Showing papers by "Susan L. Santangelo published in 1999"

An autosomal genomic screen for autism

Abstract: Collaborative Linkage Study of Autism: Stacey Barrett,4 John C. Beck,2 Raphael Bernier,1 Erica Bisson,1 Terry A. Braun,2 Thomas L. Casavant,2 Deb Childress,2 Susan E. Folstein,1* Melissa Garcia,3 Mary Beth Gardiner,3 Stephen Gilman,1 Jonathan L. Haines,3 Kelly Hopkins,3 Rebecca Landa,4 Nicole H. Meyer,2 Julie Ann Mullane,1 Daryl Y. Nishimura,2 Pat Palmer,2 Joseph Piven,2** Joy Purdy,3 Susan L. Santangelo,1,5 Charles Searby,2 Val Sheffield,2 Jennifer Singleton,2 Susan Slager,2 Tom Struchen,2 Sarah Svenson,1 Veronica Vieland,2 Kai Wang,2 Brian Winklosky1 1New England Medical Center/Tufts University School of Medicine, Boston, Massachusetts 2University of Iowa College of Medicine, Iowa City, Iowa 3Vanderbilt University School of Medicine, Nashville, Tennessee 4The Johns Hopkins University School of Medicine, Baltimore, Maryland 5Harvard University School of Public Health, Boston, Massachusetts

An autosomal genomic screen for autism. Collaborative linkage study of autism.

Abstract: Autism is a severe neurodevelopmental disorder defined by social and communication deficits and ritualistic-repetitive behaviors that are detectable in early childhood. The etiology of idiopathic autism is strongly genetic, and oligogenic transmission is likely. The first stage of a two-stage genomic screen for autism was carried out by the Collaborative Linkage Study of Autism on individuals affected with autism from 75 families ascertained through an affected sib-pair. The strongest multipoint results were for regions on chromosomes 13 and 7. The highest maximum multipoint heterogeneity LOD (MMLS/het) score is 3.0 at D13S800 (approximately 55 cM from the telomere) under the recessive model, with an estimated 35% of families linked to this locus. The next highest peak is an MMLS/het score of 2.3 at 19 cM, between D13S217 and D13S1229. Our third highest MMLS/het score of 2.2 is on chromosome 7 and is consistent with the International Molecular Genetic Study of Autism Consortium report of a possible susceptibility locus somewhere within 7q31-33. These regions and others will be followed up in the second stage of our study by typing additional markers in both the original and a second set of identically ascertained autism families, which are currently being collected. By comparing results across a number of studies, we expect to be able to narrow our search for autism susceptibility genes to a small number of genomic regions. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 88:609-615, 1999.

Predictors of Cognitive Test Patterns in Autism Families

Abstract: In a case-control study of cognitive performance, tests of intelligence, reading, spelling, and pragmatic language were administered to the parents and siblings of 90 community-ascertained probands with autism (AU group) and to the parents and siblings of 40 similarly ascertained probands with trisomy 21 Down syndrome (DS group). The two samples were comparable for age and parents' education; both groups were well-educated and had above-average intelligence. AU parents scored slightly but significantly lower on the WAIS-R Full Scale and Performance IQ, on two subtests (Picture Arrangement and Picture Completion), and on the Word Attack Test (reading nonsense words) from the Woodcock-Johnson battery. There were no differences between AU and DS siblings. As in earlier studies, AU parents, more often than DS parents, reported a history of early language-related cognitive difficulties; we were not able to replicate this in siblings. AU parents who reported such difficulties scored significantly lower on Verbal IQ, spelling, and the nonsense reading test. AU parents without a history of early language-related cognitive difficulties often had a Verbal IQ that exceeded Performance IQ by more than one standard deviation. AU siblings with early language-related difficulties had similar findings: lower Verbal IQ, poorer spelling, and poorer reading scores, compared to AU siblings without such a history. Parents with a positive history also scored worse on a measure of pragmatic language,the Pragmatic Rating Scale, but not on measures of social-related components of the broader autism phenotype. We propose that cognitive differences in a subset of autism family members are manifestations of the language-related component of the broader autism phenotype, and separate from the social-related component. This is consistent with the hypothesis that there are several genes that may interact to cause autism which segregate independently and have distinguishable manifestations in family members. The hypothesis would be further supported by finding different patterns of genetic loci linked to autism in families where one or both parents has language difficulties.

The importance of watching our weights: how the choice of weights for non-independent sib pairs can dramatically alter results.

Abstract: Handling non-independent sib pairs in families with multiple affected sibs presents a problem in likelihood-based nonparametric linkage analyses. We contrast the more stable partial-likelihood solution in MAPMAKER/SIBS with the extremely variable partial-likelihood approach used in ASPEX, and the potential inflation of lods when the problem is ignored as in BETA.