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Dissecting the locus heterogeneity of autism: significant linkage to chromosome 12q14.
Mol Psychiatry. 2007 Apr; 12(4):376-84.MP

Abstract

Autism is a common neurodevelopmental disorder with a significant genetic component and locus heterogeneity. To date, 12 microsatellite genome screens have been performed using various data sets of sib-pair families (parents and affected children) resulting in numerous regions of potential linkage across the genome. However, no universal region or consistent candidate gene from these regions has emerged. The use of large, extended pedigrees is a recognized powerful approach to identify significant linkage results, as these families potentially contain more potential linkage information than sib-pair families. A genome-wide linkage analysis was performed on 26 extended autism families (65 affected, 184 total individuals). Each family had two to four affected individuals comprised of either avuncular or cousin pairs. For analysis, we used a high-density single-nucleotide polymorphism genotyping assay, the Affymetrix GeneChip Human Mapping 10K array. Two-point analysis gave peak heterogeneity limit of detection (HLOD) of 2.82 at rs2877739 on chromosome 14q. Suggestive linkage evidence (HLOD>2) from a two-point analysis was also found on chromosomes 1q, 2q, 5q, 6p,11q and 12q. Chromosome 12q was the only region showing significant linkage evidence by multipoint analysis with a peak HLOD=3.02 at rs1445442. In addition, this linkage evidence was enhanced significantly in the families with only male affected (multipoint HLOD=4.51), suggesting a significant gender-specific effect in the etiology of autism. Chromosome-wide haplotype analyses on chromosome 12 localized the potential autism gene to a 4 cM region shared among the affected individuals across linked families. This novel linkage peak on chromosome 12q further supports the hypothesis of substantial locus heterogeneity in autism.

Authors+Show Affiliations

Center for Human Genetics, Duke University Medical Center, Durham, NC 27710, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17179998

Citation

Ma, D Q., et al. "Dissecting the Locus Heterogeneity of Autism: Significant Linkage to Chromosome 12q14." Molecular Psychiatry, vol. 12, no. 4, 2007, pp. 376-84.
Ma DQ, Cuccaro ML, Jaworski JM, et al. Dissecting the locus heterogeneity of autism: significant linkage to chromosome 12q14. Mol Psychiatry. 2007;12(4):376-84.
Ma, D. Q., Cuccaro, M. L., Jaworski, J. M., Haynes, C. S., Stephan, D. A., Parod, J., Abramson, R. K., Wright, H. H., Gilbert, J. R., Haines, J. L., & Pericak-Vance, M. A. (2007). Dissecting the locus heterogeneity of autism: significant linkage to chromosome 12q14. Molecular Psychiatry, 12(4), 376-84.
Ma DQ, et al. Dissecting the Locus Heterogeneity of Autism: Significant Linkage to Chromosome 12q14. Mol Psychiatry. 2007;12(4):376-84. PubMed PMID: 17179998.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Dissecting the locus heterogeneity of autism: significant linkage to chromosome 12q14. AU - Ma,D Q, AU - Cuccaro,M L, AU - Jaworski,J M, AU - Haynes,C S, AU - Stephan,D A, AU - Parod,J, AU - Abramson,R K, AU - Wright,H H, AU - Gilbert,J R, AU - Haines,J L, AU - Pericak-Vance,M A, Y1 - 2006/12/19/ PY - 2006/12/21/pubmed PY - 2007/6/2/medline PY - 2006/12/21/entrez SP - 376 EP - 84 JF - Molecular psychiatry JO - Mol. Psychiatry VL - 12 IS - 4 N2 - Autism is a common neurodevelopmental disorder with a significant genetic component and locus heterogeneity. To date, 12 microsatellite genome screens have been performed using various data sets of sib-pair families (parents and affected children) resulting in numerous regions of potential linkage across the genome. However, no universal region or consistent candidate gene from these regions has emerged. The use of large, extended pedigrees is a recognized powerful approach to identify significant linkage results, as these families potentially contain more potential linkage information than sib-pair families. A genome-wide linkage analysis was performed on 26 extended autism families (65 affected, 184 total individuals). Each family had two to four affected individuals comprised of either avuncular or cousin pairs. For analysis, we used a high-density single-nucleotide polymorphism genotyping assay, the Affymetrix GeneChip Human Mapping 10K array. Two-point analysis gave peak heterogeneity limit of detection (HLOD) of 2.82 at rs2877739 on chromosome 14q. Suggestive linkage evidence (HLOD>2) from a two-point analysis was also found on chromosomes 1q, 2q, 5q, 6p,11q and 12q. Chromosome 12q was the only region showing significant linkage evidence by multipoint analysis with a peak HLOD=3.02 at rs1445442. In addition, this linkage evidence was enhanced significantly in the families with only male affected (multipoint HLOD=4.51), suggesting a significant gender-specific effect in the etiology of autism. Chromosome-wide haplotype analyses on chromosome 12 localized the potential autism gene to a 4 cM region shared among the affected individuals across linked families. This novel linkage peak on chromosome 12q further supports the hypothesis of substantial locus heterogeneity in autism. SN - 1359-4184 UR - https://www.unboundmedicine.com/medline/citation/17179998/Dissecting_the_locus_heterogeneity_of_autism:_significant_linkage_to_chromosome_12q14_ L2 - http://dx.doi.org/10.1038/sj.mp.4001927 DB - PRIME DP - Unbound Medicine ER -