syndrome Exome Sequencing
Grillo, E., Rizzo, C. L., Bianciardi, L., Bizzarri, V., Baldassarri, M., Spiga, O., Furini, S., Felice, C. D., Signorini, C., Leoncini, S., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0056599 · Cited by 58 · see citing works
Self-citationIncomplete penetrance of NRXN1 deletions in families with schizophrenia
Todarello, G., Feng, N., Kolachana, B. S., Li, C., Vakkalanka, R., Bertolino, A., Weinberger, D. R., & Straub, R. E. (2014) · Schizophrenia Research · doi:10.1016/j.schres.2014.02.023 · Cited by 39 · see citing works
Klaassen, P., Duijff, S. N., de Veye, H. F. N. S., Beemer, F. A., Sinnema, G., Breetvelt, E., Schappin, R., & Vorstman, J. A. S. (2016) · American Journal of Medical Genetics Part B Neuropsychiatric Genetics · doi:10.1002/ajmg.b.32441 · Cited by 32 · see citing works
Hammer, M. F., Ishii, A., Johnstone, L. M., Tchourbanov, A. Y., Lau, B., Sprissler, R. S., Hallmark, B., Zhang, M., Zhou, J. J., Watkins, J. C., et al. (2017) · PLoS ONE · doi:10.1371/journal.pone.0180485 · Cited by 25 · see citing works
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Getting to the cores of autism
Iakoucheva, L. M., Muotri, A. R., & Sebat, J. (2019) · Cell · doi:10.1016/j.cell.2019.07.037 · Cited by 260 · see citing works
“Similarly, transcriptomic analysis of developing brain in transgenic mouse models of SETD5 (Pizzo et al., 2018), FOXP1 (Araujo et al., 2015), and TBR1 (Notwell et al., 2016) suggests that mutations in these genes leads to the dysregulation of ASD genes in trans.”
BackgroundResultInfluentialInsufficient Evidence for “Autism-Specific” Genes
Myers, S. M., Challman, T. D., Bernier, R., Bourgeron, T., Chung, W. K., Constantino, J. N., Eichler, E. E., Jacquemont, S., Miller, D. T., Mitchell, K. J., et al. (2020) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2020.04.004 · Cited by 165 · see citing works
Ts66Yah, a mouse model of down syndrome with improved construct and face validity
Duchon, A., del Mar Muñiz Moreno, M., Chevalier, C., Nalesso, V., Andre, P., Fructuoso-Castellar, M., Mondino, M., Po, C., Noblet, V., Birling, M.-C., et al. (2022) · Disease Models & Mechanisms · doi:10.1242/dmm.049721 · Cited by 58 · see citing works
- Authors
- Pizzo, L., Jensen, M., Polyak, A., Rosenfeld, J. A., Mannik, K., Krishnan, A., McCready, E., Pichon, O., Le Caignec, C., Van Dijck, A., Pope, K., Voorhoeve, E., Yoon, J., Stankiewicz, P., Cheung, S. W., Pazuchanics, D., Huber, E., Kumar, V., Kember, R. L., Mari, F., Curró, A., Castiglia, L., Galesi, O., Avola, E., Mattina, T., Fichera, M., Mandarà, L., Vincent, M., Nizon, M., Mercier, S., Bénéteau, C., Blesson, S., Martin-Coignard, D., Mosca-Boidron, A.-L., Caberg, J.-H., Bucan, M., Zeesman, S., Nowaczyk, M. J. M., Lefebvre, M., Faivre, L., Callier, P., Skinner, C., Keren, B., Perrine, C., Prontera, P., Marle, N., Renieri, A., Reymond, A., Kooy, R. F., Isidor, B., Schwartz, C., Romano, C., Sistermans, E., Amor, D. J., Andrieux, J., & Girirajan, S.
