A Genomic Screen of Autism: Evidence for a Multilocus Etiology
| Autor: | Linda Lotspeich, Luba Kalaydjieva, Joan Ferguson, Danielle Thorpe, Sue Dimiceli, Tamara Rogers, David A. Hinds, P. Brent Petersen, Helena Young, Tawna Pitts, C. Pingree, Carla Chiotti, Peter Nicholas, Patty McCague, Joan M. Hebert, A. A. Lin, Luigi Luca Cavalli-Sforza, Dona L. Wong, Boyd Salmon, Courtney Harper, Donna Spiker, Joan Yang, Richard M. Myers, Neil Risch, Loan Nguyen, Helena C. Kraemer, Joachim Hallmayer, Nassim Nouri, Susan Wiese-Slater, William M. McMahon, Saritha Vermeer |
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| Jazyk: | angličtina |
| Předmět: |
Adult
Male Linkage disequilibrium Multifactorial Inheritance Positional cloning Adolescent Genotype Genome screen Genetic Linkage Matched-Pair Analysis Autism Molecular Sequence Data Biology Identity by descent Linkage Disequilibrium Nuclear Family 03 medical and health sciences 0302 clinical medicine Sex Factors Genetic linkage Genetics Chromosomes Human Humans Genetics(clinical) Heritability of autism Autistic Disorder Child Nuclear family Genetics (clinical) 030304 developmental biology Linkage (software) Intelligence Tests 0303 health sciences Models Genetic Genetic marker Child Preschool Female 030217 neurology & neurosurgery Linkage analysis Research Article Microsatellite Repeats Statistical Distributions |
| Zdroj: | The American Journal of Human Genetics. (2):493-507 |
| ISSN: | 0002-9297 |
| DOI: | 10.1086/302497 |
| Popis: | Summary We have conducted a genome screen of autism, by linkage analysis in an initial set of 90 multiplex sibships, with parents, containing 97 independent affected sib pairs (ASPs), with follow-up in 49 additional multiplex sibships, containing 50 ASPs. In total, 519 markers were genotyped, including 362 for the initial screen, and an additional 157 were genotyped in the follow-up. As a control, we also included in the analysis unaffected sibs, which provided 51 discordant sib pairs (DSPs) for the initial screen and 29 for the follow-up. In the initial phase of the work, we observed increased identity by descent (IBD) in the ASPs (sharing of 51.6%) compared with the DSPs (sharing of 50.8%). The excess sharing in the ASPs could not be attributed to the effect of a small number of loci but, rather, was due to the modest increase in the entire distribution of IBD. These results are most compatible with a model specifying a large number of loci (perhaps ⩾15) and are less compatible with models specifying ≤10 loci. The largest LOD score obtained in the initial scan was for a marker on chromosome 1p; this region also showed positive sharing in the replication family set, giving a maximum multipoint LOD score of 2.15 for both sets combined. Thus, there may exist a gene of moderate effect in this region. We had only modestly positive or negative linkage evidence in candidate regions identified in other studies. Our results suggest that positional cloning of susceptibility loci by linkage analysis may be a formidable task and that other approaches may be necessary. |
| Databáze: | OpenAIRE |
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