Abstract
Genetic studies of autism over the past decade suggest a complex landscape of multiple genes. In the face of this heterogeneity, studies that include large extended pedigrees may offer valuable insights, as the relatively few susceptibility genes within single large families may be more easily discerned. This genome-wide screen of 70 families includes 20 large extended pedigrees of 6–9 generations, 6 moderate-sized families of 4–5 generations and 44 smaller families of 2–3 generations. The Center for Inherited Disease Research (CIDR) provided genotyping using the Illumina Linkage Panel 12, a 6K single-nucleotide polymorphism (SNP) platform. Results from 192 subjects with an autism spectrum disorder (ASD) and 461 of their relatives revealed genome-wide significance on chromosome 15q, with three possibly distinct peaks: 15q13.1–q14 (heterogeneity LOD (HLOD)=4.09 at 29 459 872 bp); 15q14–q21.1 (HLOD=3.59 at 36 837 208 bp); and 15q21.1–q22.2 (HLOD=5.31 at 55 629 733 bp). Two of these peaks replicate earlier findings. There were additional suggestive results on chromosomes 2p25.3–p24.1 (HLOD=1.87), 7q31.31–q32.3 (HLOD=1.97) and 13q12.11–q12.3 (HLOD=1.93). Affected subjects in families supporting the linkage peaks found in this study did not reveal strong evidence for distinct phenotypic subgroups.
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Acknowledgements
This work was supported by R01 MH06359, the Utah Autism Foundation, the Carmen B Pingree School for Children with Autism and GCRC M01-RR025764 from the National Center for Research Resources. Partial support for all data sets within the Utah Population Database (UPDB) was provided by the University of Utah Huntsman Cancer Institute. We thank our staff whose countless hours of work have made this study possible. We also greatly appreciate the time and effort given by the family members who participated in this study.
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Drs Coon, McMahon, Miller, and Leppert received partial salary support from Lineagen Inc. (www.lineagen.com). Lineagen is funding University of Utah research in biomarker discovery for multiple sclerosis, osteoporosis, chronic obstructive pulmonary disease, and autism.
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Allen-Brady, K., Robison, R., Cannon, D. et al. Genome-wide linkage in Utah autism pedigrees. Mol Psychiatry 15, 1006–1015 (2010). https://doi.org/10.1038/mp.2009.42
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DOI: https://doi.org/10.1038/mp.2009.42
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