- Affiliations
- Pennsylvania State University (US)
- Baylor College of Medicine (US)
- Michigan State University (US)
- McMaster University (CA)
- Centre Hospitalier Universitaire de Nantes (FR)
- Royal Children's Hospital (AU)
- Amsterdam UMC Location University of Amsterdam (NL)
- University of Pennsylvania (US)
- University of Siena (IT)
- I.R.C.C.S. Oasi Maria SS (IT)
- University of Catania (IT)
- University of Ragusa (IT)
- Centre Hospitalier Universitaire de Liège (BE)
- CHU Dijon Bourgogne (FR)
- Greenwood Genetic Center (US)
- Pitié-Salpêtrière Hospital (FR)
- University of Lausanne (CH)
- University of Antwerp (BE)
- Centre Hospitalier Universitaire de Lille (FR)
- Corresponding author
- Girirajan, Santhosh
- ORCID
- Pizzo, Lucilla
- Jensen, Matthew
- Rosenfeld, Jill A.
- Krishnan, Arjun
- McCready, Elizabeth
- Pichon, Olivier
- Pope, Kate
- Voorhoeve, Els
- Stankiewicz, Paweł
- Cheung, Sau Wai
- Huber, Emily
- Kember, Rachel L.
- Mari, Francesca
- Castiglia, Lucia
- Galesi, Ornella
- Avola, Emanuela
- Mattina, Teresa
- Fichera, Marco
- Vincent, Marie
- Nizon, Mathilde
- Mercier, Sandra
- Bénéteau, Claire
- Caberg, Jean-Hubert
- Nowaczyk, Małgorzata J.M.
- Lefebvre, Mathilde
- Faivre, Laurence
- Callier, Patrick
- Skinner, Cindy
- Keren, Boris
- Prontera, Paolo
- Marle, Nathalie
- Renieri, Alessandra
- Reymond, Alexandre
- Kooy, R. Frank
- Isidor, Bertrand
- Schwartz, Charles
- Romano, Corrado
- Sistermans, Erik
- Amor, David J.
- Girirajan, Santhosh
- Venue
- Genetics in Medicine
- Publisher
- Elsevier BV
- Published
- 2019-04
- Volume
- 21
- Issue
- 4
- Pages
- 816-825
- ISSN
- 1098-3600 (ISSN-L)
- PMC
- PMC6405313
- OpenAlex
- W2892078296
- Cited by
- 193
- References
- 44
- Citations by year
- 2026: 3 · 2025: 18 · 2024: 38 · 2023: 21 · 2022: 35 · 2021: 28 · 2020: 26 · 2019: 23 · 2018: 1
- FWCI
- 11.77
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Genetics in Medicine (publishedVersion, cc-by-nc-nd)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Pure Amsterdam UMC (publishedVersion, other-oa)
- Amsterdam UMC (VU Amsterdam) - Institutional Repository (publishedVersion, other-oa)
- SERVAL (Université de Lausanne) (acceptedVersion, cc-by-nc-nd)
- IRIS (submittedVersion, cc-by-nc-nd)
- HAL (submittedVersion)
- Minerva Access (University of Melbourne) (submittedVersion, cc-by-nc-nd)
- Open Repository and Bibliography (University of Liège) (submittedVersion)
- Use Siena air (University of Siena) (submittedVersion, other-oa)
- Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
- Funders
- National Science Foundation (31003A_160203)
- Agencia Nacional de Investigación e Innovación
- National Alliance for Research on Schizophrenia and Depression (22535)
- Simons Foundation Autism Research Initiative (399894)
- US-UK Fulbright Commission
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (160203)
- Ministero della Salute
- Jacobs Foundation
- National Institutes of Health (NIH T32, NIH-R01)
- Huck Institutes of the Life Sciences
- National Institute of General Medical Sciences (T32GM102057, R01GM121907)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomic variations and chromosomal abnormalities
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomics and Rare Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Keywords
- rare variants, genetic background, copy number variation, neurodevelopmental phenotype, cognitive impairment, autism spectrum disorder, 16p11.2 deletion, de novo mutations, family history (medicine), head size, SETD5, AUTS2, NRXN1, genetic diagnosis
- MeSH terms
- Genetic Background, Autistic Disorder, Calcium-Binding Proteins, Chromosomes, Human, Pair 16, Cognition, Cytoskeletal Proteins, Female, Gene Expression Regulation, Genetic Carrier Screening, Humans, Male, Methyltransferases, Nerve Tissue Proteins, Parents, Pedigree, Phenotype, Proteins, Transcription Factors, Cell Adhesion Molecules, Neuronal, Sequence Deletion, Neural Cell Adhesion Molecules, Siblings, DNA Copy Number Variations
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