Incorporating language phenotypes strengthens evidence of linkage to autism

Wiley - Tập 105 Số 6 - Trang 539-547 - 2001
Yuki Bradford1, Jonathan L. Haines1, Holli B. Hutcheson1, Marybeth Gardiner1, Terry A. Braun2, Val C. Sheffield2, Tom Cassavant2, Wen Huang2, Kai Wang2, Veronica J. Vieland2, Susan E. Folstein3, Susan L. Santangelo4, Joseph Piven5
1Vanderbilt University
2University of Iowa
3Department of Biostatistics and Psychiatry, Division of Statistical Genetics, University of Iowa, Iowa City, Iowa
4Tufts University
5Department of Psychiatry

Tóm tắt

AbstractWe investigated the effect of incorporating information about proband and parental structural language phenotypes into linkage analyses in the two regions for which we found the highest signals in our first‐stage affected sibling pair genome screen: chromosomes 13q and 7q. We were particularly interested in following up on our chromosome 7q finding in light of two prior reports of linkage of this region to developmental language disorder, since one of the diagnostic criteria for autism is absent or abnormal language development. We hypothesized that if the language phenotype were genetically relevant to linkage at the chromosome 7q locus, then incorporating parents phenotypes would increase the signal at that locus, and most of the signal would originate from the subset of families in which both probands had severe language delay. The results support these hypotheses. The linkage signals we obtained on chromosome 7q as well as at least one signal on chromosome 13q are mainly attributable to the subgroup of families in which both probands had language delay. This became apparent only when the parents’ history of language‐related difficulties was also incorporated into the analyses. Although based on our data, we were not able to distinguish between epistasis or heterogeneity models, we tentatively concluded that there may be more than one autism susceptibility locus related to language development. © 2001 Wiley‐Liss, Inc.

Từ khóa


Tài liệu tham khảo

10.1007/BF02172133

10.1192/bjp.126.2.127

Bass MP, 1999, Genomic screen for autistic disorder, Mol Psychiatry, 4, S13

10.1111/j.1469-7610.1994.tb02300.x

CLSA, 1999, An autosomal genomic screen for autism, Am J Med Genet (Neuropsychiatr Genet), 88, 609, 10.1002/(SICI)1096-8628(19991215)88:6<609::AID-AJMG7>3.0.CO;2-L

10.1086/301832

Durner M, 1992, Inter‐ and intrafamilial heterogeneity: effective sampling strategies and comparison of analysis methods, Am J Hum Genet, 51, 859

10.1038/ng0298-168

Folstein SE, 1999, Neurodevelopmental disorders, 431

Folstein SE, 1999, Predictors of cognitive test patterns in autism families, J Child Psychol Psychiatry, 40, 10.1111/1469-7610.00528

10.1002/gepi.1370090107

Hodge SE, 1997, Magnitude of type I error when single‐locus linkage analysis is maximized over models: a simulation study, Am J Hum Genet, 60, 217

Holmans P, 1993, Asymptotic properties of affected‐sib‐pair linkage analysis, Am J Hum Genet, 52, 362

10.1159/000053345

10.1093/hmg/7.3.571

Kruglyak L, 1996, Parametric and nonparametric linkage analysis: a unified multipoint approach, Am J Hum Genet, 58, 1347

10.1017/S0033291700032918

Lathrop GM, 1985, Multilocus linkage analysis in humans: detection of linkage and estimation of recombination, Am J Hum Genet, 46, 482

Lathrop GM, 1990, Analysis of complex diseases under oligogenic models and intrafamilial heterogeneity by the LINKAGE programs, Am J Hum Genet, 47, A188

10.1023/A:1025873925661

10.1007/BF02211841

10.1093/hmg/8.5.805

Pickles A, 1995, Latent‐class analysis of recurrence risks for complex phenotypes with selection and measurement error: a twin and family history study of autism, Am J Hum Genet, 57, 717

10.1017/S0033291700027938

10.1176/ajp.154.2.185

10.1002/(SICI)1096-8628(19970725)74:4<398::AID-AJMG11>3.0.CO;2-D

Risch N, 1990, Linkage strategies for genetically complex traits. III. the effect of marker polymorphism on analysis of affected relative pairs, Am J Hum Genet, 46, 242

10.1111/j.1469-1809.1996.tb01185.x

Sutcliffe JS, 2000, Linkage disequilibrium in autism families to markers in the 15q11–q13 autism candidate region, Am J Hum Genet, 67, A178

Tomblin J, 1998, Association of developmental language impairment with loci at 7q31, Am J Hum Genet, 63, A312

10.1002/gepi.1370090106

10.1159/000154155

Thông tin
Thông tin xuất bản

Wiley

Tập 105 Số 6

539-547

Thông tin tác giả