Examination of NRCAM, LRRN3, KIAA0716, and LAMB1 as autism candidate genes

Holli B. Hutcheson, Lana M. Olson, Yuki Bradford, Susan E. Folstein, Susan L. Santangelo, James S. Sutcliffe, Jonathan L. Haines

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Abstract

Background: A substantial body of research supports a genetic involvement in autism. Furthermore, results from various genomic screens implicate a region on chromosome 7q31 as harboring an autism susceptibility variant. We previously narrowed this 34 cM region to a 3 cM critical region (located between D7S496 and D7S2418) using the Collaborative Linkage Study of Autism (CLSA) chromosome 7 linked families. This interval encompasses about 4.5 Mb of genomic DNA and encodes over fifty known and predicted genes. Four candidate genes (NRCAM, LRRN3, KIAA0716, and LAMB1) in this region were chosen for examination based on their proximity to the marker most consistently cosegregating with autism in these families (D7S1817), their tissue expression patterns, and likely biological relevance to autism. Methods: Thirty-six intronic and exonic single nucleotide polymorphisms (SNPs) and one microsatellite marker within and around these four candidate genes were genotyped in 30 chromosome 7q31 linked families. Multiple SNPs were used to provide as complete coverage as possible since linkage disequilibrium can vary dramatically across even very short distances within a gene. Analyses of these data used the Pedigree Disequilibrium Test for single markers and a multilocus likelihood ratio test. Results: As expected, linkage disequilibrium occurred within each of these genes but we did not observe significant LD across genes. None of the polymorphisms in NRCAM, LRRN3, or KIAA0716 gave p<0.05 suggesting that none of these genes is associated with autism susceptibility in this subset of chromosome 7-linked families. However, with LAMB1, the allelic association analysis revealed suggestive evidence for a positive association, including one individual SNP (p =0.02) and three separate two-SNP haplotypes across the gene (p=0.007, 0.012, and 0.012). Conclusions: NRCAM, LRRN3, KIAA0716 are unlikely to be involved in autism. There is some evidence that variation in or near the LAMB1 gene may be involved in autism.

Original languageEnglish
Article number12
JournalBMC Medical Genetics
Volume5
DOIs
StatePublished - May 5 2004

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Autistic Disorder
Genes
Single Nucleotide Polymorphism
Chromosomes, Human, Pair 7
Linkage Disequilibrium
Chromosomes
Pedigree
Microsatellite Repeats
Haplotypes
DNA
Research

ASJC Scopus subject areas

  • Medicine(all)
  • Genetics(clinical)

Cite this

Hutcheson, H. B., Olson, L. M., Bradford, Y., Folstein, S. E., Santangelo, S. L., Sutcliffe, J. S., & Haines, J. L. (2004). Examination of NRCAM, LRRN3, KIAA0716, and LAMB1 as autism candidate genes. BMC Medical Genetics, 5, [12]. https://doi.org/10.1186/1471-2350-5-12

Examination of NRCAM, LRRN3, KIAA0716, and LAMB1 as autism candidate genes. / Hutcheson, Holli B.; Olson, Lana M.; Bradford, Yuki; Folstein, Susan E.; Santangelo, Susan L.; Sutcliffe, James S.; Haines, Jonathan L.

In: BMC Medical Genetics, Vol. 5, 12, 05.05.2004.

Research output: Contribution to journalArticle

Hutcheson, HB, Olson, LM, Bradford, Y, Folstein, SE, Santangelo, SL, Sutcliffe, JS & Haines, JL 2004, 'Examination of NRCAM, LRRN3, KIAA0716, and LAMB1 as autism candidate genes', BMC Medical Genetics, vol. 5, 12. https://doi.org/10.1186/1471-2350-5-12
Hutcheson HB, Olson LM, Bradford Y, Folstein SE, Santangelo SL, Sutcliffe JS et al. Examination of NRCAM, LRRN3, KIAA0716, and LAMB1 as autism candidate genes. BMC Medical Genetics. 2004 May 5;5. 12. https://doi.org/10.1186/1471-2350-5-12
Hutcheson, Holli B. ; Olson, Lana M. ; Bradford, Yuki ; Folstein, Susan E. ; Santangelo, Susan L. ; Sutcliffe, James S. ; Haines, Jonathan L. / Examination of NRCAM, LRRN3, KIAA0716, and LAMB1 as autism candidate genes. In: BMC Medical Genetics. 2004 ; Vol. 5.
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AU - Folstein, Susan E.

AU - Santangelo, Susan L.

AU - Sutcliffe, James S.

AU - Haines, Jonathan L.

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