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Article: An association analysis of microsatellite markers across the Prader-Willi/Angelman critical region on chromosome 15 (q11-13) and autism spectrum disorder

TitleAn association analysis of microsatellite markers across the Prader-Willi/Angelman critical region on chromosome 15 (q11-13) and autism spectrum disorder
Authors
Issue Date2005
PublisherJohn Wiley & Sons, Inc. The Journal's web site is located at http://www.interscience.wiley.com/jpages/0148-7299:1/
Citation
American Journal Of Medical Genetics - Neuropsychiatric Genetics, 2005, v. 137 B n. 1, p. 25-28 How to Cite?
AbstractAutism (OMIM 209850) is a neurodevelopmental disorder with a significant genetic component of a complex nature. Cytogenetic abnormalities in the Prader-Willi/Angelman syndrome critical region (PWACR) on chromosome 15 (q11-13) have been described in several individuals with autism. We have examined five microsatellite markers spread across the 4 Mb PWACR for linkage disequilibrium (LD) in 148 families with autism spectrum disorder (ASD) and a subset of 82 families with autism using the extended transmission disequilibrium test (ETDT). The markers examined were D15S11, D15S128, D15S1506, GABRB3, and D15S1002. In addition we have examined the microsatellite D15S822 for hemizygous deletion status in our sample as it had been previously reported to be increased in autism. We found no significant LD with any of the markers tested either in the ASD or autism families when looking at paternal and maternal meioses combined. However, as there are known imprinted genes in the region, including possibly GABRB3, we also examined for LD in paternal and maternal meioses separately. Examining paternal transmissions only, we found marginal evidence for LD with a protective allele at marker D15S11 in the ASD families (Chi-sq 7 df, P = 0.05) and marginal evidence for risk alleles at markers D15S1506 (Chi-sq 13.7, 6 df, P = 0.06), GABRB3 (Chi-sq 15.9, 8 df, P = 0.11) and D15S1002 (Chi-sq 17.7, 9 df, P = 0.08) in the autism only families. The allele responsible for the association with GABRB3 is the 191 allele which was previously reported to be overtransmitted. Hemizygous deletion of the microsatellite D15S822 was found in 3 out of 340 independent chromosomes in our sample; a rate of 0.8%. This is not significantly different to the frequency in the general population. In conclusion, our results did not rule out the involvement of this chromosomal region, but provided further evidence, albeit very limited, to implicate GABRB3. Further more systematic work in larger samples is required and confirmation that GABRB3 is imprinted is desirable. © 2005 Wiley-Liss, Inc.
Persistent Identifierhttp://hdl.handle.net/10722/175933
ISSN
2015 Impact Factor: 3.391
2015 SCImago Journal Rankings: 1.771
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorCurran, Sen_US
dc.contributor.authorRoberts, Sen_US
dc.contributor.authorThomas, Sen_US
dc.contributor.authorVeltman, Men_US
dc.contributor.authorBrowne, Jen_US
dc.contributor.authorMedda, Een_US
dc.contributor.authorPickles, Aen_US
dc.contributor.authorSham, Pen_US
dc.contributor.authorBolton, PFen_US
dc.date.accessioned2012-11-26T09:02:37Z-
dc.date.available2012-11-26T09:02:37Z-
dc.date.issued2005en_US
dc.identifier.citationAmerican Journal Of Medical Genetics - Neuropsychiatric Genetics, 2005, v. 137 B n. 1, p. 25-28en_US
dc.identifier.issn1552-4841en_US
dc.identifier.urihttp://hdl.handle.net/10722/175933-
