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Genetic refinement and physical mapping of a 2.3 Mb probable disease region associated with a bipolar affective disorder susceptibility locus on chromosome 4q35

Citation

Badenhop, RF and Moses, MJ and Scimone, A and Adams, LJ and Kwok, JBJ and Jones, AM and Davison, G and Evans, M and Kirkby, KC and Hewitt, JE and Donald, JA and Mitchell, PB and Schofield, PR, Genetic refinement and physical mapping of a 2.3 Mb probable disease region associated with a bipolar affective disorder susceptibility locus on chromosome 4q35, American Journal of Medical Genetics Part B (Neuropsychiatric Genetics), 117B, (1) pp. 23-32. ISSN 0148-7299 (2003) [Refereed Article]

DOI: doi:10.1002/ajmg.b.10023

Abstract

A susceptibility locus for bipolar affective disorder has been mapped to chromosome 4q35 in a large multigenerational pedigree. We have expanded this analysis to include 55 pedigrees (674 individuals, 214 affecteds). The evidence for linkage to 4q35 was strengthened in this larger cohort, with a maximum two-point LOD score of 3.2 for marker D4S1652. Several other markers in the region gave LOD scores greater than 1.5. Nonparametric analysis provided additional support for linkage to the 4q35 region. To further refine this region, haplotype analysis was carried out in 16 of the 55 pedigrees that showed evidence of linkage. As there is no evidence for an ancestral haplotype, nor a one-to-one correspondence between the disease and putative disease haplotype, we undertook an analysis based on pedigreespecific, identical-by-descent allele-sharing in order to define a probable disease region. This analysis indicated that the percentage sharing of alleles, identical-by-descent, in affecteds of all linked pedigrees increases from 60% at the centromeric markers to 75% for markers at the telomere. Maximal allele sharing occurred between markers D4S3051 and 4qTEL13 with this 24 cM region defining a probable disease region. We have constructed a physical map of the 4q35 interval consisting of a YAC contig and BAC clones. Based on this map the probable disease region between D4S3051 and 4qTEL13 corresponds to only 2.3 Mb. This region is very gene poor with only three known genes indicated from the YAC/BAC map. The small number of genes will facilitate systematic screening for variations associated with bipolar disorder. © 2003 Wiley-Liss, Inc.

Item Details

Item Type:Refereed Article
Research Division:Health Sciences
Research Group:Health services and systems
Research Field:Mental health services
Objective Division:Health
Objective Group:Public health (excl. specific population health)
Objective Field:Mental health
UTAS Author:Evans, M (Ms Mary Evans)
UTAS Author:Kirkby, KC (Professor Kenneth Kirkby)
ID Code:26736
Year Published:2003
Web of Science® Times Cited:16
Deposited By:Psychiatry
Deposited On:2003-08-01
Last Modified:2011-09-20
Downloads:0

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