File Download

There are no files associated with this item.

  Links for fulltext
     (May Require Subscription)

Conference Paper: Genomewide linkage analysis of age of onset of Huntington's Disease

TitleGenomewide linkage analysis of age of onset of Huntington's Disease
Authors
Issue Date2007
PublisherSpringer.
Citation
The 37th Annual Meeting of the Behavior Genetics Association (BGA 2007), Amsterdam, The Netherlands, 3-6 June 2007. In Behavior Genetics, 2007, v. 37 n. 6, p. 755 How to Cite?
AbstractThe age of onset of Huntington’s disease (HD) is highly correlated with the number of CAG repeats in the gene coding for the hungtingtin protein. However, there remains substantial unexplained variance in age of onset, since this relationship is only moderate for individuals with between 40 to 50 repeats, which make the majority of individuals with expanded repeats. Once the effect of the CAG repeat has been accounted for, the residual variance in age of onset is a heritable trait. Targeted candidate gene studies and a genome scan have suggested some loci as potential modifiers of the age of onset of HD. In this study, we have used the large Venezuelan pedigrees, which were used to locate the original HD gene, which offer much greater power than a standard sib-pair design. We have developed and applied near-optimal pedigree-member selection procedures to maximize power in the pedigrees. In this manner, we have carried out a genomewide linkage analysis employing a 6000-SNP marker panel. We have identified a novel locus at chromosome 2p25 (LOD = 4.29) that may modify the age of onset of HD. There is a second linkage peak (LOD = 3.39 at 2q35), which is consistent for sub-pedigrees of different complexities. A third linkage peak (LOD = 2.48 at 6q22) may confirm the most promising locus from a previous genome scan. Two other candidate loci are suggested on chromosome 5 (LOD = 3.31 at 5p14 and LOD = 3.14 at 5q32). All these regions harbor candidate genes that are promising HD modifier genes. The identification of these new genes may provide an invaluable help to improve our understanding of HD and develop new therapies.
Persistent Identifierhttp://hdl.handle.net/10722/105465
ISSN
2015 Impact Factor: 3.268
2015 SCImago Journal Rankings: 1.457

 

DC FieldValueLanguage
dc.contributor.authorGayan, Jen_HK
dc.contributor.authorBrocklebank, Den_HK
dc.contributor.authorAndresen, JMen_HK
dc.contributor.authorAlkorta-Aranburu, Gen_HK
dc.contributor.authorCader, MZen_HK
dc.contributor.authorRoberts, SAen_HK
dc.contributor.authorCherny, SSen_HK
dc.contributor.authorWexler, NSen_HK
dc.contributor.authorCardon, LRen_HK
dc.contributor.authorHousman, DEen_HK
dc.date.accessioned2010-09-25T22:35:16Z-
dc.date.available2010-09-25T22:35:16Z-
dc.date.issued2007en_HK
dc.identifier.citationThe 37th Annual Meeting of the Behavior Genetics Association (BGA 2007), Amsterdam, The Netherlands, 3-6 June 2007. In Behavior Genetics, 2007, v. 37 n. 6, p. 755en_HK
dc.identifier.issn0001-8244-
dc.identifier.urihttp://hdl.handle.net/10722/105465-
dc.description.abstractThe age of onset of Huntington’s disease (HD) is highly correlated with the number of CAG repeats in the gene coding for the hungtingtin protein. However, there remains substantial unexplained variance in age of onset, since this relationship is only moderate for individuals with between 40 to 50 repeats, which make the majority of individuals with expanded repeats. Once the effect of the CAG repeat has been accounted for, the residual variance in age of onset is a heritable trait. Targeted candidate gene studies and a genome scan have suggested some loci as potential modifiers of the age of onset of HD. In this study, we have used the large Venezuelan pedigrees, which were used to locate the original HD gene, which offer much greater power than a standard sib-pair design. We have developed and applied near-optimal pedigree-member selection procedures to maximize power in the pedigrees. In this manner, we have carried out a genomewide linkage analysis employing a 6000-SNP marker panel. We have identified a novel locus at chromosome 2p25 (LOD = 4.29) that may modify the age of onset of HD. There is a second linkage peak (LOD = 3.39 at 2q35), which is consistent for sub-pedigrees of different complexities. A third linkage peak (LOD = 2.48 at 6q22) may confirm the most promising locus from a previous genome scan. Two other candidate loci are suggested on chromosome 5 (LOD = 3.31 at 5p14 and LOD = 3.14 at 5q32). All these regions harbor candidate genes that are promising HD modifier genes. The identification of these new genes may provide an invaluable help to improve our understanding of HD and develop new therapies.-
dc.languageengen_HK
dc.publisherSpringer.-
dc.relation.ispartofBehavior Geneticsen_HK
dc.titleGenomewide linkage analysis of age of onset of Huntington's Diseaseen_HK
dc.typeConference_Paperen_HK
dc.identifier.emailCherny, SS: cherny@hku.hken_HK
dc.identifier.authorityCherny, SS=rp00232en_HK
dc.identifier.doi10.1007/s10519-007-9169-9-
dc.identifier.hkuros135895en_HK
dc.identifier.volume37en_HK
dc.identifier.issue6-
dc.identifier.spage755-
dc.identifier.epage755-
dc.publisher.placeUnited States-

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats