Time in Anatomy

D. Davidson, A. Burger, D. Davidson, R. Baldock

Research output: Chapter in Book/Report/Conference proceedingChapter


INTRODUCTION: Aicardi-Goutieres syndrome (AGS) is an autosomal recessive, early onset encephalopathy characterised by calcification of the basal ganglia, a chronic cerebrospinal fluid lymphocytosis and negative serological investigations for common prenatal infections. AGS may result from a perturbation of interferon alpha metabolism. The disorder is genetically heterogeneous with approximately 50% of families mapping to the first known locus at 3p21 (AGS1). METHODS: A genome-wide scan was performed in 10 families with a clinical diagnosis of AGS in whom linkage to AGS1 had been excluded. Following two-point analysis of this data set, we undertook higher-density genotyping in regions of interest using the 10 mapping pedigrees and 7 additional AGS families. RESULTS: Our results demonstrate significant linkage to a second AGS locus (AGS2) at chromosome 13q14-21 with a maximum multipoint heterogeneity LOD score of 5.75 at D13S768. The AGS2 locus lies within a 4.7 cM region as defined by a 1 LOD-unit support interval. No obvious phenotypic differences are evident between individuals from families linking to AGS1, AGS2 and other, as yet unmapped, AGS loci. CONCLUSIONS: We have identified a second AGS disease locus. Our data confirm that at least one further locus exists for this disorder. As in a number of other conditions, genetic heterogeneity represents a significant obstacle to gene identification in AGS. The localisation of AGS2 represents an important step in this process. The cloning of AGS-causing genes will provide novel insights into a neurodegenerative mechanism likely resulting from exposure of the developing human brain to abnormally high levels of interferon alpha
Original languageEnglish
Title of host publicationAnatomy Ontologies for Bioinformatics: Principles and Practice
Number of pages35
Publication statusPublished - 2008
Externally publishedYes


  • analysis
  • Brain
  • diagnosis
  • Family
  • GENE
  • genes
  • Genetic Heterogeneity
  • human
  • Lod Score
  • metabolism
  • methods
  • Pedigree
  • Syndrome


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