dc.description.abstractAutism (OMIM 209850) is a neurodevelopmental disorder with a significant genetic component of a complex nature. Cytogenetic abnormalities in the Prader-Willi/Angelman syndrome critical region (PWACR) on chromosome 15 (q11-13) have been described in several individuals with autism. We have examined five microsatellite markers spread across the 4 Mb PWACR for linkage disequilibrium (LD) in 148 families with autism spectrum disorder (ASD) and a subset of 82 families with autism using the extended transmission disequilibrium test (ETDT). The markers examined were D15S11, D15S128, D15S1506, GABRB3, and D15S1002. In addition we have examined the microsatellite D15S822 for hemizygous deletion status in our sample as it had been previously reported to be increased in autism. We found no significant LD with any of the markers tested either in the ASD or autism families when looking at paternal and maternal meioses combined. However, as there are known imprinted genes in the region, including possibly GABRB3, we also examined for LD in paternal and maternal meioses separately. Examining paternal transmissions only, we found marginal evidence for LD with a protective allele at marker D15S11 in the ASD families (Chi-sq 7 df, P = 0.05) and marginal evidence for risk alleles at markers D15S1506 (Chi-sq 13.7, 6 df, P = 0.06), GABRB3 (Chi-sq 15.9, 8 df, P = 0.11) and D15S1002 (Chi-sq 17.7, 9 df, P = 0.08) in the autism only families. The allele responsible for the association with GABRB3 is the 191 allele which was previously reported to be overtransmitted. Hemizygous deletion of the microsatellite D15S822 was found in 3 out of 340 independent chromosomes in our sample; a rate of 0.8%. This is not significantly different to the frequency in the general population. In conclusion, our results did not rule out the involvement of this chromosomal region, but provided further evidence, albeit very limited, to implicate GABRB3. Further more systematic work in larger samples is required and confirmation that GABRB3 is imprinted is desirable. © 2005 Wiley-Liss, Inc.en_US
dc.languageengen_US
dc.publisherJohn Wiley & Sons, Inc. The Journal's web site is located at http://www.interscience.wiley.com/jpages/0148-7299:1/en_US
dc.relation.ispartofAmerican Journal of Medical Genetics - Neuropsychiatric Geneticsen_US
dc.subject.meshAllelesen_US
dc.subject.meshAngelman Syndrome - Geneticsen_US
dc.subject.meshAutistic Disorder - Diagnosis - Geneticsen_US
dc.subject.meshChi-Square Distributionen_US
dc.subject.meshChromosomes, Human, Pair 15 - Geneticsen_US
dc.subject.meshFemaleen_US
dc.subject.meshHumansen_US
dc.subject.meshLinkage Disequilibriumen_US
dc.subject.meshMaleen_US
dc.subject.meshMicrosatellite Repeats - Geneticsen_US
dc.subject.meshNuclear Familyen_US
dc.subject.meshPrader-Willi Syndrome - Geneticsen_US
dc.subject.meshReceptors, Gaba-A - Geneticsen_US
dc.titleAn association analysis of microsatellite markers across the Prader-Willi/Angelman critical region on chromosome 15 (q11-13) and autism spectrum disorderen_US
dc.typeArticleen_US
dc.identifier.emailSham, P: pcsham@hku.hken_US
dc.identifier.authoritySham, P=rp00459en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1002/ajmg.b.30126en_US
dc.identifier.pmid15952184-
dc.identifier.scopuseid_2-s2.0-23044490896en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-23044490896&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume137 Ben_US
dc.identifier.issue1en_US
dc.identifier.spage25en_US
dc.identifier.epage28en_US
dc.identifier.isiWOS:000230921200005-
dc.publisher.placeUnited Statesen_US
dc.identifier.scopusauthoridCurran, S=7103220956en_US
dc.identifier.scopusauthoridRoberts, S=7403451260en_US
dc.identifier.scopusauthoridThomas, S=7404655105en_US
dc.identifier.scopusauthoridVeltman, M=6603879051en_US
dc.identifier.scopusauthoridBrowne, J=8721293700en_US
dc.identifier.scopusauthoridMedda, E=6603809191en_US
dc.identifier.scopusauthoridPickles, A=35974712300en_US
dc.identifier.scopusauthoridSham, P=34573429300en_US
dc.identifier.scopusauthoridBolton, PF=22946425500en_US

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